Zeaxanthin is required for eyespot formation and phototaxis in Euglena gracilis.

The eyespot apparatus is an organelle that forms carotenoid-rich globules in diverse flagellated microalgae and functions in phototaxis. The euglenophytes have structurally and functionally distinct eyespot apparatuses from chlorophytes. ß-Carotene is the most abundant pigment detected in chlorophytes' eyespots, while xanthophylls such as zeaxanthin and diadinoxanthin have been suggested to function in euglenophytes' eyespots. Here, we investigated the association between carotenoid composition and eyespot formation via pathway-scale mutagenesis using clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9)-mediated genome editing in the euglenophyte Euglena gracilis. Lycopene cyclase (lcy) mutants exhibited sole lycopene accumulation, defective red eyespots, and phototactic insensitivity. Conversely, ß-carotene hydroxylase (cytochrome P450 97h1, cyp97h1) mutants accumulated ß-carotene and its hydroxylated products ß-cryptoxanthin and zeaxanthin and formed phototactic eyespot apparatuses, while cyp97h1 cyp97f2 double mutants were deficient in ß-carotene hydroxylation and mostly lacked functional eyespots. Thus, zeaxanthin is required for the stable formation of functional eyespots in E. gracilis, highlighting evolutionary differences between euglenophytes and chlorophytes in the metabolic regulation of photoreactive organelle formation.

A systematic review and meta-analysis of antibiotic-loaded bone cement for prevention of deep surgical site infections following primary total joint replacement.

BACKGROUND: The use of antibiotic-loaded bone cement (ALBC) as a mean for preventing deep surgical site infections (SSI) after total joint replacement is controversial. Therefore, we have conducted a meta-analysis to evaluate the prophylactic effect of ALBC for SSI prevention in patients undergoing arthroplasty. This study was conducted to revise treatment guidelines for MRSA infections in Japan. METHODS: PubMed (Medline), Scopus, Embase, Web of Science and Cochrane library were searched for relevant articles comparing preventive effect of ALBC for patients undergoing primary total joint arthroplasty by August 2022. Primary outcome was the incidence of deep SSI. Subgroup analyses by type of surgery (total hip (THA) or knee (TKA) arthroplasty) and by causative pathogen (methicillin-resistant Staphylococcus aureus (MRSA)) were performed. RESULTS: Of the 3379 studies identified for screening, six studies involving 5745 patients were included. The use of ALBC significantly reduced the incidence of deep SSI in overall patients (risk ratio [RR] 0.60, 95% confidential interval [CI] 0.39-0.92), but the evidence level was very low. There was no significant preventive effect for ALBC compared with non-ALBC in both THA and TKA (THA, RR 0.52, 95% CI 0.23-1.16; TKA, RR 0.64, 95% CI 0.38-1.06), and for preventing MRSA-SSI (RR 0.27, 95% CI 0.03-2.41). CONCLUSIONS: Although the overall preventive effect of ALBC was significant, the evidence level was very low. Thus, the routine use of ALBC as a mean to prevent SSI in arthroplasty may not be suggested.

Trends in inpatient orthopedic surgery during the COVID-19 pandemic in Japan: a nationwide data study.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has resulted in substantial morbidity and mortality globally. The National Database of Health Insurance Claims and Specific Health Checkups of Japan (NDB) covers 99.9% of health insurance claim receipts by general practitioners. The purpose of this study is to investigate the nationwide number of inpatient orthopedic surgeries in Japan during the effect of state of emergency (SoE) due to COVID-19. METHOD: The NDB has been publicly available since 2014. We retrospectively reviewed the NDB from April 2019 to March 2022. We gathered the monthly number of all inpatient orthopedic surgeries. We also classified orthopedic surgeries into the following 11 categories by using K-codes, Japanese original surgery classification: fracture, arthroplasty, spine, arthroscopy, hardware removal, hand, infection/amputation, ligament/tendon, tumor, joint, and others. By using the average number from April to December 2019 as the reference period, we investigated the increase or decrease orthopedic surgeries during the pandemic period. RESULTS: The NDB showed that the average number of total inpatient orthopedic surgeries during the reference period was 115,343 per month. In May 2020, monthly inpatient orthopedic surgeries decreased by 29.6% to 81,169 surgeries, accounting for 70.3% of the reference period. The second SoE in 2021 saw no change, while the third and fourth SoEs showed slight decreases compared to the reference period. Hardware removal and tumor surgeries in May 2020 decreased to 45.3% and 45.5%, respectively, while fracture surgeries had relatively small decreases. CONCLUSION: According to NDB, approximately 1.3 million orthopedic inpatient surgeries were performed or claimed in a year in Japan. In May 2020, the first SoE period of the COVID-19 pandemic, the number of inpatient orthopedic surgeries in Japan decreased by 30%. Meanwhile, the decrease was relatively small during the SoE periods in 2021.

Clinical outcome and neurological development of patients with biliary atresia associated with a bleeding tendency: a single institution experience.

PURPOSE: We compared the clinical features of patients with biliary atresia (BA) associated with a bleeding tendency (BT) at the time of the diagnosis with those of patients without a bleeding tendency (NBT). METHODS: The patients' background characteristics, age in days at the first visit, Kasai portoenterostomy (KPE), and postoperative course were retrospectively analyzed. RESULTS: Nine of the 93 BA patients (9.7%) showed a BT, including 7 with intracranial hemorrhaging (ICH), 1 with gastrointestinal bleeding, and 1 with a prothrombin time (PT) of 0%. The age at the first visit was 62 ± 12 days old for BT patients and 53 ± 27 days old for NBT patients (p = 0.4); the age at KPE was 77 ± 9 days old for BT patients and 65 ± 24 days old for NBT patients (p = 0.2); the time from the first visit to surgery was 13 ± 7 days for BT patients and 11 ± 10 days for NBT patients (p = 0.5); and the native liver survival rate was 56% for BT patients and 58% for NBT patients (p = 1), with no significant difference in any of the parameters. The neurological outcomes of survivors of ICH were favorable. CONCLUSIONS: Appropriate BT correction allowed early KPE even after ICH, resulting in native liver survival rates comparable to those of NBT patients without significant neurological complications.

Estimated number of spine surgeries and related deaths in Japan from 2014 to 2020.

BACKGROUND: The total number of spine surgeries per year and their related deaths in Japan has not been adequately estimated in the literature. METHODS: We retrospectively reviewed the National Database of Health Insurance Claims and Specific Health Checkups of Japan (NDB) between April 2014 to March 2021, which covers 99.9 % of health insurance claim receipts by general practitioners. The annual number of surgeries was counted using K codes, a procedure classification unique to Japan, and classified into the following six categories; percutaneous vertebroplasty, endoscopic surgery, open discectomy, laminoplasty/laminectomy, instrumentation surgery, and others. The data distribution was also summarized by sex and age. Additionally, by reviewing DPC database-related papers for evaluation of the mortality rate after spine surgery in Japan, the number of spine surgery-related deaths was calculated. RESULTS: The NDB showed that the number of spine surgeries analyzed in this study increased from 170,081 in 2014 to 193,903 in 2019, with a slight decrease in 2020. The ratio of instrumentation surgery increased from 33.0 % in 2014 to 37.9 % in 2020. The rate of patients aged 75 or older increased 31.6 % to 39.6 %. Combining these findings with DPC data showing a mortality rate of 0.1 % to 0.4 % revealed that the estimated number of deaths related to spine surgery in Japan ranged from 200 to 800 per year. CONCLUSIONS: Approximately 200,000 spine surgeries and 200 to 800 spine surgery-related inpatient deaths were estimated to have occurred in Japan around 2020.

Evaluation of skill acquisition characteristics depending on the size of a dry box.

BACKGROUND: Few studies have analyzed the effect of the size of the working space in training on the acquisition of endoscopic skills. In this study, adult- and infant-sized dry boxes (DBs) were used to verify how the size of the working space in training affects forceps manipulation and learning curve. MATERIAL AND METHODS: Seventy-two medical students were enrolled. The task was peg transfer. The training environment was divided into adult- and infant-sized DBs. Skill evaluations were also divided into adult- and infant-sized DBs (four groups in total). The forceps manipulation characteristics and task completion time were compared before and after training. RESULTS: Regarding skill evaluations using adult-sized DBs, there were no significant differences between the infant- and adult-sized DB-trained groups. Regarding skill evaluations using infant-sized DBs, there were no significant differences between the groups before training. After training, there was no significant difference in the total path length or average acceleration of the forceps between the groups. However, the infant-sized DB-trained group had a significantly faster average forceps velocity and faster task completion time than the adult-sized DB-trained group. CONCLUSION: Training with a small DB is more efficient in acquiring smoother and faster forceps manipulation in a small working space.

Safe and secure laparoscopy-assisted jejunostomy tube placement using a percutaneous loop needle device in an infant.

ABSTRACT: We, herein, report a surgical technique for laparoscopy-assisted jejunostomy tube placement in an infant using a loop needle device to fix the jejunum and abdominal wall. A 3-year-old boy with Down's syndrome underwent nutritional management by gastrostomy due to oral feeding difficulty after radical surgery for congenital duodenal stenosis and following bile duct stenosis. However, intractable gastrostomy site leakage emerged; hence, laparoscopy-assisted gastrostomy takedown and simultaneous laparoscopy-assisted jejunostomy tube placement were planned. After laparoscopy-assisted gastrostomy closure was performed, the jejunum was extracted through the umbilical trocar wound. A jejunostomy tube kit was inserted at the left side of the umbilicus. After tube insertion into the jejunum, the jejunostomy tube was wrapped with four interrupted sutures using the Witzel technique. Suture threads were extracted by percutaneous insertion of a loop needle device, and then, the jejunum was fixed to the abdominal wall. The post-operative course was uneventful. Percutaneous insertion of a loop needle device is useful for fixing a jejunostomy tube to the abdominal wall using the Witzel technique. Our technique is safe, secure and expected to reduce the risk of dislodgement of tube and peritonitis associated with jejunostomy tube placement.

Compact magneto-optical isolator by µ-transfer printing of magneto-optical single-crystal film on silicon waveguides.

Optical isolators provide one-way propagation and are necessary to protect laser diodes from damage and unstable operation caused by reflected light. Although magneto-optical (MO) devices can operate as isolators, achieving high-density integration using conventional direct bonding methods is difficult because a large and thick growth substrate remains on the circuits. We experimentally demonstrated a compact Mach-Zehnder interferometer-based MO isolator with Si waveguides by the µ-transfer printing of a Ce:YIG/SGGG coupon. The isolator has a footprint of 0.25 mm2 with a Ce:YIG/SGGG coupon of 50 × 800 µm2 and ∼ 1-µm thickness and achieved a maximum isolation ratio of 14 dB in telecom bands.

Spatially resolved multimode excitation for smooth supercontinuum generation in a SiN waveguide.

We propose a method of supercontinuum light generation enhanced by multimode excitation in a precisely dispersion-engineered deuterated SiN (SiN:D) waveguide. Although a regularly designed SiN-based nonlinear optical waveguide exhibits anomalous dispersion with the fundamental and first-order multimode operation, the center-symmetric light pumping at the input edge has so far inhibited the full potential of the nonlinearity of SiN-based materials. On the basis of numerical analysis and simulation for the SiN:D waveguide, we intentionally applied spatial position offsets to excite the fundamental and higher-order modes to realize bandwidth broadening with flatness. Using this method, we achieved an SNR improvement of up to 18 dB at a wavelength of 0.6 µm with an offset of about 1 µm in the Y-axis direction and found that the contribution was related to the presence of dispersive waves due to the excitation of TE10, and TE01 modes.

Oxytrofalcatin Puzzle: Total Synthesis and Structural Revision of Oxytrofalcatins B and C.

The previously reported structures of oxytrofalcatins B and C possess a benzoyl indole core. However, following synthesis and NMR comparison of both the proposed structure and the synthesized oxazole, we have revised the structure of oxytrofalcatins B and C as oxazoles. The synthetic route developed herein can further our understanding of the biosynthetic pathways that govern the production of natural 2,5-diaryloxazoles.

The clinical features of patients who underwent bladder augmentation of cloacal exstrophy and their functional outcomes: the results of a nationwide survey in Japan.

PURPOSE: Cloacal exstrophy (CE) patients may need bladder reconstruction after initially undergoing surgery to obtain continence and improve their quality of life. This study attempts to clarify the clinical features of CE patients who underwent bladder augmentation (BA) and their urinary functional outcomes based on a nationwide survey in Japan. METHODS: A questionnaire survey was conducted, and 150 CE patients were enrolled. Their clinical characteristics and urinary outcomes were reviewed. RESULTS: BA was performed in 52 patients (34.7%). Most cases underwent early bladder closure at initial surgery in neonate period. The age at the BA was performed 6.4 [6-9.0] years. Among them, the most used organ for BA was ileum (n = 30, 57.7%). Regarding the outcomes, the age when the renal function was evaluated was 14.0 [10.0-20.5] years and the serum creatinine level was 0.44 [0.36-0.60] (mg/dl). Clean intermittent catheterization was required in 37 (71.2%) patients. On the other hand, no dialysis or kidney transplantation was necessary in any of these patients. CONCLUSION: The renal function and conditions of patients who underwent BA were relatively well preserved. Individualized management with a stepwise surgical approach for CE patients should thus be considered in the future.

Does protocol miconazole administration improve mortality and morbidity on surgical necrotizing enterocolitis?

PURPOSE: Our previous clinical pilot study reported that miconazole (MCZ) prevented morbidity from surgical necrotizing enterocolitis (NEC). The present study re-investigated this effect in a long-term cohort over 20 years. METHODS: We conducted a retrospective cohort study from April 1998 to March 2020. A total of 1169 extremely low-birth-weight infants (ELBWIs) admitted to our neonatal intensive care unit, including 45 with NEC (3.8%), underwent surgery. Since 2002, protocol MCZ administration for 3 weeks has been applied for neonates born before 26 weeks' gestation or weighing under 1000 g. We compared the background characteristics and clinical outcomes between patients with and without MCZ administration. RESULTS: The morbidity rate decreased after applying the MCZ protocol, but no improvement in mortality was seen. A propensity score-matched analysis indicated that treated patients by MCZ showed a delay in developing surgical NEC by 12 days. The MCZ protocol also helped increase body weight at surgery. Prophylactic MCZ administration did not improve the neurological development of the language-social and postural-motor domains in the surgical NEC patients. But cognitive-adaptive domain caught up by a chronological age of 3 years old. CONCLUSIONS: Revising the protocol to extend the dosing period may improve the outcomes of surgical NEC after the onset.

Change over time in the postoperative defecation function in female patients with anovestibular fistula at a single institution: focus on the comparison of anal transposition with anterior sagittal anorectoplasty.

PURPOSE: Anovestibular fistula (AVF) is the most common type of ARM in female patients. The present study investigated changes over time in the postoperative defecation function of female patients with AVF. METHODS: Patient data were collected from 1984 to 2021. Eighty-eight female patients with AVF were enrolled. Patients' characteristics and the long-term outcome of defecation function were reviewed and analyzed retrospectively. The bowel function was evaluated according to the Japan Society of ARM Study Group evacuation score (ES). RESULTS: Thirty-eight patients underwent anal transposition (AT), and 8 underwent anterior sagittal anorectoplasty (ASARP). The total evacuation score (ES) in AVF patients reached "excellent" at nine years old, regardless of the operative procedure. The constipation scores with AT showed better improvement than those with ASARP, but soiling scores in the ASARP group showed better improvement than those in the AT group. The postoperative complications did not affect the postoperative bowel function in AVF patients. CONCLUSION: Most patients with AVF eventually achieved a satisfactory total ES. Given the difference in defecation score transition depending on the operative procedure or postoperative complications, it may be important to perform long-term defecation management via surgical procedures.

How many cases do instructor class pediatric surgeons need to experience to be an independent operator in performing advanced endoscopic surgery? A nationwide survey to establish an ideal curriculum for pediatric endoscopic surgery in Japan.

PURPOSE: To ensure the safe spread of pediatric endoscopic surgery, it is essential to build a training curriculum, and a survey of the current situation in Japan is necessary. The present study assessed an efficient training curriculum by clarifying instructor class pediatric surgeons' experiences, including autonomy when performing advanced endoscopic surgeries. METHODS: An online nationwide questionnaire survey was conducted among pediatric surgeons who had Endoscopic Surgical Skill Qualification (ESSQ) and board-certified instructors who had skills comparable to ESSQ. We assessed participants' training experience, opinions concerning the ideal training curriculum, and the correlation between surgical experience and the level of autonomy. The Zwisch scale was used to assess autonomy. RESULTS: Fifty-two participants responded to the survey (response rate: 86.7%). Only 57.7% of the respondents felt that they had received sufficient endoscopic surgery training. Most respondents considered an educational curriculum for endoscopic surgery including off-the-job training essential during the training period. Autonomy had been acquired after experiencing two to three cases for most advanced endoscopic surgeries. CONCLUSION: This first nationwide survey in Japan showed that instructor class pediatric surgeons acquired autonomy after experiencing two to three for most advanced endoscopic surgeries. Our findings suggest that training, especially off-the-job training, has been insufficient.

Intelligent Eye-Controlled Electric Wheelchair Based on Estimating Visual Intentions Using One-Dimensional Convolutional Neural Network and Long Short-Term Memory.

When an electric wheelchair is operated using gaze motion, eye movements such as checking the environment and observing objects are also incorrectly recognized as input operations. This phenomenon is called the "Midas touch problem", and classifying visual intentions is extremely important. In this paper, we develop a deep learning model that estimates the user's visual intention in real time and an electric wheelchair control system that combines intention estimation and the gaze dwell time method. The proposed model consists of a 1DCNN-LSTM that estimates visual intention from feature vectors of 10 variables, such as eye movement, head movement, and distance to the fixation point. The evaluation experiments classifying four types of visual intentions show that the proposed model has the highest accuracy compared to other models. In addition, the results of the driving experiments of the electric wheelchair implementing the proposed model show that the user's efforts to operate the wheelchair are reduced and that the operability of the wheelchair is improved compared to the traditional method. From these results, we concluded that visual intentions could be more accurately estimated by learning time series patterns from eye and head movement data.

The influence of COVID-19 epidemic on the number of orthopaedic surgeries in Japan.

BACKGROUND: There is limited data on the impact of COVID-19 epidemic on the number of orthopaedic surgeries in Japan. METHODS: We conducted a nationwide hospital survey asking for the monthly number of orthopaedic surgeries performed at each facility from January 2019 to June 2021. Those facilities that had performed at least 100 surgeries in 2019 were included for analyses. The facilities were further grouped by prefecture and by hospital characteristics. A brief health economic evaluation was also performed. Risk ratios were compared using univariate analyses with P < 0.05 considered statistically significant. RESULTS: Questionnaire was sent to 1988 hospitals with 1671 hospitals (84%) responding. The survey data indicated a total number of orthopaedic surgeries decreased in 2020 compared to 2019 (1,061,541 vs 1,119,955 P < 0.01), and also for the first six months of 2021 compared to the same period in 2019 (530,388 vs 550,378 P < 0.01). In 2020, over 50% of all facilities in nearly all of the prefectures saw a decline in surgical procedures. The risk of incurring more than a 25% decease in the number of surgeries was significantly higher in 2020 for class I designated medical institutions compared to those that were not designated for any types of infectious diseases among the institutions with a tertiary emergency medical center in 2020 (crude risk ratio 2.9: 95% CI 1.2-7.4, p = 0.02) and in 2021 (crude risk ratio 4.7: 95% CI 1 0.9-12.1, p < 0.01). The estimated total nationwide decrease of revenue were in the range of approximately ¥29.2 to ¥116.8 billion per year for orthopaedic surgeries alone. CONCLUSION: There was a statistically significant decrease in the number of orthopaedic surgeries in Japan. The magnitude of the decline varied by prefectures and hospital characteristics, with the greater impact imposed on medical institutions with higher classification functions. The estimated immediate health economic impact was sizable.

[A case of hepatitis C virus-related mixed cryoglobulinemic vasculitis with chronic diarrhea].

A woman in her 50s with a medical history of chronic hepatitis C virus (HCV) infection presented to our hospital with arthralgia, diarrhea, and fever. We performed colonoscopy and found scattered erosions at the terminal ileum. Furthermore, the biopsy specimen from the ileum and colon showed non-specific enterocolitis. Two weeks later, she was admitted to our hospital due to worsening neuropathy, proteinuria, and skin rash. On the next day, her abdominal pain worsened, and she had bloody stools. Repeat colonoscopy performed without bowel preparation revealed multiple erosions at the colon, and biopsy specimen from the colon exhibited narrowing of the lumen of the blood vessels. The presence of serum cryoglobulin and untreated chronic HCV infection is consistent with the diagnosis of hepatitis C virus-related mixed cryoglobulinemic vasculitis.

Direct f-3f self-referencing using an integrated silicon-nitride waveguide.

We have achieved the simultaneous generation of a 2.6-octave-wide supercontinuum (SC) spectrum over 400-2500 nm and third-harmonic light solely by a dispersion-controlled silicon-nitride waveguide (SiNW). To increase the visible intensity of the SC light component, we fabricated low-loss 5-mm-long deuterated SiNWs with spot-size converters by low-temperature deposition. We succeeded in measuring the carrier-envelope-offset (CEO) signal with a 34-dB signal-to-noise ratio because this short deuterated SiNW provides a large temporal overlap between the f and 3f components. In addition, we have demonstrated this method of CEO locking at telecommunications wavelengths with f-3f self-referencing generated solely by the SiNW without the use of highly nonlinear fiber and an additional nonlinear crystal. Compared with the method of CEO locking with a highly nonlinear fiber and a standard f-2f self-referencing interferometer, this method is not only simple and compact but also stable.

Artificial intelligence-based diagnosis of upper gastrointestinal subepithelial lesions on endoscopic ultrasonography images.

BACKGROUND: Endoscopic ultrasonography (EUS) is useful for the differential diagnosis of subepithelial lesions (SELs); however, not all of them are easy to distinguish. Gastrointestinal stromal tumors (GISTs) are the commonest SELs, are considered potentially malignant, and differentiating them from benign SELs is important. Artificial intelligence (AI) using deep learning has developed remarkably in the medical field. This study aimed to investigate the efficacy of an AI system for classifying SELs on EUS images. METHODS: EUS images of pathologically confirmed upper gastrointestinal SELs (GIST, leiomyoma, schwannoma, neuroendocrine tumor [NET], and ectopic pancreas) were collected from 12 hospitals. These images were divided into development and test datasets in the ratio of 4:1 using random sampling; the development dataset was divided into training and validation datasets. The same test dataset was diagnosed by two experts and two non-experts. RESULTS: A total of 16,110 images were collected from 631 cases for the development and test datasets. The accuracy of the AI system for the five-category classification (GIST, leiomyoma, schwannoma, NET, and ectopic pancreas) was 86.1%, which was significantly higher than that of all endoscopists. The sensitivity, specificity, and accuracy of the AI system for differentiating GISTs from non-GISTs were 98.8%, 67.6%, and 89.3%, respectively. Its sensitivity and accuracy were significantly higher than those of all the endoscopists. CONCLUSION: The AI system, classifying SELs, showed higher diagnostic performance than that of the experts and may assist in improving the diagnosis of SELs in clinical practice.

Optimal timing of definitive surgery for Hirschsprung's disease to achieve better long-term bowel function.

PURPOSE: Few studies have focused on the operative age for Hirschsprung's disease (HD). We evaluated the optimal timing of surgery in HD patients based on their long-term bowel function. METHODS: HD was diagnosed in 65 pediatric patients in our institute between 1992 and 2018. Twenty-five patients underwent the Soave-Denda procedure (SD) and 40 underwent transanal endorectal pull-through (TA). We divided these patients into two groups: those who underwent surgery at < 6 months of age (younger group) and those who underwent surgery at 6-12 months of age (older group). We assessed bowel function at 5, 7, and 9 years of age. RESULTS: The bowel function of the patients who underwent the SD did not differ significantly between the groups. Similarly, the total bowel-function scores of the patients who underwent TA did not differ between the groups at any age. However, the soiling score at 7 years of age in the older group of patients who underwent TA was significantly lower than that in the younger group (p = 0.02). CONCLUSIONS: Our data suggest that to achieve optimal bowel function, TA should be performed at < 6 months of age.