Alveolar derecruitment and collapse induration as crucial mechanisms in lung injury and fibrosis.

Idiopathic pulmonary fibrosis (IPF) and bleomycin-induced pulmonary fibrosis are associated with surfactant system dysfunction, alveolar collapse (derecruitment), and collapse induration (irreversible collapse). These events play undefined roles in the loss of lung function. The purpose of this study was to quantify how surfactant inactivation, alveolar collapse, and collapse induration lead to degradation of lung function. Design-based stereology and invasive pulmonary function tests were performed 1, 3, 7, and 14 days after intratracheal bleomycin-instillation in rats. The number and size of open alveoli was correlated to mechanical properties. Active surfactant subtypes declined by Day 1, associated with a progressive alveolar derecruitment and a decrease in compliance. Alveolar epithelial damage was more pronounced in closed alveoli compared with ventilated alveoli. Collapse induration occurred on Day 7 and Day 14 as indicated by collapsed alveoli overgrown by a hyperplastic alveolar epithelium. This pathophysiology was also observed for the first time in human IPF lung explants. Before the onset of collapse induration, distal airspaces were easily recruited, and lung elastance could be kept low after recruitment by positive end-expiratory pressure (PEEP). At later time points, the recruitable fraction of the lung was reduced by collapse induration, causing elastance to be elevated at high levels of PEEP. Surfactant inactivation leading to alveolar collapse and subsequent collapse induration might be the primary pathway for the loss of alveoli in this animal model. Loss of alveoli is highly correlated with the degradation of lung function. Our ultrastructural observations suggest that collapse induration is important in human IPF.

Variation in treatment strategies of Swiss general practitioners for subclinical hypothyroidism in older adults.

QUESTIONS UNDER STUDY As the best management of subclinical hypothyroidism is controversial, we aimed to assess variations in treatment strategies depending on different Swiss regions, physician and patient characteristics. METHODS We performed a case-based survey among general practitioners (GPs) in different Swiss regions, which consisted of eight hypothetical cases presenting a female patient with subclinical hypothyroidism and nonspecific complaints differing by age, vitality status and thyroid-stimulating hormone (TSH) concentration. RESULTS A total of 262 GPs participated in the survey. There was considerable variation in the levothyroxine starting dose chosen by GPs, ranging from 25 µg to 100 µg. Across the Swiss regions, GPs in the Bern region were significantly more inclined to treat, with a higher probability of initiating treatment (60%, p = 0.01) and higher mean starting doses (45 µg, p <0.01) compared with the French-speaking region (44%, 36 µg); the Zurich region had intermediate values (52%, 39 µg). We found no association between treatment rate and other physician characteristics. GPs were more reluctant to initiate treatment in 85-year-old than in 70-year-old women (odds ratio [OR] 0.77, 95% confidence interval [CI] 0.63-0.94), and more likely to treat women with a TSH of 15 mU/l than those with a TSH of 6mU/l (OR 8.71, 95% CI 6.21-12.20). CONCLUSIONS There are strong variations in treatment strategies for elderly patients with subclinical hypothyroidism across different Swiss regions, including use of higher starting doses than the recommended 25 µg in the Swiss guidelines, which recommend a starting dose of 25 µg. These variations likely reflect the current uncertainty about the benefits of treatment, which arise from the current lack of evidence from adequately powered clinical trials.

The role of inducible nitric oxide synthase for interstitial remodeling of alveolar septa in surfactant protein D-deficient mice

Surfactant protein D (SP-D) modulates the lung's immune system. Its absence leads to NOS2-independent alveolar lipoproteinosis and NOS2-dependent chronic inflammation, which is critical for early emphysematous remodeling. With aging, SP-D knockout mice develop an additional interstitial fibrotic component. We hypothesize that this age-related interstitial septal wall remodeling is mediated by NOS2. Using invasive pulmonary function testing such as the forced oscillation technique and quasistatic pressure-volume perturbation and design-based stereology, we compared 29-wk-old SP-D knockout (Sftpd(-/-)) mice, SP-D/NOS2 double-knockout (DiNOS) mice, and wild-type mice (WT). Structural changes, including alveolar epithelial surface area, distribution of septal wall thickness, and volumes of septal wall components (alveolar epithelium, interstitial tissue, and endothelium) were quantified. Twenty-nine-week-old Sftpd(-/-) mice had preserved lung mechanics at the organ level, whereas elastance was increased in DiNOS. Airspace enlargement and loss of surface area of alveolar epithelium coexist with increased septal wall thickness in Sftpd(-/-) mice. These changes were reduced in DiNOS, and compared with Sftpd(-/-) mice a decrease in volumes of interstitial tissue and alveolar epithelium was found. To understand the effects of lung pathology on measured lung mechanics, structural data were used to inform a computational model, simulating lung mechanics as a function of airspace derecruitment, septal wall destruction (loss of surface area), and septal wall thickening. In conclusion, NOS2 mediates remodeling of septal walls, resulting in deposition of interstitial tissue in Sftpd(-/-). Forward modeling linking structure and lung mechanics describes the complex mechanical properties by parenchymatous destruction (emphysema), interstitial remodeling (septal wall thickening), and altered recruitability of acinar airspaces.

Virtual Patients in continuing medical education and residency training: a pilot project for acceptance analysis in the framework of a residency revision course in pediatrics.

AIM Virtual patients (VPs) are a one-of-a-kind e-learning resource, fostering clinical reasoning skills through clinical case examples. The combination with face-to-face teaching is important for their successful integration, which is referred to as "blended learning". So far little is known about the use of VPs in the field of continuing medical education and residency training. The pilot study presented here inquired the application of VPs in the framework of a pediatric residency revision course. METHODS Around 200 participants of a pediatric nephology lecture ('nephrotic and nephritic syndrome in children') were offered two VPs as a wrap-up session at the revision course of the German Society for Pediatrics and Adolescent Medicine (DGKJ) 2009 in Heidelberg, Germany. Using a web-based survey form, different aspects were evaluated concerning the learning experiences with VPs, the combination with the lecture, and the use of VPs for residency training in general. RESULTS N=40 evaluable survey forms were returned (approximately 21%). The return rate was impaired by a technical problem with the local Wi-Fi firewall. The participants perceived the work-up of the VPs as a worthwhile learning experience, with proper preparation for diagnosing and treating real patients with similar complaints. Case presentations, interactivity, and locally and timely independent repetitive practices were, in particular, pointed out. On being asked about the use of VPs in general for residency training, there was a distinct demand for more such offers. CONCLUSION VPs may reasonably complement existing learning activities in residency training.

Development and voluntarism in football clubs

Volunteers are still the most important resource for amateur football clubs. However, stable voluntary engagement can no longer be granted. This difficulty is confirmed by existing research across various European countries. From a club management point of view, a detailed understanding of how to attract volunteers and retain them is becoming a high priority. The purpose of this study is (1) to analyse the influence of individual characteristics and corresponding organisational conditions on volunteering and (2) to examine the decision-making processes in relation to implement effective strategies for recruiting volunteers. To answer these questions, the current state of research is summarised and then a multi-level-framework is developed which is based on the structural-individualistic social theory. The individual and context factors for volunteering are estimated in different multi-level models based on a sample of n=1,434 sport club members from 36 sport clubs in Switzerland. Results indicate that volunteering is not just an outcome of individual characteristics such as lower workloads, higher income, children belonging to the sport club, longer club membership, or a strong commitment to the club. It is also influenced by club-specific structural conditions. Concerning decision-making processes an in-depth analysis of recruitment practices for volunteers was conducted in selected clubs (case study design). based on the garbage can model. The results show that systematically designed decision-making processes with a clear regulation of responsibilities seem to solve personnel problems more purposefully and more quickly. Based on the findings some recommendations for volunteer management in football clubs are worked out.

The Perceived Prognosis of Endodontic Treatment and Implant Therapy Among Dental Practitioners

Little data concerning the perceived success of implant therapy in comparison with endodontic treatment exists. While the criteria used to measure the outcome of each modality are not the same, it is not clear if this is appreciated by practicing dentists. The purpose of the study was to evaluate the perceived outcome of implant therapy in comparison to endodontic treatment. A 23 question Web-based survey was distributed to 648 dentists who matriculated from the University of Connecticut School Of Dental Medicine over the past 30 years. The response rate was 47%. Sixty-seven percent of respondents were general dentists. Forty-nine percent of respondents did not know different criteria exist in the literature and are used to evaluate implant and root canal treatment. Fifty-four percent of dentists felt the prognosis of implant therapy was the same as or better than endodontic treatment of teeth with vital pulps. Thirty percent of responders thought root canal treatment of teeth with necrotic pulp was superior to implants and only 16% thought retreatment was preferable. Treatment planning for implant placement vs. retreatment of a restorable tooth was 46% and 32%, respectively. A third of the respondents felt that the role of endodontics will decline in the future. Dentists’ primary source of information regarding implant therapy was continuing education; however, their primary source of information regarding endodontic treatment was their dental program. Dentists felt the prognosis of implant therapy was as good or superior to endodontic treatment of teeth with vital, necrotic or previously treated pulps.

Clinical, microbiological, and immunological markers of gingival and periodontal disease induction and progression

The potential impact of periodontal disease, a suspected risk factor for systemic diseases, presents challenges for health promotion and disease prevention strategies. This study examined clinical, microbiological, and immunological factors in a disease model to identify potential biomarkers that may be useful in predicting the onset and severity of both inflammatory and destructive periodontal disease. This project used an historical cohort design based on data obtained from 47 adult, female nonhuman primates followed over a 6-year period for 5 unique projects where the ligature-induced model of periodontitis was utilized. Standardization of protocols for sample collection allowed for comparison over time. Bleeding and pocket depth measures were selected as the dependent variables of relevance to humans based upon the literature and historical observations. Exposure variables included supragingival plaque, attachment level, total bacteria, black-pigmented bacteria, Gram-negative and Gram-positive bacteria, total IgG and IgA in crevicular fluid, specific IgG antibody in both crevicular fluid and serum, and IgG antibody to four select pathogenic microorganisms. Three approaches were used to analyze the data from this study. The first approach tested for differences in the means of the response variables within the group and among longitudinal observations within the group at each time point. The second approach examined the relationship among the clinical, microbiological, and immunological variables using correlation coefficients and stratified analyses. Multivariable models using GEE for repeated measures were produced as a predictive description of the induction and progression of gingivitis and periodontal disease. The multivariable models for bleeding (gingivitis) include supragingival plaque, total bacteria and total IgG while the second also contains supragingival plaque, Gram-positive bacteria, and total IgG. Two multivariable models emerged for periodontal disease. One multivariable model contains plaque, total bacteria, total IgG and attachment level. The second model includes black-pigmented bacteria, total bacteria, antibody to Campylobacter rectus, and attachment level. Utilization of the nonhuman primate model to prospectively examine causal hypotheses can provide a focus for human research on the mechanisms of progression from health to gingivitis to periodontitis. Ultimately, causal theories can guide strategies to prevent disease initiation and reduce disease severity. ^

Gender Difference in Emotional and Behavioral Responses of Being Rendered Invisible

This study examined gender differences in emotional and behavioral responses to an experience of being invisible to others. Invisibility was defined as being ignored, slighted and overlooked by others. Participants recalled their own experience and answered questions about it and their responses on an anonymous web-based survey. Although such experiences could be very unpleasant, people may respond to such negative experiences very differently. It was hypothesized that in a patriarchal society like the United States in which men hold more power than women, that men would show emotion that was more aggressive such as anger, and respond more violently to incidents they were not respected. Women, on the other hand, were expected to be more subservient in their behavior and responses, show submissive emotions such as sadness, and respond less violently when they were not respected.

The effect of genotype-by-environment interaction on longitudinal triglyceride profiles in the Bogalusa Heart Study

Triglyceride levels are a component of plasma lipids that are thought to be an important risk factor for coronary heart disease and are influenced by genetic and environmental factors, such as single nucleotide polymorphisms (SNPs), alcohol intake, and smoking. This study used longitudinal data from the Bogalusa Heart Study, a biracial community-based survey of cardiovascular disease risk factors. A sample of 1191 individuals, 4 to 38 years of age, was measured multiple times from 1973 to 2000. The study sample consisted of 730 white and 461 African American participants. Individual growth models were developed in order to assess gene-environment interactions affecting plasma triglycerides over time. After testing for inclusion of significant covariates and interactions, final models, each accounting for the effects of a different SNP, were assessed for fit and normality. After adjustment for all other covariates and interactions, LIPC -514C/T was found to interact with age3, age2, and age and a non-significant interaction of CETP -971G/A genotype with smoking status was found (p = 0.0812). Ever-smokers had higher triglyceride levels than never smokers, but persons heterozygous at this locus, about half of both races, had higher triglyceride levels after smoking cessation compared to current smokers. Since tobacco products increase free fatty acids circulating in the bloodstream, smoking cessation programs have the potential to ultimately reduce triglyceride levels for many persons. However, due to the effect of smoking cessation on the triglyceride levels of CETP -971G/A heterozygotes, the need for smoking prevention programs is also demonstrated. Both smoking cessation and prevention programs would have a great public health impact on minimizing triglyceride levels and ultimately reducing heart disease. ^

Health information exchange: Using metrics to address quality of care and return on investment

Health Information Exchange (HIE) will play a key part in our nation’s effort to improve healthcare. The evidence of HIEs transformational role in healthcare delivery systems is quite limited. The lack of such evidence led us to explore what exists in the healthcare industry that may provide evidence of effectiveness and efficiency of HIEs. The objective of the study was to find out how many fully functional HIEs are using any measurements or metrics to gauge impact of HIE on quality improvement (QI) and on return on investment (ROI).^ A web-based survey was used to determine the number of operational HIEs using metrics for QI and ROI. Our study highlights the fact that only 50 percent of the HIEs who responded use or plan to use metrics. However, 95 percent of the respondents believed HIEs improve quality of care while only 56 percent believed HIE showed positive ROI. Although operational HIEs present numerous opportunities to demonstrate the business model for improving health care quality, evidence to document the impact of HIEs is lacking. ^

Bayesian adaptive designs for drug combinations in early phase clinical trials

Treating patients with combined agents is a growing trend in cancer clinical trials. Evaluating the synergism of multiple drugs is often the primary motivation for such drug-combination studies. Focusing on the drug combination study in the early phase clinical trials, our research is composed of three parts: (1) We conduct a comprehensive comparison of four dose-finding designs in the two-dimensional toxicity probability space and propose using the Bayesian model averaging method to overcome the arbitrariness of the model specification and enhance the robustness of the design; (2) Motivated by a recent drug-combination trial at MD Anderson Cancer Center with a continuous-dose standard of care agent and a discrete-dose investigational agent, we propose a two-stage Bayesian adaptive dose-finding design based on an extended continual reassessment method; (3) By combining phase I and phase II clinical trials, we propose an extension of a single agent dose-finding design. We model the time-to-event toxicity and efficacy to direct dose finding in two-dimensional drug-combination studies. We conduct extensive simulation studies to examine the operating characteristics of the aforementioned designs and demonstrate the designs' good performances in various practical scenarios.^

Risk and resiliency: The untold story of youth in military families

Background: Risky sexual behaviors have been shown to increase the risk of unintended pregnancy and sexually transmitted infections (STIs) among youth. Youth in military families may be especially at risk for engaging in risky sexual behaviors because they are exposed to factors that are unique to the military culture, such as multiple relocations and parental deployment. However, data on sexual behaviors among military-dependent youth are limited and few studies have examined how these factors influence the sexual behaviors among youth. Purpose: The purpose of this dissertation was to estimate the prevalence of risky sexual behaviors among military-dependent youth and to describe how military factors may influence their sexual behaviors. Methods: Youth, aged 15–19 years, who attended a military health facility in the southern United States between June 2011 and September 2011 were recruited to complete a short, paper-based survey (N= 208, males and females) and to participate in an in-depth interview (N = 25, females). For quantitative data, prevalence estimates were computed and chi-square analyses were conducted. Logistic regression analyses were also conducted, adjusting for age, gender, and parents' duty status. For qualitative data, thematic coding of transcribed interviews was performed. Common and unique themes were examined across participants' experiences. Results: Over half of the youth was sexually experienced (53.7%). Parental deployment and number of relocations were significantly associated with having had sex in the past 3 months; however no significant associations were found between these military factors and other sexual behaviors. Although some youth felt that being a military-dependent had negatively impacted their sexual decisions, most believed the military experience had little influence on their sexual decisions. Most youth in military families also perceived having higher parental expectations to avoid risky behaviors, in general, than youth in civilian families. Conclusions: The majority of military-dependent youth are sexually experienced; however, individual and parental factors may have a greater role in sexual initiation among youth than military stressors do. The findings highlight the need for implementation of evidence-based strategies to prevent teen pregnancy and STIs at military installations. Future studies with larger sample sizes are needed to further explore how youth may cope with these military factors and the impact of parental factors on the sexual behaviors of youth.^

Cancer screening behaviors among Asian Americans in Houston, Texas

Background: Cancer is the second-leading cause of death in the United States, and Asian Americans/Pacific Islanders are the only racial/ethnic group for which cancer is the leading cause of death. Regular cancer screenings help to identify precancerous lesions and cancer at an earlier stage, when the cancer is more treatable. Ethnic disparities in participation in cancer screenings are also striking, and evidence indicates that Asian Americans may have lower rates of cancer screening participation than other racial/ethnic groups. The Health of Houston Survey 2010 (HHS 2010) is an address-based survey, administered via telephone, website, and mail, of over 5,000 respondents in Houston and Harris County that provides recent data on the health status and needs of the Houston community. HHS 2010 researchers oversampled for Asians and Vietnamese Americans in order to obtain a sample size large enough to obtain statistical power. This dataset provides a unique opportunity to examine the cancer screening behaviors and predictors of Vietnamese and Chinese Americans living in Houston, Texas.^ Methods: This study was a secondary data analysis of HHS 2010 data. The data were analyzed to compare the breast, cervical, and colorectal cancer screening compliance rates of Vietnamese and Chinese Americans with other racial/ethnic groups in Houston, Texas. Key predictors of participation and barriers to cancer screening were identified.^ Results: The results of this study indicate that in Houston, Vietnamese Americans and Asian Americans as a whole have strikingly lower rates of participation in cancer screenings compared to other ethnic groups. Chinese Americans had the highest rate of noncompliance for mammography of all ethnic groups; Asian Americans and Vietnamese Americans also had high rates of noncompliance. Similarly, Vietnamese and Asian Americans had high rates of noncompliance with colorectal cancer screening recommendations. Importantly, Vietnamese, Chinese, and Asian Americans had by far the worst pap test participation, with noncompliance rates more than double that of all other racial/ethnic groups. In general, the findings indicated several key predictors in cancer screening behaviors, including English language proficiency, years lived in the United States, health insurance, college education, and income; however, the significance and patterns of these variables varied by ethnic group as well as cancer site.^ Conclusions: This secondary analysis highlights the disparities in cancer screening participation among Vietnamese, Chinese, and Asian Americans in Houston, Texas and indicate the need to identify Asian Americans as a high-risk group in need of health promotion attention. Barriers to screening and educational needs appear to be specific to each target ethnic group. Thus, health educators and health professionals in Houston must focus on the specific educational needs of the key ethnic groups that make up the Houston population. Further, more ethnic-specific research is needed to examine the health behaviors and needs of Houston's Asian American subgroups.^

Concentration profiles in batch fermentation of hydrolyzed lignocellulose

Experimental data was obtained for profiling changes in concentrations of two inhibiting compounds in batch fermentation of a synthesized liquor resembling hydrolyzed lignocellulose, a furan (furfural) and a phenolic compound (vanillin), along with standard fermentation data, i.e. substrate, biomass and ethanol concentrations. The initial inhibitor concentrations and fermentation temperatures in the 18 experiments were varied according to a two-level complete center composite experimental design. Based upon these observed variations in the fermentative behavior, the fermentation kinetics were modeled, as published in the corresponding article, including microbial conversion rates of the inhibitive compounds into their less toxic derivatives.

Trips (Frankliniella brevicaulis Hood) de las erupciones del fruto de banano (Musa acuminata Colla) en la provincia de Formosa, Argentina

El banano en la provincia de Formosa (Argentina) es uno de los principales cultivos de renta y generador de mano de obra para el productor por lo que representa un importante lugar en lo social y económico. La sanidad de los cultivos es fundamental para lograr una mayor rentabilidad. Se han observado en los frutos daños atribuibles a trips. Los objetivos de este trabajo fueron identificar la/s especie/s de trips causal de las erupciones del fruto de banano en la provincia de Formosa, realizar una descripción detallada de su morfología y caracterizar y evaluar los daños producidos. La zona de trabajo correspondió al Área-Laguna Naineck en el Departamento Pilcomayo de la provincia de Formosa considerando un total de 1.103,74 ha pertenecientes a 233 productores. Para la determinación del estado sanitario de las plantaciones con respecto a la presencia del insecto se realizó un diseño de muestreo estadístico. Se recolectaron muestras del insecto y se identificaron con ayuda de claves. La única especie de trips encontrada fue Frankliniella brevicaulis. Los daños producidos por esta especie serían debidos a las heridas causadas por la oviposición, siendo éstas posibles fuentes de entrada para el hongo Colletotrichum musae. Se observaron daños en el 100% de los cachos de banana en todas las plantaciones evaluadas.