Loss of Heterozygosity on Chromosomes 3p, 8p, 9p and 17p in the Progression of Squamous Cell Carcinoma of the Larynx

Previous molecular genetic studies of laryngeal squamous cell carcinoma (SCC)have shown certain chromosomal regions with recurring alterations. But studies of sequential molecular alterations and genetic progression model of laryngeal SCC have not been clearly defined. To identify the chromosomal alterations associated with the carcinogenesis of laryngeal SCC, we analyzed genomic DNA from microdissected squamous metaplasia, squamous dysplasia, invasive SCC, and metastatic carcinoma samples from 22 laryngeal SCC patients for loss of heterozygosity (LOH) at microsatellite loci. Ten microsatellite markers on chromosome 3p, 8p, 9p, and 17p were used. LOH at 9p21 was observed in the all stages including squamous metaplasia, squamous dysplasia, invasive SCC and metastatic carcinoma. LOH at 17p13.1, 3p25 and 3p14.2 was observed from the squamous dysplasia, invasive SCC and metastatic carcinoma. LOH at 8p21.3-p22 was observed mainly from the invasive SCC and metastatic carcinoma. The results suggest that 9p21 in the early event, 17p13.1, 3p25 and 3p14.2 in the intermediate event and 8p21.3-p22 in the late event may be involved in the laryngeal carcinogenesis

The Expression Patterns of FAM83H and PANX2 Are Associated With Shorter Survival of Clear Cell Renal Cell Carcinoma Patients

FAM83H is primarily known for its role in amelogenesis; however, recent reports suggest FAM83H might be involved in tumorigenesis. Although the studies of FAM83H in kidney cancer are limited, a search of the public database shows a significant association between FAM83H and pannexin-2 (PANX2) in clear cell renal cell carcinomas (CCRCCs). Therefore, we evaluated the clinicopathological significance of the immunohistochemical expression of FAM83H and PANX2 in 199 CCRCC patients. The expression of FAM83H and PANX2 were significantly associated with each other. In univariate analysis, individual, and co-expression pattern of FAM83H and PANX2 was significantly associated with shorter overall survival (OS) and relapse-free survival (RFS) of CCRCC patients: nuclear expression of FAM83H (OS; P < 0.001, RFS; P < 0.001), cytoplasmic expression of FAM83H (OS; P < 0.001, RFS; P < 0.001), nuclear expression of PANX2 (OS; P < 0.001, RFS; P < 0.001), cytoplasmic expression of PANX2 (OS; P < 0.001, RFS; P < 0.001), co-expression pattern of nuclear FAM83H and nuclear PANX2 (OS; P < 0.001, RFS; P < 0.001). In multivariate analysis, nuclear expression of FAM83H (OS; P < 0.001, RFS; P = 0.003) and the co-expression pattern of nuclear FAM83H and PANX2 (OS; P < 0.001, RFS; P < 0.001) were independent indicators of shorter survival of CCRCC patients. Cytoplasmic expression of FAM83H was associated with shorter RFS (P = 0.030) in multivariate analysis. In Caki-1 and Caki-2 CCRCC cells, knock-down of FAM83H decreased PANX2 expression and cell proliferation, and overexpression of FAM83H increased PANX2 expression and cell proliferation. These results suggest that FAM83H and PANX2 might be involved in the progression of CCRCC in a co-operative manner, and their expression might be used as novel prognostic indicators for CCRCC patients

SARS-CoV-2 Omicron variant causes brain infection with lymphoid depletion in a mouse COVID-19 model

Background The Omicron variant has become the most prevalent SARS-CoV-2 variant. Omicron is known to induce milder lesions compared to the original Wuhan strain. Fatal infection of the Wuhan strain into the brain has been well documented in COVID-19 mouse models and human COVID-19 cases, but apparent infections into the brain by Omicron have not been reported in human adult cases or animal models. In this study, we investigated whether Omicron could spread to the brain using K18-hACE2 mice susceptible to SARS-CoV-2 infection. Results K18-hACE2 mice were intranasally infected with 1 × 105 PFU of the original Wuhan strain and the Omicron variant of SARS-CoV-2. A follow-up was conducted 7days post infection. All Wuhan-infected mice showed > 20% body weight loss, defined as the lethal condition, whereas two out of five Omicron-infected mice (40%) lost > 20% body weight. Histopathological analysis based on H&E staining revealed inflammatory responses in the brains of these two Omicron-infected mice. Immunostaining analysis of viral nucleocapsid protein revealed severe infection of neuron cells in the brains of these two Omicron-infected mice. Lymphoid depletion and apoptosis were observed in the spleen of Omicron-infected mice with brain infection. Conclusion Lethal conditions, such as severe body weight loss and encephalopathy, can occur in Omicron-infected K18-hACE2 mice. Our study reports, for the first time, that Omicron can induce brain infection with lymphoid depletion in the mouse COVID-19 model

Development of a Cardiovascular Simulator for Studying Pulse Diagnosis Mechanisms

This research was undertaken to develop a cardiovascular simulator for use in the study of pulse diagnosis. The physical (i.e., pulse wave transmission and reflection) and physiological (i.e., systolic and diastolic pressure, pulse pressure, and mean pressure) characteristics of the radial pulse wave were reproduced by our simulator. The simulator consisted of an arterial component and a pulse-generating component. Computer simulation was used to simplify the arterial component while maintaining the elastic modulus and artery size. To improve the reflected wave characteristics, a palmar arch was incorporated within the simulator. The simulated radial pulse showed good agreement with clinical data

The severity of lower urinary tract symptoms is increased in patients with premature ejaculation among aging Korean men

Introduction and objective: The purpose of this study was to compare the severity of lower urinary tract symptoms (LUTS) between patients with and without premature ejaculation (PE). Materials and method: The relationship between the severity of LUTS and PE was investigated among 825 male subjects, who underwent medical check-up between July 2013 and July 2018 in our hospital. PE was defined by self-reported intravaginal ejaculation latency time (IELT). The severity of LUTS was determined by international prostate symptom score (IPSS), overactive bladder symptom score (OABSS), transrectal ultrasonography (TRUS), and uroflow rate. A total of 825 subjects were classified into three groups: PE-group (N = 60), Self-reported PE-group (N = 353), and Non-PE group (N = 412). Results: In comparison analysis involving the two groups, the PE-group and the Self-reported PE-group were analyzed to be statistically significantly higher in IPSS items and OABSS items, compared to the Non-PE group (P < 0.05). This showed the same results in the univariate analysis (P < 0.05). Multivariate analysis conducted with the PE-group versus the Non-PE group, and the Self-reported PE-group versus the Non-PE group, revealed significant differences in the values of total IPSS (P < 0.05). Conclusion: Comparison between the PE-group, which included the Self-reported PE-group, and the Non-PE group suggest that the severity of LUTS was comparatively higher in the PE-group. Thus, it is thought that being associated with or without PE may be a significant factor to consider, which affects LUTS severity

Association of Erectile Dysfunction and Premature Ejaculation in Men with Chronic Prostatitis

Background and objective Although several studies have reported that sexual dysfunction is associated with chronic prostatitis (CP), specific differences in self-reported questionnaires and correlation with CP are not well-known. This study aimed to evaluate the prevalence and correlation of sexual dysfunction in men with CP. Material and methods This cross-sectional study included 892 men who visited our health care center, who were then divided into two groups. In Group 1, subjects are characterized with National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) pain score ≥4, and Group 2 subjects are characterized with NIH-CPSI<4. Intravaginal Ejaculation Latency Time, Premature Ejaculatory Diagnostic Tool (PEDT), Male Sexual Health Questionnaire-ejaculation, International Index of Erectile Function (IIEF), and IIEF-5 were self-reported by participants. Total testosterone (TT) level was also checked. Data obtained were compared between the groups and the relationships identified. Results The mean age was 52.8±7.3 years, and CP was prevalent in 136 (15.2%) of the 892 participants. All questionnaire scores showed worse results in Group 1 compared to those in Group 2 (p<0.05). In total, the prevalence of erectile dysfunction (IIEF-5≤21) and premature ejaculation (PEDT≥9) were 508 (56.3%) and 290 (32.5%), respectively. A higher prevalence of erectile dysfunction (71.3% vs. 53.6%, p<0.001) and premature ejaculation (44.8% vs. 30.3%, p=0.001) was identified in Group 1 than in Group 2. By correlation analysis, IIEF-5 (r=−0.208, p=0.015) and TT (r=−0.331, p=0.011) showed correlation with NIH-CPSI pain score in Group 1. Conclusion The prevalence and severity of erectile dysfunction and premature ejaculation were higher in Group 1. Moreover, the IIEF-5 showed correlation with NIH-CPSI pain score. These results indicate that screening for erectile dysfunction and premature ejaculation in men with CP is useful for early detection of comorbidities

Baculovirus entire ORF1629 is not essential for viral replication.

It is generally accepted that ORF1629 is essential for baculovirus replication, which has enabled isolation of recombinant viruses in a baculovirus expression system using linearized viral DNA. ORF1629-defective viruses cannot replicate in insect cells; only recombinant virus with complete ORF1629 restoration by recombination can propagate, allowing for pure isolation and the development of bacmids for easy selection of recombinant viruses. We inadvertently found proliferation in insect cells of a bacmid lacking a complete ORF1629. PCR indicated no other viruses but a lack of complete ORF1629 in the proliferated bacmid, suggesting that the baculovirus propagated without a complete ORF1629. Lack of ORF1629 decreased the virus growth rate and yield; it also increased the occlusion body (OB) size but decreased its yield. These results were confirmed for Autographa californica multicapsid nucleopolyhedrovirus (AcMNPV) and Bombyx mori NPV (BmNPV). Thus, entire ORF1629 is not essential for viral replication, though it does affect the virus growth rate, yield, and size and OB production

Relationship Between the National Institutes of Health Chronic Prostatitis Symptom Index and the International Prostate Symptom Score in Middle-Aged Men According to the Presence of Chronic Prostatitis-Like Symptoms

Background and objective The characteristic symptom of chronic prostatitis (CP) is pain. Patients with CP often complain of lower urinary tract symptoms (LUTS); however, the voiding domain of the Chronic Prostatitis Symptom Index of the National Institutes of Health (NIH-CPSI) is not sufficient to evaluate LUTS. Therefore, we studied the relationship between the International Prostate Symptom Score (IPSS) and NIH-CPSI scores in men. Materials and methods We reviewed 870 men who visited our health care center for a general health check-up and com-pleted IPSS and NIH-CPSI questionnaires between January 2014 and January 2019. An NIH-CPSI pain score ≥4 was defined as the presence of a prostatitis-like symptom (Group 1), and an NIH-CPSI pain score less than <4 was defined as the absence of a prostatitis-like symptom (Group 2). The relationship between IPSS and NIH-CPSI sub-scores was investigated. The associations between the IPSS total score and NIH-CPSI sub-scores were assessed using multiple linear regres-sion analysis. Results The mean IPSS total, voiding, storage, and quality-of-life (QOL) scores were higher in Group 1 than in Group 2. Group 1 had fewer subjects in the mild group and more in the moderate and severe groups than did Group 2. Among NIH-CPSI sub-scores, pain score showed the highest correlation between IPSS total (r=0.283), voiding (r=0.266), storage (r=0.237), and QOL score (r=0.263). In regression analysis, only the NIH-CPSI pain score was associated with the IPSS total score (B=0.962, p<0.001). Conclusions The NIH-CPSI pain score showed a weak but statistically significant correlation with the IPSS, but the NIH-CPSI voiding score did not. This finding suggests that patients with CP-like symptoms need to be surveyed using the IPSS questionnaire. It will also be helpful to screen for comorbidities of benign prostatic hyperplasia and CP

The Effect of Alcohol Administration on the Corpus Cavernosum

Purpose: We studied the effects of alcohol administration on the corpus cavernosum (CC) using an animal model. Materials and Methods: CC sections and the aortic ring of rabbits were used in an organ bath study. After acute alcohol administration, changes in blood alcohol concentration and electrical stimulation induced intracavernosal pressure/mean arterial pressure (ICP/MAP) percentage were compared in rats. Cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) levels in the CC were measured using immunoassays. After chronic alcohol administration, ICP/MAP percentage, cAMP and cGMP were compared in rats. Histological changes were examined using the Masson trichrome stain and the Sircol collagen assay. Endothelial nitric oxide synthase (eNOS) expression was examined using immunohistochemistry and Western blotting. Results: Alcohol relaxed the CC in a dose-dependent manner, and the relaxation response was suppressed when pretreated with propranolol, indomethacin, glibenclamide, and 4-aminopyridine. In rats with acute alcohol exposure, the cAMP level in the CC was significantly greater than was observed in the control group (p＜0.05). In rats with chronic alcohol exposure, however, changes in cAMP and cGMP levels were insignificant, and the CC showed markedly smaller areas of smooth muscle, greater amounts of dense collagen (p＜0.05). Immunohistochemical analysis of eNOS showed a less intense response, and western blotting showed that eNOS expression was significantly lower in this group (p＜0.05). Conclusions: Acute alcohol administration activated the cAMP pathway with positive effects on erectile function. In contrast, chronic alcohol administration changed the ultrastructures of the CC and suppressed eNOS expression, thereby leading to erectile dysfunction

The Efficacy and Safety of ‘Inverted Omega En-bloc’ Holmium Laser Enucleation of the Prostate (HoLEP) for Benign Prostatic Hyperplasia: A Size-Independent Technique for the Surgical Treatment of LUTS

Purpose: To evaluate the safety, efficiency, and size-dependency of the ‘Inverted omega En-bloc (Ʊ)’ holmium laser enucleation of the prostate (HoLEP) in benign prostate hyperplasia (BPH) with lower urinary tract symptoms. Materials and Methods: A retrospective analysis of 716 consecutive patients who underwent HoLEP under the care of a single surgeon from 2014–2021. These patients were treated using the ‘Inverted omega En-bloc’ HoLEP technique for BPH. The patients were divided into 3 groups: Group 1 (<40 mL, n=328), Group 2 (40–60 mL, n=221), and Group 3 (≤60 mL, n=167). Perioperative parameters, safety, and functional outcomes were assessed and analyzed. Results: The perioperative parameters, like enucleation time (45.8±26.9 min), morcellation time (13.2±47.5 min), and catheterization duration (1.6±1.2 d) significantly differed to favor smaller prostate sizes (p<0.01). Significant improvements in the IPSS (total, voiding, storage, and quality of life), post-void residual urine, and maximum flow rate were observed 3 months post- HoLEP and continued during the 1-year follow-up period in all groups (p<0.01). The postoperative complications included urethral stricture in 11 patients (1.5%), bladder neck contracture in 12 (1.7%), urinary incontinence in 14 (2.0%), and bladder injuries in 4 (0.6%). Bladder neck contractures occurred only in Group 1. The postoperative surgical management for complications included urethral sounding (n=9, 1.3%), endoscopic internal urethrotomy (n=2, 0.3%), and re-HoLEP for bladder neck contractures in (n=12, 1.7%). The rate of re-HoLEP for regrowing adenomas was 15 (2.1%). Postoperative medications exceeding 6 months were α-blocker (n=22, 3.1%), cholinergics (n=16, 2.2%), anticholinergics (n=58, 8.1%), antidiuretics (n=18, 2.5%), and daily PDE5 inhibitor (n=38, 5.3%). Thirty-four patients (4.7%) had postoperative incidental prostate cancer. Conclusions: The inverted omega En-bloc HoLEP technique is safe and effective for the treatment of BPH. Moreover, ‘Inverted omega En-bloc’ HoLEP is a size-independent and effective method for all prostate sizes