Regulation of expression of the gene encoding the major surfactant protein (SP-A) in human fetal lung in vitro. Disparate effects of glucocorticoids on transcription and on mRNA stability.
We previously observed that dexamethasone had a biphasic effect on the levels of mRNA encoding the major surfactant protein (SP-A) in human fetal lung in vitro; at concentrations of 10(-10) and 10(-9) M, dexamethasone caused an increase in the levels of SP-A mRNA, whereas at concentrations of greater than 10(-8) M, the steroid had a pronounced inhibitory effect on SP-A mRNA levels. It was also found that dexamethasone antagonized the stimulatory effect of dibutyryl cyclic AMP (Bt2cAMP) on SP-A mRNA levels in human fetal lung in vitro. It was our objective, in the present study, to characterize further the effects of dexamethasone and Bt2cAMP on SP-A mRNA levels in human fetal lung tissue and to determine whether such effects are associated with comparable changes in the transcriptional activity of the SP-A gene. We found that the action of dexamethasone (10(-7) M) to reduce the levels of SP-A mRNA in control and Bt2cAMP-treated fetal lung explants was evident within 2 h of its addition to the culture medium; SP-A mRNA was reduced to barely detectable levels in control and in Bt2cAMP-treated tissues after 24 h of dexamethasone treatment. The action of dexamethasone to reduce SP-A mRNA levels was not prevented by co-incubation with either actinomycin D or cycloheximide. In contrast to its dose-related biphasic effects on the levels of SP-A mRNA, we found that dexamethasone caused a dose-dependent stimulation of SP-A gene transcription. Bt2cAMP also increased the transcriptional activity of the SP-A gene in the human fetal lung in vitro. In fetal lung explants incubated in the presence of dexamethasone plus Bt2cAMP, a synergistic induction of SP-A gene transcription was observed at concentrations of dexamethasone of 10(-9)-10(-7) M. Our findings are indicative that the stimulatory effects of dexamethasone (10(-10)-10(-9) M) on SP-A mRNA levels are reflective of a stimulatory effect of the steroid on SP-A gene transcription, whereas the inhibitory effects of dexamethasone (10(-7) M) on SP-A mRNA levels are the result of a dominant effect of the steroid in elevated concentrations to reduce SP-A mRNA stability.


Functional significance and physiological regulation of essential trace metals in fish.
Trace metals such as iron, copper, zinc and manganese play essential roles in various biological processes in fish, including development, energy metabolism and immune response. At embryonic stages, fish obtain essential metals primarily from the yolk, whereas in later life stages (i.e. juvenile and adult), the gastrointestine and the gill are the major sites for the acquisition of trace metals. On a molecular level, the absorption of metals is thought to occur at least in part via specific metal ion transporters, including the divalent metal transporter-1 (DMT1), copper transporter-1 (CTR1), and Zrt- and Irt-like proteins (ZIP). A variety of other proteins are also involved in maintaining cellular and systemic metal homeostasis. Interestingly, the expression and function of these metal transport- and metabolism-related proteins can be influenced by a range of trace metals and major ions. Increasing evidence also demonstrates an interplay between the gastrointestine and the gill for the regulation of trace metal absorption. Therefore, there is a complex network of regulatory and compensatory mechanisms involved in maintaining trace metal balance. Yet, an array of factors is known to influence metal metabolism in fish, such as hormonal status and environmental changes. In this Review, we summarize the physiological significance of iron, copper, zinc and manganese, and discuss the current state of knowledge on the mechanisms underlying transepithelial metal ion transport, metal-metal interactions, and cellular and systemic handling of these metals in fish. Finally, we identify knowledge gaps in the regulation of metal homeostasis and discuss potential future research directions.


Effects of surface texture and interrelated properties on marine biofouling: a systematic review.
This systematic review examines effects of surface texture on marine biofouling and characterizes key research methodologies. Seventy-five published articles met selection criteria for qualitative analysis; experimental data from 36 underwent quantitative meta-analysis. Most studies investigated fouling mechanisms and antifouling performance only in laboratory assays with one to several test species. Textures were almost exclusively a single layer of regularly arranged geometric features rather than complex hierarchical or irregular designs. Textures in general had no effect or an inconclusive effect on fouling in 46% of cases. However, effective textures more often decreased (35%) rather than increased (19%) fouling. Complex designs were more effective against fouling (51%) than were regular geometric features (32%). Ratios of feature height, width, or pitch to organism body length were significant influences. The authors recommend further research on promising complex and hierarchical texture designs with more test species, as well as field studies to ground-truth laboratory results.


Management of complete ureteral obstructions with a transluminal puncture technique.
The traditional delayed treatment of iatrogenic complete ureteral obstruction is open surgery. An easy endourological technique, transluminal re-canalization of the ureter by guide-wire puncture under fluoro-endoscopic control, which has been performed on 4 patients, is described. With the guidance of C-arm fluoroscopy, by moving the C-arm to different planes, the tip of the ureteroscope is directed to the correct plane to meet the obliterated proximal end of the ureter and under direct vision, transluminal puncture is performed using the stiff end of a 0.035-inch guide wire. Once the stiff end of the guide-wire is in the lumen of the proximal ureter, an ureteral catheter is introduced over the guide wire, the guide wire is then removed and reinserted through the ureteral catheter with its soft end leading and a double J catheter is inserted. Ureteral stricture, if later encountered, is treated with balloon dilatation. Continuity of the ureter was restored in all 4 patients. The double J stents were removed 6 weeks later and a retrograde pyelography revealed resolution of the hydronephrosis without extravasation of urine. Although a very satisfactory result was achieved in our cases, more cases are needed to show if it can be an alternative to conventional surgical repair. However, we believe that this minimally invasive technique can be used for short obliterated ureteral segments and neither delays nor does it preclude further management using open surgery.


One-piece versus two-piece zirconia abutment supported single implant crown in the esthetic region: 3-Year results from a split-mouth randomized controlled clinical trial.
To compare the clinical, radiographic, and immunological outcomes between one-piece versus two-piece zirconia abutments supported single implant crowns in the esthetic region. The study followed a split-mouth, double-blind, and randomized controlled clinical design for a duration of 3 years. Twenty-two eligible patients with 44 implants were randomly assigned to two groups: Group 1 (one-piece zirconia abutment with zirconia base, n = 22) and Group 2 (two-piece zirconia abutment with titanium base, n = 22). The primary outcome was the technical complication rate. Additionally, survival rates, cytokines concentrations in peri-implant crevicular fluid (PICF), peri-implant conditions, marginal bone loss, and pink/white esthetics score (PES/WES) were assessed as secondary outcomes. Twelve of 22 patients attended the 1-year follow-up (due to the COVID pandemic), and 19 patients attended the 3-year examination. Two abutments in Group 1 were fractured after 10 and 12 months in function. Additionally, one screw loosening occurred in Group 1 at 1-year follow-up. The 3-year technical complication rate was significantly higher in Group 1 than that in Group 2 (15.79% vs. 0%, p < .001). The 3-year implant survival rate was 100% in both groups. The concentration of IFN-γ in PICF was significantly upregulated in Group 2 (p = .018). Furthermore, the IL-6 concentration was positively correlated with BOP% (p = .020). Two-piece zirconia abutments exhibited superior technical performance compared to one-piece designs during a 3-year follow-up in the anterior region. However, further long-term research is necessary to verify the immunological stability of two-piece zirconia abutments.


Does global change increase the risk of maladaptation of Atlantic salmon migration through joint modifications of river temperature and discharge?
In freshwater ecosystems, water temperature and discharge are two intrinsically associated triggers of key events in the life cycle of aquatic organisms such as the migration of diadromous fishes. However, global changes have already profoundly altered the thermal and hydrological regimes of rivers, affecting the timing of fish migration as well as the environmental conditions under which it occurs. In this study, we focused on Atlantic salmon (Salmo salar), an iconic diadromous species whose individuals migrate between marine nursery areas and continental spawning grounds. An innovative multivariate method was developed to analyse long-term datasets of daily water temperature, discharge and both salmon juvenile downstream and adult upstream migrations in three French rivers (the Bresle, Oir and Nivelle rivers). While all three rivers have gradually warmed over the last 35 years, changes in discharge have been very heterogeneous. Juveniles more frequently used warmer temperatures to migrate. Adults migrating a few weeks before spawning more frequently used warm temperatures associated with high discharges. This has already led to modifications in preferential niches of both life stages and suggests a potential mismatch between these populations' ecological preference and changes in their local environment due to global change.


Myeloid Neoplasms Following Solid Organ Transplantation: Clinicopathologic Studies of 23 Cases.
Myeloid neoplasms (MNs) after solid organ transplant are rare, and their clinicopathologic features have not been well characterized. We retrospectively analyzed 23 such cases. The ages ranged from 2 to 76 years, with a median of 59 years at the diagnosis. The median interval between the transplant and diagnosis was 56 months (range, 8-384 months). The transplanted organs included liver in five, kidney in six, lung in five, heart in six, and heart/lung in one case(s). The types of MN included acute myeloid leukemia (AML) in 12, myelodysplastic syndrome (MDS) in five, chronic myelogenous leukemia (CML) in four, and myeloproliferative neoplasms (MPNs) in two cases. Cytogenetics demonstrated clonal abnormalities in 18 (78.3%) cases, including unbalanced changes in 10 (55.6%), Philadelphia chromosome in four (22.2%), and other balanced aberrations in four (22.2%) cases. Thirteen (56.5%) patients died, with an estimated median survival of 9 months. With disease stratification, AML and MDS have short median survivals (3.5 and 7 months, respectively), with an initial precipitous decline of the survival curve. Posttransplant MNs have a latency period between that seen in AML/MDS related to alkylators and that associated with topoisomerase II inhibitors. The cytogenetic profile suggests a mutagenic effect on leukemogenesis. The clinical outcome for AML/MDS is dismal, with death occurring at an early phase of treatment.


Pressure ulcer prevalence and prevention of nosocomial development: one hospital's experience.
A 500 bed acute care facility needed to replace their old medical-surgical patient beds and reduce the costly use of specialty beds and overlays. After a review of the literature, the facility focused on the 44-bed AIDS/Oncology unit, first trialing a new therapeutic bed, then replacing all the beds. A prevalence survey was conducted 5 days before the placement of the new beds and monthly thereafter for 6 months. It was hypothesized that (1) incidence of nosocomial pressure ulcers would decrease, (2) use of specialty beds would be reduced, resulting in significant cost savings within a few months, and (3) there would be a learning curve regarding use of the beds and proper "zoning" of patients. From April through November 1995, 256 patients were surveyed. Pre-survey, the average range on the unit for pressure ulcer prevalence was 7.5 to 15% (both nosocomial and admitted). Post-survey, the range was 3 to 16% (admitted ulcers only). Zero nosocomial pressure ulcers developed during the study period. Use of foam overlays and low air loss surfaces decreased, resulting in a savings of 83%. There were no problems with using the beds or zoning patients. These survey results suggest that other institutions could achieve similar clinical and financial outcomes by converting rental dollars to capital assets.


Crush injury of the upper limb. Early and late management.
The care of the patient with a crushed upper limb requires accurate assessment, carefully planned and executed surgical procedures, diligence, and reassessment. Often, a long period of rehabilitation is also needed. The quality of care rendered by the surgeon and therapist often affects the patient's functional end result and his chance to regain his ability to provide for himself independently.


Protective Effects of Pterostilbene on Lipopolysaccharide-Induced Acute Lung Injury in Mice by Inhibiting NF-κB and Activating Nrf2/HO-1 Signaling Pathways.
Pterostilbene (PTER) is a kind of stilbene compound with biological activity isolated from plants such as red sandalwood, blueberry and grape. It has anti-tumor, anti-bacterial, anti-oxidation and other pharmacological activities. However, the underlying mechanism of the protective effect of PTER on lipopolysaccharide (LPS)-induced acute lung injury (ALI) remained not clarified. In this study, LPS was used to establish a mouse model of ALI. Bronchoalveolar lavage fluid (BALF) was collected for inflammatory cells, and the wet-to-dry weight ratio of the lungs was measured. The activities of myeloperoxidase (MPO), antioxidant indexes such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) and oxidation index such as malondialdehyde (MDA) in lung tissues of mice were measured by the corresponding kits. The levels of Cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), TNF-α, IL-6 and IL-1β in lung tissues of mice were detected by quantitative real-time polymerase chain reaction (qRT-PCR). The activities of Nrf2, HO-1, p-p65 and p-IκB were determined by western blotting. The results showed that the model of LPS-induced ALI was successfully replicated, and it was found that PTER could significantly improve the pathological degree of ALI such as sustained the integrity of the lung tissue structure, alleviated pulmonary interstitial edema and alveolar wall thickening, reduced infiltrated inflammatory cells. PTER could decrease the number of inflammatory cells and obviously inhibit the increase of W/D ratio caused by LPS. PTER could also significantly reduce LPS-induced MPO and MDA, and increase LPS-decreased SOD, CAT and GSH-Px in the lungs. In addition, it was also found that PTER has the ability to decrease LPS-induced production of COX-2, iNOS, TNF-α, IL-6 and IL-1β. The underlying mechanism involved in the protective effect of PTER on ALI were via activating Nrf2 and HO-1, and inhibiting the phosphorylation of p65 and IκB. These results suggested that PTER can protect LPS-induced ALI in mice by inhibiting inflammatory response and oxidative stress, which provided evidence that PTER may be a potential therapeutic candidate for LPS-induced ALI intervention.


BAP1 Immunostain Status in Intraocular Biopsy Specimens for Uveal Melanoma Highly Correlates with Other Prognostic Markers.
Loss of BAP1 protein expression emerged as a negative prognostic marker in uveal melanoma (UM) and has primarily been studied in enucleations. Intraocular biopsy is frequently performed prior to UM globe-conserving therapy. We retrospectively evaluated BAP1 immunostaining of UM in 16 biopsies and 8 subsequent enucleations, and results were correlated with the UM-specific gene expression profile (GEP; n = 11), chromosome 3 status by FISH and/or chromosomal microarray (n = 12; 9 also had GEP), and clinical outcomes. UM involved the choroid in 15 (of 16) cases. Biopsy was performed for prognostication (n = 12) or diagnosis (n = 4). Treatment included brachytherapy (n = 13; 5 followed by enucleation) or enucleation only (n = 3). BAP1 nuclear immunostaining was positive in 9, negative in 4, and equivocal in 3 biopsies. For the 3 equivocal biopsies, BAP1 immunostaining was positive in 2 (of 3) subsequent enucleations. BAP1 immunostaining was concordant between all 5 remaining biopsies and enucleations. BAP1-positive biopsies had disomy 3 (n = 6) or 3p loss (n = 1) and class 1 GEP (n = 6). BAP1-negative biopsies had monosomy 3 (n = 3) and class 2 GEP (n = 2). Median follow-up was 62.5 months (range, 17-150). For BAP1-positive UM patients, 8 were alive (7 without metastatic disease) and 3 had died (1 melanoma-related death). Among BAP1-negative UM patients, 2 were alive (1 with metastatic disease) and 3 had melanoma-related deaths. BAP1 immunostaining in biopsies highly correlates with results in subsequent enucleations and with well-established UM prognostic markers, representing a potential additional prognostic tool for UM biopsies.


Characterizing mechanical properties of biological cells by microinjection.
Microinjection has been demonstrated to be an effective technique to introduce foreign materials into biological cells. Despite the advance, whether cell injection can be used to characterize the mechanical properties of cells remains elusive. In this paper, extending the previously developed mechanical model, various constitutive materials are adopted to present the membrane characteristics of cells. To demonstrate the modeling approach and identify the most appropriate constitutive material for a specific biomembrane, finite element analysis (FEA) and experimental tests are carried out. It is shown that the modeling results agree well with those from both FEA and experiments, which demonstrates the validity of the developed approach. Moreover, Yeoh and Cheng materials are found to be the best constitutive materials in representing the deformation behaviors of zebrafish embryos and mouse embryos (or oocytes), respectively. Also, the mechanical properties of zebrafish embryos at different developmental stages and mouse embryos (or oocytes) are characterized.


Disgust and fear-related UCS-expectancy bias in blood-fearful individuals.
People with specific fears tend to overestimate the occurrence of unpleasant consequences in situations involving their feared objects. Such expectancy bias logically acts in a way to confirm phobic fear and avoidance. Increasing evidence suggests that blood phobia is qualitatively different from other specific phobias. Confrontation with phobic stimuli gives rise to disgust and repulsion rather than (threat-induced) fear. Therefore, this study examined the role of disgust-related UCS expectancies following confrontation with blood phobia-relevant stimuli. Using a thought-experiment procedure, high (n = 30) and low (n = 30) blood-fearful individuals estimated the probability that the presentation of slides showing a bloody wound and a series of filler slides would be followed by a sip of nauseating juice, a threat-related electrical shock or nothing. Although participants generally expected shock and juice following blood, UCS expectancies for both aversive outcomes for blood were significantly more pronounced in high blood-fearful participants. This implicates that UCS-expectancy biases may be involved in the development and maintenance of blood phobia.


IFN-gamma and TNF-alpha regulate human NHE3 gene expression by modulating the Sp family transcription factors in human intestinal epithelial cell line C2BBe1.
Diarrhea associated with inflammatory bowel disease has been attributed to stimulated secretion of proinflammatory cytokines like IFN-gamma and TNF-alpha, which have been shown to downregulate the expression of the sodium-hydrogen exchanger-3 (NHE3) gene. In this study, we have investigated the mechanism of NHE3 gene regulation by IFN-gamma and TNF-alpha in C2BBe1 cells. In response to both IFN-gamma (30 ng/ml) and TNF-alpha (20 ng/ml), the construct containing the bp -95 to +5 region of the human NHE3 promoter, which harbors a number of cis-elements including four potential Sp1 binding sites, showed a maximum repression of 60%. Knockdown of Sp1 and Sp3 expression using small interfering RNA resulted in a significant inhibition of the NHE3 promoter activity and resistance to cytokines effects. These cytokines showed no effects on the expression of Sp1 and Sp3 mRNA and protein levels as assessed by RT-PCR and Western blot analyses, respectively. After treatment with cytokines, the binding of Sp1 and Sp3 proteins to NHE3 promoter decreased significantly, as seen by gel mobility shift assays and chromatin immunoprecipitation assays. The inhibitory effects of both cytokines on the NHE3 promoter were completely blocked by the broad-range kinase inhibitor staurosporine and the selective protein kinase A (PKA) inhibitor 8-bromoadenosine-3',5'-cyclic monophosphorothioate, Rp-isomer. The binding affinity of Sp1 and Sp3 proteins for NHE3 Sp1 probe was significantly decreased after in vitro phosphorylation of nuclear proteins by the alpha-catalytic subunit of PKA. Our data indicate that IFN-gamma and TNF-alpha may repress the NHE3 promoter activity in C2BBe1 cells by PKA-mediated phosphorylation of Sp1 and Sp3 transcription factors.


Soliton formation by decelerating interacting Airy beams.
We demonstrate a new type of soliton formation arising from the interaction of multiple two-dimensional Airy beams in a nonlinear medium. While in linear regime, interference effects of two or four spatially displaced Airy beams lead to accelerated intensity structures that can be used for optical induction of novel light guiding refractive index structures, the nonlinear cross-interaction between the Airy beams decelerates their bending and enables the formation of straight propagating solitary states. Our experimental results represent an intriguing combination of two fundamental effects, accelerated optical beams and nonlinearity, together enable novel mechanisms of soliton formation that will find applications in all-optical light localization and switching architectures. Our experimental results are supported by corresponding numerical simulations.


Salivary epigenetic biomarkers as predictors of emerging childhood obesity.
Epigenetics could facilitate greater understanding of disparities in the emergence of childhood obesity. While blood is a common tissue used in human epigenetic studies, saliva is a promising tissue. Our prior findings in non-obese preschool-aged Hispanic children identified 17 CpG dinucleotides for which differential methylation in saliva at baseline was associated with maternal obesity status. The current study investigated to what extent baseline DNA methylation in salivary samples in these 3-5-year-old Hispanic children predicted the incidence of childhood obesity in a 3-year prospective cohort. We examined a subsample (n = 92) of Growing Right Onto Wellness (GROW) trial participants who were randomly selected at baseline, prior to randomization, based on maternal phenotype (obese or non-obese). Baseline saliva samples were collected using the Oragene DNA saliva kit. Objective data were collected on child height and weight at baseline and 36 months later. Methylation arrays were processed using standard protocol. Associations between child obesity at 36 months and baseline salivary methylation at the previously identified 17 CpG dinucleotides were evaluated using multivariable logistic regression models. Among the n = 75 children eligible for analysis, baseline methylation of Cg1307483 (NRF1) was significantly associated with emerging childhood obesity at 36-month follow-up (OR = 2.98, p = 0.04), after adjusting for child age, gender, child baseline BMI-Z, and adult baseline BMI. This translates to a model-estimated 48% chance of child obesity at 36-month follow-up for a child at the 75th percentile of NRF1 baseline methylation versus only a 30% chance of obesity for a similar child at the 25th percentile. Consistent with other studies, a higher baseline child BMI-Z during the preschool period was associated with the emergence of obesity 3 years later, but baseline methylation of NRF1 was associated with later obesity even after adjusting for child baseline BMI-Z. Saliva offers a non-invasive means of DNA collection and epigenetic analysis. Our proof of principle study provides sound empirical evidence supporting DNA methylation in salivary tissue as a potential predictor of subsequent childhood obesity for Hispanic children. NFR1 could be a target for further exploration of obesity in this population.


Phosphotyrosine phosphatase associated with band 3 protein in the human erythrocyte membrane.
The anion-exchange band 3 protein is the main erythrocyte protein that is phosphorylated by tyrosine kinase. To study the regulation of band 3 phosphorylation, we examined phosphotyrisine phosphatase (PTP) activity in the human erythrocyte. We show that the human erythrocyte membrane contains a band 3-associated neutral PTP which is activated by Mg2+ and inhibited by Mn2+ and vanadate. The PTP is active in the intact cell and in the isolated membrane. A major fraction of the PTP is tightly bound to the membrane and can be extracted from it by Triton X-100; a minor part is associated with Triton X-100-insoluble cytoskeleton. The behaviour of the PTP parallels that of band 3, the major fraction of which is extractable by detergents with a minor fraction being anchored to the cytoskeleton. Moreover, band 3 is co-precipitated when the PTP is immunoprecipitated from solubilized membranes, and PTP is co-precipitated when band 3 is immunoprecipitated. The PTP appears to be related to PTP1B (identified using an antibody to an epitope in its catalytic domain and by molecular mass). The system described here has a unique advantage for PTP research, since it allows the study of the interaction of a PTP with an endogenous physiological substrate that is present in substantial amounts in the cell membrane. The membrane-bound, band 3-associated, PTP may play a role in band 3 function in the erythrocyte and in other cells which have proteins analogous to band 3.


Possible involvement of oxytocin in modulating the stress response in lactating dairy cows.
Oxytocin can attenuate the physiological and behavioral response to stress in animals. In this study we investigated the relationship between plasma oxytocin concentrations and the behavioral and physiological response of dairy cows to a repeated psychological stressor (novel environment). Twenty lactating multi-parous dairy cows were milked in a familiar milking parlor and in a novel environment. Blood samples were collected before and after milking in the familiar parlor (baseline) and on the second and fifth day in the novel parlor to measure plasma cortisol and oxytocin concentrations. Heart rate was recorded on all cows during milking in the familiar and novel environment. On all test days, the behavioral response of cows to milk cluster attachment was scored. On day 2 in the novel parlor, the oxytocin response, cortisol concentrations and heart rate were greater, and heart rate variability was lower than baseline values recorded in the familiar parlor. The results from this study suggest that oxytocin release is increased in response to exposure to a psychological stressor (novel environment) and that cows adapt to this stressor over time. After initial suppression, oxytocin levels increased over days of milking in a novel environment, whereas indicators of stress simultaneously decreased. Furthermore, the oxytocin increase was associated with habituation of the cortisol response in anticipation of milking in a novel environment, suggesting that oxytocin may be involved in habituation to a novel environment in dairy cows. This mechanism of habituation to novel environments may reflect an association between oxytocin and a "familiarization-habituation response" to repeated exposure to an initially novel environment that has previously been reported in humans.


Does behavior therapy normalize the classroom behavior of hyperactive children?
This study evaluated the effectiveness of eight weeks of intensive behavioral treatment in normalizing the classroom behavior of 28 children with attention deficit disorder with hyperactivity (ADDH). Using blind classroom observers, treatment efficacy was examined for full normalization, partial normalization, and the rate of hyperactive children classified as being like normals. Evidence for normalization was scarce. With treatment, there was no significant change in the percentage of hyperactive children classified as normal. Some normalization gains were found at midtreatment but were not sustained. Attention, activity, and impulsivity, the primary features of ADDH, were not normalized. Aggression, however, was consistently and fully normalized. The modification of aggression does not appear to remedy hyperactive behaviors. The clinical meaningfulness of treatment was minimal; the hyperactive children remained deviant in many aspects of classroom conduct.


Hyaluronate concentration in tracheal lavage fluid from clinically normal horses and horses with chronic obstructive pulmonary disease.
To establish concentration of hyaluronate (HA) in tracheal lavage fluid from healthy horses and horses with chronic obstructive pulmonary disease (COPD). ANIMALS AND SAMPLES: Tracheal lavage fluid samples (n = 42) from 18 horses, 11 with COPD, and 7 control horses. Clinical examination of the respiratory tract, tracheal lavage, and blood sample collection were performed on horses without clinical signs of respiratory tract disease and horses with clinical signs of COPD. In some horses, 1 to 5 repeated examinations were performed at 1-week intervals. Tracheal lavage fluid samples were analyzed for cell numbers, and urea concentration (made in parallel with serum samples to evaluate sample dilution effect); HA was determined by radiometric assay. Mean (+/-SEM) HA concentration in tracheal lavage fluid samples was significantly (P = 0.005) higher in horses with COPD (1,880 [+/-309] micrograms/L), compared with that in control horses (256 [+/-72] micrograms/L). The increase in HA concentration in tracheal lavage fluid of COPD-affected horses was verified by repeated sample collection and analysis. In horses with chronic respiratory tract inflammation such as COPD, tracheal lavage fluid HA concentration is about 7 times higher than reference values. High HA concentration in the tracheal or bronchoalveolar lavage fluid may reflect pathophysiologic changes in connective tissue around bronchi and bronchioli, leading to continuous increased production of HA in horses with advanced forms of COPD. Determination of tracheal lavage fluid HA concentration may be used as a marker of chronic inflammatory changes in the COPD-affected lung.


The current and future dynamics of disease in plant communities.
Pathogens are powerful evolutionary forces shaping the structure and dynamics of both individual species and of the communities of which they are part, at a broad range of genetic, ecological, spatial, and temporal scales. At all these levels their impact varies from the subtle and little recognized through to the most obvious destruction. Today the direct role of pathogens in natural plant communities is better recognized than at previous times, although the nuances of their interactions and the cascade of ramifications that can flow through changing biotic and abiotic effects are only now gaining recognition. However, as human influence on pathogens increases--either directly through enhanced if accidental dispersal, or through anthropogenic impacts on climate--we may expect to see increasing evidence of pathogens affecting plant species, community structure, and ecosystem function.


Point-of-Care Ultrasound to Confirm Umbilical Line Placement: Impact of a Simulation Enhanced Curriculum on Neonatal Intensive Care Unit Provider Competency.
Neonatal intensive care unit (NICU) provider point-of-care ultrasound (POCUS) procedural competency for umbilical line placement confirmation has not been defined, and the necessary training to achieve competency has not been previously studied. This study's objective was to test the hypothesis that a simulation-enhanced curriculum will improve NICU providers' POCUS competency to confirm umbilical line placement. Neonatal intensive care unit providers without prior ultrasound experience were randomized to a curriculum with or without simulation-based training. Competency for catheter detection, tip localization, and scan interpretation on patients was determined using learning curve-cumulative summation, a specific statistical tool designed to indicate when a predefined level of performance is reached. Differences in success rates were analyzed by χ2 test. Two thirds (22/33) of participants completed 10 scans. Three (simulation) and 1 (control) attained catheter detection competency (P = 0.28). The simulation group was more successful for catheter detection (81% vs. 69%, P = 0.04) and scan interpretation (61% vs. 48%, P = 0.04). Success did not differ by umbilical vessel location, provider role, or duration of NICU experience. A simulation-enhanced POCUS curriculum improved catheter detection rate and scan interpretation, but there was no difference in procedural competency between groups on ultrasound scans performed on patients with umbilical catheters. We speculate that more than 10 scans may be needed for NICU providers to obtain POCUS competency.


Maternal administration of solithromycin, a new, potent, broad-spectrum fluoroketolide antibiotic, achieves fetal and intra-amniotic antimicrobial protection in a pregnant sheep model.
Solithromycin (CEM-101) is a new antibiotic that is highly potent against Ureaplasma and Mycoplasma spp. and active against many other antibiotic-resistant organisms. We have explored the maternal-amniotic-fetal pharmacokinetics of CEM-101 in a pregnant sheep model to assess its potential for treating intrauterine and antenatal infection. Chronically catheterized pregnant ewes (n = 6 or 7) received either a single maternal intravenous (i.v.) infusion of CEM-101 (10 mg/kg of body weight), a single intra-amniotic (i.a.) injection (1.4 mg/kg of estimated fetal weight), or a combined i.v. and i.a. dose. Maternal plasma (MP), fetal plasma (FP), and amniotic fluid (AF) samples were taken via catheter at intervals of 0 to 72 h postadministration, and concentrations of solithromycin and its bioactive polar metabolites (N-acetyl [NAc]-CEM-101 and CEM-214) were determined. Following maternal i.v. infusion, peak CEM-101 concentrations in MP, FP, and AF were 1,073, 353, and 214 ng/ml, respectively, representing a maternal-to-fetal plasma transfer efficiency of 34%. A single maternal dose resulted in effective concentrations (>30 ng/ml) in MP, FP, and AF sustained for >12 h. NAc-CEM-101 and CEM-214 exhibited delayed accumulation and clearance in FP and AF, resulting in an additive antimicrobial effect (>48 h). Intra-amniotic solithromycin injection resulted in elevated (∼50 μg/ml) and sustained CEM-101 concentrations in AF and significant levels in FP, although the efficiency of amniotic-to-fetal transfer was low (∼1.5%). Combined i.v. and i.a. administration resulted in primarily additive concentrations of CEM-101 in all three compartments. Our findings suggest that CEM-101 may provide, for the first time, an effective antimicrobial approach for the prevention and treatment of intrauterine infection and early prevention of preterm birth.


[Recurrent encephalopathy after small bowel resection. Implication of D-lactate].
Recurrent episodes of confusion are most commonly due to transient brain dysfunction related to vascular, epileptic or metabolic abnormalities. We report here a 54-year-old patient who, in the months following an extensive surgery of the small intestine, developed several acute confusional episodes characterized by encephalopathic signs (such as behavioral changes, desorientation and somnolence), ataxia, nystagmus and dysarthria. A number of metabolic changes were demonstrated during the episodes, including metabolic acidosis with increased anion gap and an elevated blood level of D-lactate. Symptoms disappeared after treatment with antibiotics. D-lactate encephalopathy is a rare cause of recurrent confusion which could be suspected based on a characteristic association of clinical signs. Diagnosis is confirmed by appropriate dosages. We discussed the possible mechanisms leading to confusional episodes.


Knowledge creation elements for enhancing community resilience towards disaster: A Delphi study.
Knowledge capacity plays a vital role in building community resilience to disasters. However, the problem is that there is no resilience framework that integrates the knowledge creation process. This article introduces a new framework for increasing community resilience based on knowledge creation theory (KCT). This research aims to define the elements that support the Knowledge Creation for Community Resilience (KCCR) and to gain consensus from experts on these factors. This study was conducted using semi-structured interviews with five panellists and three rounds of Delphi technique to determine the assessment of 26 factors (including six additional factors) that have been identified by experts (30, 18 and 11 experts in rounds I, II and III, sequentially). The data analysis was carried out in several stages, and included Spearman's Rank Correlation Coefficient, consensus appraisal and interrater agreement (IRA) statistical evaluation. The result of the agreement level (AL) analysis shows that the majority of the constructs (96.15%) are in the 'moderate strong' category. This study shows that there is a significant consensus (with IRA index [a wg(1)] ranging from 0.529 to 1), and panellists confirm the significance of all the key constructs. Consensus was gained from experts on seven elements that support the KCCR. This study establishes a systematic, operational and multidimensional KCCR framework that combines the concepts of knowledge creation, community resilience and disaster preparedness. This framework can be used as a qualitative instrument or guidance to build community resilience based on knowledge creation and a quantitative tool for measuring community resilience in facing disasters.


Rotavirus serotypes 6 and 10 predominate in cattle.
Calf fecal rotavirus strains were serotyped in enzyme-linked immunosorbent assays, using monoclonal antibodies to the VP7s of serotypes 1, 2, 3, 5, and 6 and to the VP4 of B223 (designated serotype 10). Sixty-six percent of 162 samples were typed as serotype 6, and 7% were serotyped as serotype 10. Most of the untyped strains did not react with a monoclonal antibody directed to a common VP7 epitope, indicating insufficient virus present in the samples. However, seven untyped samples that did react with this antibody were adapted to culture and typed, and six of these also proved to belong to serotype 6 or 10. Two of these viruses belonged to a monotype within serotype 6 that did not react with the serotype 6 monoclonal antibody. The seventh isolate reacted in cross-neutralization tests with serotype 8 viruses. Bovine rotaviruses from the United Kingdom, Federal Republic of Germany, and Japan that had been shown previously to be distinct from serotype 6 were compared in neutralization tests with B223 from the United States. These viruses proved to be a closely reacting group distinct from all other rotavirus serotypes, justifying the establishment of serotype 10 as the second major type of bovine rotavirus.


Spermiogenesis and Male Fertility Require the Function of Suppressor of Hairy-Wing in Somatic Cyst Cells of Drosophila.
Drosophila Suppressor of Hairy-wing [Su(Hw)] protein is an example of a multivalent transcription factor. Although best known for its role in establishing the chromatin insulator of the gypsy retrotransposon, Su(Hw) functions as an activator and repressor at non-gypsy genomic sites. It remains unclear how the different regulatory activities of Su(Hw) are utilized during development. Motivated from observations of spatially restricted expression of Su(Hw) in the testis, we investigated the role of Su(Hw) in spermatogenesis to advance an understanding of its developmental contributions as an insulator, repressor, and activator protein. We discovered that Su(Hw) is required for sustained male fertility. Although dynamics of Su(Hw) expression coincide with changes in nuclear architecture and activation of coregulated testis-specific gene clusters, we show that loss of Su(Hw) does not disrupt meiotic chromosome pairing or transcription of testis-specific genes, suggesting that Su(Hw) has minor architectural or insulator functions in the testis. Instead, Su(Hw) has a prominent role as a repressor of neuronal genes, consistent with suggestions that Su(Hw) is a functional homolog of mammalian REST, a repressor of neuronal genes in non-neuronal tissues. We show that Su(Hw) regulates transcription in both germline and somatic cells. Surprisingly, the essential spermatogenesis function of Su(Hw) resides in somatic cyst cells, implying context-specific consequences due to loss of this transcription factor. Together, our studies highlight that Su(Hw) has a major developmental function as a transcriptional repressor, with the effect of its loss dependent upon the cell-specific factors.


The role of Ca²⁺-stimulated adenylyl cyclases in bidirectional synaptic plasticity and brain function.
The activity-dependent neuronal modification is important for many aspects of adaptive behavior and brain development. Very often, neurological disorders are associated with the alteration of neural signaling pathways that are required for activity-triggered cellular events. Mounting evidence has implicated the role of cyclic AMP (cAMP)-cAMP-dependent protein kinase (PKA)-ERK1/2-cAMP-responsive element-binding protein (CREB) cascade in numerous brain functions such as learning and memory. Ca2+-stimulated type 1 and type 8 adenylyl cyclases (AC1 and AC8) are unique enzymes that couple activity-dependent calcium influx to the activation of cAMP signaling. Here, we summarize some direct evidence to support that Ca2+-stimulated cAMP signaling regulates molecular and cellular substrates of neuronal adaptation. Specifically, the function of AC1 and AC8 in synaptic functions, such as long-term potentiation, long-term depression, and depotentiation, has been examined by using genetic deletion and overexpression approaches. Consistent with the current hypothesis, the Ca2+-stimulated cAMP production through AC1 and AC8 is required for the activity-dependent activation of the ERK1/2-CREB cascade. We further describe the phenotypes of AC1/AC8 mutant mice in memory formation and other adaptive brain functions. The findings may suggest Ca2+-stimulated AC as therapeutic target for the treatment of mental retardation, pain, addiction, anxiety, depression, and neurodegeneration.


Androgen Receptor Signaling Reduces the Efficacy of Bacillus Calmette-Guérin Therapy for Bladder Cancer via Modulating Rab27b-Induced Exocytosis.
Although intravesical bacillus Calmette-Guérin (BCG) immunotherapy has been the gold standard for nonsurgical management of non-muscle-invasive bladder cancer, a considerable number of patients exhibit resistance to the adjuvant treatment with unexplained mechanisms. This study aimed to investigate whether and how androgen receptor (AR) signals modulate BCG cytotoxicity in bladder cancer. AR knockdown or overexpression in bladder cancer lines resulted in induction or reduction, respectively, in intracellular BCG quantity and its cytotoxic activity. Microarray screening identified Rab27b, a small GTPase known to mediate bacterial exocytosis, which was upregulated in BCG-resistant cells and downregulated in AR-shRNA cells. Knockdown of Rab27b, or its effector SYTL3, or overexpression of Rab27b also induced or reduced, respectively, BCG quantity and cytotoxicity. In addition, treatment with GW4869, which was previously shown to inhibit Rab27b-dependent secretion, induced them and reduced Rab27b expression in bladder cancer cells. Meanwhile, AR expression was upregulated in BCG-resistant lines, compared with respective controls. In a mouse orthotopic xenograft model, Rab27b/SYTL3 knockdown or GW4869 treatment enhanced the amount of BCG within tumors and its suppressive effect on tumor growth. Moreover, in non-muscle-invasive bladder cancer specimens from patients subsequently undergoing BCG therapy, positivity of AR/Rab27b expression was associated with significantly higher risks of tumor recurrence. AR activation thus correlates with resistance to BCG treatment, presumably via upregulating Rab27b expression. Mechanistically, it is suggested that BCG elimination from urothelial cells is induced by Rab27b/SYTL3-mediated exocytosis. Accordingly, Rab27b inactivation, potentially via antiandrogenic drugs and/or exocytosis inhibition are anticipated to sensitize the efficacy of BCG therapy, especially in patients with BCG-refractory AR/Rab27b-positive bladder cancer.


Are serotonin 3A and 3B receptor genes associated with suicidal behavior in schizophrenia subjects?
Suicide is a major contributor to the morbidity and mortality of schizophrenia, accounting for approximately 10% of deaths in these patients. Genetic factors have been reported to modulate the risk for suicide, although the precise mechanism and magnitude of the genetic contribution are unknown. Further, suicide attempters present abnormalities in the serotonergic system. We evaluated whether genetic variants in the serotonin receptors HTR3A (rs897692, rs1150226, rs1176724, rs2276302, rs3737457, rs897687 and rs1176713) and HTR3B (rs3758987, rs10502180, rs11606194, rs17116121, rs1176744, rs17116138, rs2276307, rs3782025 and rs1176761) were susceptibility components for suicidal behavior in 154 Caucasians schizophrenia subjects (20.1% of suicide attempters). In a second step, we compared haplotype and gene-gene interaction approaches because both genes are located in the chromosome 11q23 approximately 28Kbp apart. We did not observe allelic or genotypic associations. Six haplotypes were nominally significant associated with suicide. Gene-gene interaction using Helix Tree software showed two nominally significant interactions reproduced by haplotype association. Likewise, haplotypes composed by the markers included in the best multidimensional reduction three-locus model were nominally significant. Our results suggest that HTR3A and HTR3B polymorphisms may not play a major role in the susceptibility for suicidal behavior in schizophrenia subjects. Moreover, gene-gene interaction and haplotype association may have consistent results for genes located in the same chromosome.


Side population analysis using a violet-excited cell-permeable DNA binding dye.
Hoechst 33342 side population (SP) analysis is a common method for identifying stem cells in mammalian hematopoietic and nonhematopoietic tissues. Although widely employed for stem cell analysis, this method requires an ultraviolet (UV) laser to excite Hoechst 33342. Flow cytometers equipped with UV sources are not common because of the cost of both the laser and optics that can transmit light UV light. Violet laser sources are inexpensive and are now common fixtures on flow cytometers, but have been previously shown to provide insufficient Hoechst dye excitation for consistent resolution of SP cells. One solution to this problem is to identify additional fluorescent substrates with the same pump specificity as Hoechst 33342, but with better violet excitation characteristics. DyeCycle Violet reagent has emission characteristics similar to those of Hoechst 33342, but with a longer wavelength excitation maxima (369 nm). When this dye is loaded into hematopoietic cells, a sharply resolved side population was also observed, similar in appearance to that seen with Hoechst 33342. Unlike Hoechst SP, DCV SP was similar in appearance with both violet and UV excitation. DCV SP could be inhibited fumitremorgin C, and showed the same membrane pump specificity as Hoechst 33342. Simultaneous immunophenotyping with stem cell markers in mouse bone marrow demonstrated that DCV SP was restricted to the stem cell lineage(-) Sca-1(+) c-kit(+) cells population, as is Hoechst SP. Pending confirmation by functional analysis of DCV SP cells, these results suggest that DCV efflux identified approximately the same stem cell population as did Hoechst 33342 efflux. Substituting DCV for Hoechst 33342 in the SP technique may, therefore, allow side population analysis on flow cytometers with violet lasers.


The efficiency of information transmission of sign and spoken language.
Rhe study compares sign and oral language in terms of information transmission efficiency. The sample consisted of 36 hearing people with no knowledge of sign language and 36 deaf people reasonably fluent in sign language. (The deaf participants' level of hearing loss ranged from severe to profound.) Oral and sign language comprehension was assessed by means of texts at three different difficulty levels. After being exposed to the texts, the study participants had to tell what they had understood about them, answer a set of related questions, and offer a title for each text. When the hearing group's comprehension of oral versions of the texts was compared to the deaf group's comprehension of signed versions, the deaf group showed better comprehension of the explicit content of the texts but added more invented content and made more errors.


Prenatal diagnosis for sickle cell disease. A survey of the United States and Canada.
Prenatal diagnoses for sickle cell disease in the United States and Canada numbered at least 1065 through the end of 1987. The 272 prenatal diagnoses in the United States in 1987 constituted only about 4.1% of the estimated pregnancies at risk. The termination rate for diagnosed fetuses was 39% for sickle cell anemia and 23% for hemoglobin SC disease. Prenatal hemoglobinopathy screening programs should not be judged solely on the number of terminations for affected fetuses. Other benefits are reassurance for couples shown to have an unaffected fetus and, for couples shown to have an affected fetus, preparation for the birth of a child requiring special care and information relevant to future childbearing.


Pertussis: should we immunise neurologically disabled and developmentally delayed children?
A total of 400 children with neurological disorders were studied to ascertain whether they had been immunised against pertussis, the reasons for non-immunisation, and the "validity" of these reasons, as judged by interpretation of the recommendations of the Department of Health and Social Security. The results for this group were compared with those for a group of 400 aged matched controls. The study group had a significantly lower rate of immunisation than controls (p less than 0.01); rates for both groups fell sharply after 1975. A total of 192 study patients and 186 controls were not immunised. Those children with cerebral palsy had the lowest rate of immunisation (19%) and the highest number of valid reasons for non-immunisation (63%). Paediatricians apparently advised against immunisation in 61 (32%) of the index group but in only four (2%) of the controls. The risk of serious neurological handicap after pertussis immunisation is small and there is little evidence to support the view that underlying neurological disease predisposes a child to increased risk. The advice currently given by paediatricians may need to be reconsidered.


A prospective study of dietary alpha-linolenic acid and the risk of prostate cancer (United States).
Alpha-linolenic acid (ALA) is the most common omega-3 fatty acid in the Western diet. The relation of dietary intake of ALA to prostate cancer risk remains unresolved. We prospectively evaluated total ALA and ALA from specific food sources including animal, fish, and plant sources in relation to prostate cancer risk. A cohort of 29,592 male participants (age 55-74 years) in the screening arm of the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial was followed for an average of 5.1 years. We ascertained 1,898 cases of total prostate cancer, of which 1,631 were organ-confined cases (stage T1b to T3a and N0M0) and 285 were advanced stage cases (stage>or=T3b, N1, or M1). We found no association between total ALA intake and overall prostate cancer (multivariate RR comparing extreme quintiles=0.94; 95% CI=0.81-1.09; P for trend=0.76). The corresponding RRs for organ-confined and advanced prostate cancer were 0.94 (95% CI=0.80-1.10; P for trend=0.80) and 0.83 (95% CI=0.58-1.19; P for trend=0.34), respectively. In addition, no relations were observed between ALA intake from any specific food source and the risks of total, organ-confined, or advanced prostate cancer. ALA intake also showed no association with low grade (Gleason sum<7; 1,221 cases) tumors (P for trend=0.23) or high grade (Gleason sum>or=7; n=677 cases) tumors (P for trend=0.26). In this prospective study of predominantly Caucasian men who were screened annually for newly incident prostate cancer, dietary intake of total ALA and ALA from specific food sources was not associated with risk of total prostate cancer or prostate tumors that were defined by stage and grade.


Prostaglandins and fetal cardiac output distribution in the lamb.
With the use of a triple thermodilution technique in 17 fetal lambs, combined with microsphere estimations in 7, the effects of indomethacin prostaglandin (PG) I2 and PGE2 on cardiac output and its distribution were measured. Indomethacin (0.2 mg/kg) induced a main pulmonary artery-to-aorta pressure gradient, which peaked within 45-60 min and persisted for 2-3 h. PGE2 abolished this gradient (threshold 50 ng X kg-1 X min-1), while PGI2 in doses up to 100 ng X kg-1 X min-1 increased it. Indomethacin did not change total cardiac output but altered its distribution (right ventricular output, left ventricular output) and increased the percentage of right ventricular output flowing to the lungs. Ductal flow decreased concomitantly. After indomethacin, PGI2 further decreased ductal flow, increased pulmonary flow, and decreased pulmonary vascular resistance. PGE2 restored the original right ventricular-to-total cardiac output ratio, although ductus flow did not return to base-line levels. Pulmonary resistance increased slightly, reflecting decreased pulmonary flow, associated with decreased right ventricular output. Thus PGE2 was more effective on the ductus than on the pulmonary circulation. PGI2 did not relax the ductus but was a potent pulmonary vasodilator. Neither PGI2 nor PGE2 nor indomethacin changed total cardiac output but all altered its distribution.


Using independent component analysis to remove artifact from electroencephalographic measured during stuttered speech.
The electro-encephalographic (EEG) activity of people who stutter could provide invaluable information about the association of neural processing and stuttering. However, the EEG has never been adequately studied during speech in which stuttering naturally occurs. This is owing, in part, to the masking of the EEG signal by artifact from sources such as the speech musculature and from ocular activity. The aim of this paper was to demonstrate the ability of independent component analysis (ICA) to remove artifact from the EEG of stuttering children recorded while they are speaking and stuttering. The EEG of 16 male children who stuttered and 16 who did not stutter was recorded during a reading task. The recorded EEG that contained artifact was then subjected to ICA. The results demonstrated that the EEG assessed during stuttered speech had substantially more noise than the EEG of speech that did not contain stuttering (p < 0.01). Furthermore, it was shown that ICA could effectively remove this artifact in all 16 children (p < 0.01). The results from one child highlight the findings that ICA can be used to remove dominant artifact that has prevented the study of EEG activity during stuttered speech in children.


Salivary cortisol reactivity to psychological stressors in infancy: A meta-analysis.
Measurement of salivary cortisol is a practical and non-invasive tool for studying stress reactivity to various types of stressors even in young infants. Whereas studies using physical stressors during the first months of life have found robust cortisol responses to painful stimuli, research with older infants using psychological stressors (e.g., parental separation) has produced mixed findings, limiting our understanding of potential developmental changes in cortisol reactivity across infancy. In the present study, we used meta-analysis to systematically investigate whether psychological stressor paradigms are associated with measurable cortisol responses in infants under 18 months of age and whether the magnitude of the responses is moderated by the type of psychological stressor (i.e., separation, frustration, novelty, or disruption of parental interaction), infant age, and other potential moderators. Across 47 studies (N = 4095, age range: 3-18 months), we found that commonly used psychological stressor paradigms are associated with a small (Hedges' g = .11) increase in salivary cortisol levels in typically developing infants. Stressor type moderated the effect sizes, and when effect sizes in each category were analyzed separately, only the separation studies were associated with a consistent increase in cortisol following the stressor. Age did not moderate the effect sizes either in the full set of studies or within the separate stressor types. These meta-analytic results indicate that the normative cortisol response to psychological stressors across infancy is small and emphasize the need for standardized stressor paradigms to assess cortisol responses systematically across infancy.


Effects of nucleotides adenosine monophosphate and adenosine triphosphate in combination with L-arginine on male rabbit corpus cavernosum tissue.
Purines and more specifically adenosine monophosphate (AMP) and adenosine triphosphate (ATP) have a strong relaxant effect on smooth muscle cells of the dog, rabbit and human corpus cavernosum, to approximately the same degree as nitric oxide (NO). However, purines are considered as modulators of erectile function rather than key mediators. This suggests that the use of purines combined with NO donors could be effective to treat some specific erectile disorders. The relaxation induced by the combination of l-arginine (Arg), a natural substrate for NO synthase, was assessed with a purine-nucleotide (AMP, ATP) on a rabbit corpus cavernosum model, to determine if these substances could potentiate each other's effect. When a pre-contraction was induced by phenylephrine, AMP alone induced a 43% CC relaxation rate and ATP alone a 26% rate. The relaxation rate induced by Arg was lower in comparison (8% at 5.10(-4) m vs. 25% at AMP 5.10(-4) m and 15% at ATP 5.10(-4) m). NO synthase inhibitor n-nitro-l-arginine did not modify the relaxing effect provoked by AMP suggesting that the mechanism of action of this nucleotide does not involve the NO pathway. The combination of Arg at 5.10(-4) m with either AMP or ATP at different doses ranging from 5.10(-4) to 10(-3) m significantly enhanced the relaxing response reaching rates of 62 and 80% respectively, leading to a synergistic effect. The present data indicate that a 'NO donor' combined with an 'adenosine donor' could be an effective therapeutic approach.


p27(Kip1) and Ser10-phosphorylated p27(Kip1) in breast cancer: clinical significance and expression.
The protein p27 (p27(Kip1)) is a member of the cyclin-dependent kinase inhibitor family, which negatively regulates cell cycle progression, and the phosphorylation of p27 has been proven to affect its stability and nuclear export. Clinical studies on the relation between p27 and phosphorylated p27 (p-p27Ser10) in breast invasive ductal carcinomas are still scarce. We examined the expression of p27 and p-p27Ser10 using immunohistochemistry in 107 breast invasive ductal carcinomas and analyzed the relationship of these biomarkers and tumor characteristics. Of the 107 tumor samples, 38.3% (41 of 107) overexpressed p27 and 64.5% (69 of 107) overexpressed p-p27Ser10. Analysis of correlation with clinical characteristics showed that high expression level of p-p27Ser10 was linked to poor differentiation, advanced disease stage, and lymph node metastasis, whereas a contrary trend was observed for p27 (all P<0.05). In addition, the expression of p-p27Ser10 was significantly higher in malignant tumors than in adjacent tissues, while p27 showed the opposite trend. Also, there were different levels of p27 and p-p27Ser10 in different types of breast cancer. p27 and p-p27Ser10 are involved in the development of invasive ductal carcinoma and are potential indicators to judge the degree of malignancy as well as recurrence and metastasis.


[Nursing and the family program: a successful partnership?].
This was a qualitative, descriptive study that analyzed the work of the nursing staff in the Family Health Program (PSF: Programa Saúde da Família) in Campinas from 1998 to 2002. As reference, nursing is defined as work. The study was based on interviews with ten workers from the first three family health teams. Thematically, the following issues were addressed: nursing work and team work, emphasizing the activities developed and the nursing work process. Nursing and PSF is a successful partnership that needs to be explored and addressed. By assessing this production of knowledge and procedures, it is possible to identify how broad the work of Brazilian nursing is in Family and Public Health.


Permeability and electrical properties of thin lipid membranes.
We present and discuss the permeability and electrical properties of thin lipid membranes, and the changes induced in these properties by several agents added to the aqueous phases after the membranes have formed. The unmodified membrane is virtually impermeable to ions and small "hydrophilic" solutes, but relatively permeable to water and "lipophilic" molecules. These properties are consistent with those predicted for a thin film of hydrocarbon through which matter is transported by dissolving in the membrane phase and then diffusing through it. The effect of cholesterol in reducing the water and "lipophilic" solute permeability is attributed to an increase of the "viscosity" of the hydrocarbon region, thus reducing the diffusion coefficient of molecules within this phase. The selective permeability of the membrane to iodide (I(-)) in the presence of iodine (I(2)) is attributed to the formation of polyiodides (perhaps I(5) (-)), which are presumed to be relatively soluble in the membrane because of their large size, and hence lower surface charge density. Thus, I(2) acts as a carrier for I(-). The effects of "excitability-inducing material" and the depsipeptides (particularly valinomycin) on ion permeability are reviewed. The effects of the polyene antibiotics (nystatin and amphotericin B) on ion permeability, discussed in greater detail, are the following: (a) membrane conductance increases with the 10th power of nystatin concentration; (b) the membrane is anion-selective but does not discriminate completely between anions and cations; (c) the membrane discriminates among anions on the basis of size; (d) membrane conductance decreases extraordinarily with increasing temperatures. Valinomycin and nystatin form independent conductance pathways in the same membrane, and, in the presence of both, the membrane can be reversibly shifted between a cation and anion permeable state by changes in temperature. It is suggested that nystatin produces pores in the membrane and valinomycin acts as a carrier.


Characterization of octyl glucoside-solubilized cell membrane receptors for binding measles virus.
Optimum conditions were determined for solubilizing cell membrane receptors for binding measles virus (MV). Evidence for specific receptors was shown from the saturability of MV binding to intact Vero cells or African Green Monkey erythrocytes (MRBCs). Receptors, solubilized from Vero cells and MRBC with 1.5% octyl glucoside, inhibited MV attachment, infectivity, and hemagglutination activities. Extracts from chicken erythrocytes, which did not bind MV, were inactive in all assays. MV binding activity in Vero or MRBC extracts was stable to heating (100 degrees, 10 min) or neuraminidase treatment, but was inactivated by a range of proteases, including chymotrypsin, and bound to lentil and pea lectin agaroses, to indicate a glycoprotein component.


Equivalent clinical outcomes of bleeding peptic ulcers in teaching and non-teaching hospitals: evidence for standardization of medical care in Japan.
The clinical outcomes of treatments for several medical conditions are better in teaching hospitals than in non-teaching hospitals. However, there is only limited information for comparisons of the clinical outcomes of bleeding peptic ulcers between teaching and non-teaching hospitals. A total of 4,863 patients treated by endoscopic hemostasis on admission for bleeding peptic ulcers were evaluated in 586 hospitals of the Diagnosis Procedure Combination (DPC) system. We collected their data from the database associated with the DPC system to compare the risk-adjusted length of stay (LOS) and in-hospital mortality within 30 days with respect to the hospital characteristics. The hospitals were categorized into two groups: teaching hospitals that were certified by the Japanese Society of Gastroenterology (3,332 patients in 360 hospitals) and non-teaching hospitals (1,531 patients in 226 hospitals). There was no significant difference with regard to the mean LOS and the crude in-hospital mortality within 30 days between groups (p = 0.181 and 0.174, respectively). Multiple linear regression analyses revealed that the hospital characteristics were not associated with the risk-adjusted LOS. The standardized coefficient for non-teaching hospitals was 0.019 (p = 0.172). Multiple logistic regression analyses further showed no significant difference in the in-hospital mortality within 30 days (non-teaching hospitals, odds ratio = 1.35, 95% confidence interval = 0.786 - 2.319, p = 0.277). In conclusion, both teaching and non-teaching hospitals have equivalent qualities in management of bleeding peptic ulcers. These findings suggest that the standardization of medical treatments for bleeding peptic ulcers has become disseminated in Japan.


Localized reentry. Mechanism of induced sustained ventricular tachycardia in canine model of recent myocardial infarction.
This study was undertaken to investigate the mechanism underlying sustained monomorphic ventricular tachycardia (VT) in late experimental canine myocardial infarction. The hypothesis that sustained and "organized" continuous electrical activity (CEA) displaying a reproducible pattern with recurrent components recorded by bipolar endocardial, intramural, or epicardial electrodes in 10 animals during electrically induced sustained monomorphic VT represented reentrant excitation in an anatomically small area of the ventricle, was evaluated in the light of the following observations: Organized CEA always preceded the first monomorphic ventricular complex (QRS) of VT as well as the discrete local electrograms from closely surrounding sites during the initiation of VT. The site of organized CEA corresponded to the site of origin of sustained VT determined by iso-chronous contour map analysis of activation sequence. Ventricular pacing at rates more rapid than that of VT failed to terminate VT despite ventricular capture unless it transformed CEA into discrete local electrograms. VT could be terminated in three animals, with a single, critically timed premature stimulus delivered at a critically located focus close to the site of CEA, which would result in local capture and interrupted CEA. In six animals, surgical ablation of the site of organized CEA effectively prevented the reinitiation of sustained VT by programmed cardiac stimulation. These data showed that organized CEA and sustained VT were closely associated phenomena and suggested that organized CEA probably represented an important component of the tachycardia circuit.


The role of body mass index in determining clinical and quality of life outcomes after laparoscopic anti-reflux surgery.
Current literature is conflicted regarding the efficacy of laparoscopic anti-reflux surgery (LARS) among obese patients complaining of pathologic reflux or otherwise symptomatic hiatal hernias. Controlling for other factors, this study examined the influence of preoperative body mass index (BMI) on clinical and subjective quality of life (QOL) outcomes following LARS. Patients who underwent LARS between February 2012 and April 2018 were subdivided into four BMI stratified categories according to CDC definitions: normal (18.5 to < 25), overweight (25.0 to < 30), obese Class 1 (30 to < 35), and a combination of obese Class 2 (35 to < 40) and Class 3 (≥ 40). Patient demography, perioperative data, and QOL data were collected. QOL was assessed utilizing four validated survey instruments: the Reflux Symptom Index (RSI), Gastroesophageal Reflux Disease Health-Related Quality of Life (GERD-HRQL), Laryngopharyngeal Reflux Health-Related Quality of Life (LPR-HRQL), and a modified Quality of Life in Swallowing Disorders (mSWAL-QOL) surveys. In this study, 869 patients were identified (213 NL, 323 OW, 219 OC1, 114 OC23). The majority of patients in each subgroup were female (65% NL, 68% OW, 79% OC1, 74% OC23) with similar rates of underlying hypertension, hyperlipidemia, and diabetes mellitus. Coronary artery disease rates between groups were statistically significant (p = .021). Operative time, length of hospital stay, and rates of 30-day readmission and reoperation were similar between groups. Among postoperative complications, rates of arrhythmia and UTI were more commonly reported in OC1 and OC23 populations. When assessed utilizing the RSI, GERD-HRQL, LPR-HRQL, and mSWAL-QOL instruments, QOL was similar among all groups (mean follow-up 15 months) irrespective of BMI. These findings suggest LARS in the overweight, obese, and morbidly obese populations-when compared to normal-weight cohorts in short-term follow-up-may have similar value in addressing pathological reflux manifestations and conveying quality of life benefits without added morbidity or mortality.


[Hygienic evaluation of water supply in the Khanty-Mansi Autonomous District--Yugry].
The paper considers the sources of water supply of the population of the Khanty-Mansi Autonomous District--Yugry. It gives data on the quality of water from the underground and surface sources. The reliably protected groundwater can meet the needs of the population of the Khanty-Mansi Autonomous District--Yugry for drinking water after improving its quality by aeration and filtration. An estimate of the population's provision with water is given by the towns and districts of the area. The state of most domestic water pipes was ascertained to be poor: 35.8% of the municipal water pipes and 75.0% of the departmental ones did not meet the hygienic requirements. 52.8% of water samples failed to meet the hygienic standards in sanitary and chemical indices, and 3.7% in microbiological ones, which undoubtedly affected the population's health. There are two ways of improving the water supply of the district's population: 1) to improve purification of the whole water delivered to inhabited localities and 2) to provide the population with high-quality water to be only drunk, including that to be bottled.


Pharmacokinetics and bioavailability of chromium malate and its influence on trace metals absorption after oral or intravenous administration.
In our preliminary study, chromium malate could decrease the blood glucose level in mice with diabetes and exhibits good benefits in treating glycometabolism and adipose metabolization obstacle in rats with type 2 diabetes. This study was aimed at assessing the pharmacokinetics and bioavailability of chromium malate and influence on trace metals absorption in rats. BAPP 2.3 pharmacokinetic calculating program (China Pharmaceutical University Medicine Center) was used to calculate the pharmacokinetic parameters. Models of type 2 diabetic mellitus rats were applied to analyzed Ca, Mg, Fe, Cu, and Zn contents. The results showed that mean retention time (MRT) in chromium malate group was significantly prolonged and the area under the curve (AUC) and relative bioavailability of chromium malate (male) group were significant increase compared to chromium picolinate group. The serum Ca, Mg, Fe, Cu, and Zn contents in chromium malate (at doses of 15 and 20 μg Cr/kg bw) groups were significantly increased compared to control group, chromium trichloride group, and chromium picolinate group in type 2 diabetes mellitus rats. Those results indicated that chromium malate can significantly prolong MRT and increase AUC (male). Moreover, chromium malate is more effective at treating increased serum Ca, Mg, Fe, Cu, and Zn contents compared to chromium trichloride and chromium picolinate.


Individual and contextual predictors of children's hemoglobin levels from Southern Brazilian municipalities in social vulnerability.
Few studies have investigated the simultaneous effect of individual and contextual factors on the occurrences of anemia. This study aims to evaluate the variability of children's hemoglobin levels from municipalities in social vulnerability and its association with factors of individual and municipal nature. This is a cross-sectional, multi-center study, with children data (12-59 months) collected from 48 municipalities of the Southern region of Brazil, that were included in the Brazil Without Poverty Plan. Individuals' data were collected using a structured questionnaire, and secondary and ecological data of children's municipalities were collected via national surveys and institutional websites. The outcome was defined as the hemoglobin level obtained by HemoCue. A multilevel analysis was performed using Generalized Linear Models for Location Scale and Shape using R, with a 5% significance level. A total of 1,501 children were evaluated. The mean hemoglobin level was 12.8g/dL (95%CI: 12.7-12.8), with significant variability between municipalities. Lower values of hemoglobin were observed in children who lived in municipalities with a higher urbanization rate and a lower number of Community Health Agents, in relation to the reference categories. At the individual level, lower hemoglobin values were identified for children under 24 months, not enrolled at daycares, who were beneficiaries of the conditional cash transfer program and diagnosed with underweight. The results shed light on important factors at the municipal and the individual levels that were associated to the hemoglobin levels of children living in municipalities in social vulnerability.


Human interictal epileptiform discharges are bidirectional traveling waves echoing ictal discharges.
Interictal epileptiform discharges (IEDs), also known as interictal spikes, are large intermittent electrophysiological events observed between seizures in patients with epilepsy. Although they occur far more often than seizures, IEDs are less studied, and their relationship to seizures remains unclear. To better understand this relationship, we examined multi-day recordings of microelectrode arrays implanted in human epilepsy patients, allowing us to precisely observe the spatiotemporal propagation of IEDs, spontaneous seizures, and how they relate. These recordings showed that the majority of IEDs are traveling waves, traversing the same path as ictal discharges during seizures, and with a fixed direction relative to seizure propagation. Moreover, the majority of IEDs, like ictal discharges, were bidirectional, with one predominant and a second, less frequent antipodal direction. These results reveal a fundamental spatiotemporal similarity between IEDs and ictal discharges. These results also imply that most IEDs arise in brain tissue outside the site of seizure onset and propagate toward it, indicating that the propagation of IEDs provides useful information for localizing the seizure focus.


M1-selective muscarinic allosteric modulation enhances cognitive flexibility and effective salience in nonhuman primates.
Acetylcholine (ACh) in cortical neural circuits mediates how selective attention is sustained in the presence of distractors and how flexible cognition adjusts to changing task demands. The cognitive domains of attention and cognitive flexibility might be differentially supported by the M1 muscarinic acetylcholine receptor (mAChR) subtype. Understanding how M1 mAChR mechanisms support these cognitive subdomains is of highest importance for advancing novel drug treatments for conditions with altered attention and reduced cognitive control including Alzheimer's disease or schizophrenia. Here, we tested this question by assessing how the subtype-selective M1 mAChR positive allosteric modulator (PAM) VU0453595 affects visual search and flexible reward learning in nonhuman primates. We found that allosteric potentiation of M1 mAChRs enhanced flexible learning performance by improving extradimensional set shifting, reducing latent inhibition from previously experienced distractors and reducing response perseveration in the absence of adverse side effects. These procognitive effects occurred in the absence of apparent changes of attentional performance during visual search. In contrast, nonselective ACh modulation using the acetylcholinesterase inhibitor (AChEI) donepezil improved attention during visual search at doses that did not alter cognitive flexibility and that already triggered gastrointestinal cholinergic side effects. These findings illustrate that M1 mAChR positive allosteric modulation enhances cognitive flexibility without affecting attentional filtering of distraction, consistent with M1 activity boosting the effective salience of relevant over irrelevant objects specifically during learning. These results suggest that M1 PAMs are versatile compounds for enhancing cognitive flexibility in disorders spanning schizophrenia and Alzheimer's diseases.


Gender- and puberty-dependent association between physical activity and depressive symptoms: national survey among Chinese adolescents.
The study aims to understand the possible gender difference in the associations between physical activity and depressive symptoms during pubertal transition. Participants were 30,399 children and adolescents of Han ethnicity from urban and rural areas in 8 cities in China. Physical activity (PA) and depressive symptom was assessed by adapted Youth Risk Behavior Survey and Children Depression Inventory (CDI), respectively. Pubertal development was assessed by trained physicians. In China, over 30% boys and 40% girls reported having no vigorous PA (VPA) or moderate PA (MPA) in the past week. In girls, participating in VPA 1 to 2 days/week showed protective effect for depressive symptoms; whereas in boys, participating in MPA 1 to 2 days/week showed protective effect for depressive symptoms at and after genital stage III (G3). Moderate frequency (1 to 2 days/week) in PA undertaken might be encouraged to prevent depressive symptoms among adolescents.


Patient safety in patients who occupy beds on clinically inappropriate wards: a qualitative interview study with NHS staff.
To explore NHS staff members' perceptions and experiences of the contributory factors that may underpin patient safety issues in those who are placed on a hospital ward that would not normally treat their illness (such patients are often called 'outliers' 'sleep outs' or 'boarders'). Qualitative study using semi-structured interviews. Setting A single large teaching hospital in the north of England. 29 members of NHS staff (doctors, nurses and non-clinical or management staff). Five themes describing contributory factors underlying safety issues were identified: competing demands on staff time created by having patients on inappropriate wards and patients who are on the correct specialty ward to care for; poor communication between the correct specialty ward and the clinically inappropriate ward; lack of knowledge or specialist expertise on clinically inappropriate wards; an unsuitable ward environment for patients on inappropriate wards; and the characteristics of patients who are placed on clinically inappropriate wards (specifically staff perceive patients on inappropriate wards to be medically fit and therefore of lower priority and moving patients between wards may disorientate confused or impaired patients). Examples of how these contributory factors may lead to safety issues are given. NHS staff report that placement of patients on clinically inappropriate wards is a specific patient safety concern. The application of James Reason's Swiss cheese model of accident causation suggests that placement on an inappropriate ward constitutes a 'latent condition' which may expose patients to contributory factors that underlie adverse events.


Central vein stenosis in hemodialysis vascular access: clinical manifestations and contemporary management strategies.
Central venous stenosis is a significant and frequently encountered problem in managing hemodialysis (HD) patients. Venous hypertension, often accompanied by severe symptoms, undermines the integrity of the hemodialysis access circuit. In central venous stenosis, dialysis through an arteriovenous fistula is usually inefficient, with high recirculation rates and prolonged bleeding after dialysis. Central vein stenosis is a known complication of indwelling intravascular and cardiac devices, such as peripherally inserted central catheters, long-term cuffed hemodialysis catheters, and pacemaker wires. Hence, preventing this challenging condition requires minimization of central venous catheter use. Endovascular interventions are the primary approach for treating central vein stenosis. Percutaneous angioplasty and stent placement may reestablish vascular function in cases of elastic and recurrent lesions. Currently, there is no consensus on the optimal treatment, as existing management approaches have a wide range of patency rates.


Magnetic biocatalysts and their uses to obtain biodiesel and biosurfactants.
Nanobiocatalysis, as the synergistic combination of nanotechnology and biocatalysis, is rapidly emerging as a new frontier of biotechnology. The use of immobilized enzymes in industrial applications often presents advantages over their soluble counterparts, mainly in view of stability, reusability and simpler operational processing. Because of their singular properties, such as biocompatibility, large and modifiable surface and easy recovery, iron oxide magnetic nanoparticles (MNPs) are attractive super-paramagnetic materials that serve as a support for enzyme immobilization and facilitate separations by applying an external magnetic field. Cross-linked enzyme aggregates (CLEAs) have several benefits in the context of industrial applications since they can be cheaply and easily prepared from unpurified enzyme extracts and show improved storage and operational stability against denaturation by heat and organic solvents. In this work, by using the aforementioned advantages of MNPs of magnetite and CLEAs, we prepared two robust magnetically-separable types of nanobiocatalysts by binding either soluble enzyme onto the surface of MNPs functionalized with amino groups or by cross-linking aggregates of enzyme among them and to MNPs to obtain magnetic CLEAs. For this purpose the lipase B of Candida antarctica (CALB) was used. The hydrolytic and biosynthetic activities of the resulting magnetic nanobiocatalysts were assessed in aqueous and organic media. Thus, the hydrolysis of triglycerides and the transesterification reactions to synthesize biodiesel and biosurfactants were studied using magnetic CLEAs of CALB. The efficiency and easy performance of this magnetic biocatalysis validates this proof of concept and sets the basis for the application of magnetic CLEAs at industrial scale.


A re-assigned American mink (Neovison vison) map optimal for genome-wide studies.
Our previously published second generation genetic map for the American mink (Neovison vison) has been used and redesigned in its best for genome-wide studies with maximum of efficiency. A number of 114 selected markers, including 33 newly developed microsatellite markers from the CHORI-231 mink Bacterial Artificial Chromosome (BAC) library, have been genotyped in a two generation population composed of 1200 individuals. The outcome reassigns the position of some markers on the chromosomes and it produces a more reliable map with a convenient distance between markers. A total of 104 markers mapped to 14 linkage groups corresponding to the mink autosomes. Six markers are unlinked and four markers are allocated to the X chromosome by homology but no linkage was detected. The sex-average linkage map spans 1192 centiMorgans (cM) with an average intermarker distance of 11.4cM and 1648cM when the ends of the linkage groups and the autosomal unlinked markers are added. Sex-specific genetic linkage maps were also generated. The male sex-specific map had a total length of 1014.6cM between the linked markers and an average inter-marker interval of 9.7cM. The female map has a corresponding length of 1378.6cM and an average inter-marker interval of 13.3cM. The study is complemented with additional anchorage for most of the chromosomes of the map by BAC in situ hybridization with clones containing microsatellites strategically selected from the various parts of the genome. This map provides an improved tool for genetic mapping and comparative genomics in mink, also useful for the future assembly of the mink genome sequence when this will be taken forward.


Impact of calcium nitrate supplementation on the oxygen-carrying capacity of lactating sows and their offspring.
Calcium nitrate supplementation has recently been suggested to provide potential benefits to sows and, in particular, their offspring when administered at a level of 1,200 ppm in feed shortly before farrowing through lactation. More specifically, nitrate supplementation has been suggested as one opportunity for improved placental and/or fetal blood flow and has been hypothesized in previous work to be important to the swine industry in light of the global trend toward larger litter sizes. The benefit is likely manifested through exposure to the nitrate moiety, but interestingly, nitrate has historically been considered a compound of concern for swine. High levels of nitrate once metabolized to nitrite can interfere with the oxygen-carrying capacity of hemoglobin, resulting in increased methemoglobin and, subsequently, methemoglobinemia (MetHb) if the animal is deprived of significant amounts of oxygen; however, the level of nitrate exposure necessary to induce MetHb in sows is not clearly defined. This work was undertaken to examine methemoglobin levels in sows and piglets exposed to the potentially beneficial levels of 1,200 and 6,000 ppm nitrate added to their diets over the course of the periparturient period. Other oxygen capacity blood variables were evaluated (e.g., hemoglobin, hematocrit, and various measures of hemoglobin and red blood cell volumes and concentrations), as well as performance endpoints (weight changes and feed intake) and general observations over the 27-d period. No evidence of treatment-related toxicity manifestation was observed at these supplemental levels. Nearly all oxygen-related variables were affected by time (independent of treatment), indicating adaptive general effects of farrowing. These findings support the hypothesis that MetHb is not a concern up to at least 6,000 ppm supplemental nitrate exposure, even in combination with additional nitrate in the sow's daily diet. This work is important to help swine producers understand that consideration of nitrate benefit should outweigh concern for risk of nitrate-induced toxicity.


Standardized medical image registration for radiological identification of decedents based on paranasal sinuses.
Image registration software is frequently used in clinical radiology, e.g., for follow-up diagnosis. To a certain extent, the radiological identification of decedents (RadID) is comparable to a clinical follow-up diagnosis, in that two datasets from different dates are compared in terms of their anatomical characteristics (e.g., paranasal sinuses) or surgical implants. Due to the increasing use of computed tomography (CT) for head examinations in clinical radiology and the increased use of postmortem CT (PMCT) in forensic imaging, the comparison of three-dimensional (3D) clinical CT (termed as antemortem CT (AMCT) in this article) and PMCT datasets for RadID is becoming increasingly practical. In particular, the comparison of paranasal sinuses in AMCT and PMCT imaging is considered a suitable and reliable modality for RadID. However, previous publications regarding RadID based on comparisons of 3D datasets have not considered the implementation of image registration to provide software-side support for RadID. This article demonstrates and evaluates the use of a standard medical image registration procedure for RadID by comparing paranasal sinuses.


Modulation of granulocyte LAM-1 and MAC-1 during dialysis--a prospective, randomized controlled trial.
Hemodialysis with first-use cellulosic dialysis membranes results in activation of the alternative pathway of complement and profound neutropenia followed by rebound leukocytosis. The neutropenia has been shown to be associated with increased expression of adhesion receptors and pulmonary sequestration of granulocytes. However, the mechanism underlying the return of the granulocytes has not been elucidated. We determined simultaneously the changes in the granulocyte adhesion receptor MAC-1 (CD11b-CD18) and the selectin LAM-1 receptor during dialysis using a complement activating and a non-complement activating membrane, in a randomized, cross-over study. With initiation of dialysis with cellulosic membranes, there was a rapid and prominent increase in the expression of MAC-1 receptors. At the nadir of granulocyte count, 15 minutes after initiation of dialysis with the complement activating membrane, there was a four-fold increase in the MAC-1 receptor expression. At the same time, there was a two-fold decrease in LAM-1 expression. There were no changes in the expression of two other granulocyte receptors CD11a and CD15 which are known not to be modulated during granulocyte activation. Granulocytes harvested during dialysis and which had high MAC-1 and low LAM-1 expression had a significantly decreased adherence to endothelial cell monolayers. Dialysis of the same patients with non-complement activating membranes resulted in no significant change in the expression of these receptors on granulocytes nor in their adherence to endothelial cells. These results shed new light on the mechanism of the cyclical granulocytopenia and rebound granulocytosis during dialysis with new cellulosic membranes.


Analysis of maternal and fetal cardiovascular systems during hyperglycemic pregnancy in the nonobese diabetic mouse.
Preconception or gestationally induced diabetes increases morbidities and elevates long-term cardiovascular disease risks in women and their children. Spontaneously hyperglycemic (d)-NOD/ShiLtJ female mice, a type 1 diabetes model, develop bradycardia and hypotension after midpregnancy compared with normoglycemic, age- and gestational day (GD)-matched control (c-NOD) females. We hypothesized that onset of the placental circulation at GD 9-10 and rapid fetal growth from GD 14 correlate with aberrant hemodynamic outcomes in d-NOD females. To develop further gestational time-course correlations between maternal cardiac and renal parameters, high-frequency ultrasonography was applied to d- and c-NOD mice (virgin and at GD 8-16). Cardiac output and left ventricular (LV) mass increased in c-NOD but not in d-NOD mice. Ultrasound and postmortem histopathology showed overall greater LV dilation in d-NOD than in c-NOD mice at mid to late gestation. These changes suggest blunted remodeling and altered functional adaptation of d-NOD hearts. Umbilical cord ultrasounds revealed lower fetal heart rates from GD 12 and lower umbilical flow velocities at GD 14 and GD 16 in d-NOD versus c-NOD pregnancies. From GD 14 to GD 16, d-NOD fetal losses exceeded c-NOD fetal losses. Similar aberrant responses in pregnancies of women with diabetes may elevate postpartum maternal and child cardiovascular risk, particularly if mothers lack adequate prenatal care or have poor glycemic control during gestation.


Emerging and Established Trends to Support Secure Health Information Exchange.
This work aims to provide information, guidelines, established practices and standards, and an extensive evaluation on new and promising technologies for the implementation of a secure information sharing platform for health-related data. We focus strictly on the technical aspects and specifically on the sharing of health information, studying innovative techniques for secure information sharing within the health-care domain, and we describe our solution and evaluate the use of blockchain methodologically for integrating within our implementation. To do so, we analyze health information sharing within the concept of the PANACEA project that facilitates the design, implementation, and deployment of a relevant platform. The research presented in this paper provides evidence and argumentation toward advanced and novel implementation strategies for a state-of-the-art information sharing environment; a description of high-level requirements for the transfer of data between different health-care organizations or cross-border; technologies to support the secure interconnectivity and trust between information technology (IT) systems participating in a sharing-data "community"; standards, guidelines, and interoperability specifications for implementing a common understanding and integration in the sharing of clinical information; and the use of cloud computing and prospectively more advanced technologies such as blockchain. The technologies described and the possible implementation approaches are presented in the design of an innovative secure information sharing platform in the health-care domain.


An automated interface for sedimentation velocity analysis in SEDFIT.
Sedimentation velocity analytical ultracentrifugation (SV-AUC) is an indispensable tool for the study of particle size distributions in biopharmaceutical industry, for example, to characterize protein therapeutics and vaccine products. In particular, the diffusion-deconvoluted sedimentation coefficient distribution analysis, in the software SEDFIT, has found widespread applications due to its relatively high resolution and sensitivity. However, a lack of available software compatible with Good Manufacturing Practices (GMP) has hampered the use of SV-AUC in this regulatory environment. To address this, we have created an interface for SEDFIT so that it can serve as an automatically spawned module with controlled data input through command line parameters and output of key results in files. The interface can be integrated in custom GMP compatible software, and in scripts that provide documentation and meta-analyses for replicate or related samples, for example, to streamline analysis of large families of experimental data, such as binding isotherm analyses in the study of protein interactions. To test and demonstrate this approach we provide a MATLAB script mlSEDFIT.


Achalasia and chronic opiate use: innocent bystanders or associated conditions?
High-resolution manometry identifies three subtypes of achalasia. However, type 3 differs from classic achalasia. Although opiates affect esophageal motility, opiate use and achalasia have not been studied. Patients with a new diagnosis of achalasia at Mayo Clinic Rochester between June 1, 2012 and January 3, 2014 were identified. Clinical records were reviewed to assess symptoms, opiate use, and therapy. Fifty-six patients with achalasia were identified, 14 (25%) were on opiates. Opiate prescription was unrelated to achalasia in all cases, with chronic back and joint pain constituting the majority. Of patients on opiates, five (36%) had type 3 achalasia compared with four (10%) not on opiates (P = 0.02). No patients on opiates had type 1 achalasia. Clinical presentation did not differ with opiates, although those on opiates were more likely to report chest pain (39 vs. 14%, P = 0.05) and less likely to have esophageal dilation (62 vs. 82%, P = 0.13), none with greater than 5-cm diameter. Contractile vigor was greater with opiate use, with distal contractile integral of 7149 versus 2615.5 mmHg/cm/second (P = 0.08). Treatment response was inferior on opiates, with persistent symptoms in 22% compared with 3% without opiates (P = 0.06). Opiate use is common in type 3 achalasia, with the majority of patients on opiates. No patients on opiates were diagnosed with type 1 achalasia. Manometric findings of type 3 achalasia mimic those induced by opiates, suggesting a physiologic mechanism for opiate induced type 3 achalasia. Treatment outcome is inferior with opiates, with opiate cessation perhaps preferable. Further studies assessing opiate use and achalasia are needed.