Scrupulosity: a unique subtype of obsessive-compulsive disorder.
The earliest descriptions of obsessive-compulsive disorder (OCD) were religious, as was the understanding of their origins. With the emancipation, religion in OCD was relegated to its status today: a less common symptom of OCD in most Western societies known as scrupulosity. The frequency of scrupulosity in OCD varies in the literature from 0% to 93% of cases, and this variability seems predicated on the importance of religious belief and observance in the community examined. Despite the similarities between religious ritual and compulsions, the evidence to date that religion increases the risk of the development of OCD is scarce. Scrupulosity is presented as a classic version of OCD, with obsessions and compulsions, distress, and diminished functioning similar to those of other forms of OCD. The differentiation between normal religiosity and scrupulosity is presented, and the unique aspects of cognitive-behavioral therapy in treating scrupulosity, especially in religious populations, are reviewed.


Selection of diverse polymorphic structures from a small dynamic molecular network controlled by the environment.
The complex interplay between systems and their environment plays an important role in processes ranging from self-assembly to evolution. Polymorphism, where, from the same ingredients different products can be formed, is likely to be an important enabler for evolutionary adaptation. Environmental pressures may induce polymorphic behaviour, where different pressures result in different structural organisation. Here we show that by combining covalent and non-covalent bond formation three distinct polymorphs can emerge from the same small dynamic molecular network: vesicular aggregates, self-replicating fibres and nanoribbons, depending on the nature of the solvent environment. Additionally, a particular set of conditions allows the transient co-existence of both vesicles and fibres.


An examination of objectively-measured sedentary behavior and mental well-being in adults across week days and weekends.
Limited research has explored the links between sedentary behaviour, mental health and quality of life. This study examines objectively measured sedentary behaviour and perceived mental health and quality of life across week days and weekends. 42 adults (19M, 23F; mean age 38yrs (range 18-67) & BMI 24.8kg/m2 (range 18.7-33.8) wore an activPAL monitor 24h/day for one week and completed the Hospital Anxiety and Depression Scale (HADS) and SF12 Health Survey. Average weekday and weekend day sitting time was computed. Differences between sitting (Group 1 = <8hrs/day, Group 2 = 8-10 hrs/day, Group 3 = >10hrs/day) and components of the HADS and SF12 health survey were examined using an ANCOVA with a measure of physical activity (step count) included as a covariate. Average sitting time on a weekday was 9hrs 29mins (range 5hrs 52mins to 12hrs 55mins) and 8hrs 59mins (range 4hrs, 07mins to 14hrs, 40mins) on a weekend day. There was a main effect (p<0.05) for weekday sitting time on total anxiety and depression (HADS) and mental health and vitality (SF12). Planned contrasts identified individuals in group 1 had lower anxiety and depression and higher mental health and vitality scores than individuals in groups 2 or 3 (p<0.05). No difference was found between individuals in group 2 and group 3 (p>0.05). No main effects were found for weekend sitting (p>0.05). Weekday sitting time below 8 hours/day is associated with better perceived mental health and quality of life.


Development of Criteria for a Positive Front-of-Package Food Labeling: The Israeli Case.
Efforts to shape the food environment are aimed at reducing diet-related co-morbidities. Front-of-package labeling (FOPL) may support the consumers to make an informed decision at the point of purchase and encourage industry to reformulate food products. The Israeli Ministry of Health (MOH) implemented a unique FOPL system, using two colors: A mandatory warning (red) label alongside a voluntary positive (green) label. An independent Scientific Committee, from academia, the healthcare system, and MOH was appointed to determine the core principles for the positive FOPL. The criteria were based on the Mediterranean diet principles, with adjustments to the Israeli dietary habits, focusing on the health advantages of the food and considering its processing level. The food products eligible for positive FOPL are foods in their natural form or with added spices or herbs, or those that underwent minimal processing, with no food additives. Based on population consumption data, 19.8% of food products were eligible for positive FOPL; of them, 54% were fruits and vegetables, 20% dairy, and 14% grains. An evaluation plan is needed to assess the degree of acceptance of the positive FOPL by the industry, retailers, and the public, and its impact on food consumption and on public health.


Cortisol and TGF-beta inhibit secretion of platelet-activating factor-acetylhydrolase in a monocyte-macrophage model system [corrected].
Recent studies have suggested that platelet activating factor (PAF) plays an important role in various reproductive functions, including ovulation, implantation and parturition, and that the local concentration of PAF is modulated by PAF-acetylhydrolase (PAF-AH), a potent PAF inactivator. In this study, we investigated the possible effects of various bioactive substances, which are present at high concentrations in the human pregnant uterus, on PAF-AH secretion from decidual macrophages using a monocyte-macrophage model system, human myelocytic leukaemia cells (HL-60). By treatment with 12-O-tetradecanoylphorbol-13-acetate (TPA), HL-60 cells were transformed to macrophage-like cells, which secreted PAF-AH into the culture medium time- and dose-dependently. After treatment with 10(-8) M TPA, the effects of various substances on the secretion of PAF-AH were examined. Among the substances examined, cortisol and TGF-beta suppressed PAF-AH secretion from TPA-stimulated HL-60 cells in a significant and dose-dependent way. Endothelin, epidermal growth factor, and brain natriuretic peptide had no significant effect on PAF-AH secretion from TPA-stimulated HL-60 cells. These results suggest that local PAF concentrations in the pregnant uterus might be regulated, at least partly, by cortisol and TGF-beta; thus these substances may play a role in the initiation of parturition via regulation of local PAF concentrations.


Relaxin prevents the development of severe acute pancreatitis.
To investigate the severity of acute pancreatitis (AP) is associated to the intensity of leukocyte activation, inflammatory up-regulation and microcirculatory disruption associated to ischemia-reperfusion injury. Microvascular integrity and inhibition of pro-inflammatory mediators are key-factors in the evolution of AP. Relaxin is an insulin-like hormone that has been attributed vasorelaxant properties via the nitric oxide pathway while behaving as a glucocorticoid receptor agonist. AP was induced by the bilio-pancreatic duct-outlet-exclusion closed-duodenal-loops model. Treatment with relaxin was done at different time-points. Nitric oxide synthase inhibition by L-NAME and glucocorticoid receptor (GR) blockage by mifepristone was considered. AP severity was assessed by biochemical and histopathological analyses. Treatment with relaxin reduced serum amylase, lipase, C-reactive protein, IL-6, IL-10, hsp72, LDH and 8-isoprostane as well as pancreatic and lung myeloperoxidase. Acinar and fat necrosis, hemorrhage and neutrophil infiltrate were also decreased. ATP depletion and ADP/ATP ratio were reduced while caspases 2-3-8 and 9 activities were increased. L-NAME and mifepristone decreased the efficiency of relaxin. Relaxin resulted beneficial in the treatment of AP combining the properties of a GR agonist while preserving the microcirculation and favoring apoptosis over necrosis.


A STUDY OF THE CROSS-REACTIVITY OF ANTIPURIN-6-OYL SERUM WITH DEOXYRIBONUCLEIC ACID (DNA).
The specificity of the reaction of antipurin-6-oyl sera with thermally denatured DNA has been studied by means of hapten inhibition techniques. The relative order of effectiveness of various haptens as inhibitors of the complement fixation reaction between DNA and antipurin-6-oyl serum was found to be comparable to their relative order of effectiveness as inhibitors of the precipitin reaction between purin-6-oyl-protein conjugates and antipurin-6-oyl serum. Antipurin-6-oyl antibody has been purified and has been shown to be capable of reacting with thermally denatured DNA. It is concluded that the reactivity of these purine-specific antisera with DNA is a property of antibody with specificity for the purin-6-oyl moiety. In addition, the reaction between antipurinoyl sera and DNA has been demonstrated by the techniques of radioimmunoelectrophoresis and passive cutaneous anaphylaxis.


Dispersive pulse compression in hollow-core photonic bandgap fibers.
Compression of linearly chirped picosecond pulses in hollow-core photonic bandgap fibers is investigated numerically. The modal properties of the fibers are modeled using the finite-element technique, whereas nonlinear propagation is described by a generalized nonlinear Schrödinger equation, which accounts both for the composite nature of the nonlinearity and the strong mode profile dispersion. Power limits for compression with more than 90% of the pulse energy in the main peak of the compressed pulse are investigated as a function of fiber design, and the temporal and spectral widths of the input pulse. The validity of approximate scaling rules is investigated, and figures of merit for fiber design are discussed.


Gadolinium Complexes of Highly Rigid, Open-Chain Ligands Containing a Cyclobutane Ring in the Backbone: Decreasing Ligand Denticity Might Enhance Kinetic Inertness.
In an effort to explore novel ligand scaffolds for stable and inert lanthanide complexation in magnetic resonance imaging contrast agent research, three chiral ligands containing a highly rigid (1S,2S)-1,2-cyclobutanediamine spacer and different number of acetate and picolinate groups were efficiently synthesized. Potentiometric studies show comparable thermodynamic stability for the Gd3+ complexes formed with either the octadentate (L3)4- bearing two acetate or two picolinate groups or the heptadentate (L2)4- analogue bearing one picolinate and three acetate groups (log KGdL = 17.41 and 18.00 for [Gd(L2)]- and [Gd(L3)]-, respectively). In contrast, their dissociation kinetics is revealed to be very different: the monohydrated [Gd(L3)]- is considerably more labile, as a result of the significant kinetic activity of the protonated picolinate function, as compared to the bishydrated [Gd(L2)]-. This constitutes an uncommon example in which lowering ligand denticity results in a remarkable increase in kinetic inertness. Another interesting observation is that the rigid ligand backbone induces an unusually strong contribution of the spontaneous dissociation to the overall decomplexation process. Thanks to the presence of two inner-sphere water molecules, [Gd(L2)]- is endowed with high relaxivity (r1 = 7.9 mM-1 s-1 at 20 MHz, 25 °C), which is retained in the presence of large excess of endogenous anions, excluding ternary complex formation. The water exchange rate is similar for [Gd(L3)]- and [Gd(L2)]-, while it is 1 order of magnitude higher for the trishydrated tetraacetate analogue [Gd(L1)]- (kex298 = 8.1, 10, and 127 × 106 s-1, respectively). A structural analysis via density functional theory calculations suggests that the large bite angle imposed by the rigid (1S,2S)-1,2-cyclobutanediamine spacer could allow the design of ligands based on this scaffold with suitable properties for the coordination of larger metal ions with biomedical applications.


Resonance Tube Phonation in Water-the Effect of Tube Diameter and Water Depth on Back Pressure and Bubble Characteristics at Different Airflows.
Resonance tube phonation with tube end in water is a voice therapy method in which the patient phonates through a glass tube, keeping the free end of the tube submerged in water, creating bubbles. The purpose of this experimental study was to determine flow-pressure relationship, flow thresholds between bubble types, and bubble frequency as a function of flow and back volume. A flow-driven vocal tract simulator was used for recording the back pressure produced by resonance tubes with inner diameters of 8 and 9 mm submerged at water depths of 0-7 cm. Visual inspection of bubble types through video recording was also performed. The static back pressure was largely determined by the water depth. The narrower tube provided a slightly higher back pressure for a given flow and depth. The amplitude of the pressure oscillations increased with flow and depth. Depending on flow, the bubbles were emitted from the tube in three distinct types with increasing flow: one by one, pairwise, and in a chaotic manner. The bubble frequency was slightly higher for the narrower tube. An increase in back volume led to a decrease in bubble frequency. This study provides data on the physical properties of resonance tube phonation with the tube end in water. This information will be useful in future research when looking into the possible effects of this type of voice training.


[Influence of environmental factors on the epidemiology of tuberculosis in the Astrakhan region].
The epidemiology of tuberculosis in the Astrakhan Region depends on many causes among which environmental factors do not take last places; a significant positive correlation with which was observed in 41.5 and 52% cases in the rural areas of the Astrakhan Region and in Astrakhan, respectively. The proportion of environmental factors among the causes in noticeably higher in destructive pulmonary tuberculosis, in chronic destructive forms in particular, and in first detected bacillary patients.


[Intravascular large B-cell lymphoma with multiple intracranial hemorrhages diagnosed by brain biopsy].
Central nervous system intravascular lymphoma sometimes includes multiple lesions mimicking cerebral infarction. Herein, we report our experience with a case of intravascular large B-cell lymphoma (IVLBCL) with multiple hemorrhages. A 53-year-old woman was admitted to our hospital with clonic convulsions of the left upper limb. Brain MRI revealed a large number of high-intensity areas on FLAIR and low-intensity areas on susceptibility-weighted imaging (SWI). Chest CT showed bilateral multiple high-density lesions in the lungs. Biopsy of pulmonary lesions revealed no abnormal cells. Levetiracetam was administered to prevent the seizures that were assumed to occur due to the cerebral cortex lesions; however, convulsive seizure recurred with a depressed level of consciousness. On a repeat brain MRI examination, severe, multiple new lesions were shown to have developed bilaterally in the cerebral cortex and white matter, exhibiting spotty low intensities on SWI. Biopsy of a new cerebral lesion was carried out and the lesion was pathologically diagnosed as IVLBCL with hemorrhages. IVLBCL should be noted as one of the differential diagnoses not only in case with multiple infarct lesions, but also in case with multiple hemorrhages.


Temporal auditory processing and phonological awareness in reading and writing disorders: preliminary data.
To verify if there is an association between temporal auditory tests and phonological awareness in individuals with reading and writing disorders. Sixteen children were subjects of this study, aged between 7 and 12 years old, who had reading and writing disorders confirmed after specific assessment. All participants underwent phonological awareness assessment using CONFIAS test. In order to assess the auditory temporal processing, duration and frequency pattern tests were used. The descriptive analysis indicated low performance in syllabic and phonemic activities of phonological awareness as well as in temporal auditory tests. Fisher's test indicated association between disorders in auditory temporal processing and phonological awareness (p>0.001). It suggests that disorders in temporal processing contribute to low performance in phonological awareness tasks. There was association between performance in temporal auditory tests and in the phonological awareness. Data found provide reflections about including temporal auditory assessment among procedures used in the analysis of individuals with reading and writing disorders.


Preoperative Anti-Class III β-Tubulin Antibodies As Relevant Clinical Biomarkers in Ovarian Cancer.
Class III β-tubulin (TUBB3) overexpression in ovarian cancer (OC) associates with poor prognosis. We investigated whether TUBB3 overexpression elicited anti-TUBB3 antibody production in OC patients and whether these antibodies may have diagnostic and prognostic impact. The presence of serum anti-TUBB3 antibodies was investigated in 49 untreated OC patients and 44 healthy individuals by an in-house developed ELISA that used recombinant TUBB3 as the antigen. Receiver operating characteristic (ROC) curves were generated to assess the diagnostic accuracy of the assay. Anti-TUBB3 antibodies discriminated OC patients and healthy individuals with excellent sensitivity and specificity (91.8% and 90.9%, respectively). In multivariate analysis, anti-TUBB3 antibody level emerged as an independent prognostic factor for progression free and overall survival. The ELISA was then optimized using a biotin-labeled TUBB3 C-terminal peptide424-450 instead of recombinant TUBB3 as the antigen and streptavidin-coated plates. The diagnostic role of the anti-TUBB3 antibodies was studied in an independent series of 99 OC patients and 80 gynecological benign disease patients. ROC-curve analysis showed a valuable diagnostic potential for serum anti-TUBB3 antibodies to identify OC patients with higher sensitivity and specificity (95.3% and 97.6%, respectively). Overall, our results provide evidence that preoperative anti-TUBB3 antibody level is a promising diagnostic and prognostic biomarker for the management of OC patients.


The Impact of Environmental Sustainability Labels on Willingness-to-Pay for Foods: A Systematic Review and Meta-Analysis of Discrete Choice Experiments.
Food production is a major contributor to environmental damage. More environmentally sustainable foods could incur higher costs for consumers. In this review, we explore whether consumers are willing to pay (WTP) more for foods with environmental sustainability labels ('ecolabels'). Six electronic databases were searched for experiments on consumers' willingness to pay for ecolabelled food. Monetary values were converted to Purchasing Power Parity dollars and adjusted for country-specific inflation. Studies were meta-analysed and effect sizes with confidence intervals were calculated for the whole sample and for pre-specified subgroups defined as meat-dairy, seafood, and fruits-vegetables-nuts. Meta-regressions tested the role of label attributes and demographic characteristics on participants' WTP. Forty-three discrete choice experiments (DCEs) with 41,777 participants were eligible for inclusion. Thirty-five DCEs (n = 35,725) had usable data for the meta-analysis. Participants were willing to pay a premium of 3.79 PPP$/kg (95%CI 2.7, 4.89, p ≤ 0.001) for ecolabelled foods. WTP was higher for organic labels compared to other labels. Women and people with lower levels of education expressed higher WTP. Ecolabels may increase consumers' willingness to pay more for environmentally sustainable products and could be part of a strategy to encourage a transition to more sustainable diets.


[Kinetic characteristics of spoilage processes in dairy products].
Some investigations concerned with the relationships between the storage conditions, transporting, etc and the quality of dairy products are described in terms of kinetics. The author gives some general approaches to the problems of storage conditions/storage period and the rest of storage period relating to the storage conditions. The indicators of the decomposition processes discussed in details.


CD40-CD40 ligand mediates the recruitment of leukocytes and platelets in the inflamed murine colon.
Although the CD40-CD40 ligand (CD40L) signaling pathway has been implicated in the pathogenesis of a variety of diseases, including inflammatory bowel disease, the nature of its contribution to intestinal inflammation remains poorly understood. The aim of this study was to determine whether CD40-CD40L contributes to the intestinal inflammatory response, tissue injury, and disease activity elicited by dextran sodium sulphate (DSS) through the modulation of leukocyte and platelet recruitment in the colonic microvasculature. Wild-type (WT), CD40(-/-), and CD40L(-/-) mice were fed DSS drinking water. On day 6, intravital videomicroscopy was performed to monitor leukocyte and platelet recruitment in colonic venules, with measurements obtained for tissue myeloperoxidase and histology. CD40 expression on colonic endothelium was measured using the dual-radiolabeled antibody technique. A comparison of the responses to DSS-induced colitis in CD40(-/-) and CD40L(-/-) mice to WT mice revealed a significant attenuation of disease activity and histologic damage, as well as profound reductions in the recruitment of adherent leukocytes and platelets in the mutant mice. Similar down-regulation of the blood cell recruitment responses to DSS was noted in WT mice treated with the CD40-CD40L pathway inhibitor Trapidil. CD40 expression in the colonic vasculature was greatly elevated during DSS-induced inflammation in WT mice, but not in CD40(-/-) mice. These findings implicate CD40-CD40L in the pathogenesis of DSS-induced intestinal inflammation, and suggest that modulation of leukocyte and platelet recruitment by activated, CD40-positive endothelial cells in colonic venules may represent a major action of this signaling pathway.


Protozoan and myxozoan infections in wild gilthead seabream (Sparus aurata L.) from North Lake of Tunis, Tunisia.
A total of 150 gilthead seabream Sparus aurata L., from North Lake of Tunis, Tunisia, were studied for protozoan and myxozoan parasites. The parasitological survey revealed the presence of ectoparasites (Amyloodinium ocellatum Brown, 1931, Trichodina lepsii Lom, 1962 on the gills) and endoparasites (Ceratomyxa sparusaurati Sitjà-Bobadilla, Palenzuela et Alvarez-Pellitero, 1995 infecting the gallbladder, and Eimeria sparis Sitjà-Bobadilla, Palenzuela et Alvarez-Pellitero, 1996 parasitizing the intestine). This is the first record of Amyloodinium ocellatum, Trichodina lepsii, Ceratomyxa sparusaurati, and Eimeria sparis in S. aurata from Tunisian waters. Data on prevalence and intensity of infection are provided. A comparison of the present species with previously described species in cultured gilthead seabream from other Mediterranean countries is also presented. In this study Trichodina lepsii is identified for the first time in Sparus aurata. A taxonomic description of this species based on silver nitrate method is provided.


Hyperthermia in running sled dogs.
Hyperthermia, as measured by increase in rectal temperature, was studied in a group of 22 adult mongrel sled dogs that had been selectively bred for high-speed (up to 33 km/h) races 16-50 km in distance. Under normal working conditions, rectal temperature in the sled dogs increased significantly during initial 15-20 min of run (gathered gallop) after which temperature usually stabilized or decreased slightly. Amount of increase in rectal temperature was correlated directly with ambient temperature but not with speed or distance. Significant differences in degree of hyperthermia were found among dogs but these differences were not correlated with such factors as sex, size, coat color, weight, or genetic history. Training was found to significantly diminish amount of increase in rectal temperature during work. Data from the present study were compared to those of other laboratory investigations and relationships of heat storage and radiative surface area to body weight are discussed.


[3-D imaging of skin cancers and survival].
The incidence of skin cancers is still on the rise despite information provided to the public and to cancer screening initiatives. We designed a 3D movie with the support of all Belgian university departments of dermatology. Looking at the impact of ultraviolet light in cells was the objective of this presentation. Several themes of actuality were addressed including genotoxicity of light, the primary prevention of skin cancers, the field actinodermatosis and cancerogenesis, the skin cancer epidemiology, the duality of skin melanomas with contrasted prognoses, and the recognition of melanoma stem cells.


Suppurative otitis and ascending meningoencephalitis associated with Bacteroides tectus and Porphyromonas gulae in a captive Parma wallaby (Macropus parma) with toxoplasmosis.
A 6-year-old female Parma wallaby (Macropus parma) at a zoo in California developed acute ataxia and left-sided circling. Despite intensive care, clinical signs progressed to incoordination and prostration, and the animal was euthanized. At necropsy, the left tympanic cavity was filled with homogeneous suppurative exudate that extended into the cranium expanding the meninges and neuroparenchyma in the lateral and ventral aspect of the caudal ipsilateral brainstem and medulla oblongata. Microscopically, the brainstem showed regional severe suppurative meningoencephalitis with large numbers of neutrophils, fewer macrophages, and lymphocytes admixed with fibrin, necrotic cellular debris, hemorrhage, and mineralization, with numerous intralesional Gram-negative bacilli. Bacteroides spp. and Porphyromonas spp. were isolated on anaerobic culture from the meninges, and the bacteria were further characterized by partial 16S ribosomal RNA gene sequencing as Bacteroides tectus and Porphyromonas gulae. Bacterial aerobic culture from the meninges yielded very low numbers of mixed flora and Proteus spp., which were considered contaminants. Culture of Mycoplasma spp. from middle ear and meninges was negative. Additionally, Toxoplasma gondii cysts were detected by immunohistochemistry in the heart and brain, and anti-Toxoplasma antibodies were detected in serum. The genera Bacteroides and Porphyromonas have been associated with oral disease in marsupials; but not with otitis and meningoencephalitis. The results of the present work highlight the importance of performing anaerobic cultures in the diagnostic investigation of cases of suppurative otitis and meningoencephalitis in macropods.


Evidence in sheep for pre-natal transmission of scrapie to lambs from infected mothers.
Natural scrapie transmission from infected ewes to their lambs is thought to occur by the oral route around the time of birth. However the hypothesis that scrapie transmission can also occur before birth (in utero) is not currently favoured by most researchers. As scrapie is an opportunistic infection with multiple infection routes likely to be functional in sheep, definitive evidence for or against transmission from ewe to her developing fetus has been difficult to achieve. In addition the very early literature on maternal transmission of scrapie in sheep was compromised by lack of knowledge of the role of the PRNP (prion protein) gene in control of susceptibility to scrapie. In this study we experimentally infected pregnant ewes of known PRNP genotype with a distinctive scrapie strain (SSBP/1) and looked for evidence of transmission of SSBP/1 to the offspring. The sheep were from the NPU Cheviot flock, which has endemic natural scrapie from which SSBP/1 can be differentiated on the basis of histology, genetics of disease incidence and strain typing bioassay in mice. We used embryo transfer techniques to allow sheep fetuses of scrapie-susceptible PRNP genotypes to develop in a range of scrapie-resistant and susceptible recipient mothers and challenged the recipients with SSBP/1. Scrapie clinical disease, caused by both natural scrapie and SSBP/1, occurred in the progeny but evidence (including mouse strain typing) of SSBP/1 infection was found only in lambs born to fully susceptible recipient mothers. Progeny were not protected from transmission of natural scrapie or SSBP/1 by washing of embryos to International Embryo Transfer Society standards or by caesarean derivation and complete separation from their birth mothers. Our results strongly suggest that pre-natal (in utero) transmission of scrapie may have occurred in these sheep.


Glial expression of cytokines in the brains of cerebrovascular disease patients.
We examined the immunohistochemical localization of the proinflammatory cytokines tumor necrosis factor-alpha, lymphotoxin and interferon-gamma in 22 autopsy brains of patients with either cerebrovascular disease (CVD) or other neurological diseases as well as 2 non-neurological control brains. These cytokines were coexpressed mostly in the microglia/macrophages and in a few astroglia in the brains with acute cerebral infarction and cerebral hemorrhage. In cases with cerebral infarction, they were observed as early as 33 h after the onset of the illness and persisted for up to 40 days after the onset. In one patient with cerebral hemorrhage who survived for 4 h, the cytokine-immunoreactive glial cells were confined to the margins of the hematoma. In contrast, the cytokine-immunoreactive glia were distributed diffusely in one patient with cerebral hemorrhage who died 12 days after the onset of the illness. Labeling for these cytokines was weak in the glial cells of control brains and those with neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease and multiple system atrophy, in so far as there were no concomitant acute CVD foci. The present results indicate that proinflammatory cytokines are up-regulated in the brains of patients with acute stroke, and suggest an early inflammatory response in human CVD.


Ascorbic acid levels in the aqueous humor of nocturnal and diurnal mammals.
Ascorbic acid concentration is known to be very high in the aqueous humor of humans and most animals. The role it might play in ocular function is a subject of conjecture. Some have proposed that it might protect the eye against light-induced damage. We examined the aqueous humor from 22 species of mammals to determine the range of levels and to see if there was a correlation with behavior. A wide range of ascorbic acid levels in the aqueous humor was found. Most of the animals considered to be diurnal had higher ascorbic acid levels than the nocturnal animals. This would suggest that ascorbic acid in the aqueous humor may play a protective role in those animals who are most exposed to light. Regardless, any theory proposing a role for ascorbic acid in the eye in mammals must take the wide range of ascorbic acid levels into account.


Between-center and between-country differences in outcome after aneurysmal subarachnoid hemorrhage in the Subarachnoid Hemorrhage International Trialists (SAHIT) repository.
Differences in clinical outcomes between centers and countries may reflect variation in patient characteristics, diagnostic and therapeutic policies, or quality of care. The purpose of this study was to investigate the presence and magnitude of between-center and between-country differences in outcome after aneurysmal subarachnoid hemorrhage (aSAH). The authors analyzed data from 5972 aSAH patients enrolled in randomized clinical trials of 3 different treatments from the Subarachnoid Hemorrhage International Trialists (SAHIT) repository, including data from 179 centers and 20 countries. They used random effects logistic regression adjusted for patient characteristics and timing of aneurysm treatment to estimate between-center and between-country differences in unfavorable outcome, defined as a Glasgow Outcome Scale score of 1-3 (severe disability, vegetative state, or death) or modified Rankin Scale score of 4-6 (moderately severe disability, severe disability, or death) at 3 months. Between-center and between-country differences were quantified with the median odds ratio (MOR), which can be interpreted as the ratio of odds of unfavorable outcome between a typical high-risk and a typical low-risk center or country. The proportion of patients with unfavorable outcome was 27% (n = 1599). The authors found substantial between-center differences (MOR 1.26, 95% CI 1.16-1.52), which could not be explained by patient characteristics and timing of aneurysm treatment (adjusted MOR 1.21, 95% CI 1.11-1.44). They observed no between-country differences (adjusted MOR 1.13, 95% CI 1.00-1.40). Clinical outcomes after aSAH differ between centers. These differences could not be explained by patient characteristics or timing of aneurysm treatment. Further research is needed to confirm the presence of differences in outcome after aSAH between hospitals in more recent data and to investigate potential causes.


Variations in sexual network connectivity may explain dramatic variations in sexually transmitted infection prevalence between populations and over time: a four-country analysis.
Background: The incidence of sexually transmitted infections (STIs) has been noted to vary dramatically between population groups and over time. Here, the hypothesis that changes in network connectivity underpin these changes is explored. Methods: The incidence/prevalence estimates of HIV, herpes simplex virus-2, syphilis, chlamydia, and gonorrhoea, as well as two markers of sexual network connectivity (partner concurrency and multiple partnering) by ethnic group and sexual orientation in Kenya, South Africa, the United Kingdom (UK) and the United States (USA) were extracted from published studies. Pearson's correlation was used to test the association between the markers of network connectivity and the incidence/prevalence of these five STIs. A literature review was performed to evaluate the possible causes of the increases and decreases in syphilis incidence over the past 60 years. Results: In each country, the five STIs were found to cluster in particular ethnic groups and sexual orientations and to be positively associated with the two markers of network connectivity. Syphilis incidence in the UK and USA was found to increase dramatically in the 1960s/1970s, decline in the 1980s and again increase in the late 1990s. These changes took place predominantly in men who have sex with men, and were preceded by corresponding changes in network connectivity. The large decline in antenatal syphilis prevalence in Kenya and South Africa in the 1990s were likewise preceded by declines in network connectivity. Conclusions: Although other explanatory variables are not controlled for, the present analysis is compatible with the hypothesis that differential network connectivity is a parsimonious explanation for variations in STI incidence over time and between populations.


WT1-specific serum antibodies in patients with leukemia.
WT1 is an oncogenic protein expressed by the Wilms' tumor gene and overexpressed in the majority of acute myelogenous leukemias (AMLs) and chronic myelogenous leukemias (CMLs). The current study analyzed the sera of patients with AML and CML for the presence of antibodies to full-length and truncated WT1 proteins. Sixteen of 63 patients (25%) with AML had serum antibodies reactive with WT1/full-length protein. Serum antibodies from all 16 were also reactive with WT1/NH2-terminal protein. By marked contrast, only 2 had reactivity to WT1/COOH-terminal protein. Thus, the level of immunological tolerance to the COOH terminus may be higher than to the NH2 terminus. The WT1/COOH-terminal protein contains four zinc finger domains with homology to other self-proteins. By implication, these homologies may be related to the increased immunological tolerance. Results in patients with CML were similar with antibodies reactive to WT1/full-length protein detectable in serum of 15 of 81 patients (19%). Antibodies reactive with WT1/NH2-terminal protein were present in the serum of all 15, whereas antibodies reactive with WT1/COOH-terminal protein were present in only 3. By contrast to results in leukemia patients, antibodies reactive with WT1/full-length protein were detected in only 2 of 96 normal individuals. The greater incidence of antibody in leukemia patients provides strong evidence that immunization to the WT1 protein occurred as a result of patients bearing malignancy that expresses WT1. These data provide further stimulus to test therapeutic vaccines directed against WT1 with increased expectation that the vaccines will be able to elicit and/or boost an immune response to WT1.


Haplotypes and SNPs in 13 lipid-relevant genes explain most of the genetic variance in high-density lipoprotein and low-density lipoprotein cholesterol.
Single nucleotide polymorphisms (SNPs) and derived haplotypes within multiple genes may explain genetic variance in complex traits; however, this hypothesis has not been rigorously tested. In an earlier study we analyzed six genes and have now expanded this investigation to include 13. We studied 250 families including 1054 individuals and measured lipid phenotypes. We focused on low-density cholesterol (LDL), high-density cholesterol (HDL) and their ratio (LDL/HDL). A component analysis of the phenotypic variance relying on a standard genetic model' showed that the genetic variance on LDL explained 26%, on HDL explained 38% and on LDL/HDL explained 28% of the total variance, respectively. Genotyping of 93 SNPs in 13 lipid-relevant genes generated 230 haplotypes. The association of haplotypes in all the genes tested explained a major fraction of the genetic phenotypic variance component. For LDL, the association with haplotypes explained 67% and for HDL 58% of the genetic variance relative to the polygenic background. We conclude that these haplotypes explain most of the genetic variance in LDL, HDL and LDL/HDL in these representative German families. An analysis of the contribution to the genetic variance at each locus showed that APOE (50%), CETP (28%), LIPC (9%), APOB (8%) and LDLR (5%) influenced variation in LDL. LIPC (53%), CETP (25%), ABCA1 (10%), LPL (6%) and LDLR (6%) influenced the HDL variance. The LDL/HDL ratio was primarily influenced by APOE (36%), CETP (27%) and LIPC (31%). This expanded analysis substantially increases the explanation of genetic variance on these complex traits.


[Chitinase formation by actinomycetes in deep cultures].
Actinomycetes were cultivated in the medium containing demineralized crab shells as a source of carbon. Chitinase was found in filtrates of the cultural broth of all 44 studied strains. The activity of the extracellular chitinase was determined both by decomposition of ground chitin (CHI-activity) and colloid chitin (CHI-activity). The ratio between CHI and CHX in filtrates of the cultural broth of the most active nine strains varied from one to two.


Radiation-induced micronuclei in human fibroblasts in relation to clonogenic radiosensitivity.
As part of our programme for developing predictive tests for normal tissue response to radiotherapy, we have investigated the efficacy of the cytokinesis-block micronucleus (MN) assay as a means of detecting interindividual differences in cellular radiosensitivity. A study was made of nine fibroblast strains established from vaginal biopsies of pretreatment cervical cancer patients and an ataxia telangiectasia (A-T) cell strain. Cells were irradiated in plateau phase, replated and treated with cytochalasin B 24 h later. MN formation was examined 72 h after irradiation as the number of MN in 100 binucleate cells. The method yielded low spontaneous MN yields (<7 per 100 cells), and mean induced MN frequencies after 3.5 Gy varied between cell strains from 18 to 144 per 100 cells. However, in repeat experiments, considerable intrastrain variability was observed (CV = 32%), with up to twofold differences in MN yields, although this was less than interstrain variability (CV = 62%). An analysis was made of the relationship between MN results and previously obtained clonogenic survival data. There was a significant correlation between MN yields and clonogenic survival. However, when the A-T strain was excluded from the analysis, the correlation lost significance, mainly because of one slow-growing strain which was the most sensitive to cell killing but had almost the lowest MN frequency. With current methodology, the MN assay on human fibroblasts does not appear to have a role in predictive testing of normal tissue radiosensitivity.


Merkel cell carcinoma: what makes a difference?
Merkel cell carcinoma (MCC) is a cutaneous neuroendocrine tumor that may spread via lymphatics and can therefore be staged with sentinel lymph node biopsy (SLNB). MCC is radiosensitive and chemosensitive, although the role of adjuvant therapy is still unclear. We examined the impact of different treatments on the outcome of MCC. We performed a retrospective review of state cancer registry data from California, Oregon, and Washington of patients diagnosed with primary skin MCC between 1988 and 2012 (n = 4,038). Data were analyzed using Cox regression and Kaplan-Meier methods to examine disease-specific survival. Patients with positive nodes or no documented nodal evaluation had worse survival compared with node-negative patients. No nodal evaluation had decreased survival compared with lymph node evaluation by SLNB. Completion lymph node dissection conferred improved survival in patients with a positive SLNB. In clinically node-negative patients who had a positive SLNB, radiation and chemotherapy did not affect survival. Lymph node evaluation is an important component to MCC treatment. The role of adjuvant radiation and chemotherapy needs further evaluation.


Fine-Scale Spatial Patterns of Mature and Immature Filaments and Bioorganic Compounds of the Rhodophyte Bangia atropurpurea in the Supra- and Eulittoral Zones of a Large Lake(1).
Bangia atropurpurea (Mertens ex Roth) C. Agardh is a freshwater red alga species that is distributed worldwide. B. atropurpurea is highly adaptable due to its stress-tolerance, which ensures survival under desiccation periods and under radiation extremes typical of the supra- and upper eulittoral zones. Whereas a number of previous investigations addressed some of the physiological and biochemical traits involved in stress-tolerance, we studied the spatial arrangement of the mature (multiseriate) and immature (uniseriate) filaments and of selected bioorganic compounds along a gradient defined by distance from the waterline. Substantial physiological and biochemical differences were previously observed among phenological stages in the marine environment. In this study, we showed a nonrandom spatial structure of both phenological stages and photosynthetic pigments and photoprotective compounds, R-phycocyanin and R-phycoerythrin along the supralittoral-eulittoral gradient. This observed pattern strongly suggests a complex interplay between physio-morphological regulation and spatial arrangement of mature and immature filaments in conferring the typical stress tolerance of B. atropurpurea.


The Use of Integra in Extensive Full-Thickness Scalp Burn Involving the Skull in a Child.
Extensive full-thickness burn injury of the scalp involving the skull is a challenge to reconstruct. Here, the authors report a case of a 6-year old girl who suffered extensive flame burn injury involving a scalp defect of 1,5% total body surface area. After necrosectomy, full table damage of the skull was observed with a partially exposed dura mater. Neurosurgical consultation was necessary to accomplish a vital wound bed. Subsequently, in the absence of enough adequate tissue available for flap surgery reconstruction, reconstruction was performed by using a bilayer Integra Dermal Regeneration Template (IDRT) resulting in a lasting and stable coverage of the defect. This is the first case-report describing application of IDRT on a full-thickness scalp and skull defect with exposed dura mater in a child. Our results are encouraging and demonstrate that Integra can be used in a child to successfully cover exposed dura when no viable skull remains.


A Pvs25 mRNA vaccine induces complete and durable transmission-blocking immunity to Plasmodium vivax.
Plasmodium vivax (P. vivax) is the major malaria parasite outside of Africa and no vaccine is available against it. A vaccine that interrupts parasite transmission (transmission-blocking vaccine, TBV) is considered highly desirable to reduce the spread of P. vivax and to accelerate its elimination. However, the development of a TBV against this pathogen has been hampered by the inability to culture the parasite as well as the low immunogenicity of the vaccines developed to date. Pvs25 is the most advanced TBV antigen candidate for P. vivax. However, in previous phase I clinical trials, TBV vaccines based on Pvs25 yielded low antibody responses or had unacceptable safety profiles. As the nucleoside-modified mRNA-lipid nanoparticle (mRNA-LNP) vaccine platform proved to be safe and effective in humans, we generated and tested mRNA-LNP vaccines encoding several versions of Pvs25 in mice. We found that in a prime-boost vaccination schedule, all Pvs25 mRNA-LNP vaccines elicited robust antigen-specific antibody responses. Furthermore, when compared with a Pvs25 recombinant protein vaccine formulated with Montanide ISA-51 adjuvant, the full-length Pvs25 mRNA-LNP vaccine induced a stronger and longer-lasting functional immunity. Seven months after the second vaccination, vaccine-induced antibodies retained the ability to fully block P. vivax transmission in direct membrane feeding assays, whereas the blocking activity induced by the protein/ISA-51 vaccine dropped significantly. Taken together, we report on mRNA vaccines targeting P. vivax and demonstrate that Pvs25 mRNA-LNP outperformed an adjuvanted Pvs25 protein vaccine suggesting that it is a promising candidate for further testing in non-human primates.


Can paternal environmental experiences affect the breast cancer risk in offspring? A systematic review.
Studies in recent years have shown that parental environmental experiences can affect their offspring's risk of breast cancer (BC). We assessed the effect of different paternal factors on BC risk in offspring by reviewing the existing literature. This systematic review followed the Joanna Briggs Institute's (JBI) method for systematic reviews of qualitative evidence. The primary keywords were searched in reliable databases such as PubMed, Google Scholar, Elsevier, SID, and Wiley in English until 31 December 2021. Two authors independently examined the articles in terms of inclusion criteria and quality assessment of the articles. Of the 438 studies, 19 met the inclusion criteria of this systematic review and were included in the study. Paternal factors investigated in these studies included age at delivery, diet, occupational exposures, occupation type and education. The reported relationships between these factors and breast cancer varied among different studies. Studies considered in this article show that fathers' age at the time of delivery of the child, dietary habits, overweight and occupational factors can affect the incidence of BC risk in the next generation.


Beyond the dichotomy: How ride-hailing competes with and complements public transport.
Since ride-hailing has become an important travel alternative in many cities worldwide, a fervent debate is underway on whether it competes with or complements public transport services. We use Uber trip data in six cities in the United States and Europe to identify the most attractive public transport alternative for each ride. We then address the following questions: (i) How does ride-hailing travel time and cost compare to the fastest public transport alternative? (ii) What proportion of ride-hailing trips do not have a viable public transport alternative? (iii) How does ride-hailing change overall service accessibility? (iv) What is the relation between demand share and relative competition between the two alternatives? Our findings suggest that the dichotomy-competing with or complementing-is false. Though the vast majority of ride-hailing trips have a viable public transport alternative, between 20% and 40% of them have no viable public transport alternative. The increased service accessibility attributed to the inclusion of ride-hailing is greater in our US cities than in their European counterparts. Demand split is directly related to the relative competitiveness of travel times i.e. when public transport travel times are competitive ride-hailing demand share is low and vice-versa.


[Epidermal stem cells and ex vivo cutaneous gene therapy: application to xeroderma pigmentosum].
Ex vivo cutaneous gene therapy is an alternative treatment for recessively inherited diseases with cutaneous traits. It relies on the transfer in cultured epidermal keratinocytes of the wild-type allele of the gene whose mutation is responsible for the disease. As for severely burnt patients, epithelial sheets developed from genetically corrected cells may then be grafted back to the patients. Long term correction and graft take depend on the genetic correction of stem cells. Success of such an approach has recently been reported in the case of one patient suffering from a severe case of junctional epidermolysis bullosae. Here we report a method for safely selecting keratinocytes populations after genetic manipulation. The method is non invasive and non immunogenic and allows high enrichment of genetically manipulated stem keratinocytes. This could perhaps contribute to ex vivo gene therapy approaches of cancer prone genodermatoses such as xeroderma pigmentosum.


Novelties in the early management of acute heart failure syndromes.
The recent European Society of Cardiology (ESC) guidelines delineate the diagnosis and management of distinct categories of acute heart failure syndromes. However, physicians dealing with these patients may need guidance in choosing therapeutic alternatives as soon as the dyspneic patient arrives at the emergency department, until distinct categories of the ESC guidelines are identified. Hence, this manuscript summarizes practical recommendations for the very early management of patients with acute heart failure syndromes. The recommendations are based on a clinical classification system considering the initial systolic blood pressure and other symptoms. Early initiation of diagnostic and goal-directed treatment strategies are key factors in improving patient outcomes. Early and frequent reassessment is also imperative so that adjustments to the initial therapeutic approach can be made, as clinically indicated.


The Structure, Measurement Invariance, and External Validity of the Barratt Impulsiveness Scale-Brief in a Sample of At-Risk Adolescents.
The purpose of this study was to evaluate the factor structure and measurement invariance of the Barratt Impulsiveness Scale-Brief version (BIS-Brief) in an archival sample of 315 adolescents (81% male; 63.5% Caucasian; Mage = 16.7 years) participating in a military-style residential program for at-risk youths. Additionally, correlations between BIS scores and external measures of impulsivity-related behaviors were examined. Results showed support for a previously described two-dimensional structure for the BIS-Brief, which was invariant across racial groups. Additionally, the BIS-Brief performed similarly to the total BIS-11 score in relation to external measures of impulsivity-related behaviors. However, the two dimensions exhibited some significant differences in their associations with other measures. This study supports the utility of the BIS-Brief as a brief measure of impulsivity and suggests that the dimensions of the BIS-Brief may be useful in distinguishing how different aspects of impulsivity relate to problem behaviors such as binge drinking and self-injury.


Optimal population-specific HLA imputation with dimension reduction.
Human genomics has quickly evolved, powering genome-wide association studies (GWASs). SNP-based GWASs cannot capture the intense polymorphism of HLA genes, highly associated with disease susceptibility. There are methods to statistically impute HLA genotypes from SNP-genotypes data, but lack of diversity in reference panels hinders their performance. We evaluated the accuracy of the 1000 Genomes data as a reference panel for imputing HLA from admixed individuals of African and European ancestries, focusing on (a) the full dataset, (b) 10 replications from 6 populations, and (c) 19 conditions for the custom reference panels. The full dataset outperformed smaller models, with a good F1-score of 0.66 for HLA-B. However, custom models outperformed the multiethnic or population models of similar size (F1-scores up to 0.53, against up to 0.42). We demonstrated the importance of using genetically specific models for imputing populations, which are currently underrepresented in public datasets, opening the door to HLA imputation for every genetic population.


Stop the dicing in hematopoiesis: what have we learned?
MicroRNAs (miRNAs) belong to an abundant class of highly conserved small (22nt) non-coding RNAs. MiRNA profiling studies indicate that their expression is highly cell type-dependent. DICER1 is an essential RNase III endoribonuclease for miRNA processing. Hematopoietic cell type- and developmental stage-specific Dicer1 deletion models show that miRNAs are essential regulators of cellular survival, differentiation and function. For instance, miRNA deficiency in hematopoietic stem cells and progenitors of different origins results in decreased cell survival, dramatic developmental aberrations or dysfunctions in mice. We recently found that homozygous Dicer1 deletion in myeloid-committed progenitors results in an aberrant expression of stem cell genes and induces a regained self-renewal capacity. Moreover, Dicer1 deletion causes a block in macrophage development and myeloid dysplasia, a cellular condition that may be considered as a preleukemic state. However, Dicer1-null cells do not develop leukemia in mice, indicating that depletion of miRNAs is not enough for tumorigenesis. Surprisingly, we found that heterozygous Dicer1 deletion in myeloid-committed progenitors, but not Dicer1 knockout, collaborates with p53 deletion in leukemic progression and results in various types of leukemia. Our data indicate that Dicer1 is a haploinsufficient tumorsuppressor in hematopoietic neoplasms, which is consistent with the observed downregulation of miRNA expression in human leukemia samples. Here, we review the various hematopoietic specific Dicer1 deletion mouse models and the phenotypes observed within the different hematopoietic lineages and cell developmental stages. Finally, we discuss the role for DICER1 in mouse and human malignant hematopoiesis.


The effects of carbon dioxide and temperature on microRNA expression in Arabidopsis development.
Elevated levels of CO2 and temperature can both affect plant growth and development, but the signalling pathways regulating these processes are still obscure. MicroRNAs function to silence gene expression, and environmental stresses can alter their expressions. Here we identify, using the small RNA-sequencing method, microRNAs that change significantly in expression by either doubling the atmospheric CO2 concentration or by increasing temperature 3-6 °C. Notably, nearly all CO2-influenced microRNAs are affected inversely by elevated temperature. Using the RNA-sequencing method, we determine strongly correlated expression changes between miR156/157 and miR172, and their target transcription factors under elevated CO2 concentration. Similar correlations are also found for microRNAs acting in auxin-signalling, stress responses and potential cell wall carbohydrate synthesis. Our results demonstrate that both CO2 and temperature alter microRNA expression to affect Arabidopsis growth and development, and miR156/157- and miR172-regulated transcriptional network might underlie the onset of early flowering induced by increasing CO2.


The Effects Aerobic Fitness has on Heart Rate Responses for a Custody Assistant Recruit Class Performing a Formation Run.
This study measured the heart rate (HR) responses to a formation run (group run completed along a set route) performed by higher fitness (HF), moderate fitness (MF), or lower fitness (LF) custody assistant (CA) recruits. Retrospective data from 26 recruits (12 males, 14 females) were analyzed. Prior to academy training, a YMCA step test was administered. Recruits were divided into three groups based on recovery HR: top 25% were HF; bottom 25% were LF; the rest were MF. Recruit HR was measured during a formation run completed at an ~11-minute mile · pace-1. HR zones were defined as: very light (< 57% of age-predicted maximum heart rate [HRmax]); light (57%-63% HRmax); moderate (64%-76% HRmax); vigorous (77%-95% HRmax); and very vigorous (> 95% HRmax). A one-way ANOVA, with Bonferroni post hoc, calculated between-group differences in time spent and percentage of total time in the HR zones during the run; effect sizes (d) were also calculated. HF recruits spent a significantly longer time and percentage of total time in the very light HR zone compared to the LF group (p ≤ 0.039; d = 1.20-1.35). There were no other significant between-group differences (p = 0.070-0.980). HF CA recruits spent more time in the very light training zone compared to the other groups (d = 0.92-1.35), which may not be optimal for aerobic adaptations. LF recruits spent more time in the vigorous-to-very vigorous HR zones (~45 minutes; 70% of the run). These recruits may potentially be working above their current capacity. Formation runs may not be the most efficient aerobic conditioning method for all CA recruits.


The cost-effectiveness of immediate treatment, percutaneous biopsy and active surveillance for the diagnosis of the small solid renal mass: evidence from a Markov model.
The most effective diagnostic strategy for the very small, incidentally detected solid renal mass is uncertain. We assessed the cost-effectiveness of adding percutaneous biopsy or active surveillance to the diagnosis of a 2 cm or less solid renal mass. A Markov state transition model was developed to observe a hypothetical cohort of healthy 60-year-old men with an incidentally detected, 2 or less cm solid renal mass, comparing percutaneous biopsy, immediate treatment and active surveillance. The primary outcomes assessed were the incremental cost-effectiveness ratio measured by cost per life-year gained at a willingness to pay threshold of $50,000. Model results were assessed by sensitivity analysis. Immediate treatment was the highest cost, most effective diagnostic strategy, providing the longest overall survival of 18.53 life-years. Active surveillance was the lowest cost, least effective diagnostic strategy. On cost-effectiveness analysis using a societal willingness to pay threshold of $50,000 active surveillance was the preferred choice at a $75,000 willingness to pay threshold while biopsy and treatment were acceptable ($56,644 and $70,149 per life-year, respectively). When analysis was adjusted for quality of life, biopsy dominated immediate treatment as the most cost-effective diagnostic strategy at $33,840 per quality adjusted life-year gained. Percutaneous biopsy may have a greater role in optimizing the diagnosis of an incidentally detected, 2 cm or less solid renal mass.


A unique example of structural and magnetic diversity in four interconvertible copper(II)-azide complexes with the same schiff base ligand: a monomer, a dimer, a chain, and a layer.
Four new Cu(II)-azido complexes of formula [CuL(N(3))] (1), [CuL(N(3))](2) (2), [Cu(7)L(2)(N(3))(12)](n) (3), and [Cu(2)L(dmen)(N(3))(3)](n) (4) (dmen = N,N-dimethylethylenediamine) have been synthesized using the same tridentate Schiff base ligand HL (2-[1-(2-dimethylaminoethylimino)ethyl]phenol, the condensation product of dmen and 2-hydroxyacetophenone). The four compounds have been characterized by X-ray structural analyses and variable-temperature magnetic susceptibility measurements. Complex 1 is mononuclear, whereas 2 is a single mu-1,1 azido-bridged dinuclear compound. The polymeric compound 3 possesses a 2D structure in which the Cu(II) ions are linked by phenoxo oxygen atoms and two different azide bridges (mu-1,1 and mu-1,1,3). The structure of complex 4 is a double helix in which two mu-1,3-azido-bridged alternating one-dimensional helical chains of CuL(N(3)) and Cu(dmen)(N(3))(2) are joined together by weak mu-1,1 azido bridges and H-bonds. The complexes interconvert in solution and can be obtained in pure form by carefully controlling the conditions. The magnetic properties of compounds 1 and 2 show the presence of very weak antiferromagnetic exchange interactions mediated by a ligand pi overlap (J = -1.77) and by an asymmetric 1,1-N(3) bridge (J = -1.97 cm(-1)), respectively. Compound 3 presents, from the magnetic point of view, a decorated chain structure with both ferro- and antiferromagnetic interactions. Compound 4 is an alternating helicoidal chain with two weak antiferromagnetic exchange interactions (J = -1.35 and -2.64 cm(-1)).


[Intramedullary cavernous angioma of the spinal cord: case report].
We report a case of intramedullary cavernous angioma in a 56 years old woman with history of back pain. MRI show discal protrusion and disclose an intramedullary lesion, with heterogeneous sinal. The MRI is more sensitive than CT and the most appropriate technique is the sequence eco-gradient. The diagnosis is relevant because there is a possibility of acute neurological deficit and it is frequently accompanied by cranial cavernous angiomas.


Assessment of the experiences and coping strategies of people working in the informal sector in their quest to access health care services: the case of Dar es Salaam, Tanzania.
Addressing inequities in health care provision and financing has been at the center stage of Health Sector Reform (HSR) discussions since the early 1980s. The poor, women, and informal health sector workers in most developing countries are rarely covered by formal health insurance mechanisms that are meant to ensure access to essential health services. They are also sidelined in formal banking and credit systems due to their being predominantly low income earners, with little resources to meet eligibility criteria for borrowing and also to be considered creditworthy. In light of this fact, the present paper analyzes both quantitative and qualitative data in an attempt to explore and discuss the experiences and coping strategies of women and men employed in the informal sector economy in their daily attempts to access health care services. The paper employs Malaria as a tracer disease and gender as a unit of analysis. Analysis indicated the significance, as perceived by interviewees, of both informal credit networks and formal insurance and banking systems as important shock-absorbers for vulnerable populations in their struggle to access basic health services in times of need. The paper further highlights and discusses diverse coping strategies that households employ in dealing with illness-related costs and a greater willingness to be integrated into both formal and informal financial mechanisms. The paper finally concludes that the government must take the following steps: 1) enhance existing formal and communitybased initiatives to make them sustainable, 2) devise ways to reduce the lack of flexibility in membership requirements for insurance schemes/financial institutions, and 3) reduce perverse incentives inherent in the health system that may prevent people from seeking membership in available insurance mechanisms. In addition, deliberate steps must be taken by the government to employ 'targeted measures' to ensure that health care access is improved and sustained particularly for vulnerable populations.


[Destruction of the aortic allo- and xenovalves of the heart depending on their position and time of transplantation].
The aortic valve, as well as the other valves of the heart, has a cellular structure. Collagenous fibres form the skeleton of the cellular structures, and the plexus of thinner fibres--the "walls". At early periods following the implantation destruction of thin fibres distributed along the periphery of the alveolus takes place. In the course of prolonged functioning of the allo- and xenovalves in a mitral position the large collagenous fibres collapse, defibration thereof develops and slits-vacuums and "cysts" are formed. In the valves which functioned for a long time in the tricuspid position no considerable destructive changes in the connective-tissue carcass take place.


Intragenic mutations of CDKN2B and CDKN2A in primary human esophageal cancers.
The CDKN2A and CDKN2B genes, encoding p16 and p15 respectively, are located on chromosome 9p21, a locus at which frequent homozygous and heterozygous deletions occur in many primary human tumors, including esophageal carcinoma. CDKN2A and CDKN2B inhibit cyclin dependent kinase 4 (CDK4) and CDK6 and control cellular proliferation by preventing entry into the S phase of the cell cycle. Their inactivation may contribute to uncontrolled growth in human cancer. We previously described CDKN2A exon 2 mutations in a pilot study of 43 esophageal cancers. In order to determine whether CDKN2A and CDKN2B are frequent targets of 9p21 deletion in esophageal carcinogenesis, we have now analyzed 60 primary esophageal cancers for mutations in both exons 1 and 2 of CDKN2A and CDKN2B by direct sequencing of PCR amplified genomic DNAs. In conjunction with our previously published data, we have identified a total of eight nucleic acid substitutions among 60 esophageal carcinomas; here, we describe one new CDKN2B nonsense mutation and one new silent CDKN2B mutation that occurred somatically. Taken together, these results suggest that intragenic mutations in CDKN2A and CDKN2B occur in esophageal cancer, but that they are infrequent events. In view of the known high frequency of loss of heterozygosity at the chromosome 9p21 locus in esophageal cancers, the current data suggest that intragenic mutation is not the predominant mode of inactivation of CDKN2A and CDKN2B or that other genes are targets of deletion at this locus in these cancers.


Molecular evidence for the occurrence of Contracaecum rudolphii A (Nematoda: Anisakidae) in shag Phalacrocorax aristotelis (Linnaeus) (Aves: Phalacrocoracidae) from Sardinia (western Mediterranean Sea).
Specimens of Contracaecum rudolphii Hartwich, 1964 (Nematoda: Anisakidae) from Phalacrocorax aristotelis (Linnaeus) from the Archipelago of La Maddalena (Sardinia, western Mediterranean Sea) were characterised genetically and compared with C. rudolphii A sensu D'Amelio et al. 1990 and C. rudolphii B sensu D'Amelio et al. 1990 from Phalacrocorax carbo sinensis (Blumenbach) from north-eastern Italy, and with C. rudolphii C sensu D'Amelio et al. 2007 from Phalacrocorax auritus (Lesson) from west-central Florida, USA. The sequencing of the small subunit of the mitochondrial ribosomal RNA gene (rrnS) and by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis of the same gene and of the internal transcribed spacers (ITS) of nuclear ribosomal DNA (rDNA) allowed the identification of all specimens of C. rudolphii from P. aristotelis as C. rudolphii A. The results confirmed that the definition of genetic markers, following the analysis of nuclear ribosomal and mitochondrial DNA, provides quick and practical diagnostic tools for the detection of the 3 sibling species of C. rudolphii. The occurrence of C. rudolphii in P. aristotelis is reported for the first time from the Mediterranean area, improving the picture of the dispersal patterns of the populations of these piscivorous birds, and confirming the existence of different and isolated populations between the North and South European waters.


The pattern of mobile phone use and prevalence of self-reported symptoms in elementary and junior high school students in shiraz, iran.
The use of mobile phone by children is increasing drastically. Children are likely to accumulate many years of exposure during their lives. Furthermore, as nervous systems in children are developing, children may be at a greater risk compared to adults. In this light, some scientists have suggested that the use of mobile phones should be restricted in high-risk groups such as children. This study is an attempt to explore the pattern of mobile phone use and its health effects among students from the city of Shiraz, Iran. A total of 469 (235 males and 234 females; 250 elementary and 219 junior high school) healthy students participated in this study. The students were randomly selected from three different educational districts of the city. For each student, a questionnaire regarding the possible sources of exposure to electromagnetic fields or microwave radiation, specially the pattern of mobile phone use, medical history and life style was filled out by interviewers. Only 31.42% of the students used to use mobile phones. The average daily time of using mobile phones in talk mode was 7.08±21.42 minutes. Not only the relative frequency of mobile phone ownership in boys was significantly more than the girls, but also the boys used their mobile phones more frequently. Statistically significant associations were found between the time mobile phones were used in talk mode and some symptoms. Furthermore, a statistically significant association was found between the time mobile phones were used in talk mode and the number of headaches per month, number of vertigo per month, or number of sleeping problem per month. RESULTS obtained in this study show that a large proportion of children in the city of Shiraz use mobile phones. A significant increase was found in some self-reported symptoms among users of mobile phones. These findings are in line with what is widely believed regarding the higher vulnerability of children to exhibit symptoms from using mobile phones. The findings and conclusion of the present study should be viewed in the light the nature of symptoms measurement (self-report) and the knowledge and understandings of the participants about the symptoms.


Changes in polysialic acid expression on myeloid cells during differentiation and recruitment to sites of inflammation: role in phagocytosis.
Polysialic acid (polySia) is a unique linear homopolymer of α2,8-linked sialic acid that has been studied extensively as a posttranslational modification of neural cell adhesion molecule in the central nervous system. Only two proteins are known to be polysialylated in cells of the immune system: CD56 on human natural killer cells and murine bone marrow (BM) leukocytes, and neuropilin-2 (NRP-2) on dendritic cells (DCs). We tested the hypothesis that polySia expression is regulated during maturation and migration of leukocytes and plays a role in functional activity. Using wild-type and NCAM(-/-) mice, we show that BM neutrophils express only polysialylated CD56, whereas a subset of BM monocytes expresses polysialylated CD56 and/or another polysialylated protein(s). We demonstrate that polysialylated CD56 expression is progressively down-regulated in wild-type monocytes and monocyte-derived cells during migration from BM through peripheral blood to pulmonary and peritoneal sites of inflammation. Freshly isolated monocyte-derived peritoneal macrophages are devoid of polySia yet re-express polySia on NRP-2 and an additional protein(s) after maintenance in culture. Removal of polySia from these cells enhances phagocytosis of Klebsiella pneumoniae, suggesting that down-regulation of polySia on macrophages facilitates bacterial clearance. Using wild-type and NRP-2(-/-) mice, we demonstrate that NRP-2 and an additional protein(s) are polysialylated by ST8 SiaIV in BM-derived DCs. We conclude that polySia expression in monocyte-derived cells is dynamically regulated by ST8 SiaIV activity and by expression of carrier proteins during recruitment to sites of inflammation and influences cellular interactions with microbes, contributing to innate and adaptive immune responses.


Medicago truncatula mtpt4 mutants reveal a role for nitrogen in the regulation of arbuscule degeneration in arbuscular mycorrhizal symbiosis.
Plants acquire essential mineral nutrients such as phosphorus (P) and nitrogen (N) directly from the soil, but the majority of the vascular plants also gain access to these mineral nutrients through endosymbiotic associations with arbuscular mycorrhizal (AM) fungi. In AM symbiosis, the fungi deliver P and N to the root through branched hyphae called arbuscules. Previously we identified MtPT4, a Medicago truncatula phosphate transporter located in the periarbuscular membrane that is essential for symbiotic phosphate transport and for maintenance of the symbiosis. In mtpt4 mutants arbuscule degeneration occurs prematurely and symbiosis fails. Here, we show that premature arbuscule degeneration occurs in mtpt4 mutants even when the fungus has access to carbon from a nurse plant. Thus, carbon limitation is unlikely to be the primary cause of fungal death. Surprisingly, premature arbuscule degeneration is suppressed if mtpt4 mutants are deprived of nitrogen. In mtpt4 mutants with a low N status, arbuscule lifespan does not differ from that of the wild type, colonization of the mtpt4 root system occurs as in the wild type and the fungus completes its life cycle. Sulphur is another essential macronutrient delivered to the plant by the AM fungus; however, suppression of premature arbuscule degeneration does not occur in sulphur-deprived mtpt4 plants. The mtpt4 arbuscule phenotype is strongly correlated with shoot N levels. Analyses of an mtpt4-2 sunn-1 double mutant indicates that SUNN, required for N-mediated autoregulation of nodulation, is not involved. Together, the data reveal an unexpected role for N in the regulation of arbuscule lifespan in AM symbiosis.


Genome-Wide Meta-analysis Identifies Risk Loci and Improves Disease Prediction of Age-Related Macular Degeneration.
To identify age-related macular degeneration (AMD) risk loci and to establish a polygenic prediction model. Genome-wide association study (GWAS) and polygenic risk score (PRS) construction. We included 64 885 European patients with AMD and 568 740 control participants (with overlapped samples) in the UK Biobank, Genetic Epidemiology Research on Aging (GERA), International AMD Consortium, FinnGen, and published early AMD GWASs in meta-analyses, as well as 733 European patients with AMD and 20 487 control participants from the Canadian Longitudinal Study on Aging (CLSA) and non-Europeans from the UK Biobank and GERA for polygenic risk score validation. A multitrait meta-analysis of GWASs comprised 64 885 patients with AMD and 568 740 control participants; the multitrait approach accounted for sample overlap. We constructed a PRS for AMD based on both previously reported as well as unreported AMD loci. We applied the PRS to nonoverlapping data from the CLSA. We identified several single nucleotide polymorphisms associated with AMD and established a PRS for AMD risk prediction. We identified 63 AMD risk loci alongside the well-established AMD loci CFH and ARMS2, including 9 loci that were not reported in previous GWASs, some of which previously were linked to other eye diseases such as glaucoma (e.g., HIC1). We applied our PRS to nonoverlapping data from the CLSA. A new PRS was constructed using the PRS method, PRS-CS, and significantly improved the prediction accuracy of AMD risk compared with PRSs from previously published datasets. We further showed that even people who carry all the well-known AMD risk alleles at CFH and ARMS2 vary considerably in their AMD risk (ranging from close to 0 in individuals with low PRS to > 50% in individuals with high PRS). Although our PRS was derived in individuals of European ancestry, the PRS shows potential for predicting risk in people of East Asian, South Asian, and Latino ancestry. Our findings improve the knowledge of the genetic architecture of AMD and help achieve better accuracy in AMD prediction. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.


Characterization of glucosyltransferase expressed from a Streptococcus sobrinus gene cloned in Escherichia coli.
The gene encoding a glucosyltransferase which synthesized water-insoluble glucan, gtfI, previously cloned from Streptococcus sobrinus strain MFe28 (mutans serotype h) into a bacteriophage lambda vector, was subcloned into the plasmid pBR322. The recombinant plasmid was stable in Escherichia coli and gtfI was efficiently expressed. The GTF-I expressed in E. coli was compared to the corresponding enzymes in S. sobrinus strains MFe28 (serotype h), B13 (serotype d) and 6715 (serotype g) and shown to resemble them closely in molecular mass and isoelectric point. The insoluble glucan produced by GTF-I from recombinant E. coli consisted of 1,3-alpha-D-glycosyl residues (approximately 90%). An internal fragment of the gtfI gene was used as a probe in hybridization experiments to demonstrate the presence of homologous sequences in chromosomal DNA of other streptococci of the mutans group.


Mechanical stimulation of C2C12 cells increases m-calpain expression, focal adhesion plaque protein degradation.
Myogenesis is a complex sequence of events, including the irreversible transition from the proliferation-competent myoblast stage into fused, multinucleated myotubes. During embryonic development, myogenic differentiation is regulated by positive and negative signals from surrounding tissues. Stimulation due to stretch- or load-induced signaling is now beginning to be understood as a factor which affects gene sequences, protein synthesis and an increase in Ca2+ influx in myocytes. Evidence of the involvement of Ca2+ -dependent activity in myoblast fusion, cell membrane and cytoskeleton component reorganization due to the activity of the ubiquitous proteolytic enzymes, calpains, has been reported. Whether there is a link between stretch- or load-induced signaling and calpain expression and activation is not known. Using a magnetic bead stimulation assay and C2C12 mouse myoblasts cell population, we have demonstrated that mechanical stimulation via laminin receptors leads to an increase in m-calpain expression, but no increase in the expression of other calpain isoforms. Our study revealed that after a short period of stimulation, m-calpain relocates into focal adhesion complexes and is followed by a breakdown of specific focal adhesion proteins previously identified as substrates for this enzyme. We show that stimulation also leads to an increase in calpain activity in these cells. These data support the pivotal role for m-calpain in the control of muscle precursor cell differentiation and thus strengthen the idea of its implication during the initial events of muscle development.


Expression of ID4 protein in breast cancer cells induces reprogramming of tumour-associated macrophages.
As crucial regulators of the immune response against pathogens, macrophages have been extensively shown also to be important players in several diseases, including cancer. Specifically, breast cancer macrophages tightly control the angiogenic switch and progression to malignancy. ID4, a member of the ID (inhibitors of differentiation) family of proteins, is associated with a stem-like phenotype and poor prognosis in basal-like breast cancer. Moreover, ID4 favours angiogenesis by enhancing the expression of pro-angiogenic cytokines interleukin-8, CXCL1 and vascular endothelial growth factor. In the present study, we investigated whether ID4 protein exerts its pro-angiogenic function while also modulating the activity of tumour-associated macrophages in breast cancer. We performed IHC analysis of ID4 protein and macrophage marker CD68 in a triple-negative breast cancer series. Next, we used cell migration assays to evaluate the effect of ID4 expression modulation in breast cancer cells on the motility of co-cultured macrophages. The analysis of breast cancer gene expression data repositories allowed us to evaluate the ability of ID4 to predict survival in subsets of tumours showing high or low macrophage infiltration. By culturing macrophages in conditioned media obtained from breast cancer cells in which ID4 expression was modulated by overexpression or depletion, we identified changes in the expression of ID4-dependent angiogenesis-related transcripts and microRNAs (miRNAs, miRs) in macrophages by RT-qPCR. We determined that ID4 and macrophage marker CD68 protein expression were significantly associated in a series of triple-negative breast tumours. Interestingly, ID4 messenger RNA (mRNA) levels robustly predicted survival, specifically in the subset of tumours showing high macrophage infiltration. In vitro and in vivo migration assays demonstrated that expression of ID4 in breast cancer cells stimulates macrophage motility. At the molecular level, ID4 protein expression in breast cancer cells controls, through paracrine signalling, the activation of an angiogenic programme in macrophages. This programme includes both the increase of angiogenesis-related mRNAs and the decrease of members of the anti-angiogenic miR-15b/107 group. Intriguingly, these miRNAs control the expression of the cytokine granulin, whose enhanced expression in macrophages confers increased angiogenic potential. These results uncover a key role for ID4 in dictating the behaviour of tumour-associated macrophages in breast cancer.


Meaning in Life in Long-Term Recovery in First-Episode Psychosis: An Interpretative Phenomenological Analysis.
Background: Meaning in Life (MIL) is a central aspect of service user defined personal recovery in mental health. It is unclear whether current knowledge regarding MIL is applicable to the lives of those who have experienced psychosis. As it was not possible to locate any study examining service user perspectives on MIL in first-episode psychosis (FEP), conducting in-depth qualitative research in this area offers an opportunity to develop a conceptualisation of MIL that may be transferable to the broad psychosis spectrum. Aim: The aim of the study was to explore how people find, develop, and maintain MIL approximately 21 years after their FEP diagnosis. Materials and Methods: The study aim was addressed using Interpretative Phenomenological Analysis (IPA). Participants were members of an epidemiologically complete FEP incidence cohort in Ireland. Purposive maximum variation sampling enabled the recruitment of a sample balanced across remission status, age at time of FEP onset, and gender. Semi-structured interviews were conducted circa 21 years post FEP with 16 participants. Data analysis was guided by IPA procedures. Results: Participants experienced MIL as awareness of connectedness to context - the interrelated conditions they existed in (their relationships with the self, others, systems, the environment, and time). Awareness of connectedness to context occurred in five main ways: Being myself - de-othering and authenticity (Enacting identity); Becoming significant where the self is witnessed (Belonging in life); Generating meaning within and beyond systems (Independence); Shaping and being shaped by life (Agency and patiency); and Integrating different perspectives of time (Reconciling temporality). Conclusions: Findings offer the first in-depth understanding of how people diagnosed with a FEP experience MIL in mid-later life recovery. Current tripartite MIL theories do not fully represent the array of MIL perspectives articulated by our participants. MIL concepts developed are potential areas for intervention for mental health services seeking to implement the recovery approach. Findings can be used to foster optimism among service users and their supporters for MIL attainment in psychosis and offer guidance for education, clinical practice, policy, and future research.


Historical perspective of heavy metals contamination (Cd, Cr, Cu, Hg, Pb, Zn) in the Seine River basin (France) following a DPSIR approach (1950-2005).
The Driver-Pressures-State-Impact-Response approach is applied to heavy metals in the Seine River catchment (65,000 km(2); 14 million people of which 10 million are aggregated within Paris megacity; 30% of French industrial and agricultural production). The contamination pattern at river mouth is established on the particulate material at different time scales: 1930-2000 for floodplain cores, 1980-2003 for suspended particulate matter (SPM) and bed-sediments, 1994-2003 for atmospheric fallout and annual flood deposits. The Seine has been among the most contaminated catchments with maximum contents recorded at 130 mg kg(-1) for Cd, 24 for Hg, 558 for Pb, 1620 for Zn, 347 for Cu, 275 for Cr and 150 for Ni. Today, the average levels for Cd (1.8 mg kg(-1)), Hg (1.08), Pb (108), Zn (370), Cu (99), Cr (123) and Ni (31) are much lower but still in the upper 90% of the global scale distribution (Cr and Ni excepted) and well above the natural background values determined on pre-historical deposits. All metal contents have decreased at least since 1955/65, well before metal emission regulations that started in the mid 1970's and the metal monitoring in the catchment that started in the early 1980's. In the last 20 y, major criteria changes for the management of contaminated particulates (treated urban sludge, agricultural soils, dredged sediments) have occurred. In the mid 1990's, there was a complete shift in the contamination assessment scales, from sediment management and water usage criteria to the good ecological state, now required by the 2000 European Directive. When comparing excess metal outputs, associated to river SPM, to the average metal demand within the catchment from 1950 to 2000, the leakage ratios decrease exponentially from 1950 to 2000 for Cd, Cr, Cu, Pb and Zn, meanwhile, a general increase of the demand is observed: the rate of recycling and/or treatment of metals within the anthroposphere has been improved ten-fold. Hg environmental trajectory is very specific: there is a marked decontamination from 1970 to 2000, but the leakage ratio remains very high (10 to 20%) during this period. Drivers and Pressures are poorly known prior to 1985; State evolution since 1935 has been reconstructed from flood plain cores analysis; Impacts were maximum between 1950 and 1970 but remained unknown due to analytical limitation and lack of awareness. Some Responses are lagging 10 y behind monitoring and have much evolved in the past 10 y.


Chiral cyclohexane 1,3-diones as inhibitors of mutant SOD1-dependent protein aggregation for the treatment of ALS.
Cyclohexane 1,3-diones were identified as a class of molecules exhibiting a protective effect against mutant SOD1 induced toxicity in PC-12 cells, but an optimized analogue had little or no effect on life extension in the G93A SOD1 mouse model for amyotrophic lateral sclerosis (ALS). Additional testing showed that these compounds were inactive in neurons and further analogue synthesis was carried out to identify compounds with neuronal activity. Starting from two racemic derivatives that were active in cortical neurons, two potent analogues (1b and 2b) were resolved, which were protective against mutant SOD1 induced toxicity in PC-12 cells. Both compounds were found to be active in cortical neurons and presented good ADME profiles in vitro. On the basis of these results, an ALS mouse trial with 1b was carried out, which showed slightly greater life extension than the FDA-approved ALS drug riluzole, thereby validating cyclohexane 1,3-diones as a novel therapeutic class for the treatment of ALS.


Driving cessation and increased depressive symptoms.
To understand the consequences of driving cessation in older adults, the authors evaluated depression in former drivers compared with active drivers. Depression (as assessed using the Center for Epidemiological Studies Depression Scale), driving status, sociodemographic factors, health status, and cognitive function were evaluated for a cohort of 1953 residents of Sonoma County, California, aged 55 years and older, as part of a community-based study of aging and physical performance. The authors re-interviewed 1772 participants who were active drivers at baseline 3 years later. At baseline, former drivers reported higher levels of depression than did active drivers even after the authors controlled for age, sex, education, health, and marital status. In a longitudinal analysis, drivers who stopped driving during the 3-year interval (i.e., former drivers) reported higher levels of depressive symptoms than did those who remained active drivers, after the authors controlled for changes in health status and cognitive function. Increased depression for former drivers was substantially higher in men than in women. With increasing age, many older adults reduce and then stop driving. Increased depression may be among the consequences associated with driving reduction or cessation.


Quantitative and metabolic changes of hepatic collagens in rats after carbon tetrachloride poisoning.
1. The collagen hydroxyproline in rat liver was composed of 3.5% neutral-soluble collagen, 4.9% acid-soluble collagen and 91.6% insoluble collagen. In labelling studies with [(14)C]proline in vitro, the specific radioactivities of neutral-soluble, acid-soluble and insoluble collagens in rat liver were found to be 233000, 69000 and 830d.p.m./mumol of hydroxyproline respectively after 1h. 2. During subacute carbon tetrachloride poisoning the hepatic content of insoluble collagen markedly increased, whereas those of soluble collagens did not change. During recovery from subacute poisoning hepatic contents of soluble collagens were markedly decreased. 3. After 8 weeks of carbon tetrachloride poisoning the specific radioactivities of hepatic soluble collagens increased, while that of insoluble collagen decreased. During recovery from subacute poisoning, the specific radioactivities of soluble collagens decreased to the normal range and that of insoluble collagen further decreased. 4. Hepatic collagenolytic activity solubilizing insoluble collagen, which differs from mammalian collagenase, decreased under the conditions of the subacute poisoning and also during recovery from subacute poisoning.


The RAD6 protein of Saccharomyces cerevisiae polyubiquitinates histones, and its acidic domain mediates this activity.
The RAD6 gene of the yeast Saccharomyces cerevisiae is required for post-replication repair of UV-damaged DNA, DNA damage-induced mutagenesis, and sporulation. Here we demonstrate that the protein encoded by the RAD6 gene, previously shown to be a ubiquitin-conjugating (E2) enzyme, multiply ubiquitinates histones H2A and H2B efficiently to give products containing as many as seven or more molecules of ubiquitin. We also show that the highly acidic 23-residue RAD6 carboxy-terminal tail domain, which contains a total of 20 acidic residues, is essential for the histone-polyubiquitinating activity. Because the RAD6 polyacidic tail is required for the sporulation function but not for the DNA repair and induced mutagenesis functions of RAD6, the present observations suggest that the histone-polyubiquitinating activity of RAD6 protein is essential for sporulation but not for DNA repair and induced mutagenesis. Attachment of multiple molecules of ubiquitin to histones by RAD6 protein may serve to target the histones for degradation via the ubiquitin-dependent proteolytic system or to alter chromatin structure. The in vitro system for synthesizing polyubiquitinated histones described herein provides a means for investigating these possibilities.


Interplay between static and dynamic properties of semifluxons in YBa2Cu3O(7-delta) 0-pi Josephson junctions.
We have investigated the static and dynamic properties of long YBa2Cu3O(7-delta) 0-pi Josephson junctions and compared them with those of conventional 0 junctions. Scanning SQUID microscope imaging has revealed the presence of a semifluxon at the phase discontinuity point in 0-pi Josephson junctions. Zero field steps have been detected in the current-voltage characteristics of all junctions. Comparison with simulation allows us to attribute these steps to fluxons traveling in the junction for conventional 0 junctions and to fluxon-semifluxon interactions in the case of 0-pi Josephson junctions.


Prions: generation and spread versus neurotoxicity.
Neurodegenerative diseases are characterized by the aggregation of misfolded proteins in the brain. Among these disorders are the prion diseases, which are transmissible, and in which the misfolded proteins ("prions") are also the infectious agent. Increasingly, it appears that misfolded proteins in Alzheimer and Parkinson diseases and the tauopathies also propagate in a "prion-like" manner. However, the association between prion formation, spread, and neurotoxicity is not clear. Recently, we showed that in prion disease, protein misfolding leads to neurodegeneration through dysregulation of generic proteostatic mechanisms, specifically, the unfolded protein response. Genetic and pharmacological manipulation of the unfolded protein response was neuroprotective despite continuing prion replication, hence dissociating this from neurotoxicity. The data have clear implications for treatment across the spectrum of these disorders, targeting pathogenic processes downstream of protein misfolding.


Association of paternal factors with mothers' employment postchildbirth.
The demand on Japanese women to fulfill their dual roles as mothers and labor force participants leads to a subsequent reduction of their employment hours, switching of occupations, or quitting the labor force. This study aims to examine paternal factors associated with mothers' employment status 18 months after childbirth. We used data from the 2010 cohort of the Longitudinal Survey of Newborns conducted in Japan. We restricted our analysis to 10 712 mothers who had full-time employment 1 year before childbirth. A logistic regression analysis was conducted to assess paternal factors associated with mothers' employment after childbirth. One-third of the mothers with full-time employment before childbirth were not working full-time 18 months after delivery. We found that high childcare involvement (score 13-18) of fathers (OR, 1.20; 95% CI, 1.01-1.43) and fathers with part-time employment (OR, 1.59; 95% CI, 1.12-2.26) were associated with higher odds of mothers' full-time employment. Fathers' weekly work of ≥60 h (OR, 0.79; 95% CI, 0.71-0.88) and higher annual income decreased the odds ratios by over 20%. Fathers' work arrangements and involvement in childcare play a key role in helping mothers resume employment postchildbirth.


Ultrastructural features and prevalence of tubuloreticular structures in the ocular vasculature of patients with AIDS: a study of 23 cases.
Tubuloreticular structures (TRS) are subcellular inclusions that are most commonly found in endothelial cells and lymphocytes of patients with autoimmune or collagen vascular disorders. In AIDS, TRS have been described in various tissues throughout the body including the lung, kidney, liver, muscle, and skin. Ocular tissues from 23 patients with AIDS were examined by electron microscopy. These included 17 postmortem eyes in addition to three chorioretinal and three conjunctival biopsy specimens. The overall prevalence of TRS in the ocular and conjunctival endothelial cells was found to be 83% (19/23). This is the first documented study of the prevalence of these structures in the ocular structures of patients with AIDS. Given the high frequency of their occurrence in AIDS, it is recommended that the presence of TRS in ocular or conjunctival tissues be an indication for obtaining an HIV antibody titre. Additionally, a rheumatological examination for HIV seronegative patients is suggested.


Immunobiology of gestational trophoblastic diseases.
Gestational trophoblastic diseases (GTDs) comprise a group of interrelated diseases characterized by development after gestation, widespread metastases, and high curability with chemotherapy. The good prognosis of GTDs is considered partly a result of the host immune response to paternal antigens expressed on trophoblastic cells. In this study, we review current understanding of the immunobiology of GTDs. First of all, we describe the microenvironment between trophoblastic cells and subpopulation of immune cells. Second, immunogenetics, immune microenvironment around abnormal trophoblast, and mechanism of GTDs escaping from maternal immune system surveillance were also discussed. Third, we propose the possible immunotherapy for persistent GTDs, particularly the vaccine designed on human chorionic gonadotrophin, which is generally accepted as a tumor marker for GTDs diagnosis. Due to the low incidence of GTDs and high response to chemotherapy, there have been few literatures about immunobiologic characteristics of GTDs compared with the other gynecologic malignancies, such as ovarian cancer, but the immunologic behavior of GTDs should be explored for further understanding of the etiology of these diseases and to help designing immunotherapeutic strategies for persistent GTDs.