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Computer code plays a vital role in modern science, from the conception and design of experiments through to final data analyses. Open sharing of code has been widely discussed as being advantageous to the scientific process, allowing experiments to be more easily replicated, helping with error detection, and reducing wasted effort and resources. In the case of psychology, the code used to present stimuli is a fundamental component of many experiments. It is not known, however, the degree to which researchers are sharing this type of code. To estimate this, we conducted a survey of 400 psychology papers published between 2016 and 2021, identifying those working with the open-source tools Psychtoolbox and PsychoPy that openly share stimulus presentation code. For those that did, we established if it would run following download and also appraised the code's usability in terms of style and documentation. It was found that only 8.4% of papers shared stimulus code, compared to 17.9% sharing analysis code and 31.7% sharing data. Of shared code, 70% ran directly or after minor corrections. For code that did not run, the main error was missing dependencies (66.7%). The usability of the code was moderate, with low levels of code annotation and minimal documentation provided. These results suggest that stimulus presentation code sharing lags behind other forms of code and data sharing, potentially due to less emphasis on such code in open-science discussions and in journal policies. The results also highlight a need for improved documentation to maximize code utility., (© 2024. The Psychonomic Society, Inc.)

Background & Aims: Sarcopenic obesity (SO) and dynapenic obesity (DO) represent two manifestations of excessive fat accumulation concurrent with compromised muscle mass and function, thereby necessitating an examination of their implications for health. This study aims to investigate the relationship between SO/DO and mortality, taking into account various adiposity measures and existing sarcopenia criteria, with further stratified analyses based on age and gender., Methods: The study sample comprised 1779 older adults residing in the community from the I-Lan Longitudinal Aging Study (ILAS). Body composition was assessed via dual-energy X-ray absorptiometry. The diagnosis of sarcopenia was adhered to the 2019 consensus of the Asian Working Group for Sarcopenia, while adiposity was measured by waist circumference (WC), body mass index (BMI), and fat percentage. SO/DO was defined as the coexistence of sarcopenia/dynapenia and obesity. Multivariate Cox proportional hazard regression models were adopted to examine the association between SO or DO, defined by WC, BMI, fat percentage, and mortality., Results: This 11-year follow-up study of 1779 participants aged 63.9 ± 9.2 years involved 15,068 person-years and 229 deaths. WC-defined SO (HR 1.9, 95% CI 1.1-3.3, p = 0.021) and WC-defined DO (HR 1.4, 95% CI 1.1-1.9, p = 0.022) significantly increased mortality risk, whereas definitions employing alternative adiposity metrics exhibited no statistical significance. WC-defined SO was associated with increased risk of mortality among middle-aged adults, while WC-defined DO was associated with increased risk of mortality among older adults. In sex-specific analysis, WC-defined DO was also associated with increased risk of mortality in men (HR 1.6, 95% CI 1.1-2.4, p = 0.019), while defined by other measurements showed no associations in both sexes., Conclusions: The study identified a significant link between SO/DO, defined by WC, and an 11-year mortality risk, advocating for WC-defined adiposity as an obesity measure and personalized interventions considering SO and DO's distinct impacts on mortality in middle-aged and older adults., Competing Interests: Conflict of interest The authors declare that they have no competing interests., (Copyright © 2024 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Background and Aim: Autoimmunity refers to the presence of autoantibodies and autoreactive lymphocytes against the structural molecules of an individual's cells or tissues, known as self-antigens or autoantigens. It might exist in the absence of autoimmune disease. However, how autoimmunity develops remains a mystery, despite the discovery of autoantibodies in human cord blood., Methods: Murine fetuses on day 14 of gestation were subjected to intraperitoneal injection of murine thyroid peroxidase (TPO) peptides or collagen type II (CII) at graded doses via transuterine approach. Postnatally, the recipients were examined for autoantibodies by ELISA and autoreactive lymphocytes by in vitro incorporation of tritium and for the development of autoimmune thyroiditis or arthritis., Results: At one month of age, the recipients did not secrete significant levels of anti-TPO or CII IgG 2a in sera until a dose of 0.5 µg TPO or 5.0 µg CII was injected in utero. Serum anti-TPO or CII IgG 2a persisted for at least two to four months postnatally. In recipients with elevated autoantibodies, their lymphocytes also showed proliferative responses specifically to TPO or CII. However, the development of autoantibodies and autoreactive lymphocytes was not associated with inflammatory cell infiltration of thyroid glands or paw joints even though anti-TPO or CII IgG 2a was enhanced by postnatal TPO or CII challenge., Conclusion: Fetal exposure to free autoantigens could be immunogenic, shedding new light on the in utero origin of autoantibodies and autoreactive lymphocytes. The development of autoimmunity requires a threshold intensity of autoantigen exposure in the fetus., (Copyright © 2024. Published by Elsevier Inc.)

Background: Neurosphere medium (NSM) and self-renewal medium (SRM) were widely used to isolate enteric neural stem cells (ENSCs) in the form of neurospheres. ENSCs or their neurosphere forms were neurogenic and gliogenic, but the compelling evidence for their capacity of assembling enteric neural networks remained lacking, raising the question of their aptitude for rebuilding the enteric nervous system (ENS) in ENSC therapeutics. It prompted us to explore an effective culture protocol or strategy for assembling ENS networks, which might also be employed as an in vitro model to simplify the biological complexity of ENS embedded in gut walls., Methods: NSM and SRM were examined for their capacity to generate neurospheres in mass culture of dispersed murine fetal enterocytes at serially diluted doses and assemble enteric neural networks in two- and three-dimensional cell culture systems and ex vivo on gut explants. Time-lapse microphotography was employed to capture cell activities of assembled neural networks. Neurosphere transplantation was performed via rectal submucosal injection., Results: In mass culture of dispersed enterocytes, NSM generated discrete units of neurospheres, whereas SRM promoted neural network assembly with neurospheres akin to enteric ganglia. Both were highly affected by seeding cell doses. SRM had similar ENSC mitosis-driving capacity to NSM, but was superior in driving ENSC differentiation in company with heightened ENSC apoptosis. Enteric neurospheres were motile, capable of merging together. It argued against their clonal entities. When nurtured in SRM, enteric neurospheres proved competent to assemble neural networks on two-dimensional coverslips, in three-dimensional hydrogels and on gut explants. In the course of neural network assembly from enteric neurospheres, neurite extension was preceded by migratory expansion of gliocytes. Assembled neural networks contained motile ganglia and gliocytes that constantly underwent shapeshift. Neurospheres transplanted into rectal submucosa might reconstitute myenteric plexuses of recipients' rectum., Conclusion: Enteric neurospheres mass-produced in NSM might assemble neural networks in SRM-immersed two- or three-dimensional environments and on gut explants, and reconstitute myenteric plexuses of the colon after rectal submucosal transplantation. Our results also shed first light on the dynamic entity of ENS and open the experimental avenues to explore cellular activities of ENS and facilitate ENS demystification., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Ischemia and no obstructive coronary artery disease (INOCA) disproportionately impacts women, yet the underlying pathologies are often not distinguished, contributing to adverse health care experiences and poor quality of life. Coronary function testing at the time of invasive coronary angiography allows for improved diagnostic accuracy. Despite increased recognition of INOCA and expanding access to testing, data lack on first-person perspectives and the impact of receiving a diagnosis in women with INOCA., Methods: From 2020 to 2021, we conducted structured telephone interviews with 2 groups of women with INOCA who underwent invasive coronary angiography (n=29) at Yale New Haven Hospital, New Haven, CT: 1 group underwent coronary function testing (n=20, of whom 18 received a mechanism-based diagnosis) and the other group who did not undergo coronary function testing (n=9). The interviews were analyzed using the constant comparison method by a multidisciplinary team., Results: The mean age was 59.7 years, and 79% and 3% were non-Hispanic White and non-Hispanic Black, respectively. Through iterative coding, 4 themes emerged and were further separated into subthemes that highlight disease experience aspects to be addressed in patient care: (1) distress from symptoms of uncertain cause: symptom constellation, struggle for sensemaking, emotional toll, threat to personal and professional identity; (2) a long journey to reach a definitive diagnosis: self-advocacy and fortitude, healthcare interactions brought about further uncertainty and trauma, therapeutic alliance, sources of information; (3) establishing a diagnosis enabled a path forward: relief and validation, empowerment; and (4) commitment to promoting awareness and supporting other women: recognition of sex and racial/ethnic disparities, support for other women., Conclusions: Insights about how women experience the symptoms of INOCA and their interactions with clinicians and the healthcare system hold powerful lessons for more patient-centered care. A coronary function testing-informed diagnosis greatly influences the healthcare experiences, quality of life, and emotional states of women with INOCA., Competing Interests: Disclosures Dr Spatz receives grant funding from the Centers for Disease Control and Prevention (20042801-Sub01), National Institute on Minority Health and Health Disparities (U54MD010711-01), and the US Food and Drug Administration to support projects within the Yale-Mayo Clinic Center of Excellence in Regulatory Science and Innovation (CERSI; U01FD005938), including a project to develop a novel survey tool for women with ischemia and no obstructive coronary artery disease. She also receives funding from the National Institute of Biomedical Imaging and Bioengineering (R01 EB028106-01) and the National Heart, Lung, and Blood Institute (R01HL151240). S.M. Shah receives research support from Women’s Health Research at Yale, Abbott Vascular Inc and the US Food and Drug Administration to support projects within the Yale-Mayo CERSI (U01FD005938), including a project to develop a novel survey tool for women with ischemia and no obstructive coronary artery disease. The other authors report no conflicts.

Nano-sized particles in wastewater are generally considered colloids, but their production and size distribution are not well understood. Organic nano-sized particles are more abundant than engineered nanomaterials in wastewater, where they may cause membrane fouling, harbor pathogens, and transport contaminants to the environment. To our knowledge, this study is the first to examine the seasonal behavior, removal, and the quantity and size of suspended particles (both unfiltered and filtered through a 450 nm filter) at multiple points within different processes along two water resource recovery facilities (WRRFs, formerly wastewater treatment plants). In Southern California where wastewater is often reused or reclaimed, a better understanding of nano-sized particles generation and removal may help reduce cost. We found that both types of the biological secondary treatments investigated (conventional activated sludge process and trickling filter) were more efficient in removing suspended particles larger than 450 nm than they were smaller ones. However, the results show that current treatment processes are not designed to remove nano-sized particles efficiently. We also investigated the factors that correlate with their occurrence and found that there was a significant and direct correlation between influent dissolved chemical oxygen demand (COD) and the abundance of suspended particles both larger and smaller than 450 nm, suggesting that the suspended particles increased with dissolved COD in the WRRFs and thus were biogenically generated during the wastewater treatment. Although no conclusive seasonal correlations were found, dissolved COD management may control nano-sized particle production. PRACTITIONER POINTS: Conventional secondary treatments (activated sludge and trickling filter) could efficiently remove particles but not as efficiently for nano-sized particles (40.1-52.7% removal). At one facility, particles of all sizes were found to correlate with dissolved carbon and EPS, meaning they were biogenic. Monitoring dissolved carbon or EPS precursors may help control membrane fouling post-secondary treatment, and this warrants more studies., (© 2023 Water Environment Federation.)

Extending well beyond the original use of propagating neural precursors from the central nervous system and dorsal root ganglia, neurosphere medium (NSM) and self-renewal medium (SRM) are two distinct formulas with widespread popularity in enteric neural stem cell (ENSC) applications. However, it remains unknown what growth factors or nutrients are crucial to ENSC development, let alone whether the discrepancy in their components may affect the outcomes of ENSC culture. Dispersed enterocytes from murine fetal gut were nurtured in NSM, SRM or their modifications by selective component elimination or addition to assess their effects on ENSC development. NSM generated neuriteless neurospheres, whereas SRM, even deprived of chicken embryo extract, might wire ganglia together to assemble neural networks. The distinct outcomes came from epidermal growth factor, which inhibited enteric neuronal wiring in NSM. In contrast, basic fibroblast growth factor promoted enteric neurogenesis, gangliogenesis, and neuronal wiring. Moreover, vitamin A derivatives might facilitate neuronal maturation evidenced by p75 downregulation during ENSC differentiation toward enteric neurons to promote gangliogenesis and network assembly. Our results might help to better manipulate ENSC propagation and differentiation in vitro, and open a new avenue for the study of enteric neuronal neuritogenesis and synaptogenesis.

Objective: The relative risk of SARS-CoV-2 infection and COVID-19 disease severity among people with rheumatic and musculoskeletal diseases (RMDs) compared to those without RMDs is unclear. This study was undertaken to quantify the risk of SARS-CoV-2 infection in those with RMDs and describe clinical outcomes of COVID-19 in these patients., Methods: We conducted a systematic literature review using 14 databases from January 1, 2019 to February 13, 2021. We included observational studies and experimental trials in RMD patients that described comparative rates of SARS-CoV-2 infection, hospitalization, oxygen supplementation/intensive care unit (ICU) admission/mechanical ventilation, or death attributed to COVID-19. Methodologic quality was evaluated using the Joanna Briggs Institute critical appraisal tools or the Newcastle-Ottawa scale. Risk ratios (RRs) and odds ratios (ORs) with 95% confidence intervals (95% CIs) were calculated, as applicable for each outcome, using the Mantel-Haenszel formula with random effects models., Results: Of the 5,799 abstracts screened, 100 studies met the criteria for inclusion in the systematic review, and 54 of 100 had a low risk of bias. Among the studies included in the meta-analyses, we identified an increased prevalence of SARS-CoV-2 infection in patients with an RMD (RR 1.53 [95% CI 1.16-2.01]) compared to the general population. The odds of hospitalization, ICU admission, and mechanical ventilation were similar in patients with and those without an RMD, whereas the mortality rate was increased in patients with RMDs (OR 1.74 [95% CI 1.08-2.80]). In a smaller number of studies, the adjusted risk of outcomes related to COVID-19 was assessed, and the results varied; some studies demonstrated an increased risk while other studies showed no difference in risk in patients with an RMD compared to those without an RMD., Conclusion: Patients with RMDs have higher rates of SARS-CoV-2 infection and an increased mortality rate., (© 2021 The Authors. Arthritis & Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

Objective: Individuals with HIV are at increased risk for osteoporosis. A healthy diet with adequate Ca is recommended to promote bone health. However, lengthy nutritional assessments pose barriers to routine screenings in clinical practice. This study aimed to examine the validity and reproducibility of a six-item dietary Ca screening tool among Chinese individuals with HIV., Design: We conducted a two time-point study in an outpatient setting. Volunteers self-administered the six-item tool upon enrolment and again at 1-month follow-up. At baseline, participants also completed a validated FFQ and surveys regarding demographic and clinical risk factors., Setting: Beijing, China; Shenzhen, Guangdong, China., Participants: Upon enrolment, 127 individuals with HIV participated in the study, of whom 83 completed the follow-up screening., Results: Mean age of participants was 35·2 (sd 9·3) years, average BMI was 22·8 (sd 3·8) kg/m2 and 89 % were men. Among the participants, 54·7 % reported Ca intake less than 800 mg/d. The six-item tool demonstrated fair-to-moderate relative validity with a correlation of 0·39 and 75·7 % of subjects classified in same/adjacent quartiles as the reference, and moderate-to-good reproducibility with a correlation of 0·60 and 83·1 % of subjects classified in same/adjacent quartiles. Finally, receiver operating characteristic analyses yielded a sensitivity of 87·0 % and a specificity of 39·4 % with optimised cut-off level., Conclusions: The six-item tool presented adequate validity and reproducibility to identify individuals with low Ca intake among the target population, providing a convenient instrument for categorising Ca intake in clinical practice, prompting referrals for further assessment, and raising awareness of dietary Ca in bone disease prevention.

Among adults, persons in control of a vehicle (i.e., drivers) are less likely to experience motion sickness compared to persons in the same vehicle who do not control it (i.e., passengers). This "driver-passenger effect" is well-known in adults, but has not been evaluated in children. Using a yoked-control design with seated pre-adolescent children, we exposed dyads to a driving video game. In each dyad, one child (the driver) drove the virtual vehicle. Their performance was recorded, and later shown to the other child (the passenger). Thus, visual motion stimuli were identical for the members of each dyad. During exposure to the video game, we monitored the quantitative kinematics of head and torso movements. Participants were instructed to discontinue participation immediately if they experienced any symptoms of motion sickness, however mild. Accordingly, the movements that we recorded preceded the onset of motion sickness. Results revealed that Passengers (73.08%) were more likely than Drivers (42.31%) to state that they were motion sick. Drivers tended to move more than passengers, and with a greater degree of multifractality. The magnitude of movement was greater among participants who later reported motion sickness than among those who did not. In addition, for the multifractality of movement a statistically significant interaction revealed that postural precursors of motion sickness differed qualitatively between Drivers and Passengers. Overall, the results reveal that control of a virtual vehicle reduces the risk of motion sickness among pre-adolescent children., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Despite increasing growth of interest in transcranial direct current stimulation (tDCS), its underlying mechanisms are still unclear. With many claims based on the anodal-excitation and cathodal-inhibition dichotomy originally observed in the motor cortex, surprisingly few studies have examined these fundamental polarity-specific effects beyond the motor cortex. The after-effects of tDCS on the visual cortex are of particular interest because of their potential application to vision restoration and migraine treatment. Yet the limited studies revealed conflicting results. Here we investigated whether polarity-specific tDCS effects exist in the visual cortex. In a counterbalanced within-subject crossover design, 20 healthy subjects each completed three sessions of anodal, cathodal and sham tDCS (2 mA for 20 min) applied over the visual cortex. Pattern-reversal visual evoked potentials (VEP) and their habituation slopes were measured at five time-points immediately before, after and every 15 min following the end of tDCS. Compared to sham, we found no significant tDCS induced after-effects on VEP amplitudes or habituation slopes, supported by strong evidence from Bayesian statistics. Neither were there any after-effects of tDCS on EEG power of the frequency of stimulus presentation, theta or alpha band. In conclusion, our results challenge previous findings of robust polarity-dependent after-effects of tDCS over the visual cortex., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Few studies have comprehensively and systematically analyzed nationwide samples. This study purposed to explore temporal trends and predictors of medical resource utilization and medical outcomes in these patients to obtain data that can be used to improve healthcare policies and to support clinical and administrative decision-making., Methods: This study used nationwide population data contained in the Longitudinal Health Insurance Database of Taiwan. The 14,970 inguinal hernia repair patients were enrolled in this study (age range, 18-100 years) from 1997 to 2013 in Taiwan. After temporal trends analysis of demographic characteristics, clinical characteristics, and institutional characteristics, predictors of postoperative medical resource utilization and medical outcomes were evaluated through multiple linear regression analysis and Cox regression analysis., Results: The prevalence of inguinal hernia repair per 100,000 population significantly decreased from 195.38 in 1997 to 39.66 in 2013 (p < 0.05). Demographic characteristics, clinical characteristics, and institutional characteristics were significantly associated with postoperative medical resource utilization and medical outcomes (p < 0.05). Of these characteristics, both surgeon volume and hospital volume had the strongest association., Conclusions: The inguinal hernia repair prevalence rate gradually decreased during the study period. Demographic characteristics, clinical characteristics, and institutional characteristics had strong associations with postoperative medical resource utilization and medical outcomes. Furthermore, hospital volume and surgeon volume had the strongest associations with postoperative medical resource utilization and medical outcomes. Additionally, providing the education needed to make the most advantageous medical decisions would be a great service not only to patients and their families, but also to the general population.

Despite the evidence for fetal immunization following maternal infection, it remained a mystery how the fetal immune system was primed by vertically-transmitted pathogens or microbial antigens, especially before its full maturation. We previously demonstrated the capacity of fetal macrophages for endocytosing oncoprotein and allergens to bridge towards adaptive immunity in postnatal life. To investigate the immunological consequences of fetal contact with microbial antigens and the role of fetal macrophages in the defense against infection before T-cell development, we exposed gestational day 14 murine fetuses and their macrophages to flagellin and heat-killed Salmonella Typhimurium. Recipients with in utero exposure to Salmonella antigens or adoptive transfer of microbial antigen-loaded fetal macrophages were examined for immune responses to Salmonella antigens and resistance to virulent Salmonella challenge. Fetal exposure to microbial antigens or adoptive transfer of microbial antigen-loaded fetal macrophages could confer antigen-specific adaptive immunity. However, protective immunity against lethal Salmonella challenge was only granted to those receiving heat-killed Salmonella antigens, presenting as heightened recall responses of serum anti-lipopolysaccharide immunoglobulins and interferon-gamma. In immunized recipients surviving Salmonella challenge, their serum transfer to succeeding recipients provided immediate protection from lethal Salmonella challenge in preference to lymphocyte transfer, indicating a more active role of humoral immunity in the prevention of Salmonella invasiveness. Our study sheds insight on the role of fetal macrophages in immunogenicity to transplacental pathogens regardless of fetal lymphocyte maturity, paving the way for fetal macrophage therapies to enhance vaccine responsiveness or increase resistance to pathogenic microorganisms in perinatal life.

The occurrence, fate and removal of microplastics (MPs) in a wastewater treatment plant (WWTP) in Central Italy were investigated together with their potential adverse effects on anaerobic processes. In the influent of the WWTP, 3.6 MPs . L -1 were detected that mostly comprised polyester fibers and particles in the shape of films, ranging 0.1-0.5 mm and made of polyethylene and polypropylene (PP). The full-scale conventional activated sludge scheme removed 86% of MPs, with the main reduction in the primary and secondary settling. MPs particles bigger than 1 mm were not detected in the final effluent and some loss of polymers types were observed. In comparison, the pilot-scale upflow granular anaerobic sludge blanket (UASB) + anaerobic membrane bioreactor (AnMBR) configuration achieved 94% MPs removal with the abatement of 87% of fibers and 100% of particles. The results highlighted an accumulation phenomenon of MPs in the sludge and suggested the need to further investigate the effects of MPs on anaerobic processes. Accordingly, PP-MPs at concentrations from 5 PP-MPs . gTS -1 to 50 PP-MPs . gTS -1 were spiked in the pilot-scale UASB reactor that was fed with real municipal wastewater, where up to 58% decrease in methanogenic activity was observed at the exposure of 50 PP-MPs . gTS -1 . To the best of our knowledge, the presented results are the first to report of PP-MPs inhibition on anaerobic processes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

A new biodegradable aliphatic-aromatic poly (butylene carbonate-co-terephthalate) (PBCT-85) with the molar ratio [BC]/[BT] = 85/15, successfully synthesized through transesterification and polycondensation processes, was identified using 1H-NMR spectra. Various weight ratios of PBCT/organically modified layered zinc phenylphosphonate (m-PPZn) nanocomposites were manufactured using the solution mixing process. Wide-angle X-ray diffraction and transmission electron microscopy were used to examine the morphology of PBCT-85/m-PPZn nanocomposites. Both results exhibited that the stacking layers of m-PPZn were intercalated into the PBCT-85 polymer matrix. The additional m-PPZn into PBCT-85 copolymer matrix significantly enhanced the storage modulus at -70 °C, as compared to that of neat PBCT-85. The lipase from Pseudomonas sp. was used to investigate the enzymatic degradation of PBCT-85/m-PPZn nanocomposites. The weight loss decreased as the loading of m-PPZn increased, indicating that the existence of m-PPZn inhibits the degradation of the PBCT-85 copolymers. This result might be attributed to the higher degree of contact angle for PBCT-85/m-PPZn nanocomposites. The PBCT-85/m-PPZn composites approved by MTT assay are appropriate for cell growth and might have potential in the application of biomedical materials.

Background: Envisioned as a similar process to tumorigenesis in terms of biological behaviors and molecular basis, embryogenesis necessitates an immune surveillance system to eliminate erratically transformed cells. Our previous study demonstrated that fetal macrophage-like phagocytes triggered Th2-skewed immunity following endocytosing prenatally administered ovalbumin to facilitate postnatal allergic airway responses, highlighting the critical role fetal phagocytes played in dealing with antigens present in developing fetuses and shaping subsequent immune responses. It prompted us to examine whether fetuses could mount Th1 tumoricidal immunity against tumorigenesis following in utero exposure to tumor antigens., Methods: Gestational day 14 murine fetuses underwent in utero injection of Th1-promoting human papilloma virus (HPV) E7 peptides. Postnatally, recipients were examined for immunological consequences and the resistance to TC-1 tumorigenesis., Results: Fetal exposure to HPV E7 did not cause tolerance but rather immunization in the recipients, characterized by proinflammatory Th1 polarization of their lymphocytes. Fetal macrophage-like phagocytes were responsible for taking up HPV E7 and triggering HPV E7-specific T-cell cytotoxicity and humoral immunity that rendered recipients resistant to TC-1 tumorigenesis in postnatal life. Adoptive transfer of HPV E7-loaded fetal phagocytes also elicited Th1 immunity with rapid expansion of HPV E7-specific cytotoxic CD8 + T-cell clones in response to TC-1 cell challenge so as to protect the recipients from TC-1 tumorigenesis, but failed to completely eliminate pre-existing TC-1 cells despite perceptible attenuation of local TC-1 tumor growth., Conclusions: Our study revealed that Th2-biasing fetus was not immune-privileged to foreign peptides, but competent to mount Th1 cytotoxic immunity and generate immunoglobulins against tumorigenesis following in utero exposure to Th1-promoting oncoantigen. It shed light on the role of fetal macrophage-like phagocytes in bridging toward tumor antigen-specific cellular and humoral immunity potentially as an immune surveillance system to eliminate transformed cells that might be egressing during embryogenesis and leftover until postnatal life., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Osteoporosis presents an increasing problem globally, primarily affecting older adults and postmenopausal women. Among important modifiable risk factors for osteoporosis, physical activity and calcium intake help reduce bone mineral loss and decrease the prevalence of osteoporosis. Although osteoporosis knowledge and health beliefs are associated with adopting preventive behavior and screening rates, few studies have evaluated them in Latin American populations. Materials and Methods: We conducted a cross-sectional study among female community leaders in a Peruvian periurban setting. A total of 60 women participated in the study, with a mean age of 43.7 ± 8.3 years, mean body mass index of 30.4 ± 5.3 kg/m 2 , 88% being overweight or obese, and 58.3% having completed high school education or beyond. Participants completed translated and culturally adapted Osteoporosis Knowledge Test and Osteoporosis Health Belief Scale via semistructured interviews. Results: Most participants reported high knowledge regarding osteoporosis, perceived benefits to exercise and calcium intake, and health motivation. The level of osteoporosis knowledge was highly associated with the level of education, and we found a trend for the association between level of knowledge and perceived benefits of exercise and barriers to calcium intake among participants. Conclusions: Female community leaders with high health motivation and community engagement can contribute enormously to osteoporosis prevention programs in local communities in the future., Competing Interests: No competing financial interests exist., (© The Mihaela Sava et al. 2020; Published by Mary Ann Liebert, Inc.)

The utilization of benzodiazepines (BZDs) and z-hypnotics has substantially increased with the aging of the population, but the risk of BZDs and z-hypnotics in the development of dementia remains a strong concern. This cohort study aimed to evaluate the risk of BZDs and z-hypnotics for subsequent dementia development with a special consideration of their half-lives and the concomitant use of these medications. People aged 65 years and older who were newly prescribed oral BZDs or z-hypnotics between 2003 and 2012 were identified from Taiwan's National Health Insurance Research Database. All BZDs were categorized as long-acting drugs (≥ 20 h) or short-acting drugs (< 20 h) for further comparisons, and data were collected on a quarterly basis, starting on the first date of drug prescription and ending on the date of death, occurrence of dementia, or end of the follow-up period (December 31, 2012), whichever came first. All dementia events except vascular dementia occurring during the follow-up period were identified. Among 260,502 eligible subjects, short-acting BZDs and z-hypnotics users were at greater risk of dementia than long-acting users [adjusted odds ratio (95% confidence interval) in short-acting BZD users, 1.98 (1.89-2.07); z-hypnotic users, 1.79 (1.68-1.91); and long-acting BZD users, 1.47 (1.37-1.58)]. In addition, subjects concomitantly using 2 or more BZDs or z-hypnotics had a higher risk of dementia than those who used 1 of these drugs (4.79 (3.95-5.81)). The use of BZDs and z-hypnotics was strongly associated with the risk of dementia development, especially the short-acting BZDs, z-hypnotics, and concomitant use of multiple agents. These findings deserve further interventional studies for clarification.

Conflicting data of the potential association between proton pump inhibitors (PPIs) and risk of dementia have been reported. This study aimed to examine the subsequent risk of incident dementia in older adults by categorizing subjects into different trajectories of longitudinal PPI use. A group-based trajectory modeling was used to identify distinct groups with regard to longitudinal PPI use over 3 years and to further examine the association between the trajectories of PPI use and dementia in a 5-year follow-up. Among 10,533 older adults who initiated PPIs, three distinct trajectories of longitudinal PPI use were identified: short-term (n = 7,406, 70.3%), intermittent (n = 1,528, 14.5%), and long-term users (n = 1,599, 15.2%). Long-term (hazard ratio (HR) = 0.99 (95% confidence interval (CI), 0.93-1.17)) and intermittent PPI users (HR = 0.91 (95% CI, 0.76-1.09)) were not associated with an increased risk of incident dementia compared with short-term users. Regardless of pattern of use, PPIs did not appear to significantly increase the risk of dementia over a mean follow-up period of 4 years., (© 2019 The Authors Clinical Pharmacology & Therapeutics © 2019 American Society for Clinical Pharmacology and Therapeutics.)

According to actively acquired tolerance, antigen exposure before full immune development in fetal or early neonatal life will cause tolerance to this specific antigen. In this study, we aimed to examine whether allogeneic tolerance could be elicited by in utero exposure to surface MHC antigens of allogenic cells or soluble form of MHC exosomes. Gestational day 14 FVB/N fetuses were subjected to intraperitoneal injection of allogeneic major histocompatibility complex (MHC) exosomes or highly enriched B-cells. Postnatally, the recipients were examined for the immune responses to donor alloantigens by lymphocyte proliferative reactions and skin transplantation. In utero exposure to allogeneic MHC exosomes abolished the alloreactivity of recipients' lymphocytes to the alloantigens, but could not confer skin allograft tolerance. In utero transplantation of highly enriched allogeneic B-cells generated low-level B-cell chimerism in the recipients. However, it only extended the survivals of skin allograft by a few days despite the lack of donor-specific alloreactivity of recipients' lymphocyte. Thus, an early in utero contact with exosomal or B-cell alloantigens did not lead to full skin tolerance but rather, at best, only to delayed skin rejection in the presence of microchimerism made by B-cell inocula. These results argued against the theory of actively acquired tolerance, and implicated that in utero exposure to marrow cells in previous studies was a unique model of allo-tolerance induction that involved the establishment of significant hematopoietic chimerism. Taken together with the discovery of in utero sensitization to ovalbumin in our previous studies, the immunological consequences of fetal exposure to foreign antigens might vary according to the type or nature of antigens introduced.

The Intergovernmental Panel on Climate Change (IPCC) reported that all carbon dioxide (CO 2 ) emissions generated by water resource recovery facilities (WRRFs) during treatment are modern, based on available literature. Therefore, such emissions were omitted from IPCC's greenhouse gas (GHG) accounting procedures. However, a fraction of wastewater's carbon is fossil in origin. We hypothesized that since the fossil carbon entering municipal WRRFs is mostly from soaps and detergents as dissolved organic matter, its fate can be selectively determined during the universally applied separation treatment processes. Analyzing radiocarbon at different treatment points within municipal WRRFs, we verified that the fossil content could amount to 28% in primary influent and showed varying distribution leaving different unit operations. We recorded the highest proportion of fossil carbon leaving the secondary treatment as off-gas and as solid sludge (averaged 2.08 kg fossil-CO 2 -emission-potential m -3 wastewater treated). By including fossil CO 2 , total GHG emission in municipal WRRFs increased 13%, and 23% if an on-site energy recovery system exists although much of the postdigestion fossil carbon remained in biosolids rather than in biogas, offering yet another carbon sequestration opportunity during biosolids handling. In comparison, fossil carbon contribution to GHG emission can span from negligible to substantial in different types of industrial WRRFs. With such a considerable impact, CO 2 should be analyzed for each WRRF and not omitted from GHG accounting.

Rationale: Actively acquired tolerance occurs when foreign antigens come into contact with the immature fetal immune system., Objectives: Armed with the knowledge of actively acquired tolerance, we attempted to prenatally abolish or diminish allergic responses., Methods: In utero injection of adjuvant-free ovalbumin (OVA) was conducted in Gestational Day 14 FVB/N mouse fetuses. Postnatally, mice were evaluated for their resistance to intraperitoneal OVA sensitization and oral or aerosolized OVA challenge, and then they were examined for humoral and cellular immunological profiles, airway hyperresponsiveness to bronchospastic stimuli, and lung histology. Fluorescent conjugates of OVA were used for further studies of mechanisms., Measurements and Main Results: This presumed tolerogenic action turned out to be a sensitization process with the development of anaphylaxis or heightened recall, T-helper cell type 2-skewed responses to postnatal encounter with OVA. Further postnatal aerosolized OVA stress triggered allergic lungs with functional and structural alterations of airways. The unintended consequence resulted from macrophage-like fetal phagocytes that took up OVA and differentiated toward dendritic cells. These fetal dendritic cell progenitors attenuated proteolysis of endocytosed OVA for delayed presentation in postnatal life. This specialty of fetal phagocytes effectively retains the memory of antigens internalized early before full development of the immune system, leading to an event of in utero sensitization., Conclusions: Our results have mechanical implications for prenatal imprinting of atopy and shed light on the importance of fetal phagocytes in shaping the developing immune system and initiating allergic airway diseases.

The objective of this study was to develop a high-frequency imaging platform for evaluating liver fibrosis in mice based on shear-wave elasticity imaging (SWEI). Although SWEI has been used to diagnose hepatic fibrosis clinically, it is performed at relatively low frequencies (<20 MHz). For preclinical ultrasound imaging in small animals, a high-frequency (>30 MHz) single-element transducer with mechanical scanning is often used. In this study we developed a new SWEI system based on a 40-MHz single-element transducer for imaging and a separate 20-MHz excitation transducer for producing the radiation force and the associated shear waves. Liver fibrosis was induced in ten C57BL/6 (B6) mice using carbon tetrachloride; the other ten mice served as the control group. Synchronizing the excitation beam (i.e., the beam from the excitation transducer) and the detection beam sequence (i.e., the beam from the imaging transducer) allows this mechanical-scanning setup to analyze the shear-wave dispersion relation. The liver viscoelastic properties were determined in vivo by measuring the shear-wave dispersion curve followed by fitting to the Voigt model. The mice were then killed and the fibrosis stage was evaluated (from F0 to F4) based on the METAVIR score. The measured mean values of liver elasticity and viscosity, respectively, ranged from 1.06 to 1.89 kPa and from 1.29 to 1.75 Pa∙s for normal F0 and fibrosis stages of F3 and F4. The Spearman coefficients for the correlations between the measured elasticity and viscosity at various fibrosis stages as assessed by the METAVIR score were 0.73 (p < 0.001) and 0.634 (p = 0.0013), respectively. We also found that the collagen content in the liver was linearly correlated with the measured elasticity (r(2) = 0.54, p < 0.001) and less strongly with the viscosity (r2 = 0.26, p = 0.022). Finally, the diagnosis performance of high-frequency SWEI was evaluated using multivariate receiver operating characteristic curve (ROC) analysis. The areas under the multivariate ROC curve for diagnosing fibrosis stages of F ≥ 3, F = 4, F0 vs. F3, F0 vs. F4, and F3 vs. F4 were 0.9, 0.98, 0.83, 1.0, and 0.96, respectively. Compared with traditional ROC analysis, an improved diagnosis performance was found for diagnosing fibrosis stages of F ≥ 3 and F0 vs. F3. These results demonstrate that the developed high-frequency SWEI platform can yield quantitative viscoelastic properties for diagnosing various fibrosis stages in mice. It is a promising tool for studying the progression of liver fibrosis in preclinical animal models both noninvasively and quantitatively.

Emotional faces are often salient cues of threats or other important contexts, and may therefore have a large effect on cognitive processes of the visual environment. Indeed, many behavioral studies have demonstrated that emotional information can modulate visual attention and eye movements. The aim of the present study was to investigate (1) how irrelevant emotional face distractors affect saccadic behaviors and (2) whether such emotional effects reflect a specific neural mechanism or merely biased selective attention. We combined a visual search paradigm that incorporated manipulation of different types of distractor (fearful faces or scrambled faces) and delivered anodal transcranial direct current stimulation (tDCS) over the superior temporal sulcus and the frontal eye field to investigate the functional roles of these areas in processing facial expressions and eye movements. Our behavioral data suggest that irrelevant emotional distractors can modulate saccadic behaviors. The tDCS results showed that while rFEF played a more general role in controlling saccadic behavior, rSTS is mainly involved in facial expression processing. Furthermore, rSTS played a critical role in processing facial expressions even when such expressions were not relevant to the task goal, implying that facial expressions and processing may be automatic irrespective of the task goal., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Aortic dissection and atherosclerosis are highly fatal diseases. The development of both diseases is closely associated with highly complex haemodynamics. Thus, in predicting the onset of cardiac disease, it is desirable to obtain a detailed understanding of the flowfield characteristics in the human cardiovascular circulatory system. Accordingly, in this study, a numerical model of a normal human thoracic aorta is constructed using the geometry information obtained from a phase-contrast magnetic resonance imaging (PC-MRI) technique. The interaction between the blood flow and the vessel wall dynamics is then investigated using a coupled fluid-structure interaction (FSI) analysis. The simulations focus specifically on the flowfield characteristics and pulse wave velocity (PWV) of the blood flow. Instead of using a conventional PC-MRI method to measure PWV, we present an innovative application of using the FSI approach to numerically resolve PWV for the assessment of wall compliance in a thoracic aorta model. The estimated PWV for a normal thoracic aorta agrees well with the results obtained via PC-MRI measurement. In addition, simulations which consider the FSI effect yield a lower predicted value of the wall shear stress at certain locations in the cardiac cycle than models which assume a rigid vessel wall. Consequently, the model provides a suitable basis for the future development of more sophisticated methods capable of performing the computer-aided analysis of aortic blood flows.

To investigate the major injury patterns associated with traffic accidents and evaluate the risk factors of the main injury, a survey of Taiwan's national insurance admission data between 2002 and 2011 was performed. The incidence of traffic-accidents-related hospitalization was between 9.17% and 11.54% and the average mortality rate of the inpatients admitted due to traffic accidents was 0.68%. Of all inpatients due to road traffic accidents in Taiwan, orthopedic fractures were the most common injuries that accounted for 29.36% of them. There were a total of 391,197 cases of three orthopedic fracture groups that were divided into (1) fracture of upper limb, (2) fracture of lower limb, and (3) fracture of spine and trunk. An increase in national medical cost used for inpatients with orthopedic fractures was noted and ranged from US$ 45.6 million to US$ 86 million annually. These orthopedic fracture patterns were frequently associated with other injuries especially head injuries (ranged from 14% to 26%). A significant relation to male gender, older age, low income, and admission to high-level hospital to the observed fracture patterns was observed.

Previous studies predicted the disulfide bonding patterns of cysteines using a prior knowledge of their bonding states. In this study, we propose a method that is based on the ensemble support vector machine (SVM), with the structural features of cysteines extracted without any prior knowledge of their bonding states. This method is useful for improving the predictive performance of disulfide bonding patterns. For comparison, the proposed method was tested with the same dataset SPX that was adopted in previous studies. The experimental results demonstrate that bridge classification and disulfide connectivity predictions achieve 96.5% and 89.2% accuracy, respectively, using the ensemble SVM model, which outperforms the traditional method (51.5% and 51.0%, respectively) and the model that is based on a single-kernel SVM classifier (94.6% and 84.4%, respectively). For protein chain and residue classifications, the sensitivity, specificity, and accuracy of ensemble and single-kernel SVM approaches are better than those of the traditional methods. The predictive performances of the ensemble SVM and single-kernel models are identical, indicating that the ensemble model can converge to the single-kernel model for some applications., (© 2013 Elsevier Ltd. All rights reserved.)

A direct comparison between parallel activated sludge and integrated fixed-film activated sludge (IFAS) processes was performed in this study because both treatments received the same primary effluent, although differences may still remain due to different return flow rates. Modern ultrahigh resolution electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry was applied to characterize the complexity of effluent organic matter (EfOM) and to evaluate both processes in their abilities to change the EfOM molecular composition. At different stages during the two processes a direct comparison of the performance and changes in molecular composition of the IFAS with those of the activated sludge was undertaken. Large differences in the molecular composition between both processes were only apparent in the early stage of the aeration cells and the first cell of the IFAS possibly due to the higher flow rate and a delay in aerobic bacterial degradation. Despite the double flow rate (0.263 m(3) s(-1)) in the IFAS reactors compared to the activated sludge, by the end of the treatment the EfOM composition of both processes were undistinguishable from each other. However, a much more complex EfOM was generated in both processes, suggesting that bacteria are responsible for an increase in molecular diversity in the effluent.

Southern California is an increasingly urbanized hotspot for surfing, thus it is of great interest to assess the human illness risks associated with this popular ocean recreational water sport from exposure to fecal bacteria contaminated coastal waters. Quantitative microbial risk assessments were applied to eight popular Southern California beaches using readily available enterococcus and fecal coliform data and dose-response models to compare health risks associated with surfing during dry weather and storm conditions. The results showed that the level of gastrointestinal illness risks from surfing post-storm events was elevated, with the probability of exceeding the US EPA health risk guideline up to 28% of the time. The surfing risk was also elevated in comparison with swimming at the same beach due to ingestion of greater volume of water. The study suggests that refinement of dose-response model, improving monitoring practice and better surfer behavior surveillance will improve the risk estimation., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Research has confirmed that console video games give rise to motion sickness in many adults. During exposure to console video games, there are differences in postural activity (movement of the head and torso) between participants who later experience motion sickness and those who do not, confirming a prediction of the postural instability theory of motion sickness. Previous research has not addressed relations between video games, movement and motion sickness in children. We evaluated the nauseogenic properties of a commercially available console video game in both adults and 10-year-old children. Individuals played the game for up to 50 min and were instructed to discontinue immediately if they experienced any symptoms of motion sickness, however mild. During game play, we monitored movement of the head and torso. Motion sickness was reported by 67% of adults and by 56% of children; these rates did not differ. As a group, children moved more than adults. Across age groups, the positional variability of the head and torso increased over time during game play. In addition, we found differences in movement between participants who later reported motion sickness and those who did not. Some of these differences were general across age groups but we also found significant differences between the movement of adults and children who later reported motion sickness. The results confirm that console video games can induce motion sickness in children and demonstrate that changes in postural activity precede the onset of subjective symptoms of motion sickness in children.

Nitrous oxide (N₂O) is a long-lived and potent greenhouse gas produced during microbial nitrification and denitrification. In developed countries, centralized water reclamation plants often use these processes for N removal before effluent is used for irrigation or discharged to surface water, thus making this treatment a potentially large source of N₂O in urban areas. In the arid but densely populated southwestern United States, water reclamation for irrigation is an important alternative to long-distance water importation. We measured N₂O concentrations and fluxes from several wastewater treatment processes in urban southern California. We found that N removal during water reclamation may lead to in situ N₂O emission rates that are three or more times greater than traditional treatment processes (C oxidation only). In the water reclamation plants tested, N₂O production was a greater percentage of total N removed (1.2%) than traditional treatment processes (C oxidation only) (0.4%). We also measured stable isotope ratios (δN and δO) of emitted N₂O and found distinct δN signatures of N₂O from denitrification (0.0 ± 4.0 ‰) and nitrification reactors (-24.5 ± 2.2 ‰), respectively. These isotope data confirm that both nitrification and denitrification contribute to N₂O emissions within the same treatment plant. Our estimates indicate that N₂O emissions from biological N removal for water reclamation may be several orders of magnitude greater than N₂O emissions from agricultural activities in highly urbanized southern California. Our results suggest that wastewater treatment that includes biological nitrogen removal can significantly increase urban N₂O emissions., (by the American Society of Agronomy, Crop Science Society of America, and Soil Science Society of America, Inc.)

The executive control of voluntary action involves not only choosing from a range of possible actions but also the inhibition of responses as circumstances demand. Recent studies have demonstrated that many clinical populations, such as people with attention-deficit hyperactivity disorder, exhibit difficulties in inhibitory control. One prefrontal area that has been particularly associated with inhibitory control is the pre-supplementary motor area (Pre-SMA). Here we applied non-invasive transcranial direct current stimulation (tDCS) over Pre-SMA to test its role in this behavior. tDCS allows for current to be applied in two directions to selectively excite or suppress the neural activity of Pre-SMA. Our results showed that anodal tDCS improved efficiency of inhibitory control. Conversely, cathodal tDCS showed a tendency towards impaired inhibitory control. To our knowledge, this is the first demonstration of non-invasive intervention tDCS altering subjects' inhibitory control. These results further our understanding of the neural bases of inhibitory control and suggest a possible therapeutic intervention method for clinical populations., (Copyright © 2011 Elsevier Inc. All rights reserved.)

The gold(I)-catalyzed hydroarylation of cyclohexa-1,3-dienes bearing an aryl group and a gem-diester in the tether proceeds in a 1,4-addition manner and in a diastereoselective fashion to afford perhydrophenanthrene rings. The reaction proceeded via attack of the aryl group onto the gold-activated cyclic dienes followed by rearomatization and protodeauration to generate perhydrophenanthrenes in good yields. This hydroarylation can be applied to the synthesis of perhydrocyclohepta[a]naphthalenes from aryl-tethered cycloheptadienes and the gold(I) catalyst.

Effluent dissolved organic matter (EfOM) collected from the secondary-treated wastewater of the Orange County Sanitation District (OCSD) located in Fountain Valley, California, USA was compared to natural organic matter collected from the Suwannee River (SRNOM), Florida using ultrahigh resolution electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR-MS). Furthermore, the two different treatment processes at OCSD, activated sludge and trickling filter, were separately investigated. The blend of these two effluents was further evaluated after it had passed through the microfiltration process of the Advanced Water Purification Facility (AWPF) at Orange County Water District (OCWD). EfOM contained 872 different m/z peaks that were unambiguously assigned to exact molecular formulae containing a single sulfur atom and carbon, hydrogen and oxygen atoms (CHOS formulae). In contrast, the SRNOM sample only contained 152 CHOS formulae. The trend in CHO molecular compositions was opposite with 2500 CHO formulae assigned for SRNOM but only about 1000 for EfOM. The CHOS-derived mass peaks with highest abundances in EfOM could be attributed to surfactants such as linear alkyl benzene sulfonates (LAS), their co-products dialkyl tetralin sulfonates (DATS) and their biodegraded metabolites such as sulfophenyl carboxylic acids (SPC). The differences between the treatments were found minor with greater differences between sampling dates than treatment methods used., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

The proper prediction of the location of disulfide bridges is efficient in helping to solve the protein folding problem. Most of the previous works on the prediction of disulfide connectivity pattern use the prior knowledge of the bonding state of cysteines. The DBCP web server provides prediction of disulfide bonding connectivity pattern without the prior knowledge of the bonding state of cysteines. The method used in this server improves the accuracy of disulfide connectivity pattern prediction (Q(p)) over the previous studies reported in the literature. This DBCP server can be accessed at http://120.107.8.16/dbcp or http://140.120.14.136/dbcp.

Nosocomial infections caused by multidrug-resistant (MDR) Acinetobacter baumannii have been increasing in recent years, posing a threat to public health worldwide. The susceptibility to eight antimicrobial agents of 35 clinical A. baumannii isolates from Taiwan was tested. Isolates were examined by polymerase chain reaction (PCR) and sequencing for beta-lactamase genes and mutations in the gyrA and parC genes. Expression of AdeB, an efflux pump protein, was evaluated by real-time quantitative PCR. The level of adeB expression correlated with resistance to ciprofloxacin and ampicillin/sulbactam in A. baumannii isolates. Almost all isolates with full resistance to ciprofloxacin had both high adeB expression and point mutations in parC and gyrA, but 4 intermediate-resistant isolates had only high adeB expression without point mutations in gyrA or parC, in contrast to 18 susceptible isolates with low adeB expression and without mutations in gyrA or parC. Sixteen isolates (45.7%) carrying a type 1 integron were MDR as well as being more resistant to imipenem, amikacin, gentamicin, ceftazidime or cefepime than those without the integron. The class 1 integron in A. baumannii carried different resistance gene cassettes, including 5'CS-bla(IMP-1)-aadA4-3'CS, 5'CS-aacA4-aadA1-3'CS and 5'CS-aacC1-aadA1-3'CS. In conclusion, expression of the adeB gene was associated with resistance to ciprofloxacin and ampicillin/sulbactam in A. baumannii. Multiple mutations in gyrA and parC also played a role in ciprofloxacin resistance. The major metallo-beta-lactamase contributing to imipenem resistance in A. baumannii in Taiwan was bla(IMP-1), which was carried by the class 1 integron. The class 1 integron was associated with the MDR phenotype in A. baumannii., ((c) 2010. Published by Elsevier B.V. All rights reserved.)

Cardiovascular disease is the primary cause of morbidity and mortality in the western world. Complex hemodynamics plays a critical role in the development of aortic dissection and atherosclerosis, as well as many other diseases. Since fundamental fluid mechanics are important for the understanding of the blood flow in the cardiovascular circulatory system of the human body aspects, a joint experimental and numerical study was conducted in this study to determine the distributions of wall shear stress and pressure and oscillatory WSS index, and to examine their correlation with the aortic disorders, especially dissection. Experimentally, the Phase-Contrast Magnetic Resonance Imaging (PC-MRI) method was used to acquire the true geometry of a normal human thoracic aorta, which was readily converted into a transparent thoracic aorta model by the rapid prototyping (RP) technique. The thoracic aorta model was then used in the in vitro experiments and computations. Simulations were performed using the computational fluid dynamic (CFD) code ACE+((R)) to determine flow characteristics of the three-dimensional, pulsatile, incompressible, and Newtonian fluid in the thoracic aorta model. The unsteady boundary conditions at the inlet and the outlet of the aortic flow were specified from the measured flowrate and pressure results during in vitro experiments. For the code validation, the predicted axial velocity reasonably agrees with the PC-MRI experimental data in the oblique sagittal plane of the thoracic aorta model. The thorough analyses of the thoracic aorta flow, WSSs, WSS index (OSI), and wall pressures are presented. The predicted locations of the maxima of WSS and the wall pressure can be then correlated with that of the thoracic aorta dissection, and thereby may lead to a useful biological significance. The numerical results also suggest that the effects of low WSS and high OSI tend to cause wall thickening occurred along the inferior wall of the aortic arch and the anterior wall of the brachiocephalic artery, similar implication reported in a number of previous studies.

The sequential deletion method is generally used to locate the functional domain of a protein. With this method, in order to find the various N-terminal truncated mutants, researchers have to investigate the ATG-like codons, to design various multiplex polymerase chain reaction (PCR) forward primers and to do several PCR experiments. This web server (N-terminal Truncated Mutants Generator for cDNA) will automatically generate groups of forward PCR primers and the corresponding reverse PCR primers that can be used in a single batch of a multiplex PCR experiment to extract the various N-terminal truncated mutants. This saves much time and money for those who use the sequential deletion method in their research. This server is available at http://oblab.cs.nchu.edu.tw:8080/WebSDL/.

Although the side-match vector quantizer (SMVQ) reduces the bit rate, the image coding quality by SMVQ generally degenerates as the gray level transition across the boundaries of the neighboring blocks is increasing or decreasing. This study presents a smooth side-match method to select a state codebook according to the smoothness of the gray levels between neighboring blocks. This method achieves a higher PSNR and better visual perception than SMVQ does for the same bit rate. Moreover, to design codebooks, a genetic clustering algorithm that automatically finds the appropriate number of clusters is proposed. The proposed smooth side-match classified vector quantizer (SSM-CVQ) is thus a combination of three techniques: the classified vector quantization, the variable block size segmentation and the smooth side-match method. Experimental results indicate that SSM-CVQ has a higher PSNR and a lower bit rate than other methods. Furthermore, the Lena image can be coded by SSM-CVQ with 0.172 bpp and 32.49 dB in PSNR.

The growth-promoting activity of GH, the principal hormonal determinant of body size, is mediated by insulin-like growth factor I (IGF-I). Most of the IGF-I in plasma circulates in a 150-kDa complex that contains IGF-binding protein-3 (IGFBP-3) and an acid-labile subunit (ALS). The 150-kDa complex serves as a reservoir of IGF-I and determines its bioavailability to the tissues. Formation of the 150-kDa complex depends upon the synthesis of ALS, which is synthesized primarily in liver and is regulated by GH. The present study demonstrates that GH stimulates ALS gene transcription in rat liver and ALS promoter activity in a rat hepatoma cell line. ALS messenger RNA (mRNA) and ALS nuclear transcripts were decreased to similar extents in the livers of GH-deficient hypophysectomized rats. GH increased hepatic ALS mRNA within 3-4 h to about 65% of the levels seen in sham-operated control rats. To confirm that GH stimulated ALS gene transcription, we transiently transfected an ALS promoter-luciferase reporter gene construct into H4-II-E rat hepatoma cells and primary rat hepatocytes. Recombinant human GH (hGH) stimulated promoter activity about 3-fold. In contrast, basal promoter activity was lower, and GH stimulation was absent when the ALS reporter construct was transfected into GH-responsive 3T3-F442A mouse preadipocyte fibroblasts. GH stimulation of ALS promoter activity in H4-II-E cells was mediated by functional GH receptors; nonprimate (rat and bovine) GH gave identical stimulation to hGH, and stimulation by hGH occurred at physiological concentrations. Reverse transcriptase-PCR analysis indicated that GH receptor mRNA was present in H4-II-E cells at approximately 40% of the level seen in rat liver. GH also induced the expression of the endogenous c-fos gene, indicating that the signaling pathway necessary for the activation of gene expression by GH was intact in H4-II-E cells. Thus, H4-II-E cells are a GH-responsive liver cell line that should provide a useful system in which to study the molecular mechanism of transcriptional regulation by GH of ALS and other hepatic genes.

Neither wild type nor attenuated S. typhimurium strains induced diarrheal illness in rabbits. All strains localized to the Peyer's patch at higher concentrations than in lumenal contents or adjacent ileum. Wild type S. typhimurium C5 induced a typhoid-like illness in rabbits with severe weight loss, bacteremia, persistent splenic colonization, and serum IgG response. Both attenuated strains were disseminated to spleen (day 3) but produced minimal systemic illness. They induced biliary IgA responses greater than the wild type (day 7), but minimal serum IgG responses. Both mutants of S. typhimurium are suitable for further development as live enteric vaccines to carry foreign antigens since they localize to Peyer's patch after oral inoculation, induce biliary antibody, and produce minimal systemic disease. The attenuated strains tested are systemically disseminated. It remains to be determined whether dissemination (determined by a large virulence plasmid) is necessary for the desired mucosal immune response or acceptable for an oral vaccine strain.

The PC12 cell line established from a rat pheochromocytoma has been extensively studied as a model of neuronal differentiation. Insulin-like growth factor-I (IGF-I) and IGF-II are mitogenic for PC12 cells under serum-starved conditions. IGF activity is modulated by a family of six IGF-binding proteins (IGFBPs). It recently was reported that PC12 cells produced an IGFBP that had a marked preferential binding affinity for IGF-II over IGF-I. We now show that the main IGFBP produced by PC12 cells is rat IGFBP-6 and compare its properties with those of human IGFBP-6. The predominant IGFBP in medium conditioned by undifferentiated and differentiated PC12 cells migrated on sodium dodecyl sulfate-12% polyacrylamide gel electrophoresis with an apparent molecular mass of 22.5-25 kilodaltons and was recognized by polyclonal antiserum to rat IGFBP-6 by immunoblotting. Rat IGFBP-6 mRNA (1.4 kilobases) was detected by Northern hybridization of total RNA extracted from PC12 cells using a rat IGFBP-6 cDNA probe. Rat IGFBP-6, like human IGFBP-6, is O-glycosylated; incubation with neuraminidase, fucosidase, and O-glycanase reduced its apparent molecular mass to 21 kilodaltons. Competitive binding studies of rat and human IGFBP-6 with [125I]IGF-II and unlabeled IGF-II or IGF-I demonstrated that both IGFBPs bound IGF-II with similar affinities (Ka, 1.5-1.8 x 10(11) M-1) and bound IGF-I with approximately 25- to 35-fold lower affinity than IGF-II. Thus, differences in amino acid sequence, such as deletion of nine amino-terminal residues (including two conserved cysteine residues) in rat IGFBP-6 compared with human IGFBP-6, do not alter its binding characteristics. PC12 cells should provide a useful system to define the regulation of IGFBP-6 expression and the role of IGFBP-6 in modulating IGF action.

The insulin-like growth factor-binding proteins (IGFBPs) are a family of six proteins that modulate the biological activity of IGF-I and IGF-II and determine their bioavailability to tissues. One of the IGFBPs, IGFBP-1, is distinctive in the dynamic response of its levels in human plasma to metabolic changes. Parallel changes occur in IGFBP-1 mRNA and IGFBP-1 transcription in rat liver. Using the well differentiated H4-II-E rat hepatoma cell line as a model system, we demonstrated previously that IGFBP-1 transcription is positively regulated by dexamethasone and negatively regulated by insulin. We now examine the effect of the protein synthesis inhibitor, cycloheximide, on the hormonal regulation of IGFBP-1 gene expression. Preincubation of H4-II-E cells with 10.7 microM cycloheximide for 1.5 h did not prevent the induction of IGFBP-1 mRNA and IGFBP-1 transcription (determined in nuclear run-on assays) by dexamethasone. By contrast, cycloheximide treatment abolished the decrease in IGFBP-1 mRNA induced by insulin. Insulin rapidly decreased IGFBP-1 transcription in the absence of cycloheximide (> 50% inhibition in 20 min) and caused a similar decrease in cells pretreated with cycloheximide. Cycloheximide alone also decreased IGFBP-1 transcription. Similar results were observed with a second protein synthesis inhibitor, anisomycin, which also prevented the insulin-induced decrease in IGFBP-1 mRNA without abolishing the insulin-induced inhibition of IGFBP-1 transcription. These results suggest that although insulin decreases IGFBP-1 gene transcription in the presence of protein synthesis inhibitors, IGFBP-1 mRNA levels are maintained because of stabilization of the mRNA. Stabilization was demonstrated directly in actinomycin D-treated cells, where the t1/2 of IGFBP-1 mRNA increased from approximately 2 to approximately 20 h in the presence of cycloheximide; insulin did not affect IGFBP-1 mRNA turnover. Thus, cycloheximide-sensitive labile proteins contribute to the maintenance of basal IGFBP-1 promoter activity and the rapid turnover of IGFBP-1 mRNA, which determine the dynamic regulation of IGFBP-1 gene expression.

Colonization Factor Antigen (CFA/II) from enterotoxigenic Escherichia coli (ETEC) prepared under good manufacturing practices (GMP) was successfully incorporated into biodegradable poly(D,L-lactide-co-glycolide) (PLGA) polymer microspheres (BPM) under GMP and found to be safe and immunogenic when administered intraduodenally to rabbits. Following vaccination, Peyer's patch cells responded by lymphocyte proliferation to in vitro challenge with CFA/II. Also, B cells secreting specific anti-CFA/II antibodies were found in spleens following vaccination. No pathological changes were found following total necropsies of ten rabbits vaccinated with CFA/II BPM. Sixty-three per cent of the CFA/II BPM were between 5 and 10 microns diameter by volume particle size distribution; 1.17% protein content; 2.15% moisture; < 0.01% acetonitrile; 1.6% heptane; 22 non-pathogenic bacteria and three fungi per 1 mg protein dose; and passed the general safety test. We conclude that the CFA/II BPM oral vaccine is immunogenic and safe to begin a Phase I clinical safety study following Investigational New Drug approval.

IGFBP-1 and IGFBP-2 mRNAs are increased in the livers of streptozotocin-diabetic rats. A corresponding increase is observed in transcription of the IGFBP-1 but not the IGFBP-2 gene, indicating that the increase in steady-state levels of IGFBP-2 mRNA is a post-transcriptional effect. IGFBP-1 and IGFBP-2 mRNAs also differ in the rapidity of their response to insulin treatment: hepatic IGFBP-1 mRNA is normalized within 1 h, IGFBP-2 mRNA decreases more slowly. These differences suggest that IGFBP-2 may provide more chronic adaptation to metabolic change than IGFBP-1.

Insulin-like growth factor-binding protein-1 (IGFBP-1) can inhibit or potentiate IGF action. The biological activity of IGFBP-1 is determined by many factors, including its abundance in tissues and plasma, posttranslational modifications, and localization. IGFBP-1 levels in human plasma are highly regulated. They are increased after acute fasting and in diabetes, and are rapidly reversed by refeeding and insulin treatment, respectively. Similarly, IGFBP-1 mRNA is increased in the liver of severely diabetic and ketotic rats and decreased after 4 days of insulin treatment. Insulin rapidly decreases IGFBP-1 mRNA and IGFBP-1 transcription in rat hepatoma cells. The present study asks whether the increase in IGFBP-1 mRNA in diabetic rat liver reflects increased gene transcription, whether insulin decreases IGFBP-1 mRNA through a transcriptional or posttranscriptional mechanism, and whether this decrease is sufficiently rapid to account for the dynamic fluctuations in plasma IGFBP-1. Rats were injected ip with 100 mg/kg streptozotocin and used 7 days later when they were hyperglycemic and failed to gain weight, but were not ketotic. Hepatic IGFBP-1 mRNA levels were 13.6 +/- 5.3-fold greater in diabetic than control liver and decreased to the low levels in nondiabetic controls within 1 h after insulin treatment. In run-on transcription assays, IGFBP-1 transcription was 12.6 +/- 1.5-fold greater in nuclei from diabetic than control liver and decreased to low control levels by 1 h after insulin injection. Normalization of hepatic IGFBP-1 mRNA in insulin-treated diabetic animals did not require restoration of euglycemia. IGFBP-1 mRNA and IGFBP-1 gene transcription also were increased in the kidney of diabetic ketotic rats. We propose that the dynamic regulation of IGFBP-1 gene transcription in diabetes and after insulin treatment, by determining the availability of IGFBP-1 in tissues and plasma, may be a critical factor in the modulation of IGF action.