Prevalence of lower urinary tract symptoms in children with early-treated infantile-onset Pompe disease: A single-centre cross-sectional study.

AIM: To evaluate lower urinary tract symptoms (LUTS) in children with infantile-onset Pompe disease (IOPD) who received early treatment. METHODS: Pompe disease (PD), or glycogen storage disease II is a rare autosomal recessive lysosomal storage disease that affects multiple organ systems. To our knowledge, only one study has focused on the relationship between LUTS and incontinence in children with PD. This cross-sectional study was conducted from August 2019 through March 2021 and children with IOPD, who had received early and regular enzyme replacement therapy, were enrolled. Participants or their parents completed the Dysfunctional Voiding Scoring System (DVSS) questionnaire. All children underwent uroflowmetry and postvoid residual urine measurements. Fourteen children (age, 4-9 years) with IOPD were enrolled. RESULTS: Ten patients (71.4%) had abnormal uroflow curves. In addition, results of the DVSS revealed that approximately half (42.9%) of our IOPD patients had voiding dysfunction, with urinary incontinence as the most common symptom (64.3%, 9/14). No significant correlations were found between LUTS and uroflow curves in children with IOPD. CONCLUSIONS: The frequency of LUTS and lower urinary tract dysfunction noted on uroflowmetry should encourage pediatricians to actively identify IOPD patients with LUTS, regardless of the timing and frequency of their treatments, and refer them to a urologist for further evaluation and appropriate treatment.

Reproductive outcomes of microdissection testicular sperm extraction in hypogonadotropic hypogonadal azoospermic men after gonadotropin therapy.

PURPOSE: Male infertility caused by hypogonadotropic hypogonadism (HH) is not common. The main treatment is gonadotropins for 12 months or longer. If the patient is still azoospermic, conventional or microdissection testicular sperm extraction (mTESE) may further help in sperm retrieval. We aimed to analyze the fertility outcomes of HH men treated at our institute. METHODS: From 2008 to 2020, infertile men with hormone profile showing HH were enrolled. Gonadotropin therapy was prescribed if parenthood was being considered. Assisted reproductive technology was available to help patients attain fertility depending on the results of sperm analysis. Patient outcomes, including sperm retrieval, pregnancy and live birth rates, were analyzed. RESULTS: Seventeen initially azoospermic patients were administered gonadotropins for an average of 11.1 months, and sperm was subsequently found in the ejaculate of seven patients (41%). mTESE was performed on the other ten (59%) who were still azoospermic. For these 10 patients, they had collectively undergone an average 12.1 months (range 6-23 months) of gonadotropin therapy. Sperm was retrieved in nine (90.0%) cases. After 11 cycles of TESE-ICSI, six (54.5%) successful pregnancies were recorded, resulting in five (55.6%) cases with live-born babies, including two sets of twins, and one case of missed abortion at 9 weeks of gestation. CONCLUSION: Gonadotropin therapy reversed azoospermia in a portion of the HH male patients studied. Of men who were still azoospermic after gonadotropin treatment, a majority could still have testicular sperm retrieved by mTESE for use in assisted reproductive technology, subsequently resulting in live births.

The impact of low-intensity extracorporeal shock waves on testicular spermatogenesis demonstrated in a rat model.

BACKGROUND: In rodent models, low-intensity extracorporeal shock wave therapy has been shown to negatively impact semen concentration after treatment on the penis, implying that the reproductive system in close proximity may be indirectly affected by this modality. We hypothesized that shock waves are detrimental to spermatogenesis, and the aim of this study was to evaluate the effect of shock waves on spermatogenesis after direct shockwave treatment on testes using different energy settings. METHODS: Twenty-five male Sprague Dawley rats, 8 weeks old, were divided into five groups, including one control group and four treatment groups each treated using shock waves of different intensities. All rats in the treatment groups received 2000 shocks on the left testis twice a week for 4 weeks, with shock wave intensity and frequency varied by treatment group: 0.1 mJ/mm 2 at 4 Hz for Group A, 0.15 mJ/mm 2 at 4 Hz for Group B, 0.35 mJ/mm 2 at 4 Hz for Group C, and 0.55mJ/mm 2 at 3 Hz for Group D. At the end of the experiment, sperm collected from the epididymis was evaluated for concentration and motility. Testicular spermatogenesis, the apoptotic index of germ cells, and the expression of a meiotic-specific gene were also analyzed. RESULTS: The treatment group receiving shock wave intensity at 0.55 mJ/mm 2 showed a significant decrease in sperm concentration, motility, and Johnsen score as compared to other groups. The apoptotic index of spermatogenic cells increased as the intensity of the shock wave treatment escalated, and reach a statistically significant difference at 4 weeks posttreatment. Treating testes with intensity levels of 0.55 mJ/mm 2 at 3 Hz interfere with the quality or quantity of spermatogenesis and also increases in spermatogenic cell apoptosis, whereas the expression of the SYCP3 gene significantly decreased after treatment with intensity levels of 0.10 mJ/mm 2 , 0.15 mJ/mm 2 , and 0.35 mJ/mm 2 at 4 Hz. CONCLUSION: Treating testes with intensity levels of 0.55 mJ/mm 2 at 3 Hz interfere with the quality or quantity of spermatogenesis and also increases spermatogenic cell apoptosis, whereas the expression of the SYCP3 gene significantly decreased after treatment with intensity levels of 0.10 mJ/mm 2 , 0.15 mJ/mm 2 , and 0.35 mJ/mm 2 at 4 Hz.

Development and characterization of 20 new polymorphic microsatellite markers from Mangifera indica (Anacardiaceae).

PREMISE OF THE STUDY: Twenty microsatellite loci for mango (Mangifera indica), an important commercial fruit tree in East Asia, were developed to evaluate the genetic diversity and identification of cultivars. METHODS AND RESULTS: The 20 new microsatellite markers were isolated from mango using a magnetic bead enrichment method, and polymorphisms were identified in 22 mango cultivars. The number of alleles ranged from one to nine, with expected heterozygosity ranging from 0 to 0.826. The polymorphism information content ranged from 0 to 0.756 with a mean of 0.525. CONCLUSIONS: These new microsatellite loci should be useful and convenient for further studies of the genetic diversity and identification of cultivars in mango.

Oncogenic Roles of Polycomb Repressive Complex 2 in Bladder Cancer and Upper Tract Urothelial Carcinoma.

Cancers of the urinary tract are one of the most common malignancies worldwide, causing high morbidity and mortality, and representing a social burden. Upper tract urothelial carcinoma (UTUC) accounts for 5−10% of urinary tract cancers, and its oncogenic mechanisms remain elusive. We postulated that cancers of the lower and the upper urinary tract may share some important oncogenic mechanisms. Therefore, the oncogenic mechanisms discovered in the lower urinary tract may guide the investigation of molecular mechanisms in the upper urinary tract. Based on this strategy, we revisited a high-quality transcriptome dataset of 510 patients with non-muscle invasive bladder cancer (NMIBC), and performed an innovative gene set enrichment analysis of the transcriptome. We discovered that the epigenetic regulation of polycomb repressive complex 2 (PRC2) is responsible for the recurrence and progression of lower-track urinary cancers. Additionally, a PRC2-related gene signature model was discovered to be effective in classifying bladder cancer patients with distinct susceptibility of subsequent recurrence and progression (log-rank p < 0.001 and = 0.001, respectively). We continued to discover that the same model can differentiate stage T3 UTUC patients from stage Ta/T1 patients (p = 0.026). Immunohistochemical staining revealed the presence of PRC2 components (EZH2, EED, and SUZ12) and methylated PRC2 substrates (H3K27me3) in the archived UTUC tissues. The H3K27me3 exhibited higher intensity and area intensity product in stage T3 UTUC tissues than in stage Ta/T1 tissues (p = 0.006 and 0.015, respectively), implicating stronger PRC2 activity in advanced UTUC. The relationship between H3K27 methylation and gene expression is examined using correlations. The H3K27me3 abundance is positively correlated with the expression levels of CDC26, RP11-2B6, MAPK1IP1L, SFR1, RP11-196B3, CDK5RAP2, ANXA5, STX11, PSMD5, and FGFRL1. It is also negatively correlated with CNPY2, KB-1208A12, RP11-175B9, ZNF692, RANP8, RP11-245C17, TMEM266, FBXW9, SUGT1P2, and PRH1. In conclusion, PRC2 and its epigenetic effects are major oncogenic mechanisms underlying both bladder cancer and UTUC. The epigenetically regulated genes of PRC2 in urothelial carcinoma were also elucidated using correlation statistics.

The comparison of different BCG strains in the intravesical treatment of non-muscle invasive urothelial carcinoma of urinary bladder-A real-world practice.

BACKGROUND: Bacillus Calmette-Guérin (BCG) has been well recognized as the first-line intravesical therapy for high-risk non-muscle-invasive bladder cancer (NMIBC). Oncotice, the Tice strain of BCG, serves as a viable alternative to the Connaught strain owing to the worldwide shortage of the latter. We retrospectively compared these two strains in terms of efficacy and adverse effects (AE) in patients who underwent at least one maintenance course after induction. METHODS: In this single-institution, retrospective study, patients diagnosed with NMIBC who were administered either Connaught or Tice intravesical therapy were enrolled. Recurrence was defined as the reappearance of urothelial carcinoma. Progression was defined as stage/grade advance, metastasis, or cancer-related death. The primary outcomes were recurrence-free survival (RFS) and progression-free survival (PFS), and the secondary outcome was AE. RESULTS: A total of 76 and 84 patients receiving Tice and Connaught, respectively were enrolled. The median follow-up periods for the Tice and Connaught groups were 32.0 months (range, 7-69 months) and 81.5 months (range, 9-154 months), respectively. Kaplan-Meier method showed no intergroup difference with regard to 3-year RFS and PFS. On Cox multivariate regression analysis, Tice was a significant predictor for inferior PFS (HR = 5.30; 95% CI, 1.11-25.29; p = 0.036). The AE incidence was 38.3% in the Connaught group and 25.0% in the Tice group (p = 0.079). CONCLUSION: Tice and Connaught were comparable in terms of RFS, PFS, and AE for patients with NMIBC accepting BCG induction and at least one maintenance course in our real-world practice. However, Tice was a predictor of inferior PFS on multivariate analysis.

Simple and specific dual-wavelength excitable dye staining for glycoprotein detection in polyacrylamide gels and its application in glycoproteomics.

In this study, a commercially available fluorescent dye, Lissamine rhodamine B sulfonyl hydrazine (LRSH), was designed to specifically stain the glycoproteins in polyacrylamide gels. Through the periodate/Schiff base mechanism, the fluorescent dye readily attaches to glycoproteins and the fluorescence can be simultaneously observed under either 305 nm or 532 nm excitation therefore, the dye-stained glycoproteins can be detected under a regular UV transilluminator or a more elegant laser-based gel scanner. The specificity and detection limit were examined using a standard protein mixture in polyacrylamide gels in this study. The application of this glycoprotein stain dye was further demonstrated using pregnancy urine samples. The fluorescent spots were further digested in gel and their identities confirmed through LC-MS/MS analysis and database searching. In addition, the N-glycosylation sites of LRSH-labeled uromodulin were readily mapped via in-gel PNGaseF deglycosylation and LC-MS/MS analysis, which indicated that this fluorescent dye labeling does not interfere with enzymatic deglycosylation. Hence, the application of this simple and specific dual-wavelength excitable dye staining in current glycoproteome research is promising.

Fortified S-Allyl L-Cysteine: Animal Safety, Effect on Retinal Ischemia, and Role of Wnt in the Underlying Therapeutic Mechanism.

PURPOSE: Retinal ischemia is a medical condition associated with numerous retinal vascular disorders, such as age-related macular degeneration, glaucoma, and diabetic retinopathy. This in vitro cell and in vivo animal study investigated not only the protective effect of S-allyl L-cysteine (SAC, an active component of garlic) against retinal ischemia but also its associated protective mechanisms. METHODS: Retinal ischemia was mimicked by raising the intraocular pressure to 120 mmHg for 1 hour in one eye. The effects of pre-/postischemic administration of vehicle vs. SAC 0.18 mg vs. SAC 0.018 mg vs. SAC 0.0018 mg treatments on retina cells were evaluated through cellular viability (MTT assay), flash electroretinograms (ERGs), and fluorogold retrograde labelling (retinal ganglion cell (RGC) counting). Also, protein immunoblot was utilized to assess the role of Wnt, hypoxia inducible factor (HIF)-1α, and vascular endothelium factor (VEGF) in the proposed anti-ischemic mechanism. Lastly, the safety of drug consumption was investigated for changes in the animal's body weight, ERG waves, and blood biochemical parameters (e.g., glucose levels). RESULTS: The characteristic ischemic changes including significant reduction in ERG b-wave ratio and RGC number were significantly counteracted by pre- and postischemic low dose of SAC. Additionally, ischemia-induced overexpression of Wnt/HIF-1α/VEGF protein was ameliorated significantly by preischemic low dose of SAC. In terms of the animal safety, no significant body weight and electrophysiological differences were observed among defined different concentrations of SAC without following ischemia. In low SAC dosage and vehicle groups, various blood biochemical parameters were normal; however, high and medium concentrations of SAC significantly lowered the levels of uric acid, Hb, and MCHC. CONCLUSION: This study shows that preischemic administration of low SAC dosage has been proved to be safe and most effective against rat retinal ischemia electrophysiologically and/or histopathologically. Moreover, counteracting the ischemia-induced overexpression of Wnt/HIF-1α/VEGF might presently explain SAC's anti-ischemic mechanism.

Emodin protected against retinal ischemia insulted neurons through the downregulation of protein overexpression of ß-catenin and vascular endothelium factor.

BACKGROUND: Emodin has been proved to have an anti-ischemic effect on the brain, however little research has been done on its effect on vision-threatening retinal ischemia. Thus, an investigation was carried out into the hypothetical efficacy of emodin against retinal ischemia and the role of ß-catenin/VEGF in its therapeutic mechanism. METHODS: Retinal ischemia, followed by reperfusion (IR), was inducted by raising the intraocular pressure of a Wistar rat's eye to 120 mmHg for 60 min. Additionally, pre-ischemic/post-ischemic intravitreous injections of emodin (4, 10 and 20 µM) or vehicle were carried out on the eye with retinal ischemia. MTT assay, electroretinograms, cresyl violet staining retinal thickness measurements, and fluorogold retrograde labelling of retinal ganglion cells (RGCs) as well as Western blotting were carried out. RESULTS: Cultured RGC-5 cells subjected to oxygen glucose deprivation (OGD) were used to confirm the effective concentrations of emodin (administered 1 h pre-OGD, pre-OGD emodin). The most effective and significant (P = 0.04) dose of pre-OGD emodin was observed at 0.5 µM (cell viability: 47.52 ± 3.99%) as compared to pre-OGD vehicle treatment group (38.30 ± 2.51%). Furthermore, pre-ischemic intravitreous injection of 20 µM emodin (Emo20 + IR = 0.99 ± 0.18, P < 0.001) significantly attenuated the ischemia induced reduction in ERG b-wave amplitude, as compared to pre-ischemic intravitreous vehicle (Vehicle+IR = 0.04 ± 0.02). Post-ischemic intravitreous 20 µM emodin also significantly (P < 0.001) attenuated the ischemia associated b-wave reduction (IR + Em20 = 0.24 ± 0.09). Compared with pre-ischemic intravitreous vehicle (Vehicle+IR; whole retina thickness = 71.80 ± 1.08 µm; inner retina thickness = 20.97 ± 0.85 µm; RGC =2069.12 ± 212.82/0.17mm2), the significant (P < 0.001) protective effect was also present with pre-ischemic administration of emodin. This was shown by observing cresyl violet stained retinal thickness (Emo20 + IR: whole retina = 170.10 ± 0.10 µm; inner retina = 70.65 ± 2.06 µm) and retrograde fluorogold immunolabeled RGC density (4623.53 ± 179.48/0.17mm2). As compared to the normal control (the ratio of ß-catenin/VEGF to ß-actin was set as 1 in the Sham group), the ß-catenin/VEGF protein level significantly (P < 0.001) increased after retinal ischemia and when pre-ischemic intravitreous vehicle (Vehicle+IR = 1.64 ± 0.14/7.67 ± 2.57) was carried out. However, these elevations were significantly (P = 0.02) attenuated by treatment with emodin 20 µM (Emo20 + IR = 1.00 ± 0.19/1.23 ± 0.44). CONCLUSIONS: The present results suggest that emodin might protect against retinal ischemia insulted neurons such as RGCs by significantly downregulating the upregulation of ß-catenin/VEGF protein that occurs during ischemia.

Sonography of the shoulder in hemiplegic patients undergoing rehabilitation after a recent stroke.

PURPOSE: To examine the hemiplegic shoulders for soft-tissue injury by musculoskeletal sonography and to determine the relationship between the motor functions of the upper extremity and these injuries, which play an important role in hemiplegic shoulder pain and may impede rehabilitation. METHODS: The following characteristics of 34 acute stroke patients were recorded: age, gender, height, body weight, side of hemiplegia, type and duration of stroke, Brunnstrom stage, subluxation, and degree of spasticity of the upper extremity. On the basis of the Brunnstrom stage, the patients were divided into 2 groups. Patients with stages I, II, or III were categorized under the lower Brunnstrom stage (LBS) group (n = 21), and those with stages IV, V, or VI were allocated to the higher Brunnstrom stage (HBS) group (n = 13). Both shoulders of each patient were examined by musculoskeletal sonography with a 5-10-MHz linear transducer on 2 separate occasions (i.e., at admission and 2 weeks after rehabilitation). RESULTS: With the exception of age, there were no significant differences in the demographic and clinical characteristics of the patients in the 2 groups. Shoulder musculoskeletal sonography revealed soft-tissue injury in 7 patients (33%) and 15 patients (71%) in the LBS group at admission and 2 weeks after rehabilitation, respectively (p < 0.05), and in 4 patients (31%) in the HBS group both at admission and 2 weeks after rehabilitation. CONCLUSIONS: Acute stroke patients with poor upper limb motor functions are more prone to soft-tissue injury of the shoulder during rehabilitation.