The Influence of Physical, Mental, and Cognitive Factors on Health-Related Quality of Life among Community-Dwelling Older Adults: A Focus on Central Sensitization-Related Symptoms.

Most older adults wish to maintain independence in their familiar communities. However, many experience pain and pain-related disabilities which reduce their health-related quality of life (HRQOL), leading to increased hospitalizations and mortality. This study aimed to determine the impact of physical, mental, and cognitive factors, particularly central sensitization-related symptoms (CSS), on the HRQOL of community-dwelling older adults. A total of 206 participants were included in the analysis, which measured HRQOL, basic attributes, physical functions and body pain, mental factors, cognitive factors, and CSS severity using validated tools. A correlation analysis was used to examine the association between HRQOL and each measure. Furthermore, multiple regression analysis (forced entry method) was performed to identify the factors influencing the HRQOL. The study found that pain intensity and CSS severity significantly influenced the HRQOL among community-dwelling older adults. The higher the pain intensity and CSS severity, the lower their HRQOL. The participants had mild pain and CSS, demonstrating the need to monitor, address, and treat even non-severe issues in community-dwelling older adults. This association, revealed for the first time in this study, suggests that approaches to reduce pain and CSS are important for maintaining and improving the HRQOL of community-dwelling older adults.

Membranous Expression of Heart Development Protein with EGF-like Domain 1 Is Associated with a Good Prognosis in Patients with Bladder Cancer.

OBJECTIVE: To investigate the correlation between total protein expression of heart development protein with EGF-like domain 1 (HEG1) and clinicopathological characteristics in patients with bladder cancer (BC) after radical cystectomy (RC). PATIENTS AND METHODS: We retrospectively analyzed data from 110 patients who underwent RC at Kitasato University Hospital. And we prepared an anti-HEG1 monoclonal antibody W10B9, which can detect total HEG1 protein. HEG1 protein expression in tumor cells was evaluated separately for membrane and cytoplasmic staining using immunohistochemistry. RESULTS: Membranous HEG1 expression was associated with absent lymphovascular invasion (p < 0.01) and low pT stage (p < 0.01). Kaplan-Meier analysis revealed that the membranous HEG1-positive group had significantly long recurrence-free survival (RFS) (p < 0.01) and cancer-specific survival (p = 0.01). Expression of membranous HEG1 was identified as an independent prognostic factor for RFS (p = 0.04). There were no significant differences between cytoplasmic HEG1 expression and clinicopathologic factors including prognosis. CONCLUSION: The expression of membranous HEG1 could serve as a favorable prognostic indicator in patients with BC treated with RC.

Ameliorating effects of cystine and theanine in a cancer cachexia mouse model.

Cachexia is a common cancer complication and is associated with weight loss and anorexia. In this study, we investigated the ameliorating effects of cystine and theanine on cancer cachexia using a mouse model. In mice carrying the colon cancer cell line C-26, there was a suppression of body weight increase and reduction in both internal fat and lower limb muscles. Repeated cystine and theanine administration significantly prevented weight loss, internal fat loss, lower limb muscle loss, and serum IL-6 increase in the cachexia model. These results suggested that cystine and theanine may be effective in ameliorating cancer cachexia.

Inhibitory Effect of α1 Receptor Antagonists on Paclitaxel-Induced Peripheral Neuropathy in a Rodent Model and Clinical Database.

The anticancer drug, paclitaxel, is widely used for ovarian, breast, non-small cell lung, and gastric cancers; however, it induces peripheral neuropathy as a side effect. There is insufficient evidence-based prophylaxis, and new prophylaxis and treatment methods are required. We examined the effect of α1-receptor antagonists on paclitaxel-induced peripheral neuropathy using Sprague-Dawley rats and a large adverse event database. The repeated administration of doxazosin or tamsulosin significantly reduced the response threshold to paclitaxel administration in animal models. In the sciatic nerve tissue, axonal degeneration and myelopathy were significantly suppressed. Furthermore, an analysis of the Food and Drug Administration Adverse Event Reporting System (FAERS) database suggested that the group using α1 inhibitors showed a lower reporting rate for paclitaxel-related peripheral neuropathy than the group that did not use these inhibitors (odds ratio (95% confidence interval): tamsulosin 0.21 (0.08−0.56), p < 0.01, doxazosin 0.41 (0.10−1.65), p = 0.195; any α1 receptor antagonist 0.54 (0.38−0.76), p < 0.01). Thus, doxazosin and tamsulosin may inhibit the development of paclitaxel-induced peripheral neuropathy by suppressing neurodegeneration, particularly axonal degeneration and myelopathy.

Gait Characteristics of Dynapenia, Sarcopenia, and Presarcopenia in Community-Dwelling Japanese Older Women: A Cross-Sectional Study.

Age-related decline in skeletal muscle mass and function are risk factors for reduced walking ability. This study aimed to understand the characteristic gait parameters of presarcopenia (low muscle mass only), dynapenia (low muscle function only), and sarcopenia (low muscle mass and function), which have differing skeletal muscle characteristics. Skeletal muscle mass, grip strength, and gait parameters (walking speed, cadence, step length, step width, gait angle, foot angle, stance time, swing time, and double stance time) were evaluated in 307 older Japanese women. Low muscle function was determined by grip strength and normal walking speed. Participants were assessed and divided into the normal (60.9%, n = 187), presarcopenia (25.7%, n = 79), dynapenia (5.2%, n = 16), and sarcopenia (8.1%, n = 25) groups. When compared to the normal group, the sarcopenia group had significantly slower walking speed and shorter step length (p < 0.05); the dynapenia group had significantly slower walking speed, smaller cadence, shorter step length, wider step width, and longer stance time (p < 0.05); and the presarcopenia group showed no differences. Skeletal muscle function may therefore be more strongly related to reduced walking function in older adults than body composition factors. The decrease in walking function was most pronounced in older women with dynapenia.

Omeprazole Suppresses Oxaliplatin-Induced Peripheral Neuropathy in a Rodent Model and Clinical Database.

(1) Background: Oxaliplatin is used as first-line chemotherapy not only for colorectal cancer but also for gastric and pancreatic cancers. However, it induces peripheral neuropathy with high frequency as an adverse event, and there is no effective preventive or therapeutic method. (2) Methods: The effects of omeprazole, a proton pump inhibitor (PPI), on oxaliplatin-induced peripheral neuropathy (OIPN) was investigated using an in vivo model and a real-world database. (3) Results: In a rat model, oxaliplatin (4 mg/kg, i.p., twice a week for 4 weeks) caused mechanical hypersensitivity accompanied by sciatic nerve axonal degeneration and myelin sheath disorder. Repeated injection of omeprazole (5−20 mg/kg, i.p., five times per week for 4 weeks) ameliorated these behavioral and pathological abnormalities. Moreover, omeprazole did not affect the tumor growth inhibition of oxaliplatin in tumor bearing mice. Furthermore, clinical database analysis of the Food and Drug Administration Adverse Event Reporting System (FAERS) suggests that the group using omeprazole has a lower reporting rate of peripheral neuropathy of oxaliplatin-treated patients than the group not using (3.06% vs. 6.48%, p < 0.001, reporting odds ratio 0.44, 95% confidence interval 0.32−0.61). (4) Conclusions: These results show the preventing effect of omeprazole on OIPN.

Diagnostic Potential of Circulating Tumor Cells, Urinary MicroRNA, and Urinary Cell-Free DNA for Bladder Cancer: A Review.

Early detection of primary bladder cancer (BCa) is vital, because stage and grade have been generally accepted not only as categorical but also as prognostic factors in patients with BCa. The widely accepted screening methods for BCa, cystoscopy and urine cytology, have unsatisfactory diagnostic accuracy, with high rates of false negatives, especially for flat-type BCa with cystoscopy and for low-risk disease with urine cytology. Currently, liquid biopsy has attracted much attention as being compensatory for that limited diagnostic power. In this review, we survey the literature on liquid biopsy for the detection of BCa, focusing on circulating tumor cells (CTCs), urinary cell-free DNA (ucfDNA), and urinary microRNA (umiRNA). In diagnostic terms, CTCs and umiRNA are determined by quantitative analysis, and ucfDNA relies on finding genetic and epigenetic changes. The ideal biomarkers should be highly sensitive in detecting BCa. Currently, CTCs produce an unfavorable result; however, umiRNA and ucfDNA, especially when analyzed using a panel of genes, produce promising results. However, given the small cohort size in most studies, no conclusions can yet be drawn about liquid biopsy's immediate application to clinical practice. Further large studies to validate the diagnostic value of liquid biopsy for clinical use are mandatory.

Expression of Membranous CD155 Is Associated with Aggressive Phenotypes and a Poor Prognosis in Patients with Bladder Cancer.

Objective: To investigate the relationship between clinicopathological findings and membranous CD155 (mCD155) or cytoplasmic CD155 (cCD155) expression in bladder cancer (BC). Methods: We retrospectively analyzed 103 patients with BC who underwent radical cystectomy between 1990 to 2015 at Kitasato University Hospital. Immunohistochemical staining was performed to evaluate CD155 expression in tumor cells. Cases with > 10% expression on the membrane or cytoplasm of tumor cells were positive. The Fisher's exact test was used for categorical variables and the Kaplan−Meier method was used for survival outcomes. Univariate and multivariate Cox regression hazard models were used to evaluate the survival risk factors. Results: Cases that were mCD155-positive were associated with high-grade tumors (p = 0.02), nodal status (p < 0.01), and pT stage (p = 0.04). No association with any clinicopathological factor was observed in the cCD155 cases. Kaplan−Meier analysis showed that mCD155-positive cases had shorter periods of recurrence-free survival (p = 0.015) and cancer-specific survival (p = 0.005). Only nodal status was an independent predictor for both cancer-specific survival and recurrence-free survival in multivariate analysis (p = 0.02 and p < 0.01, respectively). Conclusion: mCD155 expression may be a marker of an aggressive phenotype and a poor prognosis in patients with BC.

Effect of keishibukuryogan combined with tocopherol nicotinate on sperm parameters in patients with a varicocele.

OBJECTIVE: To evaluate the efficacy of keishibukuryogan, a traditional Kampo formula known to be an anti-Oketsu (impaired microcirculation and non-physiological blood congestion) drug, in combination with an anti-oxidant for the treatment of varicoceles. METHODS: We retrospectively analyzed 119 patients with palpable and subclinical varicoceles who were treated with 7.5 g/day of keishibukuryogan and 600 mg/day of tocopherol nicotinate. Their motile sperm concentrations at the start of medication and after 3 months were compared. As a subgroup analysis, a comparison test was carried out between patients with a high-grade varicocele and those with a low-grade varicocele. RESULTS: The mean age of the study patients was 35.6 years. Among them, 17, 41, 44 and 17 had subclinical, grade 1, grade 2 and grade 3 varicoceles, respectively. Overall, the differences in motile sperm concentration (millions/mL) before and after treatment were not significant (median 0.58, 95% confidence interval -0.12 to 1.56; P = 0.115). The results of the subgroup analysis showed that the motile sperm concentration in patients with a low-grade varicocele significantly increased (median 1.21, 95% confidence interval 0.45-2.47; P = 0.024); however, no significant improvements were seen in patients with a high-grade varicocele. CONCLUSIONS: The results of the present study showed that the combination of keishibukuryogan and an anti-oxidant had a limited effect on varicoceles, but they suggest that it is effective for the treatment of low-grade varicoceles.

Preclinical and Clinical Evidence of Therapeutic Agents for Paclitaxel-Induced Peripheral Neuropathy.

Paclitaxel is an essential drug in the chemotherapy of ovarian, non-small cell lung, breast, gastric, endometrial, and pancreatic cancers. However, it frequently causes peripheral neuropathy as a dose-limiting factor. Animal models of paclitaxel-induced peripheral neuropathy (PIPN) have been established. The mechanisms of PIPN development have been elucidated, and many drugs and agents have been proven to have neuroprotective effects in basic studies. In addition, some of these drugs have been validated in clinical studies for their inhibitory PIPN effects. This review summarizes the basic and clinical evidence for therapeutic or prophylactic effects for PIPN. In pre-clinical research, many reports exist of neuropathy inhibitors that target oxidative stress, inflammatory response, ion channels, transient receptor potential (TRP) channels, cannabinoid receptors, and the monoamine nervous system. Alternatively, very few drugs have demonstrated PIPN efficacy in clinical trials. Thus, enhancing translational research to translate pre-clinical research into clinical research is important.

Effect of cisplatin on metastatic castration-resistant prostate cancer with BRCA2 mutation: A case report.

Poly (ADP-ribose) polymerase inhibitors exhibit strong activity for treating the DNA damage repair defect in patients with prostate carcinoma (PCa). Although conventional DNA-damaging agents can theoretically lead to synthetic antitumoral effects, no report has clearly mentioned the clinical use of cisplatin for treating PCa patients with the breast cancer gene (BRCA)2 mutation. We administered 80 mg/m2 cisplatin triweekly to a patient with metastatic castration-resistant PCa (mCRPC) with the BRCA2 mutation, and after ten cycles, the prostate-specific antigen was dramatically decreased. We suggest that BRCA2 mutations may indicate the use of cisplatin for treating patients with mCRPC.

OTTER, a new method quantifying absolute amounts of tRNAs.

To maintain optimal proteome, both codon choice of each mRNA and supply of aminoacyl-tRNAs are two principal factors in translation. Recent reports have revealed that the amounts of tRNAs in cells are more dynamic than we had expected. High-throughput methods such as RNA-Seq and microarrays are versatile for comprehensive detection of changes in individual tRNA amounts, but they suffer from inability to assess signal production efficiencies of individual tRNA species. Thus, they are not the perfect choice to measure absolute amounts of tRNAs. Here, we introduce a novel method for this purpose, termed Oligonucleotide-directed Three-prime Terminal Extension of RNA (OTTER), which employs fluorescence-labeling at the 3'-terminus of a tRNA by optimized reverse primer extension and an assessment step of each labeling efficiency by northern blotting. Using this method, we quantified the absolute amounts of the 34 individual and 4 pairs of isoacceptor tRNAs out of the total 42 nuclear-encoded isoacceptors in the yeast Saccharomyces cerevisiae. We found that the amounts of tRNAs in log phase yeast cells grown in a rich glucose medium range from 0.030 to 0.73 pmol/µg RNA. The tRNA amounts seem to be altered at the isoacceptor level by a few folds in response to physiological growing conditions. The data obtained by OTTER are poorly correlated with those by simple RNA-Seq, marginally with those by microarrays and by microscale thermophoresis. However, the OTTER data showed good agreement with the data obtained by 2D-gel analysis of in vivo radiolabeled RNAs. Thus, OTTER is a suitable method for quantifying absolute amounts of tRNAs at the level of isoacceptor resolution.

Oxidative stress and male infertility.

BACKGROUND: Between 30% and 80% of patients with male infertility produce excessive reactive oxygen species (ROS) in their ejaculate even though the cause of male infertility is unexplained in approximately half of cases. The strong connection between oxidative stress (OS) and male infertility has led recent investigators to propose the term "Male Oxidative Stress Infertility (MOSI)" to describe OS-associated male infertility. METHODS: We searched the PubMed database for original and review articles to survey the effects of OS on male infertility, and then verified the effects and treatments. MAIN FINDINGS: Seminal plasma contains many antioxidants that protect sperm from ROS, because low amounts of ROS are required in the physiological fertilization process. The production of excessive ROS causes OS which can lower fertility through lipid peroxidation, sperm DNA damage, and apoptosis. Several assays are available for evaluating OS, including the MiOXSYS® analyzer to measure oxidation-reduction potential. Several measures should be considered for minimizing OS and improving clinical outcomes. CONCLUSION: Accurately diagnosing patients with MOSI and identifying highly sensitive biomarkers through proteomics technology is vital for better clinical outcomes.

The usefulness of ultrasound examination in detecting testicular nubbin in Japanese boys with non-palpable testes.

INTRODUCTION AND OBJECTIVE: In the case of non-palpable testes, we often find a small nodule which is called "testicular nubbin (TN)" in scrotum or inguinal canal. There is no agreement about the treatment for TN. This time we investigated whether or not ultrasound examination (US) can be a useful modality for detecting TN. MATERIALS AND METHODS: We recruited 66 boys who were diagnosed with non-palpable testes and who had undergone US studies. We examined age, affected side, size of the unaffected side, presence of testicular hypertrophy, and findings from US studies. Radiologists or sonographers familiar with examination of testicular nubbin carried out the ultrasound studies. When TN is detected in a patient, preservation or excision of the TN was chosen by their families. RESULTS: Sixty-six boys and 76 testes were examined. Thirty-four testes (44.7%) were diagnosed as having TN, 39 (51.3%) were undescended testes, and 3 (3.9%) were retractile testes. The median age of all participants was 13 months (range: 2-118 months). The mean ages of patients with TN, undescended testes, and retractile testes were 7.6 months, 14.5 months and 55 months, respectively. The size ratio between the affected and unaffected sides in cases of TN was 0.144 (range; 0.03-0.48) and in cases of undescended testes was 0.99 (0.46-1.2). Thirty cases of TN (88.2%) had testicular hypertrophy on the unaffected side. Only one case of TN underwent excision; viable cells were not seen. A high US region was observed in 31 (91.1%) cases with TN. CONCLUSION: US was a useful modality for detecting TN. From this study, TN can be detected if the size ratio between the affected and unaffected sides is < 0.4 and a high US region is seen. If TN can be detected using US, preservation can recommended, preventing unnecessary surgeries. However, there is no evidence on the required duration and interval of follow-up for these cases and examination will be needed over a period of time.

Impact of Tai Chi Yuttari-exercise on arteriosclerosis and physical function in older people.

OBJECTIVES: This non-randomized controlled study investigated the impact of practicing Tai Chi Yuttari-exercise for 1 year on arteriosclerosis status and physical functioning of community-dwelling older people. METHODS: Vascular and physical function were compared between 45 and 44 individuals who had and had not participated in Tai Chi Yuttari classes for 1 year, respectively. Participants deemed unsuitable for exercise by a physician, unable to walk unaided, with severely limited activities of daily living, with serious circulatory or respiratory disease, undergoing treatment for an acute or chronic motor organ disease, with seriously impaired motor function of the upper or lower limbs, with a history of myocardial infarction or cerebral stroke within the previous 6 months, and with previous serious infection were excluded. RESULTS: The mean cardio-ankle vascular index improved significantly from 8.44 at baseline to 8.20 after 6 months in the intervention group; however, no significant difference was observed at 1 year. Conversely, compared with baseline, the functional reach, gait speed, and timed up-and-go test results improved significantly after 6 months in this group; these improvements were maintained after 1 year. No significant changes in arteriosclerosis or physical function were observed in the control group. CONCLUSIONS: The practice of Tai Chi Yuttari-exercise is effective in maintaining and improving arteriosclerosis status and physical function in older people. However, it may be performed at least thrice a week for maintaining or improving arteriosclerosis status.

Factors Affecting Walking Speed in Schizophrenia Patients.

OBJECTIVE: This study investigated the factors affecting walking speed in schizophrenia patients who were inpatients at a psychiatric hospital. METHODS: The study subjects were 37 patients with schizophrenia who were hospitalized in a psychiatric hospital. The measured assessment items included age, duration of hospitalization, duration of disease, muscle strength (30-s chair stand test), balance ability (one-leg standing time with eyes open/closed, Functional Reach Test, and Timed Up & Go Test), flexibility (long sitting position toe-touching distance), walking speed (10-m maximum walking speed), and the antipsychotic drug intake. RESULTS: The walking speed was found to be correlated with the results of the 30-s chair stand test, the one-leg standing time with eyes open, the one-leg standing time with eyes closed, and the Timed Up & Go Test. Stepwise multiple regression analysis revealed that only the Timed Up & Go Test results affected walking speed. CONCLUSION: In schizophrenia patients, walking speed is influenced by balance and lower-limb muscle force, just as it is for patients without mental diseases. In schizophrenia patients, the dynamic balance ability has a strong influence on the walking speed.

Immobilization stress induces XBP1 splicing in the mouse brain.

Cells activate the unfolded protein response (UPR) to cope with endoplasmic reticulum (ER) stress. In the present study, we investigated the possible involvement of psychological stress on UPR induction in the mouse brain. When mice were exposed to immobilization stress for 8 h, XBP1 mRNA splicing was significantly induced in the hippocampus, cortex, hypothalamus, cerebellum, and brain stem. On the other hand, we did not observe any increase in XBP1 splicing in the liver, suggesting that this effect is specific to the brain. Stress-induced XBP1 splicing was attenuated 2 days after immobilization stress. We did not observe increases in any other UPR genes, such as CHOP or GRP78, in mouse brains after immobilization stress. These findings indicate an important specific role of XBP1 in response to psychological stress in the mouse brain.

Twitter use in scientific communication revealed by visualization of information spreading by influencers within half a year after the Fukushima Daiichi nuclear power plant accident.

Scientific communication through social media, particularly Twitter has been gaining importance in recent years. As such, it is critical to understand how information is transmitted and dispersed through outlets such as Twitter, particularly in emergency situations where there is an urgent need to relay scientific information. The purpose of this study is to examine how original tweets and retweets on Twitter were used to diffuse radiation related information after the Fukushima Daiichi nuclear power plant accident. Out of the Twitter database, we purchased all tweets (including replies) and retweets related to Fukushima Daiichi nuclear power plant accident and or radiation sent from March 2nd, 2011 to September 15th, 2011. This time frame represents the first six months after the East Japan earthquake, which occurred on March 11th, 2011. Using the obtained data, we examined the number of tweets and retweets and found that only a small number of Twitter users were the source of the original posts that were retweeted during the study period. We have termed these specific accounts as "influencers". We identified the top 100 influencers and classified the contents of their tweets into 3 groups by analyzing the document vectors of the text. Then, we examined the number of retweets for each of the 3 groups of influencers, and created a retweet network diagram to assess how the contents of their tweets were being spread. The keyword "radiation" was mentioned in over 24 million tweets and retweets during the study period. Retweets accounted for roughly half (49.7%) of this number, and the top 2% of Twitter accounts defined as "influencers" were the source of the original posts that accounted for 80.3% of the total retweets. The majority of the top 100 influencers had individual Twitter accounts bearing real names. While retweets were intensively diffused within a fixed population, especially within the same groups with similar document vectors, a group of influencers accounted for the majority of retweets one month after the disaster, and the share of each group did not change even after proven scientific information became more available.

Successful onco-testicular sperm extraction from a testicular cancer patient with a single testis and azoospermia.

Onco-testicular sperm extraction is used to preserve fertility in patients with bilateral testicular tumors and azoospermia. We report the case of a testicular tumor in the solitary testis of a patient who had previously undergone successful contralateral orchiectomy and whose sperm was preserved by onco-testicular sperm extraction. A 35-year-old patient presented with swelling of his right scrotum that had lasted for 1 month. His medical history included a contralateral orchiectomy during childhood. Ultrasonography revealed a mosaic echoic area in his scrotum, suggesting a testicular tumor. The lesion was palpated within the normal testicular tissue along its edge and semen analysis showed azoospermia. Radical inguinal orchiectomy and onco-testicular sperm extraction were performed simultaneously. Motile spermatozoa were extracted from normal seminiferous tubules under microscopy and were frozen. Eventual intracytoplasmic sperm injection using the frozen spermatozoa is planned. Onco-testicular sperm extraction is an important fertility preservation method in patients with bilateral testicular tumors or a history of a previous contralateral orchiectomy.