Changes in cataract and refractive surgery practice patterns among JSCRS members over the past 20 years.

PURPOSE: To evaluate changes in cataract and refractive surgery practice patterns among members of the Japanese Society of Cataract and Refractive Surgery (JSCRS) over the past 20 years. STUDY DESIGN: Questionnaire survey study. SUBJECTS AND METHODS: Clinical surveys were conducted annually between February and April from 2004 to 2023. Survey questions covered various areas, including cataract surgical techniques, anesthesia, endophthalmitis prophylaxis, toric and presbyopia-correcting intraocular lenses (IOLs), complications, and refractive surgery. RESULTS: The highest (n=554 [36.8%]) and lowest (n=316 [19.1%]) numbers of responses were collected in 2012 and 2016, respectively. In perioperative management, the intraoperative use of polyvinyl alcohol-iodine solution and topical antibiotic prescription 3 days before surgery has increased. The use of intracameral injection at the end of surgery has also significantly increased, although it has not been established as common practice. In anesthesia, there is a clear polarization between the use of topical drops and tenon injection. The use of toric IOLs and presbyopia-correcting IOLs has significantly increased from 2010 to 2023. In the latter, the use of trifocal IOLs has particularly increased. Regarding IOL power calculations, the Barrett True K and the Barrett Universal II formulas are rapidly gaining popularity for application with and without post-laser vision correction, respectively. In refractive surgery, phakic IOLs and corneal refractive therapy have attracted considerable interest, followed by laser in situ keratomileusis. CONCLUSIONS: Evaluation of annual clinical survey data over the past two decades provided valuable insights into the shifting practice patterns and clinical opinions among JSCRS members.

A comparative study of English and Japanese ChatGPT responses to anaesthesia-related medical questions.

Background: The expansion of artificial intelligence (AI) within large language models (LLMs) has the potential to streamline healthcare delivery. Despite the increased use of LLMs, disparities in their performance particularly in different languages, remain underexplored. This study examines the quality of ChatGPT responses in English and Japanese, specifically to questions related to anaesthesiology. Methods: Anaesthesiologists proficient in both languages were recruited as experts in this study. Ten frequently asked questions in anaesthesia were selected and translated for evaluation. Three non-sequential responses from ChatGPT were assessed for content quality (accuracy, comprehensiveness, and safety) and communication quality (understanding, empathy/tone, and ethics) by expert evaluators. Results: Eight anaesthesiologists evaluated English and Japanese LLM responses. The overall quality for all questions combined was higher in English compared with Japanese responses. Content and communication quality were significantly higher in English compared with Japanese LLMs responses (both P<0.001) in all three responses. Comprehensiveness, safety, and understanding were higher scores in English LLM responses. In all three responses, more than half of the evaluators marked overall English responses as better than Japanese responses. Conclusions: English LLM responses to anaesthesia-related frequently asked questions were superior in quality to Japanese responses when assessed by bilingual anaesthesia experts in this report. This study highlights the potential for language-related disparities in healthcare information and the need to improve the quality of AI responses in underrepresented languages. Future studies are needed to explore these disparities in other commonly spoken languages and to compare the performance of different LLMs.

Discovery of sparse, reliable omic biomarkers with Stabl.

Adoption of high-content omic technologies in clinical studies, coupled with computational methods, has yielded an abundance of candidate biomarkers. However, translating such findings into bona fide clinical biomarkers remains challenging. To facilitate this process, we introduce Stabl, a general machine learning method that identifies a sparse, reliable set of biomarkers by integrating noise injection and a data-driven signal-to-noise threshold into multivariable predictive modeling. Evaluation of Stabl on synthetic datasets and five independent clinical studies demonstrates improved biomarker sparsity and reliability compared to commonly used sparsity-promoting regularization methods while maintaining predictive performance; it distills datasets containing 1,400-35,000 features down to 4-34 candidate biomarkers. Stabl extends to multi-omic integration tasks, enabling biological interpretation of complex predictive models, as it hones in on a shortlist of proteomic, metabolomic and cytometric events predicting labor onset, microbial biomarkers of pre-term birth and a pre-operative immune signature of post-surgical infections. Stabl is available at https://github.com/gregbellan/Stabl .

Quantitative assessment of skin disorders induced by panitumumab: a prospective observational study.

PURPOSE: Acneiform rash is frequently observed in patients undergoing cancer treatment with anti-epidermal growth factor receptor (EGFR) antibody drugs and can often necessitate treatment discontinuation. However, the specific changes in skin parameters resulting from anti-EGFR antibody drug administration are poorly understood. Therefore, this study aimed to longitudinally and quantitatively evaluate the changes in skin parameters (transepidermal water loss [TEWL], hydration level, and sebum level) caused by anti-EGFR antibody drugs and investigate their potential as control markers for skin disorders. METHODS: This prospective study included 12 patients with colorectal cancer who received anti-EGFR antibody drugs for the first time. The assessment items included the grade of acneiform rash and skin parameters (TEWL, hydration level, and sebum level), which were observed for up to 6 weeks after administration of the medication. RESULTS: The enrolled patients were classified into two groups based on the grade of acneiform rash caused by anti-EGFR antibody drugs: "Grade 1 and lower," and "Grade 2 and higher." The skin parameters were compared between these groups. The results showed that in the "Grade 2 and higher" group, TEWL in the face (at week 2 of administration), chest (baseline, weeks 2 and 6 of administration), and back (at week 2 of administration) were significantly higher than those in the "Grade 1 and lower" group. However, the two groups showed no significant differences in hydration or sebum levels at any time point. CONCLUSION: TEWL can serve as a marker for acneiform rashes induced by anti-EGFR antibody drugs during cancer treatment.

Efficacy of Preventing Relapse Evaluated by a Multicenter Randomized Double-Blind Placebo-Controlled Withdrawal Study of Escitalopram in Japanese Adolescents with Major Depressive Disorder.

Objective: To evaluate the efficacy and safety of escitalopram (ESC) in a 48-week relapse prevention study in Japanese adolescents with major depressive disorder (MDD). Methods: This was a 48-week multicenter randomized double-blind placebo-controlled parallel-group study of patients aged 12-17 years with MDD. Patients received ESC for 12 weeks as an open-label treatment period (open-label period). Patients who achieved criteria for remission or response in the open-label period received either ESC or placebo for 36 weeks as a double-blind treatment period (double-blind period). The primary endpoint was the time to relapse during the double-blind period. Safety was evaluated in terms of type, incidence, and severity of adverse events. Results: Of the 128 patients who entered the open-label period, 80 patients entered the double-blind period, all of whom were in the primary analysis population. The primary endpoint, time to relapse, was marginally less than statistically significant between the ESC and placebo groups (p = 0.051, log-rank test). In the Cox proportional hazards model, the estimated hazard ratio [two-sided 95% confidence interval] for relapse in the placebo group versus the ESC group was 2.96 [0.94, 9.30]. There were statistically significant differences between the ESC and placebo groups in several secondary endpoints (change in Children's Depression Rating Scale-Revised, change in Clinical Global Impressions-Severity Scale, etc.). No notable safety/tolerability issues were observed in this study compared with the results of studies in Japanese adults with MDD. Conclusions: Superiority of ESC over placebo for relapse prevention in Japanese adolescents aged 12-17 years with MDD could not be verified with time to relapse evaluated by log-rank test. However, secondary endpoint results and a post hoc analysis of time to relapse suggest that ESC may be effective in preventing MDD relapse. No notable safety/tolerability issues were observed compared with the results of studies in Japanese adults with MDD. Study Registry Number: jRCT2080224520.

Spatial subsetting enables integrative modeling of oral squamous cell carcinoma multiplex imaging data.

Oral squamous cell carcinoma (OSCC), a prevalent and aggressive neoplasm, poses a significant challenge due to poor prognosis and limited prognostic biomarkers. Leveraging highly multiplexed imaging mass cytometry, we investigated the tumor immune microenvironment (TIME) in OSCC biopsies, characterizing immune cell distribution and signaling activity at the tumor-invasive front. Our spatial subsetting approach standardized cellular populations by tissue zone, improving feature reproducibility and revealing TIME patterns accompanying loss-of-differentiation. Employing a machine-learning pipeline combining reliable feature selection with multivariable modeling, we achieved accurate histological grade classification (AUC = 0.88). Three model features correlated with clinical outcomes in an independent cohort: granulocyte MAPKAPK2 signaling at the tumor front, stromal CD4+ memory T cell size, and the distance of fibroblasts from the tumor border. This study establishes a robust modeling framework for distilling complex imaging data, uncovering sentinel characteristics of the OSCC TIME to facilitate prognostic biomarkers discovery for recurrence risk stratification and immunomodulatory therapy development.

Sustenance Trial to Analyze the Effects of Black Soldier Fly Larvae Meal on the Reproductive Efficiency of Sows and the Hematological Properties of Suckling and Weaning Piglets.

The escalating demand for meat, driven by global population growth, necessitates sustainable solutions for animal feed production. This study investigated the effects of substituting conventional protein resources in sow and piglet dietary regimens with black soldier fly (BSF; Hermetia illucens) meal on reproductive efficiency, blood profile, piglet growth, and intestinal tissue morphology. The results indicate that substituting animal-derived and soy proteins with BSF meal does not compromise sow reproductive performance. Although no notable disparities were observed in piglet growth, the feed conversion ratio from the 28- to 35-day age marks were lower in the BSF-fed groups. This suggests that the animal protein-BSF substitution rate may require optimization, potentially involving chitin removal from BSF meal to enhance digestibility. Minor variations in the hematological composition and properties in piglets, with elevated high-density lipoprotein cholesterol levels in the high BSF group at the 28-day mark, were potentially attributable to the unique fatty acid composition of BSF meal. Moreover, this study potentiates future exploration into the efficacy of complete animal protein substitution with BSF meals on piglet nutrition and physiology, particularly in fattening pigs. The practical implementation of BSF meals in animal feed production holds promise for enhancing the sustainability of the swine industry.

Survey on chest CT findings in COVID-19 patients in Okinawa, Japan: differences between the delta and omicron variants.

To investigate the frequency of pneumonia and chest computed tomography (CT) findings in patients with coronavirus disease 2019 (COVID-19) during the fifth Delta variant-predominant and sixth Omicron variant-predominant waves of the COVID-19 pandemic in Okinawa, Japan. A survey on chest CT examinations for patients with COVID-19 was conducted byhospitals with board-certified radiologists who provided treatment for COVID-19 pneumonia in Okinawa Prefecture. Data from 11 facilities were investigated. Indications for chest CT; number of COVID-19 patients undergoing chest CT; number of patients with late-onset pneumonia, tracheal intubation, and number of deaths; and COVID-19 Reporting and Data System classifications of initial chest CT scans were compared by the chi-squared test between the two pandemic waves (Delta vs. Omicron variants). A total of 1944 CT scans were performed during the fifth wave, and 1178 were performed during the sixth wave. CT implementation rates, which were the number of patients with COVID-19 undergoing CT examinations divided by the total number of COVID-19 cases in Okinawa Prefecture during the waves, were 7.1% for the fifth wave and 2.1% for the sixth wave. The rates of tracheal intubation and mortality were higher in the fifth wave. Differences between the distributions of the CO-RADS classifications were statistically significant for the fifth and sixth waves (p < 0.0001). In the fifth wave, CO-RADS 5 (typical of COVID-19) was most common (65%); in the sixth wave, CO-RADS 1 (no findings of pneumonia) was most common (50%). The finding of "typical for other infection but not COVID-19" was more frequent in the sixth than in the fifth wave (13.6% vs. 1.9%, respectively). The frequencies of pneumonia and typical CT findings were higher in the fifth Delta variant-predominant wave, and nontypical CT findings were more frequent in the sixth Omicron variant-predominant wave of the COVID-19 pandemic in Okinawa, Japan.

Cell-free, high-density lipoprotein-specific phospholipid efflux assay predicts incident cardiovascular disease.

BACKGROUNDCellular cholesterol efflux capacity (CEC) is a better predictor of cardiovascular disease (CVD) events than HDL-cholesterol (HDL-C) but is not suitable as a routine clinical assay.METHODSWe developed an HDL-specific phospholipid efflux (HDL-SPE) assay to assess HDL functionality based on whole plasma HDL apolipoprotein-mediated solubilization of fluorescent phosphatidylethanolamine from artificial lipid donor particles. We first assessed the association of HDL-SPE with prevalent coronary artery disease (CAD): study I included NIH severe-CAD (n = 50) and non-CAD (n = 50) participants, who were frequency matched for sex, BMI, type 2 diabetes mellitus, and smoking; study II included Japanese CAD (n = 70) and non-CAD (n = 154) participants. We also examined the association of HDL-SPE with incident CVD events in the Prevention of Renal and Vascular End-stage Disease (PREVEND) study comparing 340 patients with 340 controls individually matched for age, sex, smoking, and HDL-C levels.RESULTSReceiver operating characteristic curves revealed stronger associations of HDL-SPE with prevalent CAD. The AUCs in study I were as follows: HDL-SPE, 0.68; apolipoprotein A-I (apoA-I), 0.62; HDL-C, 0.63; and CEC, 0.52. The AUCs in study II were as follows: HDL-SPE, 0.83; apoA-I, 0.64; and HDL-C, 0.53. Also longitudinally, HDL-SPE was significantly associated with incident CVD events independent of traditional risk factors with ORs below 0.2 per SD increment in the PREVEND study (P < 0.001).CONCLUSIONHDL-SPE could serve as a routine clinical assay for improving CVD risk assessment and drug discovery.TRIAL REGISTRATIONClinicalTrials.gov NCT01621594.FUNDINGNHLBI Intramural Research Program, NIH (HL006095-06).

Stabl: sparse and reliable biomarker discovery in predictive modeling of high-dimensional omic data.

High-content omic technologies coupled with sparsity-promoting regularization methods (SRM) have transformed the biomarker discovery process. However, the translation of computational results into a clinical use-case scenario remains challenging. A rate-limiting step is the rigorous selection of reliable biomarker candidates among a host of biological features included in multivariate models. We propose Stabl, a machine learning framework that unifies the biomarker discovery process with multivariate predictive modeling of clinical outcomes by selecting a sparse and reliable set of biomarkers. Evaluation of Stabl on synthetic datasets and four independent clinical studies demonstrates improved biomarker sparsity and reliability compared to commonly used SRMs at similar predictive performance. Stabl readily extends to double- and triple-omics integration tasks and identifies a sparser and more reliable set of biomarkers than those selected by state-of-the-art early- and late-fusion SRMs, thereby facilitating the biological interpretation and clinical translation of complex multi-omic predictive models. The complete package for Stabl is available online at https://github.com/gregbellan/Stabl.

Utility of urinary liver-type fatty acid-binding protein as a prognostic marker in adult congenital heart patients hospitalized for acute heart failure.

Progression to acute kidney injury (AKI) under treatment in adult congenital heart disease (ACHD) patients with heart failure is associated with poor prognosis, early detection and interventions are necessary. We aimed to explore the utility of urinary liver-type fatty acid binding protein (L-FABP) in ACHD patients hospitalized for acute decompensated heart failure (ADHF). We prospectively evaluated hemodynamic, biochemical data, and urinary biomarkers including urinary L-FABP in ACHD patients hospitalized in our institution from June 2019 to March 2022. The primary outcomes were the development of AKI and death. AKI was defined as serum creatinine level increased by 0.3 mg/dl or more within 5 days after hospitalization. A total of 104 ADHF patients aged 31 (36-51) years were enrolled. 26 cases (25% of ADHF patients) developed AKI during hospitalization and 4 died after hospital discharge. Serum creatinine (sCr), serum total bilirubin, brain natriuretic peptide (BNP), and urinary L-FABP in AKI patients were significantly higher than in non-AKI patients, whereas systemic oxygen saturation of the peripheral artery (SpO2) and estimated glomerular filtration ratio in AKI patients were lower than non-AKI patients. There was no difference in the intravenous diuretic dose on admission and during hospitalization between the two groups. In the receiver operating characteristic (ROC) analysis, the maximum area under the curve (AUC) of urinary biomarkers in AKI patients was urinary L-FABP (AUC = 0.769, p < 0.001) with a cutoff value of 4.86 µg/gCr. Urinary L-FABP level on admission was associated with a predictor for AKI development during hospitalization after adjusting for sCr, BNP and SpO2. Urinary L-FABP was a useful predictor for the development of AKI in ACHD patients hospitalized for ADHF. Monitoring of urinary L-FABP allows us to detect a high-risk patient earlier than the conventional biomarkers.

Labor risk factors for fetal heart rate abnormality after combined spinal-epidural analgesia.

OBJECTIVE: To explore the association between obstetric factors or outcomes and fetal heart rate (FHR) abnormalities after combined spinal-epidural analgesia (CSEA). METHODS: Women with singleton term deliveries who received CSEA at our institution between January 1 and December 31, 2017, were analyzed using medical records. We performed a logistic regression analysis to compare factors and outcomes between cases with and without new FHR abnormalities within 1 h after CSEA. RESULTS: Of the 393 women, 163 showed the new occurrence of FHR abnormality after CSEA. Rupture of the membrane (odds ratio [OR] 2.49; 95% confidence interval [CI] 1.52-4.09; P < 0.01) and dilatation of the cervix (OR 1.24; 95% CI 1.07-1.44; P < 0.01) were significantly associated with FHR abnormalities. There were significant differences in FHR abnormality rates between women with cervical dilatation of 2 cm or less and 3 cm or more (OR 2.20; 95% CI 1.01-4.81; P = 0.047) and 6 cm or less and 7 cm or more (OR 2.46; 95% CI 1.01-6.01; P = 0.048). FHR abnormalities were not significantly associated with cesarean delivery during labor, instrumental delivery, APGAR score below 7 at 1 or 5 min, or umbilical arterial blood gas pH less than 7.2. CONCLUSION: Rupture of the membrane and an advanced dilated cervix were risk factors for FHR abnormality when CSEA was initiated.

Compensation and monitoring of transmitter and receiver impairments in 10,000-km single-mode fiber transmission by adaptive multi-layer filters with augmented inputs.

We propose an adaptive multi-layer (ML) filter architecture to compensate for linear impairments that occur in transmitter (Tx) and receiver (Rx) components in ultra-long-haul optical fiber transmission systems, in which large chromatic dispersion (CD) accumulates in the received signal. The architecture consists of strictly linear (SL) and widely linear (WL) filter layers, and the coefficients of the ML filters are adaptively controlled by gradient calculation with back propagation and stochastic gradient descent. Static CD compensation is performed on the received signal and its complex conjugate before the adaptive ML filters. These augmented signals are then the inputs of the first 2×1 SL filter layer of the ML filters, for compensation of in-phase (I) and quadrature (Q) impairments on the Rx side. Tx IQ impairments and polarization effects as well as Rx IQ impairments are adaptively compensated in the ML filters. By sweeping CD compensation filters before the ML filters, this architecture mitigates the computational complexity for back propagation of the ML filters especially for ultra-long-haul transmission, while mutual non-commutativity between the WL filter for IQ impairment compensation and the CD compensation filter is appropriately solved. We evaluated the proposed adaptive ML filter architecture with augmented inputs through both simulation and wavelength-division multiplexed transmission experiments of 32-Gbaud polarization-division-multiplexed 64-quadrature amplitude modulation-based probabilistic constellation shaped signals over 10,000 km of single-mode fiber (SMF). The results demonstrated that the proposed adaptive ML filter architecture effectively compensates for Tx and Rx IQ skews in ultra-long-haul SMF transmission, and that impairments can be monitored individually from the converged filter coefficients of the corresponding layers.

Effects of dietary bamboo (Phyllostachys pubescens Mazel) culm powder on blood properties and intestinal environment of rabbits.

This study investigated the effects of bamboo powder as an alternative feed for rabbits. The normal hay diet of rabbits was replaced with bamboo culm powder (10% and 20%) and fed to the rabbits until they were 90 days old. The blood samples were collected when the rabbits were 46, 66, and 90 days old to assess the effects of bamboo powder on blood parameters. The organs and intestinal contents were harvested at the age of 90 days, and the functions and morphologies of different organs were evaluated. The concentration of short-chain fatty acids (SCFAs) and the composition of microbiota in the cecum were measured. Substituting bamboo powder did not affect the growth, hematology profile, intestinal morphologies, and cecum SCFA concentration in rabbits. In contrast, it significantly altered the cecum microbiota composition, particularly the abundance of Ruminococcus and Bacteroides related to fiber degradation and Tyzzerella spp., associated with large intestine inflammation. These findings suggest that the substitution of hay with bamboo powder in rabbit diets does not negatively affect the overall health of rabbits and could be considered an alternative feed for rabbits; nevertheless, the protein and lipid deficiency in the bamboo powder should be taken into account.

Fully automated microRNA quantification technique based on bioluminescent enzyme immunoassay.

MicroRNAs (miRNAs) are potential clinical biomarkers for the detection of various diseases. However, their quantification has not been implemented in clinical practice given the inconsistencies in their variable recovery rate and accuracy of the results. Thus, we utilized a technique based on bioluminescent enzyme immunoassay (BLEIA) to perform fully automated miRNA quantification using magnetic particles conjugated with antibodies targeting DNA-RNA hybrids, biotinylated DNA probes specific to miRNAs, and firefly luciferase-labeled streptavidin. This method enabled direct use of diluted serum and automation of all processes within 1 hr. The results revealed a wide linear range between 10 fmol/L and 1 nmol/L, high sensitivity with a detection limit of 6.3 fmol/L or below, high specificity with a false positive rate under 2.4%, and high reproducibility in intra- and inter-experimental observations (under CV 10% and r = 0.9965, respectively). Furthermore, a significant correlation was revealed between quantitative reverse transcription-polymerase chain reaction and BLEIA assay for the quantification of synthetic miRNA (r = 0.9993) and endogenous miRNA in healthy serums (r = 0.8203), respectively. Overall, we developed a fully automated miRNA quantification method based on BLEIA, which can be adopted in a clinical setting. However, further studies are needed to assess its clinical performance.

A new method for the preparation of a purified glucosylceramide and ceramide from shiitake mushroom.

Ingestion of plant and fungal glucosylceramides is known to reduce colon carcinogenesis and skin barrier damage in mice and humans. However, such effects in animal experiments have not been revealed for plant and fungal ceramides because the content of ceramides contained in plants and fungi is so low that the large amount required for animal experiments is difficult to obtain. Noting that the fungus shiitake mushroom (Lentinula edodes) is rich in a glucosylceramide, (4E,8E)-N-d-2'-hydroxypalmitoyl-1-O-ß-d-glucopyranosyl-9-methyl-4,8-sphingadienine [Glc-d19:2(4E,8E,9Me)-h16:0], we developed a new method to purify this fungal glucosylceramide using ethanol precipitation and high-performance liquid chromatography. We also developed a new method to produce large amounts of a ceramide [d19:2(4E,8E,9Me)-h16:0] from this purified glucosylceramide using human glycoside hydrolase family 30 glucocerebrosidase (imiglucerase). These methods will be useful for elucidating the physiological function by ingestion of fungal ceramides in animal experiments.

Platelet volume indices correlate to severity of heart failure and have prognostic value for both cardiac and thrombotic events in patients with congenital heart disease.

Patients with heart failure (HF) reportedly have activated platelets with increased platelet distribution width (PDW) and mean platelet volume (MPV), which lead to thrombotic events. These platelet indices are easily measured by routine blood tests and have been proposed as potential markers of cardiac events. We performed the present study to clarify whether platelet indices correlate to the severity of HF and to the prognosis of patients with congenital heart disease (CHD). We performed a retrospective single-center study including 400 patients with CHD [median age, 34 years (range 12-76); 49% males] hospitalized between 2014 and 2017. We assessed their clinical data, correlation between platelet indices and severity of HF, and prognosis of HF-related hospitalization and thrombus formation. In multivariate analysis, a significant correlation was found between PDW and logBNP (log-transformed brain natriuretic peptide; r = 0.30, p < 0.001), as well as between MPV and logBNP (r = 0.24, p < 0.001). After treatment for heart failure, a significant reduction was found in PDW (average value before treatment: 14.2; after: 13.2, p = 0.017). In multivariate logistic regression analysis, PDW [hazard ratio (HR) 1.365; 95% confidence interval (CI) 1.005-1.768] and MPV (HR 1.472; 95% CI 1.055-2.052) were predictors of HF-related hospitalization. Similarly, PDW (HR 1.998; 95% CI 1.461-2.630) and MPV (HR 1.792; 95% CI 1.155-2.781) were predictors of thrombus formation. Platelet volume indices correlate to severity of heart failure and have prognostic value for both cardiac and thrombotic events in patients with CHD.

Alteration of Oral and Perioral Soft Tissue in Mice following Incisor Tooth Extraction.

Oral and perioral soft tissues cooperate with other oral and pharyngeal organs to facilitate mastication and swallowing. It is essential for these tissues to maintain their morphology for efficient function. Recently, it was reported that the morphology of oral and perioral soft tissue can be altered by aging or orthodontic treatment. However, it remains unclear whether tooth loss can alter these tissues' morphology. This study examined whether tooth loss could alter lip morphology. First, an analysis of human anatomy suggested that tooth loss altered lip morphology. Next, a murine model of tooth loss was established by extracting an incisor; micro-computed tomography revealed that a new bone replaced the extraction socket. Body weight was significantly lower in the tooth loss (UH) group than in the non-extraction control (NH) group. The upper lip showed a greater degree of morphological variation in the UH group. Proteomic analysis and immunohistochemical staining of the upper lip illustrated that S100A8/9 expression was higher in the UH group, suggesting that tooth loss induced lip inflammation. Finally, soft-diet feeding improved lip deformity associated with tooth loss, but not inflammation. Therefore, soft-diet feeding is essential for preventing lip morphological changes after tooth loss.

A novel loop-mediated isothermal amplification-based genotyping method and its application for identifying proprotein convertase subtilisin/kexin type 9 variants in familial hypercholesterolemia.

BACKGROUND: Proprotein convertase subtilisin/kexin type 9 (PCSK9) plays a key role in regulating low-density lipoprotein levels in plasma. While PCSK9 variants are causatively associated with familial hypercholesterolemia (FH), additional genotyping methods for FH targeting PCSK9 variants are required in a clinical setting. Loop-mediated isothermal amplification (LAMP) is a unique amplification method that amplifies a target gene under isothermal conditions (60-65 °C). However, a robust standardized method has not yet been established for LAMP-based genetic screening tests for genetic diseases, including FH. The present study aimed to develop a novel modification of the LAMP method designed to genotype single nucleotide variants (SNVs) and to apply it for the detection of PCSK9 variants. METHODS: Using short quenching probes (≤ 10 nucleotides) for the loop structures of LAMP amplicons, accurate detection of SNVs was verified separately for each allele, without any additional procedures, within 3 h. The diagnostic performance of this method in detecting PCSK9 variants was validated in FH patients. RESULTS: All PCSK9 variants tested via conventional sequencing in FH patients were successfully detected using this novel LAMP method. CONCLUSIONS: We developed a LAMP-based genotyping method to detect PCSK9 variants in FH. Compared to conventional sequencing, our genotyping method is relatively convenient and time-efficient and is suitable for the screening of FH in clinical settings. Future studies on various genes are also warranted.

Nationwide multicentre comparison of preoperative biometry and predictability of cataract surgery in Japan.

AIM: To compare the preoperative biometric data and the refractive accuracy of cataract surgery among major surgical sites in a nationwide multicentre study. METHODS: We prospectively obtained the preoperative biometric data of 2143 eyes of 2143 consecutive patients undergoing standard cataract surgery at major 12 facilities and compared the preoperative biometry as well as the postoperative refractive accuracy among them. RESULTS: We found significant differences in most preoperative variables, such as axial length (one-way analysis of variance, p=0.003), anterior chamber depth (p<0.001), lens thickness (p<0.001) and central corneal thickness (p<0.001), except for mean keratometry (p=0.587) and corneal astigmatism (p=0.304), among the 12 surgical sites. The prediction error using the Sanders-Retzlaff-Kraff/Theoretical (SRK/T formula was significantly more hyperopic than that using the Barrett Universal II formula (paired t-test, p<0.001). The absolute error using the SRK/T formula was significantly larger than that using the Barrett Universal II formula (p=0.016). The prediction error using the SRK/T formula was significantly more hyperopic than that using the Barrett Universal II formula at 10 of 12 institutions, but significantly more myopic at one institution. The absolute error using the SRK/T formula was significantly larger than that using the Barrett Universal II formula at 4 of 12 institutions but significantly smaller at two institutions. CONCLUSIONS: Regional divergences of the preoperative biometry were not necessarily negligible, and the optimised intraocular lens power calculation formula was individually different among the 12 facilities. Our findings highlight the importance of individual optimisation of these formulas at each facility, especially in consideration of these biometric variations.Trial registration numberClinical Trial Registry; 000039976.