Effects of down-regulated carbonic anhydrase 8 on cell survival and glucose metabolism in human colorectal cancer cell lines.

Carbonic anhydrase 8 (CA8) is a member of the α-carbonic anhydrase family but does not catalyze the reversible hydration of carbon dioxide. In the present study, we examined the effects of CA8 on two human colon cancer cell lines, SW480 and SW620, by suppressing CA8 expression through shRNA knockdown. Our results showed that knockdown of CA8 decreased cell growth and cell mobility in SW620 cells, but not in SW480 cells. In addition, downregulated CA8 resulted in a significant decrease of glucose uptake in both SW480 and SW620 cells. Interestingly, stable downregulation of CA8 decreased phosphofructokinase-1 expression but increased glucose transporter 3 (GLUT3) levels in SW620 cells. However, transient downregulation of CA8 fails to up-regulate GLUT3 expression, indicating that the increased GLUT3 observed in SW620-shCA8 cells is a compensatory effect. In addition, the interaction between CA8 and GLUT3 was evidenced by pull-down and IP assays. On the other hand, we showed that metformin, a first-line drug for type II diabetes patients, significantly inhibited cell migration of SW620 cells, depending on the expressions of CA8 and focal adhesion kinase. Taken together, our data demonstrate that when compared to primary colon cancer SW480 cells, metastatic colon cancer SW620 cells respond differently to downregulated CA8, indicating that CA8 in more aggressive cancer cells may play a more important role in controlling cell survival and metformin response. CA8 may affect glucose metabolism- and cell invasion-related molecules in colon cancer, suggesting that CA8 may be a potential target in future cancer therapy.

Altered glucose metabolism and its association with carbonic anhydrase 8 in Machado-Joseph Disease.

Machado-Joseph disease (MJD), also known as spinocerebellar ataxia type 3 (SCA3), is an autosomal dominant neurodegenerative disease. This disorder is caused by polyglutamine (polyQ)-containing mutant ataxin-3, which tends to misfold and aggregate in neuron cells. We previously demonstrated a protective function of carbonic anhydrase 8 (CA8) in MJD disease models and a decreased glycolytic activity associated with down-regulated CA8 in a human osteosarcoma (OS) cell model. Given that a reduction in body weight accompanied by gait and balance instability was observed in MJD patients and transgenic (Tg) mice, in this study, we aimed to examine whether metabolic defects are associated with MJD and whether CA8 expression is involved in metabolic dysfunction in MJD. Our data first showed that glucose uptake ability decreases in cells harboring mutant ataxin-3, but increases in cells overexpressing CA8. In addition, the expressions of glucose transporter 3 (GLUT3) and phosphofructokinase-1 (PFK1) were significantly decreased in the presence of mutant ataxin-3. Consistently, immunohistochemistry (IHC) showed that GLUT3 was less expressed in cerebella of aged MJD Tg mice, indicating that the dysfunction of GLUT3 may be associated with late-stage disease. On the other hand, transient down-regulation of CA8 revealed decreased expressions of GLUT3 and PFK1 in HEK293 cells harboring wild-type (WT) ataxin-3, but no further reduction of GLUT3 and PFK1 expressions were observed in HEK293 cells harboring mutant ataxin-3. Moreover, immunoprecipitation (IP) and immunofluorescence (IF) demonstrated that interactions exist between ataxin-3, CA8 and GLUT3 in MJD cellular and Tg models. These lines of evidence suggest that CA8 plays an important role in glucose metabolism and has different impacts on cells with or without mutant ataxin-3. Interestingly, the decreased relative abundance of Firmicutes/Bacteroidetes (F/B) ratio in the feces of aged MJD Tg mice coincided with weight loss and metabolic dysfunction in MJD. Taken together, our results are the first to demonstrate the effects of CA8 on glucose metabolism and its involvement in the metabolic defects in MJD disease. Further investigations will be required to clarify the underlying mechanisms for the metabolic defects associated with MJD.

[Critical Care Nursing in Targeted Temperature Management (TTM) After Cardiac Arrest].

Targeted temperature management (TTM) is a complex and sophisticated intensive-care procedure that is included in the American Heart Association guidelines for treating patients who remain unconscious after resuscitation from cardiac arrest. TTM has been demonstrated to reduce brain injury associated with reperfusion after resuscitation and to improve the neurological prognosis in patients with cardiac arrest. The TTM process may be divided into four phases: induction, maintenance, rewarming, and normothermia. The critical element in TTM is the quick lowering and slow raising of body temperature, which should be fine-tuned to maintain temperature stability and minimize variation. Caregivers should monitor the physiological changes caused by core body temperature change closely and manage possible complications such as shivering, hypo- and hyper-glycemia, electrolyte imbalance, skin injury, arrhythmia, and infection. Based on contemporary evidence and clinical experience, this article provides critical care nurses a summary and key points of each stage of TTM when used to take care of resuscitated patients after cardiac arrest. We hope this work may help improve patient safety and quality of care during the TTM procedure.

Expression and Functional Study of Single Mutations of Carbonic Anhydrase 8 in Neuronal Cells.

Carbonic anhydrase 8 (CA8), an isozyme of α-carbonic anhydrases, lacks the ability to catalyze the reversible hydration of CO2 to bicarbonate and proton. Previous studies have shown that single point mutations of CA8, CA8-S100P, and CA8-G162R, are associated with novel syndromes including congenital ataxia and mild cognitive impairment. Our previous results demonstrated that overexpression of wild type (WT) CA8 promoted cell proliferation, neurite outgrowth, anti-apoptosis, invasion and migration abilities in neuronal cells. In this study, we examined the expressions and functions of CA8-S100P and CA8-G162R in neuroblastoma cells lines, compared with those of WT CA8. Our results show that the protein expressions of mutant CA8-S100P and CA8-G162R were significantly decreased in Neuro-2a and SK-N-SH cells. Interestingly, CA8-S100P demonstrated a significant increase in cell proliferation in both Neuro-2a and SK-N-SH cells. However, both CA8 mutations showed significantly decreased effects on cell protection and migration in SK-N-SH cells. Surprisingly, a significant increase of invasive ability was observed in SK-N-SH cells with overexpression of CA8-S100P as compared with those with overexpression of WT CA8 under retinoic acid (RA) treatment. In addition, we found that Neuro-2a cells with overexpression of CA8-S100P and CA8-G162R showed significantly increased neurite outgrowth. Taken together, our data suggest that the expressions of CA8-S100P and CA8-G162R in neuronal cells alter cell morphology, proliferation, mobility and viability; indicating that the homozygous point mutations of CA8 lead to not only the loss of WT CA8 function, but also the gain of novel functions leading to neuromuscular dysfunction.

Data Missingness Patterns in Homicide Datasets: An Applied Test on a Primary Data Set.

Research on homicide missing data conventionally posits a Missing At Random pattern despite the relationship between missing data and clearance. The latter, however, cannot be satisfactorily modeled using variables traditionally available in homicide datasets. For this reason, it has been argued that missingness in homicide data follows a Nonignorable pattern instead. Hence, the use of multiple imputation strategies as recommended in the field for ignorable patterns would thus pose a threat to the validity of results obtained in such a way. This study examines missing data mechanisms by using a set of primary data collected in New Jersey. After comparing Listwise Deletion, Multiple Imputation, Propensity Score Matching, and Log-Multiplicative Association Models, our findings underscore that data in homicide datasets are indeed Missing Not At Random.

Protective roles of carbonic anhydrase 8 in Machado-Joseph Disease.

Machado-Joseph disease (MJD)/Spinocerebellar ataxia type 3 (SCA3) is an inherited neurodegenerative disease that can lead to a regression of motor coordination and muscle control in the extremities. It is known that expansion of CAG repeats encodes abnormally long polyQ in mutant ataxin-3, the disease protein. It is also noted that mutant ataxin-3 interacts with 1,4,5-trisphosphate receptor type 1 (IP3R1) and induces abnormal Ca2+ release. Previously, we have shown a significant increase in the expression of carbonic anhydrase VIII (CA8) in SK-N-SH-MJD78 cells, which are human neuroblastoma cells overexpressing mutant ataxin-3 with 78 glutamine repeats. In the current study, we showed the presence of significantly increased CA8 expression in MJD mouse cerebellum in either early or late disease stage, with a gradual decrease in CA8 expression as the MJD mice naturally aged. By immunofluorescence and immunoprecipitation analysis, we also found that CA8 co-localized and interacted with mutant ataxin-3 in SK-N-SH-MJD78 cells harboring overexpressed CA8 (SK-MJD78-CA8). In addition, we found that SK-MJD78-CA8 cells, as well as cerebellar granule neurons (CGNs) of MJD transgenic (Tg) mouse with overexpressed CA8, were more resistant to reactive oxygen species (ROS) stress than the control cells. Importantly, overexpression of CA8 in SK-MJD78-CA8 cells and in MJD CGNs rescued abnormal Ca2+ release and caused an increase in cell survival. In summary, we demonstrate the protective function of CA8 in MJD disease models and speculate that the declining expression of CA8 following an initial increased expression may be related to the late onset phenomenon of MJD.

Far-infrared Radiation Improves Motor Dysfunction and Neuropathology in Spinocerebellar Ataxia Type 3 Mice.

Spinocerebellar ataxia type 3 (SCA3) is a polyglutamine neurodegenerative disease resulting from the misfolding and accumulation of a pathogenic protein, causing cerebellar dysfunction, and this disease currently has no effective treatments. Far-infrared radiation (FIR) has been found to protect the viability of SCA3 cells by preventing mutant ataxin-3 protein aggregation and promoting autophagy. However, this possible treatment still lacks in vivo evidence. This study assessed the effect of FIR therapy on SCA3 in vivo by using a mouse model over 28 weeks. Control mice carried a healthy wild-type ATXN3 allele that had a polyglutamine tract with 15 CAG repeats (15Q), whereas SCA3 transgenic mice possessed an allele with a pathological polyglutamine tract with expanded 84 CAG (84Q) repeats. The results showed that the 84Q SCA3 mice displayed impaired motor coordination, balance abilities, and gait performance, along with the associated loss of Purkinje cells in the cerebellum, compared with the normal 15Q controls; nevertheless, FIR treatment was sufficient to prevent those defects. FIR significantly improved performance in terms of maximal contact area, stride length, and base support in the forepaws, hindpaws, or both. Moreover, FIR treatment supported the survival of Purkinje cells in the cerebellum and promoted the autophagy, as reflected by the induction of autophagic markers, LC3II and Beclin-1, concomitant with the reduction of p62 and ataxin-3 accumulation in cerebellar Purkinje cells, which might partially contribute to the rescue mechanism. In summary, our results reveal that FIR confers therapeutic effects in an SCA3 transgenic animal model and therefore has considerable potential for future clinical use.

Promoter analysis and transcriptional regulation of human carbonic anhydrase VIII gene in a MERRF disease cell model.

Myoclonic epilepsy with ragged-red fibers (MERRF) is a maternally inherited mitochondrial neuromuscular disease. We previously reported a significant decrease of mRNA and protein levels of nuclear DNA-encoded carbonic anhydrase VIII (CA8) in MERRF cybrids harboring A8344G mutation in mitochondrial DNA (mtDNA). In this study, we established a reporter construct of luciferase gene-carrying hCA8 promoter containing several putative transcription factor-binding sites, including GC-box, AP-2 and TATA-binding element in the 5'flanking region of the hCA8 gene. Using a series of mutated hCA8 promoter constructs, we demonstrated that a proximal GC-box, recognized by Sp1 and other Sp family members, may be a key cis-element functioning at the promoter. Additionally, a significant increase of the hCA8 promoter activity was observed in the wild-type and mutant cybrids with over-expression of eGFP-Sp1, but no detectable increase in the CA8 protein expression. In contrast, over-expression of Flag-Sp1 and Flag-Sp4 significantly increased the hCA8 promoter activity as well as endogenous CA8 protein expression in neuron-like HEK-293 T cells. However, down-regulation of Sp1, but not Sp4, in 293 T cells revealed a significant reduction of CA8 expression, suggesting that Sp1 is a predominant transcription factor for regulation of CA8 activity. Furthermore, our data indicate that chromatin structure may be involved in the expression of hCA8 gene in MERRF cybrids. Taken together, these results suggest that Sp1 transactivates hCA8 gene through the proximal GC box element in the promoter region. The key modulator-responsive factor to the mtDNA mutation and how it may affect nuclear hCA8 gene transcription need further investigations.

Prison Experience and Reoffending: Exploring the Relationship Between Prison Terms, Institutional Treatment, Infractions, and Recidivism for Sex Offenders.

Given that sex offenders have been found to serve longer prison terms compared with other types of violent criminals, it has been suggested that the influence of imprisonment may impact subsequent reoffending. However, institutional factors are often overlooked in risk assessment studies and very few risk assessment instruments include institutional items within their models. The current study explores prison experience explanations for recidivism among convicted sex offenders and indicates that, with respect to time served, both institutional treatment and institutional infractions demonstrate a significant impact. Findings indicate that misconduct in custody was positively associated with revocation and sexual recidivism. Moreover, longer periods of incarceration significantly increase postrelease reoffending for high-risk sex offenders. Policy implications are made regarding further modifications to risk assessment instruments that will take into account institutional risk factors.

Oncogenic roles of carbonic anhydrase 8 in human osteosarcoma cells.

Carbonic anhydrase 8 (CA8), a member of the carbonic anhydrase family, is one of the three isozymes that do not catalyze the reversible hydration of carbon dioxide due to the lack of one important histidine. In the present study, we observed increased expression of CA8 in more aggressive types of human osteosarcoma (OS) cells and found that CA8 expression is correlated with disease stages, such that more intense expression occurs in the disease late stage. We also demonstrated that overexpression of CA8 in human OS (HOS) cells significantly increased cell proliferation both in vitro and in vivo. Downregulated CA8 sensitized cells to apoptotic stress induced by staurosporine and cisplatin, suggesting a specific role of CA8 to protect cells from stresses. In addition, downregulation of CA8 in HOS cells reduced cell invasion and colony formation ability in soft agar and further decreased matrix metalloproteinase 9 and focal adhesion kinase expression, indicating that CA8 might facilitate cancer cell invasion via the activation of FAK-MMP9 signaling. Interestingly, HOS cells with CA8 knockdown showed a significant decrease in glycolytic activity and cell death under glucose withdrawal, further indicating that CA8 may be involved in regulating aerobic glycolysis and enhancing cell viability. Knockdown of CA8 significantly decreased phosphorylated Akt expression suggesting that the oncogenic role of CA8 may be mediated by the regulation of Akt activation through p-Akt induction. Importantly, the inhibition of glycolysis by 2-deoxyglucose sensitized CA8 HOS-CA8-myc cells to cisplatin treatment under low glucose condition, highlighting a new therapeutic option for OS cancer.

Roles of carbonic anhydrase 8 in neuronal cells and zebrafish.

BACKGROUND: Carbonic anhydrase 8 (CA8) is an isozyme of α-carbonic anhydrases (CAs). Previous studies showed that CA8 can be detected in human adult brain, with more intense expression in the cerebellum. Single mutations in CA8 were reported to cause novel syndromes like ataxia, mild mental retardation or the predisposition to quadrupedal gait. METHODS: In the present study, we examine the functions of CA8 in neuronal cell lines, mouse cerebellar granule neurons and zebrafish. RESULTS AND CONCLUSIONS: We demonstrated that overexpression of CA8 in neuronal cells significantly decreased cell death under staurosporine treatment. Moreover, CA8 overexpression significantly increased cell migration and invasion ability in neuronal cells and in mouse cerebellar granule neurons, implicating that CA8 may be involved in neuron motility and oncogenesis. By using zebrafish as an animal model, motor reflection of 3dpf zebrafish embryos was significantly affected after the down-regulation of CA8 through ca8 morpholino. CONCLUSIONS: We concluded that CA8 overexpression desensitizes neuronal cells to STS induced apoptotic stress and increases cell migration and invasion ability in neuronal cells. In addition, down-regulated CA8 decreases neuron mobility in neuronal cells and leads to abnormal calcium release in cerebellar granule neurons. Knockdown of the ca8 gene results in an abnormal movement pattern in zebrafish. GENERAL SIGNIFICANCE: Our findings provide evidence to support that the impaired protective function of CA8 contributes to human neuropathology, and to suggest that zebrafish can be used as an animal model to study the biological functions of human CA8 in vivo.

Effects of carbonic anhydrase-related protein VIII on human cells harbouring an A8344G mitochondrial DNA mutation.

MERRF (myoclonus epilepsy associated with ragged-red fibres) is a maternally inherited mitochondrial encephalomyopathy with various syndromes involving both muscular and nervous systems. The most common mutation in MERRF syndrome, the A8344G mutation in mtDNA, has been associated with severe defects in the respiratory function of mitochondria. In the present study, we show that there is a significant decrease in CA8 (carbonic anhydrase-related protein VIII) in cybrids harbouring the MERRF A8344G mutation. CA8 deficiency and mutations were found to be associated with a distinctive lifelong gait disorder in wdl (Waddles) mice and novel syndromes characterized by cerebellar ataxia and mental retardation in humans. The results of the present study showed that overexpression of CA8 in MERRF cybrids significantly decreased cell death induced by STS (staurosporine) treatment, suggesting a protective function of CA8 in cells harbouring the A8344G mutation of mtDNA. Interestingly, an increase in the formation of LC3-II (microtubule-associated protein 1 light chain 3-II) was found in the cybrids with down-regulated CA8 expression, suggesting that reduced expression of CA8 leads to autophagy activation. Furthermore, cybrids exhibiting down-regulated CA8 showed increased cytosolic Ca2+ signals and reduced levels of phospho-Akt compared with those in the cybrids with overexpressed CA8, indicating that phospho-Akt is involved in the protection of cells by CA8. Our findings suggest that CA8 is involved in the autophagic pathway and may have a protective role in cultured cells from patients with MERRF. Targeting CA8 and the downstream autophagic pathway might help develop therapeutic agents for treatment of MERRF syndrome in the future.

Prognostic factors for successful varicocelectomy to treat varicocele-associated male infertility.

The present study identified prognostic factors for successful varicocelectomy for the treatment of varicocele-induced male infertility. All varicoceles were diagnosed and graded by physical examination and ultrasound. Pre- and postoperative analysis of semen specimens measured sperm density, morphology and motility. 'Responder' and 'non-responder' status was determined by semen analyses at 3, 6 and 12 months postoperatively. Varicocele Grades 1, 2 and 3 were found in 16, 36 and 28 patients, respectively; 49 patients (61.3%) were responders based on improved seminograms. Significant postoperative increases were noted in sperm density (from 18.20 ± 14.76 × 10(6) to 32.36 ± 24.81 × 10(6)mL(-1); P<0.001), sperm morphology (from 57.21 ± 17.35% to 62.66 ± 15.18%; P=0.006) and percentage motility (from 29.89 ± 14.71% to 50.92 ± 19.30%; P<0.001). Multivariate logistic regression indicated that age (odds ratio (OR) 0.56; P<0.001) and preoperative sperm density (OR 1.22; P=0.001) had significant unfavourable and favourable associations, respectively, with the likelihood of successful varicocelectomy. Furthermore, a preoperative sperm density of 12 × 10(6)mL(-1) as a cut-off point was able to predict successful varicocelectomy with a sensitivity of 77.6% and specificity of 77.4% (area under the curve=0.85; P<0.001; 95% confidence interval 0.76-0.92). Age and preoperative sperm density are prognostic factors for successful varicocelectomy. The results of the present study may allow clinicians to predict surgical improvement in fertility in patients with varicocele.

Dialysate cyclophilin A as a predictive marker for historical peritonitis in patients undergoing peritoneal dialysis.

Introduction: No markers have been used to diagnose historical peritoneal dialysis (PD)-related peritonitis. Cyclophilin A (CypA) is associated with glucose toxicity and inflammation. We hypothesize that dialysate CypA can be a marker for historical peritonitis (at least 3 months free from peritonitis). Method: An enzyme-linked immunosorbent assay kit was used to measure the concentration of dialysate CypA. Clinical and laboratory data were collected to correlate with historical peritonitis. Mann-Whitney U test and Chi-square test were used for analysis. Receiver operating characteristic (ROC) analysis was used to evaluate predictive power. Results: Out of a total of 31 patients who had undergone PD for at least 2 years, 18 had no history of PD-related peritonitis, while 13 had experienced PD-related peritonitis at least once. Overall, the patients in this population were in good health (normal white blood cell count, no anemia, normal electrolyte and serum albumin levels). There were no significant differences between patients with and without a history of peritonitis, except for blood white blood cell count (5650.6 ± 1848.4 vs. 7154.6 ± 2056.8, p = 0.032) and dialysate CypA value (24.27 ± 22.715 vs. 54.41 ± 45.63, p = 0.020). In the univariate analysis, only the dialysate CypA level showed a statistically significant association with historical peritonitis (HR = 1.030, 95 % CI = 1.010-1.062, p = 0.046). The AUC for dialysate CypA (>34.83 ng/mL) was 0.748, with a sensitivity of 0.615 and specificity of 0.833. Conclusion: PD peritonitis poses a significant threat to the long-term use of peritoneal dialysis. Based on our study, even in the absence of concurrent infection, dialysate CypA can serve as a predictive marker for historical peritonitis, demonstrating high predictive power along with fair sensitivity and good specificity.

Functional recovery of human cells harbouring the mitochondrial DNA mutation MERRF A8344G via peptide-mediated mitochondrial delivery.

We explored the feasibility of mitochondrial therapy using the cell-penetrating peptide Pep-1 to transfer mitochondrial DNA (mtDNA) between cells and rescue a cybrid cell model of the mitochondrial disease myoclonic epilepsy with ragged-red fibres (MERRF) syndrome. Pep-1-conjugated wild-type mitochondria isolated from parent cybrid cells incorporating a mitochondria-specific tag were used as donors for mitochondrial delivery into MERRF cybrid cells (MitoB2) and mtDNA-depleted Rho-zero cells (Mitoρ°). Forty-eight hours later, translocation of Pep-1-labelled mitochondria into the mitochondrial regions of MitoB2 and Mitoρ° host cells was observed (delivery efficiencies of 77.48 and 82.96%, respectively). These internalized mitochondria were maintained for at least 15 days in both cell types and were accompanied by mitochondrial function recovery and cell survival by preventing mitochondria-dependent cell death. Mitochondrial homeostasis analyses showed that peptide-mediated mitochondrial delivery (PMD) also increased mitochondrial biogenesis in both cell types, but through distinct regulatory pathways involving mitochondrial dynamics. Dramatic decreases in mitofusin-2 (MFN2) and dynamin-related protein 1/fission 1 were observed in MitoB2 cells, while Mitoρ° cells showed a significant increase in optic atrophy 1 and MFN2. These findings suggest that PMD can be used as a potential therapeutic intervention for mitochondrial disorders.

Altered expression of carbonic anhydrase-related protein XI in neuronal cells expressing mutant ataxin-3.

Spinocerebellar ataxia type 3/Machado-Joseph disease (SCA3/MJD) is a late-onset neurodegenerative disorder caused by the expansion of a polyglutamine tract within the gene product, ataxin-3. Microarray analysis revealed a dramatic differential expression of carbonic anhydrase-related protein XI (CA-RPXI/CA11) in the presence or absence of mutant ataxin-3. Therefore, we examined the expression and distribution of all three CA-RPs (CA8, 10, and 11) in human neuronal cells that stably express mutant ataxin-3. Compared with the cells containing normal ataxin-3, protein expression of CA8 and CA11 is significantly increased in human neuroblastoma cells harboring mutant ataxin-3. Semi-quantitative RT-PCR demonstrated that all three CA-RPs exhibited significantly higher transcript levels in neuronal cells expressing mutant ataxin-3. Interestingly, CA11 is distributed not only in the cytoplasm but also within the nuclei of the stably transfected mutant cells when compared with the sole cytoplasmic distribution in cells containing normal ataxin-3. In addition, results from transient transfection assays in SK-N-SH and Neuro2a (N2a) cells also confirmed the nuclear localization of CA11 in the presence of truncated ataxin-3. Most importantly, immunohistochemical staining of the MJD transgenic mouse and post-mortem MJD human brain also revealed that CA11 is highly expressed in both cytoplasm and nuclei of the brain cells. Recruitment of CA11 into nuclear inclusions containing mutant ataxin-3 revealed a possible correlation between CA11 and disease progression. Although the exact function of CA-RPs is still undefined in the central nervous system, our findings suggest that CA-RPs, especially CA11, may play specific roles in the pathogenesis of Machado-Joseph disease.

Can the Sandwich Method Be an Alternative Treatment Choice for BPH Patients With Large Prostates?

OBJECTIVE: To compare the efficacy and safety of the sandwich method with GreenLight photoselective vaporization (GLPVP) and bipolar transurethral resection (B-TURP) with those of the enucleation method in patients with BPH and a prostate volume ≥ 80 g. METHODS: Patients with BPH who underwent either the sandwich method with GLPVP and B-TURP or the enucleation method between 2014 and 2021 were included in the analysis. The primary outcome was the comparison of uroflowmetry results between the 2 groups. Safety analysis of the complication rates was also compared. RESULTS: The cohort included 55 patients in the sandwich group and 41 patients in the enucleation group. In the efficacy analysis, both groups showed comparable uroflowmetry results, except for a higher postoperative average flow rate in the enucleation group. Regarding perioperative parameters, the sandwich method required a longer operating time, and the enucleation group had a higher incidence of manual Foley irrigation. Both groups demonstrated similar postoperative complications. CONCLUSION: The sandwich method exhibited comparable efficacy and safety to the enucleation method in patients with BPH with a prostate volume ≥ 80 g. Thus, for surgeons who are familiar with GLPVP and B-TURP, the sandwich method may be an alternative surgical approach for BPH patients with large prostates.

Replacement Instead of Discontinuation of Bacillus Calmette-Guérin Instillation in Non-Muscle-Invasive Bladder Cancer.

BACKGROUND: To evaluate the efficacy of intravesical chemotherapy replacement in patients with intermediate- and high-risk non-muscle-invasive bladder cancer (NMIBC), who underwent bacillus Calmette-Guérin (BCG) instillation but discontinued due to global shortages or toxicity of BCG. METHODS: This retrospective study included patients with intermediate- and high-risk NMIBC who received BCG intravesical instillation. Those who discontinued the treatment were divided into the pure BCG group and chemotherapy replacement group. Comparisons between these groups were performed. The primary endpoint was bladder recurrence-free survival (RFS). RESULTS: A total of 480 patients were included. Baseline characteristics were similar between groups, but the total instillation times were higher in the chemotherapy replacement group than in the pure BCG group (n = 14.9 vs. 10.5). The chemotherapy replacement group had a better three-year RFS (p = 0.022). On multivariate analysis, the pure BCG group had significantly increased all-time and 3-year recurrences (hazard ratio 2.015 and 2.148) compared to the chemotherapy replacement group. CONCLUSIONS: Chemotherapy replacement has a better three-year RFS than no instillation in patients with intermediate- and high-risk NMIBC who received BCG instillation but facing treatment stoppage.

Body composition as a predictor of oncological outcome in patients with non-muscle-invasive bladder cancer receiving intravesical instillation after transurethral resection of bladder tumor.

Introduction: Body status, categorized as sarcopenia or obesity and assessed using body mass index and body composition, affects the outcome of bladder cancer patients. However, studies comparing disease progression, recurrence, or overall survival in patients with non-muscle-invasive bladder cancer (NMIBC) with different body compositions are lacking. Therefore, we conducted a retrospective study to identify the impact of body composition, sarcopenia, and obesity on the oncological prognosis of patients with NMIBC who underwent transurethral resection of bladder tumor (TURBT) with Bacillus Calmette-Guerin (BCG) intravesical instillation (IVI). Methods: Patients with NMIBC who had undergone TURBT with adjuvant IVI with BCG from March 2005 to April 2021 were included. Body composition parameters were evaluated using computed tomography images of the third lumbar vertebrae and further categorized by sarcopenia and obesity. Oncological outcomes including recurrence-free survival (RFS), progression-free survival, and overall survival (OS) after treatment were analyzed. Results: A total of 269 patients were enrolled. Subcutaneous adipose tissue (SAT) density was a significant predictor of RFS, whereas psoas muscle density was a significant predictor of OS in the multivariate analysis. Patients with sarcopenia but without obesity tolerated significantly fewer BCG IVIs than patients without sarcopenia or obesity. Patients with sarcopenia had poorer RFS and OS than those without sarcopenia. In contrast, patients with obesity had better OS than those without obesity. Discussion: Body composition parameters, including SAT density and psoas muscle density, emerged as significant predictors of OS and RFS, respectively. Hence, our findings indicate that body composition is a helpful measurement to assess the oncological outcomes of patients with NMIBC.

Complaint of insomnia as a predictor of aging symptoms in males at a men's health clinic.

INTRODUCTION: Issues of men's health have been greatly researched by scholars in recent decades. At men's health clinics, many patients complain of both insomnia and aging males' symptoms (AMS). These symptoms might be influenced by biological, psychological or even social factors. The aim of this study was to investigate different aspects of the relationship between insomnia and aging symptoms. METHODS: This cross-sectional study included 231 males from a men's health clinic. Participants completed a set of general data and screening assessments, including the AMS rating scale, insomnia severity index (ISI), Beck depression inventory-II (BDI-II) and Beck anxiety inventory Chinese version (BAI), to investigate the severity of aging symptoms, insomnia, depression and anxiety. RESULTS: The ISI correlated significantly with the AMS scale, both with (partial correlation coefficient = 0.470) and without (r = 0.580) controlled variances of depression and anxiety. Using linear regression, aging symptoms were statistically predicted by the severity of the ISI, and a substantial proportion of the variance was explained (adjusted R(2) = 0.410). When all variables were included, this proportion rose to 55.3% (adjusted R(2) = 0.553). CONCLUSION: We suggest that insomnia is a good predictor of aging symptoms across all age groups of men.