Androgen receptor CAG repeat lengths in prostate cancer: correlation with age of onset.
The androgen receptor (AR) is a structurally conserved member of the nuclear receptor superfamily. The amino-terminal domain is required for transcriptional activation and contains a region of polyglutamine encoded by CAG trinucleotide repeats. In humans, the number of CAG repeats is polymorphic; the average number is 22 in Caucasian males. Expansion of CAG repeats in the AR has clinical implications for human disease. As androgen influences prostate cancer growth, polymorphisms in CAG repeat length may affect the clinical course of patients with prostate cancer. To test for an association between clinical parameters of human prostate cancer and CAG repeat length, we analyzed normal lymphocyte DNA from 109 patients. The CAG region of the AR was amplified by the PCR. Reaction products were then amplified using end-labeled internal primers, cut at the internal PstI site and assayed on sequencing gels using a sequence ladder as a size standard. Sequence analysis of several samples validated this method for measurement of CAG repeat number. The median age of patients was 63 yr (range, 42-83), with 104 Caucasian, 2 African American, 1 Asian, and 2 other racial origin. The median repeat length was 25 for patients with stage A, 22 for patients with stage B, 22 for patients with stage C, and 23 for patients presenting with stage D disease. A significant correlation between CAG repeat length and age at onset was observed, whereas correlations with stage, level of prostate-specific antigen at diagnosis, and time to prostate-specific antigen relapse were not significant. Shorter CAG repeat lengths may be associated with the development of prostate cancer in men at a younger age. These data suggest that CAG repeat length can affect the risk of developing prostate cancer.


Systematic Thermodynamics of Layered Perovskites: Ruddlesden-Popper Phases.
Perovskite, CaTiO3, is the prototype of an extensive group of materials. They are capable of considerable chemical modification, with the further capability of undergoing structural modification by the intercalation of thin sheets of intrusive materials (both inorganic and organic) between the cubic perovskite layers, to form a range of "layered" perovskites. These changes bring about alterations in their electronic, structural, and other properties, permitting some "tuning" toward specific ends. This paper collects the limited known thermodynamic data for layered perovskites of various chemical compositions and demonstrates by example that the thermodynamic layer values are substantially additive. This additivity may be exploited by summing properties of the constituent oxides, by adding differences between adjacent compositions within a series, or even by substitution of oxides for one another, thus permitting prediction beyond the known range of compositions. Strict additivity implies full reversibility so that the additive product may be unstable and may undergo structural changes, producing materials with new and potentially useful properties such as ferroelectricity, polarity, giant magnetoresistance, and superconductivity.


Protein kinase C inhibition and x-linked inhibitor of apoptosis protein degradation contribute to the sensitization effect of luteolin on tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis in cancer cells.
Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is an important member of the TNF superfamily with great potential in cancer therapy. Luteolin is a dietary flavonoid commonly found in some medicinal plants. Here we found that pretreatment with a noncytotoxic concentration of luteolin significantly sensitized TRAIL-induced apoptosis in both TRAIL-sensitive (HeLa) and TRAIL-resistant cancer cells (CNE1, HT29, and HepG2). Such sensitization is achieved through enhanced caspase-8 activation and caspase-3 maturation. Further, the protein level of X-linked inhibitor of apoptosis protein (XIAP) was markedly reduced in cells treated with luteolin and TRAIL, and ectopic expression of XIAP protected against cell death induced by luteolin and TRAIL, showing that luteolin sensitizes TRAIL-induced apoptosis through down-regulation of XIAP. In search of the molecular mechanism responsible for XIAP down-regulation, we found that luteolin and TRAIL promoted XIAP ubiquitination and proteasomal degradation. Next, we showed that protein kinase C (PKC) activation prevented cell death induced by luteolin and TRAIL via suppression of XIAP down-regulation. Moreover, luteolin inhibited PKC activity, and bisindolylmaleimide I, a general PKC inhibitor, simulated luteolin in sensitizing TRAIL-induced apoptosis. Taken together, these results present a novel anticancer effect of luteolin and support its potential application in cancer therapy in combination with TRAIL. In addition, our data reveal a new function of PKC in cell death: PKC activation stabilizes XIAP and thus suppresses TRAIL-induced apoptosis.


[Effects of Short-time Conservation Tillage Managements on Greenhouse Gases Emissions from Soybean-Winter Wheat Rotation System].
Field experiments including one soybean growing season and one winter-wheat growing season were adopted. The experimental field was divided into four equal-area sub-blocks which differed from each other only in tillage managements, which were conventional tillage (T) , no-tillage with no straw cover ( NT) , conventional tillage with straw cover (TS) , and no-tillage with straw cover (NTS). CO₂ and N₂O emission fluxes from soil-crop system were measured by static chamber-gas chromatograph technique. The results showed that: compared with T, in the soybean growing season, NTS significantly increased the cumulative amount of CO₂ (CAC) from soil-soybean system by 27.9% (P = 0.045) during the flowering-podding stage, while NT significantly declined CAC by 28.9% (P = 0.043) during the grain filling-maturity stage. Compared with T, NT significantly declined the cumulative amount of N₂O (CAN) by 28.3% (P = 0.042) during the grain filling-maturity stage. In the winter-wheat growing season, compared with T, TS and NT significantly declined CAC by 24.3% (P = 0.032) and 36.0% (P = 0.041) during the elongation-booting stage, and also declined CAC by 26.8% (P = 0.027) and 33.1% (P = 0.038) during the maturity stage. During the turning-green stage, compared with T treatment, NT, NTS, and TS treatments had no significant effect on CAN, while NTS significant declined CAN by 42.0% (P = 0.035) compared with NT. Our findings suggested that conservation tillage managements had a more significant impact on CO₂ emission than 20 emission from soil-crop system.


Progressive dilation for bladder tissue expansion.
The use of gastrointestinal tissue for augmentation cystoplasty is associated with numerous complications. We previously reported the development of a system in which ureters were progressively dilated and used for ureterocystoplasty. We have now applied a similar system for the progressive expansion of native bladder tissue. We investigated whether the expanded bladder tissue retained normal functional and phenotypic characteristics. Urodynamic studies were performed in 5 beagle dogs and the bladder was divided horizontally into a superior bladder neo-reservoir, and an intact smaller bladder inferiorly with both ureters left intact and draining. A silicone catheter was threaded into the newly formed, superiorly located neo-reservoir, and connected to an injection port which was secured subcutaneously. A saline antibiotic solution was injected daily into the palpable injection port 4 weeks after surgery, dilating the neo-reservoir through the silicone catheter. Baseline and weekly cystograms were performed. Urodynamic studies of the neo-reservoirs were done immediately before sacrifice. Animals were sacrificed 3 months after the initial intervention and the bladder was examined grossly and microscopically. Within 30 days after progressive dilation, the neo-reservoir volume was expanded at least 10-fold according to radiography and cystometrograms. Urodynamic studies of the dilated neo-reservoirs showed normal compliance in all animals. Microscopic examination of the expanded neo-reservoir tissue revealed normal histology. A series of immunocytochemical studies demonstrated that the dilated bladder tissue maintained normal phenotypic characteristics. The system of progressive dilation is effective in expanding bladder tissue which is able to retain normal phenotypic and functional characteristics.


Smoking cessation reduces systemic inflammation and circulating endothelin-1.
Smoking increases systemic inflammation and circulating endothelin-1 (ET-1), both of which contribute to an elevated risk of cardiovascular disease (CVD). The present study sought to test the hypothesis that a 12-week smoking cessation intervention would contribute to a long-term reduction in circulating ET-1, tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6). 30 individuals participated in a 12-week evidence-based smoking cessation program at Augusta University. Serum cotinine, plasma inflammatory cytokines, and plasma ET-1 were determined at baseline, immediately after the 12-week cessation program (end of treatment, EOT), and 12-months (12M) following the cessation program. Serum cotinine was significantly reduced (p < 0.001) at EOT and 12M following the smoking cessation program. Compared to BL (7.0 ± 1.6 pg/mL), TNF-α was significantly reduced at EOT (6.3 ± 1.5 pg/mL, p = 0.001) and 12M (5.2 ± 2.7 pg/mL, p < 0.001). ET-1 was significantly lower at EOT (1.9 ± 0.6 pg/mL, p = 0.013) and at 12M (2.0 ± 0.8 pg/mL, p = 0.091) following smoking cessation compared with BL (2.3 ± 0.6 pg/mL). BL concentrations of cotinine were significantly associated with basal ET-1 (r = 0.449, p = 0.013) and the change in cotinine at 12M following smoking cessation was significantly associated with the change in plasma ET-1 at 12M (r = 0.457, p = 0.011). Findings from the present pilot investigation demonstrate that a 12-week smoking cessation program reduces circulating concentrations of ET-1 and TNF-α for at least a year. The reduction in serum cotinine was associated with the decrease in circulating ET-1. The attenuation in ET-1 and inflammation may in part, contribute to the lower risk of CVD that is observed with smoking cessation.


A combined pH and temperature precipitation step facilitates the purification of tobacco-derived recombinant proteins that are sensitive to extremes of either parameter.
Incubation at pH 4.0 or blanching at ∼65°C facilitates the purification of biopharmaceutical proteins from plants by precipitating most of the host cell proteins (HCPs) before chromatography. However, both methods are compatible only with pH or thermostable target proteins whereas many target proteins may irreversibly denature, e.g., at pH < 4.0. Here, we developed a combined pH/temperature treatment for clarified tobacco extracts and intact leaves. The latter were subjected to a blanching procedure, i.e., the submersion into a hot buffer. Using a design of experiments approach we identified conditions that remove ∼70% of HCPs at ∼55°C, using the thermosensitive antibody 2G12 and the pH-sensitive DsRed as model proteins. We found that pH and temperature exerted a combined effect during the precipitation of HCPs in the pH range 5.0-7.0 at 35°C-60°C. For clarified extracts, the temperature required to achieve a DsRed purity threshold of 20% total soluble protein (TSP) increased from 54°C to 63°C when the pH was increased from 6.4 to 7.3. The pH-stable antibody 2G12 was less responsive to the combined treatment, but the purity of 1% TSP was achieved at 35°C instead of 44°C when the pH was reduced from 6.3 to 5.8. When blanching intact leaves, product losses were not exacerbated at pH 4.0. Indeed, the highest DsRed purity (58% TSP) was achieved at this pH, combined with a temperature of 60°C and an incubation time of 30 min. In contrast, the highest 2G12 purity (0.7% TSP) was achieved at pH 5.1 and 40°C with an incubation time of 20 min. Our data suggest that a combined pH/temperature regime can avoid extreme values of either parameter; therefore, broadening the applicability of these simple purification techniques to other recombinant proteins.


Geographic variation in prostate cancer survival in New South Wales.
To determine whether the previously reported urban-rural differential in prostate cancer survival remains after adjusting for demographic and clinical factors, and to investigate temporal trends in this differential. Retrospective population-based survival analysis of 68 686 men diagnosed with prostate cancer from January 1982 to December 2007 in New South Wales. Survival rate and relative excess risk (RER) of death over 10 years of follow-up in relation to geographic remoteness after adjusting for other prognostic factors. Overall, 10-year survival increased during the study period, increasing from 57.5% in 1992-1996 and 75.7% in 1997-2001 to 83.7% in 2002-2007. The increasing trends were also observed across categories of geographic remoteness and socioeconomic status. Urban-rural differentials were significant (P < 0.001) after adjusting for five important prognostic factors, with men living outside major cities having higher risk of death from prostate cancer (RER, 1.18 and 1.32 for inner regional and rural areas, respectively). Socioeconomic status was also a significant factor (P < 0.001) for prostate cancer mortality, with the risk of dying being 34% to 40% higher for men living in socioeconomically disadvantaged areas than those living in least disadvantaged areas. There was no evidence that this inequality is reducing over time, particularly for men living in inner regional areas. Despite the increasing awareness of urban-rural differentials in cancer outcomes, little progress has been made. Appropriately detailed data, including details of tumour characteristics, treatment and comorbid conditions, to help understand why these inequalities exist are required urgently so interventions and policy changes can be guided by appropriate evidence.


Nursing acute psychiatric patients: a quantitative and qualitative study.
Political and managerial attention has focused on the consequences of the failure of community services to provide effective care to a small number of people with severe mental illness. However, the nature and value of care in hospitals have received less scrutiny. This paper addresses deficiencies in our knowledge about nursing care in acute psychiatric wards. It reports the findings from a recently completed study for the United Kingdom Department of Health. Four key developments are identified which, together, pose significant problems for nursing in acute wards: the increasingly diverse patient mix in wards; the volume of administrative duties performed by nurses; the weakness of multidisciplinary team working; and inappropriate education. In conclusion, the challenges for managers and clinicians responsible for local policy and practice and, by extension, those at the centre responsible for such services, are examined.


Treatment of potato tubers with the synthetic cytokinin 1-(α-ethylbenzyl)-3-nitroguanidine results in rapid termination of endodormancy and induction of transcripts associated with cell proliferation and growth.
Perennial plants undergo repression of meristematic activity in a process called dormancy. Dormancy is a complex metabolic process with implications for plant breeding and crop yield. Endodormancy, a specific subclass of dormancy, is characteristic of internal physiological mechanisms resulting in growth suppression. In this study, we examine transcriptional changes associated with the natural cessation of endodormancy in potato tuber meristems and in endodormant tubers treated with the cytokinin analog 1-(α-ethylbenzyl)-3-niroguanidine (NG), which terminates dormancy. RNA-sequencing was used to examine transcriptome changes between endodormant and non-dormant meristems from four different harvest years. A total of 35,091 transcripts were detected with 2132 differentially expressed between endodormant and non-dormant tuber meristems. Endodormant potato tubers were treated with the synthetic cytokinin NG and transcriptome changes analyzed using RNA-seq after 1, 4, and 7 days following NG exposure. A comparison of natural cessation of dormancy and NG-treated tubers demonstrated that by 4 days after NG exposure, potato meristems exhibited transcriptional profiles similar to the non-dormant state with elevated expression of multiple histones, a variety of cyclins, and other genes associated with proliferation and cellular replication. Three homologues encoding for CYCD3 exhibited elevated expression in both non-dormant and NG-treated potato tissues. These results suggest that NG terminates dormancy and induces expression cell cycle-associated transcripts within 4 days of treatment.


Economic Outcomes in Patients with Chemotherapy-Naïve Metastatic Castration-Resistant Prostate Cancer Treated with Enzalutamide or Abiraterone Acetate Plus Prednisone.
Prostate cancer (PC) is the second leading cause of cancer death among US men and accounts for considerable healthcare expenditures. We evaluated economic outcomes in men with chemotherapy-naïve metastatic castration-resistant PC (mCRPC) treated with enzalutamide or abiraterone acetate plus prednisone (abiraterone). We performed a retrospective analysis on 3174 men (18 years or older) utilizing the Veterans Health Administration (VHA) database from 1 April 2014 to 31 March 2018. Men with mCRPC were included if they had at least one pharmacy claim for enzalutamide or abiraterone (first claim date = index date) following surgical or medical castration, had no chemotherapy treatment within 12 months prior to the index date, and had continuous VHA enrollment for at least 12 months pre- and post-index date. Men were followed until death, disenrollment, or end of study and were 1:1 propensity score matched (PSM). All-cause and PC-related resource use and costs per patient per month (PPPM) in the 12 months post index were compared between matched cohorts. We identified 1229 men with mCRPC prescribed enzalutamide and 1945 prescribed abiraterone with mean ages of 74 and 73 years, respectively. After PSM, each cohort had 1160 patients. The enzalutamide cohort had fewer all-cause (2.51 vs 2.86; p < 0.0001) and PC-related outpatient visits (0.86 vs 1.03; p < 0.0001), with corresponding lower all-cause ($2588 vs $3115; p < 0.0001) and PC-related ($1356 vs $1775; p < 0.0001) PPPM outpatient costs compared with the abiraterone cohort. All-cause total costs (medical and pharmacy) PPPM ($8085 vs $9092; p = 0.0002) and PC-related total costs PPPM ($6321 vs $7280; p < 0.0001) were significantly lower in the enzalutamide cohort compared with the abiraterone cohort. Enzalutamide-treated men with chemotherapy-naïve mCRPC had significantly lower resource utilization and healthcare costs compared with abiraterone-treated men.


Inhibition of prostate cancer cell growth by activated eosinophils.
Host Immune response to prostate cancer primarily involves the CTL and NK effector cells. Recent immunotherapeutic strategies incorporating cytokine genes into the tumor cell and/or dendritic cells have had encouraging results. In this study, we describe the inhibitory activity of a third potential effector cell, the eosinophil, against DU 145 and PC-3 prostate tumor cells growth in vitro. Subconfluent monolayer cultures of DU 145 and PC-3 cells were incubated with peripheral blood eosinophils from allergic or asthmatic individuals and also with eosinophil cultured supernatants. Newly established eosinophil cell lines were also studied. After harvesting, the plates were washed and stained with Hematoxylin/eosin (H/E) then photographed. The combination of monolayer cell growth inhibition and colony formation inhibition assays were used to evaluate eosinophil inhibitory activity. In the colony formation inhibition assay one hundred cells per well in 6-well plates were incubated overnight, after which peripheral blood eosinophils, conditioned media and cytokines, IL-4 and TNF-alpha were added. The plates were harvested after 10 days incubation period. Colonies were stained and counted. Hypo- and hyperdense peripheral blood eosinophils from allergic and asthmatic individuals as well as eosinophil cell lines established from these subpopulations inhibited both DU 145 and PC-3 cell growth at 58-78% and 10-38%, respectively. IL-5 up-regulated eosinophil cell line activity by 21-24%. The conditioned media which contained the released mediators of activated eosinophils were potent in their actions on both DU 145 and PC-3, inhibiting colony formation by as much as 90-100%. These results clearly demonstrate the inhibitory potential of activated eosinophils and their released "soup" of mediators and therefore support the hypothesis that eosinophils may participate in host response to prostate cancer together with CTLs and NK cells. Furthermore, this study offers insights into possible strategies for enhancing eosinophilic activity in prostate cancer.


Epstein-Barr virus genome packaging factors accumulate in BMRF1-cores within viral replication compartments.
Productive replication of Epstein-Barr virus (EBV) during the lytic cycle occurs in discrete sites within nuclei, termed replication compartments. We previously proposed that replication compartments consist of two subnuclear domains: "ongoing replication foci" and "BMRF1-cores". Viral genome replication takes place in ongoing replication foci, which are enriched with viral replication proteins, such as BALF5 and BALF2. Amplified DNA and BMRF1 protein accumulate in BMRF1-cores, which are surrounded by ongoing replication foci. We here determined the locations of procapsid and genome-packaging proteins of EBV via three-dimensional (3D) surface reconstruction and correlative fluorescence microscopy-electron microscopy (FM-EM). The results revealed that viral factors required for DNA packaging, such as BGLF1, BVRF1, and BFLF1 proteins, are located in the innermost subdomains of the BMRF1-cores. In contrast, capsid structural proteins, such as BBRF1, BORF1, BDLF1, and BVRF2, were found both outside and inside the BMRF1-cores. Based on these observations, we propose a model in which viral procapsids are assembled outside the BMRF1-cores and subsequently migrate therein, where viral DNA encapsidation occurs. To our knowledge, this is the first report describing capsid assembly sites in relation to EBV replication compartments.


Self-renewal vs. differentiation of mouse embryonic stem cells.
Embryonic stem (ES) cells are typically derived from the inner cell mass of the preimplantation blastocyst and can both self-renew and differentiate into all the cells and tissues of the embryo. Because they are pluripotent, ES cells have been used extensively to analyze gene function in development via gene targeting. The embryonic stem cell is also an unsurpassed starting material to begin to understand a critical, largely inaccessible period of development. If their differentiation could be controlled, they would also be an important source of cells for transplantation to replace cells lost through disease or injury or to replace missing hormones or genes. Traditionally, ES cells have been differentiated in suspension culture as embryoid bodies, named because of their similarity to the early postimplantation-staged embryo. Unlike the pristine organization of the early embryo, differentiation in embryoid bodies appears to be largely unpatterned, although multiple cell types form. It has recently been possible to separate the desired cell types from differentiating ES cells in embryoid bodies by using cell-type-restricted promoters driving expression of either antibiotic resistance genes or fluorophores such as EGFP. In combination with growth factor exposure, highly differentiated cell types have successfully been derived from ES cells. Recent technological advances such as RNA interference to knock down gene expression in ES cells are also producing enriched populations of cells and elucidating gene function in early development.


Being in a "Green" Building Elicits "Greener" Recycling, but Not Necessarily "Better" Recycling.
Previous observational work revealed that transient populations in a sustainable building disposed of waste more accurately when compared to patrons in a non-sustainable building. The current study uses an experimental design to replicate this observed effect and to investigate whether or not the built environment influences motivational factors to impact behavior. We find support that a building designed and built to communicate an atmosphere of sustainability can influence waste disposal behavior. Participants in the sustainable building used the garbage receptacle significantly less and compensated by tending to select the containers and organics receptacle more, which actually resulted in more errors overall. Our findings suggest that building atmospherics can motivate people to recycle more. However, atmospherics alone do not appear to be sufficient to elicit the desired performance outcome.


Caring for the elderly: a European perspective on today and tomorrow.
There is always a temptation to suppose that one's own problems (whether personal or national) are unique. They rarely are. The "problem" of the elderly is no exception and so there is no particular point in looking to the specific characteristics of one's own health, social service, and social security systems for causes. There is, however, every reason to be looking at them for the consequences. They can also exacerbate the causes. In this paper we sketch the principal features (economic, social, and demographic) that have contributed to the "problem" of the elderly in Europe and then outline the main intellectual issues that need to be explored and resolved. That sounds a bit pompous but, if one is to avoid an intellectual morass consisting of the various assertions about needs, obligations, and so on that emanate from rival concerned parties and various professional interests on the one hand, and simplistic political slogans whose only virtue is that they cut the Gordian Knot (but provide no real enlightenment) on the other, then we need to be doing just this. We shall take a few things for granted: that cost-containment is not the be-all-and-end-all of policy; that value for money depends equally on what you get as on what you spend; that overall expenditure per head is mainly determined by income per head (though some countries have managed to get and stay below the regression line); and that it "ain't so" that all one needs to do is to "leave it to the market." To have justified each of these would have taken too much space so we can only assert them and trust that, in swallowing these camels, you won't strain at the gnats to come.


Cardiac extracellular proteome profiling and membrane topology analysis using glycoproteomics.
Extracellular proteins are easily accessible, which presents a subproteome of molecular targets that have high diagnostic and therapeutic potential. Efforts have been made to catalog the cardiac extracellular matridome and analyze the topology of identified proteins for the design of therapeutic targets. Although many bioinformatics tools have been developed to predict protein topology, topology has been experimentally validated for only a very small portion of membrane proteins. The aim of this study was to use a glycoproteomics and MS approach to identify glycoproteins in the extracellular matridome of the infarcted left ventricle (LV) and provide experimental evidence for topological determination. Glycoproteomics analysis was performed on eight biological replicates of LV samples from wild-type mice at 7 days following myocardial infarction using SPE of glycopeptides, followed by mass spectrometric identification of N-linked glycosylation sites for topology assessment. We identified hundreds of glycoproteins, and the identified N-glycosylation sites provide novel information on the correct topology for membrane proteins present in the infarct setting. Our data provide the foundation for future studies of the LV infarct extracellular matridome, which may facilitate the discovery of drug targets and biomarkers.


Immersion before dry simulated dive reduces cardiomyocyte function and increases mortality after decompression.
Diving and decompression performed under immersed conditions have been shown to reduce cardiac function. The mechanisms for these changes are not known. The effect of immersion before a simulated hyperbaric dive on cardiomyocyte function was studied. Twenty-three rats were assigned to four groups: control, 1 h thermoneutral immersion, dry dive, and 1 h thermoneutral immersion before a dive (preimmersion dive). Rats exposed to a dive were compressed to 700 kPa, maintained for 45 min breathing air, and decompressed linearly to the surface at a rate of 50 kPa/min. Postdive, the animals were anesthetized and the right ventricle insonated for bubble detection using ultrasound. Isolation of cardiomyocytes from the left ventricle was performed and studied using an inverted fluorescence microscope with video-based sarcomere spacing. Compared with a dry dive, preimmersion dive significantly increased bubble production and decreased the survival time (bubble grade 1 vs. 5, and survival time 60 vs. 17 min, respectively). Preimmersion dive lead to 18% decreased cardiomyocyte shortening, 20% slower diastolic relengthening, and 22% higher calcium amplitudes compared with controls. The protein levels of the sarco-endoplasmic reticulum calcium ATPase (SERCA2a), Na+/Ca2+ exchanger (NCX), and phospholamban phosphorylation in the left ventricular tissue were significantly reduced after both dry and preimmersion dive compared with control and immersed animals. The data suggest that immersion before a dive results in impaired cardiomyocyte and Ca2+ handling and may be a cellular explanation to reduced cardiac function observed in humans after a dive.


Determinants of patient satisfaction and willingness to return with emergency care.
To identify emergency department process of care measures that are significantly associated with satisfaction and willingness to return. Patient satisfaction and willingness to return at 5 urban, teaching hospital EDs were assessed. Baseline questionnaire, chart review, and 10-day follow-up telephone interviews were performed, and 38 process of care measures and 30 patient characteristic were collected for each respondent. Overall satisfaction was modeled with ordinal logistic regression. Willingness to return was modeled with logistic regression. During a 1-month study period, 2,899 (84% of eligible) on-site questionnaires were completed. Telephone interviews were completed by 2,333 patients (80% of patients who completed a questionnaire). Patient-reported problems that were highly correlated with satisfaction included help not received when needed (odds ratio [OR] 0.345; 95% confidence interval [CI] 0.261 to 0.456), poor explanation of causes of problem (OR 0.434; 95% CI 0.345 to 0.546), not told about potential wait time (OR 0.479; 95% CI 0.399 to 0.577), not told when to resume normal activities (OR 0.691; 95% CI 0.531 to 0.901), poor explanation of test results (OR 0.647; 95% CI 0.495 to 0.845), and not told when to return to the ED (OR 0.656; 95% CI 0. 494 to 0.871). Other process of care measures correlated with satisfaction include nonacute triage status (OR 0.701, 95% CI 0.578 to 0.851) and number of treatments in the ED (OR 1.164 per treatment; 95% CI 1.073 to 1.263). Patient characteristics that significantly predicted less satisfaction included younger age and black race. Determinants of willingness to return include poor explanation of causes of problem (OR 0.328; 95% CI 0.217 to 0.495), unable to leave a message for family (OR 0.391; 95% CI 0.226 to 0. 677), not told about potential wait time (OR 0.561; 95% CI 0.381 to 0.825), poor explanation of test results (OR 0.541; 95% CI 0.347 to 0.846), and help not received when needed (OR 0.537; 95% CI 0.340 to 0.846). Patients with a chief complaint of hand laceration were less willing to return compared with a reference population of patients with abdominal pain. Willingness to return is strongly predicted by overall satisfaction (OR 2.601; 95% CI 2.292 to 2.951). These data identify specific process of care measures that are determinants of patient satisfaction and willingness to return. Efforts to increase patient satisfaction and willingness to return should focus on improving ED performance on these identified process measures.


Microscopic Techniques for the Analysis of Micro and Nanostructures of Biopolymers and Their Derivatives.
Natural biopolymers, a class of materials extracted from renewable sources, is garnering interest due to growing concerns over environmental safety; biopolymers have the advantage of biocompatibility and biodegradability, an imperative requirement. The synthesis of nanoparticles and nanofibers from biopolymers provides a green platform relative to the conventional methods that use hazardous chemicals. However, it is challenging to characterize these nanoparticles and fibers due to the variation in size, shape, and morphology. In order to evaluate these properties, microscopic techniques such as optical microscopy, atomic force microscopy (AFM), and transmission electron microscopy (TEM) are essential. With the advent of new biopolymer systems, it is necessary to obtain insights into the fundamental structures of these systems to determine their structural, physical, and morphological properties, which play a vital role in defining their performance and applications. Microscopic techniques perform a decisive role in revealing intricate details, which assists in the appraisal of microstructure, surface morphology, chemical composition, and interfacial properties. This review highlights the significance of various microscopic techniques incorporating the literature details that help characterize biopolymers and their derivatives.


A community study of severe mental retardation in the West Midlands and the importance of the fragile X chromosome in its aetiology.
This paper describes a community based study of 156 boys with idiopathic, severe mental retardation. The boys were examined and a pedigree taken before the cytogenetic results were known. The prevalence of the fragile X chromosome among this group of boys was high: 9% in the whole group and 11% after 39 boys with specific features had been excluded. The fragile X syndrome is therefore an important cause of idiopathic, severe retardation. Its clinical features of large head, large testes, and IQ in the 35 to 70 range were often but not always present in the 14 boys identified in this study. In the whole group, the recurrence of severe mental subnormality was high: 1 in 8 for brothers and 1 in 25 for sisters. This high recurrence was partly due to the fragile X syndrome, partly to X linked mental retardation not accompanied by cytogenetic abnormalities, and partly due to autosomal recessive disease. Autosomal recessive disease was perhaps higher in the West Midlands than elsewhere (such as British Columbia, for example 1) because of the disproportionate contribution by Asian immigrants.


Bedside assessment of extravascular lung water by dilution methods: temptations and pitfalls.
To review the advantages and limitations of dilution methods to assess extravascular lung water (EVLW) at the bedside and to discuss the clinical value of EVLW measurements. Experimental and clinical studies were searched in PUBMED by using "extravascular lung water" and "dilution method" as keywords and further selected as studies investigating either the reliability or the clinical usefulness of dilution methods to assess EVLW. Related articles and the reference lists of selected studies were scanned for additional relevant references. Both the double-indicator (thermo-dye) dilution and the single-indicator (cold saline) dilution methods showed close agreement with gravimetric measurement of EVLW (the reference ex vivo method) and have the advantage of being available at the bedside. Most limitations of dilution methods have been described in experimental conditions and lead to an underestimation of EVLW. These limitations include large pulmonary vascular obstruction, focal lung injury, and lung resection. Dilution methods provide an easy and clinically acceptable estimation of EVLW in most critically ill patients, including those with acute respiratory distress syndrome (ARDS). Assessing EVLW may be useful to predict outcome, to diagnose pulmonary edema, to better characterize patients with ARDS, to guide fluid therapy, and to assess the value of new treatments or ventilatory strategies in patients with pulmonary edema.


Meta-analysis of the Risk of Infections After Anterior Cruciate Ligament Reconstruction by Graft Type.
An infection after anterior cruciate ligament (ACL) reconstruction is a relatively rare but challenging complication. There are no meta-analyses comparing the incidence of infections after ACL reconstruction with the various available graft choices. To compare the incidence of infections after ACL reconstruction with bone-patellar tendon-bone (BPTB) autografts compared with hamstring autografts, with a secondary aim of comparing the incidence of infections after reconstruction with autografts compared with allografts. Meta-analysis. A systematic review was performed to identify level 1 and 2 studies that reported the incidence of infections by graft type after ACL reconstruction. Studies that evaluated patients undergoing primary ACL reconstruction with an autograft, allograft, or combination of autograft and allograft and reported the number of postoperative infections by graft type utilized were considered for inclusion. Studies were excluded if they included revision ACL reconstruction or did not specify the number of infections by graft type. Study findings were reviewed, and meta-analysis was performed when data were sufficiently homogeneous. Twenty-one studies meeting criteria were identified from the literature review. Meta-analysis revealed a significant difference in the incidence of deep infections between BPTB autografts and hamstring autografts, with the BPTB group displaying a 77% lower incidence of infections compared with the hamstring group (relative risk [RR], 0.23; 95% CI, 0.097-0.54). The incidence of infections was 66% lower with BPTB autografts compared with all other graft types, with a pooled RR of 0.33 (95% CI, 0.15-0.71). There was no significant difference in the incidence of infections after ACL reconstruction with autografts compared with allografts (RR, 1.035; 95% CI, 0.589-1.819). The findings of this meta-analysis demonstrate a significantly lower incidence of deep infections after ACL reconstruction with BPTB autografts compared with hamstring autografts but not compared with allografts. Although the overall infection rate after ACL reconstruction is relatively low, the significantly higher rate of infections with hamstring autografts compared with BPTB autografts should be a consideration when discussing graft choices for ACL reconstruction.


Early-Life Intranasal Colonization with Nontypeable Haemophilus influenzae Exacerbates Juvenile Airway Disease in Mice.
Accumulating evidence suggests a connection between asthma development and colonization with nontypeable Haemophilus influenzae (NTHi). Specifically, nasopharyngeal colonization of human infants with NTHi within 4 weeks of birth is associated with an increased risk of asthma development later in childhood. Monocytes derived from these infants have aberrant inflammatory responses to common upper respiratory bacterial antigens compared to those of cells derived from infants who were not colonized and do not go on to develop asthma symptoms in childhood. In this study, we hypothesized that early-life colonization with NTHi promotes immune system reprogramming and the development of atypical inflammatory responses. To address this hypothesis in a highly controlled model, we tested whether colonization of mice with NTHi on day of life 3 induced or exacerbated juvenile airway disease using an ovalbumin (OVA) allergy model of asthma. We found that animals that were colonized on day of life 3 and subjected to induction of allergy had exacerbated airway disease as juveniles, in which exacerbated airway disease was defined as increased cellular infiltration into the lung, increased amounts of inflammatory cytokines interleukin-5 (IL-5) and IL-13 in lung lavage fluid, decreased regulatory T cell-associated FOXP3 gene expression, and increased mucus production. We also found that colonization with NTHi amplified airway resistance in response to increasing doses of a bronchoconstrictor following OVA immunization and challenge. Together, the murine model provides evidence for early-life immune programming that precedes the development of juvenile airway disease and corroborates observations that have been made in human children.


Treatment of rheumatoid arthritis with electromagnetic millimeter waves applied to acupuncture points--a randomized double blind clinical study.
The aim of the study was to evaluate the efficacy and safety of electromagnetic millimeter waves (MW) applied to acupuncture points in patients with rheumatoid arthritis (RA). Twelve patients with RA were exposed to MW with power 2.5 mW and band frequency 54-64 GHz. MW were applied to the acupuncture points of the affected joints in a double blind manner. At least 2 and maximum 4 points were consecutively exposed to MW during one session. Total exposure time consisted of 40 minutes. According to the study design, group I received only real millimeter wave therapy (MWT) sessions, group II only sham sessions. Group III was exposed to MW in a random cross-over manner. Pain intensity, joint stiffness and laboratory parameters were recorded before, during and immediately after the treatment. The study was discontinued because of beneficial therapeutic effects of MWT. Patients from group I (n=4) reported significant pain relief and reduced joint stiffness during and after the course of therapy. Patients from group II (n=4) revealed no improvement during the study. Patients from group III reported the changes of pain and joint stiffness only after real MW sessions. After further large-scale clinical investigations MWT may become a non-invasive adjunct in therapy of patients with RA.


Axillary artery to contralateral axillary vein graft fistula in chronic hemodialysis patients.
Vascular access failure is a severe and common complication for hemodialysis patients. The possible vascular access sites are limited in dialysis patients. Axillary artery to contralateral axillary vein arteriovenous fistula (AVF) is one of the possibilities. However, the clinical outcome of this procedure is still un-defined. The purpose of this study is to review the clinical outcome of axillary artery to contralateral axillary vein AVF as a hemodialysis vascular access. We retrospectively reviewed native or graft arteriovenous fistula records for chronic hemodialysis patients at Chang Gung Memorial Hospital in Kaohsiung, Taiwan, from January 1986 to March 2001. Records were reviewed for all chronic hemodialysis patients, with more than 2000 individuals receiving more than 10,000 fistulas. Eight patients received axillary artery to contralateral axillary vein AVF. The mean age for these patients was 61.7 +/- 16.3 year-old at time of surgery. All patients had received multiple native or graft arteriovenous fistula creation. The 2-year and 4-year AVF graft survival is 87.5% and 43.8% respectively. One patients developed brachial plexopathy after operation. Another patient had venous hypertension distal to the AVF site. Both patients were managed conservatively. There is no AVF-related mortality in these patients. We conclude that axillary artery to contralateral axillary vein graft fistula may be a feasible alternative choice for chronic hemodialysis access.


Safety and efficacy of radionuclide therapy with high-activity In-111 pentetreotide in patients with progressive neuroendocrine tumors.
The intent of this study was to evaluate the safety and efficacy of high-activity 111In-pentetreotide in patients with neuroendocrine tumors. Thirty-two patients with pentetreotide-avid neuroendocrine tumors received therapy from August 2005 to November 2006. Fourteen (14) patients received 1 treatment and 18 patients received 2 treatments. Patients were followed an average of 12.73 months (range 1.2-24.5). Seventeen (17) patients (53%) had grade I or II hematologic toxicities, and 1 patient had grade III thrombocytopenia. One patient had grade II liver toxicity, which appeared 4 weeks after therapy and resolved on week 5. No patient had renal toxicity. Of the patients who completed 2 treatment cycles, 2 of 18 patients had partial disease regression, and 16 of 18 patients with previously progressive disseminated neuroendocrine disease achieved stable disease by imaging criteria. A decrease in serum tumor markers was observed in 14 of 18 patients given 2 therapies. A clinical response was achieved in 84% of the patients. Upon interim analysis, median survival was approximately 13 months (range 1.2-24.5). These results show that high-activity 111In-pentetreotide therapy is effective in patients with progressive disseminated neuroendocrine tumors.


Prospects and development of algal-bacterial biotechnology in environmental management and protection.
The coexistence of algae and bacteria in nature dates back to the very early stages when life came into existence. The interaction between algae and bacteria plays an important role in the planet ecology, cycling nutrients, and feeding higher trophic levels, and have been evolving ever since. The emerging concept of algal-bacterial consortia is gaining attention, much towards environmental management and protection. Studies have shown that algal-bacterial synergy does not only promote carbon capture in wastewater bioremediation but also consequently produces biofuels from algal-bacterial biomass. This review has evaluated the optimistic prospects of algal-bacterial consortia in environmental remediation, biorefinery, carbon sequestration as well as its contribution to the production of high-value compounds. In addition, algal-bacterial consortia offer great potential in bloom control, dye removal, agricultural biofertilizers, and bioplastics production. This work also emphasizes the advancement of algal-bacterial biotechnology in environmental management through the incorporation of Industry Revolution 4.0 technologies. The challenges include its pathway to greener industry, competition with other food additive sources, societal acceptance, cost feasibility, environmental trade-off, safety and compatibility. Thus, there is a need for further in-depth research to ensure the environmental sustainability and feasibility of algal-bacterial consortia to meet numerous current and future needs of society in the long run.


Nocturnal but not short hours quotidian hemodialysis requires an elevated dialysate calcium concentration.
Interest in quotidian (daily) hemodialysis (HD) is growing. Some advocate short-hours high-efficiency daily HD (SDH) and others long-hours slow-flow nocturnal HD (NH) while the patient is asleep, both being used 5 to 7 d/week. The London Daily/Nocturnal Hemodialysis Study was the first attempt to obtain data of SDH and NH that may be compared with conventional thrice weekly HD (CH). This was a 4-yr observational study designed to enter and follow 40 patients: 10 receiving SDH, 10 receiving NH, and 20 receiving CH. The CH patients were cohort control subjects matched for each SDH and NH patient by age, gender, comorbidity, and original dialysis modality (in-center, home, self-care, or satellite HD). All SDH and NH treatments were at home. Data collection to December 2001 was analyzed. Then enrollment had been completed and all patients had been followed for 15 mo, eight SDH plus six NH for 18 mo, seven SDH plus six NH for 21 mo, and seven SDH and five NH for 24 mo. This report gives data on calcium and phosphorus metabolism in these patients. All patients were initially dialyzed against a 1.25-mmol/L calcium bath. Predialysis serum calcium levels became lower in NH versus SDH patients by the first month and at 9 mo were 2.67 +/- 0.25 mmol/L (M +/- SD) in SDH, 2.40 +/- 0.16 mmol/L in NH, and 2.52 +/- 0.21 mmol/L in CH (SDH versus NH, P = 0.038; SDH versus CH versus NH, NS). Predialysis phosphorus levels were better controlled by NH than by SDH or CH, and with NH, all phosphate binders were discontinued. By 12 mo, a rise in bone alkaline phosphatase was seen in NH patients (but not in SDH or CH patients), which peaked at 15 to 18 mo (NH 191 IU/L +/- 70; SDH 82 +/- 34; CH 80 +/- 36; P < 0.002) and similarly with intact parathyroid hormone (iPTH) levels (NH 159 pmol/L +/- 75; SDH 13.1 +/- 10; CH 18 +/- 18; P < 0.00001). Because of these changes, the dialysate calcium concentration was increased to 1.75 mmol/L for the NH patients. Postdialysis calcium then rose to 2.57 +/- 0.21, and alkaline phosphatase and iPTH normalized completely by 21 mo. These observations prompted mass balance studies that showed that a 1.25-mmol/L calcium dialysate was associated with a mean net calcium loss of 2.1 mmol/h of dialysis time, whereas 1.75-mmol/L calcium dialysate provides a net gain of 3.7 mmol/h. In addition, the mass balance studies showed that phosphate removal by NH (43.5 +/- 20.7 mmol) was significantly (P < 0.05) higher than by SHD (24.2 +/- 13.9 mmol) but not by CH (34.0 +/- 8.7 mmol) on a per-treatment basis. With the increased frequency of treatments provided by quotidian dialysis, the weekly phosphorus removal (261.2 +/- 124.2 mmol) by NH was significantly higher than by SDH (P = 0.014) and CH (P = 0.03). This allowed the discontinuation of P binders in the NH group, which in turn eliminated approximately 8 g elemental Ca/wk oral intake. This, together with a 4 g elemental Ca/wk dialysate loss induced by a 1.25-mmol/L Ca bath, explains the changes in Ca, alkaline phosphatase, and iPTH seen in the NH patients. The SDH patients have weekly dialysis times similar to CH and still require P binders and do not become Ca deficient using 1.25-mmol/L Ca dialysate. With NH but not SDH, an elevated dialysate Ca concentration is required.


Gaps between hypertension treatment guidelines and clinical practice in Japan: Baseline survey results from Fukushima Research of Hypertension (FRESH).
This observational study assessed the achievement of treatment goals, as defined by the Japanese Society of Hypertension Guidelines for the Management of Hypertension (JSH 2004). These goals are: <140/80 mm Hg in elderly patients (65 years and older), <130/80 mm Hg in patients with diabetes or kidney disease, and <130/85 mm Hg in younger patients (younger than 65). From July 2006 to May 2007, 72 physician members of the Fukushima Hypertension Conference enrolled a total of 3320 patients from Fukushima Prefecture, Japan. The median age of the patients was 71 years and 46% were male. The success rate was 27% among patients with diabetes mellitus or renal disease, 30% among those younger than 65 years, and 66% among the elderly without the diseases. Factors significantly associated with an increased risk of failure to achieve goals were obesity, dyslipidemia, family histories of diabetes mellitus or hypertension, and number of antihypertensive drugs used. The presence of atherosclerotic complications decreased the risk. This study revealed low achievement rates, identified the importance of weight control and family histories, and indicated a need for better management to prevent complications.


[Anniversary of profile preparing of air physicians on the department of organization and tactics of medical service].
The article presents stages of forming of heading of organization and tactics of medical service of the Air Forces in MMedA by Kirov S.M. (OTMS AF). The Academy celebrates the 50th anniversary in 2009 year. The following directions were basic ones of scientific searches in department OTMS: elaboration of system of treatment-evacuation measures in air armies and units of long-range aviation, substantiation of using of military transport aviation in medical service's purposes, medical-tactics characteristic of combustions for the purpose of creation of model of thermal damages in conditions of nuclear war. At the beginning of 1980s the heading of OTMS AF for scientific-methodic matter became self consistent, completed by professors, having professional education, provided by necessary educational-methodical materials. There were published or prepared for publishing about 30 study guides and textbooks, written by department professors or with their participation.


[The state of regional hemodynamics after performance of operations of the portogastroesophageal blood flow disconnection in liver cirrhosis].
There were examined 112 patients, to whom the various kinds of separating operations were done. After the gastroesophageal junction suturing performance the even venous pressure raising in all parts of the stomach was noted. After performance of the original intervention, directed on the hemorrhage from varicose gastroesophageal veins elimination, the pressure in the high gastric portion had lowered and hyperdynamical state of blood circulation in this zone had normalized. The operation performance for separation of gastroesophageal venous system from the v. porta system had promoted the pressure lowering in upper portion of stomach veins and in v. gastroepiploica. After performance of the operations, directed on separation of portoesophageal blood flow, the pressure and volumetric speed of the blood flow in v. porta had raised.


[Contents, positioning and quality analysis in Spanish websites related to nutrition and eating behavior disorders].
Eating disorders are serious psychological disorders with an increased incidence in last years. One of the factors that determine the high prevalence of eating disorders in our society is the lack of knowledge about nutrition. One of the reasons of this lack of knowledge could be the presence of online resources without scientific validity. OBJECTIVE AND SCOPE: The aim of this study was to analyze the scientific quality and positioning of websites in Spanish that have information on nutrition, eating disorders and obesity. For this purpose, a web search was conducted in the Google Chrome browser using the key words: diet, anorexia, bulimia, obesity and nutrition, and selecting the first 20 results of each search at the rates offered by SeoQuake positioning (Page Rank, Alexa Rank y SEMrush Rank). The variables used for the analysis were: information related to eating habits and diets, information on healthy eating, information about eating disorders and their diagnostics, and formative information about general health topics with professional criteria. Only the 50% of the webpages accomplished the inclusion criteria for this study. Most of them did not follow the guidelines established by e- Europe assessment for quality. The median of the Webpage's PageRank was 2, except those associated with health institutions. Given the scarcity of healthcare websites with scientific rigor is essential to review the existing one and to create new online spaces whose supervision must be carried out by specialists in health and nutrition.


Constant DI pacing suppresses cardiac alternans formation in numerical cable models.
Cardiac repolarization alternans describe the sequential alternation of the action potential duration (APD) and can develop during rapid pacing. In the ventricles, such alternans may rapidly turn into life risking arrhythmias under conditions of spatial heterogeneity. Thus, suppression of alternans by artificial pacing protocols, or alternans control, has been the subject of numerous theoretical, numerical, and experimental studies. Yet, previous attempts that were inspired by chaos control theories were successful only for a short spatial extent (<2 cm) from the pacing electrode. Previously, we demonstrated in a single cell model that pacing with a constant diastolic interval (DI) can suppress the formation of alternans at high rates of activation. We attributed this effect to the elimination of feedback between the pacing cycle length and the last APD, effectively preventing restitution-dependent alternans from developing. Here, we extend this idea into cable models to study the extent by which constant DI pacing can control alternans during wave propagation conditions. Constant DI pacing was applied to ventricular cable models of up to 5 cm, using human kinetics. Our results show that constant DI pacing significantly shifts the onset of both cardiac alternans and conduction blocks to higher pacing rates in comparison to pacing with constant cycle length. We also demonstrate that constant DI pacing reduces the propensity of spatially discordant alternans, a precursor of wavebreaks. We finally found that the protective effect of constant DI pacing is stronger for increased electrotonic coupling along the fiber in the sense that the onset of alternans is further shifted to higher activation rates. Overall, these results support the potential clinical applicability of such type of pacing in improving protocols of implanted pacemakers, in order to reduce the risk of life-threatening arrhythmias. Future research should be conducted in order to experimentally validate these promising results.


The structure and function of actin cytoskeleton in mature glutamatergic dendritic spines.
Dendritic spines are actin-rich protrusions from the dendritic shaft, considered to be the locus where most synapses occur, as they receive the vast majority of excitatory connections in the central nervous system (CNS). Interestingly, hippocampal spines are plastic structures that contain a dense array of molecules involved in postsynaptic signaling and synaptic plasticity. Since changes in spine shape and size are correlated with the strength of excitatory synapses, spine morphology directly reflects spine function. Therefore several neuropathologies are associated with defects in proteins located at the spines. The present work is focused on the spine actin cytoskeleton attending to its structure and function mainly in glutamatergic neurons. It addresses the study of the structural plasticity of dendritic spines associated with long-term potentiation (LTP) and the mechanisms that underlie learning and memory formation. We have integrated the current knowledge on synaptic proteins to relate this plethora of molecules with actin and actin-binding proteins. We further included recent findings that outline key uncharacterized proteins that would be useful to unveil the real ultrastructure and function of dendritic spines. Furthermore, this review is directed to understand how such spine diversity and interplay contributes to the regulation of spine morphogenesis and dynamics. It highlights their physiological relevance in the brain function, as well as it provides insights for pathological processes affecting dramatically dendritic spines, such as Alzheimer's disease.


Preoperative treatment selection in rectal cancer: a population-based cohort study.
Preoperative radiotherapy and chemoradiotherapy for rectal cancer reduce local recurrence rates but is also associated with side effects. Thus, it is important to identify patients in whom the benefits exceed the risks. This study assessed the pretherapeutic parameters influencing the selection to preoperative treatment. Data on all patients in the Stockholm-Gotland area, Sweden, who underwent elective trans-abdominal surgery for rectal cancer in 2000-2010, was retrieved from the Regional Cancer Registry and the Swedish National Patient Register. Clinical variables were analysed in relation to selected preoperative therapy. Odds Ratios were derived from univariable and multivariable logistic regression models. In total 2619 patients were included. Of these 1789 (68.3%) received preoperative radiotherapy or chemoradiotherapy. Over time, use of preoperative therapy increased (p < 0.001). In a multivariable model, age (≥ 80 years) and comorbidity (Charlson Comorbidity Index score ≥ 2) were strongly correlated to omittance of preoperative treatment (OR: 0.05; 95% CI: 0.04-0.07 and 0.29; 95% CI: 0.21-0.39) but there was no difference between genders. Pre-treatment tumour stage was a strong predictor for selection to preoperative (chemo-) radiotherapy. However, 8.2% of patients with intermediate or advanced tumours were selected to no preoperative treatment while 55.0% of patients with early tumours were selected to preoperative therapy. The use of preoperative (chemo-) radiotherapy increased over time. Suboptimal adherence to guidelines appears to exist leading to a risk of overtreatment and to a small extent also undertreatment. More robust selection criteria, also including age and comorbidity should be developed.


Attention-deficit/hyperactivity disorder and Williams syndrome: shared behavioral and neuropsychological profiles.
We compared verbally matched attention-deficit/hyperactivity disorder (ADHD), Williams syndrome (WS), and typically developing individuals (N = 19 each group) on behavioral symptoms (Conners ADHD rating scale) and neuropsychological functioning. Neuropsychological tasks included those that assessed short-term memory and executive functions from the CANTAB (Cambridge Neuropsychological Test Automated Battery) neuropsychological battery. Children with WS scored within the abnormal range and did not differ in severity from ADHD children on the Conners Oppositionality, Cognitive Problems/Inattention, Hyperactivity, and ADHD Index subscales. The WS and ADHD groups also showed similar patterns of neuropsychological functioning, particularly in working memory (WM) strategy use and delayed short-term memory (STM). The findings may have clinical implications for the management of individuals with WS, highlighting the potential significance of behavioral, educational, and pharmacological strategies and treatments known to be useful in the treatment of children with ADHD for individuals with WS.


Epidemiological survey of hepatitis C in a region considered to have high prevalence: the state of Minas Gerais, Brazil.
The prevalence of hepatitis C virus (HCV) infection is affected by demographic, virological, clinical, and lifestyle-related factors and varies in different regions in Brazil or worldwide. The present study aimed to clarify the epidemiological patterns of HCV infection in the interior region of Brazil. This study was conducted in the Southern Triangle Macro-region of the state of Minas Gerais, Brazil, according to the guidelines of the National Program for the Prevention and Control of Viral Hepatitis. The participants answered a structured questionnaire on social and epidemiological factors. Immunochromatographic rapid tests were used for the qualitative detection of antibodies against HCV in whole blood (Alere HCV® Code 02FK10) in adult subjects by a free-standing method. Of 24,085 tested individuals, 184 (0.76%) were anti-HCV positive. The majority of anti-HCV-positive individuals were born between 1951 and 1980 (n=146 [79.3%]), with 68 women and 116 men. Identified risk factors included syringe and/or needle sharing (p = 0.003), being in prison (p = 0.004), and having tattoos or piercings (p = 0.005) and were significantly associated with the decade of birth. The study shows the importance of testing populations at risk for HCV infection, including incarcerated individuals, those with tattoos or piercings, those who share or have shared syringes or needles, and those in high-risk birth cohorts (1950s, 1960s, and 1970s) in the Southern Triangle Macro-region.


Effect of pregnancy on the metabolic clearance rate and the volume of distribution of oxytocin in the baboon.
Pharmacokinetic parameters of oxytocin (OT) metabolism were determined during the last third of pregnancy and again 4-8 wk after delivery in the baboon. Animals were placed on a tether system with venous and arterial access and a continuous monitoring of uterine contractions during gestation. Two methods of determining OT pharmacokinetics were utilized (bolus injection vs. continuous infusion). The metabolic clearance rate of OT as determined during the bolus trials (n = 7) was 22.2 +/- 1.5 ml.min-1.kg-1 in pregnancy and 16.3 +/- 1.4 ml.min-1.kg-1 postpartum (P < 0.05), respectively, and 23.7 +/- 2.8 vs. 16.9 +/- 3.7 ml.min-1.kg-1 (P < 0.05), respectively, as determined during the 1-h infusion trials (n = 4). The initial dilution volume and the volume of distribution at steady state of OT after administration did not differ between pregnant and postpartum animals (P > 0.05). The mean residence time (MRT) of OT was shorter during pregnancy, 7.7 +/- 0.8 vs. 10.8 +/- 1.2 min postpartum (P < 0.05). In summary, OT metabolism during pregnancy in the baboon is characterized by 1) increased clearance rate (1.4-fold), 2) accelerated turnover due to the shorter MRT, and 3) unaltered distribution.


Lung morphology and surfactant function in cardiogenic pulmonary edema: a narrative review.
The conventional analysis of acute cardiogenic pulmonary edema involves the development of high pulmonary capillary pressures resulting in hydrostatic gradients for fluid flux out of capillaries into the interstitial space and alveolar spaces. However, some patients respond poorly to diuretic management. The PubMed database was searched to identify experimental studies on pulmonary edema in animals, experimental studies on surfactant function, including patients with pulmonary edema, and clinical studies reporting barrier dysfunction and/or injury in patients with acute pulmonary edema. Studies with animal models demonstrate that high capillary pressures can cause barrier disruption in alveolar capillary units which increases permeability and the transfer of fluid and protein into lung parenchyma. Fluid in alveolar spaces alters surfactant function which increases fluid flux out of capillaries into the lung parenchyma secondary to larger transcapillary hydrostatic gradients. Patients with acute cardiogenic pulmonary edema have increased levels of surfactant protein B in their plasma which reflect barrier disruption and increased levels of tumor necrosis factor alpha which reflect acute tissue injury. Increased surfactant protein B plasma levels are associated with abnormal gas exchange in patients with chronic heart failure. Patients with exercise-induced left ventricular dysfunction have increased levels of surfactant protein B after short periods of exercise. Pathology studies in patients with chronic heart failure have found increased connective tissue in alveolar capillary units and increased numbers of type II alveolar cells, and these changes represent an adaptive response in these patients. Clinicians need to consider the possibility of barrier dysfunction and disruption in patients with both acute and chronic pulmonary edema and understand that diuresis may have a limited effect on symptoms in some patients.


Redox pioneer: Professor Stuart A. Lipton.
[Figure: see text] Stuart A. Lipton, M.D., Ph.D. is recognized here as a Redox Pioneer because of his publication of four articles that have been cited more than 1000 times, and 96 reports which have been cited more than 100 times. In the redox field, Dr. Lipton is best known for his work on the regulation by S-nitrosylation of the NMDA-subtype of neuronal glutamate receptor, which provided early evidence for in situ regulation of protein activity by S-nitrosylation and a prototypic model of allosteric control by this post-translational modification. Over the past several years, Lipton's group has pioneered the discovery of aberrant protein nitrosylation that may contribute to a number of neurodegenerative disorders, including Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis (Lou Gehrig's disease). In particular, the phenotypic effects of rare genetic mutations may be understood to be enhanced or mimicked by nitrosative (and oxidative) modifications of cysteines and thereby help explain common sporadic forms of disease. Thus, Lipton has contributed in a major way to the understanding that nitrosative stress may result from modifications of specific proteins and may operate in conjunction with genetic mutation to create disease phenotype. Lipton (collaborating with Jonathan S. Stamler) has also employed the concept of targeted S-nitrosylation to produce novel neuroprotective drugs that act at allosteric sites in the NMDA receptor. Lipton has won a number of awards, including the Ernst Jung Prize in Medicine, and is an elected fellow of the AAAS. Antioxid. Redox Signal. 19, 757-764.


The Impact of Local Estrogen on the Urogenital Microbiome in Genitourinary Syndrome of Menopause: A Randomized-Controlled Trial.
The postmenopausal urinary bladder microbiome is not well defined. The aims of this study were to characterize the effect of vaginal estrogen on the vaginal and urinary bladder microbiome in postmenopausal women and describe any clinical associations with the symptoms of genitourinary syndrome of menopause. This was a participant-masked, randomized controlled trial comparing the effect of a 12-week course of an estrogen-containing vaginal ring to a placebo vaginal ring. Standardized evaluations were performed at baseline and 12 weeks. Vaginal samples were obtained for pH, vaginal maturation index, and microbiome analysis. Concomitant catheterized urine samples were obtained for microbiome analysis. 16S ribosomal RNA gene sequencing was performed to characterize the resident microbial communities, with Lactobacillus relative abundance as the primary outcome variable. Genitourinary syndrome of menopause symptoms was measured using validated questionnaires (Pelvic Floor Distress Inventory-Short Form, Female Sexual Function Index, Vulvovaginal Symptoms Questionnaire). Of the 39 postmenopausal women randomized, baseline characteristics were similar between arms, with a mean age of 62 years and mean vaginal pH of 5.0. Using intention-to-treat analysis, there were no significant changes in vaginal or urinary Lactobacillus relative abundance. Two participants in each arm removed their ring prior to the end of the study. Eighty percent of participants experienced at least 1 bothersome genitourinary syndrome of menopause symptom. Vulvovaginal dryness and urinary frequency were most common at baseline, whereas painful intercourse and urinary urgency were most common at the final visit, none of which were statistically significant. Our study did not show a significant change in the bacterial composition of the vaginal or urinary bladder microbiome after either vaginal ring in this relatively asymptomatic postmenopausal population.


The efficacy of a leptospirosis vaccine in preventing leptospiruria in pigs.
A commercially manufactured leptospirosis vaccine containing serovars pomona and hardjo and licensed for use in cattle and sheep was investigated to determine if it would prevent leptospiruria in pigs exposed to serovar pomona. Twenty piglets were each vaccinated twice at an interval of three weeks. Twenty other piglets were unvaccinated and served as controls. Three weeks after the second dose of vaccine all animals were exposed for 64 to 89 days to a natural infection with pomona. During the investigation blood samples were examined serologically and urine samples were examined by dark ground microscopy and cultured for the presence of leptospirae. Attempts were made to culture leptospirae from kidneys at slaughter. Kidneys were also examined histologically for evidence of leptospira infection. One vaccinated animal developed a respiratory disease. It was treated with antibiotics and removed from the trial. Leptosphuria was demonstrated in six of the remaining 19 vaccinated pigs and leptospirae were found in nine of 578 (1.5%) urine samples examined from these animals during the period of exposure. In contrast leptospiruria occurred in 19 of 20 unvaccinated pigs and leptospirae were found in 253 of 642 (39.4%) urine samples examined from these animals. Histopathological lesions consistent with leptospirosis were found in kidneys examined from two of 16 vaccinates and 17 of 18 non-vaccinates. Antibodies to serovar pomona were detected in 12 of 19 vaccinated pigs examined three weeks after the second dose of vaccine and before exposure to infection, and in all of 18 unvaccinated pigs examined after exposure to infection. It was concluded that use of this vaccine in pigs resulted in a significant degree of protection against leptospiruria.


Peripheral nerve hyperexcitability syndromes.
Peripheral nerve hyperexcitability (PNH) syndromes can be subclassified as primary and secondary. The main primary PNH syndromes are neuromyotonia, cramp-fasciculation syndrome (CFS), and Morvan's syndrome, which cause widespread symptoms and signs without the association of an evident peripheral nerve disease. Their major symptoms are muscle twitching and stiffness, which differ only in severity between neuromyotonia and CFS. Cramps, pseudomyotonia, hyperhidrosis, and some other autonomic abnormalities, as well as mild positive sensory phenomena, can be seen in several patients. Symptoms reflecting the involvement of the central nervous system occur in Morvan's syndrome. Secondary PNH syndromes are generally seen in patients with focal or diffuse diseases affecting the peripheral nervous system. The PNH-related symptoms and signs are generally found incidentally during clinical or electrodiagnostic examinations. The electrophysiological findings that are very useful in the diagnosis of PNH are myokymic and neuromyotonic discharges in needle electromyography along with some additional indicators of increased nerve fiber excitability. Based on clinicopathological and etiological associations, PNH syndromes can also be classified as immune mediated, genetic, and those caused by other miscellaneous factors. There has been an increasing awareness on the role of voltage-gated potassium channel complex autoimmunity in primary PNH pathogenesis. Then again, a long list of toxic compounds and genetic factors has also been implicated in development of PNH. The management of primary PNH syndromes comprises symptomatic treatment with anticonvulsant drugs, immune modulation if necessary, and treatment of possible associated dysimmune and/or malignant conditions.


Disclosing clinical performance: the case of cardiac surgery.
In recent years, the clinical performance of named cardiac surgeons in England has been disclosed. This paper aims to explore the nature and impact of disclosure of clinical performance. The paper draws on literature from across the social sciences to assess the impact of disclosure, as a form of transparency, in improving clinical performance. Specifically, it employs the "programme theory" of disclosure. The "programme theory" of disclosure involves identification, naming, public sanction and recipient response. Named individual (consultant) surgeons have been identified through disclosure but this masks the contribution of the clinical team, including junior surgeons. Mortality is the prime performance measure but given low mortality rates, there are problems interpreting this measure. The naming of surgeons has been achieved through disclosure on web sites, developed between the health-care regulator and the surgical profession itself. However, participation remains voluntary. The intention of disclosure is that interested parties (especially patients) will shun poorly performing surgeons. However, these parties' willingness and ability to exercise this sanction appears limited. Surgeons' responses are emergent but about a quarter of surgeons are not participating currently. Fears that surgeons would avoid high-risk patients seem to have been unrealised. While disclosure may have a small effect on individual reputations, the surgical profession as a whole has embraced disclosure. While the aim of disclosure has been to create a transparent medical system and to improve clinical performance, disclosure may have the opposite effect, concealing some performance issues and possibly strengthening professional autonomy. Disclosure therefore represents greater transparency in health-care but it is uncertain whether it will improve performance in the ways that the policy intends.


Potentials of mean force and permeabilities for carbon dioxide, ammonia, and water flux across a Rhesus protein channel and lipid membranes.
As a member of the ubiquitous ammonium transporter/methylamine permease/Rhesus (Amt/MEP/Rh) family of membrane protein channels, the 50 kDa Rhesus channel (Rh50) has been implicated in ammonia (NH(3)) and, more recently, also in carbon dioxide (CO(2)) transport. Here we present molecular dynamics simulations of spontaneous full permeation events of ammonia and carbon dioxide across Rh50 from Nitrosomonas europaea. The simulations show that Rh50 is functional in its crystallographic conformation, without the requirement for a major conformational change or the action of a protein partner. To assess the physiological relevance of NH(3) and CO(2) permeation across Rh50, we have computed potentials of mean force (PMFs) and permeabilities for NH(3) and CO(2) flux across Rh50 and compare them to permeation through a wide range of lipid membranes, either composed of pure lipids or composed of lipids plus an increasing cholesterol content. According to the PMFs, Rh50 is expected to enhance NH(3) flux across dense membranes, such as membranes with a substantial cholesterol content. Although cholesterol reduces the intrinsic CO(2) permeability of lipid membranes, the CO(2) permeabilities of all membranes studied here are too high to allow significant Rh50-mediated CO(2) flux. The increased barrier in the PMF for water permeation across Rh50 shows that Rh50 discriminates 40-fold between water and NH(3). Thus, Rh50 channels complement aquaporins, allowing the cell to regulate water and NH(3) flux independently. The PMFs for methylamine and NH(3) are virtually identical, suggesting that methylamine provides an excellent model for NH(3) in functional experiments.


Animal models of osteoarthritis.
Animal models of osteoarthritis are used to study the pathogenesis of cartilage degeneration and to evaluate potential antiarthritic drugs for clinical use. Animal models of naturally occurring osteoarthritis (OA) occur in knee joints of guinea pigs, mice and other laboratory animal species. Transgenic models have been developed in mice. Commonly utilized surgical instability models include medial meniscal tear in guinea pigs and rats, medial or lateral partial meniscectomy in rabbits, medial partial or total meniscectomy or anterior cruciate transection in dogs. Additional models of cartilage degeneration can be induced by intra-articular iodoacetate injection or by administration of oral or parenteral quinolone antibiotics. None of these models have a proven track record of predicting efficacy in human disease since there are no agents that have been proven to provide anything other than symptomatic relief in human OA. However, agents that are active in these models are currently in clinical trials. Methodologies, gross and histopathologic features and comparisons to human disease will be discussed for the various models.


Leaf and seed micronutrient accumulation in soybean cultivars in response to integrated organic and chemical fertilizers application.
Plant nutrients can be influenced by organic materials of soils. An experiment was conducted to evaluate the effect of organic amendments on elements uptake by soybean cultivars in a silty loam soil in Mazandaran province, Iran. The experiment was carried out in split plot based on randomized complete block design with three replications in 2006. Main plots were included 8 fertilizer treatments consisted of 20 and 40 Mg ha(-1) Municipal Solid Waste Compost (MSW), Vermicompost (VC) and Sewage Sludge (SS) which enriched with 50% chemical fertilizers needed by soil, only chemical fertilizer treatment and control. Sub plots consisted of three genotypes of soybean (032, 033 and JK). Grain yield was determined and soybean leaves and seeds were digested and analyzed for Mn, Cu, Zn and Fe. Results showed that yield and elements content in soybean leaves and seeds (Mn, Cu, Zn and Fe) were influenced by all treatments. The 40 Mg ha(-1) of sewage sludge enriched with chemical fertilizers produced maximum grain yield. Different soybean cultivars had also significant differences in terms of leaf and seed micronutrients accumulation. Maximum grain yield was observed in JK and 033. Mean comparisons showed that interaction effects of fertilizer and cultivar had significant differences on Mn, Cu and Fe content in soybean leaves, so that the maximum Cu content was observed in 032 cultivars with 40 Mg ha(-1) enriched sewage sludge and municipal waste compost. Also the highest amount of Fe was obtained for JK cultivar when the 40 Mg ha(-1) of municipal compost was used. Among different mentioned traits, Fe and Cu content in leaf and seed and Zn content in leaf had a positive and significant correlation with grain yield.


Proteomic Analysis of Emodin Treatment in Neuropathic Pain Reveals Dysfunction of the Calcium Signaling Pathway.
Neuropathic pain (NP) is a syndrome of pain mediated by distinct pathophysiological processes, and current treatments are not fully satisfactory. Emodin is an effective component of Chinese traditional medicine and has an alleviating effect on NP, but the pharmacological mechanism is not clear. We used isobaric tags for relative and absolute quantitation (iTRAQ) technique integrated with liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis to identify potential targets of emodin in a rat peripheral nerve chronic constriction injury (CCI) model. A total of 177 differentially expressed proteins were identified among the sham group, CCI group, and emodin group, with a threshold of 1.2-fold change and a P value ≤ 0.05. Among them, 100 differentially expressed proteins (51 up-regulated and 49 down-regulated) were identified in the CCI group compared with sham group. Moreover, 108 differentially expressed proteins (65 up-regulated and 43 down-regulated) were identified in the emodin group with the CCI group as reference. The enrichment analysis of Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) revealed an important role of calcium signaling pathway, neurotransmitter regulation, and long-term potentiation (LTP) in emodin-treated CCI model. Real-time quantitative fluorescence PCR (qRT-PCR) and Western blot analysis revealed that emodin decreased expression of calcium signaling related proteins, including calmodulin (CaM) dependent protein kinase II (CaMK II), phospholipase Cβ1 (PLCβ1), protein kinase C (PKC), protein kinase C (PKA), and tropomyosin-related kinase B (TrkB), compared with the CCI group. Overall, these findings indicated that emodin might alleviate NP by regulating the calcium signaling pathway.


Synthesis, utilization, and structure of the tetrahydropterin intermediates in the bovine adrenal medullary de novo biosynthesis of tetrahydrobiopterin.
The biosynthesis of two tetrahydropterin intermediates (H4pterin-1 and H4pterin-2), their conversion to tetrahydrobiopterin, and their overall chemical structures are described. A new high performance liquid chromatographic separation of these and other tetrahydropterins is also described. The biosynthesis of tetrahydrobiopterin from dihydroneopterin triphosphate proceeds in the presence of the bovine adrenal medullary biosynthetic enzymes, Mg2+, NADPH. The biosynthesis of H4pterin-2 occurs under identical conditions, and the compound accumulates in the presence of 1 to 10 microM of N-acetylserotonin, an inhibitor of sepiapterin reductase. At higher concentrations of the inhibitor, the synthesis of H4pterin-2 is also inhibited, and H4pterin-1 accumulates. H4pterin-1 also accumulates in the absence of NADPH. In the presence of NADPH the biosynthetic enzymes convert both intermediates to tetrahydrobiopterin at rates which are greater than the rate of conversion of dihydroneopterin triphosphate to tetrahydrobiopterin. Electrochemical, UV/VIS, oxidation, and ionization properties identify the compounds as tetrahydropterins. The side chain structures of the compounds were determined by a combination of chemical means. The structures of the compounds are 6R-(1',2'-dioxopropyl)-tetrahydropterin (H4pterin-1) and 6R-(L-1'-hydroxy-2'-oxopropyl)-tetrahydropterin (H4pterin-2). The data indicate that the biosynthesis of tetrahydrobiopterin from dihydroneopterin triphosphate proceeds in three steps: 1) formation of H4pterin-1 in the presence of Mg2+, 2) NADPH-dependent conversion of H4pterin-1 to H4pterin-2, and 3) NADPH-dependent conversion of H4pterin-2 to tetrahydrobiopterin.


Maternally reported food allergies and other food-related health problems in infants: characteristics and associated factors.
Our goal was to identify the frequency, demographics, and diagnostic characteristics associated with maternally reported food allergies and other food-related health problems among infants aged < or = 1 year. We analyzed data from the 2005-2007 Infant Feeding Practices Study II, a longitudinal survey of 2441 US mothers of healthy singletons from pregnancy through their infant's first year. Doctor diagnosis and symptoms-based criteria were used to identify a probable-food-allergic group from maternal reports of infant health problems with food. More than one fifth of the 2441 mothers reported that their infant had a food-related problem; 6% (n = 143) had a probable food allergy, and 15% (n = 359) had other food-related problems. Forty percent of the infants with a food-related health problem were evaluated by a doctor. Gastrointestinal symptoms were more commonly reported in early infancy compared with skin-related symptoms, which were reported in later infancy, and 27% received medical treatment for the symptoms. Characteristics associated with increased incidence of probable food allergy included family histories of food allergy and type 1 diabetes, gestational diabetes, living in rural or urban areas, being black, and being male. Among all infants with a food-related health problem, the majority experienced their first problem by 6 months of age. Foods recognized to be major allergens were most commonly reported as the source of an allergy. Food-related problems occurred at a high frequency in the first year of life. A better understanding of the demographics, family history, disease manifestations, and diagnoses may provide insight into public health efforts to minimize or prevent food allergies in infancy and to help differentiate food-allergic problems from nonallergic food problems in this age group.


Rationale for the Use of Pirfenidone in Heart Failure With Preserved Ejection Fraction.
Heart failure with preserved ejection fraction (HFpEF) is a major public health problem with growing prevalence and poor outcomes, mainly due to the lack of an effective treatment. HFpEF pathophysiology is heterogeneous and complex. Recently a "new paradigm" has been proposed, suggesting that cardiovascular and non-cardiovascular coexisting comorbidities lead to a systemic inflammatory state, perturbing the physiology of the endothelium and the perivascular environment and engaging molecular pathways that ultimately converge to myocardial fibrosis. If inflammation and fibrosis are the "fil rouge" in the heterogeneous spectrum of HFpEF, anti-fibrotic and anti-inflammatory drugs may have a role in its treatment. Pirfenidone is an orally bioavailable drug with antifibrotic and anti-inflammatory properties already approved for the treatment of idiopathic pulmonary fibrosis. Pirfenidone has been recently tested in animal models of myocardial fibrosis with promising results. Here we will review the rationale underlying the potential therapeutic effect of Pirfenidone in HFpEF.


Cigarette smokers' perceptions of smoking cessation and associated factors in Karachi, Pakistan.
The study explored the perceptions of adult smokers with cardiovascular and respiratory diseases regarding cigarette smoking cessation. We also explored factors that may hinder or facilitate smoking cessation process. Qualitative descriptive exploratory design SAMPLE: Purposive sample of 13 adult smokers with cardiovascular or respiratory diseases visiting outpatient cardiac and respiratory clinics at a private tertiary care hospital MEASUREMENTS: In-depth, face-to-face, and semi-structured interviews were conducted. The interviews were digitally recorded and transcribed verbatim followed by a six steps process of manual thematic analysis of data. Meaningful statements were assigned codes and grouped into categories. Categories were clustered under three themes representing individual factors, socio-cultural factors, and institutional factors. Smoking cessation is influenced by personal, cultural, as well as social aspects. Institutionally, there is a need to recognize that smoking is a learned behavior; hence, prohibiting public smoking will potentially contribute to non-smoking behaviors. Although the nature of misconceptions varies, this is imperative to ensure consistency in messaging, programming, and supports led by healthcare professionals.


Mandibular radiomorphometric assessment of bone mineral density in survivors of pediatric hematopoietic stem-cell transplantation.
Hematopoietic stem-cell transplantation (HSCT) childhood survivors of hematologic malignancies are prone to develop late osteopenia and osteoporosis. The purpose of this retrospective study was to quantitatively and qualitatively assess bone mineral density (BMD) in HSCT childhood survivors and to compare the effectiveness of both qualitative and quantitative assessment methods. DESIGN BMD assessment using panoramic radiographs of childhood HSCT survivors aged 3.69-18.88 years using two radiomorphometric indexes. Case-control double-blinded comparison of panoramic radiographic images from childhood HSCT survivors and age- and sex-matched healthy controls. Quantitative assessment was performed by measuring the cortical bone width bilaterally at the mental foramen level. Qualitative assessment was performed using the mandibular cortical index bilaterally on all panoramic images. Radiographs were taken 6.59-83.95 months after bone marrow transplantation [median±SD=25.92±24.9 months]. Fifty-two panoramic radiographic images were analyzed: 21 from HSCT survivors and 31 from healthy controls aged 3.69-25.1 years [mean±SD=11.89±5.28 years]. The mandibular cortical bone width was 17% smaller in childhood HSCT survivors than in healthy controls (case group: 2.420, control group: 3.307; p=0.00617). Qualitative analysis revealed an increased frequency of severe mandibular cortical erosion in childhood HSCT survivors, although no significant difference was observed (case group: 1.540, control group: 1.490; p=0.32). The interobserver agreement was 85% (Kappa index). HSCT childhood survivors exhibit quantitative and qualitative mandibular bone impairments. Further studies are needed to establish an association between mandibular cortical bone impairment and osteoporosis.


Debates, divisions, and decisions: recombinant DNA advisory committee (RAC) authorization of the first human gene transfer experiments.
Possibly the most far-reaching, controversial research currently being conducted in the international biological science community involves human gene therapy experimentation. In this paper, I report the dynamics of the political process which ultimately found the Recombinant DNA Advisory Committee (RAC) of the National Institutes of Health approving for the first time protocols of this genre. A full appreciation of the policy-making dialogue shows that significant participants perceived the process from very different vantage points regarding the way in which the American political system works and the way in which it ought to work. I argue that, if we are to understand how the RAC should proceed in orchestrating a human gene therapy policy agenda, then we must flesh out and critically analyze these competing vantage points. To that end, I postulate seven possible "action models" for characterizing how protocol assessments of the type at issue might be developed given the nature of our politics, reaching the conclusion that one of these models holds out the most promise for synthesizing efficaciously the key factors involved. In conclusion, I discuss how the RAC might profitably employ this preferred strategy in these and other cases.


Stable expression of Leptospira interrogans antigens in auxotrophic Mycobacterium bovis BCG.
Mycobacterium bovis BCG has been proposed as an effective live vector for multivalent vaccines. The development of mycobacterial genetic systems to express foreign antigens and the adjuvanticity of BCG are the basis for the potential use of this attenuated mycobacterium as a recombinant vaccine vector. Stable plasmid vectors without antibiotic resistance markers are needed for heterologous antigen expression in BCG. Our group recently described the construction of a BCG expression system using auxotrophic complementation as a selectable marker. In this work, LipL32 and LigAni antigens of Leptospira interrogans were cloned and expressed in M. bovis BCG Pasteur and in the auxotrophic M. bovis BCG ΔleuD strains under the control of the M. leprae 18 kDa promoter. Stability of the plasmids during in vitro growth and after inoculation of the recombinant BCG strains in hamsters was compared. The auxotrophic complementation system was highly stable, even during in vivo growth, as the selective pressure was maintained, whereas the conventional vector was unstable in the absence of selective pressure. These results confirm the usefulness of the new expression system, which represents a huge improvement over previously described expression systems for the development of BCG into an effective vaccine vector.


Hospital discharge data used as feedback in planning research and education for primary care.
Are research and training programs in pediatrics, internal medicine, and obstetrics and gynecology (OB-GYN) comprehensive enough to give trainees proficiency in primary care? Controversy exists about which subject areas should be added to the training schema to make them more applicable in primary care. One approach to this controversy is to use the most frequent of serious patient problems that are outside these disciplines as feedback into the process of selecting areas for more comprehensive training. In this study, patients' serious problems were defined as those requiring hospitalization. Diagnoses from the National Hospital Discharge Survey were grouped into categories of morbidity by age and sex. The most frequent categories outside the three disciplines were identified. For pediatrics these problems were trauma, mental disorders, and unintended pregnancy; for internal medicine, trauma, mental and gynecologic disorders, and unintended pregnancy; for OB-GYN, trauma and mental, cardiovascular, pulmonary, gastrointestinal, and arthritic disorders. Since primary care is largely ambulatory care, the next step in the resolution of the controversy would be to define the competency level needed for the prevention, early recognition, and early management of these disorders in the ambulatory care setting. Once defined, competency levels can be examined among trainees in the three specialties, and areas where competency is found inadequate can be emphasized. Although hospitalization data are not the only logical criteria for choosing areas for emphasis, these feedback data offer a method of integrating patients' most frequent severe problems into the selection process.


Identification of conserved traits in fluorescent pseudomonads with antifungal activity.
A collection of 29 fluorescent pseudomonads, some with known biological control activity against a range of phytopathogenic fungi, were characterized phenotypically and genotypically by comparing carbon source utilization patterns, suppression of Pythium ultimum both in planta and in vitro and the potential to produce known secondary metabolites. Fatty acid profiling and restriction fragment length polymorphism (RFLP) analysis of the ribosomal DNA operon (ribotyping) were used to determine the diversity of isolates. A small group of genetically related Pseudomonas spp. with similar properties was identified; each isolate produced a diffusible bioactive product in vitro and was active against Pythium ultimum in planta. However, other isolates that were able to suppress damping off disease but did not inhibit hyphal extension in vitro clustered outside this group. Phenotypic analyses revealed that the accumulation of C17:0 cyclopropane fatty acid (17CFA) and the production of hydrogen cyanide correlated significantly with biological control activity and with the antagonism of fungal development. The potential of 17CFA as a marker for the selection of fluorescent pseudomonads with biocontrol agent (BCA) potential was demonstrated by the isolation of a novel active strain. This was selected after the screening of 13 clonal groups of fluorescent pseudomonads identified from 500 isolates from the phytosphere of sugar beet. Levels of 17CFA synthesis possibly reflect the efficacy of the rpoS allele in particular strains.


Concentrations of sperm, protein and a sperm membrane glycoprotein within boar epididymal luminal fluids.
Boar rete testis fluid and luminal contents from nine epididymal segments were collected for analysis. From proximal to distal, segments were designated A, B, C (caput), Da, Db, Ea (corpus) and Eb, Fa, Fb (cauda). Concentrations of sperm, protein and soluble sperm membrane glycoprotein S2P3 were lowest in the caput epididymidis (region A) and highest in the proximal corpus epididymidis (region Da). At region Da, approximately 94% of the fluid that had entered the epididymis had been reabsorbed. More total protein was found in the luminal fluid of region Da than could be accounted for on the basis of concentration via fluid removal. The proximal cauda epididymidis was the major luminal protein-removing region. However, large amounts of glycoprotein S2P3 were removed from the luminal fluids during passage through the caput epididymidis, and smaller amounts were removed during passage through the cauda epididymidis.