Genetic etiology of truncus arteriosus excluding 22q11.2 deletion syndrome and identification of c.1617del, a prevalent variant in TMEM260, in the Japanese population.

Truncus Arteriosus (TA) is a congenital heart disease characterized by a single common blood vessel emerging from the right and left ventricles instead of the main pulmonary artery and aorta. TA accounts for 4% of all critical congenital heart diseases. The most common cause of TA is 22q11.2 deletion syndrome, accounting for 12-35% of all TA cases. However, no major causes of TA other than 22q11.2 deletion have been reported. We performed whole-genome sequencing of 11 Japanese patients having TA without 22q11.2 deletion. Among five patients, we identified pathogenic variants in TMEM260; the biallelic loss-of-function variants of which have recently been associated with structural heart defects and renal anomalies syndrome (SHDRA). In one patient, we identified a de novo pathogenic variant in GATA6, and in another patient, we identified a de novo probably pathogenic variant in NOTCH1. Notably, we identified a prevalent variant in TMEM260 (ENST00000261556.6), c.1617del (p.Trp539Cysfs*9), in 8/22 alleles among the 11 patients. The c.1617del variant was estimated to occur approximately 23 kiloyears ago. Based on the allele frequency of the c.1617del variant in the Japanese population (0.36%), approximately 26% of Japanese patients afflicted with TA could harbor homozygous c.1617del variants. This study highlights TMEM260, especially c.1617del, as a major genetic cause of TA in the Japanese population.

Epidemiological analysis of the patients with psoriasis in Asian countries and region using the same clinical case cards between 2020 and 2022.

Although many epidemiological surveys for patients with psoriasis have been reported based on individual countries or facilities, there has been no study encompassing the major countries or the region in Asia. The Asian Society for Psoriasis (ASP) has been conducting an epidemiological study across various Asian countries and regions to elucidate the and compare the epidemiology of psoriasis. A total of 1948 cases were analyzed, with 938 cases from Japan, 530 cases from China, 325 cases from Korea, 141 cases from Chinese Taipei, and 14 cases from Thailand, all of which were enrolled between 2020 and 2022. In the Asian region total, the male-female ratio was 1.87:1 and the peak age at disease onset was 20-29 years. The proportion of psoriasis vulgaris (PsV), psoriatic arthritis (PsA), and pustular psoriasis (PP) was 80.1%, 17.7%, and 2.2%, respectively, and PsA was more commonly associated with nail symptoms than psoriasis vulgaris (PsV). Of the patients, 13% had a familial history of psoriasis and the most frequently affected family member was the father. Regarding treatment, 78.3% of the patients received topical medications, 9.0% underwent phototherapy, 34.0% received oral medications, and 36.1% were treated with biological agents. This study provided valuable information on the epidemiology and treatment of psoriasis using the registry data collected with the common reporting form in the same period in major Asian countries and regions. Male predominance is a distinctive feature of psoriasis in Asia. This epidemiological data registry in the ASP will continue afterwards.

Clinical Prognosis of Vocal Cord Paralysis After Cardiothoracic Surgery in Infants.

We aimed to clarify the long-term outcomes and prognosis of vocal cord paralysis (VCP) after cardiothoracic surgery in infants as well as the usefulness of laryngeal ultrasound (LUS) as screening for VCP. Overall, 967 infants aged 1-year-old or younger who underwent cardiothoracic surgery between 2008 and 2022 were included in this study. We divided the patients into two groups based on the period on whether they underwent screening without or with LUS and compared the incidence of VCP between the groups. There were no differences in the patients' preoperative characteristics between the two periods, whereas the incidence of VCP was significantly higher in period 2 than in period 1 (11.0% vs. 3.2%, p < 0.0001). The incidence of VCP among the procedures, including aortic arch repair, was > 50% and significantly increased from period 1 to period 2. The sensitivity and specificity of LUS was 87% and 90%, respectively. Symptoms of VCP improved in 92% of patients. Repeated flexible laryngoscopy revealed that the residual rate of VCP was 68%, 52%, and 48% at 6, 12, and 24 months, respectively. In conclusion, symptoms of postoperative VCP improved in most cases; however, paralysis persisted in half of the patients. As a screening method, LUS is useful for evaluating postoperative VCP. A more accurate understanding of VCP is needed to improve postoperative outcomes.

Rare Case of Neonatal Cardiac Ischemia Due to Intermittent Aortic Insufficiency.

We report a case of a 23-day-old girl who presented with repeated life-threatening myocardial ischemia from intermittent aortic insufficiency because of fixation of the left coronary cusp against the aortic wall. The patient underwent aortic valve repair with partial commissuroplasty of the left-right and left-noncommissures. After the surgical intervention the patient has been well, with no ischemic event for over 1 year. This diagnosis should be considered as a differential diagnosis in pediatric cases with myocardial ischemia.

A Case Report of Synchronous Prostate Cancer and Rectal Gastrointestinal Stromal Tumor and its Management.

A 72-year-old Japanese man presented to the hospital with complaints of gross hematuria. Contrast enhanced com-puted tomography revealed a broad-based, approximately 3-cm bladder tumor near the right ureteral orifice and a 5-cm mass located between the prostate and rectum. The patient underwent transurethral resection of the bladder tumor and a transrectal biopsy of the lesion. Histological examination of the specimens suggested that the patient had a muscle invasive adenocarcinoma from transurethral resection and a rectal gastrointestinal stromal tumor in TRUS biopsy. Patient underwent total pelvic exenteration and ileal and colonic stomas to divert urine and faeces. Final pathology report of the resected specimen revealed a rectal gastrointestinal stromal tumor and prostatic ad-enocarcinoma, which had invaded the urinary bladder and seminal vesicles. Synchronous gastrointestinal stromal tumor in rectum and prostate cancer treated with total pelvic exenteration has not been reported before in literature.

Japanese guidelines for the management and treatment of generalized pustular psoriasis: The new pathogenesis and treatment of GPP.

Generalized pustular psoriasis (GPP) is a rare disease characterized by recurrent fever and systemic flushing accompanied by extensive sterile pustules. The committee of the guidelines was founded as a collaborative project between the Japanese Dermatological Association and the Study Group for Rare Intractable Skin Diseases under the Ministry of Health, Labour, and Welfare Research Project on Overcoming Intractable Diseases. The aim of the guidelines was to provide current information to aid in the treatment of patients with GPP in Japan. Its contents include the diagnostic and severity classification criteria for GPP, its pathogenesis, and recommendations for the treatment of GPP. Since there are few clinical trial data with high levels of evidence for this rare disease, recommendations by the committee are described in the present guidelines.

Quantum Zeno Effect assisted Spectroscopy of a single trapped Ion.

The quantum Zeno effect (QZE) is not only interesting as a manifestation of the counterintuitive behavior of quantum mechanics, but may also have practical applications. When a spectroscopy laser is applied to target atoms or ions prepared in an initial state, the Rabi flopping of an auxiliary transition sharing one common level can be inhibited. This effect is found to be strongly dependent on the detuning of the spectroscopy laser and offers a sensitive spectroscopy signal which allows for high precision spectroscopy of transitions with a small excitation rate. We demonstrate this method with direct frequency comb spectroscopy using the minute power of a single mode to drive a dipole allowed transition in a single trapped ion. Resolving the individual modes of the frequency comb demonstrates that the simple instantaneous quantum collapse description of the QZE can not be applied here, as these modes need several pulses to build up.

A case of retroperitoneal fibrosis responding to steroid therapy

ABSTRACT A 69-year-old man presented at the hospital with complaints of prolonged stomach pain extending from the week prior. Enhanced computed tomography (CT) revealed a low density area in the retroperitoneal space. A radiologist diagnosed the patient with retroperitoneal fibrosis. One week later, an enhanced CT revealed an exponential increase of the low density area and slight right hydronephrosis. Upon admission, prednisolone administration was initiated at a dose of 40mg/day. The size of the retroperitoneal soft tissue mass decreased gradually. Although the dose of prednisolone was tapered to 5mg, the patient is doing well without any sign of recurrence.

Multi-pass-cell-based nonlinear pulse compression to 115 fs at 7.5 µJ pulse energy and 300 W average power.

We demonstrate nonlinear pulse compression by multi-pass cell spectral broadening (MPCSB) from 860 fs to 115 fs with compressed pulse energy of 7.5 µJ, average power of 300 W and close to diffraction-limited beam quality. The transmission of the compression unit is >90%. The results show that this recently introduced compression scheme for peak powers above the threshold for catastrophic self-focusing can be scaled to smaller pulse energies and can achieve a larger compression factor than previously reported. Good homogeneity of the spectral broadening across the beam profile is verified, which distinguishes MPCSB among other bulk compression schemes.

Single ion fluorescence excited with a single mode of an UV frequency comb.

Optical frequency combs have revolutionized the measurement of optical frequencies and improved the precision of spectroscopic experiments. Besides their importance as a frequency-measuring ruler, the frequency combs themselves can excite target transitions (direct frequency comb spectroscopy). The direct frequency comb spectroscopy may extend the optical frequency metrology into spectral regions unreachable by continuous wave lasers. In high precision spectroscopy, atoms/ions/molecules trapped in place have been often used as a target to minimize systematic effects. Here, we demonstrate direct frequency comb spectroscopy of single 25Mg ions confined in a Paul trap, at deep-UV wavelengths. Only one mode out of about 20,000 can be resonant at a time. Even then we can detect the induced fluorescence with a spatially resolving single photon camera, allowing us to determine the absolute transition frequency. The demonstration shows that the direct frequency comb spectroscopy is an important tool for frequency metrology for shorter wavelengths where continuous wave lasers are unavailable.Frequency combs are useful tools in high precision measurement including atomic transitions and atomic clocks. Here the authors demonstrate direct frequency comb spectroscopy to shorter wavelengths by probing a transition frequency in a trapped Mg+ ion using a single mode of a UV frequency comb.

A case of retroperitoneal fibrosis responding to steroid therapy.

A 69-year-old man presented at the hospital with complaints of prolonged stomach pain extending from the week prior. Enhanced computed tomography (CT) revealed a low density area in the retroperitoneal space. A radiologist diagnosed the patient with retroperitoneal fibrosis. One week later, an enhanced CT revealed an exponential increase of the low density area and slight right hydronephrosis. Upon admission, prednisolone administration was initiated at a dose of 40mg/day. The size of the retroperitoneal soft tissue mass decreased gradually. Although the dose of prednisolone was tapered to 5mg, the patient is doing well without any sign of recurrence.

Pediatric case of anaplastic lymphoma kinase-positive anaplastic large cell lymphoma forming a solitary skin tumor on the forearm.

A 5-year-old girl noticed a rapidly growing reddish nodule on her right forearm. Although oral antibiotics had been administrated for 2 weeks, the tumor enlarged. Skin biopsy revealed excessive infiltration of atypical neoplastic cells expressing CD4, CD30 and anaplastic lymphoma kinase (ALK). These histological and immunohistochemical findings were consistent with anaplastic large cell lymphoma (ALCL). Computed tomography showed multiple lymphadenopathy, but lymph node biopsy and bone marrow examination did not show any evidence of systemic dissemination. However, due to the positive results for ALK and multiple lymphadenopathy, we diagnosed ALK-positive ALCL forming a solitary skin tumor on the forearm. The patient received chemotherapy and presented marked improvement. This paper discusses the difficulty of diagnosing pediatric ALK-positive ALCL limited to the skin and reviews the medical published work.

Cartilage Oligomeric Matrix Protein Increases in Photodamaged Skin.

Cartilage oligomeric matrix protein (COMP) is a structural component of cartilage. Recent studies have described COMP as a pathogenic factor that promotes collagen deposition in fibrotic skin disorders such as scleroderma and keloid skin. Although collagen, a major dermis component, is thought to decrease in photoaged skin, recent reports have demonstrated the presence of tightly packed collagen fibrils with a structural resemblance to fibrosis in the papillary dermis of photoaged skin. Here we examined how photoaging damage relates to COMP expression and localization in photoaged skin. In situ hybridization revealed an increase in COMP-mRNA-positive cells with the progress of photoaging in preauricular skin (sun-exposed skin). The signal intensity of immunostaining for COMP increased with photoaging in not only the papillary dermis but also the reticular dermis affected by advancing solar elastosis. Immunoelectron microscopy detected the colocalization of COMP with both elastotic materials and collagen fibrils in photoaged skin. Ultraviolet light A irradiation of human dermal fibroblasts induced COMP expression at both the mRNA and protein levels. Ultraviolet light A-induced COMP expression was inhibited by an anti-transforming growth factor-ß antibody or SB431542, an activin receptor-like kinase 5 inhibitor. These results suggest that the transforming growth factor-ß-mediated upregulation of COMP expression may contribute to the modulation of dermal extracellular matrix in the photoaging process.

Doppler Cooling Trapped Ions with a UV Frequency Comb.

We demonstrate Doppler cooling of trapped magnesium ions using a frequency comb at 280 nm obtained from a frequency tripled Ti:sapphire laser. A comb line cools on the 3s_{1/2}-3p_{3/2} transition, while the nearest blue-detuned comb line contributes negligible heating. We observe the cooling-heating transition and long-term cooling of ion chains with several sympathetically cooled ions. Spatial thermometry shows that the ion is cooled to near the Doppler limit. Doppler cooling with frequency combs has the potential to open many additional atomic species to laser cooling by reaching further into the vacuum and extreme ultraviolet via high-harmonic generation and by providing a broad bandwidth from which multiple excitation sidebands can be obtained.

High average power coherent vuv generation at 10 MHz repetition frequency by intracavity high harmonic generation.

Intracavity high harmonic generation was utilized to generate high average-power coherent radiation at vacuum ultraviolet (vuv) wavelengths. A ytterbium-doped fiber-laser based master-oscillator power-amplifier (MOPA) system with a 10 MHz repetition frequency was developed and used as a driving laser for an external cavity. A series of odd-order harmonic radiations was generated extending down to ∼ 30 nm (41 eV in photon energy). The 7th harmonic radiation generated was centered at 149 nm and had an average output power of up to 0.5 mW. In this way, we developed a sub-mW coherent vuv-laser with a 10 MHz repetition frequency, which, if used as an excitation laser source for photo-electron spectroscopy, could improve the signal count-rate without deterioration of the spectral-resolution caused by space-charge effects.

Notch signaling may be involved in the abnormal differentiation of epidermal keratinocytes in psoriasis.

Localization of each keratin isoform differs among epidermal layers. Proliferating basal cells synthesize keratin 14 (K14) and suprabasal cells express keratin 10 (K10) in normal skin. Notch signaling is essential for keratinocyte differentiation. Notch1 is expressed in all epidermal layers, Notch2 in the basal cell layer and Notch3 in basal cell and spinous cell layers in normal epidermis. It has been poorly elucidated how localization and expression levels of Notch molecules are related to epidermal molecular markers K10 and K14 in psoriatic skin with abnormal differentiation of epidermal tissue. This study aimed to investigate the relationship between abnormal differentiation of epidermal cells in psoriatic skin and expression of Notch molecules. We investigated keratins (K14 and K10) and Notches (1, 2, 3 and 4) using immunohistochemistry in psoriatic skin (n=30) and normal skin (n=10). In normal skin, K14 and K10 were discretely observed in the basal cell layer and suprabasal layer, respectively. In psoriatic skin, K14 was expressed in the pan epidermal layer while it and K10 were co-expressed in some middle suprabasal layer cells. Notch1, 2, 3, and 4 localized in all epidermal layers in normal skin. In psoriatic skin, Notch1, 2, and 4 mainly localized in suprabasilar layers and Notch3 is lacalized in pan epidermal, suprabasilar, and basilar layers. Protein and mRNA of Notch1, 2, and 3 isoforms decreased in psoriatic epidermis compared with normal epidermis. These data suggest that decrements in these Notch molecules might cause aberrant expression of K10 and K14 leading to anomalous differentiation of the epidermis in psoriatic lesions.

A Case of Delayed Flare-up Allergic Dermatitis Caused by Jellyfish Sting.

A 7-year-old boy, taking lessons at a yacht school at Enoshima in Kanagawa prefecture in Japan, recognized a linear eruption on his left lower leg during practice in August 2012. As it gradually enlarged, he visited a local medical clinic. The eruption initially improved with topical treatment but exacerbated in October of the same year. Although topical treatment was started again, there was minimal improvement, so the patient visited our hospital in December. At his first visit, he had a hard linear nodule on his left lower leg, and papules with excoriation were scattered over the lower limbs. Considering eczema, topical steroid treatment and occlusive dressing technique were started but the nodule remained. Based on the clinical course, clinical features, and laboratory findings, the lesion was considered to be delayed flare-up allergic dermatitis caused by a jellyfish sting [1].

A case of foreign body granuloma induced by subcutaneous injection of leuprorelin acetate─clinical analysis for 335 cases in our hospital─.

We experienced a case of granuloma formation by subcutaneous injection of leuprorelin acetate for treatment of prostate cancer. This patient was an 80-year-old man visiting the clinic of gastroenterological surgery as an outpatient after gastric cancer surgery with a one-week's history of rash on the abdomen. Based on the history of gastric cancer and prostate cancer, though ultrasonography and CT were performed, the possibility of metastatic skin tumor could still not be ruled out. Finally, finding of a foreign-body granuloma in the subcutaneous adipose tissue was recognized histological. Then, an interview with the patient revealed that he had received subcutaneous injection of a 3-month depot formulation of leupurorelin acetate at the site of the lesion about two months earlier. Among urologists, as side effects for treatment, foreign body granuloma induced by subcutaneous injection of leuprorelin maybe well known. Therefore, it is tried to analyze as to clinical findings, especially granuloma formation for 335 cases that received leuprorelin acetate treatment at our hospital. In this report, we analyzed reported case and 335 cases that received leuprorelin acetate treatment at our hospital and summarized the cases that developed the granuloma formation by it.