Human metapneumovirus infection in lung transplant recipients: clinical presentation and epidemiology.
In immunocompromised patients, respiratory viruses are likely to lead to lower respiratory tract infections that cause severe morbidity and mortality. We conducted a prospective study from September 2003 to March 2004 to investigate the epidemiology and impact of human metapneumovirus (hMPV) on lung transplant recipients. We collected 265 nasopharyngeal aspirates and bronchoalveolar lavages: 51 samples originated from immunocompromised adults, 49 from lung transplant recipients, and 2 from a bone marrow recipient. Additionally, 209 samples from hospitalized non-immunocompromised children and 5 samples from immunocompromised children were analyzed for replicating hMPV by a combined cell culture and reverse transcriptase polymerase chain reaction method that includes DNA sequencing of selected isolates. Twelve samples from lung transplant recipients (25%), 29 from non-immunocompromised children (14%), and 2 from a child with a renal transplant were positive for hMPV. Most of the cases clustered within 2 outbreaks in October/November and March. In immunocompromised patients, hMPV was isolated throughout the entire observation period. The same viral strains circulated in hospitalized children and in lung transplant recipients. A different strain was isolated during the interepidemic period, suggesting that hMPV infections may be transmitted among lung transplant recipients independently from the community outbreak situation. Clinical signs and symptoms varied from no symptoms to severe pneumonia or acute graft rejection. Significantly, the only deaths occurred in the hMPV-positive group. Of interest, identification of replicating hMPV significantly correlated with rejection symptoms present at the time point of sample collection. Results of the study suggest that hMPV may be added to the list of pathogens that are possibly associated with episodes of allograft rejection.


Preparation of gadopentetic acid-loaded chitosan microparticles for gadolinium neutron-capture therapy of cancer by a novel emulsion-droplet coalescence technique.
Biodegradable gadopentetic acid (Gd-DTPA)-loaded chitosan microparticles (Gd-microCPs) were prepared as a device for gadolinium neutron-capture therapy (Gd-NCT) by a novel emulsion-droplet coalescence technique: a water-in-oil (w/o) emulsion A containing chitosan and Gd-DTPA in droplets and a w/o emulsion B containing NaOH in droplets were mixed and stirred to solidify chitosan as a result of collision and coalescence between droplets of each emulsion. Gd-microCPs prepared by using 100% deacetylated chitosan in 25% Gd-DTPA solution were 4.1 microns (non-lyophilized) and 3.3 microns (lyophilized) in mass median diameter, and were 3.4% in gadolinium content, corresponding to 11.7% as Gd-DTPA. The particle size and gadolinium content of Gd-microCPs were not affected by Gd-DTPA concentration in the chitosan medium. However, the deacetylation degree of chitosan influenced the particle size; as the deacetylation degree of chitosan decreased, the particle size increased. The incorporated Gd-DTPA was not released entirely from Gd-microCPs in an isotonic phosphate buffered saline solution despite the high water-solubility of Gd-DTPA (less than 0.8% with every type of Gd-microCPs). These results indicated that ion-complex formation might be contributable to incorporation of Gd-DTPA. As a preliminary study, it was confirmed that the loss of gamma-ray emission by gadolinium-loading in microparticle was negligible in the thermal neutron irradiation test in vitro. These results suggested that Gd-microCPs could be a useful device for intratumoral injection into solid tumor on Gd-NCT.


Brain delivery of buspirone hydrochloride chitosan nanoparticles for the treatment of general anxiety disorder.
The present work discusses the preparation, characterization and in vivo evaluation of thiolated chitosan nanoparticles (TCS-NPs) of buspirone hydrochloride (BUH) for brain delivery through intranasal route. TCS NPs were prepared by ionic gelation method and characterized for various parameters. The NPs formed were having particle size of 226.7±2.52nm with PDI 0.483±0.031. Drug entrapment efficiency (EE) and loading capacity (LC) were found to be 81.13±2.8 and 49.67±5.5%. The cumulative percentage drug permeation through nasal mucosa was 76.21%. Bioadhesion study carried out on porcine mucin and showed a bioadhesion efficiency of 90.218±0.134%. Nose-to-brain delivery of placebo NPs was investigated by confocal laser scanning microscopy (CLSM) technique using rhodamine-123 as a marker. The brain concentration achieved after intranasal administration of TCS-NPs was 797.46±35.76ng/ml with tmax 120min which was significantly higher than achieved after intravenous administration on BUH solution 384.15±13.42ng/ml and tmax of 120min and intranasal administration of BUH solution 417.77±19.24ng/ml and tmax 60min.


Oral somatosensory awareness.
Oral somatosensory awareness refers to the somatic sensations arising within the mouth, and to the information these sensations provide about the state and structure of the mouth itself, and objects in the mouth. Because the oral tissues have a strong somatosensory innervation, they are the locus of some of our most intense and vivid bodily experiences. The salient pain of toothache, or the habit of running one's tongue over one's teeth when someone mentions "dentist", provide two very different indications of the power of oral somatosensory awareness in human experience and behaviour. This paper aims to review the origins and structure of oral somatosensory awareness, focussing on quantitative, mechanistic studies in humans. We first extend a model of levels of bodily awareness to the specific case of the mouth. We then briefly summarise the sensory innervation of oral tissues, and their projections in the brain. We next describe how these peripheral inputs give rise to perceptions of objects in the mouth, such as foods, liquids and oral devices, and also of the mouth tissues themselves. Finally, we consider the concept of a conscious mouth image, and the somatosensory basis of "mouth feel". The theoretical framework outlined in this paper is intended to facilitate scientific studies of this important site of human experience.


Mechanisms of intermittent ventricular parasystole due to type II second degree entrance block.
Three patients with intermittent ventricular parasystole are reported in whom the presence of second degree entrance block of type II or a type similar to that was shown. In all the patients, when a sinus beat occurred within a certain (the first) critical period after the preceding ectopic beat, the parasystolic focus was protected from this sinus impulse. When, on the other hand, a sinus beat occurred beyond another (the second) critical period after the ectopic beat, this sinus impulse reached and discharged the focus without an appreciable conduction delay. In one patient the second critical period was equal to the first one, while, in the other two, the second one was longer than the first one. In these two patients, when a sinus beat occurred between the two critical periods after the ectopic beat, this sinus impulse reached and discharged the focus after marked delay, and thereafter became a manifest or concealed re-entrant ventricular extrasystole. On the basis of these observations, an attempt was made to clarify the difference in mechanism between type I and type II second degree entrance block.


A GC-MS Method for Detection and Quantification of Cathine, Cathinone, Methcathinone and Ephedrine in Oral Fluid.
The stimulating herbal drug khat (cathine, cathinone) and its analog methcathinone are common substances of abuse in most countries. A GC-MS method was developed and validated for the detection and quantification of cathine, cathinone, methcathinone and ephedrine in oral fluid specimens. The analytes and internal standard (amphetamine-d5) were extracted from 0.5 mL oral fluids by ethyl acetate, and then the dried extracts were derivatized with heptafluorobutyric anhydride at 70°C for 30 min. The MS was used in selected ion monitoring mode. Ions monitored were m/z 117, 240 and 330 for cathine, m/z 77, 105 and 240 for cathinone, m/z 105, 210 and 254 for methcathinone, m/z 210, 254 and 344 for ephedrine and m/z 244 and 336 for amphetamine-d5 The calibration curves were linear (r(2)> 0.98) in the concentration range 20-2,000 ng/mL for all analytes. The intra- and inter-assay imprecisions were within (1.6-12.5%) and (1.5-9.5%), respectively, for all analytes. Intra-assay accuracies were between -5.9 and 6.7% for all analytes. The method was successfully applied to detect and quantify the target analytes from oral fluid specimens collected from Khat and methcathinone users.


Telemedicine in the Management of ADHD: Literature Review of Telemedicine in ADHD.
Objective: Telemedicine has been used successfully in several medical specialties with favorable patient outcomes, satisfaction, in a cost-effective manner. However, its use in the context of ADHD remains unclear. Our main aim was to investigate what is known about the use of telemedicine in ADHD. Method: We conducted a systematic search of the literature assessing telemedicine in ADHD in PubMed, PsycINFO, and Medline. Included were original articles published in English with the main aim to assess the use of telemedicine in ADHD. Results: Only 11 articles met our inclusion and exclusion criteria, coming from only three systematic trials of telemedicine in ADHD. The studies suggest that telemedicine is valued by its users, is well accepted, and is associated with improved outcomes. Conclusion: The limited research indicates that telemedicine has potential to expand the delivery of clinical services to patients with ADHD. More work is needed to further evaluate this finding.


Cell growth effects of Epstein-Barr virus leader protein.
B lymphoblastoid cell lines immortalized with P3HR1/633 Epstein-Barr virus (EBV), which has a deletion in the EBV nuclear antigen leader protein (EBNA-LP) gene, were transfected with a vector expressing wild-type EBNA-LP. The EBNA-LP transfectants grew out faster under G418 selection than control cells but expression of EBNA-LP made no significant difference to growth rate or saturation density of the resulting established cell lines. When the cells expressing EBNA-LP were allowed to grow to saturation and then diluted in fresh medium they underwent DNA synthesis more rapidly than control cultures.


Peroxynitrite-mediated oxidation of dichlorodihydrofluorescein and dihydrorhodamine.
The oxidations of dichlorodihydrofluorescein and dihydrorhodamine by peroxynitrite are zero-order in the indicator between pH 3 and 10. The yield of the oxidized products, dichlorofluorescein and rhodamine, significantly increased at pH values>7, and the maximal molar yields were 0.47 +/- 0.04 mol rhodamine and 0.54 +/- 0.06 mol, dichlorofluorescein per mol peroxynitrite at pH 8.5. The increase in yield of oxidized products as a function of pH indicates that the peroxynitrite anion may form an adduct with the indicator, followed by protonation and oxidation of the indicator. Carbon dioxide decreased the yield of fluorescent products to about 5%, relative to peroxynitrite, and the rate of product formation is again zero-order in the indicator. Given this yield, it is proposed that nitrogen dioxide and trioxocarbonate (*1-) are the reactive species that oxidize the indicators.


Colon capsule endoscopy: toward the future.
Colon capsule endoscopy is a wireless and minimally invasive technique for visualization of the whole colon. With recent improvements of technical features in second-generation systems, a more important role for colon capsule endoscopy is rapidly emerging. Although several limitations and drawbacks are yet to be resolved, its usefulness as a tool for colorectal cancer screening and monitoring disease activity in inflammatory bowel diseases has become more apparent with increased use. Further investigations, including multicenter trials, are required to evaluate the substantial role of the colon capsule in managing colorectal diseases.


Temporal and Longitudinal Mercury Trends in Burbot (Lota lota) in the Russian Arctic.
Current understanding of mercury (Hg) dynamics in the Arctic is hampered by a lack of data in the Russian Arctic region, which comprises about half of the entire Arctic watershed. This study quantified temporal and longitudinal trends in total mercury (THg) concentrations in burbot (Lota lota) in eight rivers of the Russian Arctic between 1980 and 2001, encompassing an expanse of 118 degrees of longitude. Burbot THg concentrations declined by an average of 2.6% annually across all eight rivers during the study period, decreasing by 39% from 0.171 μg g-1 wet weight (w.w.) in 1980 to 0.104 μg g-1 w.w. in 2001. THg concentrations in burbot also declined by an average of 1.8% per 10° of longitude from west to east across the study area between 1988 and 2001. These results, in combination with those of previous studies, suggest that Hg trends in Arctic freshwater fishes before 2001 were spatially and temporally heterogeneous, as those in the North American Arctic were mostly increasing while those in the Russian Arctic were mostly decreasing. It is suggested that Hg trends in Arctic animals may be influenced by both depositional and postdepositional processes.


Conjugated linoleic acid pork research.
The driving force behind most conjugated linoleic acid (CLA) research in swine has been related to potential improvements in animal production. Early work that used rodent models indicated that feeding CLA could potentially reduce body fat, increase lean content, increase growth rate, and improve feed conversion efficiency. Producer-backed funding organizations were, therefore, receptive to proposals to extend this research to pigs, and many studies have been completed worldwide. In general, improvements in body composition were found, but evidence indicating that CLA improves growth rate or feed conversion was limited. Inclusion of CLA into pig diets was, however, shown to increase muscle marbling fat and fat hardness, and both of these characteristics have the potential to increase carcass value. Currently, Badische Anilin- & Soda-Fabrik AG (BASF) has the international marketing license to include synthetic CLA in animal feeds, but to date this practice is not approved in Canada or the United States. If and when approval is granted, the next step in realizing CLA's economic potential would be to seek approval for claiming CLA enrichment in pork and pork products. Given the ability of swine to accumulate relatively high amounts of CLA in their tissues, pork and pork products could become an important vehicle for delivery of physiologically significant amounts of CLA to consumers.


Global scientific productivity in the field of PET: a 10-year survey of research activities.
The objective of this study was to assess global research output in the field of PET and to provide a general picture of PET research. Publications on PET from 2007 to 2016 were identified using the Web of Science. The total number of papers, the number of papers adjusted by gross domestic product (GDP)/population size, total citations, and average citations were investigated. A total of 40 670 papers were identified in the field of PET between 2007 and 2016. The number of papers published per year were significantly increased during this period (P=0.000). High-income countries published the maximum papers (89.95%), followed by middle-income countries (10.05%), whereas no papers were published by authors from low-income countries. The USA published the largest number of papers (11 936), followed by Japan (3667), Germany (3424), China (2508), and the UK (2424), and the USA had the highest total number of citations (361 498). The UK had the highest average citations (31.81). Positive correlations were found between the total number of papers and GDP (P=0.000, r=0.909)/population (P=0.000, r=0.772). When normalized by GDP, Denmark ranked the first (23.56), followed by The Netherlands (17.18) and Belgium (15.32). When adjusted for population, Denmark ranked the first (111.55), followed by The Netherlands (87.91) and Switzerland (86.93). Global scientific production represents a rapid increase in the PET field in recent years. The majority of PET papers are from high-income countries. The USA is the most prolific country, whereas some smaller European countries may be more prolific relative to their GDP/population.


Validation of osmotic fragility test and dichlorophenol indophenol precipitation test for screening of thalassemia and Hb E.
The strategy for screening of thalassemia and Hb E by a combination of osmotic fragility (OF) test and dichlorophenol indophenol precipitation (DCIP) test was validated with 436 unrelated Thai subjects. Hemoglobin (Hb) typing, Hb A2 quantitation, PCR and DNA sequence analysis were used as confirmatory methods for diagnosis of thalassemia and hemoglobinopathy. The sensitivity and specificity of this strategy was 100% and 79.7%, respectively. The results assessed by two medical scientists were exactly the same with 93.3% accuracy in comparison with the confirmatory methods. A combination of OF and DCIP has been shown to be a reliable, rapid, simple and sensitive strategy for screening thalassemia and Hb E in the Thai population.


Reactive oxygen species as mediators of angiogenesis signaling: role of NAD(P)H oxidase.
Angiogenesis, a process of new blood vessel growth, contributes to various pathophysiologies such as cancer, diabetic retinopathy and atherosclerosis. Accumulating evidence suggests that cardiovascular diseases are associated with increased oxidative stress in blood vessels. Reactive oxygen species (ROS) such as superoxide and H2O2 cause blood vessels to thicken, produce inflammation in the vessel wall, and thus are regarded as "risk factors" for vascular disease, whereas ROS also act as signaling molecules in many aspects of growth factor-mediated physiological responses. Recent reports suggest that ROS play an important role in angiogenesis; however, its underlying molecular mechanisms remain unknown. Vascular endothelial growth factor (VEGF) induces angiogenesis by stimulating endothelial cell (EC) proliferation and migration primarily through the receptor tyrosine kinase VEGF receptor2 (Flk1/KDR). VEGF binding initiates tyrosine phosphorylation of KDR, which results in activation of downstream signaling enzymes including ERK1/2, Akt and eNOS, which contribute to angiogenic-related responses in EC. Importantly, the major source of ROS in EC is a NAD(P)H oxidase and EC express all the components of phagocytic NAD(P)H oxidase including gp91phox, p22phox, p47phox, p67phox and the small G protein Rac1. We have recently demonstrated that ROS derived from NAD(P)H oxidase are critically important for VEGF signaling in vitro and angiogenesis in vivo. Furthermore, a peptide hormone, angiotensin II, a major stimulus for vascular NAD(P)H oxidase, also plays an important role in angiogenesis. Because EC migration and proliferation are primary features of the process of myocardial angiogenesis, we would like to focus on the recent progress that has been made in the emerging area of NAD(P)H oxidase-derived ROS-dependent signaling in ECs, and discuss the possible roles in angiogenesis. Understanding these mechanisms may provide insight into the components of NAD(P)H oxidase as potential therapeutic targets for treatment of angiogenesis-dependent diseases such as cancer and atherosclerosis and for promoting myocardial angiogenesis in ischemic heart diseases.


Subjective reactions to international research participation: An illustration of ethical considerations with women heading households in Sri Lanka.
There are unique ethical considerations in conducting international research with war and disaster-affected populations that are important for ensuring adequate protection of participants. Of particular importance is the distress that participants may experience as a result of being asked about traumatic stressors, psychological symptoms, and life problems. In this study, trauma-affected Tamil women in Eastern Sri Lanka were asked to report on their research-participation experience after taking part in a larger study on risk and resiliency. Results indicated that most participants experienced emotional upset as a result of taking part in the study. However, the degree of distress was generally not more than they anticipated, and most participants reported they would have participated had they known in advance how they would feel. Most participants perceived some benefit as a result of participating and agreed that items were personally relevant. Emotional distress from participation positively correlated with culturally specific symptoms of anxiety and depression. Contextual stressors and social support were not associated with participation-related distress. We discuss these findings as well as general issues that might arise in international research with trauma-affected populations. (PsycINFO Database Record (c) 2019 APA, all rights reserved).


Chemical ionization tandem mass spectrometer for the in situ measurement of methyl hydrogen peroxide.
A new approach for measuring gas-phase methyl hydrogen peroxide [(MHP) CH(3)OOH] utilizing chemical ionization mass spectrometry is presented. Tandem mass spectrometry is used to avoid mass interferences that hindered previous attempts to measure atmospheric CH(3)OOH with CF(3)O(-) clustering chemistry. CH(3)OOH has been successfully measured in situ using this technique during both airborne and ground-based campaigns. The accuracy and precision for the MHP measurement are a function of water vapor mixing ratio. Typical precision at 500 pptv MHP and 100 ppmv H(2)O is ±80 pptv (2 sigma) for a 1 s integration period. The accuracy at 100 ppmv H(2)O is estimated to be better than ±40%. Chemical ionization tandem mass spectrometry shows considerable promise for the determination of in situ atmospheric trace gas mixing ratios where isobaric compounds or mass interferences impede accurate measurements.


Lipid content and apoptosis of in vitro-produced bovine embryos as determinants of susceptibility to vitrification.
The objective was to evaluate supplementation of fetal calf serum (FCS) and phenazine ethosulfate (PES), a metabolic regulator that inhibits fatty acid synthesis, in culture media during in vitro production (IVP) of bovine embryos. Taking oocyte fertilization (n = 4,320) as Day 0, four concentrations of FCS (0, 2.5, 5, and 10%) and three periods of exposure to PES (without addition-CONTROL; after 60 h-PES Day 2.5 of embryo culture; and after 96 h-PES Day 4) were evaluated. Increasing FCS concentration in the culture media enhanced lipid accumulation (P < 0.05), increased apoptosis in fresh (2.5%: 19.1 ± 1.8 vs 10%: 28.4 ± 2.3, P < 0.05; mean ± SEM) and vitrified (2.5%: 42.8 ± 2.7 vs 10%: 69.2 ± 3.4, P < 0.05) blastocysts, and reduced blastocoele re-expansion after vitrification (2.5%: 81.6 ± 2.5 vs 10%: 67.3 ± 3.5, P < 0.05). The addition of PES in culture media, either from Days 2.5 or 4, reduced lipid accumulation (P < 0.05) and increased blastocoele re-expansion after vitrification ( 72.0 ± 3.0 vs PES Day 2.5: 79.9 ± 2.8 or PES Day 4: 86.2 ± 2.4, P < 0.05). However, just the use of PES from D4 reduced apoptosis in vitrified blastocysts ( 52.0 ± 3.0 vs PES Day 4: 39.2 ± 2.4, P < 0.05). Independent of FCS withdrawal or PES addition to culture media, the in vivo control group had lesser lipid accumulation, a lower apoptosis rate, and greater cryotolerance (P < 0.05). The increased lipid content was moderately correlated with apoptosis in vitrified blastocysts (r = 0.64, P = 0.01). In contrast, the increased apoptosis in fresh blastocysts was strongly correlated with apoptosis in vitrified blastocysts (r = 0.94, P < 0.0001). Therefore, using only 2.5% FCS and the addition of PES from Day 4, increased the survival of IVP embryos after vitrification. Moreover, embryo quality, represented by the fresh apoptosis rate, was better than lipid content for predicting embryo survival after vitrification.


Mixed-phenotype acute leukemia: A cohort and consensus research strategy from the Children's Oncology Group Acute Leukemia of Ambiguous Lineage Task Force.
Optimal chemotherapy for treating mixed-phenotype acute leukemia (MPAL) and the role of hematopoietic stem cell transplantation (HSCT) remain uncertain. Major limitations in interpreting available data are MPAL's rarity and the use of definitions other than the currently widely accepted criteria: the World Health Organization 2016 (WHO2016) classification. To assess the relative efficacy of chemotherapy types for treating pediatric MPAL, the Children's Oncology Group (COG) Acute Leukemia of Ambiguous Lineage Task Force assembled a retrospective cohort of centrally reviewed WHO2016 MPAL cases selected from banking studies for acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). Patients were not treated in COG trials; treatment and outcome data were captured separately. The findings were then integrated with the available, mixed literature to develop a prospective trial in pediatric MPAL. The central review confirmed that 54 of 70 cases fulfilled WHO2016 criteria for MPAL. ALL induction regimens achieved remission in 72% of the cases (28 of 39), whereas AML regimens achieved remission in 69% (9 of 13). The 5-year event-free survival (EFS) and overall survival (OS) rates for the entire cohort were 72% ± 8% and 77% ± 7%, respectively. EFS and OS were 75% ± 13% and 84% ± 11%, respectively, for those receiving ALL chemotherapy alone without HSCT (n = 21). The results of the COG MPAL cohort and a literature review suggest that ALL chemotherapy without HSCT may be the preferred initial therapy. A prospective trial within the COG is proposed to investigate this approach; AML chemotherapy and/or HSCT will be reserved for those with treatment failure as assessed by minimal residual disease. Embedded biology studies will provide further insight into MPAL genomics.


Costs and functional consequences of U.S. roadway crashes.
The comprehensive cost of U.S. motor vehicle crashes was almost $333 billion in 1988. Comprehensive costs add the value of lost quality of life to monetary costs. This paper estimates costs by injury severity for three severity classification systems. It also estimates the functional capacity loss and probability of permanent work-related disability resulting from nonfatal injury. Using only monetary costs in safety decision making inappropriately favors mobility over safety. Comprehensive costs are one appropriate choice. Another acceptable choice is to use years of functional capacity loss plus direct costs to perform cost-effectiveness analysis.


Sociocultural perspective on child occupant protection.
During the past decade substantial effort has been devoted to increasing the use of child safety restraints. This has involved educational programs and, more recently, legislation mandating restraint use by children. Neither of these approaches has had major documented effects on proper restraint use. Misuse is currently high and use decreases dramatically among toddlers and older children. It is maintained that the complexity of the problems of nonuse and misuse has not been fully recognized. A more comprehensive perspective on the issue is presented, focusing on the social and cultural issues involved in attempting to change parental behavior regarding their children's use of restraints. A structured approach to programs for the promotion of safety restraint use suggested by this perspective is presented, highlighting actions that are already being taken and those that need to be taken to develop a comprehensive attack on both nonuse and misuse of safety restraints.


Increased cartilage oligomeric matrix protein concentrations in equine digital flexor tendon sheath synovial fluid predicts intrathecal tendon damage.
To evaluate digital flexor tendon sheath (DFTS) synovial fluid cartilage oligomeric matrix protein (COMP) concentrations as a molecular marker for intrathecal pathology. Case control study. Horses (n=46) with DFTS tenosynovitis; 23 fresh cadaver horses. DFTS synovial fluid samples were collected from clinical cases with noninfected DFTS tenosynovitis and from control DFTS. Clinical and surgical findings were recorded, and dissection of control limbs was performed to confirm the DFTS to be grossly normal. Synovial fluid COMP was quantified using a homologous competitive inhibition ELISA. Abnormalities were identified tenoscopically: intrathecal tendon/ligament tearing was identified in 37 cases and 9 had other lesions. In control horses, synovial fluid COMP was higher in younger horses. Clinical cases with intrathecal tendon/ligament tearing had higher synovial fluid COMP than either clinical cases with other lesions, or controls. In horses ≥5 years old, the sensitivity and specificity of the assay was high for diagnosing intrathecal tendon/ligament tearing. COMP concentrations in DFTS synovial fluid were significantly greater than those in normal horses with noninfected tenosynovitis caused by intrathecal tendon/ligament tearing, but not by other lesions.


Mitophagy in three cases of immune-mediated necrotizing myopathy associated with anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase autoantibodies: ultrastructural and immunohistochemical studies.
Immune-mediated necrotizing myopathy (IMNM) associated with anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) autoantibodies occurs in patients both with and without history of statin-intake. The mechanisms of muscle fiber degeneration in this condition remain unknown. We studied pathological changes in muscle biopsies from three patients lacking history of statin-intake. Ultrastructural observations showed accumulation of degenerating mitochondria, glycogen granules and autophagic vacuoles, forming large composites in three cases, along with various nonspecific changes. The autophagic vacuoles often contained remnants of mitochondria, indicating mitophagy. Furthermore, upregulation of B-cell lymphoma 2/adenovirus E1B 19 kD-interacting protein 3 (BNIP3), a protein involved in mitophagy, was observed in two cases examined. In three cases of sporadic inclusion body myositis, two polymyositis, and three IMNM with anti-signal recognition particle antibody, BNIP3 was upregulated less frequently, and ultrastructural change of mitophagy was rarely seen. These findings suggested that mitophagy plays an important role in muscle fiber degeneration in IMNM with anti-HMGCR autoantibodies.


Trends in head and neck cancer incidence in relation to smoking prevalence: an emerging epidemic of human papillomavirus-associated cancers?
The trends in head and neck cancer incidence and smoking prevalence are reviewed, discussing where such trends parallel but also how and why they may not. In the U.S., public health efforts at tobacco control and education have successfully reduced the prevalence of cigarette smoking, resulting in a lower incidence of head and neck cancer. Vigilance at preventing tobacco use and encouraging cessation should continue, and expanded efforts should target particular ethnic and socioeconomic groups. However, an unfortunate stagnation has been observed in oropharyngeal cancer incidence and likely reflects a rising attribution of this disease to oncogenic human papillomavirus, in particular type 16 (HPV-16). For the foreseeable future, this trend in oropharyngeal cancer incidence may continue, but with time the effects of vaccination of the adolescent and young adult female population should result in a lower viral prevalence and hopefully a reduced incidence of oropharyngeal cancer. To hasten the reduction of HPV-16 prevalence in the population, widespread vaccination of adolescent and young adult males should also be considered.


Inhibition of innate co-receptor TREM-1 signaling reduces CD4(+) T cell activation and prolongs cardiac allograft survival.
The innate receptor "triggering-receptor-expressed-on-myeloid-cells-1" (TREM-1) enhances downstream signaling of "pattern recognition receptor" (PRR) molecules implicated in inflammatory responses. However the mechanistic role of TREM-1 in chronic heart rejection has yet to be elucidated. We examined the effect of TREM-1(+) antigen-presenting cells (APC) on alloreactive CD4(+) lymphocytes. Bm12 donor hearts were transplanted into wild-type MHC-class-II-mismatched C57BL/6J recipient mice. Progressive allograft rejection of bm12-donor hearts with decreased organ function, severe vasculopathy and allograft fibrosis was evident within 4 weeks. TREM-1(+) CD11b(+) MHC-II(+) F4/80(+) CCR2(+) APC and IFNγ-producing CD4(+) cells were detected during chronic rejection. Peptide inhibition of TREM-1 attenuated graft vasculopathy, reduced graft-infiltrating leukocytes and prolonged allograft survival, while being accompanied by sustained low levels of CD4(+) and CD8(+) cell infiltration. Remarkably, temporary inhibition of TREM-1 during early immune activation was sufficient for long-term allograft survival. Mechanistically, TREM-1 inhibition leads to reduced differentiation and proliferation of IFNγ-producing Th1 cells. In conclusion, TREM-1 influences chronic heart rejection by regulating the infiltration and differentiation of CD4(+) lymphocytes.


[Semmelweis and his outstanding contribution to medicine: washing hands saves lives].
Ignaz Semmelweis was a Hungarian obstetrician who in the nineteenth century, preceding the discoveries of Pasteur and Lister, proposed the infectious etiology of puerperal sepsis. With a simple antiseptic procedure, he achieved marked reduction of the prevalence of this disease. However, he needed to fight against the reluctance of his colleagues who didn't accept his observations although they were, for the first time in the history of science, supported by statistical significance analysis. This report describes biographical data of this revolutionary physician and the circumstances of his strange death based on information not often revealed.


Correlation of lung parenchymal MR signal intensity with pulmonary function tests and quantitative computed tomography (CT) evaluation: a pilot study.
To evaluate the effect of ventilatory impairment on MR signal intensity of the lung parenchyma. Subjects were five normal volunteers (age = 30 +/- 7.9 years, mean +/- SD) and 19 male patients with chronic obstructive lung disease (COPD) (mean age = 70.4 +/- 6.5 years). Coronal MR images were obtained over entire lung fields at full inspiration and full expiration with cardiac triggering on a 1.5T system. Changes in the mean lung intensity between the two respiratory states were normalized by each intercept of the linear regression lines of the signal changes, and the slope of the relationship was calculated. Computed tomography (CT) images were also obtained in COPD patients at full inspiration using a multidetector row CT scanner. Attenuation values less than -950 Hounsfield units (HU) (RA-950) represented the percentage of relative lung area on the CT. The mean slope of COPD patients (0.365 +/- 0.074) was less steep than that of the normal subjects (0.570 +/- 0.124, P < 0.001). In COPD patients, the slope correlated significantly with forced expiratory volume in one second (FEV1, r = 0.508, P = 0.026), but not with RA-950. In COPD patients, lung signal change measured by MRI correlates with airflow obstruction, but not with volume of the emphysema measured by lung CT.


[Chemotherapy of highly malignant thyroid tumors].
In a prospective phase II study 15 patients suffering from anaplastic thyroid carcinoma or thyroid sarcoma were treated by surgery and chemotherapy. Chemotherapy varied according to age of the patient and histological subtype of the tumour. The following regimen was used: 100 mg/m2 BSA CDDP, 20 mg/m2 mitoxantrone and 1.5 mg/m2 vincristine. 10 patients responded to chemotherapy, 4 of whom had a complete response. Responders showed a longer mean and median survival time (20.8 months versus 4.5 ms, 15.5 ms vs. 3.8 ms, respectively) than non-responders. In the group responding to chemotherapy no evidence of metachronous metastases was found. Local recurrence was absent only in the patients showing a complete response. Anaplastic carcinomas with areas of differentiated thyroid carcinoma and small cell carcinomas (after exclusion of malignant lymphoma of the thyroid) showed a higher response rate to chemotherapy than spindle or giant cell carcinoma or thyroid sarcoma.


The cytotoxic, inflammatory and oxidative potential of coconut oil-substituted diesel emissions on bronchial epithelial cells at an air-liquid interface.
Diesel emissions contain high levels of particulate matter (PM) which can have a severe effect on the airways. Diesel PM can be effectively reduced with the substitution of diesel fuel with a biofuel such as vegetable oil. Unfortunately, very little is known about the cellular effects of these alternative diesel emissions on the airways. The aim of this study was to test whether coconut oil substitution in diesel fuel reduces the adverse effect of diesel emission exposure on human bronchial epithelial cells. Human bronchial epithelial cells were cultured at air-liquid interface for 7 days and exposed to diesel engine emissions from conventional diesel fuel or diesel fuel blended with raw coconut oil at low (10%), moderate (15%) and high (20%) proportions. Cell viability, inflammation, antioxidant production and xenobiotic metabolism were measured. Compared to conventional diesel, low fractional coconut oil substitution (10% and 15%) reduced inflammation and increased antioxidant expression, whereas higher fractional coconut oil (20%) reduced cell viability and increased inflammation. Therefore, cellular responses after exposure to alternative diesel emission are dependent on fuel composition.


Fructose prevents 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced ATP depletion and toxicity in isolated hepatocytes.
The loss of viability of isolated rat hepatocytes exposed to either 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) or its toxic metabolite 1-methyl-4-phenylpyridinium ion (MPP+) was prevented by addition of fructose to the incubation medium. This protection was dependent on fructose concentration, being complete at 10 mM. Addition of fructose dramatically delayed MPTP- and MPP+-induced depletion of ATP and was accompanied by a significant accumulation of lactate, indicating the occurrence of enhanced glycolytic production of ATP. Glucose was much less effective against MPTP and MPP+ toxicity, probably because it is a relatively poor substrate for glycolysis in liver cells. We conclude that depletion of ATP is a critical event in MPTP cytotoxicity in our in vitro model system, and that the use of alternative sources of ATP production may represent an important protective device against the effects of this toxic agent.


Defective phosphoinositide metabolism in primary hypertension.
An increase in free cytosolic calcium content has been reported in essential hypertension. Since within the membrane, the phosphoinositides participate in the control of cell calcium homeostasis, we investigated whether impaired phosphoinositide metabolism could account for the calcium handling abnormality observed in hypertensives. In erythrocyte membranes of hypertensives the activity of kinases involved in polyphosphoinositide formation appears to be impaired and could be related to the alteration in calcium handling binding capacity and ATP-dependent calcium transport. In platelets of hypertensives, the hyperactivity of phospholipase C (observed even in the absence of calcium in the external medium) is likely to be responsible for the hypersensitivity of cells to various agonists. These observations are consistent with the hypothesis that in cells from hypertensives, a membrane defect linked to phosphoinositide metabolism is involved in the overall calcium handling defect.


Effect of glyburide on glycogen metabolism in cultured rat hepatocytes.
Sulfonylurea agents decrease hepatic glucose production and fasting glucose levels in type II diabetic patients without changing fasting insulin concentrations. This raises the possibility that these drugs may act directly on hepatic carbohydrate metabolism. Cultured rat hepatocytes were used to test this hypothesis. To ascertain whether this in vitro system was suitable to demonstrate an effect of sulfonylurea agents (eg, the well-documented insulin-potentiating action), we initially measured the effect of glyburide (2 micrograms/mL) on insulin-stimulated net glucose-14C incorporation into glycogen. Glyburide increased sensitivity to insulin (ie, shifted the dose-response curve to the left) without affecting either responsiveness or insulin binding. Thus, the ED50 was significantly lowered (8.4 v 15.2 ng/mL), whereas the percent increase (181% v 170%) over the basal level, specific tracer insulin binding (5.3% v 5.1% per mg protein), and the Scatchard plots were similar. Since an effect of sulfonylurea agents could be demonstrated in this system, and the glycogen pathways supply 75% of hepatic glucose production after an overnight fast, we next measured the direct effect of glyburide (2 micrograms/mL) on glycogen storage and breakdown. Glycogenolysis was assessed by measuring the breakdown of prelabeled glycogen (from galactose-14C) and glycogen synthesis by the incorporation of glucose-C14 into glycogen. Glyburide significantly inhibited glycogenolysis and stimulated glycogen synthesis. Furthermore, glyburide significantly stimulated glycogen synthase while glycogen phosphorylase was unaffected. In conclusion, glyburide directly inhibited glycogenolysis, stimulated glycogen synthesis and glycogen synthase, and potentiated the action of insulin on glycogen synthesis at a postbinding site in cultured rat hepatocytes.(ABSTRACT TRUNCATED AT 250 WORDS)


Animal models relevant to human epilepsies.
Animal studies have significantly contributed to our understanding of epileptogenesis and action mechanisms of antiepileptic drugs. The relevance of animal models to human epilepsies depend on how faithfully they reproduce the clinical and EEG features of human forms. In principle the definition of animal model of epilepsies should be reserved to animals presenting with recurrent seizures, either spontaneous of experimentally induced, persisting over time. Therefore acute experimental procedures designed to induce seizure and in vitro preparations should be referred to as models of seizures and models of epileptogenic mechanisms respectively rather models of epilepsies. The adequacy of a given animal model to study basic mechanisms of epilepsies and/or drug efficacy depend on the type of information that the investigator want to draw from it.


Effects of BCG and Corynebacterium parvum on immune reactivity in melanoma patients.
Sixteen patients with disseminated melanoma were immunised with either BCG (8 cases) or C. parvum (8 cases) on three occasions at 21 day intervals. Blood for assay was taken immediately before the first immunisation and weekly for eight weeks thereafter. Total white count tended to increase but little change was seen in lymphocyte and monocyte counts. Serum IgG increased after BCG BUT NOT WITH C. parvum, serum IgA and IgM did not alter. The 'E' rosette % did show some increase mainly after C. parvum, and 'B' lymphoid cells (sIg staining) increased slightly after BCG; the 'EA' rosette % fell following C. parvum but not after BCG. Lymphocyte PHA blastogenesis increased after immunisation, particularly with BCG. Non-specific lymphocytotoxicity (51 Cr Chang target) demonstrated dramatic increases for 'non T' and 'K' cell function and a smaller increase in 'T' cell cytotoxicity following immunisation. These increases in cytotoxicity were maintained by the 21 day immunisation schedule.


Osteoblast-like cells from estrogen receptor alpha knockout mice have deficient responses to mechanical strain.
In vivo, bones' osteogenic response to mechanical loading involves proliferation of surface osteoblasts. This response is replicated in vitro and involves ERK-mediated activation of the estrogen receptor (ER) alpha and upregulation of estrogen response element activity. This proliferative response can be blocked by selective estrogen receptor modulators and increased by transfection of additional ERalpha. We have now investigated the mechanisms of ER involvement in osteoblast-like cells' early responses to strain by comparing the responses of primary cultures of these cells derived from homozygous ERalpha knockout (ERKO) mice (ERalpha-/-) with those from their wildtype (ERalpha+/+) and heterozygous (ERalpha+/-) littermates and from ER/beta knockout (BERKO) mice (ERbeta+/+, ERbeta+/-, and ERbeta-/-). Whereas ERalpha+/+, ERalpha+/-, ERbeta+/+, and ERbeta-/- cells proliferate in response to a single 10-minute period of cyclic strain, ERalpha-/- cells do not. Transfection of fully functional, but not mutant, ERalpha rescues the proliferative response to strain in these cells. The strain-related response of ERalpha-/- cells is also deficient in that they show no increased activity of an AP-I driven reporter vector and no strain-related increases in NO production. Their strain-related increase in prostacyclin production is retained. They proliferate in response to fibroblast growth factor-2 but not insulin-like growth factor (IGF)-I or IGF-II, showing the importance of ERalpha in the IGF axis and the ability of ERalpha-/- cells to proliferate normally in response to a mitogenic stimulus that does not require functional ERalpha. These data indicate ERalpha's obligatory involvement in a number of early responses to mechanical strain in osteoblast-like cells, including those that result in proliferation. They support the hypothesis that reduction in ERalpha expression or activity after estrogen withdrawal results in a less osteogenic response to loading. This could be important in the etiology of postmenopausal osteoporosis.


Finite element analysis and clinical complications in mandibular implant-overdentures opposing maxillary dentures.
Denture fracture is a common clinical complication caused by improper material selection, design, or fabrication technique. This study aimed to investigate the effect of two attachment systems on fracture risk of the implant-overdentures (IOD) via finite element analysis (FEA), using the force distributions obtained from patients' occlusal analyses and to compare the obtained results with the clinical complications associated with these attachments. A three-dimensional jaw model comprised of the edentulous bones was constructed. Three types of mandibular prostheses including complete denture (CD) (model LCD), IOD with Locator attachment (model LID-L), and IOD with telescopic attachment (model LID-T), as well as a maxillary CD (model UCD) were assembled. The vertical occlusal forces at anterior and posterior quadrants were obtained from the patients wearing mandibular CDs or IODs. The FEA results were further compared with the mechanical failures of different prostheses observed at patient recalls. In overall, the fracture risk of mandibular prostheses was lower than the maxillary compartments. The UCD opposing LCD underwent higher strains than that opposing LID-L and LID-T, which was mostly concentrated at the anterior mid-palatal polished surface. On the other hand, LID-L showed the lowest strain, followed by LID-T, and LCD. The obtained results were consistent with the clinical complications observed in the patient recalls.


Amphibian skin secretomics: application of parallel quadrupole time-of-flight mass spectrometry and peptide precursor cDNA cloning to rapidly characterize the skin secretory peptidome of Phyllomedusa hypochondrialis azurea: discovery of a novel peptide family, the hyposins.
This study reports the variety of peptides present in the skin secretory peptidome of Phyllomedusa hypochondrialis azurea. Peptide structures, along with post-translational modifications, were elucidated by QTOF MS/MS analysis, cDNA sequencing, or a combination of both. Twenty-two peptides, including 19 novel structures, were identified from six different structural classes, including tryptophyllins, dermorphins, and a novel group of peptides termed hyposins. The study demonstrates the power of this combined approach to mine the rich peptidome compliment of the amphibian defensive skin secretome.


Photodistributed blue-gray pigmentation of the skin associated with long-term imipramine use.
A 72-year-old white woman presented with progressively increasing slate-gray pigmentation of the face and extensor aspect of the forearms, which she had been suffering from for 8 years. She had been taking imipramine for approximately 30 years. Her other medications included ranitidine and anacin. Physical examination revealed slate-gray hyperpigmentation of the skin photodistributed on the face (Figs 1, 2) and extensor aspects of the forearms. Relative sparing of the skin folds, mucous membranes, sclerae, teeth, and nails was noted. The remainder of the physical examination revealed no abnormalities. Skin biopsy specimens from the right cheek and right forearm were obtained. Histologic examination revealed collections of variably sized, round to ovoid, yellow-brown globular deposits in the upper and mid dermis (Fig. 2). The deposits were identified within macrophages and free within the dermis. The epidermis was unremarkable and free of deposits. The deposits stained for melanin with a Fontana-Masson stain, but did not stain for iron.


The fossil trade: paying a price for human origins.
Fossils have been traded for centuries. Over the past two hundred years the market has developed into an organized enterprise, with fossils serving multiple functions as objects of scientific study, collectors' items, and investments. Finding fossils, digging them up or purchasing them, transporting, studying, and conserving them, and putting them on display was and still is expensive. Since the early nineteenth century, funding bodies, academic institutions and museums, philanthropists, dealers, collectors, amateurs, and professional paleontologists have constituted elaborate networks driven by collaboration, necessity, ambition, accolades, and capital to generate knowledge and produce geological artifacts, increasing our understanding of the natural world, advancing careers and institutions, and contributing to personal fortunes. The emergence of paleoanthropology as a scientific discipline around 1900 generated a scientific focus on the human story that was easy to sell. The scarcity of ancient human remains made it close to impossible for a commercial market to evolve, yet finding them required serious funding. Elaborate schemes for financing expeditions and excavations went hand in hand with individual aspirations, patronage, philanthropy, networks, and alliance building, as concession rights and access to sponsors were objects of regular political intrigues and often bitter disputes.


Low-molecular-weight heparin and other antithrombotic agents in the setting of a primarily medical treatment of unstable coronary artery disease.
Antithrombotic treatment of acute coronary syndromes (ACS) comprises aspirin and (low-molecular-weight) heparin. Adjunctive treatment with intravenous glycoprotein IIb/IIIa receptor antagonists may be used in high-risk individuals, especially when they undergo percutaneous coronary interventions. Results from large-scale trials studying the efficacy and safety of oral glycoprotein IIb/IIIa blockers in patients with ACS have been disappointing. Thrombolytic therapy is not indicated in ACS.


Hepatocellular carcinoma cells resist necrosis during anoxia by preventing phospholipase-mediated calpain activation.
Although hepatocellular carcinoma (HCC) cells are more resistant to anoxic injury than normal hepatocytes, the mechanisms responsible for this differential sensitivity remain obscure. Because enhanced calpain protease activity contributes to hepatocyte necrosis, we tested the hypothesis that HCC cells resist anoxia by preventing calpain activation. Cell viability in two rat HCC cell lines (N1S1 and McA-RH7777 cells) was fourfold greater compared to rat hepatocytes after 4 h of anoxia. Although calpain activity increased twofold in rat hepatocytes during anoxia, no increase in calpain activity occurred in HCC cells. Western and Northern blot analysis revealed greater or equivalent expression of calpains and calpastatin in HCC cells compared to hepatocytes. Because increases in cytosolic free Ca++ (Cai++) and phospholipid degradation products regulate calpains in vitro, we measured Cai++ and phospholipid degradation. Ca++i did not change in any cell types during 60 min of anoxia. In contrast, phospholipid degradation was fourfold greater in hepatocytes compared to HCC cells. Melittin, a phospholipase A2 activator, increased calpain activity and cell necrosis in all cell types; melittin-induced cell necrosis was ameliorated by a calpain protease inhibitor. In summary, these data demonstrate for the first time 1) calpain activation without a measureable increase in Ca++i, 2) phospholipase-mediated calpain activation in hepatocytes and HCC cells, and 3) the adaptive mechanism responsible for the resistance of HCC cells to anoxia-an inhibition of phospholipid-mediated calpain activation. Interruption of phospholipase-mediated calpain activation may be a therapeutic strategy for preventing anoxic cell injury.


Sustained exposure to the investigational Kisspeptin analog, TAK-448, down-regulates testosterone into the castration range in healthy males and in patients with prostate cancer: results from two phase 1 studies.
Kisspeptin-54, an endogenous naturally occurring ligand of the G protein-coupled receptor-54, stimulates GnRH-gonadotropin secretion and suppresses metastases in animal models of cancer but is subject to rapid degradation and inactivation. TAK-448 is an investigational oligopeptide analog of the fully active 10-amino acid C terminus of kisspeptin-54. This phase 1 study evaluated the safety, pharmacokinetics, and pharmacodynamics of TAK-448 in healthy subjects and patients with prostate cancer (PC). Healthy subjects aged 50 years or older received TAK-448 sc as a single-bolus or 2-hour infusion (0.01-6 mg/d; part A) and as a 14-day sc administration (0.01-1 mg/d; part B). In a subsequent, open-label, phase 1 study in PC patients aged 40-78 years, TAK-448 was given as a 1-month depot formulation. Eighty-two healthy subjects received TAK-448; 30 received placebo. Grades 1-2 adverse events were reported in 26% of subjects during TAK-448 treatment. All dosing regimens resulted in dose-proportional exposures. The maximum observed plasma concentration occurred after 0.25-0.5 hours, and median terminal elimination half-life was 1.4-5.3 hours. T increased approximately 1.3- to 2-fold by 48 hours after a single bolus or 2 hour injections, whereas during the 14-day infusion, at doses above 0.1 mg/d, T dropped to below-baseline values by 60 hours and reached a subsequently sustained below-castration level by day 8. In PC patients, T decreased to less than 20 ng/dL in four of five patients dosed with 12 or 24 mg TAK-448 sc-depot injections. The prostate-specific antigen decreased greater than 50% in all patients dosed with 24 mg. Continuous TAK-448 infusion was well tolerated by healthy males and resulted in sustained T suppression. Depot injection in patients with PC similarly reduced T and resulted in prostate-specific antigen responses.


[Current opinion in pathogenesis of pheochromocytoma].
Pheochromocytoma is a neuroendocrine tumor with significant clinical relevance. Is one of the causes of secondary hypertension. Most of the tumors are benign, but sometimes malignant cases are seen and there prognosis is unfavorable. So far, none of the factors which could initiate development of pheochromocytoma are known, besides genetic ones. In this review, most common familial syndromes connected with pheochromocytoma are characterized.


Mixing behavior of colyophilized binary systems.
The purpose of this study was to investigate the factors which govern the mixing of amorphous sucrose with trehalose, poly(vinylpyrrolidone) (PVP), dextran, and poly(vinylpyrrolidone-co-vinyl acetate) (PVP/VA). These materials were chosen as model systems to represent multicomponent freeze-dried pharmaceutical preparations. Mixtures were prepared by colyophilization of the components from aqueous solutions. The glass transition temperatures (Tg) of these mixtures were measured using differential scanning calorimetry (DSC) and were compared to predictions based on simple mixing rules. FT-Raman spectroscopy was used to probe selected mixtures for evidence of molecular interactions between components. Colyophilized mixtures were confirmed to be amorphous by X-ray powder diffraction. The Tg values of the various mixtures generally were lower than values predicted from free volume and thermodynamic models, indicating that mixing is not ideal. The FT-Raman spectra of colyophilized sucrose-PVP and sucrose-PVP/VA mixtures provided evidence for interaction between the components through hydrogen bonding. Hydrogen bonds formed between components in colyophilized sucrose-additive mixtures are formed at the expense of hydrogen bonds within sucrose and in some cases within the additive. A thermodynamic analysis of these mixtures indicates that mixing is endothermic, which is consistent with a net loss in the degree of hydrogen bonding on mixing. There is also a positive excess entropy of mixing which accompanies the net loss in hydrogen bonds. Despite this gain in excess entropy, the excess free energy of mixing is positive, consistent with the observed deviations in Tg from values predicted using models which assume ideal mixing.


HER2/neu in systemic therapy for women with breast cancer: a systematic review.
Amplification and/or overexpression of the HER2/neu gene is associated with a poor prognosis in breast cancer. Many studies have suggested that this gene may be associated with the relative efficacy of chemotherapy and endocrine therapy options. A systematic review of the evidence was conducted. MEDLINE, EMBASE, the Cochrane Library, the American Society of Clinical Oncology annual meeting proceedings, and the San Antonio Breast Cancer Symposia proceedings were all searched to November 2006 for reports of analysis by HER2/neu status of the relative efficacy of the treatment arms in randomized controlled trials. Thirty-five trials were identified. A meta-analysis of trials of tamoxifen versus observation found no significant interaction between treatment and HER2/neu status, although one trial not included in the meta-analysis did find interaction. A meta-analysis of adjuvant anthracycline-based chemotherapy trials found a significant interaction (difference in disease-free survival log-hazard ratios -0.31, 95% confidence interval -0.50 to -0.13; difference in overall survival log-hazard ratios -0.34, 95% confidence interval -0.53 to -0.14). Significant interaction was also found in a meta-analysis of disease-free survival in trials of adjuvant taxane therapy versus non-taxane therapy (difference in disease-free survival log-hazard ratios -0.36, 95% confidence interval -0.68 to -0.04). HER2/neu overexpression and/or amplification was associated with greater efficacy of the anthracycline or taxane regimen. Current evidence supports the conclusion that the benefit of both anthracycline-based and taxane-based adjuvant chemotherapy is associated on HER2/neu status, with patients with HER2/neu-positive cancers benefiting more from these therapies than those with HER2/neu-negative cancers.


Physical activity of young people in the Torres Strait and Northern Peninsula Region: an exploratory study.
The present study explored the practices of, and perceived barriers to, physical activity of young people living in remote communities in the Torres Strait and Northern Peninsula Area of Far North Queensland. A cross-sectional survey exploring physical activity practices of children attending primary and secondary schools in two communities in the Torres Strait, Far North Queensland. A total of 367 primary and secondary school-aged children (aged 9-16 years). Only 50% of the children reported being active for more than 30 min a day and approximately 25% of both primary and high school children surveyed were 'pretty much active only at week-ends'. The major barriers cited to being active were related to the climate, lack of equipment and child-specific activities and low self-perception of ability. A large proportion of school students in the Torres Strait and Northern Peninsula Area reported low levels of physical activity. The main barriers cited to being active suggest that structural and family-based strategies are required to help young people, especially girls, to engage in more physical activity. There is also a need for skills and confidence-building activities delivered in a non-competitive environment for those who feel that they lack the necessary skills to participate fully.


Endolymphatic sac surgery for Meniere's disease: a composite study of 339 cases.
This paper analyzes 339 consecutively performed endolymphatic mastoid sac shunts. Regardless of the method used, vertigo was controlled and hearing either improved or stabilized in approximately 70% of the cases. Overall, vertigo was controlled in approximately 80% of the cases. Similar results were obtained in cases of Meniere's syndrome and vestibular Meniere's disease. It is suggested here that, regardless of the method employed, there remains a high likelihood that the symptoms will recur, and the question is raised as to whether sac surgery may merely induce a temporary remission of the disease process. Consequently, it is hereby proposed that there is a need to devise a method to permanently drain the endolymph in order to more effectively control the disease on a permanent basis. Until this is achieved, however, sac surgery would appear to be the most appropriate surgical treatment for Meniere's disease.


Association of cord blood nevirapine concentration with reported timing of dose and HIV-1 transmission.
To correlate nevirapine presence and concentration in cord bloods of infants born to HIV-1 infected women with report of timing of dose and HIV-1 transmission at 6 weeks of age. All available cord blood samples from the infants of mothers enrolled in the HIVNET 012 trial who were randomly assigned to receive either nevirapine or zidovudine at the onset of labor were tested for a nevirapine concentration. Nevirapine was detected in the cord blood of 244 of 259 (94%) infants whose mothers reported they took nevirapine in labor more than 1 h before delivery and in 12 of 13 (92%) infants whose mothers reported they took nevirapine less than 1 h before delivery. The median nevirapine cord blood concentration was 1238 ng/ml [interquartile range (IQR), 905-1474 ng/ml] and 122 ng/ml (IQR, 64-321 ng/ml) for women who reported taking nevirapine more or less than 1 h before delivery, respectively (P < 0.001). The median nevirapine cord blood concentration of infants who were HIV-1 negative at birth, but positive at 6-8 weeks of age (n = 11), was 916 ng/ml (IQR, 737-1245 ng/ml) compared with 1192 ng/ml (IQR, 875-1471 ng/ml) for uninfected infants (n = 236). Cord blood nevirapine concentration correlated well with report of nevirapine administration and timing of dose before delivery. The nevirapine cord blood concentration was modestly lower in infected infants, although the number of infants infected between birth and 6-8 weeks of age was small (n = 11). The high adherence rate in the HIVNET 012 study supports the efficacy, simplicity and deliverability of this regimen.


The fine structure of merozoites of Babesia bovis in the gut epithelium of Boophilus microplus.
Electron microscopic studies on merozoites of Babesia bovis in epithelial cells of the gut of Boophilus microplus revealed that the pellicle apparently consists of 3 membranes, and an osmiophilic layer intimately associated with microtubules. Micropores in the pellicle were often associated with micronemes. An unidentified tubular structure extended from the anterior polar ring to the nuclear region where it appeared to be associated with the nuclear envelope. A Golgi complex, typical protozoan mitochondria, food vacuoles and rhoptries could not be identified.


Serum resistin is inversely related to breast cancer risk in premenopausal women.
Adipokines have been suggested as potential mediators linking obesity and breast cancer. Resistin is the least-studied adipokine with diverse findings regarding its association with disease development and progression. The present study aimed to determine resistin serum levels in breast cancer in relation to the histological type of disease and to investigate their association with breast cancer risk. The study included 216 women, of which 163 were diagnosed with breast cancer (58 with IDC, 52 with DCIS and 53 with LN) and 53 were healthy. Serum levels of resistin, leptin and adiponectin were quantitatively determined in duplicates by ELISA. Differences in resistin levels among patient groups were evaluated with Kruskal-Wallis and Mann-Whitney tests. The association of resistin with breast cancer risk was evaluated by multiple logistic regression analysis. Resistin levels varied between histological types of breast cancer (p = 0.044). Significant differences in serum resistin were observed in IDC patients compared to those with DCIS and to controls (p < 0.014 and p < 0.03, respectively). Decreased levels of resistin, adiponectin and leptin were observed in premenopausal patients. Resistin was associated with a reduced risk for ductal carcinoma only in premenopausal women (OR: 0.364, 95% CI: 0.154-0.862, p < 0.022). Our findings indicate that resistin levels were inversely related to breast cancer risk in premenopausal women, supporting a protective role of resistin for these patients. Further advances in adipokine research may lead to tangible benefits for overweight/obese women at an increased risk for breast cancer.


Exploring women's attitudes and intentions to seek care from nurse practitioners across different age groups.
Because public acceptance is critical for the successful integration of nurse practitioners into the Canadian health care system, the current study explored how women of different ages perceive nurse practitioners. Middle-aged women held more positive views of health care professionals in general and were more likely to indicate that they would seek help from nurse practitioners compared to younger and older women. Across all three age groups, respondents were more likely to seek help from physicians than from nurse practitioners, especially for acute (versus preventive) health concerns.


Learning and memory in the autoimmune BXSB mouse: effects of neocortical ectopias and environmental enrichment.
Approximately 40-60% of BXSB mice have ectopic cell clusters in layer 1 of neocortex. Prior studies have shown distinct behavioral differences between those with ectopias and their non-ectopic littermates. In this study, female BXSB mice were reared after weaning in either enriched environments or standard cages. Following an initial round of behavioral testing, all mice were housed in standard cages and retested. Enriched cage mice (both ectopic and non-ectopic) showed increased activity, greater speed, and enhanced learning scores across a variety of tests. Additionally, prior test experience itself had significant positive effects on Hebb-Williams maze learning. The presence of ectopias resulted in better Morris maze learning for standard cage reared mice. Further, ectopic mice, regardless of their housing condition, showed better long-term retention in the Morris maze than did their non-ectopic counterparts. These findings show that abnormalities in corticogenesis need not always result in functional deficit.


Corticospinal output during muscular fatigue differs in multiple sclerosis patients compared to healthy controls.
In multiple sclerosis (MS), fatigue is a common and often disabling symptom. It has multiple causes with central motor fatigue playing an important role. The objective of this study was to analyse the central motor conduction changes in relation to muscle contraction force during muscle fatigue and recovery in MS patients compared to healthy controls. A total of 23 MS patients with fatigue and 13 healthy subjects were assessed during 2 minutes of fatiguing exercise of the abductor digiti minimi muscle of the hand and the subsequent 7 minutes of recovery. Central motor conduction was quantified by transcranial magnetic stimulation using the triple stimulation protocol and calculating a central conduction index (CCI). Force declined to 36% of the pre-exercise level (SD 16%; p < 0.01) in MS patients and to 44% (SD 9%, p < 0.01) in healthy subjects (group differences, not statistically significant). The decline of the CCI was significantly less marked in patients (-20%, SD 26%, p < 0.05) than in healthy subjects (-57%, SD 15%, p < 0.05; group differences, p < 0.05). The decline of force and CCI were not correlated in either group. During a fatiguing exercise, the decline in central motor conduction is significantly less pronounced in MS patients than healthy subjects, although the reduction of force is similar.


Indocyanine green angiography in angioid streaks.
To define the indocyanine green angiographic aspects of angioid streaks, peau d'orange and choroidal new vessels. Fifty-seven consecutive patients (112 eyes) with angioid streaks were evaluated by fluorescein angiography and indocyanine green angiography. Indocyanine green angiography showed angioid streaks in all eyes. We identified three different indocyanine green patterns of streaks (four groups): fluorescent (63%), hypofluorescent (8%), 'track-like' (19%) and mixed (10%). Angioid streaks were visualized better by indocyanine green angiography and red-free retinography than fluorescein angiography. Peau d'orange was seen better and found to be more widespread by indocyanine green angiography. Fluorescein angiography visualized choroidal neovascularization better, except for occult forms. Our findings show that angioid streaks have different indocyanine green angiography patterns. Considering that the hypofluorescent pattern was significantly observed in younger patients, indocyanine green angiography aspects might be correlated with different stages of the disease.


[Use of proteins, covalently bound to agar gel, for specific sorption in electrophoresis].
A method is developed for electrophoretic fractionation of serum proteins in agar gel with simultaneous specific sorption of gamma-globulin fraction, migrating during the electrophoresis through specific immunosorbents incorporated into agar gel. The reaction was carried out in a special apparatus designed for the electrophoresis in two perpendicular directions. The sorbent was separated from impurities by passing the current in the first direction. The unspecific sorbent did not alter the electrophoretic mobility of migrating proteins, but the specific sorbents immobilized completely both antibodies and antigens. The antibodies were shown to bind repeatedly to the immunoglobulins, which had been linked to the sorbent. The method facilitated distinctly the estimation of antigens and antibodies in complicated mixtures. By analogy with affinity chromatography a term "affinity electrophoresis" was used for designation of the method described.


Identification of His5,Trp7,Tyr8-GnRH (chicken GnRH II) in amphibian brain.
GnRH immunoreactive and bioactive peptides in Xenopus laevis brain extract were investigated by high performance liquid chromatography (HPLC), radioimmunoassay with region-specific antisera raised against GnRH (mammalian), His5,Trp7,Tyr8-GnRH (chicken II) and Tyr3,Leu5,Glu6,Trp7,Lys8-GnRH (lamprey), and by assessment of biological activity. Two immunoreactive peptides eluted in the same positions as GnRH and His5,Trp7,Tyr8-GnRH respectively in HPLC systems which were specifically designed to separate four known natural vertebrate GnRHs (mammalian, chicken I and II, salmon). The immunological properties of these two immunoreactive peaks, determined by relative interaction with three region-specific antisera raised against mammalian GnRH and two specific His5,Trp7,Tyr8-GnRH antisera, were identical to those of GnRH and His5,Trp7,Tyr8-GnRH. The immunoreactive peak co-eluting with His5,Trp7,Tyr8-GnRH represented approximately one-third of the total brain GnRH. Both immunoreactive peaks stimulated luteinizing hormone (LH) release in a chicken dispersed pituitary cell bioassay, and the amounts of LH release stimulated by the two peaks were appropriate for these peaks being GnRH and His5,Trp7,Tyr8-GnRH. A small hydrophobic peak with GnRH immunoreactivity eluted in the same position as Trp7,Leu8-GnRH (salmon), while Gln8-GnRH (chicken I) and lamprey GnRH were not detected. Two additional rather hydrophilic peptides cross-reacted with a COOH-terminus-directed antiserum and had LH-releasing activity. LH-releasing activity was also detected in hydrophobic HPLC fractions. In summary, these data provide evidence for the presence of both GnRH and a second peptide with properties identical to His5,Trp7,Tyr8-GnRH in X. laevis brain.(ABSTRACT TRUNCATED AT 250 WORDS)


[The physical and psychological rehabilitation of women who have had a myocardial infarct].
The study was performed of the effect of bicycle exercise and occupational therapy (embroidery, knitting, sewing, drawing, etc.) on physical and psychological status of postmyocardial infarction females at the in-hospital stage of rehabilitation. It was found that occupational therapy improved the psychological status and life quality, whereas low-intensity physical training increased performance status in relevant women.


[Electroencephalography in clinical research into psychoses (author's transl)].
At present EEG investigations in heterogenous acute schizophrenic and psychotic syndromes suggest changes in the regulating, reticulo-thalamo-cortical, functional system. One may further assume that cerebral functional changes consist of a dissociation of normally closely linked functional systems. In favor are findings in functional psychoses ("Funktionspsychosen"), also the dissociation of usually coordinated systems in normal psychologic changes during going to sleep and REM stages of dreams. A further thalamohippocampo-reticulo system which might act in parallel to the activating reticular system has become important in EEG research into psychoses. Changes here probably in part of focal EEG phenomenon localized in the temporal region. Here, too, EEG findings in schizophrenic syndromes requiring further proof emerge.


Biculturality and homosexuality.
In an effort to sensitize service providers to bicultural socialization, a small but growing literature has surfaced in which theories are proposed explaining the socialization process, cultural identification, and evolution of self-concept for those functioning in two cultures. In this article, the authors examine the extent to which previously developed explanatory theories of cultural and ethnic identity and bicultural socialization apply to the experience of sexual minorities, and offer a conceptual framework for adequately assessing the experience of homosexual clientele. The multifaceted nature of the practitioner's role is discussed, and gender-sensitive practice methods are given that may assist sexual minorities in developing optimum functioning.


[Correlation between clinical pathologic factors and enzymatic activity of orotate Phosphoribosyl transferase (OPRT), Dihydropyrimidine dehydrogenase (DPD) and Thymidylate synthase (TS) in colorectal cancer].
Orotate Phosphoribosyl Transferase (OPRT), Dihydropyrimidine dehydrogenase (DPD) and Thymidylate synthase (TS) are initial key enzymes in the 5-FU metabolic pathway. In this study, we measured the activities of OPRT, DPD and TS. We also investigated the correlation between these 3 enzymatic activities and the clinical pathologic factors (Histological typing, extent of tumor invasion,extent of metastasis to the lymph nodes,stage, lymphatic invasion and venous invasion). We had surveyed 79 cases of colorectal cancers surgically removed. Poorly-differentiated adenocarcinoma showed a tendency to lower OPRT and higher DPD, as compared to moderately or well-differentiated adenocarcinomas. In case with metastasis to lymph nodes, OPRT showed a tendency to lower activities, but a significant difference was not noticed. TS showed no relation to any of these pathologic factors. In each application of 5-FU, measuring the activities of these three enzymes is important for estimation of the antitumoral effect. With poorly-differentiated adenocarcinoma, it is estimated that many cases would show high DPD and if the enzyme activities can not be measured, so administration of TS-1, which includes DPD inhibitor, may be considered.


Dehydrocoupling reactions of dimethylamine-borane by Pt(II) complexes: a new mechanism involving deprotonation of boronium cations.
Coordinatively unsaturated Pt(II) complex [Pt(I(t)Bu')(I(t)Bu)](+) stabilized by N-heterocyclic carbene (NHC) ligands dehydrogenates N,N-dimethylamineborane through a mechanism that involves hydride abstraction, assisted by an amine, to yield a platinum-hydride complex [PtH(I(t)Bu')(I(t)Bu)] with concomitant formation of the boronium cation [(NHMe2)2BH2](+). This latter species is very likely in equilibrium with the THF stabilized borenium cation [(NHMe2)(THF)BH2](+), bearing an acidic NH group that is able to protonate the platinum hydride [PtH(I(t)Bu')(I(t)Bu)] releasing H2, the amino borane H2B-NMe2 and regenerating the catalytic [Pt](+) species.


Prophylaxis of serious cytomegalovirus infection in renal transplant candidates using live human cytomegalovirus vaccine. Interim results of a randomized controlled trial.
We report the interim results of a randomized, double-blind, placebo-controlled, clinical trial of prophylactic, live, attenuated cytomegalovirus (CMV) vaccination (Towne strain of CMV) of renal transplant candidates (RTCs). One hundred seventy-two RTCs were treated and subsequently underwent transplantation and followed up for at least one year and up to five years after transplantation. Eighty-eight RTCs received vaccine, and 84 received placebo. Results were analyzed according to the prevaccination serologic status (anti-CMV antibody titer) of the recipient (R- or R+) and the donor (D- or D+). The overall incidence of CMV disease was highest in the R-D+ group and almost absent in the R-D- group. There was no difference in the incidence of CMV infection or disease between vaccinated and respective placebo control recipients in either the R-D+, R+D+, R+D-, or R-D- groups. In contrast, the severity of CMV disease was significantly decreased in R-D+ vaccinees vs R-D+ placebo-treated recipients. Moreover, in the R-D+ group, one- and five-year cadaver renal allograft actuarial survival rates were 73% and 62%, respectively, for CMV vaccinees vs 40% and 25%, respectively, for control placebo patients. We conclude that seronegative cadaver RTCs may benefit from vaccination with live, attenuated, Towne strain CMV vaccine before transplantation.


Hepatitis G virus co-infection in liver transplantation recipients with chronic hepatitis C and nonviral chronic liver disease.
Hepatitis G virus (HGV) is a newly described RNA virus that is parenterally transmitted and has been found frequently in patients with chronic hepatitis C infection. To determine the impact of hepatitis G virus co-infection on morbidity and mortality following liver transplantation, we measured HGV RNA by polymerase chain reaction in pre and posttransplantation sera from a cohort of patients transplanted for chronic hepatitis C and a control group of patients transplanted for nonviral causes who were negative for hepatitis C virus (HCV) RNA in serum. The overall prevalence rate of HGV RNA in transplanted patients with chronic hepatitis C was 20.7%. HGV infection was present before transplantation in 13% while it appeared to have been acquired at the time of transplantation in 7.4%. Mean serum alanine aminotransferase activity, hepatic histological activity, and patient and graft survival were similar between HGV-positive and HGV-negative patients. The prevalence rate of HGV RNA in transplanted controls was 64% (P < .01) with a significantly higher rate of acquisition of HGV infection following transplantation (53%, P < .001) when compared with patients with chronic hepatitis C. Mean serum alanine aminotransferase activity was significantly lower in the control patients with HGV infection alone following transplantation than in patients co-infected with hepatitis C (37 +/- 9 vs. 70 +/- 33 U/L, P < .01). Thus, HGV is frequently found in transplantation patients co-infected with hepatitis C although it appears to have minimal clinical impact. In patients transplanted for nonviral causes of end-stage liver disease, a high rate of hepatitis G acquisition at the time of transplantation may occur but does not appear to predispose to chronic hepatitis.


Characteristics of Cancer Rehabilitation Fellowship Training Programs in the USA.
Cancer rehabilitation is emerging as a specialized field within Physical Medicine and Rehabilitation. The purpose of this systemic review is to summarize the various cancer rehabilitation fellowship programs in the USA and the scope of training in this discipline. Currently, four institutions offer such a training program. All of the fellowship directors were contacted about characteristics of their programs. The oldest program has been in existence since 2007. All of these programs are 1 year in duration and have between one and two fellowship positions annually. There have been total of 29 graduates as of July 2017. With regard to cancer rehabilitation care delivery model, all four centers reported inpatient consult teams and outpatient rehabilitation. Outpatient experience included electrodiagnosis, botulin toxin, and ultrasound-guided injections. Three of the four programs also reported the presence of an acute inpatient cancer rehabilitation service. A number of clinical rotations are available at each of the four programs with considerable variation. Comprehensive educational efforts are present in all programs with varying expectations for research.


Clinical and microbiological factors associated with mortality in candidemia in adult patients 2007-2016.
Background: Candidemia is a life-threatening infection with high mortality. Our aim was to evaluate the Candida species distribution, antifungal susceptibilities and risk factors associated with 30-day mortality in candidemia in Southern Finland. Methods: We present a retrospective analysis of candidemia cases from the hospital district of Helsinki and Uusimaa during 2007-2016. Patients younger than 18 years old were excluded. A total of 386 candida isolates from 374 episodes of candidemia were identified in 350 adult patients. Results: Candida albicans was the leading cause of candidemia (60.4%), followed by C. glabrata (21.5%), C. parapsilosis (5.2%) and C. dubliniensis (5.2%). There was no statistically significant change in the distribution of C. albicans vs non-albicans species during the study period. Thirty-day overall mortality was 30.7%. When patients who received no antifungal treatment were excluded from the mortality analysis, 30-day mortality was 23.0%. Severity of underlying illnesses (OR 20.55, 95% CI 5.98-70.60), ICU stay at the onset of candidemia (OR 5.06, 95% CI 1.75-14.68) and age >65 years (OR 3.98, 95% CI 1.97-8.02) were independent risk factors of 30-day mortality in multivariable analysis. However, there was no statistically significant association between 30-day mortality and an early start of an effective antifungal. Conclusion: There was not a significant shift to non-albicans species as the cause of candidemia in Southern Finland during the 10-year study period. Furthermore, we did not find an association between 30-day mortality and the early start of an antifungal treatment. Comorbidity considerably increased the risk of fatal outcome.


[Polycystic ovary syndrome: a disorder of insulin action and an increased risk for onset of non-insulin-dependent diabetes].
Hyperandrogenemia may be the most common endocrinopathy in women, affecting up to 10% of all women and as many as 30% of certain subgroups. Women with polycystic ovary syndrome have a unique disorder of insulin action and are at increased risk to develop NIDDM. NIDDM in women with PCOS has earlier age of onset than it does in the general population. Insulin-induced receptor autophosphorylation is diminished in 50% of PCOS women. PCOS may be a disease of abnormal protein tyrosine kinase receptor signaling. IGF-I and IGF-II play an important role in regulating ovarian androgen production via receptors.


Vitamin D, effects on brain development, adult brain function and the links between low levels of vitamin D and neuropsychiatric disease.
Increasingly vitamin D deficiency is being associated with a number of psychiatric conditions. In particular for disorders with a developmental basis, such as autistic spectrum disorder and schizophrenia the neurobiological plausibility of this association is strengthened by the preclinical data indicating vitamin D deficiency in early life affects neuronal differentiation, axonal connectivity, dopamine ontogeny and brain structure and function. More recently epidemiological associations have been made between low vitamin D and psychiatric disorders not typically associated with abnormalities in brain development such as depression and Alzheimer's disease. Once again the preclinical findings revealing that vitamin D can regulate catecholamine levels and protect against specific Alzheimer-like pathology increase the plausibility of this link. In this review we have attempted to integrate this clinical epidemiology with potential vitamin D-mediated basic mechanisms. Throughout the review we have highlighted areas where we think future research should focus.


The Behavior Rating Scale for Dementia of the Consortium to Establish a Registry for Alzheimer's Disease. The Behavioral Pathology Committee of the Consortium to Establish a Registry for Alzheimer's Disease.
The purpose of the study was to develop a standardized instrument, the Behavior Rating Scale for Dementia, for rating psychopathology in patients with probable Alzheimer's disease and to conduct a multicenter pilot study of this instrument. The rating scale was developed collaboratively on the basis of clinical experience and existing instruments. Items were scaled according to frequency of psychopathology and were administered to an informant who was familiar with the subject. The scale was administered in a standardized manner by trained examiners who had met predetermined certification standards. The study group consisted of 303 subjects with probable Alzheimer's disease who had undergone standardized clinical evaluations by the Consortium to Establish a Registry for Alzheimer's Disease. Subjects had an average of 15 problems rated as present in the preceding month. Wide variability in the nature of disturbances was found, with a number of items rated as present since the illness began but not in the past month. Interrater agreement was high. Factor analysis suggested eight preliminary factors that mapped onto clinically relevant domains: depressive features, psychotic features, defective self-regulation, irritability/agitation, vegetative features, apathy, aggression, and affective lability. The Behavior Rating Scale for Dementia provides a standardized, reliable measure that can be administered to caregivers of demented subjects. On the basis of the present study, the scale has been revised slightly. After additional studies in progress, the Behavior Rating Scale for Dementia will be available for general use in assessing a wide range of psychopathology in dementia.


Haemostaseome-associated SNPs: has the thrombotic phenotype a greater influence than ethnicity? GMT study from Aquitaine including Basque individuals.
The Genetic Markers for Thrombosis (GMT) study compared the relative influence of ethnicity and thrombotic phenotype regarding the distribution of SNPs implicated in haemostasis pathophysiology ("haemostaseome"). We assessed 384 SNPs in three groups, each of 480 subjects: 1) general population of Aquitaine region (Southwestern France) used as control; 2) patients with venous thromboembolism from the same area; and 3) autochthonous Basques, a genetic isolate, who demonstrate unusual characteristics regarding the coagulation system. This study sought to evaluate i) the value of looking for a large number of genes in order to identify new genetic markers of thrombosis, ii) the value of investigating low risk factors and potential preferential associations, iii) the impact of ethnicity on the characterisation of markers for thrombosis. We did not detect any previously unrecognised SNP significantly associated with thrombosis risk or any preferential associations of low-risk factors in patients with thrombosis. The sum of ϰ² values for our 110 significant SNPs demonstrated a smaller genetic distance between patients and controls (321 cumulated ϰ² value) than between Basques and controls (1,570 cumulated ϰ² value). Hence, our study confirms the genetic particularity of Basques especially regarding a significantly lower expression of the non-O blood group (p< 0.0004). This is mitigated by a higher prevalence of factor II Leiden (p< 0.02) while factor V Leiden prevalence does not differ. Numerous other differences covering a wide range of proteins of the haemostaseome may result in an overall different genetic risk for venous thromboembolism.


Sequence of pituitary-adrenal cortical hormone responses to low-dose physostigmine administration in young adult women and men.
We previously demonstrated greater HPA axis activation in adult men compared to adult women following low-dose administration of the anticholinesterase inhibitor, physostigmine (PHYSO). Because blood sampling was done infrequently following PHYSO, the rise times of AVP, ACTH1-39, and cortisol could not be determined. In the present study, we determined the sequence of hormone increases by frequent blood sampling following PHYSO. Twelve adult women and 12 adult men underwent three test sessions 5-7 days apart: PHYSO, saline control, and repeat PHYSO. As in the earlier study, PHYSO produced no side effects in half the subjects and mild side effects in the other half, with no significant female-male differences. None of the hormone responses was significantly correlated with the presence or absence of side effects. In both women and men, the AVP increase preceded the ACTH1-39 increase, which in turn preceded the cortisol increase. The AVP and ACTH AUCs were significantly positively correlated in both women and men, supporting AVP as an acute stimulus to ACTH secretion. Also as in the earlier study, the AVP response to PHYSO was more than twice as great in men as in women, but the difference was not statistically significant. We therefore analyzed the results of both studies combined (N=26 women and 26 men). The men had a significantly greater AVP response and a trend toward a greater ACTH1-39 response compared to the women. These findings further support the concept of sexual diergism (functional sex difference) in the influence of CNS cholinergic systems on HPA hormone secretion.


Biological influence of Ca/P ratio on calcium phosphate coatings by sol-gel processing.
The objective of this work has been to develop low temperature sol-gel glass coatings to modify the substrate surface and to evaluate their bioactivity and biocompatibility. Glasses, based on SiO2·CaO·P2O5, were synthesized by the sol-gel technique using tetraethyl orthosilicate, calcium nitrate tetrahydrate and triethyl phosphate as precursors of SiO2, CaO and P2O5, respectively. Those materials, still in the sol phase, have been used to coat substrates by means of the dip-coating technique. Attenuated total reflectance Fourier transform infrared (ATR-FTIR) has been used for characterize coatings and a microstructural analysis has been obtained using scanning electron microscopy (SEM). The potential applications of the coatings in the biomedical field were evaluated by bioactivity and biocompatibility tests. The coated substrate was immersed in simulated body fluid (SBF) for 21days and the hydroxyapatite deposition on its surface was subsequently evaluated via SEM-EDXS analysis, as an index of bone-bonding capability. In order to study the cell behavior and response to our silica based materials, prepared via the sol-gel method, with various Ca/P ratio and coating substrate, we have used the human osteoblast-like U2OS cell line.


Mueller matrix decomposition of diffuse reflectance imaging in skeletal muscle.
Propagation of polarized light in skeletal muscle is significantly affected by anisotropic muscle structures. To completely characterize muscle polarization properties, we acquired the whole Mueller matrix images of the diffuse reflectance. A polar decomposition algorithm was applied to extract the individual diattenuation, retardance, and depolarization images from the measured Mueller matrix. The decomposed polarization properties in muscle show distinctly different patterns from those obtained in isotropic scattering media. Stretching the prerigor muscle sample induced clear changes in the raw polarization reflectance images. However, muscle stretching induced minimal changes in the decomposed Mueller matrix images.


Quick extended x-ray absorption fine structure instrument with millisecond time scale, optimized for in situ applications.
In order to learn about in situ structural changes in materials at subseconds time scale, we have further refined the techniques of quick extended x-ray absorption fine structure (QEXAFS) and quick x-ray absorption near edge structure (XANES) spectroscopies at beamline X18B at the National Synchrotron Light Source. The channel cut Si (111) monochromator oscillation is driven through a tangential arm at 5 Hz, using a cam, dc motor, pulley, and belt system. The rubber belt between the motor and the cam damps the mechanical noise. EXAFS scan taken in 100 ms is comparable to standard data. The angle and the angular range of the monochromator can be changed to collect a full EXAFS or XANES spectrum in the energy range 4.7-40.0 KeV. The data are recorded in ascending and descending order of energy, on the fly, without any loss of beam time. The QEXAFS mechanical system is outside the vacuum system, and therefore changing the mode of operation from conventional to QEXAFS takes only a few minutes. This instrument allows the acquisition of time resolved data in a variety of systems relevant to electrochemical, photochemical, catalytic, materials, and environmental sciences.


Radiation-induced thyroid carcinogenesis as a function of time and dietary iodine supply: an in vivo model of tumorigenesis in the rat.
It is believed that a combination of environmental factors with mutagens induces carcinomas derived from thyroid follicular cells. In this study we tried to ascertain whether a single short-term exposure to external radiation is sufficient to induce thyroid carcinomas in rats under long-term high or low dietary iodine intake. Rats were tested over a period of 110 wk under high (approximately 10-fold of normal), normal, and low (approximately 0.1-fold of normal) daily iodine intake. Forty-day-old animals were subjected to single external radiation of 4 Gy or sham radiation. Thyroid function was tested weekly, and thyroid morphology was determined after 15, 35, 55, and 110 wk. Iodine deficiency, but not high iodine intake, led to a decrease in T(3) and T(4) plasma levels, but to an increase in TSH, which became significant after 9 and 11 wk of treatment, respectively. Both high and low iodine treatment significantly increased the proliferation rate and induced thyroid adenomas, but no malignancies after 55 and 110 wk. Radiation with 4 Gy resulted in a significant destruction of the follicular structure. Under high and low iodine intakes (50-80% of animals), but not under normal iodine supply, thyroid carcinomas were observed in irradiated rats. Thus, the increased proliferation rate induced under the experimental conditions described in this study is apparently not sufficient to cause thyroid carcinomas, but the presence of a mutagen-like radiation is required. This model may help to define genetic alterations long before histological changes are detectable.


Too Much Oxygen: Hyperoxia and Oxygen Management in Mechanically Ventilated Patients.
Hyperoxia, or excess oxygen supplementation, prevails in the intensive care unit (ICU) without a beneficial effect and, in some instances, may cause harm. Recent interest and surge in clinical studies in mechanically ventilated critically ill patients has brought this to the attention of clinicians and researchers. Hyperoxia can cause alveolar injury, pulmonary edema, and subsequent systemic inflammatory response and is known to augment ventilator-associated lung injury. Liberal oxygenation practices are also associated with increased mortality in subsets of critically ill patients with post-cardiac arrest, stroke, and traumatic brain injury. Most clinicians agree that oxygen titration should be done and, with appropriate safeguards, lower oxygenation targets may be acceptable and possibly beneficial in many critically ill patients. However, this problem is often overlooked. The use of periodic reminders and decision support may facilitate implementation of more precise oxygen titration at the bedside of critically ill patients. For implementing practice change, studies involving education and guidance of all health care staff involved in oxygen management are critical.