Investigations on the endometrial response to intrauterine administration of N-acetylcysteine in oestrous mares.
In mares, mating-induced persistent endometritis contributes to low fertility. The condition is in part related to delayed clearance of mucus accumulated within the uterine lumen. The objective of this study was to investigate the endometrial response of healthy mares to intrauterine (i.u.) treatment with N-acetylcysteine (NAC). Oestrous mares (n = 12) were randomly assigned to a treatment (TM) or control (C) group and received an i.u. infusion of 5% NAC and saline (total volume 140 ml), respectively. Endometrial biopsies were collected in five of the mares 24 h after treatment, in the remaining seven mares 72 h after treatment. Endometrial biopsies were evaluated for integrity of the luminal epithelium, number of polymorphonuclear neutrophils (PMN), staining for cyclooxygenase 2 (COX2), staining with Kiel 67 antigen (Ki-67), lectins and periodic acid-Schiff (PAS). The integrity of endometrial epithelial cells was not affected by treatment (no statistical differences between groups or times). At 24 h after treatment, the mean number of PMN in endometrial biopsies from NAC- and C-mares did not differ, but at 72 h after treatment, number of PMN was significantly higher (p < 0.05) in C (3.9 ± 0.6 PMN/field) compared with NAC-treated mares (2.3 ± 0.2 PMN/field). At 72 h after treatment, the intensity of staining for COX2 was significantly higher after saline than after NAC treatment (p < 0.05). In the epithelium, no differences in staining for the proliferation marker Ki-67 were seen with respect to time and treatment. Score for the lectin wheat germ agglutinin (WGA) was slightly higher in NAC-treated mares than in C-mares 72 h after treatment (p < 0.05). Score for PAS staining of mucus in deep uterine glands differed significantly between groups at 24 h after treatment (p < 0.05). The present study demonstrates that NAC does not adversely affect the endometrial function. Moreover, an anti-inflammatory effect on the equine endometrium was observed.


Terlipressin for hepatorenal syndrome: A meta-analysis of randomized trials.
Hepatorenal syndrome (HRS) is a severe complication of end-stage renal disease whose management still constitutes a big challenge. Various approaches have been used for hepatorenal syndrome treatment, including vasoconstrictor therapy. Terlipressin, a vasopressin analogue, has frequently been used. To evaluate the efficacy and safety of terlipressin in patients with HRS by performing a systematic review with a meta-analysis of controlled, clinical trials. Only prospective, placebo-controlled, randomized clinical trials (RCTs) were included. We used the random effects model of DerSimonian and Laird, with heterogeneity and subgroups analyses. The primary end-point of interest was the HRS reversal after terlipressin (or placebo) therapy in study patients vs. control patients (as a measure of efficacy). The secondary outcome was the rate of ischemic side-effects in study patients vs. placebo patients (as a measure of tolerability). The additional end-point was the impact of terlipressin on survival in the HRS population. We identified five studies involving 243 unique patients with HRS. Pooling of study results showed a significant increase in HRS reversal among study (terlipressin) versus control (placebo) patients; the pooled odd ratio (OR) of HRS reversal was 8.09; 95% CI, 3.521; 18.59; p=0.0001. The p-value was 0.5 for our test of study heterogeneity. In a subgroup analysis excluding case-control trials these results did not change. The rate of severe ischemic events was higher in study than control patients, pooled OR=2.907; 95% CI, 1.094; 7.723 (p=0.032). The test for heterogeneity was not significant. Terlipressin use had no significant impact upon survival (pooled OR for survival rate, 2.064; 95% CI, 0.939; 4.538; p=0.07). No significant heterogeneity (NS) was found. Our meta-analysis shows that terlipressin has higher efficacy than placebo in reversing renal function in the HRS population. There was no apparent impact of terlipressin therapy on survival in HRS patients but further large-size trials are needed. Terlipressin use in the HRS population requires careful selection of patients and close clinical surveillance. These results support the use of terlipressin for reversal of renal function in the HRS population.


The significance of direct sunlight and polarized skylight in the ant's celestial system of navigation.
As textbook knowledge has it, bees and ants use polarized skylight as a backup cue whenever the main compass cue, the sun, is obscured by clouds. Here we show, by employing a unique experimental paradigm, that the celestial compass system of desert ants, Cataglyphis, relies predominantly on polarized skylight. If ants experience only parts of the polarization pattern during training but the full pattern in a subsequent test situation, they systematically deviate from their true homeward courses, with the systematics depending on what parts of the skylight patterns have been presented during training. This "signature" of the polarization compass remains unaltered, even if the ants can simultaneously experience the sun, which, if presented alone, enables the ants to select their true homeward courses. Information provided by direct sunlight and polarized skylight is picked up by different parts of the ant's compound eyes and is channeled into two rather separate systems of navigation.


Efficacy of orally administered oxolinic acid and Vetoquinol, an oxolinic acid ester, for the treatment of furunculosis in Atlantic salmon Salmo salar held in seawater.
This study was performed to determine the efficacy of orally administered oxolinic acid and Vetoquinol, an oxolinic acid ester, in the treatment of experimental induced furunculosis in Atlantic salmon Salmo salar held in seawater. Two strains of the causative bacterium Aeromonas salmonicida subsp. salmonicida, 1 sensitive (VI-88/09/03175) and 1 resistant (3475/90) to oxolinic acid, were used. In 2 trials, cohabitational challenges were performed by introducing 8 fish challenged in advance by an intraperitoneal injection of 2.2 x 10(4) colony forming units of strain 3475/90 (Trial 1) or strain VI-88/09/03175 (Trial 2) to 10 aquaria each containing 40 healthy fish. The treatment groups in both trials consisted of 4 groups receiving either oxolinic acid (2 groups) or Vetoquinol (2 groups) and 1 control group. An unchallenged, unmedicated group was used to determine the natural mortality in the population. The recommended therapeutic dose of 25 mg oxolinic acid kg-1 fish at Days 1, 2, 4, 6, 8 and 10 following initiation of treatment was used. Oral medication initiated at Day 10 (Trial 1) or Day 11 (Trial 2) following challenge significantly (p < 0.05) lowered the specific mortality in all drug-treated groups compared to the untreated control groups. Mortality in Vetoquinol-treated groups was significantly (p < 0.05) lower than in oxolinic acid-treated groups in Trial 1 whereas no significant (p < 0.05) difference in survival rate was found between the medicated groups in Trial 2.


Expression of aquaporin-1 in human trabecular meshwork cells: role in resting cell volume.
Drainage of aqueous humor from the human eye appears dependent on intracellular volume of trabecular meshwork (TM) cells, the predominant cell type of the human outflow pathway. Thus, the modulation of water and solute flux across the plasma membrane of TM cells is predicted to be an important factor in regulating outflow facility. Aquaporin (AQP)-1 is a hexahelical integral membrane protein that functions as a regulated channel for water and cations in fluid-secreting and -absorbing tissues. AQP1 is present in many tissues of the human eye, including the TM; however, its role in outflow facility is unknown. The purpose of the present study was twofold: to evaluate the prospect of manipulating AQP1 protein levels in TM cells using sense and antisense mRNA and to investigate the functional role of AQP1 in TM cells. An adenovirus (AV) expression system was used to alter AQP1 protein levels. AQP1 protein expression was monitored using immunoblot analysis, and resting cell volume was measured by forward light scatter, electronic cell sizing, and [(14)C]-sucrose/urea equilibration. Permeability of TM monolayers to [(14)C]-sucrose was also assessed as an indirect evaluation of cell volume. AV-mediated gene transfer of AQP1 cDNA to TM cells resulted in a titer-dependent increase in recombinant AQP1, whereas transfer of antisense cDNA decreased native AQP1 protein by 71.7% +/- 5.5% (P < 0.01) after 5 days. A novel finding of this study is that mean resting volumes of AQP1(s) AV-infected TM cells in suspension were 8.7% +/- 3.0% greater (P < 0.05) than control cells. Conversely, AQP1 antisense (as) AV-infected cells had resting volumes 7.8% +/- 2.9% less than control cells (P < 0.05). Similar effects of AQP1 expression on resting cell volume were observed in TM monolayers. Consistent with this finding, paracellular permeability of AQP1(s) AV-infected TM monolayers to [(14)C]-sucrose decreased by 8.0% +/- 1.4% (P < 0.001). In addition to influencing the osmotic permeability of TM plasma membranes, the level of AQP1 protein expression influences resting intracellular volume and thus paracellular permeability of TM cell monolayers in vitro. These data suggest that AQP1 expression may affect outflow facility in vivo.


Crash-related mortality and model year: are newer vehicles safer?
The objective of this study was to determine whether occupants of newer vehicles experience a lower risk of crash-related mortality. The occurrence of death was studied in relation to vehicle model year (MY) among front seat vehicular occupants, age ≥ 16 captured in the National Automotive Sampling System Crashworthiness Data System (NASS-CDS) between 2000 and 2008. The associations between death and other occupant, vehicular and crash characteristics were also explored. Multiple logistic regression models for the prediction of death were built with model year as the independent variable and other characteristics linked to death as covariates. Imputation was used for missing data; weighted data was used. A total of 70,314 cases representing 30,514,372 weighted cases were available for analysis. Death occurred in 0.6% of the weighted population. Death was linked to age>60, male gender, higher BMI, near lateral direction of impact, high delta v, rollover, ejection and vehicle mismatch, and negatively associated with seatbelt use and rear and far lateral direction of impact. Mortality decreased with later model year groups (MY<94 0.78%, MY 94-97 0.53%, MY 98-04 0.51% and MY 05-08 0.38%, p=<0.0001). After adjustment for confounders, MY 94-97, MY 98-04 and MY 05-08 showed decreased odds of death [OR 0.80 (0.69-0.94), 0.82 (0.70-0.97), and 0.67 (0.47-0.96), respectively] when compared to MY <94. Newer vehicles are associated with lower crash-related mortality. Their introduction into the vehicle fleet may explain, at least in part, the decrease in mortality rates in the past two decades.


Microbial biofilms: biosurfactants as antibiofilm agents.
Current microbial inhibition strategies based on planktonic bacterial physiology have been known to have limited efficacy on the growth of biofilm communities. This problem can be exacerbated by the emergence of increasingly resistant clinical strains. All aspects of biofilm measurement, monitoring, dispersal, control, and inhibition are becoming issues of increasing importance. Biosurfactants have merited renewed interest in both clinical and hygienic sectors due to their potential to disperse microbial biofilms in addition to many other advantages. The dispersal properties of biosurfactants have been shown to rival those of conventional inhibitory agents against bacterial and yeast biofilms. This makes them suitable candidates for use in new generations of microbial dispersal agents and for use as adjuvants for existing microbial suppression or eradication strategies. In this review, we explore aspects of biofilm characteristics and examine the contribution of biologically derived surface-active agents (biosurfactants) to the disruption or inhibition of microbial biofilms.


Gravity of human impacts mediates coral reef conservation gains.
Coral reefs provide ecosystem goods and services for millions of people in the tropics, but reef conditions are declining worldwide. Effective solutions to the crisis facing coral reefs depend in part on understanding the context under which different types of conservation benefits can be maximized. Our global analysis of nearly 1,800 tropical reefs reveals how the intensity of human impacts in the surrounding seascape, measured as a function of human population size and accessibility to reefs ("gravity"), diminishes the effectiveness of marine reserves at sustaining reef fish biomass and the presence of top predators, even where compliance with reserve rules is high. Critically, fish biomass in high-compliance marine reserves located where human impacts were intensive tended to be less than a quarter that of reserves where human impacts were low. Similarly, the probability of encountering top predators on reefs with high human impacts was close to zero, even in high-compliance marine reserves. However, we find that the relative difference between openly fished sites and reserves (what we refer to as conservation gains) are highest for fish biomass (excluding predators) where human impacts are moderate and for top predators where human impacts are low. Our results illustrate critical ecological trade-offs in meeting key conservation objectives: reserves placed where there are moderate-to-high human impacts can provide substantial conservation gains for fish biomass, yet they are unlikely to support key ecosystem functions like higher-order predation, which is more prevalent in reserve locations with low human impacts.


Downregulation of miRNA17-92 cluster marks Vγ9Vδ2 T cells from patients with rheumatoid arthritis.
We aimed to evaluate the phenotype, function, and microRNA (miRNA)17-92 cluster expression in Vγ9Vδ2 T-cell subsets and the correlation with immune response in rheumatoid arthritis (RA) patients. Peripheral blood from 10 early RA untreated patients and 10 healthy donors (HD) was obtained. Polyclonal Vγ9Vδ2 T-cell lines were generated and analysed by flow cytometry. Analysis of miRNA17-92 cluster expression was performed by real-time polymerase chain reaction (RT-PCR), and expression of mRNA target genes was also studied. A remarkable change in the distribution of Vγ9Vδ2 T-cell functional subsets was observed in the peripheral blood of RA patients compared with HD, with an expansion of effector subsets and reduction of naive cells which was accompanied by modifications in proinflammatory cytokine expression. Vγ9Vδ2 T cells with a TEM (effector memory) phenotype and producing proinflammatory cytokines were correlated with disease activity score (DAS28). The comparison of miRNA expression among Vγ9Vδ2 T-cell subsets from RA patients and HD showed a lower level of miR-106a-5p and miR-20a-5p, and a higher level of miR-21a-5p, among Vγ9Vδ2 TEM cells, and a lower level of miR-19b-3p among Vγ9Vδ2 TCM (central memory) cells was also found. These differentially expressed miRNAs correlated with higher levels of expression of interleukin (IL)-8, IL-6, and PDCD4 genes. Our results provide evidence for a role of miR-106a, miR-19-3p, miR-20a, and miR-21a in the regulation of Vγ9Vδ2 T-cell function in RA patients and suggest the possibility that the miRNA17-92 family and Vγ9Vδ2 T cells contribute to the pathogenesis of RA.


Female reproductive factors are associated with objectively measured physical activity in middle-aged women.
Physical activity improves health and may delay the onset of several chronic diseases. For women in particular, the rate of these diseases accelerates at middle age; therefore it is important to identify the determinants of health-enhancing physical activity during midlife in this population. In this study, we focused on determinants that are unique to the female sex, such as childbearing and menopause. The main objective was to characterize the level of physical activity and differences between active and inactive middle-aged Finnish women. In addition, we examined the association of physical activity with female reproductive factors at midlife. The study population consisted of 647 women aged 48 to 55 years who participated in our Estrogenic Regulation of Muscle Apoptosis (ERMA) study during the period from 2015 to 2016. Physical activity was measured objectively using hip-worn accelerometers for seven consecutive days. The outcome measures included the amounts of light intensity physical activity and moderate to vigorous intensity physical activity accumulated in bouts of at least 10 minutes (MVPA10). MVPA10 was used to determine whether women were placed in the active (≥150 min/week) or inactive (<150 min/week) group. Multiple linear regression models were performed with physical activity measures as dependent variables and cumulative reproductive history index, menopausal symptoms, and pelvic floor dysfunction as independent variables. We found that a large portion (61%) of Finnish middle-aged women did not meet the physical activity recommendations of 150 minutes of MVPA10 per week. In the studied cohort, 78% of women experienced menopausal symptoms, and 54% exhibited pelvic floor dysfunction. Perceived menopausal symptoms were associated with greater light physical activity. Perceived pelvic floor dysfunction was associated with lower MVPA10. According to the fully adjusted multiple linear regression models, reproductive factors explained 6.0% of the variation of MVPA10 and 7.5% of the variation of light physical activity. The results increase our knowledge of the factors related to physical activity participation among middle-aged women and indicate that menopausal symptoms and pelvic floor dysfunction should be identified and considered when promoting physical activity for women during midlife. The results emphasize that awareness of female reproductive factors, especially menopausal symptoms and pelvic floor dysfunction, is important for physical activity counseling to effectively help women in performing and sustaining health-enhancing amounts of physical activity. Specifically, the condition of the pelvic floor should be taken into account when identifying the proper activity type and intensity level so that health benefits of physical activity can still be attained without worsening symptoms.


Extracellular Electron Transfer Powers Enterococcus faecalis Biofilm Metabolism.
Enterococci are important human commensals and significant opportunistic pathogens. Biofilm-related enterococcal infections, such as endocarditis, urinary tract infections, wound and surgical site infections, and medical device-associated infections, often become chronic upon the formation of biofilm. The biofilm matrix establishes properties that distinguish this state from free-living bacterial cells and increase tolerance to antimicrobial interventions. The metabolic versatility of the enterococci is reflected in the diversity and complexity of environments and communities in which they thrive. Understanding metabolic factors governing colonization and persistence in different host niches can reveal factors influencing the transition to biofilm pathogenicity. Here, we report a form of iron-dependent metabolism for Enterococcus faecalis where, in the absence of heme, extracellular electron transfer (EET) and increased ATP production augment biofilm growth. We observe alterations in biofilm matrix depth and composition during iron-augmented biofilm growth. We show that the ldh gene encoding l-lactate dehydrogenase is required for iron-augmented energy production and biofilm formation and promotes EET.IMPORTANCE Bacterial metabolic versatility can often influence the outcome of host-pathogen interactions, yet causes of metabolic shifts are difficult to resolve. The bacterial biofilm matrix provides the structural and functional support that distinguishes this state from free-living bacterial cells. Here, we show that the biofilm matrix can immobilize iron, providing access to this growth-promoting resource which is otherwise inaccessible in the planktonic state. Our data show that in the absence of heme, Enterococcus faecalis l-lactate dehydrogenase promotes EET and uses matrix-associated iron to carry out EET. Therefore, the presence of iron within the biofilm matrix leads to enhanced biofilm growth.


Longitudinal study of the immune response and memory following natural bovine respiratory syncytial virus infections in cattle of different age.
Human and bovine respiratory syncytial virus (HRSV and BRSV) are closely genetically related and cause respiratory disease in their respective host. Whereas HRSV vaccines are still under development, a multitude of BRSV vaccines are used to reduce clinical signs. To enable the design of vaccination protocols to entirely stop virus circulation, we aimed to investigate the duration, character and efficacy of the immune responses induced by natural infections. The systemic humoral immunity was monitored every two months during two years in 33 dairy cattle in different age cohorts following a natural BRSV outbreak, and again in selected individuals before and after a second outbreak, four years later. Local humoral and systemic cellular responses were also monitored, although less extensively. Based on clinical observations and economic losses linked to decreased milk production, the outbreaks were classified as moderate. Following the first outbreak, most but not all animals developed neutralising antibody responses, BRSV-specific IgG1, IgG2 and HRSV F- and HRSV N-reactive responses that lasted at least two years, and in some cases at least four years. In contrast, no systemic T cell responses were detected and only weak IgA responses were detected in some animals. Seronegative sentinels remained negative, inferring that no new infections occurred between the outbreaks. During the second outbreak, reinfections with clinical signs and virus shedding occurred, but the signs were milder, and the virus shedding was significantly lower than in naïve animals. Whereas the primary infection induced similar antibody titres against the prefusion and the post fusion form of the BRSV F protein, memory responses were significantly stronger against prefusion F. In conclusion, even if natural infections induce a long-lasting immunity, it would probably be necessary to boost memory responses between outbreaks, to stop the circulation of the virus and limit the potential role of previously infected adult cattle in the chain of BRSV transmission.


Obstetric management of adolescents with bleeding disorders.
Adolescents with bleeding disorders who become pregnant must contend with the dual challenges of their bleeding disorder and their pregnancy. Adolescents are more likely to terminate a pregnancy than adult women, and when they do carry a pregnancy, they are more likely to deliver prematurely. Otherwise, they are at risk for the same complications that adult women with bleeding disorders experience, particularly bleeding complications postpartum. Since one half to two thirds of adolescent pregnancies are unplanned, issues related to reproduction should be addressed during routine visits with the pediatrician, hematologist or gynecologist. Girls who are at risk of being carriers for hemophilia A and B, severe von Willebrand disease, and other severe bleeding disorders should have their bleeding disorder status determined before they become pregnant. During pregnancy, a plan should be established to ensure that both mother and fetus deliver safely. Young women at risk for severe bleeding or at risk of having a severely affected infant should be referred for prenatal care and delivery to a center where, in addition to specialists in high-risk obstetrics, there is a hemophilia treatment center or a hematologist with expertise in hemostasis. Prior to delivery or any invasive procedures, young women at risk for severe bleeding should receive prophylaxis. Since administration of desmopressin may result in hyponatremia, whenever available, virally inactivated or recombinant clotting factor concentrates should be used for replacement as opposed to fresh frozen plasma or cryoprecipitate.


Spontaneous Ca2+ Influx in Drosophila Pupal Neurons Is Modulated by IP3-Receptor Function and Influences Maturation of the Flight Circuit.
Inositol 1,4,5-trisphosphate receptors (IP3R) are Ca2+ channels on the neuronal endoplasmic reticulum (ER) membrane. They are gated by IP3, produced upon external stimulation and activation of G protein-coupled receptors on the plasma membrane (PM). IP3-mediated Ca2+ release, and the resulting depletion of the ER store, triggers entry of extracellular Ca2+ by store-operated Ca2+ entry (SOCE). Mutations in IP3R attenuate SOCE. Compromised IP3R function and SOCE during pupal development of Drosophila leads to flight deficits and mimics suppression of neuronal activity during pupal or adult development. To understand the effect of compromised IP3R function on pupal neuronal calcium signaling, we examined the effects of mutations in the IP3R gene (itpr) on Ca2+ signals in cultured neurons derived from Drosophila pupae. We observed increased spontaneous Ca2+ influx across the PM of isolated pupal neurons with mutant IP3R and also a loss of SOCE. Both spontaneous Ca2+ influx and reduced SOCE were reversed by over-expression of dOrai and dSTIM, which encode the SOCE Ca2+ channel and the ER Ca2+-sensor that regulates it, respectively. Expression of voltage-gated Ca2+ channels (cac, Ca-α1D and Ca-αT) was significantly reduced in itpr mutant neurons. However, expression of trp mRNAs and transient receptor potential (TRP) protein were increased, suggesting that TRP channels might contribute to the increased spontaneous Ca2+ influx in neurons with mutant IP3R. Thus, IP3R/SOCE modulates spontaneous Ca2+ influx and expression of PM Ca2+ channels in Drosophila pupal neurons. Spontaneous Ca2+ influx compensates for the loss of SOCE in Drosophilaitpr mutant neurons.


Development of valid and reliable tools for student evaluation of teaching.
The objective of this project was to develop valid and reliable course and instructor student evaluation tools (SETs) of teaching for utilization by a college of pharmacy. A collection of 119 course and instructor evaluation items was compiled from a review of the primary literature and grouped into six different themes (subscales): organization, communication, motivation, rapport, fairness, and learning. Input was sought from the college of pharmacy faculty to reduce the list of items to a more manageable pilot tool (27 for course evaluations; 29 for instructor evaluations) for developing pilot SETs. The results were analyzed for internal consistency and reliability using Cronbach's alpha, and whether factor structures aligned with the content structure using Confirmatory Factor Analysis (CFA). The Cronbach's alpha for all six subscales in the designed instructor evaluation and for three of the six subscales in the designed course evaluation were above 0.9, indicating high internal consistency and reliability. The CFA results indicated a moderate model fit with factor loadings for all items above 0.6. The correlation coefficients between each dimension were about 0.8, indicating high correlations among dimensions. Those data items found to be valid were then used to construct new course and instructor evaluation instruments, both consisting of three validated items in each of the six themes (subscales). This report describes the process that one college of pharmacy employed to develop a valid and reliable SET. The methodology can inform other colleges and schools of pharmacy who wish to design, revise, or develop their own SETs.


Cortical dynamics of emotional autobiographical memory retrieval differ between women and men.
Retrieval of autobiographical memories entails periods of search, access, and elaboration. Women's reports of their memories feature more detail and emotional content relative to men's. A key question is how these gender differences relate to unfolding changes in cortical activity during retrieval. We recorded EEG activity from 32 scalp electrodes as women and men were cued to retrieve positive, negative, and neutral autobiographical memories. Alpha (9-12Hz) oscillations were prominent at all EEG channels. Alpha coherence between channels was calculated as a measure of ms-level cortical synchrony. Across participants and memory types, a frontal cluster showed pronounced decreases in coherence with other channels during the first second of autobiographical retrieval. In the following second, a left parietal-centered cluster showed increased coherence with other channels. This effect strengthened and spread in the third second of retrieval, perhaps reflecting trace elaboration and/or evaluation of the memory. Although women and men gave similar subjective ratings of their memories, the second-by-second pattern of alpha coherence during autobiographical retrieval differed by gender and memory type. Specifically, women sustained the increased pattern of left-parietal coherence throughout the trial, whereas for men, alpha coherence in this cluster returned to baseline by second two for neutral memories and by second three for emotional memories. Examination of the temporal dynamics of cortical oscillations provides novel insight into autobiographical memory retrieval processes and to gendered retrieval in particular, suggesting that women may persist with elaboration and/or evaluation to a greater extent than men.


Effects of zinc and other metal ions on the stability and activity of Escherichia coli alkaline phosphatase.
Measurement of the ultraviolet circular dichroism of apo-(alkaline phosphatase) in urea solutions showed substantial denaturation in 3m-urea. A zinc-deficient mutant alkaline phosphatase behaved similarly. The stability of the enzyme in 6m-urea was followed as a function of its zinc content and was found to be dependent on the first two of the four zinc atoms bound by apoenzyme. Phosphatase activity was mostly dependent on a second pair of zinc atoms. Mn(2+), Co(2+), Cu(2+) or Cd(2+) also restored structural stability. Sedimentation-velocity and -equilibrium experiments revealed that dissociation of the dimer accompanied apoenzyme denaturation in urea concentrations of 1m or higher, without treatment with disulphide-reducing agent.


Prevalence of Hepatitis C virus infection in a sample of homeless veterans.
This study measures the prevalence of Hepatitis C Virus (HCV) infection in a sample of homeless veterans treated in a Domiciliary Care for Homeless Veterans (DCHV) program in Massachusetts. We also examine risk factors and correlates for HCV infection, including substance abuse and service in Vietnam. Patients admitted to the DCHV program over a 5-year period (n=418) were systematically tested for HCV infection. Blood test data were merged with standardized data collection forms to assess socio-demographic characteristics, military history, and medical and psychiatric history. The overall prevalence rate of HCV infection was 44.02%, a rate more than ten times higher than the national rate for men age 20-59 and more than twice as high as other VA patient samples. Adjusting for age, significant risk factors in this sample included a history of substance abuse (OR=6.86, p<0.0001) and service during the Vietnam era (OR=4.66, p=0.01). Comparisons of the tested sample with other homeless veterans treated in 34 similar programs nationally indicated that this sample did not significantly differ from other treated homeless veterans with respect to demographics or HCV risk factors. We found a high prevalence of HCV infection in this population that is not likely to be geographically unique, and may indicate particularly high risk for homeless men. Substance abuse is the most important risk factor, and we hypothesize that the effect of Vietnam-era service is a proxy for unreported drug use. We advise an increase in screening and education for all homeless populations, particularly those with a history of injection drug use. Public systems of care, including the VA, should expect increasing costs of care related to HCV infection as prevalent cases develop serious medical sequelae of HCV infection.


A study to evaluate the cause of bone demineralization in gynecological cancer survivors.
An association between treatment for gynecological cancers and risk of osteoporosis has never been formally evaluated. Women treated for these cancers are now living longer than ever before, and prevention of treatment-induced morbidities is important. We aimed to distinguish, in gynecological cancer survivors, whether cancer therapy has additional detrimental effects on bone health above those attributable to hormone withdrawal. We performed a retrospective cross-sectional analysis of dual energy x-ray absorptiometry (DEXA) scan results from 105 women; 64 had undergone bilateral salpingo-oophorectomy (BSO) followed by chemotherapy or radiotherapy for gynecological malignancies, and 41 age-matched women had undergone BSO for benign etiologies. All were premenopausal prior to surgery. The median age at DEXA scan for the cancer group was 42 years, and 66% had received hormonal replacement therapy (HRT) following their cancer treatment. For the benign group, the median age was 40 years, and 87% had received HRT. Thirty-nine percent of cancer survivors had abnormal DEXA scan results compared to 15% of the control group, with the majority demonstrating osteopenia. The mean lumbar spine and femoral neck bone mineral densities (BMDs) were significantly lower in cancer patients. A history of gynecological cancer treatment was associated with significantly lower BMD in a multivariate logistic regression. Women treated for gynecological malignancies with surgery and adjuvant chemotherapy have significantly lower BMDs than age-matched women who have undergone oophorectomy for noncancer indications. Prospective evaluation of BMD in gynecological cancer patients is recommended to facilitate interventions that will reduce the risk of subsequent fragility fractures.


An algorithm for power line detection and warning based on a millimeter-wave radar video.
Power-line-strike accident is a major safety threat for low-flying aircrafts such as helicopters, thus an automatic warning system to power lines is highly desirable. In this paper we propose an algorithm for detecting power lines from radar videos from an active millimeter-wave sensor. Hough Transform is employed to detect candidate lines. The major challenge is that the radar videos are very noisy due to ground return. The noise points could fall on the same line which results in signal peaks after Hough Transform similar to the actual cable lines. To differentiate the cable lines from the noise lines, we train a Support Vector Machine to perform the classification. We exploit the Bragg pattern, which is due to the diffraction of electromagnetic wave on the periodic surface of power lines. We propose a set of features to represent the Bragg pattern for the classifier. We also propose a slice-processing algorithm which supports parallel processing, and improves the detection of cables in a cluttered background. Lastly, an adaptive algorithm is proposed to integrate the detection results from individual frames into a reliable video detection decision, in which temporal correlation of the cable pattern across frames is used to make the detection more robust. Extensive experiments with real-world data validated the effectiveness of our cable detection algorithm.


Interaction between protein tyrosine phosphatase and protein tyrosine kinase is involved in androgen-promoted growth of human prostate cancer cells.
Steroid hormones play key roles in regulating cell proliferation and differentiation in targeting tissues. However, in advanced cancers, the steroid hormone regulation is frequently attenuated through a yet unknown mechanism even in the presence of functional steroid hormone receptors. We investigate the functional role of tyrosine phosphorylation signaling in the hormone-refractory growth of human prostate tumors. Initial studies demonstrate that the androgen-responsive phenotype of human prostate cancer cells associates with a low phosphotyrosine (p-Tyr) level of ErbB-2, which is regulated by cellular prostatic acid phosphatase (PAcP), a protein tyrosine phosphatase. In prostate cancer cells, the p-Tyr level, but not the protein level, of ErbB-2 inversely correlates with the androgen-responsiveness of cell proliferation. Androgen-stimulated cell growth concurs with a down-regulation of cellular PAcP, an elevated p-Tyr level of ErbB-2, and the activation of mitogen-activated protein kinases. Furthermore, only the ErbB-2 inhibitor AG 879, but not the EGFR inhibitor AG 1478, abolishes androgen-induced cell proliferation. Forced expression of ErbB-2 can also attenuate androgen promotion of cell growth. Data taken collectively conclude that in human prostate cancer cells, the tyrosine phosphorylation of ErbB-2 regulated by cellular PAcP plays a key role in regulating androgen-mediated proliferation signaling. Oncogene (2000).


Impacts of Combustion Conditions and Photochemical Processing on the Light Absorption of Biomass Combustion Aerosol.
The aim was to identify relationships between combustion conditions, particle characteristics, and optical properties of fresh and photochemically processed emissions from biomass combustion. The combustion conditions included nominal and high burn rate operation and individual combustion phases from a conventional wood stove. Low temperature pyrolysis upon fuel addition resulted in "tar-ball" type particles dominated by organic aerosol with an absorption Ångström exponent (AAE) of 2.5-2.7 and estimated Brown Carbon contributions of 50-70% to absorption at the climate relevant aethalometer-wavelength (520 nm). High temperature combustion during the intermediate (flaming) phase was dominated by soot agglomerates with AAE 1.0-1.2 and 85-100% of absorption at 520 nm attributed to Black Carbon. Intense photochemical processing of high burn rate flaming combustion emissions in an oxidation flow reactor led to strong formation of Secondary Organic Aerosol, with no or weak absorption. PM1 mass emission factors (mg/kg) of fresh emissions were about an order of magnitude higher for low temperature pyrolysis compared to high temperature combustion. However, emission factors describing the absorption cross section emitted per kg of fuel consumed (m(2)/kg) were of similar magnitude at 520 nm for the diverse combustion conditions investigated in this study. These results provide a link between biomass combustion conditions, emitted particle types, and their optical properties in fresh and processed plumes which can be of value for source apportionment and balanced mitigation of biomass combustion emissions from a climate and health perspective.


The challenge of long-term climate change.
Climate policy needs to address the multidecadal to centennial time scale of climate change. Although the realization of short-term targets is an important first step, to be effective climate policies need to be conceived as long-term programs that will achieve a gradual transition to an essentially emission-free economy on the time scale of a century. This requires a considerably broader spectrum of policy measures than the primarily market-based instruments invoked for shorter term mitigation policies. A successful climate policy must consist of a dual approach focusing on both short-term targets and long-term goals.


Perceptions of a mental health questionnaire: the ethics of using population-based controls.
Mental health surveys are used extensively in epidemiological research worldwide. The ethical questions that arise regarding their risk of causing psychological distress or other potential harm have not been studied in the general population. We have investigated how study participants serving as controls in a population-based study perceived an anonymous postal questionnaire focusing on mental health and wellbeing. Parents were contacted from the Swedish Census Bureau as part of a larger follow-up study on palliative care conducted in 2001. Eligible parents had a child of the same gender, year of birth and were from the same counties in Sweden as parents who had lost a child to cancer. Five percent reported being negatively affected. The principle negative effect on participants was that self-reflection reminded them of their difficulties. Of the 418 respondents, 52% reported that they were positively affected by study participation and 95% perceived the inquiry as valuable. These findings support the use of population-based controls in future research.


Are surface properties integrated into visuohaptic object representations?
Object recognition studies have almost exclusively involved vision, focusing on shape rather than surface properties such as color. Visual object representations are thought to integrate shape and color information because changing the color of studied objects impairs their subsequent recognition. However, little is known about integration of surface properties into visuohaptic multisensory representations. Here, participants studied objects with distinct patterns of surface properties (color in Experiment 1, texture in Experiments 2 and 3) and had to discriminate between object shapes when color or texture schemes were altered in within-modal (visual and haptic) and cross-modal (visual study followed by haptic test and vice versa) conditions. In Experiment 1, color changes impaired within-modal visual recognition but had no effect on cross-modal recognition, suggesting that the multisensory representation was not influenced by modality-specific surface properties. In Experiment 2, texture changes impaired recognition in all conditions, suggesting that both unisensory and multisensory representations integrated modality-independent surface properties. However, the cross-modal impairment might have reflected either the texture change or a failure to form the multisensory representation. Experiment 3 attempted to distinguish between these possibilities by combining changes in texture with changes in orientation, taking advantage of the known view-independence of the multisensory representation, but the results were not conclusive owing to the overwhelming effect of texture change. The simplest account is that the multisensory representation integrates shape and modality-independent surface properties. However, more work is required to investigate this and the conditions under which multisensory integration of structural and surface properties occurs.


The composition, diversity, and distribution of mosquito fauna (Diptera: Culicidae) in Kosovo.
The aim of this study is to identify the mosquito species that currently exist and their distributions in Kosovo in order to determine current potential endemic zones and areas at a higher risk for future epidemics. These scientific data will be shared with public health authorities for implementing mosquito control programs. During a two-year period of monitoring in 48 localities in 23 provinces in Kosovo, a total of 1,604 mosquitoes representing 13 species and six genera were collected and morphologically identified. Members of species complexes were also classified to species using DNA barcoding. In total, 13 species were identified with Culex pipiens s.l., the predominant species with an abundance rate of 39%. The remaining 12 species identified were grouped into five genera: Anopheles, Aedes, Coquillettidia, Culiseta, Uranotaenia, including species that are vectors of arboviruses in other parts of the world.


The double-edged sword: does biomechanism increase or decrease judges' sentencing of psychopaths?
We tested whether expert testimony concerning a biomechanism of psychopathy increases or decreases punishment. In a nationwide experiment, U.S. state trial judges (N = 181) read a hypothetical case (based on an actual case) where the convict was diagnosed with psychopathy. Evidence presented at sentencing in support of a biomechanical cause of the convict's psychopathy significantly reduced the extent to which psychopathy was rated as aggravating and significantly reduced sentencing (from 13.93 years to 12.83 years). Content analysis of judges' reasoning indicated that even though the majority of judges listed aggravating factors (86.7%), the biomechanical evidence increased the proportion of judges listing mitigating factors (from 29.7 to 47.8%). Our results contribute to the literature on how biological explanations of behavior figure into theories of culpability and punishment.


The Lectin Complement Pathway Is Involved in Protection Against Enteroaggregative Escherichia coli Infection.
Enteroaggregative Escherichia coli (EAEC) causes acute and persistent diarrhea worldwide. Still, the involvement of host factors in EAEC infections is unresolved. Binding of recognition molecules from the lectin pathway of complement to EAEC strains have been observed, but the importance is not known. Our aim was to uncover the involvement of these molecules in innate complement dependent immune protection toward EAEC. Binding of mannose-binding lectin, ficolin-1, -2, and -3 to four prototypic EAEC strains, and ficolin-2 binding to 56 clinical EAEC isolates were screened by a consumption-based ELISA method. Flow cytometry was used to determine deposition of C4b, C3b, and the bactericidal C5b-9 membrane attack complex (MAC) on the bacteria in combination with different complement inhibitors. In addition, the direct serum bactericidal effect was assessed. Screening of the prototypic EAEC strains revealed that ficolin-2 was the major binder among the lectin pathway recognition molecules. However, among the clinical EAEC isolates only a restricted number (n = 5) of the isolates bound ficolin-2. Using the ficolin-2 binding isolate C322-17 as a model, we found that incubation with normal human serum led to deposition of C4b, C3b, and to MAC formation. No inhibition of complement deposition was observed when a C1q inhibitor was added, while partial inhibition was observed when ficolin-2 or factor D inhibitors were used separately. Combining the inhibitors against ficolin-2 and factor D led to virtually complete inhibition of complement deposition and protection against direct bacterial killing. These results demonstrate that ficolin-2 may play an important role in innate immune protection against EAEC when an appropriate ligand is exposed, but many EAEC strains evade lectin pathway recognition and may, therefore, circumvent this strategy of innate host immune protection.


Use of the 4Kscore test to predict the risk of aggressive prostate cancer prior to prostate biopsy: Overall cost savings and improved quality of care to the us healthcare system.
The 4Kscore® Test (BioReference Laboratories, Elmwood Park, NJ) is a blood test that accurately determines the risk of aggressive prostate cancer and significantly reduces prostate biopsies and associated overdiagnosis and overtreatment of indolent cancer. A budget impact model was developed to test the hypothesis that the 4Kscore Test can improve quality of care and deliver cost savings for patients who are suspected of having prostate cancer and would otherwise undergo prostate biopsy under the current standard of care (SOC) in the United States. The direct costs (diagnosis plus treatment) utilized in the model are based on Medicare payment data and were calculated over a 1-year time horizon. The model compares SOC, in which all patients have prostate biopsy, to a "4Kscore strategy," in which the 4Kscore Test is used to guide the decision to biopsy the prostate. A set of one-way sensitivity analyses was conducted to examine the robustness of the findings. Savings of more than $169 million (15.6% of total SOC costs) were realized in the 4Kscore strategy versus SOC ($917 M versus $1,086 M, respectively) in a cohort of 100,000 patients. Sensitivity analyses demonstrated that the findings are robust. Most cost savings for the 4Kscore strategy were realized in patients who, when managed by SOC, are found to have no prostate cancer or Gleason score 6 pathology. The patients with Gleason score 6 exhibited the greatest benefits from the 4Kscore strategy, avoiding both an unnecessary prostate biopsy and subsequent overtreatment. The 4Kscore Test was shown to significantly reduce costs to the healthcare system while improving patients' quality of care. Providers and their patients suspected of having prostate cancer should consider using the 4Kscore Test prior to proceeding with prostate biopsy.


Learning spinal manipulation: a comparison of two teaching models.
The goal of the present study was to quantify the high-velocity, low-amplitude spinal manipulation biomechanical parameters in two cohorts of students from different teaching institutions. The first cohort of students was taught chiropractic techniques in a patient-doctor positioning practice setting, while the second cohort of students was taught in a "complete practice" manipulation setting, thus performing spinal manipulation skills on fellow student colleagues. It was hypothesized that the students exposed to complete practice would perform the standardized spinal manipulation with better biomechanical parameters. Participants (n = 88) were students enrolled in two distinct chiropractic programs. Thoracic spine manipulation skills were assessed using an instrumented manikin, which allowed the measurement of applied force. Dependent variables included peak force, time to peak force, rate of force production, peak force variability, and global coordination. The results revealed that students exposed to complete practice demonstrated lower time to peak force values, higher peak force, and a steeper rate of force production compared with students in the patient-doctor positioning scenario. A significant group by gender interaction was also noted for the time to peak force and rate of force production variables. The results of the present study confirm the importance of chiropractic technique curriculum and perhaps gender in spinal manipulation skill learning. It also stresses the importance of integrating spinal manipulation skills practice early in training to maximize the number and the quality of significant learner-instructor interactions.


Analysis of chiral amino acids in conventional and transgenic maize.
In this work, a new chiral micellar electrokinetic chromatography with laser-induced fluorescence detection (chiral-MEKC-LIF) method is proposed to identify and quantify D- and L-amino acids in three lines of transgenic maize and their corresponding nontransgenic parental lines grown under identical conditions. The optimized procedure includes amino acids extraction, derivatization with FITC and chiral-MEKC-LIF separation in a background electrolyte composed of 100 mM sodium tetraborate, 80 mM SDS, and 20 mM beta-CD at pH 10.0. The D- and L-forms of Arg, Ser, Ala, Glu, and Asp, corresponding to the majority amino acids usually found in maize, are separated in less than 25 min with efficiencies up to 890,000 plates/m and high sensitivity (i.e., LODs as low as 160 nM were obtained for D-Arg for a signal-to-noise ratio of three), allowing the detection of 1% D-Arg in the presence of 99% of its opposite enantiomer. Using this method, different D-amino acids are detected in all investigated maize samples providing the reproducible quantification of the D-enantiomeric excess (% d-aa) for each amino acid calculated as % D-aa = 100D-aa/(D-aa + L-aa). Thus, significant differences were observed among the % d-aa values for the different conventional varieties (Aristis, Tietar, and PR33P66 maize) as could be expected from their natural variability. More interestingly, comparing each conventional maize with its corresponding transgenic line, very similar % D-aa values were obtained for one of the studied maize couples (Tietar vs Tietar-Bt) what could be presented as a new proof of their substantial equivalence. However, significant differences in the % d-aa values were observed for the other lines of maize studied. It is concluded that enantioselective procedures can open new perspectives in the study of transgenic organisms in order to corroborate (or not) the equivalence with their conventional counterparts.


On global-local artificial neural networks for function approximation.
We present a hybrid radial basis function (RBF) sigmoid neural network with a three-step training algorithm that utilizes both global search and gradient descent training. The algorithm used is intended to identify global features of an input-output relationship before adding local detail to the approximating function. It aims to achieve efficient function approximation through the separate identification of aspects of a relationship that are expressed universally from those that vary only within particular regions of the input space. We test the effectiveness of our method using five regression tasks; four use synthetic datasets while the last problem uses real-world data on the wave overtopping of seawalls. It is shown that the hybrid architecture is often superior to architectures containing neurons of a single type in several ways: lower mean square errors are often achievable using fewer hidden neurons and with less need for regularization. Our global-local artificial neural network (GL-ANN) is also seen to compare favorably with both perceptron radial basis net and regression tree derived RBFs. A number of issues concerning the training of GL-ANNs are discussed: the use of regularization, the inclusion of a gradient descent optimization step, the choice of RBF spreads, model selection, and the development of appropriate stopping criteria.


Frequency of diabetes and other comorbidities in chronic inflammatory demyelinating polyradiculoneuropathy and their impact on clinical presentation and response to therapy.
To determine the prevalence of different comorbidities in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), and their impact on outcome, treatment choice and response. Using a structured questionnaire, we collected information on comorbidities from 393 patients with CIDP fulfilling the European Federation of Neurological Societies and Peripheral Nerve Society criteria included in the Italian CIDP database. One or more comorbidities were reported by 294 patients (75%) and potentially influenced treatment choice in 192 (49%) leading to a less frequent use of corticosteroids. Response to treatment did not differ, however, from that in patients without comorbidities. Diabetes (14%), monoclonal gammopathy of undetermined significance (MGUS) (12%) and other immune disorders (16%) were significantly more frequent in patients with CIDP than expected in the general European population. Patients with diabetes had higher disability scores, worse quality of life and a less frequent treatment response compared with patients without diabetes. Patients with IgG-IgA or IgM MGUS had an older age at CIDP onset while patients with other immune disorders had a younger age at onset and were more frequently females. IgM MGUS was more frequent in patients with motor CIDP than in patients with typical CIDP. Comorbidities are frequent in patients with CIDP and in almost 50% of them have an impact on treatment choice. Diabetes, MGUS and other immune diseases are more frequent in patients with CIDP than in the general population. Only diabetes seems, however, to have an impact on disease severity and treatment response possibly reflecting in some patients a coexisting diabetic neuropathy.


Characterization and Predictive Value of Near Infrared 2-Deoxyglucose Optical Imaging in Severe Acute Pancreatitis.
Studying the uptake of 2-deoxy glucose (2-DG) analogs such as 2-Deoxy-2-[18F] fluoroglucose (FDG) is a common approach to identify and monitor malignancies and more recently chronic inflammation. While pancreatitis is a common cause for false positive results in human studies on pancreatic cancer using FDG, the relevance of these findings to acute pancreatitis (AP) is unknown. FDG has a short half-life. Thus, with an aim to accurately characterize the metabolic demand of the pancreas during AP in real-time, we studied the uptake of the non-radioactive, near infrared fluorescence labelled 2-deoxyglucose analog, IRDye® 800CW 2-DG probe (NIR 2-DG; Li-Cor) during mild and severe biliary AP. Wistar rats (300 g; 8-12/group) were administered NIR 2-DG (10 nM; I.V.). Mild and severe biliary AP were respectively induced by biliopancreatic duct ligation (DL) alone or along with infusing glyceryl trilinoleate (GTL; 50 μL/100 g) within 10 minutes of giving NIR 2-DG. Controls (CON) only received NIR 2-DG. Imaging was done every 5-10 minutes over 3 hrs. Average Radiant Efficiency [p/s/cm²/sr]/[μW/cm²] was measured over the pancreas using the IVIS 200 in-vivo imaging system (PerkinElmer) using the Living Image® software and verified in ex vivo pancreata. Blood amylase, lipase and pancreatic edema, necrosis were measured over the course of AP. NIR 2-DG uptake over the first hour was not influenced by AP induction. However, while the signal declined in controls and rats with mild AP, there was significantly higher retention of NIR 2-DG in the pancreas after 1 hour in those with GTL pancreatitis. The increase was > 3 fold over controls in the GTL group and was verified to be in the pancreas ex vivo. In vitro, pancreatic acini exposed to GTL had a similar increase in NIR 2-DG uptake which was followed by progressively worse acinar necrosis. Greater retention of NIR 2-DG in vivo was associated with worse pancreatic necrosis, reduced ATP concentrations and mortality, which were not predicted by the blood parameters. In-vivo fluorescent imaging of a non-radioactive near infrared 2-DG optical probe can predict the AP severity early during the disease.


Climate change and safety at work with ionizing radiations.
The accident at Tokyo Electric Power Company's (TEPCO's) Fukushima Daiichi nuclear power plant (NPP) has been one of the dominant topic in nuclear safety and it has brought new attention on the matter of accidents in NPPs due to external events related to natural causes. Climate change has risen new risks and the growing probability of extreme external events has increased exposure and vulnerability of workers in the nuclear sector. However extreme natural events are a threat not only to NPPs but to all facilities dealing with radioactive material and in an emergency scenario they can affect the effectiveness and implementation of safety devices and procedures and also prevent communications, causing delays in the readiness of response. It is clear that adaptation strategies are necessary to cope with emerging changes in climate and a new nuclear safety culture is growing, that addresses accidents initiated not only by internal but also by external events.


Deiodinases: implications of the local control of thyroid hormone action.
The deiodinases activate or inactivate thyroid hormone, and their importance in thyroid hormone homeostasis has become increasingly clear with the availability of deiodinase-deficient animals. At the same time, heightened interest in the field has been generated following the discovery that the type 2 deiodinase can be an important component in both the Hedgehog signaling pathway and the G protein-coupled bile acid receptor 1-mediated (GPBAR1-mediated) signaling cascade. The discovery of these new roles for the deiodinases indicates that tissue-specific deiodination plays a much broader role than once thought, extending into the realms of developmental biology and metabolism.


Duct system of the rabbit lacrimal gland: structural characteristics and role in lacrimal secretion.
To develop a nomenclature for the lacrimal duct system in the rabbit, based on the anatomic and structural characteristics of each duct segment, and to provide RT-PCR and immunofluorescence data to support the notion that the duct system plays important roles in lacrimal function. Paraffin-embedded lacrimal glands (LGs) were stained with hematoxylin and eosin (H&E) and evaluated with a stereomicroscope. Cryosections of LG were stained with cresyl violet, and acinar cells and ductal epithelial cells were isolated from each duct segment by laser capture microdissection (LCM). mRNA levels from these cells were analyzed by real-time RT-PCR. Standard protocol was followed for immunofluorescence detection of ionic transporters. The lacrimal duct system was divided into six segments on the basis of morphologic characteristics: the intercalated, intralobular, interlobular, intralobar, interlobar, and main excretory ducts. Although the morphologic features change incrementally along the entire duct system, the gene expression of ionic transporters and aquaporins, including AE3, AQP4, AQP5, CFTR, ClC2gamma, KCC1, NHE1, NKAalpha1, NKAbeta1, NKAbeta2, NKAbeta3, and NKCC1 varied greatly among duct segments. Immunofluorescence results were generally in accordance with the abundance of mRNAs along the acinus-duct axis. Most LG research has focused on the acinar cells, with relatively little attention being paid to the lacrimal ducts. The lack of knowledge regarding the lacrimal ducts was so profound that a precise nomenclature had not been established for the duct system. The present data establish a nomenclature for each segment of the lacrimal duct system and provide evidence that ducts play critical roles in lacrimal secretion.


Age differences in autobiographical memories of negative events.
This study examined whether older adults recollect autobiographical memories of negative events so as to minimize unpleasant emotions to a greater extent than do younger adults. A sample of healthy older adults (N = 126) and younger adults (N = 119) completed the Autobiographical Memory Questionnaire and a measure of PTSD symptoms in response to their most negative recalled event. Results supported the hypothesis that older adults rated their negative memories as having: 1) less of a sense of traveling back to the time the event occurred, 2) less associated visceral emotional reactions, 3) fewer associated negative emotions, and 4) fewer PTSD symptoms, all relative to younger adults. In addition, older adults exhibited higher ratings of belief in accuracy, higher ratings that the memory comes as a coherent story, and more associated positive emotions, again all relative to younger adults. After controlling for differences between the types of events younger and older adults reported and how long ago the event occurred, the above age differences remained statistically significant, though the effect sizes were attenuated in some cases. These results are consistent in their support for the positivity effect, and suggest that older adults modify their recollections of negative events in a manner that is emotionally adaptive for them.


Detection of quinolone-resistant Neisseria gonorrhoeae.
The present National Committee for Clinical Laboratory Standards (NCCLS) guideline for testing Neisseria gonorrhoeae quinolone susceptibility defines only a susceptible category for ciprofloxacin, enoxacin, lomefloxacin, and ofloxacin, while susceptible, intermediate, and resistant categories are defined for fleroxacin. To further define the criteria for detection of quinolone resistance in gonococci, by standard disk diffusion and agar dilution methodologies recommended by the NCCLS, we tested 29 strains of quinolone-resistant N. gonorrhoeae (QRNG) recently isolated from ofloxacin-treated patients who were considered clinical failures. Regression analyses were performed on these results together with those of another 20 strains showing reduced susceptibility and 13 fully susceptible strains (ofloxacin MICs of < or = 0.25 microgram/ml). With 5-micrograms ofloxacin disks, resistance in 27 (93.1%) of the QRNG strains (MICs of > 1 microgram/ml) was detected by the criterion of a zone diameter of < 22 mm, while in the remaining 2 (6.9%), the disks failed to detect resistance. A cluster of 15 highly resistant strains showed ofloxacin MICs of > 4 micrograms/ml and zone diameters of < 13 mm. When tested with 5-micrograms ciprofloxacin disks, the corresponding values for resistance and high-level resistance of these QRNG strains were < 25 mm (MICs of > 0.5 micrograms/ml) and < 15 mm (MICs of > 2 micrograms /ml), respectively. Six strains for which ofloxacin MICs were > or = 8 micrograms/ml showed no zones at all with both 5-micrograms ofloxacin and 5-micrograms ciprofloxacin disks. These QRNG strains are now firmly established in the Southeast Asia region, and it is important for clinical laboratories to recognize these clinically resistant strains and to monitor their spread.


Colchicine's effects on lipoprotein particle concentrations in adults with metabolic syndrome: A secondary analysis of a randomized controlled trial.
Colchicine has received renewed interest for its potential beneficial effects in secondary prevention of cardiovascular disease. This was presumed to be primarily because of its anti-inflammatory effects; however, limited data exist regarding colchicine's impact on other cardiovascular risk factors. The aim of this study was to examine if colchicine's anti-inflammatory actions would lead to reduced circulating concentrations of oxidized low-density lipoprotein (oxLDL) in metabolically unhealthy individuals. We also examined if colchicine would improve concentrations of other atherogenic lipoprotein subfractions. This is a secondary analysis of a double-blind, randomized, placebo-controlled pilot study in which 40 adults with metabolic syndrome were randomized to colchicine 0.6 mg or placebo twice daily for 3 months. Blood samples were collected in the fasted state. OxLDL was measured using enzyme-linked immunosorbent assay. Nuclear magnetic resonance spectroscopy was used to measure other lipoprotein particle subfraction concentrations. Compared with placebo, colchicine reduced markers of inflammation, including C-reactive protein, erythrocyte sedimentation rate, and GlycA (P < .01). Concentrations of oxLDL (P = .019) and small LDL (P = .022) appeared significantly increased in the colchicine arm. Colchicine had no significant effect on other lipoprotein subfractions or lipoprotein particle sizes (all P > .05). Although colchicine may have benefit in secondary prevention of cardiovascular disease in at-risk individuals, we found no evidence that these effects are because of improvements in circulating atherogenic lipoprotein particle concentrations. Further studies are needed to confirm whether colchicine increases circulating oxLDL and small LDL levels in adults with metabolic syndrome. If true, additional research is warranted to elucidate the mechanisms underlying these associations.


A Computational Model of Innate Directional Selectivity Refined by Visual Experience.
The mammalian visual system has been extensively studied since Hubel and Wiesel's work on cortical feature maps in the 1960s. Feature maps representing the cortical neurons' ocular dominance, orientation and direction preferences have been well explored experimentally and computationally. The predominant view has been that direction selectivity (DS) in particular, is a feature entirely dependent upon visual experience and as such does not exist prior to eye opening (EO). However, recent experimental work has shown that there is in fact a DS bias already present at EO. In the current work we use a computational model to reproduce the main results of this experimental work and show that the DS bias present at EO could arise purely from the cortical architecture without any explicit coding for DS and prior to any self-organising process facilitated by spontaneous activity or training. We explore how this latent DS (and its corresponding cortical map) is refined by training and that the time-course of development exhibits similar features to those seen in the experimental study. In particular we show that the specific cortical connectivity or 'proto-architecture' is required for DS to mature rapidly and correctly with visual experience.


Biomarkers for Alzheimer's disease: current status and prospects for the future.
Accumulating data from the clinical research support that the core Alzheimer's disease (AD) cerebrospinal fluid (CSF) biomarkers amyloid-β (Aβ42), total tau (T-tau), and phosphorylated tau (P-tau) reflect key elements of AD pathophysiology. Importantly, a large number of clinical studies very consistently show that these biomarkers contribute with diagnostically relevant information, also in the early disease stages. Recent technical developments have made it possible to measure these biomarkers using fully automated assays with high precision and stability. Standardization efforts have given certified reference materials for CSF Aβ42, with the aim to harmonize results between assay formats that would allow for uniform global reference limits and cut-off values. These encouraging developments have led to that the core AD CSF biomarkers have a central position in the novel diagnostic criteria for the disease and in the recent National Institute on Aging and Alzheimer's Association biological definition of AD. Taken together, this progress will likely serve as the basis for a more general introduction of these diagnostic tests in clinical routine practice. However, the heterogeneity of pathology in late-onset AD calls for an expansion of the AD CSF biomarker toolbox with additional biomarkers reflecting additional aspects of AD pathophysiology. One promising candidate is the synaptic protein neurogranin that seems specific for AD and predicts future rate of cognitive deterioration. Further, recent studies bring hope for easily accessible and cost-effective screening tools in the early diagnostic evaluation of patients with cognitive problems (and suspected AD) in primary care. In this respect, technical developments with ultrasensitive immunoassays and novel mass spectrometry techniques give promise of biomarkers to monitor brain amyloidosis (the Aβ42/40 or APP669-711/Aβ42 ratios) and neurodegeneration (tau and neurofilament light proteins) in plasma samples, but future studies are warranted to validate these promising results further.


Residential Proximity to Major Roadways Is Associated With Increased Levels of AC133+ Circulating Angiogenic Cells.
Previous studies have shown that residential proximity to a roadway is associated with increased cardiovascular disease risk. Yet, the nature of this association remains unclear, and its effect on individual cardiovascular disease risk factors has not been assessed. The objective of this study was to determine whether residential proximity to roadways influences systemic inflammation and the levels of circulating angiogenic cells. In a cross-sectional study, cardiovascular disease risk factors, blood levels of C-reactive protein, and 15 antigenically defined circulating angiogenic cell populations were measured in participants (n=316) with moderate-to-high cardiovascular disease risk. Attributes of roadways surrounding residential locations were assessed using geographic information systems. Associations between road proximity and cardiovascular indices were analyzed using generalized linear models. Close proximity (<50 m) to a major roadway was associated with lower income and higher rates of smoking but not C-reactive protein levels. After adjustment for potential confounders, the levels of circulating angiogenic cells in peripheral blood were significantly elevated in people living in close proximity to a major roadway (CD31(+)/AC133(+), AC133(+), CD34(+)/AC133(+), and CD34(+)/45(dim)/AC133(+) cells) and positively associated with road segment distance (CD31(+)/AC133(+), AC133(+), and CD34(+)/AC133(+) cells), traffic intensity (CD31(+)/AC133(+) and AC133(+) cells), and distance-weighted traffic intensity (CD31(+)/34(+)/45(+)/AC133(+) cells). Living close to a major roadway is associated with elevated levels of circulating cells positive for the early stem marker AC133(+). This may reflect an increased need for vascular repair. Levels of these cells in peripheral blood may be a sensitive index of cardiovascular injury because of residential proximity to roadways.


Unilateral orchidectomy in donkey (Equus asinus): Evaluation of different surgical techniques, histological and morphological changes on remaining testis.
Unilateral orchidectomy (UO) is required when further breeding potential is important. It is sometimes necessary to remove a single testis in a matured stallion for therapeutic reasons. In this study, twelve donkeys were used to evaluate three techniques of unilateral castration, histological and morphological changes on the remaining testis. Results of the study showed that each of the surgical techniques used had its advantages and disadvantages in comparison with the other two techniques. Therefore the selection among the three techniques depends on the surgeon preferences and the environment in which the unilateral orchidectomy is performed. The volume of the remaining testis recorded at the end of the study was significantly greater than that estimated at the start of the study (p < 0.05). The percentage of sperm motility obtained from the remaining testis was significantly decreased (p < 0.05). Histological examination of the testis in open surgery (group I) (where the scrotum was left opened) revealed severe hemorrhages, edema and fibrosis. The test is showed degenerative changes in the seminiferous tubules and interstitial orchitis. Histological examination of the testes removed using a closed technique, (in groups II and III) where the scrotum wound was sutured, revealed hyperplasia of spermatogenic series and Leydig cells. In conclusion, unilateral orchidectomy had compensatory effects on the weight and volume of remaining testis. Adverse effects on sperm motility and viability can affect the fertility of the animal.


Subjective ratings of odorants by women with chemical sensitivity.
The purpose of the present study was to investigate whether women with chemical sensitivity rated the intensity and pleasantness of three odorants [peppermint, vanilla, and propylene glycol (PG)] and odorless room air differently than women without chemical sensitivity. The ratings of the experimental group (women with self-reported chemical sensitivity and no history of sexual abuse) were compared to those of two control groups who did not report chemical sensitivity [sexually abused (SA) women and healthy women without sexual abuse history]. All subjects were exposed to odorants and odorless control stimuli once a week for 3 consecutive weeks. Our findings indicate that women with chemical sensitivity perceive odorants as neither more or less intense nor more or less pleasant than women without chemical sensitivity. Moreover, the control women without sexual abuse outperformed the women in the other two groups by correctly identifying the target bottle containing the odorant. These findings suggest that perception of odorants alone is unlikely to account for the symptoms associated with chemical sensitivity. These findings, along with those of Doty et al. (1988), support the notion that olfactory-sensory function does not differ between individuals with and without chemical sensitivity.


A guide to guidelines for the treatment of posttraumatic stress disorder in adults: An update.
Clinical practice guidelines (CPGs) are used to support clinicians and patients in diagnostic and treatment decision-making. Along with patients' preferences and values, and clinicians' experience and judgment, practice guidelines are a critical component to ensure patients are getting the best care based on the most updated research findings. Most CPGs are based on systematic reviews of the treatment literature. Although most reviews are now restricted to randomized controlled trials, others may consider nonrandomized effectiveness trials. Despite a reliance on similar procedures and data, methodological decisions and the interpretation of the evidence by the guideline development panel can result in different recommendations. In this article, we will describe key methodological points for 5 recently released CPGs on the treatment of posttraumatic stress disorder in adults and highlight some of the differences in both the process and the subsequent recommendations. (PsycINFO Database Record (c) 2019 APA, all rights reserved).


Prognostic risk estimates of patients with multiple sclerosis and their physicians: comparison to an online analytical risk counseling tool.
Prognostic counseling in multiple sclerosis (MS) is difficult because of the high variability of disease progression. Simultaneously, patients and physicians are increasingly confronted with making treatment decisions at an early stage, which requires taking individual prognoses into account to strike a good balance between benefits and harms of treatments. It is therefore important to understand how patients and physicians estimate prognostic risk, and whether and how these estimates can be improved. An online analytical processing (OLAP) tool based on pooled data from placebo cohorts of clinical trials offers short-term prognostic estimates that can be used for individual risk counseling. The aim of this study was to clarify if personalized prognostic information as presented by the OLAP tool is considered useful and meaningful by patients. Furthermore, we used the OLAP tool to evaluate patients' and physicians' risk estimates. Within this evaluation process we assessed short-time prognostic risk estimates of patients with MS (final n = 110) and their physicians (n = 6) and compared them with the estimates of OLAP. Patients rated the OLAP tool as understandable and acceptable, but to be only of moderate interest. It turned out that patients, physicians, and the OLAP tool ranked patients similarly regarding their risk of disease progression. Both patients' and physicians' estimates correlated most strongly with those disease covariates that the OLAP tool's estimates also correlated with most strongly. Exposure to the OLAP tool did not change patients' risk estimates. While the OLAP tool was rated understandable and acceptable, it was only of modest interest and did not change patients' prognostic estimates. The results suggest, however, that patients had some idea regarding their prognosis and which factors were most important in this regard. Future work with OLAP should assess long-term prognostic estimates and clarify its usefulness for patients and physicians facing treatment decisions.


Test but not treat: Community members' experiences with barriers and facilitators to universal antiretroviral therapy uptake in rural KwaZulu-Natal, South Africa.
Antiretroviral therapy (ART) has revolutionised the care of HIV-positive individuals resulting in marked decreases in morbidity and mortality, and markedly reduced transmission to sexual partners. However, these benefits can only be realised if individuals are aware of their HIV-positive status, initiated and retained on suppressive lifelong ART. Framed using the socio-ecological model, the present study explores factors contributing to poor ART uptake among community members despite high acceptance of HIV-testing within a Treatment as Prevention (TasP) trial. In this paper we identify barriers and facilitators to treatment across different levels of the socio-ecological framework covering individual, community and health system components. This research was embedded within a cluster-randomised trial (ClinicalTrials.gov, number NCT01509508) of HIV treatment as Prevention in rural KwaZulu-Natal, South Africa. Data were collected between January 2013 and July 2014 from resident community members. Ten participants contributed to repeat in-depth interviews whilst 42 participants took part in repeat focus group discussions. Data from individual interviews and focus group discussions were triangulated using community walks to give insights into community members' perception of the barriers and facilitators of ART uptake. We used thematic analysis guided by a socio-ecological framework to analyse participants' narratives from both individual interviews and focus group discussions. Barriers and facilitators operating at the individual, community and health system levels influence ART uptake. Stigma was an over-arching barrier, across all three levels and expressed variably as fear of HIV disclosure, concerns about segregated HIV clinical services and negative community religious perceptions. Other barriers were individual (substance misuse, fear of ART side effects), community (alternative health beliefs). Facilitators cited by participants included individual (expectations of improved health and longer life expectancy following ART, single tablet regimens), community (availability of ART in the community through mobile trial facilities) and health system factors (fast and efficient service provided by friendly staff). We identified multiple barriers to achieving universal ART uptake. To enhance uptake in HIV care services, and achieve the full benefits of ART requires interventions that tackle persistent HIV stigma, and offer people with HIV respectful, convenient and efficient services. These interventions require evaluation in appropriately designed studies.


Time-of-Day Variation in SARS-CoV-2 RNA Levels during the Second Wave of COVID-19.
Circadian rhythms influence and coordinate an organism's response to its environment and to invading pathogens. We studied the diurnal variation in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA in nasal/throat swabs collected in late 2020 to spring 2021 in a population immunologically naïve to SARS-CoV-2 and prior to widespread vaccination. SARS-CoV-2 diagnostic PCR data from 1698 participants showed a significantly higher viral load in samples obtained in the afternoon, in males, and in hospitalised patients when linear mixed modelling was applied. This study illustrates the importance of recording sample collection times when measuring viral replication parameters in clinical and research studies.


The role of social influences and tobacco availability on adolescent smokeless tobacco use.
To examine the potential explanatory effect of various demographic, social influence, sanction, and tobacco availability variables on the use of smokeless tobacco (ST) by adolescent males. The data used in our analyses are from a community-based tobacco policy intervention trial that included a 60-item baseline school survey. During Spring 1993, all 8th, 9th, and 10th-grade students enrolled in 14 school districts in small Minnesota cities were surveyed. We used mixed-model logistic regression to determine which variables were significantly correlated with smokeless tobacco use by males in the past week. Of this sample of 2924 adolescent males, 10% (n = 291) reported using smokeless tobacco in the past week. Compared to the overall sample, smokeless tobacco users reported higher family and friend use of smokeless tobacco. In addition, 64% of users reported smoking in the past 30 days, and almost half (49.1%) said they had attempted to purchase tobacco in the past 30 days. Variables found to be significantly associated with smokeless tobacco use in the past week included younger age, having a best friend using tobacco, inflated perceptions of their peers' use of tobacco products, beliefs that school and parental sanctions are not high for tobacco use, recent tobacco purchase, and perceived belief that tobacco is not difficult to obtain from social sources. This study confirms previous research correlating demographic and social influence factors with ST use and demonstrates the role that sanction and availability variables play in ST use.


Posturography measures and efficacy of different physical treatments in somatic tinnitus.
Somatic modulation in tinnitus has been demonstrated by several studies although few investigations have been published on the efficacy of physical treatments in tinnitus subjects. In the present study the prevalence of somatic components to tinnitus were evaluated and the efficacy of two different physical treatments were compared: InterX® transcutaneous dynamic electrical stimulation and manual osteopathic therapy. Furthermore, posturographic measurements were analysed to verify the postural control in tinnitus subjects. 40 consecutive tinnitus patients, aged 18-65, were randomly selected for treatment (once a week for 2 months): 20 tinnitus subjects were treated with osteopathic manipulations, 20 with InterX®. They were evaluated pre and post therapy with audiogram up to 16 kHz, tinnitus pitch and loudness match, MML, THI questionnaire, posturography, structured interview with special attention on postural and movement influence on tinnitus, physical evaluation and osteopathic evaluation. 40 controls with no tinnitus, underwent audiological tests, postural and osteopathic evaluation for comparison. In our population, tinnitus sufferers presented more frequently musculoscheletal strains assessed with osteopathic visit and postural problems assessed with posturography measures in comparison with controls. Posturographic test, showed an average oscillating areas significantly greater in tinnitus participants (p ≤ 0.05), compared with control subjects. On the average in the treated groups, the enveloped areas were not significantly affected by either of the treatments. Tinnitus improved subjectively in most patients: loudness decreased, % time of awareness, % time of annoyance and quality of life was overall perceived as improved. This was mostly evident in subjects with muscular strain and tensions. This study indicates the benefit of physical, manipulation therapy for those patients with somatic modulation of their tinnitus, further studies are needed to establish the diagnostic or prognostic role of posturographic measurements.


Sawfly Genomes Reveal Evolutionary Acquisitions That Fostered the Mega-Radiation of Parasitoid and Eusocial Hymenoptera.
The tremendous diversity of Hymenoptera is commonly attributed to the evolution of parasitoidism in the last common ancestor of parasitoid sawflies (Orussidae) and wasp-waisted Hymenoptera (Apocrita). However, Apocrita and Orussidae differ dramatically in their species richness, indicating that the diversification of Apocrita was promoted by additional traits. These traits have remained elusive due to a paucity of sawfly genome sequences, in particular those of parasitoid sawflies. Here, we present comparative analyses of draft genomes of the primarily phytophagous sawfly Athalia rosae and the parasitoid sawfly Orussus abietinus. Our analyses revealed that the ancestral hymenopteran genome exhibited traits that were previously considered unique to eusocial Apocrita (e.g., low transposable element content and activity) and a wider gene repertoire than previously thought (e.g., genes for CO2 detection). Moreover, we discovered that Apocrita evolved a significantly larger array of odorant receptors than sawflies, which could be relevant to the remarkable diversification of Apocrita by enabling efficient detection and reliable identification of hosts.


Treatment of invasive candidiasis in neutropenic patients: systematic review of randomized controlled treatment trials.
Candidemia and invasive candidiasis (CIC) is associated with considerable morbidity and mortality, with a paucity of controlled data in neutropenic patients. A systematic review was conducted of available data for the treatment of CIC during neutropenia. A structured OVID search of multiple databases was performed. Data from randomized controlled trials of CIC and of empirical antifungal therapy in febrile neutropenic patients was included. A total of 17 trials randomizing 342 neutropenic patients were included. Eight of the studies compared amphotericin B (AmB) to other non-polyene antifungal agents. Pooling of results favored use of comparator compounds (odds ratio [OR] 0.73; 95% confidence interval [CI] 0.42-1.29). To strengthen our analysis, a pre-planned sensitivity analysis was also conducted. Overall, there was a non-significant benefit in favor of non-polyene compounds. Across studies, echinocandins provided the benefit of favorable outcomes with fewest side effects and toxicity.


Toward a Common Terminology for the Gyri and Sulci of the Human Cerebral Cortex.
The gyri and sulci of the human brain were defined by pioneers such as Louis-Pierre Gratiolet and Alexander Ecker, and extensified by, among others, Dejerine (1895) and von Economo and Koskinas (1925). Extensive discussions of the cerebral sulci and their variations were presented by Ono et al. (1990), Duvernoy (1992), Tamraz and Comair (2000), and Rhoton (2007). An anatomical parcellation of the spatially normalized single high resolution T1 volume provided by the Montreal Neurological Institute (MNI; Collins, 1994; Collins et al., 1998) was used for the macroscopical labeling of functional studies (Tzourio-Mazoyer et al., 2002; Rolls et al., 2015). In the standard atlas of the human brain by Mai et al. (2016), the terminology from Mai and Paxinos (2012) is used. It contains an extensively analyzed individual brain hemisphere in the MNI-space. A recent revision of the terminology on the central nervous system in the Terminologia Anatomica (TA, 1998) was made by the Working Group Neuroanatomy of the Federative International Programme for Anatomical Terminology (FIPAT) of the International Federation of Associations of Anatomists (IFAA), and posted online as the Terminologia Neuroanatomica (TNA, 2017: http://FIPAT.library.dal.ca) as the official FIPAT terminology. This review deals with the various terminologies for the cerebral gyri and sulci, aiming for a common terminology.


PROTEIN SYNTHESIS DURING DEVELOPMENT: CONTROL THROUGH MESSENGER RNA.
Utilization of long-lived messenger RNA appears to be the exception rather than the rule in cells which are differentiating and synthesizing large amounts of specialized product at the same time. The fact that polyribosomes synthesize protein after RNA synthesis is turned off by actinomycin D is used to demonstrate messenger RNA of long half-life. The data suggest that most tissues examined have short-lived messenger RNA's, but the ocular lens can synthesize protein after an incubation of 24 hours in 40 microg of actinomycin D per milliliter. A common basis for the presence of long-lived messenger RNA in the cells of the lens, the feather, and in reticulocytes is discussed.


A new computerized adaptive test advancing the measurement of health-related quality of life (HRQoL) in children: the Kids-CAT.
Assessing health-related quality of life (HRQoL) via Computerized Adaptive Tests (CAT) provides greater measurement precision coupled with a lower test burden compared to conventional tests. Currently, there are no European pediatric HRQoL CATs available. This manuscript aims at describing the development of a HRQoL CAT for children and adolescents: the Kids-CAT, which was developed based on the established KIDSCREEN-27 HRQoL domain structure. The Kids-CAT was developed combining classical test theory and item response theory methods and using large archival data of European KIDSCREEN norm studies (n = 10,577-19,580). Methods were applied in line with the US PROMIS project. Item bank development included the investigation of unidimensionality, local independence, exploration of Differential Item Functioning (DIF), evaluation of Item Response Curves (IRCs), estimation and norming of item parameters as well as first CAT simulations. The Kids-CAT was successfully built covering five item banks (with 26-46 items each) to measure physical well-being, psychological well-being, parent relations, social support and peers, and school well-being. The Kids-CAT item banks proved excellent psychometric properties: high content validity, unidimensionality, local independence, low DIF, and model conform IRCs. In CAT simulations, seven items were needed to achieve a measurement precision between .8 and .9 (reliability). It has a child-friendly design, is easy accessible online and gives immediate feedback reports of scores. The Kids-CAT has the potential to advance pediatric HRQoL measurement by making it less burdensome and enhancing the patient-doctor communication.


Improved PCR-DGGE for high resolution diversity screening of complex sulfate-reducing prokaryotic communities in soils and sediments.
In this study we evaluated a high resolution PCR-DGGE strategy for the characterization of complex sulfate-reducing microbial communities inhabiting natural environments. dsrB fragments were amplified with a two-step nested PCR protocol using combinations of primers targeting the dissimilatory (bi)sulfite reductase genes. The PCR-DGGE conditions were initially optimized using a dsrAB clone library obtained from a vegetated intertidal riparian soil along the river Rhine (Rozenburg, the Netherlands). Partial dsrB were successfully amplified from the same environmental DNA extracts used to construct the library, DGGE-separated and directly sequenced. The two approaches were in good agreement: the phylogenetic distribution of clones and DGGE-separated dsrB was comparable, suggesting the presence of sulfate-reducing prokaryotes (SRP) belonging to the families 'Desulfobacteraceae,' 'Desulfobulbaceae' and 'Syntrophobacteraceae,' and to the Desulfomonile tiedjei- and Desulfobacterium anilini-groups. The nested PCR-DGGE was also used to analyze sediment samples (Appels, Belgium) from a series of microcosms subjected to a tidal flooding regime with water of different salinity, and proved to be a valid tool also to monitor the SRP community variation over time and space as a consequence of environmental changes.


Nonlinear dependence between the surface reflectance and the duty-cycle of semiconductor nanorod array.
The nonlinear dependence between the duty-cycle of semiconductor nanorod array and its surface reflectance minimization is demonstrated. The duty-cycle control on thin-SiO2 covered Si nanorod array is performed by O(2-) plasma pre-etching the self-assembled polystyrene nanosphere array mask with area density of 4 × 10(8) rod/cm(-2). The 120-nm high SiO2 covered Si nanorod array is obtained after subsequent CF4/O2 plasma etching for 160 sec. This results in a tunable nanorod diameter from 445 to 285 nm after etching from 30 to 80 sec, corresponding to a varying nanorod duty-cycle from 89% to 57%. The TM-mode reflection analysis shows a diminishing Brewster angle shifted from 71° to 54° with increasing nanorod duty-cycle from 57% to 89% at 532 nm. The greatly reduced small-angle reflectance reveals a nonlinear trend with enlarging duty-cycle, leading to a minimum surface reflectance at nanorod duty-cycle of 85%. Both the simulation and experiment indicate that such a surface reflectance minimum is even lower than that of a uniformly SiO2 covered Si substrate on account of its periodical nanorod array architecture with tuned duty-cycle.


An Outbreak of Leaf Spot Caused by Corynespora cassiicola on Korean Raspberry in Korea.
In September and October 2010, leaf spots were observed on Korean raspberry (Rubus crataegifolius Bunge) plants in farmers' fields in Hapcheon, Gyeongnam Province, South Korea. Disease incidence ranged from 50 to 80% among fields. Circular- to irregular-shaped spots surrounded by yellow halos occurred frequently on the leaves of Korean raspberry plants. Brown spots became dark with wavy borders and ranged from 20 to 300 mm in diameter. Infected leaves became chlorotic, blighted, and eventually died. Fungal hyphae covered the lesions with abundant conidia and conidiophores. Fresh leaf specimens were collected from infected plants and the putative causal pathogen was isolated onto potato dextrose agar (PDA). A total of 30 isolates of the fungus were collected from diseased plants collected in the field. Fungal colonies were gray to brown on PDA. Colonies formed conidia, 38 to 210 × 8 to 20 μm, which were solitary or catenary, obclavate to cylindrical, smooth, straight or curved, and subhyaline to pale brown or brown. Conidiophores, 98 to 840 × 4 to 12 μm, were slightly or conspicuously swollen at apex, single, simple, straight or slightly flexuous, pale to midbrown, smooth, septate, thick, monotretic, and determinate or in tufts. Morphological characteristics of the fungal specimens were similar to descriptions of Corynespora cassiicola (1). A representative isolate of the pathogen was used to inoculate leaves of Korean raspberry plants for pathogenicity testing. Five leaves of a 3-month-old potted plant were sprayed with a suspension of conidia in water. Conidia were harvested from PDA cultures and adjusted to 2 × 104 conidia/ml with a hemocytometer. Five leaves sprayed with sterile distilled water served as controls. Inoculated plants were placed in a humid chamber with 100% relative humidity at 30°C for 24 h and then moved to a greenhouse. Symptoms similar to those observed in the farmers' fields developed on the inoculated leaves within 12 days, whereas the controls remained asymptomatic. The causal fungus was reisolated from the lesions of inoculated plants to satisfy Koch's postulates. To confirm the identity of the fungus, the complete internal transcribed spacer (ITS) rDNA region was amplified and sequenced (3). Amplification of the ITS region generated a 559-bp sequence (GenBank Accession No. JQ340026) with 100% similarity to sequences of C. cassiicola in GenBank (Accession No. GU138988) causing leaf spot on cassava (2). Based on the symptoms, morphological characteristics, pathogenicity, and molecular identification, this fungus was identified as C. cassiicola (1). To our knowledge, this is the first report of leaf spot caused by C. cassiicola on Korean raspberry. The recent occurrence of leaf spot on Korean raspberry suggests that C. cassiicola is spreading widely and posing a serious threat to these plants in Korea. References: (1) M. B. Ellis et al. No. 303 in: CMI Descriptions of Pathogenic Fungi and Bacteria. Surrey, Kew, UK, 1971. (2) X.-B. Liu et al. Plant Dis. 94:916, 2010. (3) T. J. White et al. Page 315 in: PCR Protocols: A Guide to Methods and Applications. M. A. Innis et al., eds. Academic Press, Inc., New York, 1990.