Nephrotic syndrome due to minimal-change disease superimposed on anti-glomerular basement membrane antibody positive glomerulonephritis; a case report.

BACKGROUND: The prognosis for renal function in anti-GBM glomerulonephritis (anti-GBM GN) is extremely poor, and when renal impairment progresses severely, it is difficult to expect improvement. In addition, it is also known that once the disease activity can be controlled by aggressive treatment, its recurrence is rare. We experienced an anti-GBM GN that improved from severe renal dysfunction and relapsed. A possible cause was the superimpose of nephrotic syndrome due to minimal change disease (MCD). CASE PRESENTATION: A 30-year-old man was admitted to our hospital because of general malaise, fever, oliguria and renal dysfunction. The patient's laboratory data showed serum creatinine as high as 6.6 mg/dl, and severe inflammation (C-reactive protein 20.6 mg/dl). Anti-glomerular basement membrane antibody (anti-GBM Ab) was detected in his serum, which led to the diagnosis of anti-GBM GN. Treatment was initiated with high-dose glucocorticoid (GC) and plasma exchange therapy (PE), and the patient's renal function and oliguria improved rapidly and he was discharged 40 days after admission. Renal biopsy findings showed cellular crescents associated with linear IgG depositions along the glomerular tufts compatible with anti-GBM GN, but only about one-third of the glomeruli was involved, suggesting that it still remains an early stage of the disease. However, 2 months after discharge, he had a relapse and was readmitted due to severe proteinuria with positive anti-GBM Ab. On the second admission, after high-dose GC and PE combined with intravenous cyclophosphamide, and remission was achieved. Despite the relatively minor renal biopsy findings, the patient showed rapid renal dysfunction and relatively rapid improvement with our treatment. Electron microscopy of the renal biopsy tissue showed significant foot process effacement on podocytes in the apparently normal glomeruli, without electron dense deposits. CONCLUSION: On the basis of clinical course and renal pathology, it is suggested that the present case was a rare complication of an early stage of anti-GBM GN and minimal change nephrotic syndrome. Although the simultaneous development of anti-GBM GN and MCD with anti-GBM antibody is unclear, it might have been precipitated by influenza infection or some unknown factor.

Effect of incomplete blinking on tear film stability.

PURPOSE: The purpose of this study is to assess changes in tear film stability caused by incomplete blinking. METHODS: Eleven subjects (mean age, 21.3 years) participated in this study. All subjects had a visual acuity of 20/20 or better and normal ocular health. The subjects were asked to play a game for 60 min on a personal computer as part of a visual display terminal (VDT) experiment. Each subject's blinking was observed by a Web camera that was attached to the top of the display. Every 15 min, the VDT experiment was interrupted for measurement. An RT-7000 (Tomey Co., Ltd., Nagoya, Japan) was used to measure ring breakup time as a parameter of tear film stability. An OPD-Scan II ARK-10000 (NIDEK Co., Ltd., Aichi, Japan) was used to measure corneal aberrations. RESULTS: Although the total blink rate changed very little, the complete and incomplete blink rates fluctuated during the VDT experiment. Both types were plotted along symmetrical cubic approximation curves. Noninvasive (ring) breakup time at 30 min (4.33 ± 2.57 s) was significantly shorter (p < 0.01) than that at baseline before the VDT experiment (8.62 ± 1.54 s). After 30 min, the incomplete blink rate began decreasing (fewer incomplete blinks), whereas the complete blink rate began increasing. Ring breakup time increased (improved) after 45 min; however, the incomplete blink rate began to increase again after approximately 50 min. CONCLUSIONS: Even if the total blink rate decreases, the tear film remains stable so long as almost all blinks are complete. The incomplete blinking contributes to tear film instability and is variable with prolonged VDT exposure. Our study indicated that the tear film stability was determined by blinking quality, and the predominance of blinking type relates to tear film stability.

Corrigendum: Estimation of subjective quality of life in schizophrenic patients using speech features.

[This corrects the article DOI: 10.3389/fresc.2023.1121034.].

Estimation of subjective quality of life in schizophrenic patients using speech features.

Introduction: Patients with schizophrenia experience the most prolonged hospital stay in Japan. Also, the high re-hospitalization rate affects their quality of life (QoL). Despite being an effective predictor of treatment, QoL has not been widely utilized due to time constraints and lack of interest. As such, this study aimed to estimate the schizophrenic patients' subjective quality of life using speech features. Specifically, this study uses speech from patients with schizophrenia to estimate the subscale scores, which measure the subjective QoL of the patients. The objectives were to (1) estimate the subscale scores from different patients or cross-sectional measurements, and 2) estimate the subscale scores from the same patient in different periods or longitudinal measurements. Methods: A conversational agent was built to record the responses of 18 schizophrenic patients on the Japanese Schizophrenia Quality of Life Scale (JSQLS) with three subscales: "Psychosocial," "Motivation and Energy," and "Symptoms and Side-effects." These three subscales were used as objective variables. On the other hand, the speech features during measurement (Chromagram, Mel spectrogram, Mel-Frequency Cepstrum Coefficient) were used as explanatory variables. For the first objective, a trained model estimated the subscale scores for the 18 subjects using the Nested Cross-validation (CV) method. For the second objective, six of the 18 subjects were measured twice. Then, another trained model estimated the subscale scores for the second time using the 18 subjects' data as training data. Ten different machine learning algorithms were used in this study, and the errors of the learned models were compared. Results and Discussion: The results showed that the mean RMSE of the cross-sectional measurement was 13.433, with k-Nearest Neighbors as the best model. Meanwhile, the mean RMSE of the longitudinal measurement was 13.301, using Random Forest as the best. RMSE of less than 10 suggests that the estimated subscale scores using speech features were close to the actual JSQLS subscale scores. Ten out of 18 subjects were estimated with an RMSE of less than 10 for cross-sectional measurement. Meanwhile, five out of six had the same observation for longitudinal measurement. Future studies using a larger number of subjects and the development of more personalized models based on longitudinal measurements are needed to apply the results to telemedicine for continuous monitoring of QoL.

Prevention of Surgery-Induced Dry Eye by Diquafosol Eyedrops after Femtosecond Laser-Assisted Cataract Surgery.

Purpose: To analyze the protective effects of diquafosol eyedrops on the ocular surface following femtosecond laser-assisted cataract surgery (FLACS). Design: A prospective, randomized contralateral study. Methods: Bilateral FLACS with a trifocal IOL (PanOptix) implantation was performed in 40 eyes in 20 patients (10 males, 10 females, average age 68.8 ± 6.3 years old). Patients received 3% diquafosol eyedrops six times daily in one randomly chosen eye (diquafosol group), and physiological saline six times a day in the other eye (control group). Other medication included 1.5% levofloxacin, 0.1% dexamethasone and 0.1% diclofenac three times daily in both eyes. The pre and post-operative tear break-up time (BUT), superficial punctate keratopathy (SPK) scores and visual function were compared between both eyes, and all patients answered the dry-eye-related quality of life score (DEQS) questionnaire. Results: The BUT between groups was similar pre-operatively and on the first day post-op; however, the BUT was statistically longer in the diquafosol group compared to saline at 1 week (5.5/3.7 s) and 2 weeks (4.8/3.0 s) (p < 0.05). There was no difference in the SPK score, best corrected distance visual acuity, tear meniscus height, contrast sensitivity, DEQS and Schirmer test at all time points. Spherical aberration was statistically lower in the diquafosol group at 1 week. The protective effects of diquafosol on the BUT was more pronounced in patients with a pre-operative BUT of less than 5 s compared with those with a BUT longer than 6 s. Conclusions: Diquafosol eyedrops prevented the shortening of the BUT following FLACS, even in patients with short pre-operative BUT values.

Efficacy of Femtosecond Laser-Assisted Cataract Surgery for Cataracts due to Atopic Dermatitis.

We retrospectively evaluated the efficacy and safety of femtosecond laser-assisted cataract surgery (FLACS) for cataracts due to atopic dermatitis, which are often complicated by intumescent white cataract (IWC) and subcapsular fibrosis. Thirty-seven eyes of 30 cataract patients diagnosed with atopic dermatitis were included in the study. Nine eyes had IWC, and 13 eyes had anterior subcapsular fibrosis characteristic of atopic cataracts. Free-floating capsulotomy was achieved in 32 eyes (86%). Three eyes with fibrosis extending across the line of capsulotomy required manual excision. Incomplete capsulotomies due to anterior capsular tags were present in 4 eyes in the IWC group, which was significantly higher compared to non-IWC cases (p < 0.05). Radial anterior capsular tear, vitreous loss, and intraocular lens dislocation did not occur in any of the cases. FLACS can be performed safely in atopic cataract despite the presence of anterior subcapsular fibrosis and/or IWC.

Prevalence of strabismus in patients with pathologic myopia.

BACKGROUND: To determine the prevalence and clinical features of strabismus in patients with pathologic myopia. METHODS: Medical records of a total of 636 highly myopic patients were retrospectively reviewed. Pathologic myopia was defined as spherical equivalent (SE) of at least -8D, or axial length >26.5 mm in patients older than 9 years, <-4D in those younger than 5 years, <-6D in those aged from 6 to 8 years. Myopic refractive degree, axial length measurements, best-corrected visual acuity and eye position were then analyzed. RESULTS: Among 636 patients with pathologic myopia, 520 (81.8%) had orthophoria, 85 (13.4%) had exotropia and 31 (4.9%) had esotropia at near distance. At long distance, 499 (86.5%) had orthophoria, 51 (8.8%) had exotropia and 27 (4.7%) had esotropia. Vertical heterotropia was seen in 103 patients (16.2%). The mean axial length was significantly longer and the mean age was higher in esotropia than orthophoria and in patients with vertical heterotropia than without vertical heterotropia. There were 16 patients with myopic strabismus fixus or acquired progressive esotropia. CONCLUSIONS: This study confirmed the relatively high prevalence of horizontal and vertical strabismus in patients with pathologic myopia.

Effect of oral administration of clinically relevant doses of dexamethasone on regulation of cytochrome P450 subfamilies in hepatic microsomes from dogs and rats.

OBJECTIVE: To evaluate the effect of oral administration of dexamethasone (DEX) at clinically relevant doses on metabolic activities of cytochrome P450 (CYP) isoenzymes in dogs and rats. ANIMALS: 15 healthy 1-year-old male Beagles and 20 healthy 10-week-old male Wistar rats. PROCEDURE: Hepatic microsomes were harvested from dogs treated orally with DEX at 2.5 and 7.5 mg for 5 days and from rats treated orally with DEX at 0.75, 6, and 48 mg/kg for 5 days. 7-ethoxyresorufin, tolbutamide, bufuralol, and midazolam were used as CYP1A, CYP2C, CYP2D, and CYP3A substrates, respectively. Concentrations of metabolites formed by CYPs were measured by use of high-performance liquid chromatography, except for the resorufin concentrations measured by use of a fluorometric method. Reaction velocity-substrate concentration data were analyzed to obtain maximum reaction velocity (Vmax) and Michaelis-Menten constant (Km). RESULTS: Values of Vmax for midazolam 4-hydroxylation were significantly decreased by treatment with DEX at 2.5 and 7.5 mg in dogs, although values of Km were not affected. Values of Vmax for bufuralol 1'-hydroxylation were also decreased by treatment with DEX. In rats, values of Vmax for midazolam 4- hydroxylation were significantly decreased by treatment with DEX at 0.75 and 6 mg/kg but significantly increased at 48 mg/kg. Other reactions were not affected by treatment with DEX. CONCLUSIONS AND CLINICAL RELEVANCE: Our results indicate that DEX downregulates the CYP3A subfamily when administered at clinically relevant doses to dogs. The effect of downregulation of CYP3A in dogs treated with DEX should be considered to avoid adverse effects from coadministration of drugs.

Severe abdominal pain exacerbated by fetal movement is an early sign of the onset of uterine rupture.

OBJECTIVE: Uterine rupture is a rare but serious obstetric complication. However, prediction and diagnosis at an early stage remain difficult. Herein, we report a case of primary uterine rupture found earlier by a specific symptom. CASE REPORT: A 29-year-old patient was scheduled to undergo a cesarean section (CS) due to placenta previa. However, at Week 35, she began experiencing abdominal pain and uterine contractions. Subsequently, she began experiencing severe pain, which was enhanced by fetal movements. An emergency CS was performed due to continuous uncontrollable pain. When the abdominal cavity was opened, we found that much of the amniotic cavity had prolapsed outside the uterus. Despite performing total hysterectomy, both the mother and child had positive clinical courses. Uterine rupture was discovered early because of emergency CS. CONCLUSION: This case suggests that abnormal pain exacerbated by fetal movement can be a characteristic early sign of uterine rupture.

Strong enhancement of recombinant cytosine deaminase activity in Bifidobacterium longum for tumor-targeting enzyme/prodrug therapy.

In our previous studies, a strain of the nonpathogenic, anaerobic, intestinal bacterium, Bifidobacterium longum (B. longum), was found to be localized selectively and to proliferate within solid tumors after systemic administration. In addition, B. longum transformed with the shuttle-plasmid encoding the cytosine deaminase (CD) gene expressed active CD, which deaminated the prodrug 5-fluorocytosine (5-FC) to the anticancer agent 5-fluorouracil (5-FU). We also reported antitumor efficacy with the same plasmid in several animal experiments. In this study, we constructed a novel shuttle-plasmid, pAV001-HU-eCD-M968, which included the mutant CD gene with a mutation at the active site to increase the enzymatic activity. In addition, the plasmid-transformed B. longum produces mutant CD and strongly increased (by 10-fold) its 5-FC to 5-FU enzymatic activity. The use of B. longum harboring the new shuttle-plasmid increases the effectiveness of our enzyme/prodrug strategy.

Expression of periplasmic alpha-amylase of Xanthomonas campestris K-11151 in Escherichia coli and its action on maltose.

A gene encoding the periplasmic alpha-amylase of Xanthomonas campestris K-11151 was cloned into Escherichia coli using pUC19 as a vector. An ORF of 1578 bp was deduced to be the amylase structural gene. The primary structure of the enzyme had little identity with other alpha-amylases, except with the enzyme from Bacillus megaterium. The enzyme was expressed in E. coli from the lac promoter of pUC19 and was found to be transported to the periplasmic space. The expressed enzyme showed the same thermal stability, optimum temperature and substrate specificity as the enzyme from X. campestris. The enzyme formed maltotetraose, but not 6(1)- nor 6(2)-maltosyl-maltose, from maltose by the reverse reaction, and the tetraose was then hydrolysed to maltotriose and glucose. The addition of maltotriose enhanced the production of glucose from maltose. In addition, maltose was formed by the condensation of glucose by the enzyme. Thus, the periplasmic alpha-amylase of X. campestris was shown to produce glucose from maltose by hydrolysing maltotetraose and possibly higher maltooligosaccharides, which were the products of a condensation reaction, as a major pathway, and by direct hydrolysis of maltose as a minor pathway.

Effects of physical training on bone mineral density and bone metabolism.

The purpose of this study was to examine the influences of long-term walking training and walking and jumping training on bone mineral density (BMD) and bone metabolism. Data from 28 healthy premenopausal women was assessed. The subjects were divided into the walking group (WG; 17 women mean+/-SE age 35+/-2 years), and the walking and jumping group (WJG; 11 women mean+/-SE age 39+/-1 years). BMD was measured in the lumbar spine and proximal femur using dual energy X-ray absorptiometry (DXA). As markers of bone metabolism, this study was to measure bone formation markers, bone-alkaline phosphatase (B-ALP: measured by enzyme immunoassay/EIA) and osteocalcin (BGP: by radioimmunoassay/RI) as well as bone resorption markers, parathyroid hormone (PTH: measured by/RI) and type I collagen cross-linked N-telopeptides (NTx: by EIA). Despite the significant decrease in body weight (p<0.05), no corresponding decrease in BMD was observed. Moreover, no significant difference in bone markers BGP, PTH, and NTx was observed. B-ALP was significantly increased (p<0.05) after one year, and the rate of this increase was greater in the WJG than in the WG. It is thus concluded that walking training for one year is beneficial for the promotion of bone formation, and that jumping stimulus maintain BMD effectively.

Targeting a complex transcriptome: the construction of the mouse full-length cDNA encyclopedia.

We report the construction of the mouse full-length cDNA encyclopedia,the most extensive view of a complex transcriptome,on the basis of preparing and sequencing 246 libraries. Before cloning,cDNAs were enriched in full-length by Cap-Trapper,and in most cases,aggressively subtracted/normalized. We have produced 1,442,236 successful 3'-end sequences clustered into 171,144 groups, from which 60,770 clones were fully sequenced cDNAs annotated in the FANTOM-2 annotation. We have also produced 547,149 5' end reads,which clustered into 124,258 groups. Altogether, these cDNAs were further grouped in 70,000 transcriptional units (TU),which represent the best coverage of a transcriptome so far. By monitoring the extent of normalization/subtraction, we define the tentative equivalent coverage (TEC),which was estimated to be equivalent to >12,000,000 ESTs derived from standard libraries. High coverage explains discrepancies between the very large numbers of clusters (and TUs) of this project,which also include non-protein-coding RNAs,and the lower gene number estimation of genome annotations. Altogether,5'-end clusters identify regions that are potential promoters for 8637 known genes and 5'-end clusters suggest the presence of almost 63,000 transcriptional starting points. An estimate of the frequency of polyadenylation signals suggests that at least half of the singletons in the EST set represent real mRNAs. Clones accounting for about half of the predicted TUs await further sequencing. The continued high-discovery rate suggests that the task of transcriptome discovery is not yet complete.