Navigating local smoke-free multi-unit housing policy adoption.
California state-funded local tobacco control projects have instituted smoke-free multi-unit housing (MUH) policy adoption campaigns in order to secure voluntary policy throughout the state. While landlords can legally prohibit smoking at MUH complexes in California, they often oppose such measures. The objective of this study was to analyze voluntary smoke-free policy campaigns of state-funded local projects by focusing on the challenges they faced. Specifically, we examined 40 local campaigns in California led by county health departments and community based organizations, focusing on the barriers the local projects often had to overcome to enact policy. Our results identify arguments and issues typically raised by MUH property landlords, including the notion of tenant smoker and privacy rights, potential negative effects of smoke-free policy, and issues concerning the enforcement of policy. Moreover, relationships between local project personnel and MUH management often soured, which sometimes derailed smoke-free policy campaigns altogether. Our findings provide agencies with insights from the MUH property landlord perspective that will serve to inform future campaign strategy.


Differential gene expression in Acromyrmex leaf-cutting ants after challenges with two fungal pathogens.
Social insects in general and leaf-cutting ants in particular have increased selection pressures on their innate immune system due to their social lifestyle and monoclonality of the symbiotic fungal cultivar. As this symbiosis is obligate for both parties, prophylactic behavioural defences against infections are expected to increase either ant survival or fungus-garden survival, but also to possibly trade off when specific infections differ in potential danger. We examined the effectiveness of prophylactic behaviours and modulations of innate immune defences by a combination of inoculation bioassays and genome-wide transcriptomic studies (RNA-Seq), using an ant pathogen (Metarhizium brunneum) and a fungus-garden pathogen (Escovopsis weberi) and administering inoculations both directly and indirectly (via the symbiotic partner). Upon detection of pathogen conidia, ant workers responded by increasing both general activity and the frequency of specific defence behaviours (self-grooming, allo-grooming, garden-grooming) independent of the pathogen encountered. This trend was also evident in the patterns of gene expression change. Both direct and indirect (via fungus garden) inoculations with Metarhizium induced a general up-regulation of gene expression, including a number of well-known immune-related genes. In contrast, direct inoculation of the fungus garden by Escovopsis induced an overall down-regulation of ant gene expression, whereas indirect inoculation (via the ants) did not, suggesting that increased activity of ants to remove this fungus-garden pathogen is costly and involves trade-offs with the activation of other physiological pathways.


Differential DNA repair underlies mutation hotspots at active promoters in cancer genomes.
Promoters are DNA sequences that have an essential role in controlling gene expression. While recent whole cancer genome analyses have identified numerous hotspots of somatic point mutations within promoters, many have not yet been shown to perturb gene expression or drive cancer development. As such, positive selection alone may not adequately explain the frequency of promoter point mutations in cancer genomes. Here we show that increased mutation density at gene promoters can be linked to promoter activity and differential nucleotide excision repair (NER). By analysing 1,161 human cancer genomes across 14 cancer types, we find evidence for increased local density of somatic point mutations within the centres of DNase I-hypersensitive sites (DHSs) in gene promoters. Mutated DHSs were strongly associated with transcription initiation activity, in which active promoters but not enhancers of equal DNase I hypersensitivity were most mutated relative to their flanking regions. Notably, analysis of genome-wide maps of NER shows that NER is impaired within the DHS centre of active gene promoters, while XPC-deficient skin cancers do not show increased promoter mutation density, pinpointing differential NER as the underlying cause of these mutation hotspots. Consistent with this finding, we observe that melanomas with an ultraviolet-induced DNA damage mutation signature show greatest enrichment of promoter mutations, whereas cancers that are not highly dependent on NER, such as colon cancer, show no sign of such enrichment. Taken together, our analysis has uncovered the presence of a previously unknown mechanism linking transcription initiation and NER as a major contributor of somatic point mutation hotspots at active gene promoters in cancer genomes.


Systematic review and meta-analysis of the duration of clinical effect of onabotulinumtoxinA in cervical dystonia.
Botulinum toxins are considered first-line therapy for treatment of cervical dystonia (CD) and must be injected on a repeat basis. Understanding the duration of clinical benefit of botulinum toxins and its impact on health care utilization are thus important in the contemporary environment. However, there is currently no overall consensus on the duration of effect of onabotulinumtoxinA in the treatment of CD. We performed a systematic review and meta-analysis to identify the duration of effect of onabotulinumtoxinA in CD and investigate factors that may influence it. A systematic literature search identified prospective or retrospective studies reporting duration of effect of onabotulinumtoxinA for the treatment of CD. Inclusion criteria included peer-reviewed, non-review, English-language articles published between January 1980 and January 2013. A formal meta-analysis using Comprehensive Meta-Analysis Version 2 was conducted to identify the duration of effect of onabotulinumtoxinA in the treatment of CD; both fixed and random effects models were performed. Subgroup analyses were performed to identify factors that influenced the duration of effect of onabotulinumtoxinA. A total of 18 studies (including >1,900 patients) met the inclusion criteria and were used for the meta-analysis. The mean duration of effect of onabotulinumtoxinA in CD was found to be 93.2 days (95% CI 91.8-94.6 days) for the fixed effects model and 95.2 days (95% CI 88.9-101.4 days) for the random effects model. A meta-regression found that dose of onabotulinumtoxinA and country of origin influenced the duration of effect of onabotulinumtoxinA, whereas quality score of the article and study type did not. In particular, doses ≥180 Units were associated with longer durations of effect than doses <180 Units (107-109 days vs. 86-88 days, respectively; p < 0.01). Limitations included pooling studies that used discrete definitions of duration and had different designs and study quality. Based on the published literature, the mean duration of effect of onabotulinumtoxinA in CD was 93-95 days (13.2-13.5 weeks). This suggests that, in general, patients with CD treated with onabotulinumtoxinA should require ~4 treatments per year.


[Gas chromatography in express diagnosis of candidiasis and monitoring of antifungal therapy efficacy by D-arabinitol and mannose levels in pediatric patients].
Seventy three children (40 blood and 43 liquor specimens) were examined with the use of gas chromatography (GC) to detect background concentrations of Candida metabolites. The criterium of the children enrollment to the control group was the absence of the clinical and laboratory signs of the fungal infection. The normal contents of the fungus metabolites were considered to be 0.51 +/- 0.28 microgram/ml for D-arabinitol and 17.7 +/- 10.4 micrograms/ml for mannose in the serum and 7.24 +/- 3.04 micrograms/ml for D-arabinitol and 67.1 +/- 47.4 micrograms/ml for mannose in the liquor. Fifty four children at the age of 1 month to 12 years with the signs of the fungal infection requiring systemic antifungal therapy were also examined. Prior to the use of antifungal drugs the routine microbiological tests and GC detection of the fungus metabolites were performed. The fungus was isolated with the cultural method from the blood in 2 patients (6.3 per cent), from the mucosa in 25 (71.4 per cent) out of 32 patients with fungal complications at the background of cytostatic therapy and neutropenia, from the liquor in 3 (21.4 per cent) out of 14 patients with meningitis and from the urine in 8 (100 per cent) out of 8 patients with urinary infection. The GC examination revealed increased levels of the Candida metabolites in 96 per cent of the children. A favourable time course of the infection at the background of amphotericin B or fluconasol use was recorded by the clinical indices which correlated with a reliable decrease of the contents of D-arabinitol and mannose to the normal. The use of GC is recommended in express diagnosis of candidiasis especially when the results of the cultural tests are negative as well as in monitoring of the fungal therapy efficacy.


Identification and sequence analysis of the Marek's disease virus serotype 2 homologous genes of the herpes simplex virus type 1 UL25, UL26 and UL26.5 genes.
We identified and determined the nucleotide sequence of Marek's disease virus serotype 2 (MDV2) UL25, UL26 and UL26.5 homologous genes of herpes simplex virus type 1 (HSV-1). The UL25, UL26 and UL26.5 genes of HSV-1 encode virion proteins (UL25 and UL26.5) and serine protease (UL26). The deduced amino acid sequences of the three proteins show a high degree of homology to counterparts of HSV-1. By northern blot analyses we found that four transcripts whose sizes are 4.9, 3.9, 2.0 and 1.3 kb are transcribed from the domains of MDV2 genome containing the three genes. This is the first report dealing with UL25, UL26 and UL26.5 homologues of HSV-1 in MDV serotypes.


Curcumin and Type 2 Diabetes Mellitus: Prevention and Treatment.
Type 2 diabetes mellitus (T2DM) is an ensemble of metabolic diseases that has reached pandemic dimensions all over the world. The multifactorial nature of the pathology makes patient management, which includes lifelong drug therapy and lifestyle modification, extremely challenging. It is well known that T2DM is a preventable disease, therefore lowering the incidence of new T2DM cases could be a key strategy to reduce the global impact of diabetes. Currently, there is growing evidence on the efficacy of the use of medicinal plants supplements for T2DM prevention and management. Among these medicinal plants, curcumin is gaining a growing interest in the scientific community. Curcumin is a bioactive molecule present in the rhizome of the Curcuma longa plant, also known as turmeric. Curcumin has different pharmacological and biological effects that have been described by both in vitro and in vivo studies, and include antioxidant, cardio-protective, anti-inflammatory, anti-microbial, nephro-protective, anti-neoplastic, hepato-protective, immunomodulatory, hypoglycaemic and anti-rheumatic effects. In animal models, curcumin extract delays diabetes development, improves β-cell functions, prevents β-cell death, and decreases insulin resistance. The present review focuses on pre-clinical and clinical trials on curcumin supplementation in T2DM and discusses the peculiar mechanisms by which curcumin might ameliorate diabetes management.


In vitro biomedical applications of functionalized iron oxide nanoparticles, including those not related to magnetic properties.
Superparamagnetic iron oxide nanoparticles (SPION) are very promising contrast media, especially for molecular imaging, due to their superior NMR efficacy. They even have wider biomedical applications such as in drug and gene delivery, tissue engineering and bioseparation, or as sensitive biological nanosensors. By coupling them to affinity ligands, SPION can bind to drugs, proteins, enzymes, antibodies or nucleotides. For in vitro biomedical applications, the detection of molecular interaction is possible by using a diversity of systems capable of sensing the magnetic properties of these materials. The goal of the present work was to develop and validate various in vitro biomedical applications of ultrasmall superparamagnetic particles of iron oxide (USPIO), including some that are not related to their magnetic properties. USPIO coated with dextran, starch or bisphosphonate exposing carboxylate groups were synthesized and some of them were functionalized by conjugating various biomolecules, such as biotin, streptavidin and apoptosis, or VCAM-1 specific peptides. The in vitro biomedical applications assessed in the present work included: (1) the relaxometric measurement of antibody concentration, cell receptor expression, molecular interaction, and enzymatic activity in aqueous suspensions; (2) MRI visualization of cells and detection of molecular interaction in an ELISA system; (3) ELISA applications of USPIO derivatives; and (4) detection of specific biomolecules by histochemistry. Our results confirm that rapid and simple in vitro detection of a diversity of functionalized SPION with relevance in medicine is possible by the existing NMR techniques and by chemical staining reactions. The protocols can be applied to minimally prepared biological samples (e.g. whole blood, blood plasma or serum, cell suspensions, biopsies, histological preparations, etc.), and often do not need complicated systems of signal amplification. The use of SPION labeled compounds could furthermore contribute to cost reductions in the diagnosis and in patient care.


1H, 13C, and 15N resonance assignments of Fusarium solani pisi cutinase and preliminary features of the structure in solution.
Essentially complete (96%) sequence-specific assignments were made for the backbone and side-chain 1H, 13C, and 15N resonances of Fusarium solani pisi cutinase, produced as a 214-residue heterologous protein in Escherichia coli, using heteronuclear NMR techniques. Three structural features were noticed during the assignment. (1) The secondary structure in solution corresponds mostly with the structure from X-ray diffraction, suggesting that both structures are globally similar. (2) The HN of Ala32 has a strongly upfield-shifted resonance at 3.97 ppm, indicative of an amide-aromatic hydrogen bond to the indole ring of Trp69 that stabilizes the N-terminal side of the parallel beta-sheet. (3) The NMR data suggest that the residues constituting the oxyanion hole are quite mobile in the free enzyme in solution, in contrast to the existence of a preformed oxyanion hole as observed in the crystal structure. Apparently, cutinase forms its oxyanion hole upon binding of the substrate like true lipases.


Evidence for a preglomerular oxygen diffusion shunt in rat renal cortex.
Although blood flow to the renal cortex is high and oxygen extraction is low, the renal cortex is remarkably susceptible to hypoxia. Because erythropoietin production has been localized mainly to the renal cortex, the aim of this study was to find a common denominator for both the high susceptibility to hypoxia and oxygen sensing within the renal cortex. By direct measurement of oxygen pressure with microcoaxial needle sensors at superficial glomeruli of the in situ kidney of anesthetized Munich-Wistar-Frömter rats, we obtained mean partial pressure of O2 (PO2) values of 46 +/- 13 (SD) mmHg (n = 71). The simultaneously measured systemic PO2 in arterial blood was 90 +/- 8 mmHg (n = 54). Changing the respirator gas from air to pure oxygen enhanced systemic arterial PO2 to 593 +/- 27 mmHg, whereas PO2 at the superficial glomeruli increased only to a mean of 80 +/- 28 mmHg (n = 71). These data suggest significant preglomerular shunting of oxygen within the cortical vasculature, most likely between interlobular vessels, which are arranged in a countercurrent fashion and represent quantitatively the largest contact area between arteries and veins within the renal cortex.


Textured Breast Implants: A Closer Look at the Surface Debris Under the Microscope.
Texturing of breast implants is done to decrease the risk of associated complications. Each manufacturer utilizes unique and at times proprietary techniques to texture the surface of their implants. Little is known about the integrity of this surface structure texturing or the propensity for the surfaces to shed particulate matter. This study aimed to determine the extent of surface particulate shedding from 3 textured implants approved by the US Food and Drug Administration (FDA), which are manufactured by Allergan, Mentor, and Sientra. Control images of each of the 3 textured breast implants were obtained with scanning electron microscopy (SEM). A liquid adhesive, ethylene vinyl acetate (EVA) copolymer was then applied to the external shell of the implants, allowed to cool, and peeled from the surface. Images of the EVA copolymer were taken with SEM to qualitatively analyze displacement of surface particulate debris. Scanning electron microscopy imaging of the implants was repeated for qualitative comparisons with the control images. The peeled copolymer of the 3 implants exhibited surface shedding. Comparison of the 3 breast implants showed the shedding to be greatest for the Allergan implant. This study highlights the dynamic surface material properties of the 3 FDA-approved breast implants. Shedding of particulate matter from the implant surfaces can be precipitated by moderate adhesion. Our qualitative examination of SEM findings showed more debris shed from the Allergan breast implants than from the Mentor or Sientra implants.


[Clinical problems of optimum bioavailability, in particular in cytostatic therapy (author's transl)].
The clinical application of cytostatic drugs requires knowledge of their biochemistry, pharmacology, pharmacokinetics as well as their action at the cellular level within the generation cycle. The principles apply to tumor cells as well as to normal, rapidly proliferating tissues. The intensive research on cancer treatment all over the world is leading to a rapid accumulation of experimental data about the action of single cytostatic drugs in tissue culture and on transplantable animal tumor systems, especially in rodents. Clinical chemotherapy in human malignancies today preferentially uses combinations of different cytostatics. Inumerable combinations of drugs are available, especially if variations in respect to drug dose and intervals of drug application are taken into consideration. The experimental basis for such combinations of drugs and drug interactions is scanty. Using the pyrimidine analog cytosine arabinoside and the two antibiotics daunorubicin and doxyrubicin (adriamycin) as examples, it is demonstrated that information on the pharmacolinetic behaviour of cytostatic drugs is a prerequisite for their success in clinical application, but is on its own insufficient to predict the tumor response.


Association of Public Works Disasters with Substance Use Difficulties: Evidence from Flint, Michigan, Five Years after the Water Crisis Onset.
Public works environmental disasters such as the Flint water crisis typically occur in disenfranchised communities with municipal disinvestment and co-occurring risks for poor mental health (poverty, social disconnection). We evaluated the long-term interplay of the crisis and these factors with substance use difficulties five years after the crisis onset. A household probability sample of 1970 adults living in Flint during the crisis was surveyed about their crisis experiences, use of substances since the crisis, and risk/resilience factors, including prior potentially traumatic event exposure and current social support. Analyses were weighted to produce population-representative estimates. Of the survey respondents, 17.0% reported that substance use since the crisis contributed to problems with their home, work, or social lives, including 11.2% who used despite a doctor's warnings that it would harm their health, 12.3% who used while working or going to school, and 10.7% who experienced blackouts after heavy use. A total of 61.6% of respondents reported using alcohol since the crisis, 32.4% using cannabis, and 5.2% using heroin, methamphetamine, or non-prescribed prescription opioids. Respondents who believed that exposure to contaminated water harmed their physical health were more likely to use substances to the detriment of their daily lives (RR = 1.32, 95%CI: 1.03-1.70), as were respondents with prior potentially traumatic exposure (RR = 2.99, 95%CI: 1.90-4.71), low social support (RR = 1.94, 95%CI: 1.41-2.66), and PTSD and depression (RR's of 1.78 and 1.49, respectively, p-values < 0.01). Public works disasters occurring in disenfranchised communities may have complex, long-term associations with substance use difficulties.


Propofol Promotes Ankle Fracture Healing in Children by Inhibiting Inflammatory Response.
BACKGROUND The present study aimed to investigate the potential effects of propofol on ankle fracture healing in children and the underlying molecular mechanisms. MATERIAL AND METHODS We first detected the levels of inflammatory cytokines from peripheral blood in children with or without ankle fracture using quantitative real-time polymerase chain reaction (qRT-PCR) and ELISA assay. Then, effects of propofol on inflammatory response in MG-63 cells were investigated. MG-63 cells were pre-treated with or without propofol and then stimulated with 1 μM bradykinin (BK). The productions of cytokines from MG-63 cells were determined by using qRT-PCR and Western blot assay. The expression levels of p-p38, NF-κB p-p65, NLRP3, ASC, caspase-1, and COX-2 were measured by Western blot and/or qRT-PCR. RESULTS The results showed that, compared with the healthy children, the levels of tumor necrosis factor (TNF-α), interleukin (IL)-1β, and IL-6 were significantly up-regulated in children with fractured ankles. No cytotoxicity was observed in MG-63 cells after propofol treatment. BK treatment significantly enhanced TNF-α, IL-1β, and IL-6 expression levels, and these enhancements were reduced by propofol treatment in a dose-dependent manner. Moreover, BK-induced up-regulation of p-p38, NF-κB p-p65, NLRP3, ASC, caspase-1, and COX-2 was dose-dependently down-regulated by propofol treatment. CONCLUSIONS Propofol prevents inflammation in MG-63 cells by regulating p38MAPK-NF-κB pathway, NLRP3 inflammasome, and COX-2 expression. Our findings indicate the benefits of propofol in fracture healing, and provide a more theoretical basis for the clinical treatment of fractures.


A new direction in Chinese herbal medicine ameliorates for type 2 diabetes mellitus: Focus on the potential of mitochondrial respiratory chain complexes.
Diabetes is a common chronic disease. Chinese herbal medicine (CHM) has a history of several thousand years in the treatment of diabetes, and active components with hypoglycemic effects extracted from various CHM, such as polysaccharides, flavonoids, terpenes, and steroidal saponins, have been widely used in the treatment of diabetes. Research exploring the potential of various CHM compounds to regulate the mitochondrial respiratory chain complex to improve type 2 diabetes mellitus (T2DM). The literature data were primarily obtained from authoritative databases such as PubMed, CNKI, Wanfang, and others within the last decade. The main keywords used include "type 2 diabetes mellitus", "Chinese medicine", "Chinese herbal medicine", "mitochondrial respiratory chain complex", and "mitochondrial dysfunction". Chinese herbal medicine primarily regulates the activity of mitochondrial respiratory chain complexes in various tissues such as liver, adipose tissue, skeletal muscle, pancreatic islets, and small intestine. It improves cellular energy metabolism through hypoglycemic, antioxidant, anti-inflammatory and lipid-modulating effects. Different components of CHM can regulate the same mitochondrial respiratory chain complexes, while the same components of a particular CHM can regulate different complex activities. The active components of CHM target different mitochondrial respiratory chain complexes, regulate their aberrant changes and effectively improve T2DM and its complications. Chinese herbal medicine can modulate the function of mitochondrial respiratory chain complexes in various cell types and exert their hypoglycemic effects through various mechanisms. CHM has significant therapeutic potential in regulating mitochondrial respiratory chain complexes to improve T2DM, but further research is needed to explore the underlying mechanisms and conduct clinical trials to assess the safety and efficacy of these medications. This provides new perspectives and opportunities for personalized improvement and innovative developments in diabetes management.


Metabolic activation of nonpolar sediment extracts results in enhanced thyroid hormone disrupting potency.
Traditional sediment risk assessment predominantly considers the hazard derived from legacy contaminants that are present in nonpolar sediment extracts, such as polychlorinated biphenyls (PCBs), dioxins, furans (PCDD/Fs), and polyaromatic hydrocarbons (PAHs). Although in vivo experiments with these compounds have shown to be thyroid hormone disrupting (THD), in vitro their THD potency is not observed in nonpolar sediment extracts. This is hypothesized to be due to the absence of in vitro biotransformation which will result in bioactivation of the lipophilic compounds into THD hydroxyl metabolites. This study reveals that indeed metabolically activated nonpolar contaminants in sediments can competitively bind to thyroid hormone transport proteins. Sediment fractions were incubated with S9 rat microsomes, and the metabolites were extracted with a newly developed method that excludes most of the lipids to avoid interference in the applied nonradioactive 96-well plate TTR competitive binding assay. Metabolic activation increased the TTR binding potency of nonpolar fractions of POP-polluted sediments up to 100 times, resulting in potencies up to 240 nmol T4 equivalents/g sediment equivalent (nmol T4-Eq/g SEQ). This demonstrates that a more realistic in vitro sediment THD risk characterization should also include testing of both polar and medium polar sediment extracts for THD, as well as bioactivated nonpolar sediment fractions to prevent underestimation of its toxic potency.


Poly(butyl cyanoacrylate) nanoparticle containing an organic photoCORM.
Carbon monoxide (CO) is a gasotransmitter, which has shown therapeutic effects in recent studies. Photo carbon monoxide releasing molecules (PhotoCORMs) allow the delivery of CO to be controlled by light. In this work, a new organic photoCORM DK4 is studied. DK4 is a diketone type photoCORM, which releases two CO molecules under visible light and simultaneously generates a fluorescent anthracene derivative. However, this type of CORM suffers from a deactivating hydration reaction and often needs to be incorporated in polymers or micelles. The two highly hydrophobic tert-butyl groups of DK4 protect it from the hydration reaction. DK4 functions in 1% DMSO aqueous solution, in which other DKs are deactivated. DK4 was incorporated in a poly(butyl cyanoacrylate) (PBCA) nanoparticle. PBCA has been used as a tissue adhesive and has been extensively studied for delivery of drugs to the brain. The PBCA/DK4 nanoparticle showed good photoactivity and low cytotoxicity, and thus is a promising material for studying the biomedical effects of CO.


Diagnosis and prognosis disclosure among cancer patients. Results from an Italian mortality follow-back survey.
The observed cultural changes in truth-telling attitudes suggest a radical change in the practice of delivering information to cancer patients, but limited research is available from countries known for their policy of non-disclosure. This study estimates the proportion of Italian who died of cancer who had received information about diagnosis and prognosis, and explores the variables associated with disclosure. This is a mortality follow-back survey of 1271 non-professional caregivers of Italians who died of cancer in 2002, representative of the approximate 160 000 Italian annual cancer deaths. Caregivers were interviewed after the patient's death about the process of diagnosis and prognosis disclosure. It was estimated that 37% of people who died of cancer had received information about diagnosis and 13% about poor prognosis. A consistent proportion, although non-informed, knew the diagnosis (29%) and the poor prognosis (50%). The probability to be informed was higher for patients living in the north of Italy, young, well educated, with longer survival, and with breast or head and neck tumor. These findings suggest that not necessarily the observed cultural changes towards a less paternalistic approach in medical care translate into an effective change in the quantity of information delivered to the patients.


Reliability of squat and countermovement jump tests in children 6 to 8 years of age.
The aim of this study was to determine the reliability of the squat jump test (SJ) and countermovement jump test (CMJ), in fifty-six children (30 girls and 26 boys) with ages ranging from 6 to 8 years. Each subject performed two evaluation sessions (T1, T2) with seven days between tests. The results show that the CMJ test has a high intratrial reproducibility in T1 and T2 measured through intraclass correlation coefficient (ICC ≥ 0.95). The ICC for the SJ test had a high value (0.99) only in T1. The variability for both tests among children under 9 years of age is higher than those reported for adult subjects in other studies. The intersession reliability was questionable with a high methodical error (ME= 9.86-15.1%, for the SJ and CMJ, respectively) and a significant worsening of the results of CMJ in T2 (p < .05).


Changes in the number of binding sites for ribonucleic acid polymerase in chromatin of WI-38 fibroblasts stimulated to proliferate.
1. When WI-38 human diploid fibroblasts form confluent monolayers, DNA synthesis and cell division almost completely cease. A change of medium causes these density-inhibited cells to proliferate and within 1h after the application of the stimulus there is an increase in template activity of the chromatin isolated from stimulated cells. 2. The number of binding sites for Escherichia coli RNA polymerase was determined on chromatin from WI-38 cells by two different methods, i.e. incorporation of [(3)H]UTP into RNA in the absence of reinitiation, and incorporation of [gamma-(32)P]GTP into chain termini. 3. Both methods indicate that the capacity of chromatin to bind E. coli RNA polymerase is increased in WI-38 cells stimulated to proliferate. 4. The increase in the number of binding sites for E. coli RNA polymerase parallels the increase in chromatin template activity and suggests that the latter reflects an increase in the number of initiation sites, rather than an increase in the rate of transcription.


Well-constructed a water stable Cu-BTC@TpPa-1 binary composite with excellent capture ability toward malachite green.
Adsorptive removal of dyes (e.g., malachite green (MG)) from wastewater using commercially available adsorbents is not significantly efficient. Metal-organic frameworks (MOFs) such as Cu-BTC is considered as an excellent adsorbent in adsorption-separation filed. However, the water instability of Cu-BTC restricts its potential utilization in dye wastewater purification. In this paper, we have developed a novel metal/covalent-organic frameworks (Cu-BTC@TpPa-1) binary composite by solvothermal method. This composite serves as a multifunctional platform for the effective removal of MG from water. This Cu-BTC@TpPa-1 obviously keeps structural integrity soaked in water for 7 days. And its heat resistant performance can achieve 360 °C because of the TpPa-1 protection, which is outdistance to that of Cu-BTC. The adsorbed capacity of MG over Cu-BTC@TpPa-1 is exceptionally high, with an uptake of up to 64.12 mg/g, which is superior compared to previous adsorbents, highlighting its superior adsorption capabilities. The adsorptive performance was controlled by the associative effects of Cu-BTC and TpPa-1 with an association effect of π-complexation and electrostatic attraction. The Cu-BTC@TpPa-1 might be a prospective adsorbent for MG capture from industrial wastewater.


Asystole after the first dose of ceftriaxone.
The incidence of ceftriaxone-related hypersensitivity skin reactions is between 1% and 3%, whereas anaphylaxis is rare. To the best of our knowledge, the following case is the first report of asystole after the administration of single-dose ceftriaxone. A 55-year-old man was admitted to our emergency department because of high fever, abdominal pain, dysuria, and weakness. To determine the cause of his fever, blood and urine cultures were obtained. Then, an infusion of 1 g ceftriaxone was started slowly. One minute later, cardiac arrest occurred. The rhythm was asystole. Cardiopulmonary resuscitation and tracheal intubation were performed immediately, and the ceftriaxone infusion was discontinued. Within 20 minutes, circulation was restored. The time of onset was suggestive of ceftriaxone-induced anaphylaxis. The patient was discharged in good clinical condition on the 10th day of admission. Emergency physicians should be mindful of the possibility of anaphylaxis and asystole that could occur with the first dose of ceftriaxone and should also make sure to offer receiving detailed informed patient consent, too.


Renal effects of moderate hemorrhage in the conscious pregnant rat.
Studies were performed in conscious, chronically catheterized virgin, 8- to 9-day-pregnant, and 15- to 16-day-pregnant Sprague-Dawley rats in baseline state and after removal of 7.5% total blood volume. Measurements were made of glomerular filtration rate (GFR), renal plasma flow (RPF), renal vascular resistance (RVR), arterial blood pressure (AP), and urinary electrolyte excretion. In baseline state, GFR and RPF were elevated at days 8-9 and days 15-16 of pregnancy (vs. virgins) due to a gestational renal vasodilation. The fall in hematocrit indicates substantial plasma volume expansion by days 15-16 of pregnancy. After removal of 7.5% total blood volume, little change occurred in AP in any group. However, the renal vasculature provided a sensitive response to moderate hemorrhage, since RPF fell and RVR increased similarly in virgin, 8- to 9-day- and 15- to 16-day-pregnant rats. GFR was protected in virgin and 8- to 9-day-pregnant rats but fell significantly in late pregnancy. Urinary electrolyte excretion tended to fall but was not significantly reduced by hemorrhage in any group. These studies indicate that renal vascular response to moderate hemorrhage is similar in virgin, early, and late pregnancy. Thus effector mechanisms that sense volume and regulate RVR must be continually reset to respond to progressive plasma volume expansion of pregnancy as normal.


Autoimmunity, inflammatory bowel disease and hyposplenism.
The presence or absence of nine autoantibodies were assessed in 44 patients with ulcerative colitis (17 with hyposplenism) and 22 patients with Crohn's disease (eight with hyposplenism). The purpose of the study was to determine whether hyposplenism in inflammatory bowel disease is associated with an increased tendency to autoimmunity, or whether autoimmunity is linked not to hyposplenism itself but to the underlying bowel disease. The results strongly suggest that the latter hypothesis is correct. There was a much higher frequency of autoantibodies in patients with ulcerative colitis than in those with Crohn's disease (P < or = 0.01), suggesting that autoimmune factors are more important in the pathogenesis of ulcerative colitis than in Crohn's disease.


Estimating the Mechanical Behavior of the Knee Joint During Crouch Gait: Implications for Real-Time Motor Control of Robotic Knee Orthoses.
Individuals with cerebral palsy frequently exhibit crouch gait, a pathological walking pattern characterized by excessive knee flexion. Knowledge of the knee joint moment during crouch gait is necessary for the design and control of assistive devices used for treatment. Our goal was to 1) develop statistical models to estimate knee joint moment extrema and dynamic stiffness during crouch gait, and 2) use the models to estimate the instantaneous joint moment during weight-acceptance. We retrospectively computed knee moments from 10 children with crouch gait and used stepwise linear regression to develop statistical models describing the knee moment features. The models explained at least 90% of the response value variability: peak moment in early (99%) and late (90%) stance, and dynamic stiffness of weight-acceptance flexion (94%) and extension (98%). We estimated knee extensor moment profiles from the predicted dynamic stiffness and instantaneous knee angle. This approach captured the timing and shape of the computed moment (root-mean-squared error: 2.64 Nm); including the predicted early-stance peak moment as a correction factor improved model performance (root-mean-squared error: 1.37 Nm). Our strategy provides a practical, accurate method to estimate the knee moment during crouch gait, and could be used for real-time, adaptive control of robotic orthoses.


Perceptions of pediatric emergency medicine fellows and program directors about research education.
Pediatric emergency medicine (PEM) fellows who entered training after January 1995 are required to complete three years of fellowship training. Additionally, they are required to receive instruction in related basic sciences and to demonstrate research competence. To determine: 1) whether PEM fellows and program directors perceive their programs as providing adequate training in research principles, 2) the manner in which these principles are taught, and 3) the commitment of fellows and program directors to research and research training. Pediatric emergency medicine fellows who participated in the Fourth Annual PEM Fellows Conference (Miami, Florida, March 1997) were surveyed. The survey was then extended via mail to all PEM fellows and program directors in the United States and Canada. A total of 159 of the 220 fellows (72%) in the United States and Canada returned completed questionnaires. Fifty-three of 70 PEM fellows (76%) who attended the conference completed questionnaires, and 106 of 167 fellows (63%) who did not attend the conference responded by mail. Fifty-three of the 63 program directors (84%) returned completed questionnaires. Of 159 responding fellows, 86 (54%), and of 53 responding program directors, 29 (58%) reported that their programs lacked adequate training in one or more of the surveyed research areas. Thirteen program directors (25%) reported no formal research training in their curricula. Programs that included formal research training were perceived to have higher overall quality than programs that failed to offer such formal training. Sixty-six of 158 responding fellows (42%) anticipated an ongoing commitment to research in their careers. One hundred fourteen of 153 responding fellows (75%) indicated that, if given the option, they would have pursued a two-year "clinical track" PEM board certification that did not include a research requirement. More than half of surveyed PEM fellows and program directors perceived important deficiencies in research education within their training programs. Further research is necessary in order to evaluate the validity of these perceptions.


An Investigative Laboratory Exercise Examining the Cell Signaling and Regulatory Properties of Neurons in the Regenerating Forelimbs of the Axolotl Ambystoma mexicanum.
Many students understand the electrical properties of neurons and can adequately describe the creation and transmission of electrical impulses. However, students often have difficulty when it comes to understanding how neurons have an equally important role in cell signaling. This latter function is crucial in the establishment of proper cell fate during regeneration. I have devised a lab that includes in its goals: 1) an investigation into the cell signaling role of neurons, 2) experience with non-lethal invasive surgery, 3) an opportunity for student-collected data, and 4) the chance to work with charismatic animals. In addition, the exercise provides insight into development because development and regeneration follow similar pathways. The lab also introduces the topic of stem cells. Finally, the eventual regeneration of the denervated limb can provide an opportunity to discuss the mechanisms of nerve repair. A critical event in urodele limb regeneration is the formation of a blastema. This event requires an intact nerve supply. Nerves secrete a substance called the neurotrophic growth factor(s) that appear to stimulate the reentry of blastema cells into the cell cycle, through a complex series of signaling events. In this laboratory exercise, students examine this effect by amputating both front limbs, but denervating only one. They then compare limb regeneration under and exempt from nerve control within the same animal. Students control for denervation using a behavioral assay, and monitor limb growth for six weeks. All sixteen of the surgeries were successful, and all showed the expected difference between the denervated and the control limb.


[Pseudo-allergic drug reactions: pathophysiology and diagnosis].
The symptomatology of allergic diseases may be imitated by non-immunological, so-called "pseudo-allergic" reactions. Phenocopies of any type of allergic reaction may occur. Pseudo-allergic drug reactions may be caused by the active components as well as by additives. Anaphylactoid pseudo-allergic reactions are of special clinical interest. Their pathomechanism has not been conclusively elucidated yet. Based on clinical and experimental data, we discuss some hypothetic mechanisms of a few compounds, always keeping in mind the possibility of allergic mechanisms not yet identified. For the diagnosis of pseudo-allergic drug reactions we need provocation tests, as skin tests are not possible, and routine in-vitro assays are not available.


Structurally Linked Dynamics in Lactate Dehydrogenases of Evolutionarily Distinct Species.
We present new findings about how primary and secondary structure affects the role of fast protein motions in the reaction coordinates of enzymatic reactions. Using transition path sampling and committor distribution analysis, we examined the difference in the role of these fast protein motions in the reaction coordinate of lactate dehydrogenases (LDHs) of Apicomplexa organisms Plasmodium falciparum and Cryptosporidium parvum. Having evolved separately from a common malate dehydrogenase ancestor, the two enzymes exhibit several important structural differences, notably a five-amino acid insertion in the active site loop of P. falciparum LDH. We find that these active site differences between the two organisms' LDHs likely cause a decrease in the contribution of the previously determined LDH rate-promoting vibration to the reaction coordinate of P. falciparum LDH compared to that of C. parvum LDH, specifically in the coupling of the rate-promoting vibration and the hydride transfer. This effect, while subtle, directly shows how changes in structure near the active site of LDH alter catalytically important motions. Insights provided by studying these alterations would prove to be useful in identifying LDH inhibitors that specifically target the isozymes of these parasitic organisms.


Limbus versus pupil center for ocular alignment measurement with corneal reflexes.
To investigate the accuracy of ocular misalignment measurement, using corneal reflections. Corneal reflex positions were measured relative to two landmarks, the limbus center and the entrance pupil center, using high-resolution digital images for cyclopean gaze angles from 0 degree to 18.8 degrees (34.04 prism diopters; PD) to the right and to the left in 10 subjects. Distance h from the center of the corneal curvature to each landmark was determined from linear regressions and showed significant differences between both conditions: mean hlimbus was 5.243 mm, and mean hpupil was 4.884 mm. From these, limbus- and entrance-pupil-center-related Hirschberg ratios were determined as 11 degrees/mm (19.43 PD/mm) and 11.82 degrees/mm (20.92 PD/ mm), respectively; and ocular alignment was calculated for both conditions. Simulated angles of strabismus were calculated as the binocular difference between ocular alignment of the right and left eyes (condition 1), and as the monocular difference between the ocular alignment of right eyes and left eyes separately (condition 2). Condition 1: Errors in simulated angles of strabismus were approximately twice as large for entrance pupil center compared with those in limbus-center-based evaluation; in the primary position, the 95% pupil-related confidence interval of the binocular difference was +/- 5.217 degrees (9.1 PD), compared with +/- 3.174 degrees (5.5 PD) for the limbus-related option. Condition 2: Errors were approximately equal. The entrance pupil center is a less reliable landmark than is the limbus center for measuring ocular alignment by using corneal reflections, because of unreliable positions of the entrance pupil center; different mean Hirschberg ratios should be used in both conditions.


Generalized View of Protein Folding: In Medio Stat Virtus.
Proteins are often described in textbooks as being only "marginally stable" but many proteins, specifically those with a high free energy of unfolding are, in fact, so stable that they exist only in the fully folded state except under harsh denaturing conditions. Proteins that are truly only marginally stable, those with a low free energy of unfolding, exist as an equilibrium mixture of folded and unfolded forms under "normal" conditions. To some extent such proteins have some features in common with "intrinsically disordered" proteins. We analyzed the relationship between these marginally stable proteins and intrinsically disordered proteins in order to fully understand the twilight zone that distinguishes the two ensembles in the hope of clarifying the fuzzy borders of the current classification that divides the protein world into folded and intrinsically disordered ones. Our analysis suggests that the division may be too drastic and misleading, because it puts within the same category proteins with very different behaviors. We propose a restricted, albeit operational, definition of "marginally stable proteins", referring by this term only to proteins whose free energy difference between the folded and unfolded states falls in the interval 0-3 kcal/mol. These proteins have special features because they normally exist as equilibrium mixtures of folded and unfolded species or as molten globule states. This coexistence makes marginally stable proteins ideal tools to study even small environmental changes to which they may behave as natural sensors.


Oscillatory EEG Activity During REM Sleep in Elderly People Predicts Subsequent Dream Recall After Awakenings.
Several findings underlined that the electrophysiological (EEG) background of the last segment of sleep before awakenings may predict the presence/absence of dream recall (DR) in young subjects. However, little is known about the EEG correlates of DR in elderly people. Only an investigation found differences between recall and non-recall conditions during NREM sleep EEG in older adults, while-surprisingly-no EEG predictor of DR was found for what concerns REM sleep. Considering REM sleep as a privileged scenario to produce mental sleep activity related to cognitive processes, our study aimed to investigate whether specific EEG topography and frequency changes during REM sleep in elderly people may predict a subsequent recall of mental sleep activity. Twenty-one healthy older volunteers (mean age 69.2 ± 6.07 SD) and 20 young adults (mean age 23.4 ± 2.76 SD) were recorded for one night from 19 scalp derivations. Dreams were collected upon morning awakenings from REM sleep. EEG signals of the last 5 min were analyzed by the Better OSCillation algorithm to detect the peaks of oscillatory activity in both groups. Statistical comparisons revealed that older as well as young individuals recall their dream experience when the last segment of REM sleep is characterized by frontal theta oscillations. No Recall (Recall vs. Non-Recall) × Age (Young vs. Older) interaction was found. This result replicated the previous evidence in healthy young subjects, as shown in within- and between-subjects design. The findings are completely original for older individuals, demonstrating that theta oscillations are crucial for the retrieval of dreaming also in this population. Furthermore, our results did not confirm a greater presence of the theta activity in healthy aging. Conversely, we found a greater amount of rhythmic theta and alpha activity in young than older participants. It is worth noting that the theta oscillations detected are related to cognitive functioning. We emphasize the notion that the oscillatory theta activity should be distinguished from the non-rhythmic theta activity identified in relation to other phenomena such as (a) sleepiness and hypoarousal conditions during the waking state and (b) cortical slowing, considered as an EEG alteration in clinical samples.


Human Skin Explant Preparation and Culture.
The ex vivo experimentation with surgically discarded human skin represents a unique methodology amenable for mechanism and pharmacologic agent studies without the involvement of human subjects. Here, we describe a protocol that includes preparation, culture, and stimulation of human skin explants, and subsequent analyses by quantitative reverse transcription PCR and immunostaining. This protocol may also be applied for ex vivo studies of murine skin, reducing animal numbers and potentially harmful treatments. In our hands, this protocol has been used for wound healing, viral infection, and hair growth-related studies. Graphical abstract: Cartoon of explant skin culture. Skin explant sits on top of a gelatin surgical sponge saturated with culture medium at an air-liquid interface.


Clindamycin phosphate scavenges hydroxyl radical.
Clindamycin phosphate (CLDMP) is effective against Gram-positive and anaerobic bacteria, and is known to have anti-inflammatory properties. To further study the anti-inflammatory properties of CLDMP, we examined the scavenging effects on superoxide anion and hydroxyl radical using an electron spin resonance (ESR) spin trapping method. In a hypoxanthine-xanthine oxidase reaction system, CLDMP did not scavenge superoxide anion. In a Fenton reaction system, however, CLDMP reduced the level of hydroxyl radical, and the scavenging activity of CLDMP against hydroxyl radical was more potent than that of mannitol. As the concentration which inhibits the formation of hydroxyl radical by 50% (IC(50)) of CLDMP was changed by the addition of a 10-fold amount of a spin trapping agent, 5,5-dimethyl-1-pyrroline-N-oxide, it is strongly suggested that CLDMP scavenges hydroxyl radical directly. This is the first report of the direct scavenging effect of CLDMP on hydroxyl radical, and the effect may improve the inflammatory response caused by invading bacteria.


Mitochondrial DNA, ecology and morphology: interpreting the phylogeography of the Nesotes (Coleoptera: Tenebrionidae) of Gran Canaria (Canary Islands).
The genus Nesotes (Coleoptera: Tenebrionidae) is represented in the Canary Islands by 19 endemic species, the majority of which are single island endemics. Nesotes conformis and N. fusculus are described on four and three islands, respectively, but each forms a paraphyletic assemblage between Gran Canaria and the other islands. The other described species for Gran Canaria are N. quadratus, N. lindbergi and N. piliger. Thirty-six individuals representing the five species on Gran Canaria have been sequenced for 675 bp of the mitochondrial DNA (mtDNA) cytochrome oxidase II gene. Neighbour-joining analysis of maximum likelihood distances resulted in five distinct mtDNA lineages for N. quadratus, two of which also include mitotypes of N. conformis. Each of the other three species is found on only one mtDNA lineage. We propose from the molecular data that differentiation in a widespread N. quadratus-type ancestor was followed by morphological adaptation to coastal, pine and laurel forest habitats.


The Connection Between Sex as Self-Injury and Sexual Violence.
Nonsuicidal self-injury (NSSI) is a suggested diagnosis recognized by DSM-5 as in need of further research. Recent studies conclude that sex as self-injury (SASI) and NSSI share similar functions, such as being used as emotional regulation. SASI has been associated with earlier sexual abuse, but the understanding of the association between sexual violence and SASI is still limited. The aim of this study was to further investigate the connection between sexual violence and the experience of SASI. How could SASI be related to sexual violence? The study used a qualitative design and was based on an anonymous questionnaire published on the websites of Swedish NGOs, providing help and support to women and youths, such as those in women's shelters. In total, 139 informants with a mean age of 27.9 years (range 15-64 years) were included in the study. Three main themes were found: (1) Normalization of sexual violence and a shift in boundaries could be seen as consequences of earlier experiences of sexual violence leading to SASI; (2) SASI could escalate into sexual violence through increased need of emotional regulation, increased risk-taking, and risk of victimization; (3) SASI could be used to regain control of re-experiences, the body, sexuality, and shame after sexual abuse. In conclusion, a complex connection was identified whereby SASI could escalate into sexual violence, and earlier experiences of sexual violence could lead to SASI in a vicious loop. Hence, SASI should be seen as a risk factor for further victimization and sexual abuse.


What influences intention to become a postgraduate trainer?
Only a small proportion of eligible dentists become dental vocational trainers. The aim of this study was to apply Social Cognitive Theory to further an understanding of beliefs underpinning intention to become a dental vocational trainer. Primary care dentists. A self-administered questionnaire was distributed at all continuing professional development courses during November 2004 regardless of course enrolment numbers, content or duration. Intention to train. Predictive measures Attitude toward being a trainer, attitude toward attending the trainer course, and confidence in ability to train (training self-efficacy). Of the 316 respondents, 47% intended never to train. Training self-efficacy accounted for the majority of variance in intention to train (15%, step 1) with attitude to training accounting for a further 4% (step 2) (Hosmer and Lemeshow test: Chi-square = 7.36, df = 8, p = 0.498; 95% CI for EXP(b): training self-efficacy = 1.38-2.06, attitude = 1.17-2.08). Attitude to the trainer course did not enter the regression model. The most influential belief relating to intention to train was confidence in teaching, and for intention never to train was evaluating a trainee's skills. Both intenders and non-intenders believed training and attending training courses would be time-consuming and financially costly, suggesting these are not primary factors in making the decision to become a trainer. Using a psychological model provided a starting point for understanding intention to become a vocational trainer and a rationale for the format of future interventions. Results suggest intention to train may be influenced by targeting dentists' confidence in teaching and performing evaluative aspects of training.


Enterotoxigenic bacteria in food and water from an Ethiopian community.
Food and water samples from an Ethiopian community were screened for the presence of enterotoxin-producing bacteria. Using the Chinese hamster ovary cell assay, 40 of 213 isolates (18.8%) produced heat-labile (LT) enterotoxin. These LT-producing isolates comprised 33 of 177 (18.6%) strains from 24 of 68 food samples (35.3%) and 7 of 36 (19.4%) isolates of 4 of 17 water samples (23.5%). One LT-producing strain each of Salmonella emek and of Shigella dysenteriae was found. Three pseudomonads, all LT producers, produced heat-stable enterotoxin as gauged by the suckling mouse test. Two strains of LT-enterotoxigenic Escherichia coli O68 were found in water samples. No enterotoxigenic E. coli were isolated from food samples, but 13 of the LT-producing strains were Enterobacter, Klebsiella, Serratia, and Proteus species, and 7 food samples yielded more than one species of enterotoxigenic bacterium. Of the enterotoxigenic isolates from food, 15 were oxidase-positive strains of the genera Aeromonas, Pseudomonas, Achromobacter, Flavobacterium, and Vibrio. LT-enterotoxigenic Enterobacter, Acinetobacter, Klebsiella, Proteus, Providencia, and Serratia species represented 20 of the food and water isolates. Culture supernatant fluids of representative strains of oxidase-positive and oxidase-negative species giving positive reactions in Chinese hamster ovary cell tests induced fluid accumulation in rabbit ileal loops. Eight of the food samples and two of the water samples contained more than one isolate or species of enterotoxigenic bacterium. The stability of the LT production by oxidase-positive bacteria and non-E. coli strains was assessed by the rabbit skin and adrenal cell tests after 9 months and 1 year of storage, respectively, in Trypticase soy broth with glycerol at -70 degrees C. Only 33% of the oxidase-positive strains were still LT enterotoxigenic. Of the oxidase-negative strains, 50 and 33% were LT producing at 9 months and 1 year, respectively. None of the E. coli isolates, both enterotoxigenic and nonenterotoxigenic, possessed K88, K99, or colonization factor antigen. The survey demonstrates the presence in food and water of enterotoxigenic bacteria of the same species as those isolated from cases of infantile diarrhea in the same community, although a correlation between these sources and infantile diarrhea remains to be established.


The Influence Between C-C Chemokine Receptor 5 Genetic Polymorphisms and the Type-1 Human Immunodeficiency Virus: A 20-Year Review.
Acquired immune deficiency syndrome (AIDS) is an infectious disease caused by the types 1 and 2 human immunodeficiency virus (HIV-1 and HIV-2). Clinical outcomes in patients are highly varied and delineated by complex interactions between virus, host, and environment, such as with help of co-receptors, for example, the C-C chemokine receptor 5 (CCR5). This work aimed to describe the scientific evidence relating the influence of CCR5 polymorphisms in association studies for HIV-1 disease susceptibility, severity, and transmissibility. This is a systematic review of the literature on single nucleotide polymorphisms (SNPs) and the deletion [Insertion and Deletion (Indel)] Δ32 of CCR5. The search for articles was based on the ScienceDirect, PubMed, and Coordination for the Improvement of Higher Education Personnel (CAPES) databases for the period between 2001 and 2021. The final sample consisted of 32 articles. †SNP rs1799987 is one of the genetic polymorphisms most associated with the criteria of susceptibility and severity of HIV-1, having distinct consequences in genotypic, allelic, and clinical analysis in the variability of investigated populations. As for the transmission character of the disease, the G mutant allele of rs1799987 corresponds to the highest positive association. ‡Furthermore, the results on Indel Δ32 corroborate the absence and rarity of this variant in some populations. Finally, mitigating the severity of cases, SNPs rs1799988 and rs1800023 obtained significant attribution in individuals in the studied populations. It is shown that the reported polymorphisms express significant influences for the evaluation of diagnostic, therapeutic, and prophylactic measures for HIV-1 having fundamental particularities in the molecular, genetic, and transcriptional aspects of CCR5.


Quercetin inhibits collagen-stimulated platelet activation through inhibition of multiple components of the glycoprotein VI signaling pathway.
The regulation of platelet function by pharmacological agents that modulate platelet signaling has proven a successful approach to the prevention of thrombosis. A variety of molecules present in the diet have been shown to inhibit platelet activation, including the antioxidant quercetin. In this report we investigate the molecular mechanisms through which quercetin inhibits collagen-stimulated platelet aggregation. The effect of quercetin on platelet aggregation, intracellular calcium release, whole cell tyrosine phosphorylation and intracellular signaling events including tyrosine phosphorylation and kinase activity of proteins involved in the collagen-stimulated glycoprotein (GP) signaling pathway were investigated. We report that quercetin inhibits collagen-stimulated whole cell protein tyrosine phosphorylation and intracellular mobilization of calcium, in a concentration-dependent manner. Quercetin was also found to inhibit various events in signaling generated by the collagen receptor GPVI. This includes collagen-stimulated tyrosine phosphorylation of the Fc receptor gamma-chain, Syk, LAT and phospholipase Cgamma2. Inhibition of phosphorylation of the Fc receptor gamma-chain suggests that quercetin inhibits early signaling events following stimulation of platelets with collagen. The activity of the kinases that phosphorylate the Fc receptor gamma-chain, Fyn and Lyn, as well as the tyrosine kinase Syk and phosphoinositide 3-kinase was also inhibited by quercetin in a concentration-dependent manner, both in whole cells and in isolation. The present results provide a molecular basis for the inhibition by quercetin of collagen-stimulated platelet activation, through inhibition of multiple components of the GPVI signaling pathway, and may begin to explain the proposed health benefits of high quercetin intake.


Phenotypic and genotypic methods for typing Campylobacter jejuni and Campylobacter coli in poultry.
Human campylobacteriosis, an infection caused by the bacterium Campylobacter, is a major issue in the United States food system, especially for poultry products. According to the Center for Disease Control, campylobacterosis is estimated to affect over 2.4 million people annually. Campylobacter jejuni and Campylobacter coli are 2 species responsible for the majority of campylobacterosis infections. Phenotypic and genotypic typing methods are often used to discriminate between bacteria at the species and subspecies level and are often used to identify pathogenic organisms, such as C. jejuni and C. coli. This review describes the design as well as advantages and disadvantages for 3 current phenotypic techniques (biotyping, serotyping, and multilocus enzyme electrophoresis) and 6 genotypic techniques (multilocus sequence typing, PCR, pulse-field gel electrophoresis, ribotyping, flagellin typing, and amplified fragment length polymorphisms) for typing pathogenic Campylobacter spp.


Photochemically Induced Ionic Reactions of Cycloalkenes: Cyclohexenes and cycloheptenes undergo cationic reactions upon ultraviolet irradiation in protic solvents.
Sensitized ultraviolet irradiation of cyclohexenes and cycloheptenes in protic solvents causes reactions which seemingly proceed by way of carbocation intermediates. These intermediates, in turn, may arise from a photochemically produced trans cycloalkene which is so highly strained that protonation by even weak acids such as methanol may proceed readily. This picture is supported by product analysis, deuterium labeling experiments, and stereochemical studies.


Antiretroviral therapy in HIV-infected children.
The pediatric highly-active antiretroviral therapy (HAART) has shown enormous progress in recent years but still, a high percentage of children continue to experience treatment failure. The main causes found responsible are the development of drug resistance, inadequate dosing and poor adherence. This review is aimed at exploring the current status of antiretroviral therapy in children with focus on the interaction between disease, drug and patient behavior, all of which are strongly correlated .An overview of HIV viral characteristics and of the available antiretroviral drug classes currently combined to avoid development of resistance has been also discussed.


Breathomics for the clinician: the use of volatile organic compounds in respiratory diseases.
Exhaled breath analysis has the potential to provide valuable insight on the status of various metabolic pathways taking place in the lungs locally and other vital organs, via systemic circulation. For years, volatile organic compounds (VOCs) have been proposed as feasible alternative diagnostic and prognostic biomarkers for different respiratory pathologies.We reviewed the currently published literature on the discovery of exhaled breath VOCs and their utilisation in various respiratory diseasesKey barriers in the development of clinical breath tests include the lack of unified consensus for breath collection and analysis and the complexity of understanding the relationship between the exhaled VOCs and the underlying metabolic pathways. We present a comprehensive overview, in light of published literature and our experience from coordinating a national breathomics centre, of the progress made to date and some of the key challenges in the field and ways to overcome them. We particularly focus on the relevance of breathomics to clinicians and the valuable insights it adds to diagnostics and disease monitoring.Breathomics holds great promise and our findings merit further large-scale multicentre diagnostic studies using standardised protocols to help position this novel technology at the centre of respiratory disease diagnostics.


It is not a big deal: a qualitative study of clinical biobank donation experience and motives.
The success of biobanking is directly linked to the willingness of people to donate their biological materials for research and storage. Ethical issues related to patient consent are an essential component of the current biobanking agenda. The majority of data available are focused on population-based biobanks in USA, Canada and Western Europe. The donation decision process and its ethical applications in clinical populations and populations in countries with other cultural contexts are very limited. This study aimed to evaluate the decision-making experience of the clinical biobank donors, as well as psychological and social motivators and deterrents of this decision and associated ethical risks. Semi-structured interviews were conducted in two medical institutions, in St Petersburg (Russia), in 2016-2017, among 13 donors of a clinical biobank (pregnant women, cardiac patients, and patients with multiple sclerosis) and three donation organisers-medical specialists involved in recruiting donors for a clinical biobank. Analysis of interview data was based on qualitative content analysis. Donors of a clinical biobank express beliefs in the absence of risks associated with the donation. The primary motivators for donating to the biobank were: prosocial, indirect reciprocity (response to or anticipation of an act in kind by a third party), intrinsic motivation (to enhance their self-esteem and satisfying their curiosity about the donation process), and comparability with personal values. A high level of trust in biomedical research and the particular physician can contribute to a favourable decision. The overall decision-making process regarding the biobank donation could be described as quick and not based on a careful reading of informed consent documents. The integration of biobank donation decision-making in the process of medical care might prompt patient to donate to biobank without proper consideration. The specific type of therapeutic misconception-the presence of unrealistic hope that donation could provide a direct benefit for a third person in need was discovered. Patients recruited to a clinical biobank in Russia have virtually no concerns as to the storage of their biomaterials. The donation decision is mainly motivated by prosocial attitudes and other factors that are similar to the motivating factors of blood donation. The fact of going through inpatient treatment and poor differentiation between donation for other people's benefit and for research purposes can make the process of obtaining consent more ethically problematic.


Metagenomic islands of hyperhalophiles: the case of Salinibacter ruber.
Saturated brines are extreme environments of low diversity. Salinibacter ruber is the only bacterium that inhabits this environment in significant numbers. In order to establish the extent of genetic diversity in natural populations of this microbe, the genomic sequence of reference strain DSM 13855 was compared to metagenomic fragments recovered from climax saltern crystallizers and obtained with 454 sequencing technology. This kind of analysis reveals the presence of metagenomic islands, i.e. highly variable regions among the different lineages in the population. Three regions of the sequenced isolate were scarcely represented in the metagenome thus appearing to vary among co-occurring S. ruber cells. These metagenomic islands showed evidence of extensive genomic corruption with atypically low GC content, low coding density, high numbers of pseudogenes and short hypothetical proteins. A detailed analysis of island gene content showed that the genes in metagenomic island 1 code for cell surface polysaccharides. The strain-specific genes of metagenomic island 2 were found to be involved in biosynthesis of cell wall polysaccharide components. Finally, metagenomic island 3 was rich in DNA related enzymes. The genomic organisation of S. ruber variable genomic regions showed a number of convergences with genomic islands of marine microbes studied, being largely involved in variable cell surface traits. This variation at the level of cell envelopes in an environment devoid of grazing pressure probably reflects a global strategy of bacteria to escape phage predation.


Dealkylative intercepted rearrangement reactions of sulfur ylides.
Sulfur ylides are well-known to undergo sigmatropic rearrangement reaction. Herein, we describe a novel reactivity of sulfur ylides, which provides access to the product of a formal functional group metathesis upon dealkylative interception of the rearrangement process. Using a simple iron catalyst and in situ generated diazoalkanes this method provides access to α-mercaptoacetonitrile derivatives.


Genetic evidence for male-biased dispersal in the Qinghai toad-headed agamid Phrynocephalus vlangalii and its potential link to individual social interactions.
Sex-biased dispersal has profound impacts on a species' biology and several factors have been attributed to its evolution, including mating system, inbreeding avoidance, and social complexity. Sex-biased dispersal and its potential link to individual social interactions were examined in the Qinghai toad-headed agamid (Phrynocephalus vlangalii). We first determined the pattern of sex-biased dispersal using population genetic methods. A total of 345 specimens from 32 sites in the Qaidam Basin were collected and genotyped for nine microsatellite DNA loci. Both individual-based assignment tests and allele frequency-based analyses were conducted. Females revealed much more genetic structure than males and all results were consistent with male-biased dispersal. First-generation migrants were also identified by genetic data. We then examined eight social interaction-related morphological traits and explored their potential link to sex-biased dispersal. Female residents had larger heads and longer tails than female migrants. The well-developed signal system among females, coupled with viviparity, might make remaining on natal sites beneficial, and hence promote female philopatry. Dominant females with larger heads were more likely to stay. Contrary to females, male migrants had larger heads and belly patches than residents, suggesting that dispersal might confer selective advantages for males. Such advantages may include opportunities for multiple mating and escaping from crowded sites. Large belly patches and several other morphological traits may assist their success in obtaining mates during dispersal. Furthermore, a relatively high relatedness (R = 0.06) among females suggested that this species might have rudimentary social structure. Case studies in "less" social species may provide important evidence for a better understanding of sex-biased dispersal.


Chromogranin-reactive endocrine cells in argyrophilic carcinomas ("carcinoids") and normal tissue of the breast.
Breast carcinomas, either positive or negative with the Grimelius' silver procedure, benign fibroadenomas, duct papillomas, and areas of histologically normal breast tissue were tested immunocytochemically with the mouse monoclonal antibody LK2H10 directed against human chromogranin. This is regarded as a general stain for polypeptide-hormone-producing cells and tumors. In 3 of the 9 cases of argyrophilic carcinoma, but in none of 12 ductal infiltrating carcinomas, chromogranin-positive cells were found: the number of reactive cells was very low in 1 case, while in the other 2 carcinomas about 50% of the argyrophilic cells appeared stained. In areas of histologically normal breast tissue, rare argyrophilic chromogranin-positive cells were detected. This study is the first reported evidence concerning the presence of endocrinelike cells probably belonging to the diffuse neuroendocrine system in the normal mammary parenchyma. Our data are consistent with the endocrine nature of at least some of the breast argyrophilic carcinomas.


Understanding domain movements and interactions of Pseudomonas aeruginosa lipase with lipid molecule tristearoyl glycerol: A molecular dynamics approach.
Lipases are biocatalysts which exhibit optimal activity at the aqueous-lipid interface. Molecular Dynamics (MD) Simulation studies on lipases have revealed the structural changes occurring in the enzyme, at the loop-helix-loop, often designated as the "lid", which is responsible for its interfacial activation. In recent years, MD simulation of lipases at molecular level have been studied in detail, whereas very few studies are carried over on its interaction with lipid molecules. Hence, in the current study we have investigated molecular interaction of bacterial lipase (Pseudomonas aeruginosa lipase, PAL) with a lipid molecule (tristearoyl glycerol, TGL). This provides an insight into the interfacial activation of the enzyme. The lipid molecule was placed near the lids of the enzyme and MD simulations were performed for 100 ns to understand the nature and site of the interaction. The results clearly indicate that, the presence of a lipid molecule near the lids affects the motion of the enzyme through changes in conformation. Lipid molecule near the lids reduces the movements of both lids, and the TGL molecule was observed moving towards the active site. The movement of the lids, surface accessibility and the domain movements of PAL are discussed and the results provide valuable insight in to the role played by the two lids in the interfacial activation of PAL with TGL.


Welcome to the neighbourhood: interspecific genotype by genotype interactions in Solidago influence above- and belowground biomass and associated communities.
Intra- and interspecific plant-plant interactions are fundamental to patterns of community assembly and to the mixture effects observed in biodiversity studies. Although much research has been conducted at the species level, very little is understood about how genetic variation within and among interacting species may drive these processes. Using clones of both Solidago altissima and Solidago gigantea, we found that genotypic variation in a plant's neighbours affected both above- and belowground plant traits, and that genotype by genotype interactions between neighbouring plants impacted associated pollinator communities. The traits for which focal plant genotypic variation explained the most variation varied by plant species, whereas neighbour genotypic variation explained the most variation in coarse root biomass. Our results provide new insight into genotypic and species diversity effects in plant-neighbour interactions, the extended consequences of diversity effects, and the potential for evolution in response to competitive or to facilitative plant-neighbour interactions.


Nitric oxide levels in human preneoplastic colonocytes determine their susceptibility toward antineoplastic agents.
The efficacy of antineoplastic compounds can depend heavily on the genetic background of the cells exposed to the drugs. This becomes evident by the fact that HT-29 human colon cancer cells but not primary murine nontransformed colonocytes are efficiently submitted to apoptosis by the flavonoid flavone. By determining caspase-3 activation, plasma membrane disintegration, and nuclear fragmentation, we show here that flavone also does not promote apoptosis in preneoplastic NCOL-1 colonocytes derived from a nontransformed human biopsy specimen. In clear contrast, the antitumor drug camptothecin potently induces apoptosis in NCOL-1 cells associated with a specific down-regulation of the antiapoptotic factor bcl-XL at the mRNA and protein levels and with the activation of the mitochondrial apoptosis pathway. Confocal microscopy revealed an increased production of superoxide anion radicals in the mitochondria of NCOL-1 cells that preceded the apoptotic events. However, in the case of flavone, the mitochondrial oxygen radicals were effectively scavenged by physiological concentrations of nitric oxide (NO), whereas in the case of camptothecin, the available nitric oxide was rapidly scavenged by the production of large quantities of cytosolic superoxide anions. Increasing the levels of nitric oxide inside NCOL-1 cells by sodium nitroprusside prevented the apoptosis induction by camptothecin. Reducing the levels of nitric oxide by using the NO synthase inhibitor, Nomega-nitro-l-arginine methyl ester in NCOL-1 cells or using HT-29 cells that intrinsically have low NO levels enabled flavone to trigger the apoptosis pathway. In conclusion, our studies demonstrate that the intracellular levels of nitric oxide significantly change the apoptotic response to antineoplastic agents in colonic cells.


CADM1, MAL and miR124-2 methylation analysis in cervical scrapes to detect cervical and endometrial cancer.
Gene promoter hypermethylation is recognised as an essential early step in carcinogenesis, indicating important application areas for DNA methylation analysis in early cancer detection. The current study was set out to assess the performance of CADM1, MAL and miR124-2 methylation analysis in cervical scrapes for detection of cervical and endometrial cancer. A series of cervical scrapes of women with cervical (n=79) or endometrial (n=21) cancer, cervical intraepithelial neoplasia grade 3 (CIN3) (n=16) or CIN2 (n=32), and women without evidence of CIN2 or worse (n=120) were assessed for methylation of CADM1, MAL and miR124-2. Methylation analysis was done by the PreCursor-M assay, a multiplex quantitative methylation-specific PCR. All samples of women with cervical cancer (79/79, 100%), independent of the histotype, and 76% (16/21; 95% CI 58.0% to 94.4%) of women with endometrial cancer scored positive for DNA methylation for at least one of the three genes. In women without cancer, methylation frequencies increased significantly with severity of disease from 19.2% (23/120; 95% CI 12.1% to 26.2%) in women without CIN2 or worse to 37.5% (12/32; 95% CI 20.7% to 54.3%) and 68.8% (11/16; 95% CI 46.0% to 91.5%) in women with CIN2 and CIN3, respectively. Overall methylation positivity and the number of methylated genes increased proportionally to the lesion severity. DNA methylation analysis of CADM1, MAL and miR124-2 in cervical scrapes consistently detects cervical cancer and the majority of CIN3 lesions, and has the capacity to broaden its use on cervical scrapes through the detection of a substantial subset of endometrial carcinomas.


Falls among frail older people in residential care.
A prospective study was carried out to investigate the incidence, circumstances, and injuries from falls among frail older people living in three different types of Swedish residential care settings. The settings were senior citizens' apartments, an old people's home, and a group dwelling for people with dementia. The falls were registered during the three-year study period on a semi-structured fall report, and injurious falls were categorized according to severity. In total 428 falls occurred among 121 residents. The incidence rate of falls at the group dwelling was twice the rates of the old people's home and senior citizens' apartments (4282 compared with 1709 and 2114 falls per 1000 person-years respectively). Some 27% of the falls occurred during the night (2100h to 0600h) and 28% were related to a visit to the lavatory. The presence of acute disease at the time of a fall was diagnosed in 23% of the falls. Some type of injury occurred in 118 falls (28%) and 36 of these (8%) led to moderate or serious injuries. In total 48 fractures were diagnosed. In a preventive programme for falls and injuries in residential care settings, areas of particular interest should include falls after mealtimes and falls at night, conditions of acute diseases, rising up from sitting, walking, and activities in progress, especially visits to the lavatory.


Predictors of fielding performance in professional baseball players.
The ultimate zone-rating extrapolation (UZR/150) rates fielding performance by runs saved or cost within a zone of responsibility in comparison with the league average (150 games) for a position. Spring-training anthropometric and performance measures have been previously related to hitting performance; however, their relationships with fielding performance measures are unknown. To examine the relationship between anthropometric and performance measurements on fielding performance in professional baseball players. Body mass, lean body mass (LBM), grip strength, 10-yd sprint, proagility, and vertical-jump mean (VJMP) and peak power (VJPP) were collected during spring training over the course of 5 seasons (2007-2011) for professional corner infielders (CI; n = 17, fielding opportunities = 420.7 ± 307.1), middle infielders (MI; n = 14, fielding opportunities = 497.3 ± 259.1), and outfielders (OF; n = 16, fielding opportunities = 227.9 ± 70.9). The relationships between these data and regular-season (100-opportunity minimum) fielding statistics were examined using Pearson correlation coefficients, while stepwise regression identified the single best predictor of UZR/150. Significant correlations (P < .05) were observed between UZR/150 and body mass (r = .364), LBM (r = .396), VJPP (r = .397), and VJMP (r = .405). Of these variables, stepwise regression indicated VJMP (R = .405, SEE = 14.441, P = .005) as the single best predictor for all players, although the addition of proagility performance strengthened (R = .496, SEE = 13.865, P = .002) predictive ability by 8.3%. The best predictor for UZR/150 was body mass for CI (R = .519, SEE = 15.364, P = .033) and MI (R = .672, SEE = 12.331, P = .009), while proagility time was the best predictor for OF (R = .514, SEE = 8.850, P = .042). Spring-training measurements of VJMP and proagility time may predict the defensive run value of a player over the course of a professional baseball season.


Effect of Personalized Incentives on Dietary Quality of Groceries Purchased: A Randomized Crossover Trial.
Many factors are associated with food choice. Personalized interventions could help improve dietary intake by using individual purchasing preferences to promote healthier grocery purchases. To test whether a healthy food incentive intervention using an algorithm incorporating customer preferences, purchase history, and baseline diet quality improves grocery purchase dietary quality and spending on healthy foods. This was a 9-month randomized clinical crossover trial (AB-BA) with a 2- to 4-week washout period between 3-month intervention periods. Participants included 224 loyalty program members at an independent Rhode Island supermarket who completed baseline questionnaires and were randomized from July to September 2018 to group 1 (AB) or group 2 (BA). Data analysis was performed from September 2019 to May 2020. Participants received personalized weekly coupons with nutrition education during the intervention period (A) and occasional generic coupons with nutrition education during the control period (B). An automated study algorithm used customer data to allocate personalized healthy food incentives to participant loyalty cards. All participants received a 5% grocery discount. Grocery Purchase Quality Index-2016 (GPQI-16) scores (range, 0-75, with higher scores denoting healthier purchases) and percentage spending on targeted foods were calculated from cumulative purchasing data. Participants in the top and bottom 1% of spending were excluded. Paired t tests examined between-group differences. The analytical sample included 209 participants (104 in group 1 and 105 in group 2), with a mean (SD) age of 55.4 (14.0) years. They were predominantly non-Hispanic White (193 of 206 participants [94.1%]) and female (187 of 207 participants [90.3%]). Of 161 participants with income data, 81 (50.3%) had annual household incomes greater than or equal to $100 000. Paired t tests showed that the intervention increased GPQI-16 scores (between-group difference, 1.06; 95% CI, 0.27-1.86; P = .01) and percentage spending on targeted foods (between-group difference, 1.38%; 95% CI, 0.08%-2.69%; P = .04). During the initial intervention period, group 1 (AB) and group 2 (BA) had similar mean (SD) GPQI-16 scores (41.2 [6.6] vs 41.0 [7.5]) and mean (SD) percentage spending on targeted healthy foods (32.0% [10.8%] vs 31.0% [10.5%]). During the crossover intervention period, group 2 had a higher mean (SD) GPQI-16 score than group 1 (42.9 [7.7] vs 41.0 [6.8]) and mean (SD) percentage spending on targeted foods (34.0% [12.1%] vs 32.0% [13.1%]). This pilot trial demonstrated preliminary evidence for the effectiveness of a novel personalized healthy food incentive algorithm to improve grocery purchase dietary quality. ClinicalTrials.gov Identifier: NCT03748056.


Beta-adrenergic receptor blockade in angiosarcoma: Which beta-blocker to choose?
Beta-blockers are currently studied to improve therapeutic options for patients with angiosarcoma. However, most of these patients have no cardiovascular co-morbidity and it is therefore crucial to discuss the most optimal pharmacological properties of beta-blockers for this population. To maximize the possible effectiveness in angiosarcoma, the use of a non-selective beta-blocker is preferred based on in vitro data. To minimize the risk of cardiovascular adverse events a beta-blocker should ideally have intrinsic sympathomimetic activity or vasodilator effects, e.g. labetalol, pindolol or carvedilol. However, except for one case of carvedilol, only efficacy data of propranolol is available. In potential follow-up studies labetalol, pindolol or carvedilol can be considered to reduce the risk of cardiovascular adverse events.


Highly sensitive and selective detection of single-nucleotide polymorphisms using gold nanoparticle MutS enzymes and a micro cantilever resonator.
Mutant DNAs are important markers useful for the diagnosis of human disease. Single-nucleotide polymorphisms (SNPs) represent the most common types of DNA mutations. As there is only a one base pair change in a single nucleotide between the SNP and the wild-type DNA, it is difficult to distinguish the SNPs. In this report, a highly sensitive and selective detection and discrimination of SNPs is performed using MutS, gold nanoparticles (AuNP) and a resonator. A single mismatched base exists between the SNP mutation and the probe DNA on the resonator, and MutS binds to the DNA at the location of the mismatch. As MutS is attached to AuNP (MutS-AuNP), both MutS and AuNP are adsorbed onto the resonator. The detection is based on the resonance frequency shift of the resonator following the adsorption of MutS-AuNP on the resonator. Highly sensitive detection of DNA mutations was achieved using AuNPs that act as mass amplifiers, and the obtained limit of detected was 100 fM. Additionally, our proposed method detected mutations in the presence of as little as 0.1% wild-type, and discrimination of specific mutations was also achieved. The results obtained from our proposed method suggest its potential for diagnosing cancer patients.


Regulation of food intake by metabolic fuels in white-crowned sparrows.
Migratory birds rely on increased fat storage and fatty acid utilization to meet seasonal changes of energy expenditure and as a result increase food intake and fat stores before migration. To determine whether their feeding behavior is sensitive to carbohydrate and/or fatty acid utilization, white-crowned sparrows maintained on short daylength (9L15D) were injected intraperitoneally with 2-deoxy-D-glucose (2-DG) or 2,5-anhydro-D-mannitol (2,5-AM). Low doses of 2-DG (25 or 50 mg/kg) had no effect on food intake, and higher doses (100 or 300 mg/kg) significantly suppressed feeding after 1 and 2 h. No dose of 2-DG increased meal size. Similarly, low doses of 2,5-AM (25, 50, or 100 mg/kg) had no effect on food intake, and higher doses (300 and 600 mg/kg) significantly suppressed intake. These data suggest that decreased carbohydrate metabolism does not elicit feeding in this species. Importantly, these drugs, as well as insulin and glucagon, were demonstrated to increase plasma fatty acids as well as to decrease feeding. Injections of tributyrin (100, 300, 600, or 2,000 mg/kg i.p.) or glycerol (300, 450, and 600 mg/kg) also significantly suppressed 60-min and 120-min food intake dose dependently in these birds, and equimolar glucose (1,200 mg/kg) had no effect. We conclude that feeding by the white-crowned sparrow is unresponsive to manipulations of carbohydrate metabolism and is decreased after manipulations that increase plasma lipids.


The p300 as a marker of waning attention and error propensity.
Action errors can occur when routine responses are triggered inappropriately by familiar cues. Here, EEG was recorded as volunteers performed a "go/no-go" task of long duration that occasionally and unexpectedly required them to withhold a frequent, routine response. EEG components locked to the onset of relevant go trials were sorted according to whether participants erroneously responded to immediately subsequent no-go trials or correctly withheld their responses. Errors were associated with a significant relative reduction in the amplitude of the preceding P300, that is, a judgement could be made bout whether a response-inhibition error was likely before it had actually occurred. Furthermore, fluctuations in P300 amplitude across the task formed a reliable associate of individual error propensity, supporting its use as a marker of sustained control over action.


Radiation arteritis following treatment for Wilms' tumor: an unusual case of weight loss.
Wilms' tumor is the most common pediatric primary renal cancer and is highly responsive to surgery and chemotherapy. The role of radiotherapy has evolved in the last three decades from the use of stepwise incremental doses in all patients to the current concept of added radiotherapy in advanced cases or in those with unfavorable pathology. To the authors' knowledge, this is the first case of a young woman with prior history of Wilms' tumor and significant weight loss due to radiation arteritis involving the abdominal vasculature. A 31-year-old woman presented with a history of weight loss and severe malnutrition. An angiogram revealed that the aorta was occluded below the renal artery. The celiac artery and the superior mesenteric artery were occluded at the origin, and large intercostal collaterals reconstituted the pelvic circulation. She was initially treated with total parenteral nutrition (TPN) and underwent an infrarenal aortic bypass surgery. Histopathology of the aorta revealed intimal fibrocalcific thickening and changes consistent with radiation-induced arteritis. Later, she was readmitted with progressive hepatic insufficiency. Despite intensive medical therapy, she died of multi-organ failure.


X-ray fibre diffraction of cartilage proteoglycan aggregates containing hyaluronic acid.
Ordered conformations of proteoglycan-hyaluronic acid aggregates in the intercellular matrix in cartilage were observed by X-ray diffraction. The sodium salt form of three samples, (a) aggregated proteoglycan, (b) disaggregated proteoglycan and (c) reconstituted disaggregated proteoglycan, give essentially similar X-ray fibre-type diffraction photographs. The patterns correlate with the chondroitin 4-sulphate component and can be interpreted as twofold helical conformations, similar to that observed previously for the free acid form of chondroitin 4-sulphate (Isaac & Atkins, 1973). The information takes us one step nearer the situation found in cartilage in vivo.


Ontogenetic bases of canine dimorphism in anthropoid primates.
This study tests hypotheses regarding the ontogeny of canine tooth size dimorphism in five anthropoid primate species (Saguinus fuscicollis, Macaca mulatta, Cercocebus atys, Papio hamadryas, and Mandrillus sphinx). Canine measurements and chronological age data are analyzed to determine if bimaturism, a sex difference in the age at which eruption ceases, accounts for canine tooth sexual dimorphism. Canine height measurements are evaluated through a variety of regression techniques. Results show a lack of sexual dimorphism in Saguinus. While size dimorphism is absent in the deciduous teeth of all species analyzed, the adult teeth in cercopithecines become increasingly dimorphic through ontogeny. Female adult tooth eruption regularly precedes male tooth eruption, and regression-based eruption trajectories for both sexes intersect at about the age at which the female tooth reaches adult size. Males erupt the tooth later and more rapidly than females. Males also reach a larger adult size than females by erupting the tooth for much longer periods of time. Bimaturism is primary in the production of dimorphism, but rates of eruption show modest variation. These results point to the scheduling of sexual selection through intermale competition as a primary factor determining male eruption timing, rates of eruption, and adult size. Life history factors may play a role in determining the relations between the scheduling of intrasexual competition and canine eruption. Female contributions to sexual dimorphism are apparent in these species, suggesting that similar levels of dimorphism can be attained through diverse ontogenetic pathways.


Hepatitis B virus-associated antigen deposition in renal tissue from patients with systemic lupus erythematosus.
To determine the significance of hepatitis B virus (HBV)-associated antigen deposition in renal tissue from patients with systemic lupus erythematosus (SLE). The medical records of 166 inpatients with lupus nephritis and 384 controls without SLE were analyzed retrospectively. Patients with SLE were classified as positive or negative depending on whether HBV-associated antigen deposition was detected in renal biopsies. HBV-associated antigen deposition was mainly detected in renal tissue from patients with SLE (50.6%), primary renal glomerular disease (20.8%), and allergic purpura (21.7%). It was not detected in renal tissue from patients with diabetic nephropathy, hypertensive nephrosclerosis, thin basement membrane nephropathy, or Alport syndrome. Hepatitis B surface antigen and core antigen were deposited in the mesangial region and vascular loops. The positive group had a significantly higher frequency of IgG, IgA, and IgM deposition than the negative group (53.6% vs 30.5%; p < 0.01). There was no significant difference in the types of lupus nephritis observed between the 2 groups. There was a high prevalence of HBV-associated antigen deposition in renal tissue of patients with SLE by indirect immunofluorescence, which may result mainly from the cross-reactivity with deposited immunoglobulins.


Usefulness of plasma galectin-3 levels in systolic heart failure to predict renal insufficiency and survival.
Galectin-3 plays an important role in fibroblast activation and fibrosis in animal models. Increased galectin-3 levels are associated with poor long-term survival in heart failure (HF). We examined the relation between plasma galectin-3 levels and myocardial indexes of systolic HF. We measured plasma galectin-3 in 133 subjects with chronic HF and 45 with advanced decompensated HF using echocardiographic and hemodynamic evaluations. In the chronic HF cohort, median plasma galectin-3 level was 13.9 ng/ml (interquartile range 12.1 to 16.9). Higher galectin-3 was associated with more advanced age (r = 0.22, p = 0.010), poor renal function (estimated glomerular filtration rate, r = -0.24, p = 0.007; cystatin C, r = 0.38, p <0.0001) and predicted all-cause mortality (hazard ratio 1.86, 95% confidence interval 1.36 to 2.54, p <0.001). In multivariate analysis, galectin-3 remained an independent predictor of all-cause mortality after adjusting for age, estimated glomerular filtration rate, left ventricular (LV) ejection fraction, and mitral early diastolic myocardial relaxation velocity at septal mitral annulus (hazard ratio 1.94, 95% confidence interval 1.30 to 2.91, p = 0.001). However, galectin-3 did not predict the combined end point of all-cause mortality, cardiac transplantation, or HF hospitalization (p >0.05). Furthermore, there were no relations between galectin-3 and LV end-diastolic volume index (r = -0.05, p = 0.61), LV ejection fraction (r = 0.10, p = 0.25), or LV diastolic function (mitral early diastolic myocardial relaxation velocity at septal mitral annulus, r = 0.06, p = 0.52; left atrial volume index, r = 0.08, p = 0.41). In the advanced decompensated HF cohort, we did not observe any relation between galectin-3 and echocardiographic or hemodynamic indexes. In conclusion, high plasma galectin-3 levels were associated with renal insufficiency and poorer survival in patients with chronic systolic HF. However, we did not observe a relation between galectin-3 and echocardiographic or hemodynamic indexes.