Contact-number-driven virus evolution: A multi-level modeling framework for the evolution of acute or persistent RNA virus infection.

Viruses evolve in infected host populations, and host population dynamics affect viral evolution. RNA viruses with a short duration of infection and a high peak viral load, such as SARS-CoV-2, are maintained in human populations. By contrast, RNA viruses characterized by a long infection duration and a low peak viral load (e.g., borna disease virus) can be maintained in nonhuman populations, and the process of the evolution of persistent viruses has rarely been explored. Here, using a multi-level modeling approach including both individual-level virus infection dynamics and population-scale transmission, we consider virus evolution based on the host environment, specifically, the effect of the contact history of infected hosts. We found that, with a highly dense contact history, viruses with a high virus production rate but low accuracy are likely to be optimal, resulting in a short infectious period with a high peak viral load. In contrast, with a low-density contact history, viral evolution is toward low virus production but high accuracy, resulting in long infection durations with low peak viral load. Our study sheds light on the origin of persistent viruses and why acute viral infections but not persistent virus infection tends to prevail in human society.

Association between perceived value of adopting new behaviors and incident disability among Japanese community-dwelling older adults.

OBJECTIVES: This longitudinal observational cohort study aimed to clarify the relationship between perceived value (PV) to adopt new behaviors and incident disability in community-dwelling older adults. METHOD: Participants were 5073 community-dwelling older adults aged ≥65 years in Japan (Mage = 74.0 ± 5.6 years; female = 55.1%). The mean follow-up time was 34.5 months. Baseline data were collected during health checkups in a prospective cohort study. Measurements included engagement in physical activity (PA), cognitive activity (CA), and social activity (SA), PV, health and physical conditions, and demographic characteristics. PV was assessed by asking whether participants thought it was valuable to adopt new behaviors related to PA, CA, and SA. Participants were classified as having higher/lower PV, PA, CA, and SA. Cox proportional hazard models were used to analyze the association between PV and incident disability. PV was examined both as an independent variable and in combination as follows: higher PV and higher PA/CA/SA (high/high); lower PV and higher PA/CA/SA (low/high); higher PV and lower PA/CA/SA (high/low); and lower PV and lower PA/CA/SA (low/low). RESULTS: Higher PV was significantly associated with a lower hazard ratio (HR) for incident disability. The low/high, high/low, and low/low significantly increased the HR compared to high/high in the analyses of PV & PA and CA. The analysis of PV & SA showed that only low/low increased the HR compared to high/high. CONCLUSION: Having both higher PV and higher activity engagement may contribute to preventing disability development. Both support for activities and value education in older adults may be needed.

Diversity in productive activities enhances life satisfaction among Japanese community-dwelling older adults: A cross-sectional study.

Few studies have reported an association between diversity in productive activities and life satisfaction; hence, this cross-sectional study conducted in Japan aimed to clarify this association. We assessed the life satisfaction of 4,498 Japanese community-dwelling older adults engaged in productive activities (e.g., paid work, volunteering, taking care of children, and supporting others) using the Life Satisfaction Scale. We took the sum of the number of engaging productive activities as the diversity in productive activities score. A dose-response relationship was observed for each additional productive activity on life satisfaction. Participants who engaged in one, two, three, or four productive activities were more likely to have higher life satisfaction than those who did not engage; the odds ratios (95 % confidence intervals) were 1.19 (1.02-1.39), 1.19 (1.00-1.42), 1.71 (1.37-2.13), and 2.27 (1.58-3.27), respectively. Diversity in productive activities may enhance higher life satisfaction likelihood among Japanese community-dwelling older adults.

Teicoplanin and vancomycin as treatment for glycopeptide-susceptible Enterococcus faecium bacteraemia: a propensity score-adjusted non-inferior comparative study.

OBJECTIVES: Limited evidence is available regarding alternative therapeutic agents to vancomycin in treating glycopeptide-susceptible Enterococcus faecium (GSEF) bacteraemia. This study assessed the effectiveness and safety of teicoplanin compared with vancomycin for treating GSEF bacteraemia. PATIENTS AND METHODS: This was a retrospective, non-inferiority cohort study. Patients aged ≥18 years who developed GSEF bacteraemia and received either teicoplanin or vancomycin were included. The primary effectiveness outcome was the clinical success at the end of treatment, with a generalized linear model using the propensity score for selecting the agent as a covariate. We used an absolute difference of 20% in clinical success as the non-inferiority margin. Using multivariable logistic regression, the primary safety outcome was the incidence of acute kidney injury (AKI). RESULTS: In total, 164 patients (74 and 90 in the teicoplanin and vancomycin groups, respectively) were included. Overall, 64.9% (48/74) and 48.9% (44/90) of patients in the teicoplanin and vancomycin groups, respectively, achieved the primary effectiveness outcome. A generalized linear analysis showed an adjusted effectiveness difference of 9.9% (95% CI, -0.9% to 20.0%; P = 0.07), indicating non-inferiority of teicoplanin versus vancomycin. The incidence of AKI was 8.1% (6/74) and 24.4% (22/90) in the teicoplanin and vancomycin groups, respectively, with an adjusted OR of 0.242 (95% CI, 0.068 to 0.864; P = 0.029), indicating significantly lower AKI risk in the teicoplanin than in the vancomycin group. CONCLUSIONS: Teicoplanin is a safe and useful alternative therapeutic agent for treating GSEF bacteraemia.

Males and females contribute differently to the evolution of habitat segregation driven by hybridization.

Costly heterospecific mating interactions, such as hybridization, select for prezygotic reproductive isolation. One of the potential traits responding to the selection arising from maladaptive hybridization is habitat preference, whose divergence results in interspecific habitat segregation. Theoretical studies have so far assumed that habitat preference is a sexually shared trait. However, male and female habitat preferences can experience different selection pressures. Here, by combining analytical and simulation approaches, we theoretically examine the evolution of sex-specific habitat preferences. Habitat segregation can have demographic consequences, potentially generating eco-evolutionary dynamics. We thus explicitly consider demography in the simulation model. We also vary the degrees of species discrimination to examine how mate choice influences the evolution of habitat preferences. Results show that both sexes can reduce hybridisation risk by settling in the habitats where abundant conspecific mates reside. However, when females can discriminate species, excess conspecific male aggregation intensifies male-male competition for mating opportunities, posing an obstacle to conspecific aggregation. Meanwhile, conspecific female aggregation attracts conspecific males, by offering the mating opportunity. Therefore, under effective species discrimination, females play a leading role in initiating habitat use divergence. Simulations typically result in either the coexistence with established habitat segregation or the extinction of one of the species. The former result is especially likely when the species differ to some extent in habitat preferences upon secondary contact. Our results disentangle the selection pressures acting on male and female habitat preferences, deepening our understanding of the evolutionary process of habitat segregation due to hybridization.

Disentangling the growth curve of microbial culture.

Many researchers have studied the population dynamics of microbe of microbes as a typical example of population dynamics. The Monod equation, which mainly focuses on the growth and stationary phases, is used when plotting a growth curve. However, the growth potential in the late stage of culture has been overlooked. Previous studies considered the direct degradation of products to the limiting substrate. In this study, we considered microbial growth during the stationary phase, which enables us to describe the dynamics precisely. The microbes were divided into two populations: one grew by consuming the limiting substrate and the other degraded the products by metabolism. According to the numerical analysis of our model, microbes may choose one of two strategies: one consumes substrates and expands quickly, and the other grows slowly while cleaning up the environment in which they thrive. Furthermore, we found three types of microbial growth depending on their ability to detect metabolite accumulation. Using experimentally measured data, this model can estimate the dynamics of cell density, the substrates, and the metabolites used. The model's disentangling of growth curves offers novel interpretive possibilities for culture system dynamics.

Information and Communication Technology Use for Alleviation of Disability Onset in Socially Isolated Older Adults: A Longitudinal Cohort Study.

INTRODUCTION: Delaying the onset of disability is important for maintaining independence and quality of life in community-dwelling older adults. Given that social isolation is a significant risk factor for disability, effective means associated with social isolation are needed to alleviate disability. Although information and communication technology (ICT) may be a reasonable measure considering the recent social contexts due to the coronavirus disease 2019 pandemic, further insights are required. This study aimed to investigate whether ICT use can alleviate the onset of disability in community-dwelling older adults with and without social isolation. METHODS: This longitudinal cohort study on 4,346 community-dwelling independent Japanese older adults (mean age, 73.5 ± 5.3 years) was conducted between 2017 and 2018. Participants were classified into four groups based on social isolation (the condition where two or more of the following measures were met: domestic isolation, less social contact, and social disengagement) and ICT users (those who had recently used a computer or a smartphone) and followed up to assess disability incidence for 24 months after baseline assessments. Cox proportional-hazards regression models were used to identify the effect of social isolation and ICT use on the risk of disability onset by adjusting for age, sex, education history, number of medications, eye disease, level of annual income, Mini-Mental State Examination, Geriatric Depression Scale 15, and gait speed. RESULTS: The group comprised nonsocial isolation and ICT users (44.7%), social isolation and ICT users (5.4%), nonsocial isolation and ICT nonusers (41.7%), and social isolation and ICT nonusers (8.2%). At the follow-up, 2.2%, 2.4%, 5.5%, and 12.4% of the participants in the above order developed disability (p < 0.01). Cox regression models revealed a significantly higher risk of disability onset in the social isolation and ICT nonusers group than in the social isolation and ICT users group (HR = 2.939; 95% confidence interval (CI) 1.029-8.397; p = 0.044). In the subgroup analysis stratified by social isolation, ICT use significantly reduced the risk of disability onset in the socially isolated group (HR = 0.320; 95% CI 0.109-0.943; p = 0.039), although the same association was not observed in the nonsocially isolated group (HR = 0.845; 95% CI 0.565-1.264; p = 0.411). CONCLUSION: ICT use can alleviate the onset of disability in socially isolated older adults in a community setting. Considering ICT-applied methods for alleviating disability is beneficial for older adults in social isolation.

Difference in employment status and onset of disability among Japanese community-dwelling older adults: a prospective cohort study.

OBJECTIVE: This prospective cohort study investigates the relationship between the onset of disability and employment status. METHODS: We investigated 3,741 community-dwelling adults aged 70 or older, who participated in a population-based cohort study in Japan. Their onset of disability was monitored monthly using the long-term care insurance certification registration system, for five years from baseline. Based on an employment status questionnaire, we categorized participants into three groups: (1) employee, (2) self-employed, and (3) not working. Covariates included demographic information, medical history, number of medications, educational level, living alone, social group engagement, smoking status, walking speed, instrumental activities of daily living, global cognitive function, and depressive symptoms. Missing values were managed using multiple imputation. Cox proportional hazard models were used to calculate hazard ratios (HRs) with 95% confidence intervals (CIs) for incident disability risk by employment status. RESULTS: The disability incidence rates were 15.3/1,000 (95% CIs: 10.7-22.0) person-years among employees, and 33.0/1000 (95% CIs: 24.4-44.6) and 39.6/1000 (95% CIs: 36.5-43.0) person-years among self-employed and non-working participants, respectively. The adjusted HRs for the onset of disability among non-working and self-employed participants were 1.69 (95% CIs: 1.16-2.46, p = 0.007) and 1.63 (95% CIs: 1.01-2.62, p = 0.044) compared with employees, respectively. Similar results were found among men. Among women, disability onset was not associated with employment status. CONCLUSIONS: Older adults' risk of disability onset differed according to their employment status. Older employees had a lower risk of disability onset than those not working or self-employed.

[Tricuspid Valve Replacement for Isolated Tricuspid Valve Infective Endocarditis without Risk Factor].

A 78-year-old Japanese male with previous gastric cancer and untreated diabetes mellitus was admitted to hospital for persistent fever and leg edema. Blood culture was positive for Streptococcus angino'sus, and echocardiography showed isolated tricuspid valve infective endocarditis. Infection was controlled with intravenous antibiotics, but surgery was indicated because of persistent severe regurgitation and large vegetation of 15 mm in size. As the tricuspid valve anterior leaflet was extensively damaged, he underwent valve replacement using a bioprosthetic valve. The patient was discharged 25 days postoperatively with additional antibiotics, and he has been free from recurrent endocarditis for 6 months.

Parental Population Range Expansion before Secondary Contact Promotes Heterosis.

AbstractPopulation genomic analysis of hybrid zones is instrumental to our understanding of the evolution of reproductive isolation. Many temperate hybrid zones are formed by the secondary contact between two parental populations that have undergone postglacial range expansion. Here, we show that explicitly accounting for historical parental isolation followed by range expansion prior to secondary contact is fundamental to explaining genetic and fitness patterns in these hybrid zones. Specifically, ancestral population expansion can result in allele surfing, where neutral or slightly deleterious mutations drift to high frequency at the expansion front. If these surfed deleterious alleles are recessive, they can contribute to substantial heterosis in hybrids produced at secondary contact, counteracting negative effects of Bateson-Dobzhansky-Muller incompatibilities (BDMIs) and hence weakening reproductive isolation. When BDMIs are linked to such recessive deleterious alleles, the fitness benefit of introgression at these loci can facilitate introgression at the BDMIs. The extent to which this occurs depends on the strength of selection against the linked deleterious alleles and the distribution of recombination across the chromosome. Finally, surfing of neutral loci can alter the expected pattern of population ancestry; thus, accounting for historical population expansion is necessary to develop accurate null genomic models of secondary contact hybrid zones.

The phoenix hypothesis of speciation.

Genetic divergence among allopatric populations builds reproductive isolation over time. This process is accelerated when populations face a changing environment that allows large-effect mutational differences to accumulate, but abrupt change also places populations at risk of extinction. Here we use simulations of Fisher's geometric model with explicit population dynamics to explore the genetic changes that occur in the face of environmental changes. Because evolutionary rescue leads to the fixation of mutations whose phenotypic effects are larger on average compared with populations not at risk of extinction, these mutations are thus more likely to lead to reproductive isolation. We refer to the formation of new species from the ashes of populations in decline as the phoenix hypothesis of speciation. The phoenix hypothesis predicts more substantial hybrid fitness breakdown among populations surviving a higher extinction risk. The hypothesis was supported when many loci underlie adaptation. With only a small number of potential rescue mutations, however, mutations that fixed in different populations were more likely to be identical, with such parallel changes reducing isolation. Consequently, reproductive isolation builds fastest in populations subject to an intermediate extinction risk, given a limited number of mutations available for adaptation.

Fascia Iliaca Block Reduces Remifentanil Requirement in Conscious Sedation for Transcatheter Aortic Valve Implantation　- A Randomized Clinical Trial.

BACKGROUND: Whether nerve block improves the quality of conscious sedation (CS) in patients undergoing transcatheter aortic valve implantation (TAVI) is unclear. This study investigated whether fascia iliaca block (FIB) reduced the remifentanil requirement and relieved pain in CS for TAVI.Methods and Results: This prospective study randomized 72 patients scheduled for elective TAVI under CS into 2 groups, with (FIB) and without (control) FIB (n=36 in each group). The sedation targeted a Bispectral Index <90 with a Richmond Agitation-Sedation Scale of -2 to -1. Dexmedetomidine (0.7 µg/kg, i.v.) combined with remifentanil (0.03 µg/kg/min, i.v.) and propofol (0.3 mg/kg/h, i.v.) was used to commence sedation. FIB using 30 mL of 0.185% ropivacaine was implemented 2 min before TAVI. Patient sedation was maintained with dexmedetomidine (0.4 µg/kg/h, i.v.) supplemented with remifentanil (0-0.02 µg/kg/min, i.v.). Remifentanil (20 µg, i.v.) was used as a rescue dose for intraprocedural pain. Compared with the control group, FIB reduced the both the total (median [interquartile range] 83.0 [65.0-98.0] vs. 34.5 [26.0/45.8)] µg; P<0.001) and continuous (25.3 [20.9/31.5] vs. 9.5 [6.8/12.5] ng/kg/min; P<0.001) doses of remifentanil administered. CONCLUSIONS: FIB reduced the remifentanil requirement and relieved pain in patients undergoing TAVI with CS. Therefore, FIB improved the quality of CS in TAVI.

Successful treatment of pneumonia caused by multidrug-resistant Pseudomonas aeruginosa after allogeneic hematopoietic stem cell transplantation with colistin and amikacin inhalation therapy.

Pseudomonas aeruginosa is a Gram-negative bacillus that often causes severe infections during immunosuppression in patients with hematologic malignancies. P. aeruginosa can easily acquire drug resistance, and often develops into multidrug-resistant P. aeruginosa (MDRP). Although many antibiotics are used in combination to treat MDRP infections, colistin and amikacin are less likely to be transferred to the lungs, and inhalation therapy may be used. Herein, we report a Case of pneumonia caused by MDRP after allogeneic hematopoietic stem cell transplantation (HSCT) treated with inhaled colistin and amikacin. This 61-year-old female patient was diagnosed with myelodysplastic syndromes and underwent allogeneic HSCT from an 8/8 HLA-matched unrelated donor after reduced-intensity conditioning. On the day of the stem cell infusion, the patient's sputum culture was found to be positive for MDRP. The patient subsequently developed bacteremia, pneumonia, and lung abscess caused by MDRP, and we administered multidrug antibiotic therapy including colistin and amikacin inhalation therapy. The patient's blood cultures were subsequently turned negative, and the lung abscess disappeared. To our knowledge, this is the first case of MDRP pneumonia after HSCT in which colistin and amikacin inhalation therapy was effective.

Late kidney injury after transcatheter aortic valve replacement.

BACKGROUND: Information on early to late-phase kidney damage in patients who underwent transcatheter aortic valve replacement (TAVR) is scarce. We aimed to identify the predictive factors for late kidney injury (LKI) at 1-year and patient prognosis beyond 1-year after TAVR. METHODS: We retrospectively reviewed 1,705 patients' data from the Japanese TAVR multicenter registry. Acute kidney injury (AKI) and LKI, defined as an increase of at least 0.3 mg/dL in creatinine level, a relative 50% decrease in kidney function from baseline to 48 hours and 1-year, were evaluated. The patients were categorized into the 4 groups as AKI-/LKI- (n = 1.362), AKI+/LKI- (n = 95), AKI-/LKI+ (n = 199), and AKI+/LKI+ (n = 46). RESULTS: The cumulative 3-year mortality rates were significantly increased across the four groups (12.5%, 15.8%, 24.6%, 25.8%, P < .001). Multivariate analysis revealed that chronic kidney disease, coronary artery disease, periprocedural AKI, and heart failure-related re-admission within 1-year were significantly associated with LKI. The Cox regression analysis revealed that AKI-/LKI+ and AKI+/LKI+ were independent predictors of increased late mortality beyond 1-year after TAVR (P = .001 and P = .01). CONCLUSIONS: LKI was influenced by adverse cardio-renal events and was associated with increased risks of late mortality beyond 1-year after TAVR.

Recurrent speciation rates on islands decline with species number.

In an archipelagic system, species diversity is maintained and determined by the balance among speciation, extinction and migration. As the number of species increases, the average population size of each species decreases, and the extinction likelihood of any given species grows. By contrast, the role of reduced population size in geographic speciation has received comparatively less research attention. Here, to study the rate of recurrent speciation, we adopted a simple multi-species two-island model and considered symmetric interspecific competition on each island. As the number of species increases on an island, the competition intensifies, and the size of the resident population decreases. By contrast, the number of migrants is likely to exhibit a weaker than proportional relationship with the size of the source population due to rare oceanic dispersal. If this is the case, as the number of species on the recipient island increases, the impact of migration strengthens and decelerates the occurrence of further speciation events. According to our analyses, the number of species can be stabilized at a finite level, even in the absence of extinction.

Clinical risk model for predicting 1-year mortality after transcatheter aortic valve replacement.

OBJECTIVES: Estimating 1-year life expectancy is an essential factor when evaluating appropriate indicators for transcatheter aortic valve replacement (TAVR). BACKGROUND: It is clinically useful in developing a reliable risk model for predicting 1-year mortality after TAVR. METHODS: We evaluated 2,588 patients who underwent TAVR using data from the Optimized CathEter vAlvular iNtervention (OCEAN) Japanese multicenter registry from October 2013 to May 2017. The 1-year clinical follow-up was achieved by 99.5% of the entire population (n = 2,575). Patients were randomly divided into two cohorts: the derivation cohort (n = 1,931, 75% of the study population) and the validation cohort (n = 644). Considerable clinical variables including individual patient's comorbidities and frailty markers were used for predicting 1-year mortality following TAVR. RESULTS: In the derivation cohort, a multivariate logistic regression analysis demonstrated that sex, body mass index, Clinical Frailty Scale, atrial fibrillation, peripheral artery disease, prior cardiac surgery, serum albumin, renal function as estimated glomerular filtration rate, and presence of pulmonary disease were independent predictors of 1-year mortality after TAVR. Using these variables, a risk prediction model was constructed to estimate the 1-year risk of mortality after TAVR. In the validation cohort, the risk prediction model revealed high discrimination ability and acceptable calibration with area under the curve of 0.763 (95% confidence interval, 0.728-0.795, p < .001) in the receiver operating characteristics curve analysis and a Hosmer-Lemeshow χ2 statistic of 5.96 (p = .65). CONCLUSIONS: This risk prediction model for 1-year mortality may be a reliable tool for risk stratification and identification of adequate candidates in patients undergoing TAVR.

[Metastatic Cardiac Tumor in the Left Atrium from Esophageal Cancer].

Metastatic cardiac lesions are clinically silent and are usually found a necropsy. The most common primary tumor resulting in cardiac metastases is carcinoma of the lung, with there being only a few reports of metastases from esophageal cancer. We report two cases of metastatic cardiac tumors in the left atrium from esophageal cancer and perform a review of the literature. Case 1:A 62-year-old woman underwent esophagectomy and adjuvant chemotherapy. No other metastases were observed. Case 2:A 49-year-old man also underwent esophagectomy and adjuvant chemotherapy for lymph node and liver metastases. In both patients, the left atrial tumors were detected on recent follow-up computed tomography. Left atrial tumors often cause cerebral emboli with neurological sequelae. Therefore, surgical resection and cryo-ablation for the prevention of local recurrence were performed on the metastatic tumors. Local recurrence was not observed after the surgery in both patients. Although chemotherapy is usu-ally the most beneficial treatment for metastatic cardiac lesions, left atrial tumor should be treated with surgical resection because of the high risk of cerebral emboli. We suggest that surgical resection with cryo-ablation may prevent local recurrence.

Concise Review: Laying the Groundwork for a First-In-Human Study of an Induced Pluripotent Stem Cell-Based Intervention for Spinal Cord Injury.

There have been numerous attempts to develop stem cell transplantation approaches to promote the regeneration of spinal cord injury (SCI). Our multicenter team is currently planning to launch a first-in-human clinical study of an induced pluripotent stem cell (iPSC)-based cell transplant intervention for subacute SCI. This trial was conducted as class I regenerative medicine protocol as provided for under Japan's Act on the Safety of Regenerative Medicine, using neural stem/progenitor cells derived from a clinical-grade, integration-free human "iPSC stock" generated by the Kyoto University Center for iPS Cell Research and Application. In the present article, we describe how we are preparing to initiate this clinical study, including addressing the issues of safety and tumorigenesis as well as practical problems that must be overcome to enable the development of therapeutic interventions for patients with chronic SCI. Stem Cells 2019;37:6-13.

Preservation of the value of rice paddy fields: Investigating how to prevent farmers from abandoning the fields by means of evolutionary game theory.

The evolution of group cooperation is still an evolutionary puzzle and has been studied from the perspective of not only evolutionary ecology but also social sciences. Some socio-ecological problems are caused by collapse of group cooperation. By applying theoretical studies about the evolution of cooperation, we can elucidate what causes the problems and find solutions. One of the appropriate examples is maintaining rice paddy field landscapes, which are a grand spectacle in Asia, and some are UNESCO world heritage sites. These magnificent landscapes and the associated biodiversity are at risk of abandonment for social and financial reasons. Rice paddy fields can be preserved not only by regular cultivation, which requires farmers to invest effort in cultivation, but also by the maintenance of common facilities such as irrigation canals. To investigate how this landscape might be preserved, we developed an agent-based model in which each farmer makes two types of efforts: an effort for land cultivation and an effort for collective action such as common facility maintenance. Additionally, we consider the side effects of rice production such as field deterioration from abandonment and water use competition. These factors determine the utility of each player who imitates the level of efforts necessary to invest in land cultivation and common facility maintenance of one with higher utility. This decision-making of each player can be described by the evolutionary game theory. We find that maintenance effort promotes cultivation effort, but not vice versa, even though we usually consider that each farmer's cultivation effort makes rice field landscape sustainable. We also find that if players and their near neighbors are responsible for maintaining their common facilities together, they continue to maintain them and cultivate, but if all players are responsible for maintaining all facilities in the whole farmland, players are likely to quit facility maintenance and stop cultivation. Competition for water use among all players, however, promotes cultivation more than competition among neighbors only. Therefore, rice paddy field landscapes can be sustainable if neighbors, but not the whole players, are responsible for maintaining their common facilities and cooperate together, and if the water usage of all players, but not neighbors, influences the productivity of each rice field.

Poor penetration of cefcapene into aqueous humor after oral administration of cefcapene pivoxil to patients undergoing cataract surgery.

OBJECTIVES: Studies on the penetration of orally administered cephalosporins to the aqueous humor are scarce. Therefore, in this study, we determined the concentration of cefcapene, a third-generation cephalosporin administrated orally as pivalate ester (cefcapene pivoxil), in the aqueous humor of patients undergoing cataract surgery to assess its potential for preventing postoperative endophthalmitis. METHODS: Forty-four patients were administered a single dose of 100 mg cefcapene pivoxil preoperatively. Blood and aqueous humor samples were obtained at the time of surgery, and cefcapene concentrations were measured using ultra-performance liquid chromatography with tandem mass spectrometric detection. RESULTS: The samples were obtained from 41 eyes of 39 patients (two patients underwent surgery in both eyes). The median cefcapene concentrations in the aqueous humor after 1-2 h, 2-3 h, and later than 3 h were 8.3, 18.4, and 23.7 ng/mL, respectively. The median cefcapene concentrations in serum after 1-2 h, 2-3 h, and later than 3 h were 198.5, 287.2, and 170.3 ng/mL, respectively. Aqueous humor penetration of cefcapene after 1-2 h, 2-3 h, and later than 3 h was 4.1, 7.9, and 13.5% respectively. CONCLUSIONS: Aqueous humor penetration of orally-administered cefcapene pivoxil in patients undergoing cataract surgery was poor. Therefore, cefcapene pivoxil was unlikely to be effective for preventing endophthalmitis after cataract surgery.