Flexible gaze-following in rhesus monkeys.
Humans are characterized by complex social cognitive abilities that emerge early in development. Comparative studies of nonhuman primates can illuminate the evolutionary history of these social capacities. We examined the cognitive skills that rhesus monkeys (Macaca mulatta) use to follow gaze, a foundational skill in human social development. While rhesus monkeys can make inferences about others' gaze when competing, it is unclear how they think about gaze information in other contexts. In study 1, monkeys (n = 64) observed a demonstrator look upwards either in a barrier condition where a box was overhead, so that monkeys could not see the target of her gaze, or a no barrier condition where nothing blocked her view. In study 2, monkeys (n = 59) could approach to observe the target of the demonstrator's gaze when the demonstrator looked behind a barrier on the ground or, in the no barrier condition, behind a window frame in the same location. Monkeys were more likely to directly look up in study 1 if they could initially see the location where the demonstrator was looking, but they did not preferentially reorient their bodies to observe the out-of-view location when they could not see that location. In study 2, monkeys did preferentially reorient, but at low rates. This indicates that rhesus monkeys can use social cognitive processes outside of competitive contexts to model what others can or cannot see, but may not be especially motivated to see what others look at in non-competitive contexts, as they reorient infrequently or in an inconsistent fashion. These similarities and differences between gaze-following in monkeys and children can help to illuminate the evolution of human social cognition.


Occupational toxicant inhalation injury: the World Trade Center (WTC) experience.
Clinical descriptive data is presented on a group of 554 former workers and volunteers (with more than 90 different occupations) at the World Trade Center (WTC) disaster site. A subsample of 168 workers (30% of the group) was selected to examine lower airway disease risk in relation to smoking and WTC exposure variables. Five diagnostic categories clearly predominate: upper airway disease (78.5%), gastroesophageal reflux disease (57.6%), lower airway disease (48.9%), psychological (41.9%) and chronic musculoskeletal illnesses (17.8%). The most frequent pattern of presentation was a combination of the first three of those categories (29.8%). Associations were found between arrival at the WTC site within the first 48 h of the terrorist attack and lower airway and gastroesophageal reflux disease, and between past or present cigarette smoking and lower airway disease. Occupational exposures at the WTC remain consistently associated with a disease profile, which includes five major diagnostic categories. These conditions often coexist in different combinations, which (as expected) mutually enhances their clinical expression, complicates medical management, and slows recovery. Cigarette smoking and early arrival at the WTC site appear to be risk factors for lower airway disease diagnosis.


Perinatal interventions and survival in resource-poor settings: which work, which don't, which have the jury out?
Perinatal conditions make the largest contribution to the burden of disease in low-income countries. Although postneonatal mortality rates have declined, stillbirth and early neonatal mortality rates remain high in many countries in Africa and Asia, and there is a concentration of mortality around the time of birth. Our article begins by considering differences in the interpretation of 'intervention' to improve perinatal survival. We identify three types of a single action, a collection of actions delivered in a package and a broader social or system approach. We use this classification to summarise the findings of recent systematic reviews and meta-analyses. After describing the growing evidence base for the effectiveness of community-based perinatal care, we discuss current concerns about integration: of women's and children's health programmes, of community-based and institutional care, and of formal and informal sector human resources. We end with some thoughts on the complexity of choices confronting women and their families in low-income countries, particularly in view of the growth in non-government and private sector healthcare.


Psychometric testing of the Norwegian version of the Nutritional Form For the Elderly among older home-dwelling people.
Nutritional screening instruments need to be evaluated in terms of reliability and validity and being able to demonstrate sensitivity and specificity for use in clinical practice and research. The aims of this study were to test the reliability and validity of the Norwegian version of the Nutritional Form For the Elderly (NUFFE-NO) in a sample of older home-dwelling people, and to use the short form of the Mini Nutritional Assessment (MNA-SF) as a standard. A postal questionnaire, including the two instruments, background variables, and health-related questions, was sent to 6033 home-dwelling older people (65+ years) in southern Norway. In total, 2106 persons responded and were included. Data were analyzed statistically regarding homogeneity, concurrent and construct validity, sensitivity, and specificity of NUFFE-NO. A Cronbach's alpha coefficient of 0.71 and significant item-to-total correlations were obtained as measures of homogeneity. Concurrent validity was assessed by a correlation coefficient of -0.37 (P < 0.001) between NUFFE-NO and MNA-SF. NUFFE-NO could separate known nutritional at-risk groups as a measure of construct validity. A cut-off point of ≥4 for identification of older people at nutritional risk was found for NUFFE-NO with MNA-SF as a standard. NUFFE-NO shows adequate psychometric properties regarding homogeneity and construct validity. MNA-SF was not found to be the most suitable standard to use, because a low correlation coefficient was obtained as a measure of concurrent validity and a lower cut-off point was found compared with another study using the Mini Nutritional Assessment (MNA(®)) as a standard for NUFFE-NO. The obtained cut-off point of ≥4 is not recommended for use in practice or research, because many false positive nutritional at-risk persons would then be identified. Further studies with suitable design have to be performed among older home-dwelling people using the MNA as a standard.


Left ventricular volume shifts and aortic root expansion during isovolumic contraction.
Aortic valve opening involves conformational changes of the aortic root, including the ventricular-aortic junction (VAJ), sinotubular junction (STJ), and cusps. Moreover, the aortic root is contiguous with the left ventricular outflow tract (LVOT), which changes diameter throughout the cardiac cycle. Aortic root expansion prior to valve opening facilitates outward displacement of aortic cusp attachments, which helps flatten the cusps, thereby reducing cusp stress and fatigue, ultimately enhancing functional valve durability. The mechanisms underlying aortic root expansion prior to valve opening, however, remain incompletely characterized. The study aim was to establish a link between such aortic root expansion and intraventricular volume shifts into the LVOT during isovolumic contraction (IVC). Miniature radiopaque markers were implanted on the left ventricle, VAJ, STJ, and aortic cusps of six sheep. After one week, 3-D marker coordinates were obtained using biplane videofluoroscopy (60 Hz). Triangular areas at the VAJ and STJ were calculated; LV main chamber (non-LVOT) and LVOT volumes were calculated using multiple tetrahedra. End-diastole was defined as the peak of the electrocardiogram R-wave, and end-IVC when aortic cusp separation began. During IVC, blood within the left ventricle was redistributed to the LVOT: mean LVOT volume was increased (+0.2 +/- 0.1 ml, p = 0.009) as non-LVOT volume fell (-0.8 +/- 0.4 ml, p = 0.006). Concomitantly, the aortic root expanded as both VAJ and STJ areas increased (+0.23 +/- 0.12 cm2 (p = 0.005) and +0.25 +/- 0.14 cm2 (p = 0.007), respectively) prior to aortic cusp separation. Aortic root expansion prior to valve opening is closely related to intraventricular volume shifts into the LVOT during IVC. Such volume shifts may 'prime' the aortic valve for ejection. These findings expand our understanding of cardiac dynamics by showing that blood acts as a coupling link between various cardiac units. Preservation of these normal aortic root dynamics may enhance the efficacy and durability of aortic surgical interventions.


Hydrodifluoromethylation of Alkenes with Difluoroacetic Acid.
A facile method for the regioselective hydrodifluoromethylation of alkenes is reported using difluoroacetic acid and phenyliodine(III) diacetate in tetrahydrofuran under visible-light activation. This metal-free approach stands out as it uses inexpensive reagents, does not require a photocatalyst, and displays broad functional group tolerance. The procedure is also operationally simple and scalable, and provides access in one step to high-value building blocks for application in medicinal chemistry.


Early and later vocalization skills in children with and without cleft palate.
The purpose of this study was to describe the early vocalization skills in children with cleft lip and palate (CLP) at 6 and 12 months of age and compare these early vocalization measures to later speech and vocabulary development at 30 months of age. The participants in the study included 13 children without cleft lip or palate (NCLP) who were typically developing and 13 children with CLP matched for age, gender and socioeconomic status. Standardized measures of cognition, language, hearing, and prelinguistic vocalization measures were administered at 6 and 12 months and speech production, and vocabulary measures were collected at 30 months of age. Group differences were observed in both receptive and expressive language development at 12 and 30 months of age. Group differences were observed in the frequency of babbling and Mean Babbling Level at 12 months and speech sound accuracy and vocabulary production at 30 months of age. Significant correlation coefficients were observed between babbling frequency at 6 months and consonant inventory size, vocabulary at 30 months for the children with clefts and PCC-R for noncleft children. This study documented that young children with clefts have persistent vocalization and vocabulary deficits well beyond palate closure. Measures of babbling frequency, Mean Babbling Level and consonant inventories provide clinically effective means of identifying these early deficits. Additionally, these measures may provide a tool for monitoring the effects of early intervention programs that promote facilitation of sound and vocabulary development.


MicroRNAs in kidney injury and disease.
MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression by degrading or repressing the translation of their target messenger RNAs. As miRNAs are critical regulators of cellular homeostasis, their dysregulation is a crucial component of cell and organ injury. A substantial body of evidence indicates that miRNAs are involved in the pathophysiology of acute kidney injury (AKI), chronic kidney disease and allograft damage. Different subsets of miRNAs are dysregulated during AKI, chronic kidney disease and allograft rejection, which could reflect differences in the physiopathology of these conditions. miRNAs that have been investigated in AKI include miR-21, which has an anti-apoptotic role, and miR-214 and miR-668, which regulate mitochondrial dynamics. Various miRNAs are downregulated in diabetic kidney disease, including the miR-30 family and miR-146a, which protect against inflammation and fibrosis. Other miRNAs such as miR-193 and miR-92a induce podocyte dedifferentiation in glomerulonephritis. In transplantation, miRNAs have been implicated in allograft rejection and injury. Further work is needed to identify and validate miRNAs as biomarkers of graft function and of kidney disease development and progression. Use of combinations of miRNAs together with other molecular markers could potentially improve diagnostic or predictive power and facilitate clinical translation. In addition, targeting specific miRNAs at different stages of disease could be a promising therapeutic strategy.


Spatial autocorrelation of local patch extinctions drives recovery dynamics in metacommunities.
Human activities put ecosystems under increasing pressure, often resulting in local extinctions. However, it is unclear how local extinctions affect regional processes, such as the distribution of diversity in space, especially if extinctions show spatial patterns, such as being clustered. Therefore, it is crucial to investigate extinctions and their consequences in a spatially explicit framework. Using highly controlled microcosm experiments and theoretical models, we ask here how the number and spatial autocorrelation of extinctions interactively affect metacommunity dynamics. We found that local patch extinctions increased local diversity (α-diversity) and inter-patch diversity (β-diversity) by delaying the exclusion of inferior competitors. Importantly, recolonization dynamics depended more strongly on the spatial distribution than on the number of patch extinctions: clustered local patch extinctions resulted in slower recovery, lower α-diversity and higher β-diversity. Our results highlight that the spatial distribution of perturbations should be taken into account when studying and managing spatially structured communities.


Prophylactic platelet transfusion for prevention of bleeding in patients with haematological disorders after chemotherapy and stem cell transplantation.
Platelet transfusions are used in modern clinical practice to prevent and treat bleeding in thrombocytopenic patients with bone marrow failure. Although considerable advances have been made in platelet transfusion therapy in the last 40 years, some areas continue to provoke debate especially concerning the use of prophylactic platelet transfusions for the prevention of thrombocytopenic bleeding. To determine the most effective use of platelet transfusion for the prevention of bleeding in patients with haematological disorders undergoing chemotherapy or stem cell transplantation. This is an update of a Cochrane review first published in 2004. We searched for randomised controlled trials (RCTs) in the Cochrane Central Register of Controlled Trials (CENTRAL Issue 4, 2011), MEDLINE (1950 to Nov 2011), EMBASE (1980 to Nov 2011) and CINAHL (1982 to Nov 2011), using adaptations of the Cochrane RCT search filter, the UKBTS/SRI Transfusion Evidence Library, and ongoing trial databases to 10 November 2011. RCTs involving transfusions of platelet concentrates, prepared either from individual units of whole blood or by apheresis, and given to prevent bleeding in patients with haematological disorders. Four different types of prophylactic platelet transfusion trial were included. In the original review one author initially screened all electronically derived citations and abstracts of papers, identified by the review search strategy, for relevancy. Two authors performed this task in the updated review. Two authors independently assessed the full text of all potentially relevant trials for eligibility. Two authors completed data extraction independently. We requested missing data from the original investigators as appropriate. There were 18 trials that were eligible for inclusion, five of these were still ongoing.Thirteen completed published trials (2331 participants) were included for analysis in the review. The original review contained nine trials (718 participants). This updated review includes six new trials (1818 participants).Two trials (205 participants) in the original review are now excluded because fewer than 80% of participants had a haematological disorder.The four different types of prophylactic platelet transfusion trial, that were the focus of this review, were included within these thirteen trials.Three trials compared prophylactic platelet transfusions versus therapeutic-only platelet transfusions. There was no statistical difference between the number of participants with clinically significant bleeding in the therapeutic and prophylactic arms but the confidence interval was wide (RR 1.66; 95% CI 0.9 to 3.04).The time taken for a clinically significant bleed to occur was longer in the prophylactic platelet transfusion arm. There was a clear reduction in platelet transfusion usage in the therapeutic arm. There was no statistical difference between the number of participants in the therapeutic and prophylactic arms with platelet refractoriness, the only adverse event reported.Three trials compared different platelet count thresholds to trigger administration of prophylactic platelet transfusions. No statistical difference was seen in the number of participants with clinically significant bleeding (RR 1.35; 95% CI 0.95 to 1.9), however, this type of bleeding occurred on fewer days in the group of patients transfused at a higher platelet count threshold (RR 1.72; 95% CI 1.33 to 2.22).The lack of a difference seen for the number of participants with clinically significant bleeding may be due to the studies, in combination, having insufficient power to demonstrate a difference, or due to masking of the effect by a higher number of protocol violations in the groups of patients with a lower platelet count threshold. Using a lower platelet count threshold led to a significant reduction in the number of platelet transfusions used. There were no statistical differences in the number of adverse events reported between the two groups.Six trials compared different doses of prophylactic platelet transfusions. There was no evidence to suggest that using a lower platelet transfusion dose increased: the number of participants with clinically significant (WHO grade 2 or above) (RR 1.02; 95% CI 0.93 to 1.11), or life-threatening (WHO grade 4) bleeding (RR 1.87; 95% CI 0.86 to 4.08). A higher platelet transfusion dose led to a reduction in the number of platelet transfusion episodes, but an increase in total platelet utilisation. Only one adverse event, wheezing after transfusion, had a significantly higher incidence when standard and high dose transfusions were compared but this difference was not seen when low dose and high dose transfusions were compared. It is therefore likely to be a type I error (false positive).One small trial compared prophylactic platelet transfusions versus platelet-poor plasma. The risk of a significant bleed was decreased in the prophylactic platelet transfusion arm (RR 0.47; 95% CI 0.23 to 0.95) and this was statistically significant.All studies had threats to validity; the majority of these were due to methodology of the studies not being described in adequate detail.Although it was not the main focus of the review, it was interesting to note that in one of the pre-specified sub-group analyses (treatment type) two studies showed that patients receiving an autologous transplant have a lower risk of bleeding than patients receiving intensive chemotherapy or an allogeneic transplant (RR 0.73, 95% CI 0.65 to 0.82). These conclusions refer to the four different types of platelet transfusion trial separately. Firstly, there is no evidence that a prophylactic platelet transfusion policy prevents bleeding. Two large trials comparing a therapeutic versus prophylactic platelet transfusion strategy, that have not yet been published, should provide important new data on this comparison. Secondly, there is no evidence, at the moment, to suggest a change from the current practice of using a platelet count of 10 x 10(9)/L. However, the evidence for a platelet count threshold of 10 x 10(9)/L being equivalent to 20 x 10(9)/L is not as definitive as it would first appear and further research is required. Thirdly, platelet dose does not affect the number of patients with significant bleeding, but whether it affects number of days each patient bleeds for is as yet undetermined. There is no evidence that platelet dose affects the incidence of WHO grade 4 bleeding.Prophylactic platelet transfusions were more effective than platelet-poor plasma at preventing bleeding.


Relationship between insulin resistance, weight loss, and coronary heart disease risk in healthy, obese women.
Several popular books have recently been published stating that being insulin-resistant favors weight gain and/or prevents weight loss. Because this view seems to have gained widespread support in the general population, we thought it important to perform the current study testing the hypothesis that differences in insulin-mediated glucose disposal do not affect weight loss in response to calorie-restricted diets. For this purpose, we studied the change in weight and risk factors for coronary heart disease (CHD) in healthy women volunteers, defined as being obese on the basis of a body mass index (BMI) greater than 30.0 kg/m(2). The insulin suppression test was used to stratify obese women at baseline into insulin-resistant and insulin-sensitive subgroups on the basis of their steady-state plasma glucose (SSPG) concentration at the end of a 180-minute infusion of octreotide, exogenous insulin, and glucose. They were then instructed on a calorie-restricted diet plus sibutraminine (15 mg/day) for a total period of 4 months. Baseline measurements also included determination of fasting lipid and lipoprotein concentrations, and hourly (8 AM to 4 PM) determinations of plasma glucose and insulin concentrations before and after breakfast and lunch. Twenty-four women completed the 4-month period of calorie restriction: 13 classified as insulin-resistant (SSPG = 219 +/- 7 mg/dL) and 11 as insulin-sensitive (SSPG = 69 +/- 6 mg/dL). The insulin-resistant group also had higher (P =.03) plasma triglyceride (TG) concentrations and a higher ratio of total to high-density lipoprotein (HDL) cholesterol concentration (P =.02) at baseline. Both groups lost a significant amount of weight during the study, and there was no difference between the weight loss in the insulin-resistant (8.6 +/- 1.3 kg) and insulin-sensitive (7.9 +/- 1.4 kg) groups. Weight loss in the insulin-resistant group was also associated with a significant decrease in SSPG concentration (219 +/- 7 to 144 +/- 14 mg/dL), associated with significantly lower fasting TG concentrations (P <.001) and day-long concentrations of plasma glucose and insulin (P <.005). None of these variables changed in the insulin-sensitive group. These results indicate that: (1) CHD risk factors in obese women vary as a function of being insulin-resistant or insulin-sensitive; (2) dramatic variations in insulin-mediated glucose disposal do not modulate weight loss in response to calorie-restricted diets, and (3) weight loss is effective in reducing CHD risk in insulin-resistant, obese women. Given these data, it seems obvious that attempts to reduce CHD risk factors by weight loss should focus on obese individuals who are also insulin-resistant.


Sexual and injection-related risks in Puerto Rican-born injection drug users living in New York City: A mixed-methods analysis.
These data were collected as part of the National HIV Behavioral Surveillance (NHBS) study. NHBS is a cross-sectional study to investigate HIV behavioral risks among core risk groups in 21 U.S. cities with the highest HIV/AIDS prevalence. This analysis examines data from the NHBS data collection cycle with IDU conducted in New York City in 2009. We explored how the recency of migration from Puerto Rico (PR) to New York City (NYC) impacts both syringe sharing and unprotected sex among injection drug users (IDU) currently living in NYC. We used a mixed-methods approach to examine differences in risk between US-born IDU, PR IDU who migrated to NYC more than three years ago (non-recent migrants), and PR IDU who migrated in the last three years (recent migrants). Respondent-driven sampling (RDS) was used to recruit the sample (n = 514). In addition, qualitative individual and group interviews with recent PR migrants (n = 12) and community experts (n = 2) allowed for an in-depth exploration of the IDU migration process and the material and cultural factors behind continued risk behaviors in NYC. In multiple logistic regression controlling for confounding factors, recent migrants were significantly more likely to report unprotected sexual intercourse with casual or exchange partners (adjusted odds ratio [AOR]: 2.81; 95% confidence intervals [CI]: 1.37-5.76) and receptive syringe sharing (AOR = 2.44; 95% CI: 1.20-4.97) in the past year, compared to US-born IDU. HIV and HCV seroprevalence were highest among non-recent migrants. Qualitative results showed that risky injection practices are partly based on cultural norms acquired while injecting drugs in Puerto Rico. These same results also illustrate how homelessness influences risky sexual practices. Poor material conditions (especially homelessness) may be key in triggering risky sexual practices. Cultural norms (ingrained while using drugs in PR) around injection drug use are perpetuated in their new setting following an almost natural flow. These norms may have a particular stronghold over risky drug injection practices. These results indicate that culturally appropriate HIV and HCV prevention and education services are needed. In addition, homelessness should be addressed to reduce risky sexual practices.


Shoulder Arthroplasty for Humeral Head Avascular Necrosis Is Associated With Increased Postoperative Complications.
Humeral head avascular necrosis (AVN) of differing etiologies may lead to shoulder arthroplasty due to subchondral bone collapse and deformity of the articular surface. There have been no large studies evaluating the complications for these patients after they undergo total shoulder arthroplasty (TSA). The first objective of this study is to evaluate the complication rate after TSA in patients with humeral head AVN. The secondary objective is to compare the complication rates among the different etiologies of the AVN. Patients who underwent TSA were identified in the PearlDiver database using ICD-9 codes. Patients who underwent shoulder arthroplasty for humeral head AVN were identified using ICD-9 codes and were subclassified according to AVN etiology (posttraumatic, alcohol use, chronic steroid use, and idiopathic). Complications evaluated included postoperative infection within 6 months, dislocation within 1 year, revision shoulder arthroplasty up to 8 years postoperatively, shoulder stiffness within 1 year, and periprosthetic fracture within 1 year and systemic complications within 3 months. Postoperative complication rates were compared to controls. The study cohorts included 4129 TSA patients with AVN with 141,778 control TSA patients. Patients with posttraumatic AVN were significantly more likely to have a postoperative infection (OR 2.47, P < 0.001), dislocation (OR 1.45, P = 0.029), revision surgery (OR 1.53, P = 0.001), stiffness (OR 1.24, P = 0.042), and systemic complication (OR 1.49, P < 0.001). Steroid-associated AVN was associated with a significantly increased risk for a postoperative infection (OR 1.72, P = 0.004), revision surgery (OR 1.33, P = 0.040), fracture (OR 2.76, P = 0.002), and systemic complication (OR 1.59, P < 0.001). Idiopathic and alcohol-associated AVN were not significantly associated with any of the postoperative evaluated complications. TSA in patients with humeral head AVN is associated with significantly increased rates of numerous postoperative complications compared to patients without a diagnosis of AVN, including infection, dislocation, revision arthroplasty, stiffness, periprosthetic fracture, and medical complications. Specifically, AVN due to steroid use or from a posttraumatic cause appears to be associated with the statistically highest rates of postoperative TSA complications. Given these findings, orthopedic surgeons should be increasingly aware of this association, which should influence the shared decision-making process of undergoing TSA in patients with humeral head AVN.


Vasodilator-Stimulated Phosphoprotein Activity Is Required for Coxiella burnetii Growth in Human Macrophages.
Coxiella burnetii is an intracellular bacterial pathogen that causes human Q fever, an acute flu-like illness that can progress to chronic endocarditis and liver and bone infections. Humans are typically infected by aerosol-mediated transmission, and C. burnetii initially targets alveolar macrophages wherein the pathogen replicates in a phagolysosome-like niche known as the parasitophorous vacuole (PV). C. burnetii manipulates host cAMP-dependent protein kinase (PKA) signaling to promote PV formation, cell survival, and bacterial replication. In this study, we identified the actin regulatory protein vasodilator-stimulated phosphoprotein (VASP) as a PKA substrate that is increasingly phosphorylated at S157 and S239 during C. burnetii infection. Avirulent and virulent C. burnetii triggered increased levels of phosphorylated VASP in macrophage-like THP-1 cells and primary human alveolar macrophages, and this event required the Cα subunit of PKA. VASP phosphorylation also required bacterial protein synthesis and secretion of effector proteins via a type IV secretion system, indicating the pathogen actively triggers prolonged VASP phosphorylation. Optimal PV formation and intracellular bacterial replication required VASP activity, as siRNA-mediated depletion of VASP reduced PV size and bacterial growth. Interestingly, ectopic expression of a phospho-mimetic VASP (S239E) mutant protein prevented optimal PV formation, whereas VASP (S157E) mutant expression had no effect. VASP (S239E) expression also prevented trafficking of bead-containing phagosomes to the PV, indicating proper VASP activity is critical for heterotypic fusion events that control PV expansion in macrophages. Finally, expression of dominant negative VASP (S157A) in C. burnetii-infected cells impaired PV formation, confirming importance of the protein for proper infection. This study provides the first evidence of VASP manipulation by an intravacuolar bacterial pathogen via activation of PKA in human macrophages.


First Report of Garlic Rust Caused by Puccinia allii on Allium sativum in Minnesota.
High-quality garlic is an emerging crop grown in Minnesota for local markets, community supported agriculture, and select restaurants. In July 2010, Allium sativum cv. German Extra Hardy Porcelain plants showing foliar symptoms typical of rust infection were brought to the Plant Disease Clinic at the University of Minnesota by a commercial grower from Fillmore County, Minnesota. Infected leaves showed circular to oblong lesions (1 to 3 mm long), which ranged in color from yellow-orange (uredinia) to black (telia). Urediniospores collected from uredinia were globoid to ellipsoid, yellowish in color, and measured 18 ± 1 × 30 ± 2 μm with a wall thickness of 2.4 ± 0.5 μm. Teliospores were two celled, 18 ± 3 × 47 ± 10 μm, with a projected cross-sectional area (1) of 826 ± 87 μm2; cell walls were smooth, brown, 1.6 ± 0.3 μm (proximal cell) to 2.1 ± 0.5 μm (distal cell) thick, and 4.2 ± 0.8 μm at the apex. The pathogen was identified as Puccinia allii (2) and a sample was deposited in the U.S. National Fungus Collection (BPI 884132). DNA was extracted from infected leaf tissue and the nuclear ribosomal internal transcribed spacer region (ITS) and 5' end of the large subunit (LS) was amplified and sequenced as described by Anikster et al. (1). The 1,257-bp sequence from the sample collected in Minnesota (GenBank Accession No. JX402206) was identical to ITS/LS sequence of a sample of P. allii collected from garlic in California (GenBank Accession No. AF511077), with the exception that MN sequence contained nine "A"s rather than 10 in the hyper-variable area at the 3' end of the ITS region. P. allii has been shown to be a species complex comprising at least two different types, "leek type" and "garlic type" (1). Based on the ITS sequence and the projected cross-sectional area of the teliospores, the sample of P. allii from MN is consistent with the garlic type. Garlic rust occurred in localized foci late in the growing season and therefore did not cause significant loss to the 2010 crop. Reoccurrence of garlic rust was not reported in either 2011 or 2012 growing seasons in Minnesota. P. allii all but eliminated commercial garlic production in California in the late 1990s (1) and has the potential to cause significant negative impact to the emerging garlic crop in Minnesota. However, the epidemiology of garlic rust in the northern U.S. is not well understood and therefore predicting the risk of the Minnesota garlic crop to rust is difficult. References: (1) Y. Anikster et al. Phytopathology 94:569, 2004. (2) L. J. Szabo et al, Rust. Pages 41-44 in: Compendium of Onion and Garlic Diseases and Pests, Second Edition. H. F. Schwartz and S. K. Mohan, eds. APS Press, St. Paul, 2008.


Multimode laser emission from dye doped polymer optical fiber.
Multimode laser emission is observed in a polymer optical fiber doped with a mixture of Rhodamine 6G (Rh 6G) and Rhodamine B (Rh B) dyes. Tuning of laser emission is achieved by using the mixture of dyes due to the energy transfer occurring from donor molecule (Rh 6G) to acceptor molecule (Rh B). The dye doped poly(methyl methacrylate)-based polymer optical fiber is pumped axially at one end of the fiber using a 532 nm pulsed laser beam from a Nd:YAG laser and the fluorescence emission is collected from the other end. At low pump energy levels, fluorescence emission is observed. When the energy is increased beyond a threshold value, laser emission occurs with a multimode structure. The optical feedback for the gain medium is provided by the cylindrical surface of the optical fiber, which acts as a cavity. This fact is confirmed by the mode spacing dependence on the diameter of the fiber.


Analysis of failure in living donor liver transplantation: differential outcomes in children and adults.
Over the past decade we have reported excellent outcomes in pediatric living-donor liver transplantation (LDLT) with recipient survival exceeding 90%. Principles established in these patients were extended to LDLT in adults. To compare outcomes in donors and recipients between adult and pediatric LDLT in a single center, we reviewed patient records of 45 LDLT performed between 1/98 and 2/01: 23 adult LDLT (54 +/- 6.5 yr) and 22 pediatric LDLT (33.7 +/- 53.5 months). Preoperative liver function was worse in adults (International Normalized Ratio [INR] 1.5 +/- 0.4 vs. INR 1.2 +/- 0.5; p = 0.032). 4 adults (17%) met criteria for status 1 or 2A. Only 1 child was transplanted urgently. Analysis included descriptive statistics and Kaplan-Meier estimation. Donor mortality was 0% with 1 re-exploration, 2.4%. Median hospital stay (LOS) was 6.0 days (range, 4-12 days). Donor morbidity and LOS did not differ by sex, extent of hepatectomy, or adult and pediatric LDLT ( p = 0.49). In contrast, recipient outcomes were worse for adults. Adult 1 year graft survival was 65% (3 retransplants [ReTx], 5 deaths) vs. 91% for children (1 ReTx, 1 death) p = 0.02. Graft losses in adults were due to sepsis (n = 3), small for size (n = 2), suicide, and hepatic artery thrombosis (HAT), whereas in children graft losses were due to portal thrombosis and total parenteral nutrition (TPN) liver failure. Biliary leaks occurred in 22% of adults and 9% of children. Hepatic vein obstruction occurred in 17% of adults and in none of the children. Median LOS was comparable (adult, 16.5 days (range, 7-149 days); child, 17 days (range, 10-56 days), p = 0.2). Graft function (total bilirubin (TBili) < 5mg/dl, INR < 1.2, aspartate aminotransferase (AST) < 100 U/l) normalizing by day 4 in children and by day 14 in adults. Adults fared worse, with an array of problems not seen in children, in particular, hepatic vein obstruction and small-for-size syndrome. Biliary leaks were diagnosed later in adults and were lethal in 3 cases; this was later avoided with biliary drainage in adult recipients. Finally, use of LDLT in decompensated adults led to death in 3 of 4 patients, and should be restricted to elective use.


Temporal Association Between Nonfatal Self-Directed Violence and Tree and Grass Pollen Counts.
Prior research suggests a possible association between pollen and suicide. No studies have examined the relationship between pollen and attempted suicide. This study examines the temporal association between airborne pollen counts and nonfatal suicidal and nonsuicidal self-directed violence (SDV) requiring an emergency department visit. Data on daily emergency department visits due to nonfatal SDV as identified by ICD-9 diagnosis criteria were extracted from emergency department medical records of Parkland Memorial Hospital in Dallas, Texas, between January 2000 and December 2003. Concurrent daily airborne tree, grass, and ragweed pollen data from the city of Dallas were extracted from the National Allergy Bureau online database. The data were analyzed using the time series method of generalized autoregressive conditional heteroskedasticity. There were statistically significant and positive temporal associations between tree pollen counts and the number of nonfatal SDV events among women (P = .04) and between grass pollen counts and number of nonfatal SDV events among both men (P = .03) and women (P < .0001). There was no significant temporal association found between ragweed pollen counts and number of nonfatal SDV events. The study findings suggest that an increase in nonfatal SDV is associated with changes in tree and grass pollen counts. This is the first study that has examined an association between seasonal variation in tree and grass pollen levels and nonfatal SDV event data. The study also used a narrowly defined geographic area and temporal window. The findings suggest that pollen count may be a factor influencing seasonal patterns in suicidal behavior.


Antigen-receptor complex stimulation triggers protein kinase C-dependent CD11a/CD18-cytoskeleton association in T lymphocytes.
Although it is well accepted that intercellular adhesion involving the CD11a/CD18 (LFA-1) complex is critical in a wide array of T cell-dependent processes, recent demonstrations of an LFA-1 high avidity state, induced by triggering the T cell receptor (TCR) complex, has raised questions about the intracellular signals generated and molecular events leading to effective cell coupling, as well as their orderly sequence. In this study, we assessed the effects of T cell activation on the actin-based cytoskeleton, and LFA-1, as well as their interaction. Crosslinking the TCR complex with anti-CD3 mAb resulted in actin polymerization and colocalization with LFA-1, as detected by fluorescence microscopy. This association was confirmed by immunoprecipitating LFA-1 from the detergent insoluble, cytoskeletal-associated membrane fraction after TCR crosslinking. These consequences were inhibited by the protein kinase C (PKC) inhibitor staurosporine or by PKC desensitization, as was a transient CD11a hyperphosphorylation, induced by monoclonal anti-CD3. Furthermore, a small percentage of beta 2-deficient T cells maintained the ability to rearrange the cytoskeleton in response to TCR complex activation, with F-actin-VLA4 colocalization. These results provide evidence that the important consequences of TCR-induced signal transduction include a PKC-dependent cytoskeletal rearrangement, involving an association between leukocyte integrins and F-actin. We discuss the implications of these findings with respect to effective T cell functions.


Vibrio vulnificus biotype 2 serovar E gne but not galE is essential for lipopolysaccharide biosynthesis and virulence.
This work aimed to establish the role of gne (encoding UDP-GalNAc 4-epimerase activity) and galE (encoding UDP-Gal-4-epimerase activity) in the biosynthesis of surface polysaccharides, as well as in the virulence for eels and humans of the zoonotic serovar of Vibrio vulnificus biotype 2, serovar E. DNA sequence data revealed that gne and galE are quite homologous within this species (> or =90% homology). Mutation in gne of strain CECT4999 increased the surface hydrophobicity, produced deep alterations in the outer membrane architecture, and resulted in noticeable increases in the sensitivity to microcidal peptides (MP), to eel and human sera, and to phagocytosis/opsonophagocytosis. Furthermore, significant attenuation of virulence for eels and mice was observed. By contrast, mutation in galE did not alter the cellular surface, did not increase the sensitivity to MP, serum, or phagocytosis, and did not affect the virulence for fish and mice. The change in the attenuated-virulence phenotype produced by a mutation in gne was correlated with the loss of the O-antigen lipopolysaccharide (LPS), while the capsule was maintained. Complementation of a gne-deficient mutant restored the LPS structure together with the whole virulence phenotype. In conclusion, gne, but not galE, is essential for LPS biosynthesis and virulence in the zoonotic serovar of V. vulnificus biotype 2.


Topical amitriptyline-ketamine for treatment of rectal, genital, and perineal pain and discomfort.
Pain in the rectal, genital, and perineal area is a common condition treated by pain physicians. These chronic pain syndromes are therapeutically challenging because both interventional and drug therapies often are ineffective. To determine if pelvic pain can be treated effectively with compounded topical amitriptyline-ketamine. A retrospective review of medical records. A single academic medical center in the United States. We identified all patients treated with topical amitriptyline-ketamine from January 1, 2004, through November 28, 2011. Medical records were evaluated to determine the diagnosis for which the medication was prescribed. Treatment efficacy and any adverse effects were recorded. Of the 1,068 patients who received amitriptyline-ketamine, 13 had the medication prescribed for genital, rectal, or perineal pain and had medication efficacy recorded. Of these 13 patients, one (8%) had complete relief, 6 (46%) had substantial relief, 4 (31%) had some relief, and 2 (15%) had no response. One patient reported occasional irritation while using topical amitriptyline-ketamine with lidocaine; no other patients reported local or systemic adverse effects. Retrospective review; lack of uniform system for pain grading; concurrent use of other medications. Topical amitriptyline-ketamine provided a high rate of pain relief with a low adverse-effect burden in patients with pelvic pain. This topical medication could offer an effective, noninvasive, nonopioid therapy for pain in the rectum, perineum, and genitals.


Incidental pancreatic lipomas diagnosed by computed tomography.
Fatty tumours of the pancreas are rarely reported. With the advent of the imaging techniques, diagnosis of such tumours based on radiologic imaging is increasing. Between June 2006 and June 2012, four patients with pancreatic lipomas that were diagnosed by computed tomography were reviewed retrospectively with regard to their imaging findings. There were 3 male and one female patient with a mean age of 60.8 years (from 53 to 67 years). A single well-bordered nodular fatty lesion with well-delineated thin homogeneous capsule was seen in all patients. The mean densitometric measurement of the lesions was -76 Hounsfield units (HU) (from -83 HU to -63 HU). The size of the lesions was from 7 mm to 12 mm with a mean of 8.75mm. They were located in the tail, body and neck of the pancreas in two, one and one patient, respectively. There was no associated pancreatobiliary pathology. Histopathologic evaluation was not planned because of their incidental diagnosis in these asymptomatic patients. Pancreatic lipomas are silent lesions, incidentally found during imaging procedures. They have specific computed tomography findings and do not require any additional diagnostic imaging.


Genomic instability, driver genes and cell selection: Projections from cancer to stem cells.
Cancer cells and stem cells share many traits, including a tendency towards genomic instability. Human cancers exhibit tumor-specific genomic aberrations, which often affect their malignancy and drug response. During their culture propagation, human pluripotent stem cells (hPSCs) also acquire characteristic genomic aberrations, which may have significant impact on their molecular and cellular phenotypes. These aberrations vary in size from single nucleotide alterations to copy number alterations to whole chromosome gains. A prominent challenge in both cancer and stem cell research is to identify "driver aberrations" that confer a selection advantage, and "driver genes" that underlie the recurrence of these aberrations. Following principles that are already well-established in cancer research, candidate driver genes have also been suggested in hPSCs. Experimental validation of the functional role of such candidates can uncover whether these are bona fide driver genes. The identification of driver genes may bring us closer to a mechanistic understanding of the genomic instability of stem cells. Guided by terminologies and methodologies commonly applied in cancer research, such understanding may have important ramifications for both stem cell and cancer biology. This article is part of a Special Issue entitled: Stress as a fundamental theme in cell plasticity.


Diversity of Pain Medicine Trainees and Faculty in the United States: A Cross-Sectional Analysis of Fellowship Training from 2009-2019.
Diversity and equity in medicine remain pivotal to care delivery. Data analysis on sex and racial diversity of pain medicine fellowship trainees and faculty in the United States are scant. We sought to characterize demographic and retention patterns among pain medicine fellows and faculty, who represent the emerging chronic pain management workforce. cross-sectional retrospective analysis. We conducted an analysis of data from the American Association of Medical Colleges (AAMC) and the United States Accreditation Council on Graduate Medical Education (ACGME)-approved residency and fellowship training-programs for each year from 2009 through 2019, inclusively. We compared changes in sex, racial/ethnicity composition and retention rates of fellows and faculty in the United States by practice setting. From 2009 to 2019, there was a 14% increase in the number of ACGME pain fellowship programs. From 2009 to 2019, the ratio of men to women pain fellows ranged from 5:1 to 3.7:1. Compared with their self-identified White peers, Asian (OR 0.44; 95% CI: 0.34-0.58), Black (OR 0.46; 95% CI: 0.30-0.72), and Native American/Alaskan Native (OR 0.26; 95% CI: 0.08-0.80) identifying individuals had significantly lower odds of being a pain fellow, P < 0.05. There was no significant difference in female (OR = 0.4, 95% CI: 0.148-1.09) and Black (OR 0.36; 95% CI: 0.11-1.12) program-directors. Pain-fellow in-state retention was 53%. The demographics of pain medicine training programs reflect a persistent male vs. female gap with underrepresentation of racial minorities. Further research is needed to elucidate reasons underlying these disparities.


Identification and characterization of the 'missing' terminal enzyme for siroheme biosynthesis in α-proteobacteria.
It has recently been shown that the biosynthetic route for both the d1 -haem cofactor of dissimilatory cd1 nitrite reductases and haem, via the novel alternative-haem-synthesis pathway, involves siroheme as an intermediate, which was previously thought to occur only as a cofactor in assimilatory sulphite/nitrite reductases. In many denitrifiers (which require d1 -haem), the pathway to make siroheme remained to be identified. Here we identify and characterize a sirohydrochlorin-ferrochelatase from Paracoccus pantotrophus that catalyses the last step of siroheme synthesis. It is encoded by a gene annotated as cbiX that was previously assumed to be encoding a cobaltochelatase, acting on sirohydrochlorin. Expressing this chelatase from a plasmid restored the wild-type phenotype of an Escherichia coli mutant-strain lacking sirohydrochlorin-ferrochelatase activity, showing that this chelatase can act in the in vivo siroheme synthesis. A ΔcbiX mutant in P. denitrificans was unable to respire anaerobically on nitrate, proving the role of siroheme as a precursor to another cofactor. We report the 1.9 Å crystal structure of this ferrochelatase. In vivo analysis of single amino acid variants of this chelatase suggests that two histidines, His127 and His187, are essential for siroheme synthesis. This CbiX can generally be identified in α-proteobacteria as the terminal enzyme of siroheme biosynthesis.


[Occupational noise as a risk factor for work-related injuries].
To assess whether exposure to occupational noise is an important risk factor for work-related injuries. A population-based case-control study was performed. Data collection was carried out from May 16, 2002 to October 15, 2002 in the city of Botucatu, southeast Brazil. Cases were defined as workers who had suffered typical work-related injuries in a 90-day period previously to the study, and who identified through systematic random sampling of their households. Controls were non-injured workers randomly sampled from the same population, matched on 3:1 ratio according to sex, age group and census track. A multiple logistic regression model was adjusted, where the independent variable was exposure to occupational noise, controlled for covariates of interest. A total of 94 cases and 282 controls were analyzed. An adjusted multiple regression model showed that "work always exposed to high-level noise" and "work sometimes exposed to high-level noise" were associated to a relative risk for work-related injuries of about 5.0 (95% CI: 2.8-8.7; p<0.001) and 3.7 (95% CI: 1.8-7.4; p=0.0003) respectively, when work not exposed to noise was taken as a reference, controlled for several covariates. Based on the study findings, investing in hearing conservation programs, particularly those for controlling noise emission at its source, is justifiable aiming at both hearing health maintenance and reduction of work-related injuries.


Analytical chemistry of synthetic routes to psychoactive tryptamines. Part II. Characterisation of the Speeter and Anthony synthetic route to N,N-dialkylated tryptamines using GC-EI-ITMS, ESI-TQ-MS-MS and NMR.
The degree of alkylation of the side chain nitrogen in tryptamines is one important factor that affects psychoactivity. The method of Speeter and Anthony is considered to be one of the most important synthetic preparative methods. The final step in this reaction is based on the reduction of a (substituted) indole-3-yl-glyoxalylamide to the desired tryptamine with metal hydride. Twelve symmetrically and 13 asymmetrically N,N-disubstituted glyoxalylamides and their corresponding tryptamine derivatives have been synthesised and characterised by gas chromatography EI-ion trap mass spectrometry, electrospray-triple quadrupole-tandem mass spectrometry and NMR spectroscopy. Mass spectral and NMR similarities and differences between the investigated compounds are discussed. A solvent dependency is observed that has to be taken into consideration for the unambiguous assignment of (1)H- and (13)C-NMR chemical shifts. The (1)H-NMR study demonstrated that one can evaluate the rotamer populations of the asymmetrical glyoxalylamides. In a forensic or clinical scenario where single or multiple reaction monitoring approaches are contemplated, the appropriate ion transitions of choice may then focus on the two main fragmentations, namely beta-cleavage ([M+H](+)-->CH(2)N(+)R(2)R(3)) and/or alpha-cleavage ([M+H](+)-->[3-vinylindole](+)), respectively. The synthesis, NMR and MS analytical data presented provide the forensic analyst and clinical biochemist with a detailed and self-consistent body of information and mechanisms for the spectral identification of the more likely psychoactive tryptamines that may be met.


Functional heterogeneity of cytotoxic T cells and tumor resistance to cytotoxic hits limit anti-tumor activity in vivo.
Cytotoxic T cells (CTLs) can eliminate tumor cells through the delivery of lethal hits, but the actual efficiency of this process in the tumor microenvironment is unclear. Here, we visualized the capacity of single CTLs to attack tumor cells in vitro and in vivo using genetically encoded reporters that monitor cell damage and apoptosis. Using two distinct malignant B-cell lines, we found that the majority of cytotoxic hits delivered by CTLs in vitro were sublethal despite proper immunological synapse formation, and associated with reversible calcium elevation and membrane damage in the targets. Through intravital imaging in the bone marrow, we established that the majority of CTL interactions with lymphoma B cells were either unproductive or sublethal. Functional heterogeneity of CTLs contributed to diverse outcomes during CTL-tumor contacts in vivo. In the therapeutic settings of anti-CD19 CAR T cells, the majority of CAR T cell-tumor interactions were also not associated with lethal hit delivery. Thus, differences in CTL lytic potential together with tumor cell resistance to cytotoxic hits represent two important bottlenecks for anti-tumor responses in vivo.


Development and preliminary validation of the Menopause Symptoms Treatment Satisfaction Questionnaire (MS-TSQ).
The Menopause Symptoms Treatment Satisfaction Questionnaire, an eight-item questionnaire with a 4-week recall period, was developed to assess women's satisfaction with treatment for symptoms associated with menopause. We describe the development and initial testing of the scale. Following standard instrument-development procedures, focus groups were conducted with menopausal women experiencing hot flushes to generate potential constructs. Multiple items were drafted to address each construct. An iterative process of cognitive testing, item revision, and item reduction was followed to identify the most appropriate items and optimal response scales. The psychometric validation of the questionnaire used data collected through a multicenter, randomized, double-blind, placebo-controlled study including 543 postmenopausal women. Psychometric analyses were conducted to explore potential item reduction and to address questionnaire scaling and scoring. Internal consistency reliability, construct validity, and discriminant validity of the new scale were also examined. The questionnaire includes items addressing the control of daytime and nighttime hot flushes; effects of treatment on sleep, mood, libido, and cognition; medication tolerability; and overall satisfaction. Correlation analyses indicated that the items are related to each other without being overly redundant and that the item set is best described using a one-factor model. The subsequent scale score demonstrated sound internal consistency reliability, strong construct validity, and good discriminant validity. The results of the development and initial validation are favorable. It is expected that the questionnaire will prove to be a worthwhile tool for assessing women's satisfaction with treatment for menopausal symptoms.


CABS-flex standalone: a simulation environment for fast modeling of protein flexibility.
CABS-flex standalone is a Python package for fast simulations of protein structure flexibility. The package combines simulations of protein dynamics using CABS coarse-grained protein model with the reconstruction of selected models to all-atom representation and analysis of modeling results. CABS-flex standalone is designed to allow for command-line access to the CABS computations and complete control over simulation process. CABS-flex standalone is equipped with features such as: modeling of multimeric and large-size protein systems, contact map visualizations, analysis of similarities to the reference structure and configurable modeling protocol. For instance, the user may modify the simulation parameters, distance restraints, structural clustering scheme or all-atom reconstruction parameters. With these features CABS-flex standalone can be easily incorporated into other methodologies of structural biology. CABS-flex standalone is distributed under the MIT license, which is free for academic and non-profit users. It is implemented in Python. CABS-flex source code, wiki with examples of use and installation instructions for Linux, macOS and Windows are available from the CABS-flex standalone repository at https://bitbucket.org/lcbio/cabsflex.


Remote COPD Severity and Exacerbation Detection Using Heart Rate and Activity Data Measured from a Wearable Device.
Chronic obstructive pulmonary disease (COPD) is one of the leading causes of human mortality worldwide. Traditionally, estimating COPD severity has been done in controlled clinical conditions using cough sounds, respiration, and heart rate variability, with the latter reporting insights on the autonomic dysfunction caused by the disease. Advancements in remote monitoring and wearable device technologies, in turn, have allowed for remote COPD monitoring in daily life conditions. In this study, we explore the potential for predicting COPD severity and exacerbation using a low-cost wearable device that measures heart rate and activity data. We collected smartwatch sensor data from 35 COPD patients over a period of three months. Our evaluation shows that future trajectory of the disease can be predicted using only the first few days of continuous unobtrusive wearable data collected from COPD patients. Using features extracted from wearable device an Isolation Forest was able to predict exacerbation with an area under curve (AUC) 0.69 thus showing improvement over a random choice classifier.


Dynamic changes in Mcl-1 expression regulate macrophage viability or commitment to apoptosis during bacterial clearance.
Macrophages are critical effectors of bacterial clearance and must retain viability, despite exposure to toxic bacterial products, until key antimicrobial functions are performed. Subsequently, host-mediated macrophage apoptosis aids resolution of infection. The ability of macrophages to make this transition from resistance to susceptibility to apoptosis is important for effective host innate immune responses. We investigated the role of Mcl-1, an essential regulator of macrophage lifespan, in this switch from viability to apoptosis, using the model of pneumococcal-associated macrophage apoptosis. Upon exposure to pneumococci, macrophages initially upregulate Mcl-1 protein and maintain viability for up to 14 hours. Subsequently, macrophages reduce expression of full-length Mcl-1 and upregulate a 34-kDa isoform of Mcl-1 corresponding to a novel BH3-only splice variant, Mcl-1(Exon-1). Change in expression of Mcl-1 protein is associated with mitochondrial membrane permeabilization, which is characterized by loss of mitochondrial inner transmembrane potential and translocation of cytochrome c and apoptosis-inducing factor. Following pneumococcal infection, macrophages expressing full-length human Mcl-1 as a transgene exhibit a delay in apoptosis and in bacterial killing. Mcl-1 transgenic mice clear pneumococci from the lung less efficiently than nontransgenic mice. Dynamic changes in Mcl-1 expression determine macrophage viability as well as antibacterial host defense.


Urban AHECs: a comparison with rural AHECs.
The first generation of projects in the Federal Area Health Education Center (AHEC) Program was funded in 1972. Those AHEC projects, located in predominantly rural areas, focused on problems that resulted from the geographic maldistribution of health professionals, especially primary care physicians. Education programs for health professionals, students, and practitioners were used to influence the geographic distribution of health professionals and to improve access to and quality of health care for underserved populations. In 1976, the Congress redrafted the law authorizing the expenditure of funds for AHECs and emphasized that improving access to health care in urban underserved areas also was to be addressed by the program. During the early years of urban AHEC development, it was not clear which lessons learned from rural AHEC experiences could be applied to urban communities and what would be the best focus for AHEC activities in the complex urban environment. Some said that urban areas were so different from rural areas--in economic, racial, and cultural terms and in the subtlety of barriers to health care--as to make the rural AHEC experience largely irrelevant. Others maintained that basic AHEC principles could be applied, regardless of setting, with changes only in tactics to address the problems of the urban inner city. Now that 18 of the total 53 AHECs nationally are urban, and a decade of experience in developing them has been accumulated, it is appropriate to compare the types of educational interventions supported by AHECs in urban and rural environments and the relative priorities of such programs. In this report we examine the experiences of the California AHEC System, which includes 17 urban and rural centers and the 9 medical schools with which they are affiliated. Although the AHEC Program concept was found to be equally applicable to both urban and rural settings, significant differences in implementation were noted. Those differences were evidenced both by relative budgets,such as the large expenditures for undergraduate medical education in urban areas and for nursing in rural areas, and by subtler differences in the types of programs developed within budget categories


Frequency volume charts should be used in men with lower urinary tract symptoms.
A frequency volume chart is a simple, easy-to-use, non-invasive tool that is useful in the assessment of patients with lower urinary tract symptoms. Though more sophisticated techniques are now available for diagnosis, the frequency volume chart should still be considered the first line investigation. In this review we summarize the indications and value of this age old investigation. Urologists and primary care physicians should use the frequency volume chart more frequently in their practice.


Combined submerged and solid substrate fermentation for the bioconversion of lignocellulose.
A novel two-stage bioreactor has been designed for a combined submerged (SF) and solid substrate fermentation (SSF) of wheat straw. The straw was pretreated with steam, and cellulases from the culture fluid of Trichoderma reesei were adsorbed on it for increased bioconvertibility. SSF was conducted in the top part of the bioreactor by inoculating the straw with a 36-h mycelial culture of T. reesei, or Coriolus versicolor. In the bottom part of the fermenter, Endomycopsis fibuliger was grown in SF. The SF liquor was recirculated through the SSF stage at 24 h intervals to remove glucose and other metabolites that may inhibit growth, and to maintain optimum moisture level and temperature. The removed glucose and other metabolites provided nutrients for the yeast in the SF stage. The combined fermentation resulted in overall higher biomass yield, increased bioconversion, increased cellulase production, and increased digestibility compared with single SSF or SF.


F-Wave Duration as a Specific and Sensitive Tool for the Diagnosis of Restless Legs Syndrome/Willis-Ekbom Disease.
Restless legs syndrome, also known as Willis-Ekbom disease (RLS/WED), is a frequent condition, though its pathophysiology is not completely understood. The diagnosis of RLS/WED relies on clinical criteria, and the only instrumental tool, the suggested immobilization test, may lead to equivocal results. Recently, neurophysiological parameters related to F-wave duration have been proposed as a diagnostic aid. The aim of this study is to assess and compare the diagnostic values of these parameters in diagnosis of RLS/WED. Fifteen women affected by primary RLS/WED and 17 age- and sex- matched healthy subjects. A complete electroneurographic evaluation, including nerve conduction studies (NCS), cutaneous silent period (CSP), and F-wave parameters, namely amplitude, F-wave duration (FWD), and the ratio between FWD and duration of the corresponding compound muscle action potential (FWD/CMAPD). No subject showed alterations of the NCS. However, FWD and FWD/CMAPD of both upper and lower limbs were significantly longer in patients than controls. Tibial FWD/CMAPD best discriminated RLS/WED patients from controls. A cutoff of 2.06 yielded a sensitivity of 69.2%, a specificity of 94.1%, a positive predictive power of 90%, and a negative predictive power of 80% (area under the curve = 0.817; 95% confidence interval = 0.674-0.959). The combination of ulnar or tibial FWD/CMAPD increases the sensitivity (85.7%) while slightly decreasing the specificity (87.5%, positive predictive value: 85.7%, negative predictive value: 87.5%). Lower limb FWD/CMAPD ratio may represent a supportive diagnostic tool, especially in cases of evening lower leg discomfort of unclear interpretation.


Alternative diagnosis in the putative ventilator-associated pneumonia patient not meeting lavage-based diagnostic criteria.
The clinical picture of ventilator-associated pneumonia (VAP) can be mimicked by other infectious and non-infectious diseases. The aim of this study was to determine the alternative diagnoses and to develop a diagnostic flow chart for patients suspected of having VAP not meeting the diagnostic broncho-alveolar lavage (BAL) criteria. Adult intensive care patients with a clinical suspicion of VAP and negative BAL results were included. The clinical suspicion of VAP was based on the combination of clinical, radiological, and microbiological criteria. BAL was considered positive if cell differentiation revealed ≥ 2% cells with intracellular organisms and/or quantitative culture results of ≥ 10(4) cfu/ml. The most likely alternative diagnosis of fever and pulmonary densities was retrospectively determined by two authors independently. In all, 110 of 207 patients with suspected VAP did not meet the diagnostic BAL criteria and required further diagnostic evaluation. In 67 patients an alternative diagnosis for fever could be found. In 51 patients an alternative diagnosis of both fever and pulmonary densities could be established. In almost 40% of patients no alternative diagnosis could be provided. Non-bacterial pneumonia was diagnosed in 10 patients with Herpes simplex virus 1 (HSV-1) as the most common pathogen. In eight patients non-infectious pneumonitis was diagnosed. Due to the wide range of alternative diagnoses and applied tests the diagnostic work-up proved to be necessarily individualized and guided by repeated clinical assessment. The most frequently found alternative diagnoses were viral pneumonia and non-infectious pneumonitis.


Cost-effectiveness analysis of screening modalities for breast cancer in Japan with special reference to women aged 40-49 years.
Although the introduction of screening mammography in Japan would be expected to reduce mortality from breast cancer, the optimal screening modality in terms of cost-effectiveness remains unclear. We compared the cost-effectiveness ratio, defined as the cost required for a life-year saved, among the following three strategies: (1) annual clinical breast examination; (2) annual clinical breast examination combined with mammography; and (3) biennial clinical breast examination combined with mammography for women aged 30-79 years using a hypothetical cohort of 100 000. The sensitivity, specificity and early breast cancer rates were derived from studies conducted from 1995 to 2000 in Miyagi Prefecture. The treatment costs were based on a questionnaire survey conducted at 13 institutions in Japan. We used updated parameters that were needed in the analysis. Although the effectiveness of treatment in terms of the number of expected survival years was highest for annual combined modality, biennial combined modality had a higher cost-effectiveness ratio, followed by annual combined modality and annual clinical breast examination in all age groups. In women aged 40-49 years, annual combined modality saved 852.9 lives and the cost/survival duration was 3 394 300 yen/year, whereas for biennial combined modality the corresponding figures were 833.8 and 2 025 100 yen/year, respectively. Annual clinical breast examination did not confer any advantages in terms of effectiveness (815.5 lives saved) or cost-effectiveness (3 669 900 yen/year). While the annual combined modality was the most effective with respect to life-years saved among women aged 40-49 years, biennial combined modality was found to provide the highest cost-effectiveness.


Oxidized-LDL and Fe3+/ascorbic acid-induced oxidative modifications and phosphatidylserine exposure in human platelets are reduced by melatonin.
Low-density lipoprotein (LDL) modifications and platelet activation are major risk factors for cardiovascular diseases. When platelets are exposed to oxidative stress, they become activated. Oxidized LDL (ox-LDL) and metal-catalysed oxidation systems such as Fe3+/ascorbic acid increase free radical production. We wanted to verify whether melatonin has a protective effect against oxidative modifications and phosphatidylserine externalization in platelets induced by ox-LDL and Fe3+/ascorbic acid. For in vitro effects of melatonin on platelets, ADP-activated platelets were incubated with ox-LDL or Fe3+/ascorbic acid for 1 h at 37 degrees C with or without melatonin. Then platelet malondialdehyde, protein carbonyl and glutathione levels were measured. Platelet phosphatidylserine exposure was measured with annexin-V using flow cytometry. Malondialdehyde, protein carbonyl and phosphatidylserine levels of platelets treated with Fe3+/ascorbic acid significantly increased compared to the control group. Glutathione contents of Fe3+/ascorbic acid-treated platelets significantly decreased. Melatonin pre-treatment of Fe3+/ascorbic acid-treated platelets caused a mar ked reduction in malondialdehyde and phosphatidylserine levels and a marked increase in glutathione levels. Melatonin also caused non-significant reduction in protein carbonyl contents of Fe3+/ascorbic acid-treated platelets. Malondialdehyde, protein carbonyl and phosphatidylserine levels of platelets treated with ox-LDL also significantly increased compared to the control group. Platelet glutathione levels non-significantly decreased with ox-LDL. With addition of melatonin, malondialdehyde, protein carbonyl and phosphatidylserine levels of platelets treated with ox-LDL significantly decreased. These data suggest that melatonin may protect platelets from iron overload-induced and ox-LDL-induced oxidative modifications and also from the triggering signals of apoptosis activation, possibly due to its scavenger effect on toxic free radicals.


Metabolism and Disposition of a Novel B-Cell Lymphoma-2 Inhibitor Venetoclax in Humans and Characterization of Its Unusual Metabolites.
Venetoclax (ABT-199), a B-cell lymphoma-2 (Bcl-2) protein inhibitor, is currently in clinical development for the treatment of hematologic malignancies. We characterized the absorption, metabolism, and excretion of venetoclax in humans. After a single oral dose of [14C]venetoclax to healthy volunteers, the recovery of total radioactive dose was 100%, with feces being the major route of elimination of the administered dose, whereas urinary excretion was minimal (<0.1%). The extent of absorption was estimated to be at least 65%. Venetoclax was primarily cleared by hepatic metabolism (∼66% of the administered dose). ∼33% of the administered dose was recovered as the parent drug and its nitro reduction metabolite M30 [2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-N-((3-amino-4-(((tetrahydro-2H-pyran-4-yl)methyl)amino)phenyl)sulfonyl)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)benzamide] (13%) in feces. Biotransformation of venetoclax in humans primarily involves enzymatic oxidation on the dimethyl cyclohexenyl moiety, followed by sulfation and/or nitro reduction. Nitro reduction metabolites were likely formed by gut bacteria. Unchanged venetoclax was the major drug-related material in circulation, representing 72.8% of total plasma radioactivity. M27 (oxidation at the 6 position of cyclohexenyl ring followed by cyclization at the α-carbon of piperazine ring; 4-[(10aR,11aS)-7-(4-chlorophenyl)-9,9-dimethyl-1,3,4,6,8,10,10a,11a-octahydropyrazino[2,1-b][1,3]benzoxazin-2-yl]-N-[3-nitro-4-(tetrahydropyran-4-ylmethylamino)phenyl]sulfonyl-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide) was identified as a major metabolite, representing 12% of total drug-related material. M27 was primarily formed by cytochrome P450 isoform 3A4 (CYP3A4). Steady-state plasma concentrations of M27 in human and preclinical species used for safety testing suggested that M27 is a disproportionate human metabolite. M27 is not expected to have clinically relevant on- or off-target pharmacologic activities.


Visceral Hypersensitivity and Altered Colonic Motility in Type 2 Diabetic Rat.
Abnormal visceral sensitivity and disordered motility are common in patients with diabetes mellitus. The purpose of the present study was to investigate whether visceral sensation and bowel motility were altered in a rat model of type 2 diabetes mellitus accompanied by weight loss. A type 2 diabetic rat model in adulthood was developed by administrating streptozotocin (STZ; 90 mg/kg, i.p.) to neonatal rats. Eight weeks after STZ administration, rats with blood glucose level of 200 mg/dL or higher were selected and used as diabetic group (n = 35) in this study. Abdominal withdrawal reflex and arterial pulse rate were measured to examine visceral nociception induced by colorectal distension (0.1-1.0 mL). The amplitude, frequency, and area under the curve (AUC) of spontaneous phasic contractions of colonic circular muscles were recorded in vitro to examine colonic motility. STZ-treated diabetic rats gained significantly less weight for 8 weeks than control (P < 0.01). Forty-eight percent of the diabetic rats showed enhanced visceral nociceptive response to colorectal distension. Diabetic rats did not differ from control rats in colorectal compliance. However, the frequency and AUC, not the amplitude, of colonic spontaneous contraction in vitro was significantly decreased in diabetic rats compared to control rats (P < 0.01 in frequency and P < 0.05 in AUC). These results demonstrate visceral hypersensitivity and colonic dysmotility in a rat model of type 2 diabetes mellitus accompanied by weight loss.


The kinetics of competitive radioligand binding predicted by the law of mass action.
Although equilibrium competitive radioligand binding studies are often used to characterize hormone and neurotransmitter receptors, the kinetics of such experiments have not been extensively explored. The interactions of the radioligand and competitor with the receptors can be described by two differential equations which can be solved to yield a single equation describing the binding of the radioligand as a function of time. This equation has several applications: First, it can be used to simulate competitive binding reactions under defined conditions. Second, fitting experimental data to this equation allows one to determine the association and dissociation rate constants of the competing ligand, parameters that cannot be derived from equilibrium experiments. Furthermore, this method can be used to determine the KI of the competing drug from data acquired before equilibrium is reached. Third, mathematical analysis of the binding equation allowed us to answer two specific questions regarding the kinetics of competitive radioligand binding: how long such an incubation takes to equilibrate, and how the IC50 varies over time. The answers to these questions depended, to a large extent, on the relative values of the dissociation rate constants of the radioligand and competitor, which can be determined as noted above. When the competitor dissociates from the receptors more rapidly than the radioligand, the IC50 first decreases and then increases, but never has a value less than the KI. At low radioligand concentrations, equilibrium is reached in the same amount of time required of the radioligand to dissociate completely from the receptors as determined in an "off-rate experiment." At higher concentrations of radioligand this time is halved. When the competitor dissociates from the receptor more slowly than does the radioligand, then the time required to equilibrate depends only on the dissociation rate constant of the competitor, and the IC50 decreases over time.


Trends in smoking initiation among adolescents and young adults--United States, 1980-1989.
The evaluation of efforts to prevent tobacco use among adolescents requires accurate surveillance of both smoking prevalence and smoking initiation rates. Although several surveillance systems provide timely data about adolescent smoking prevalence (1), data characterizing rates of smoking initiation among adolescents have been limited. To improve characterization of trends in smoking initiation among young persons, data from the Tobacco Use Supplement of the 1992 and 1993 Current Population Surveys (CPS) (2) were used to estimate smoking initiation rates for persons who were adolescents (aged 14-17 years) or young adults (aged 18-21 years) during 1980-1989. This report summarizes the results of that analysis.


Intervascular pit membranes with a torus in the wood of Ulmus (Ulmaceae) and related genera.
• The distribution of intervascular pit membranes with a torus was investigated in juvenile wood samples of 19 species of Ulmus and seven related genera. • A staining solution of safranin and alcian blue (35 : 65) was recommended to distinguish torus-bearing pit membranes using light microscopy. • Intervascular pit membranes connecting relatively wide vessel elements resembled those of most angiosperms, as they were of uniform thickness. By contrast, bordered pit pairs with round to oval pit apertures and indistinct pit canals that connected narrow (incomplete) vessel elements or vascular tracheids with distinct helical thickenings were frequently characterized by a torus in ring-porous wood samples of Ulmus and Zelkova. Tori were lacking in diffuse-porous species of Ampelocera, Aphananthe, Gironniera, Holoptelea, Phyllostylon, Trema and Ulmus. • Our observations suggest that tori are more common in cold temperate climates than in warm (sub)tropical environments. This may indicate that narrow tracheary elements with torus-bearing pit membranes provide an auxiliary conducting system which is of low conductivity, but offers greater resistance to freezing-induced cavitation.


Azaphilones biosynthesis complements the defence mechanism of Trichoderma guizhouense against oxidative stress.
Filamentous fungi are known as producers of a large array of diverse secondary metabolites (SMs) that aid in securing their environmental niche. Here, we demonstrated that the SMs have an additional role in fungal defence against other fungi: Trichoderma guizhouense, a mycoparasite, is able to antagonize Fusarium oxysporum f. sp. cubense race 4 (Foc4) by forming aerial hyphae that kill the host with hydrogen peroxide. At the same time, a gene cluster comprising two polyketide synthases is strongly expressed. Using functional genetics, we characterized this cluster and identified its products as azaphilones (termed as trigazaphilones). The trigazaphilones were found lacking of antifungal toxicity but exhibited high radical scavenging activities. The antioxidant property of trigazaphilones was in vivo functional under various tested conditions of oxidative stress. Thus, we conclude that the biosynthesis of trigazaphilones serves as a complementary antioxidant mechanism and defends T. guizhouense against the hydrogen peroxide that it produces to combat other fungi like Foc4.


The availability and cost of antibiotics for treating PID in the Central Region of Ghana and implications for compliance with national treatment guidelines.
The availability and cost of antibiotics for treating pelvic inflammatory disease (PID) were assessed in 17 drug-dispensing outlets in 5 districts of the Central Region, Ghana. The outlets included the dispensaries of 2 regional and 4 district hospitals, 4 privately-owned pharmacies and 7 chemical seller shops. The most common antibiotics available, including co-trimoxazole, metronidazole, benzylpenicillin, amoxycillin, chloramphenicol and gentamicin, were also the lowest-priced drugs. Conversely, the most expensive antibiotics including ceftriaxone, ciprofloxacin, cefuroxime and spectinomycin, were also the least commonly available. Recommended anti-gonococcal antibiotics (ciprofloxacin, ceftriaxone) may not be prescribed if they are not available in the districts.


Early initiated postoperative rehabilitation reduces fatigue in patients with operable lung cancer: A randomized trial.
Little is known about the optimal amount and timing of exercise strain in concern of the operation wound and with regard improvement of physical function and quality of life (QOL) after surgery for lung cancer. On this background, we decided to investigate the effect of early vs. late initiated postoperative rehabilitation in patients with operable lung cancer on exercise capacity, functional capacity, muscle strength, and QOL. The study was designed as a two-armed randomized controlled trial with randomization to either early initiated postoperative rehabilitation (14 days after surgery (ERG)) or a control arm with late initiated postoperative rehabilitation (14 weeks after surgery (LRG)). The primary endpoint was a change in maximum oxygen consumption (VO2peak) from baseline to post intervention 26 weeks following lung resection. Fatigue was measured with EORTC QLQ C30 LC13. From April 2013 to June 2016, 582 patients with operable NSCLC were screened for eligibility. With 119 patients randomized in the early rehabilitation group (ERG) and 116 randomized to late rehabilitation group (LRG). There was no significant difference from baseline to 26 weeks between ERG and LRG (p = 0.926). There was a significant difference from baseline to 14 weeks between groups (p = 0.0018). There was a significant difference from 14 weeks to 26 weeks between the two groups (p < 0.001). We found no significant differences in QOL but we found a significant difference between ERG and LRG from baseline to 14 weeks in fatigue level in favour of ERG. This is the first randomized controlled trial to investigate the effects of early vs. late initiated postoperative rehabilitation in patients with lung cancer. There is no difference in the commencement (early vs. late) of a postoperative exercise program for patients with lung cancer on exercise capacity. But to reduce fatigue patients should be recommended to initiate early exercise programs.


Associations between exposure to information and communication technology (ICT) and reported discomfort among adolescents.
Use of Information and Communication Technologies (ICT) are common among adolescents in their daily activities.Exposure to ICT has been associated with discomfort and musculoskeletal disorders in adults, with growing concern about the potential risks to children and adolescents' physical health. The objectives of this study were to (i) quantify self-reported discomfort and exposure to ICT among adolescents; and (ii) determine if associations exist between discomfort and levels of exposure. The participant group comprised 33 Australian adolescents aged 12-15 years. The study used self-reports by participants for a one week period. Intensity and location of discomfort was reported via a written discomfort log. ICT exposure and physical activity were reported through an electronic time-use diary. The most common ICT types reported by participants were television, mobile phones and desktop and laptop computers. Discomfort was reported by 86% of participants. The most frequently reported areas were the legs, head/neck, back and shoulders. There was no statistical association found between ICT exposure and discomfort. The majority of participants exceeded the recommended 60 minutes per day of moderate to vigorous physical activity. High exposure to ICT and high prevalence of low level discomfort was reported by the participants. Participating in regular physical activity may have some protective effect against ICT-related discomfort.


Resonance frequencies of honeybee (Apis mellifera) wings.
During flight, insect wings bend and twist under the influence of aerodynamic and inertial forces. We tested whether wing resonance of honeybees (Apis mellifera) matches the wingbeat frequency, against the 'stiff element' hypothesis that the wing's first longitudinal mode exceeds the wingbeat frequency. Six bees were immobilized with their right wing pair outspread, and stimulated with a shaker while the normal modes were recorded with a scanning Doppler laser vibrometer. The lowest normal mode of the wings was the first longitudinal bending mode and, at 602±145 Hz, was greater than the wingbeat frequency of 234±13.9 Hz. Higher-order normal modes of the wing tended to incorporate nodal lines in the chordwise direction of the trailing edge, suggesting that their mode shape did not strongly resemble wing deformation during flapping flight. These results support the stiff element hypothesis for Apis mellifera.


Construction of an autonomously concatenated hybridization chain reaction for signal amplification and intracellular imaging.
Biomolecular self-assembly has spurred substantial research efforts for the development of low-cost point-of-care diagnostics. Herein, we introduce an isothermal enzyme-free concatenated hybridization chain reaction (C-HCR), in which the output of the upstream hybridization chain reaction (HCR-1) layer acts as an intermediate input to activate the downstream hybridization chain reaction (HCR-2) layer. The initiator motivates HCR-1 through the autonomous cross-opening of two functional DNA hairpins, yielding polymeric dsDNA nanowires composed of numerous tandem triggers T as output of the primary sensing event. The reconstituted amplicon T then initiates HCR-2 and transduces the analyte recognition into an amplified readout, originating from the synergistic effect between HCR-1 and HCR-2 layers. Native gel electrophoresis, atom force microscopy (AFM) and fluorescence spectra revealed that C-HCR mediated the formation of frond-like branched dsDNA nanowires and the generation of an amplified FRET signal. As a versatile and robust amplification strategy, the unpreceded C-HCR can discriminate DNA analyte from its mutants with high accuracy and specificity. By incorporating an auxiliary sensing module, the integrated C-HCR amplifier was further adapted for highly sensitive and selective detection of microRNA (miRNA), as a result of the hierarchical and sequential hybridization chain reactions, in human serum and even living cells through an easy-to-integrate "plug-and-play" procedure. In addition, the C-HCR amplifier was successfully implemented for intracellular miRNA imaging by acquiring an accurate and precise signal localization inside living cells, which was especially suitable for the ex situ and in situ amplified detection of trace amounts of analyte. The C-HCR amplification provides a comprehensive and smart toolbox for highly sensitive detection of various biomarkers and thus should hold great promise in clinical diagnosis and assessment. The infinite layer of multilayered C-HCR is anticipated to further strengthen the amplification capacity and reliability (anti-invasion performance) of intracellular imaging approach, which is of great significance for its bioanalytical applications.


Photodegradation of the endocrine-disrupting chemical 4-nonylphenol in biosolids applied to soil.
There is increasing concern about the environmental fate and impact of biosolids-associated anthropogenic organic chemicals, among which 4-nonylphenol (4-NP) is one of the most studied chemicals. This is primarily because 4-NP is an endocrine disruptor and has been frequently detected in environmental samples. Due to its high hydrophobicity, 4-NP has high affinity for biosolids. Land application of 4-NP-containing biosolids could potentially introduce large quantities of this chemical into the environment. A laboratory experiment was conducted to investigate the effect of artificial sunlight on 4-NP degradation in biosolids applied to soil. When exposed to artificial sunlight for 30 d, the top-5-mm layer of biosolids showed a 55% reduction of 4-NP, while less than 15% of the 4-NP was degraded when the biosolids were kept in the dark. Our results indicate that sensitized photolysis reaction plays an important role in reducing the levels of 4-NP in land-applied biosolids. Surface application rather than soil incorporation of biosolids could be effective in reducing biosolids-associated organic chemicals that can be degraded through photolysis reactions. However, the risks of animal ingestion, foliar deposition, and runoff should also be evaluated when biosolids are applied on the soil surface.


Co-induction of activity-dependent genes in songbirds.
Song behavior in songbirds induces the expression of activity-dependent genes in brain areas involved in perceptual processing, production and learning of song. This genomic response is thought to represent a link between neuronal activation and long-term changes in song-processing circuits of the songbird brain. Here we demonstrate that Arc, an activity-regulated gene whose product has dendritic localization and is associated with synaptic plasticity, is rapidly induced by song in the brain of zebra finches. We show that, in the context of song auditory stimulation, Arc expression is induced in several telencephalic auditory areas, most prominently the caudomedial nidopallium and mesopallium, whereas in the context of singing, Arc is also induced in song control areas, namely nucleus HVC, used as a proper name, the robust nucleus of the arcopallium and the interface nucleus of the nidopallium. We also show that song-induced Arc expression co-localizes at the cellular level with those of the transcriptional regulators zenk and c-fos, and that the song induction of these three genes is dependent on activation of the mitogen-activated protein kinase signaling pathway. These findings provide evidence for an involvement of Arc in the brain's response to birdsong. They also demonstrate that genes representing distinct genomic and cellular regulatory programs, namely early effectors and transcription factors, are co-activated in the same neuronal cells by a naturally learned stimulus.


An analysis of factors determining serum leptin concentration in healthy and infected newborns.
The effect leptin on fetal growth in healthy and infected newborns is not well known. This study is aimed at: 1) evaluating serum leptin concentration in full term and preterm, healthy and infected newborns, according to their gender, birth asphyxia, intrauterine and neonatal infections, and 2) assessing the correlation between serum leptin levels and anthropometric parameters among healthy and infected newborns. The study involved 146 newborns: 73 full-term and 73 preterm, 86 male and 60 female, 56 healthy and 90 infected, aged from 2nd to 4th day of life. Anthropometric parameters, including: birth weight, length, head and chest circumference, and serum leptin concentration were measured in all the subjects. Intrauterine and neonatal infections were diagnosed by the standard criteria. In this study, it was found that both healthy and infected, but full-term newborns had significantly higher mean leptin concentration than the premature ones (p<0.05). Statistically significant (p<0.05), positive correlations were found between serum leptin level and gestational age, birth weight, head and chest circumference, both in healthy, and in infected newborns. Findings of this study suggest that the serum leptin concentration in full term newborns is higher than in the preterm ones, and in females it is higher than in males, 2) among both healthy and infected newborns, there is a positive, linear correlation between the serum leptin concentration and anthropometric parameters, 3) intrauterine and neonatal infections do not have a significant influence on serum leptin concentration. The role of leptin in fetal growth deserves further research.


An internationally standardised antisaccade protocol.
Detailed measurements of saccadic latency--the time taken to make an eye movement to a suddenly-presented visual target--have proved a valuable source of detailed and quantitative information in a wide range of neurological conditions, as well as shedding light on the mechanisms of decision, currently of intense interest to cognitive neuroscientists. However, there is no doubt that more complex oculomotor tasks, and in particular the antisaccade task in which a participant must make a saccade in the opposite direction to the target, are potentially more sensitive indicators of neurological dysfunction, particularly in neurodegenerative conditions. But two obstacles currently hinder their widespread adoption for this purpose. First, that much of the potential information from antisaccade experiments, notably about latency distribution and amplitude, is typically thrown away. Second, that there is no standardised protocol for carrying out antisaccade experiments, so that results from one laboratory cannot easily be compared with those from another. This paper, the outcome of a recent international meeting of oculomotor scientists and clinicians with an unusually wide experience of such measurements, sets out a proposed protocol for clinical antisaccade trials: its adoption will greatly enhance the clinical and scientific benefits of making these kinds of measurements.


Antityrosinase activity of Euphorbia characias extracts.
Tyrosinase is a well-known key enzyme in melanin biosynthesis and its inhibitors have become increasingly important because of their potential use as hypopigmenting agents. In the present study, the anti-melanogenic effect of aqueous and ethanolic extracts from Euphorbia characias leaves, stems, and flowers in cell-free and cellular systems was examined. All the extracts showed inhibitory effects against mushroom tyrosinase with leaf extracts exhibiting the lowest IC50 values of 24 and 97 µg/mL for aqueous and ethanolic extracts respectively. Enzyme kinetic analysis indicated that leaf aqueous extract acts as a mixed type inhibitor, while ethanolic extract shows a competitive inhibition effect on mushroom tyrosinase using L-DOPA as substrate. In addition, the inhibitory effect of leaf extracts on tyrosinase activity and melanin production was examined in murine melanoma B16F10 cells. Cellular tyrosinase activity as well as levels of melanin synthesis are reduced in a dose-dependent manner by extracts in cells treated with α-melanocyte stimulating hormone (α-MSH). The effects are comparable, and sometimes even better, than that of kojic acid, a well known tyrosinase inhibitor used for reference. All these results suggest that E. characias could be a great source of the natural inhibitors from tyrosinase and has the potential to be used as a whitening agent in therapeutic fields.


Association of mitogen-activated protein kinases with microtubules in mouse macrophages.
Taxol, a microtubule-binding diterpene, mimics many effects of lipopolysaccharide (LPS) on mouse macrophages. The LPS-mimetic effects of taxol appear to be under the same genetic control as responses to LPS itself. Thus we have postulated a role for microtubule-associated proteins (MAP) in the response of macrophages to LPS. Stimulation of macrophages by LPS quickly induces the activation of mitogen-activated protein kinases (MAPK). MAPK are generally considered cytosolic enzymes. Herein we report that much of the LPS-activatable pool of MAPK in primary mouse peritoneal macrophages is microtubule associated. By immunofluorescence, MAPK were localized to colchicine- and nocodazole-disruptible filaments. From both mouse brain and RAW 264.7 macrophages, MAPK could be coisolated with polymerized tubulin. Fractionation of primary macrophages into cytosol-, microfilament-, microtubule-, and intermediated filament-rich extracts revealed that approximately 10% of MAPK but none of MAPK kinase (MEK1A and MEK2) was microtubule bound. Exposure of macrophages to LPS did not change the proportion of MAPK bound to microtubules, but preferentially activated the microtubule-associated pool. These findings confirm the prediction that LPS activates a kinase bound to microtubules. Together with LPS-mimetic actions of taxol and the shared genetic control of responses to LPS and taxol, these results support the hypothesis that a major LPS-signaling pathway in mouse macrophages may involve activation of one or more microtubule-associated kinases.


Ecological determinants in microbial colonization of the murine gastrointestinal tract: adherence of Torulopsis pintolopesii to epithelial surfaces.
Torulopsis pintolopesii is a yeast indigenous to the gastrointestinal tracts of conventional mice and rats from many colonies. In such natively colonized animals, the organism forms layers on the surface of the epithelium in the secreting portion of the stomach and can be cultured from all areas of the gastrointestinal tract. When given in water or food to germfree mice or specific pathogen-free mice possessing an indigenous microbiota free of yeast, T. pintolopesii also can be cultured from all areas of the tract at population levels ranging from 10(5) to 10(8) cells per g (wet weight). Likewise, as in its native hosts, the organism forms layers on gastric surfaces in the associated animals. The layers form on the secreting surface in both the specific pathogen-free and monoassociated ex-germfree mice. In the latter animal, however, a layer of yeast also forms on the nonsecreting gastric surface. In tests of its capacity to adhere to gastrointestinal surfaces in vitro, the organism adheres to epithelia from all areas of the mouse tract. These findings support an hypothesis that the capacity of T. pintolopesii to adhere to epithelial surfaces may be only one determinant influencing it to form layers on the gastric secreting surface in its native hosts.