Effects of different exercise intensities or durations on salivary IgA secretion.

PURPOSE: This study aimed to examine changes in salivary immunoglobulin A (s-IgA) secretion at different intensities or durations of acute exercise. METHODS: Twelve healthy untrained young males were included in randomized crossover trials in Experiment 1 (cycling exercise for 30 min at a work rate equivalent to 35%, 55%, and 75% maximal oxygen uptake [ V ˙ O2max]) and Experiment 2 (cycling exercise at 55% V ˙ O2max intensity for 30, 60, and 90 min). Saliva samples were collected at baseline, immediately after, and 60 min after each exercise. RESULTS: Experiment 1: The percentage change in the s-IgA secretion rate in the 75% V ˙ O2max trial was significantly lower than that in the 55% V ˙ O2max trial immediately after exercise (- 45.7%). The percentage change in the salivary concentration of cortisol, an s-IgA regulating factor, immediately after exercise significantly increased compared to that at baseline in the 75% V ˙ O2max trial (+ 107.6%). A significant negative correlation was observed between the percentage changes in saliva flow rate and salivary cortisol concentration (r = - 0.52, P < 0.01). Experiment 2: The percentage change in the s-IgA secretion rate in the 90-min trial was significantly lower than that in the 30-min trial immediately after exercise (-37.0%). However, the percentage change in salivary cortisol concentration remained the same. CONCLUSION: Our findings suggest that a reduction in s-IgA secretion is induced by exercise intensity of greater than or equal to 75% V ˙ O2max for 30 min or exercise duration of greater than or equal to 90 min at 55% V ˙ O2max in healthy untrained young men.

Changes in roller skiing economy among Nordic combined athletes leading up to the competition season.

The purpose of this study was to compare roller skiing economy during different training phases in Nordic combined (NC) athletes and determine the aerobic and anaerobic factors responsible for changes in skiing economy. Seven elite NC athletes underwent incremental load tests on a large buried treadmill in both spring and autumn using roller skis. Measurements included oxygen uptake, respiratory exchange ratio, and blood lactate concentration. Roller skiing economy was calculated from aerobic and anaerobic energy system contributions, and overall roller skiing economy was determined by combining the two. Comparisons were made between the skiing economies obtained in the two measurement sessions. Physical characteristics and incremental test performance remained consistent between the two measurement sessions. The overall skiing economy at each speed significantly improved toward the competition season (p < 0.05). Similarly, the contribution of anaerobic energy system at each speed showed significant improvement (p < 0.05). In contrast, the contribution of aerobic energy system did not change between the two measurement sessions. This study reveals that NC athletes enhance their skiing economy at the same speed during submaximal efforts in preparation for the competition season. This improvement is predominantly associated with an improvement in the contribution of anaerobic energy system.

Duloxetine improves chronic orofacial pain and comorbid depressive symptoms in association with reduction of serotonin transporter protein through upregulation of ubiquitinated serotonin transporter protein.

ABSTRACT: Chronic orofacial pain (COP) is relieved by duloxetine (DLX) and frequently causes depressive symptoms. The aim of this study was to confirm effects of DLX on pain and depressive symptoms, and to associate with their effectiveness in platelet serotonin transporter (SERT) expression, which is a target molecule of DLX and plasma serotonin concentration in COP patients with depressive symptoms. We assessed for the severity of pain and depressive symptoms using the Visual Analog Scale (VAS) and 17-item Hamilton Depression Rating Scale (HDRS), respectively. Chronic orofacial pain patients were classified into 2 groups based on their HDRS before DLX-treatment: COP patients with (COP-D) and without (COP-ND) depressive symptoms. We found that the VAS and HDRS scores of both groups were significantly decreased after DLX treatment compared with those before DLX treatment. Upregulation of total SERT and downregulation of ubiquitinated SERT were observed before DLX treatment in both groups compared with healthy controls. After DLX treatment, there were no differences in total SERT of both groups and in ubiquitinated SERT of COP-D patients compared with healthy controls; whereas, ubiquitinated SERT of COP-ND patients remained downregulated. There were positive correlations between changes of serotonin concentrations and of VAS or HDRS scores in only COP-D patients. Our findings indicate that DLX improves not only pain but also comorbid depressive symptoms of COP-D patients. Duloxetine also reduces platelet SERT through upregulation of ubiquitinated SERT. As the result, decrease of plasma serotonin concentrations may be related to the efficacy of DLX in relieving pain and depression in COP patients.

Gut microbiota alternation with training periodization and physical fitness in Japanese elite athletes.

Introduction: The gut microbiome plays a fundamental role in host homeostasis through regulating immune functions, enzyme activity, and hormone secretion. Exercise is associated with changes in gut microbiome composition and function. However, few studies have investigated the gut microbiome during training periodization. The present study aimed to investigate the relationship between training periodization and the gut microbiome in elite athletes. Methods: In total, 84 elite athletes participated in the cross-sectional study; and gut microbiome was determined during their transition or preparation season period. Further, 10 short-track speed skate athletes participated in the longitudinal study, which assessed the gut microbiome and physical fitness such as aerobic capacity and anaerobic power in the general and specific preparation phase of training periodization. The gut microbiome was analyzed using 16S rRNA sequencing. Results: The cross-sectional study revealed significant differences in Prevotella, Bifidobacterium, Parabacteroides, and Alistipes genera and in enterotype distribution between transition and preparation season phase periodization. In the longitudinal study, training phase periodization altered the level of Bacteroides, Blautia, and Bifidobacterium in the microbiome. Such changes in the microbiome were significantly correlated with alternations in aerobic capacity and tended to correlate with the anaerobic power. Discussion: These findings suggest that periodization alters the gut microbiome abundance related to energy metabolism and trainability of physical fitness. Athlete's condition may thus be mediated to some extent by the microbiota in the intestinal environment.

Inhalation adherence for asthma and COPD improved during the COVID-19 pandemic: a questionnaire survey at a university hospital in Japan.

Background: Good adherence to an inhaled medication protocol is necessary for the management of asthma and chronic obstructive pulmonary disease (COPD), and several interventions to improve adherence have been reported. However, the impact of patient life changes and psychological aspects on treatment motivation is obscure. Here, we investigated changes in inhaler adherence during the COVID-19 pandemic and how lifestyle and psychological changes affected it.Methods: Seven-hundred sixteen adult patients with asthma and COPD who had visited Nagoya University Hospital between 2015 and 2020 were selected. Among them, 311 patients had received instruction at a pharmacist-managed clinic (PMC). We distributed one-time cross-sectional questionnaires from January 12 to March 31, 2021. The questionnaire covered the status of hospital visits, inhalation adherence before and during the COVID-19 pandemic, lifestyles, medical conditions, and psychological stress. The Adherence Starts with Knowledge-12 (ASK-12) was used to assess adherence barriers.Results: Four-hundred thirty-three patients answered the questionnaire. Inhalation adherence was significantly improved in both diseases during the COVID-19 pandemic. The most common reason for improved adherence was fear of infection. Patients with improved adherence were more likely to believe that controller inhalers could prevent COVID-19 from becoming more severe. Improved adherence was more common in patients with asthma, those not receiving counseling at PMC, and those with poor baseline adherence.Conclusions: Inhalation adherence for asthma and COPD improved in the COVID-19 pandemic. The patients seemed to realize the necessity and benefits of the medication more strongly than before the pandemic, which motivated them to improve adherence.

[Promoting Appropriate Use of Medications by "Lectures and Practices Regarding Medicine" for the Regional Community Residents].

We held lectures and practices for the regional community residents with the aim of promoting appropriate use of medications. To evaluate the usefulness of our activity, we conducted medicine-related questionnaire surveys (pre- and post-questionnaires) before and after the lectures and practices, and satisfaction with the activity questionnaire surveys (post-questionnaires) after them. We also evaluated the effect of age difference on the results by dividing the participants into elderly (age ≥65) and non-elderly (age <65), before the analysis. In the both (elderly and non-elderly) groups, the ratio of positive answers in several items of post-questionnaire regarding appropriate use of medications was higher than that of pre-questionnaire. These results suggest that the basic medicine-related knowledge improved by attending the lectures and practices, and indicate that the knowledge of the regional community residents is higher than we imagined. Furthermore, there was no difference in the ratio of positive answers between the both groups, suggesting that our activity is applicable to a wide range of age groups. Our activity benefitted the participants, and not only provided education to the regional community residents regarding appropriate drug use, but also lead to the development of regional community activity, by the coming together of the regional community residents of various age.

Training cessation and subsequent retraining of a world-class female Olympic sailor after Tokyo 2020: A case study.

Olympic sailing is a complex sport where sailors are required to predict and interpret weather conditions while facing high physical and physiological demands. While it is essential for sailors to develop physical and physiological capabilities toward major competition, monitoring training status following the competition is equally important to minimize the magnitude of detraining and facilitate retraining. Despite its long history in the modern Olympics, reports on world-class sailors' training status and performance characteristics across different periodization phases are currently lacking. This case study aimed to determine the influence of training cessation and subsequent retraining on performance parameters in a world-class female sailor. A 31-year old female sailor, seventh in the Women's Sailing 470 medal race in Tokyo 2020, completely stopped training for 4 weeks following the Olympics, and resumed low-intensity training for 3 weeks. Over these 7 weeks, 12.7 and 5.3% reductions were observed in 6 s peak cycling power output and jump height, respectively, with a 4.7% decrease in maximal aerobic power output. Seven weeks of training cessation-retraining period induced clear reductions in explosive power production capacities but less prominent decreases in aerobic capacity. The current findings are likely attributed to the sailor's training characteristics during the retraining period.

Associations between Oral Human Herpesvirus-6 and -7 and Periodontal Conditions in Older Adults.

BACKGROUND: The associations between oral human herpesvirus-6 (HHV-6) and HHV-7, periodontal conditions, and lifestyle-related diseases, such as hypertension, diabetes, and dyslipidemia, have not been fully investigated in older adults. METHODS: Seventy-four older patients who visited Hiroshima University Hospital were enrolled. Tongue swab samples were employed, and a real-time polymerase chain reaction was performed to detect HHV-6 and HHV-7 DNA. Dental plaque accumulation, probing pocket depth, and bleeding on probing (BOP) (i.e., a sign of periodontal inflammation) were examined. The periodontal inflamed surface area (PISA) value (i.e., an indicator of the severity of periodontitis) was also examined. RESULTS: Of the 74 participants, one participant (1.4%) was HHV-6 DNA-positive and 36 participants (48.6%) were HHV-7 DNA-positive. A significant association between HHV-7 DNA and probing depth was found (p = 0.04). The HHV-7 DNA-positive participants had a higher positive rate of a ≥6-mm periodontal pocket with BOP (25.0%) than the HHV-7 DNA-negative participants (7.9%). Additionally, the HHV-7 DNA-positive participants had a higher PISA value than the HHV-7 DNA-negative participants. However, there was no significant association between HHV-7 and the PISA value (p = 0.82). No significant association was found between HHV-7 and lifestyle-related diseases (p > 0.05). CONCLUSIONS: Oral HHV-7 infection is associated with a deep periodontal pocket.

Influence of the Menstrual Cycle on Muscle Glycogen Repletion After Exhaustive Exercise in Eumenorrheic Women.

ABSTRACT: Matsuda, T, Takahashi, H, Nakamura, M, Ogata, H, Kanno, M, Ishikawa, A, and Sakamaki-Sunaga, M. Influence of the menstrual cycle on muscle glycogen repletion after exhaustive exercise in eumenorrheic women. J Strength Cond Res 37(4): e273-e279, 2023-The purpose of this study was to investigate the effect of the menstrual cycle on muscle glycogen repletion postexercise. Eleven women with regular menstrual cycles (age: 20.2 ± 1.3 years, height: 161.1 ± 4.8 cm, and body mass: 55.5 ± 5.7 kg) were assessed in 3 phases of the cycle: the early follicular phase (E-FP), late follicular phase (L-FP), and luteal phase (LP). Each test day began with glycogen-depleting exercise, followed by 5 hours of recovery. Muscle glycogen concentrations, using 13 C-magnetic resonance spectroscopy, and estradiol, progesterone, blood glucose, blood lactate, free fatty acid (FFA), and insulin concentrations were measured at t = 0, 120, and 300 minutes postexercise. During the 5-hour recovery period, subjects consumed 1.2g·(kg body mass) -1 ·h -1 of carbohydrates every 30 minutes. The muscle glycogen concentrations increased at t = 120 and t = 300 minutes postexercise ( p < 0.01) but were not significantly different between the menstrual cycle phases ( p = 0.30). Blood lactate concentrations were significantly higher in the L-FP and LP than in the E-FP ( p < 0.05). Nonetheless, the blood glucose, FFA, insulin concentrations, and the exercise time until exhaustion in the E-FP, L-FP, and LP were similar (blood glucose, p = 0.17; FFA, p = 0.50; insulin, p = 0.31; exercise time, p = 0.67). In conclusion, the menstrual cycle did not influence muscle glycogen repletion after exercise.

Prevalence of oral Epstein-Barr virus and Porphyromonas gingivalis and their association with periodontal inflamed surface area: A cross-sectional study.

We previously reported that oral herpesviruses, such as Epstein-Barr virus (EBV), are associated with periodontitis. However, the relationship between oral EBV or dual oral EBV and Porphyromonas gingivalis infections and periodontal inflammation severity remains unclear. We conducted this study to determine the relationship between oral EBV and P gingivalis prevalence and the periodontal inflamed surface area (PISA) in middle-aged and older adults. We analyzed 205 patients (median age, 70 years) who visited Hiroshima University Hospital. Tongue swab samples were used to investigate the presence of EBV and P gingivalis DNA using real-time PCR. Probing pocket depth and bleeding on probing were measured at 6 sites per tooth. PISA scores were calculated based on the results of probing pocket depth and bleeding on probing. Propensity scores were calculated via logistic regression analysis of 8 clinical factors: age, sex, smoking status, remaining teeth, denture use, hypertension, diabetes, and hyperlipidemia. EBV DNA was present in 41 of the 205 participants (20.0%). Thirty-seven EBV-positive or -negative participants in 74 matched pairs after propensity-score matching were examined via univariate analysis. EBV-positive participants exhibited higher plaque control record scores and PISAs than did EBV-negative participants. EBV DNA was significantly associated with plaque control record scores and PISA (both P = .04). Of the 205 participants, 111 were positive for P gingivalis (54.1%). Nineteen participants (9.3%) were infected with both oral EBV and P gingivalis. Logistic regression analysis revealed that dual infection with EBV and P gingivalis was significantly associated with diabetes (odds ratio = 3.37, 95% confidence interval: 1.13-10.1; P = .03). Oral EBV prevalence is associated with oral hygiene and the spread of inflamed periodontal tissue. Diabetes may be a risk factor for dual infection with oral EBV and P gingivalis.

Pre-cooling with ingesting a high-carbohydrate ice slurry on thermoregulatory responses and subcutaneous interstitial fluid glucose during heat exposure.

The purpose of this study was to compare the effects of ingesting ice slurries with two different carbohydrate contents on body temperatures and the subcutaneous interstitial fluid glucose level during heat exposure. Seven physically active men underwent one of three interventions: the ingestion of 7.5 g/kg of a control beverage (CON: 26°C), a normal-carbohydrate ice slurry (NCIS: -1°C), or a high-carbohydrate ice slurry (HCIS: -5°C). The participants were monitored for a 120-min period that included 10 min of rest, 25 min of exposure to the experimental cooling intervention (during which the beverage was ingested), and 85 min of seated rest in a climate chamber (36°C, 50% relative humidity). The rectal temperature in the HCIS and NCIS trials was lower than that in the CON trial from 40 to 75 min. The infrared tympanic temperature was also lower in the HCIS and NCIS trials than in the CON trial from 20 to 50 min, whereas the deep thigh or mean skin temperatures were not significantly different among the three groups. From 90 to 120 min, the subcutaneous interstitial fluid glucose level in the NCIS trial was lower than that at 65 min; however, reductions were not seen in the HCIS and CON trials. These findings suggest that both HCIS ingestion and conventional NCIS ingestion were effective cooling strategies for reducing thermal strain, while HCIS ingestion may also enable a higher subcutaneous interstitial fluid glucose level to be maintained, ensuring an adequate supply of required muscle substrates.

Influence of menstrual cycle on muscle glycogen utilization during high-intensity intermittent exercise until exhaustion in healthy women.

The present study investigated the effects of the menstrual cycle on muscle glycogen and circulating substrates during high-intensity intermittent exercise until exhaustion in healthy women who habitually exercised. In total, 11 women with regular menstrual cycles completed three tests, which comprised the early follicular phase (E-FP), late follicular phase (L-FP), and luteal phase (LP) of the menstrual cycle. High-intensity intermittent exercise until exhaustion was performed on each test day. Evaluation of muscle glycogen concentration by 13C-magnetic resonance spectroscopy and measurement of estradiol, progesterone, blood glucose, lactate, free fatty acids (FFA), and insulin concentrations were conducted before exercise (Pre) and immediately after exercise (Post). Muscle glycogen concentrations from thigh muscles at Pre and Post were not significantly different between menstrual cycle phases (P = 0.57). Muscle glycogen decreases by exercise were significantly greater in L-FP (59.0 ± 12.4 mM) than in E-FP (48.3 ± 14.4 mM, P < 0.05). Nonetheless, blood glucose, blood lactate, serum FFA, serum insulin concentrations, and exercise time until exhaustion in E-FP, L-FP, and LP were similar. The study results suggest that although exercise time does not change according to the menstrual cycle, the menstrual cycle influences muscle glycogen utilization during high-intensity intermittent exercise until exhaustion in women with habitual exercise activity. Novelty: This study compared changes in muscle glycogen concentration across the menstrual cycle during high-intensity intermittent exercise until exhaustion using 13C-magnetic resonance spectroscopy. Our results highlight the influence of the menstrual cycle on muscle glycogen during high-intensity intermittent exercise in healthy women.

Case Report: Countermeasures Against Heat and Coronavirus for Japanese Athletes at the Tokyo 2020 Olympics and Paralympic Games.

The Tokyo 2020 Olympics and Paralympic Games were held in the hottest environment in the history of the games. Additionally, the worldwide coronavirus disease 2019 (COVID-19) pandemic necessitated daily polymerase chain reaction (PCR) testing during the games, wearing a mask became mandatory publicly, and it was an unheard and unique Olympic with no spectators. Heat acclimation, hydration, and body cooling are essential for safe and high-performance activities in hot environments. In 2015, the Japan Institute of Sports Sciences launched the "Heat Countermeasure Project" to conduct experiments and practical research on heat countermeasures and investigate issues related to heat countermeasures in each athletic event. The results obtained were proposed to various Japan national sports teams, and support for heat countermeasures for the Tokyo 2020 games was promoted in consultation with national federations. Furthermore, due to the COVID-19 pandemic, infectious disease countermeasures for the Tokyo 2020 Games during support were a must. Moreover, athletes, coaches, and team staff could not avoid implementing heat countermeasures while adopting measures against infectious diseases. This study aimed to clarify the issues faced with heat countermeasures and report on heat acclimation training and cooling support efforts, considering measures against infectious diseases.

A clinical survey of dehydration during winter training in elite fencing athletes.

BACKGROUND: Fencing is suggested as one of the most dangerous sporting events in terms of dehydration because of the uniform and gear covering the entire body. We aimed to elucidate the change in hydration status before and after training in elite fencing athletes in winter along with the assessment of sex and fencing style differences. METHODS: Twenty-seven elite fencing athletes (14 males and 13 females) belonging to the Japanese National Team participated in this clinical survey. Dehydration status before and after winter training was assessed using body mass change, fluid intake, urine osmolarity, urine specific gravity (USG), and sodium, potassium, chlorine, and creatinine levels. RESULTS: More than half of the participants (59.3%) drank water and tea during training. The change rate of body mass (males vs. females, 1.61±0.82% vs. 0.45±0.68%, P<0.01; foil vs. epee, 2.25±0.45% vs. 1.16±0.72%, P<0.05) and sweating rate (males vs. females, 938±251 g/h vs. 506±92 g/h, P<0.01; foil vs. epee, 1136±156 g/h vs. 796±207 g/h, P<0.05) during training showed significant differences between sexes and fencing styles. Of all participants, 66.7% were dehydrated (USG≥1.020), and 37.0% were seriously dehydrated (USG≥1.030) before training. CONCLUSIONS: Fencing athletes may be susceptible to severe dehydration before training, even in winter. Additionally, males and foil fencers appear to be at a greater risk than females and epee fencers of developing dehydration during exercise.

In-play optimal cooling for outdoor match-play tennis in the heat.

The purpose of this study was to compare the efficacy of four cooling interventions used for reducing physiological and perceptual strain and improving exercise performance during outdoor match-play tennis in the heat. Eight competitive tennis players played four counter-balanced simulated outdoor matches in the heat (WBGT: 28.4-32.5°C) at 24- or 48-h intervals. Each match comprised 3 sets for which the "no-ad" rule was applied to limit duration variability. Players underwent the following cooling interventions: ad libitum fluid ingestion (CON), ad libitum fluid ingestion and ice vest (VEST), total ingestion of approximately 1000 g ice slurry and ice vest (Combined: BINE), or total ingestion of approximately 400 g ice slurry and ice vest (Low-combined: L-BINE). Gastrointestinal temperature was lower in the BINE and the L-BINE trials than in the CON trial at the set-break of set 1, and these differences in gastrointestinal temperature persisted throughout the remainder of the match (p < 0.05). The ratio of moderate-high intensity activity (≥10 km/h) in set 3 was significantly higher in the L-BINE trial than that in the BINE trial (p < 0.05). In the CON and BINE trials, high intensity activity was significantly lower in set 3 compared with set 1 and 2, respectively. Cooling by optimal ice slurry ingestion and ice vest may be a more effective strategy in mitigating the development of heat strain during outdoor match-play tennis in the heat.Highlights Cooling by optimal ice slurry ingestion and ice vest may be a more effective strategy in mitigating the development of heat strain during outdoor match-play tennis in the heat.Ingesting of large amounts ice slurry may be caused the bloating and stomach discomfort, in turn declined in the ratio of moderate-high intensity activity in the second half of match-play tennis in hot outdoor environments.Future studies should not only utilize match characteristics, but also measure on-court tennis specific performance.

Duloxetine attenuates pain in association with downregulation of platelet serotonin transporter in patients with burning mouth syndrome and atypical odontalgia.

OBJECTIVE: The aim of this study was evaluation of the association between severity of pain and expression of total or ubiquitinated serotonin transporter (SERT) protein in patients with burning mouth syndrome and atypical odontalgia (BMS/AO), who were treated by duloxetine. METHODS: Patients with BMS/AO were assessed for severity of pain using the visual analog scale (VAS), and expression of total and ubiquitinated SERT protein in platelets before (baseline) and 12 weeks after duloxetine-treatment. RESULTS: The expression of total and ubiquitinated SERT protein at baseline in all patients (n = 33) were higher and lower, respectively, compared to those in healthy controls. 12 weeks after duloxetine-treatment, there was no difference in the total SERT protein levels between patients (n = 21) and healthy controls. In the 16 patients who could be measured, mean VAS scores and total SERT protein levels were significantly decreased after the treatment, compared to those at baseline. There was tendency for a positive correlation between total SERT protein levels and VAS scores in these patients. CONCLUSIONS: Our findings indicate that duloxetine relieves pain in association with downregulation of platelet SERT expression in patients with BMS/AO.

Ion Capture and Release Ability of Glass Ionomer Cement Containing Nanoporous Silica Particles with Different Pore and Particle Size.

This study prepared glass ionomer cement (GIC) containing nanoporous silica (NPS) (GIC-NPS) at 5 wt% concentrations using 3 types of NPS with different pore and particle sizes and evaluated the differences in their cationic ion capture/release abilities and mechanical properties. The cationic water-soluble dye was used as cationic ion. The test GIC-NPS complexes captured dyes by immersion in 1 wt% dye solutions. All the GIC-NPS complexes released dyes for 28 d, and the amount of dye released from the complexes increased with decreasing pore size; however, the particle size of NPS did not affect the amount of dye released. Additionally, GIC-NPS was able to recharge the dye, and the amount of released the dye by the complexes after recharge was almost identical to the amount released on the first charge. Although not significantly different, the compressive strength of GIC-NPS was slightly greater than that of GIC without NPS regardless of the type of NPS. These results suggest that the degree of capture and release of cationic molecules, such as drugs, can be controlled by optimizing the pore size of NPS without sacrificing its mechanical strength when its content is 5 wt%.

Adenovirus Vectors Expressing Eight Multiplex Guide RNAs of CRISPR/Cas9 Efficiently Disrupted Diverse Hepatitis B Virus Gene Derived from Heterogeneous Patient.

Hepatitis B virus (HBV) chronically infects more than 240 million people worldwide, causing chronic hepatitis, cirrhosis, and hepatocellular carcinoma (HCC). Genome editing using CRISPR/Cas9 could provide new therapies because it can directly disrupt HBV genomes. However, because HBV genome sequences are highly diverse, the identical target sequence of guide RNA (gRNA), 20 nucleotides in length, is not necessarily present intact in the target HBV DNA in heterogeneous patients. Consequently, possible genome-editing drugs would be effective only for limited numbers of patients. Here, we show that an adenovirus vector (AdV) bearing eight multiplex gRNA expression units could be constructed in one step and amplified to a level sufficient for in vivo study with lack of deletion. Using this AdV, HBV X gene integrated in HepG2 cell chromosome derived from a heterogeneous patient was cleaved at multiple sites and disrupted. Indeed, four targets out of eight could not be cleaved due to sequence mismatches, but the remaining four targets were cleaved, producing irreversible deletions. Accordingly, the diverse X gene was disrupted at more than 90% efficiency. AdV containing eight multiplex gRNA units not only offers multiple knockouts of genes, but could also solve the problems of heterogeneous targets and escape mutants in genome-editing therapy.

Survey of chemotherapy-induced nausea and vomiting in patients with urothelial carcinoma.

Chemotherapy-induced nausea and vomiting (CINV) can cause anorexia, weight loss and deterioration of patient quality of life. It is one of the most unpleasant adverse effects of chemotherapy treatment regimens. For the optimal treatment of gastrointestinal symptoms during urothelial carcinoma chemotherapy, the present study investigated the association between gastrointestinal symptoms and therapeutic effects of gemcitabine plus platinum [cisplatin (GC) or carboplatin (GCa)] therapies. The incidence and frequency of nausea/vomiting with GC split therapy (gemcitabine, 1,000 mg/m2 on days 1 and 8; split-dose cisplatin, 35 mg/m2 on days 1 and 8; 21-day schedule) and GCa therapy [gemcitabine, 750-1,000 mg/m2 on days 1, 8 and 15; carboplatin, area under the blood concentration-time curve=5 mg min/ml (Calvert formula) on day 2; 28-day schedule] were lower compared with those of GC therapy (gemcitabine, 1,000 mg/m2 on days 1, 8 and 15; single-dose cisplatin 70 mg/m2 on day 2; 28-day schedule). However, no differences in therapeutic outcomes were observed among therapies. GCa therapy, regardless of renal function, and GC split therapy demonstrated significant increases compared with GC therapy in alleviating gastrointestinal symptoms associated with cancer chemotherapy in patients with urothelial carcinoma. Overall, these results suggested that split-dose cisplatin administration or the use of carboplatin instead of cisplatin may be useful in patients who experience CINV without compromising treatment effectiveness.

The Associations of Periodontopathic Bacteria and Oral Candida with Periodontal Inflamed Surface Area in Older Adults Receiving Supportive Periodontal Therapy.

The periodontal inflamed surface area (PISA) has been proposed for assessment of the total periodontal inflammatory status in people with periodontitis. This study was performed to investigate the associations of periodontopathic bacteria and candida with PISA in older people. We enrolled 100 patients aged ≥ 60 years who visited Hiroshima University Hospital. PISA and periodontal epithelial surface area (PESA) were calculated in each patient. Oral rinse samples were collected for DNA extraction. Periodontopathic bacteria and candida were detected by polymerase chain reaction. The mean values of PISA and PESA were significantly greater in T.forsythia-positive patients than in T.forsythia-negative patients. T.forsythia/C. albicans double-positive patients exhibited significantly greater PISA values than did non-double-positive patients. Additionally, PISA values were significantly greater in T. forsythia//T. denticola/C. albicans triple-positive patients than in T. forsythia//T. denticola/C. albicans non-triple-positive patients (p = 0.02). Propensity score-matching was performed between periodontopathic bacteria-positive and -negative patients using propensity scores generated from clinical factors. Importantly, T.forsythia/T. denticola double-positive patients exhibited significantly greater PISA values than non-double-positive patients among 72 propensity score-matched patients. Our preliminary results highlight the importance of the presence of T.forsythia and T. denticola for periodontal inflammation severity in older Japanese people.