Suppressed carrier scattering in CdS-encapsulated PbS nanocrystal films.
One of the key challenges facing the realization of functional nanocrystal devices concerns the development of techniques for depositing colloidal nanocrystals into electrically coupled nanoparticle solids. This work compares several alternative strategies for the assembly of such films using an all-optical approach to the characterization of electron transport phenomena. By measuring excited carrier lifetimes in either ligand-linked or matrix-encapsulated PbS nanocrystal films containing a tunable fraction of insulating ZnS domains, we uniquely distinguish the dynamics of charge scattering on defects from other processes of exciton dissociation. The measured times are subsequently used to estimate the diffusion length and the carrier mobility for each film type within the hopping transport regime. It is demonstrated that nanocrystal films encapsulated into semiconductor matrices exhibit a lower probability of charge scattering than that of nanocrystal solids cross-linked with either 3-mercaptopropionic acid or 1,2-ethanedithiol molecular linkers. The suppression of carrier scattering in matrix-encapsulated nanocrystal films is attributed to a relatively low density of surface defects at nanocrystal/matrix interfaces.


Association between the quality of primary care, insurance coverage, and diabetes-related health outcomes in a cohort of older adults in China: results from the China Health and Retirement Longitudinal Study.
This study aims to identify the association between diabetes diagnosis, health outcomes, insurance scheme, and the quality of county-level primary care in a cohort of older Chinese adults. Data from the China Health and Retirement Longitudinal Study, a nationally-representative panel survey of people aged 45 and over in China. Among participants with valid diabetes-related and hypertension-related medical history and biomarkers (n=8207), participants with diabetes (n=1318) were identified using biomarkers and self-reported medical history. Individual models were run using complete case analysis. Among 1318 individuals with diabetes in 2011, 59.8% were unaware of their disease status. Diagnosis rates were significantly higher among participants with more generous public health insurance coverage (OR 3.58; 95% CI 2.15 to 5.98) and among those with other comorbidities such as dyslipidemia (OR 2.88; 95% CI 2.03 to 4.09). After adjusting for demographics, individuals with more generous public health insurance coverage did not have better glucose control at 4 years follow-up (OR 0.55; 95% CI 0.26 to 1.18) or fewer inpatient hospital admissions at 4 years (OR 1.29; 95% CI 0.72 to 2.33) and 7 years follow-up (OR 1.12; 95% CI 0.62 to 2.05). Individuals living in counties with better county-level primary care did not have better glucose control at 4 years follow-up (OR 0.69; 95% CI 0.01 to 33.36), although they did have fewer inpatient hospital admissions at 4 years follow-up (OR 0.03; 95% CI 0.00 to 0.95). Diabetes diagnosis was a significant independent predictor of both better glucose control at 4 years follow-up (OR 13.33; 95% CI 8.56 to 20.77) and increased inpatient hospital stays at 4 years (OR 1.72; 95% CI 1.20 to 2.47) and 7 years (OR 1.82; 95% CI 1.28 to 2.58) follow-up. These findings suggest that participants with diabetes are often diagnosed concurrently with other comorbid disease conditions or after diabetes-related complications have already developed, thus leading to worse health outcomes in subsequent years despite improvements in health associated with better primary care. These findings suggest the importance of strengthening primary care and insurance coverage among older adults to focus on diagnosing and treating diabetes early, in order to prevent avoidable health complications and promote healthy aging.


Overcoming measurement time variability in brain machine interface.
We introduce a subspace learning approach for multi-channel Local Field Potentials (LFP), and demonstrate its application in movement direction decoding for 8 directions movement. We show that the subspace learning method can effectively address the issue of signal instability across recording sessions by extracting recurrent features from the data. We present results for movement direction decoding, where we trained on two recording sessions, and evaluated decoding performance on a third session. We combine our method with a classifier based on Error-Correcting Output Codes (ECOC) and Common Spatial Patterns (CSP) and found improvement in Decoding Power (DP) from 76% to 88% for a subject known to have strong inter-session variability. Furthermore, we saw an increase from 86% to 90% DP with another subject which exhibited significantly less variability.


Moringa oleifera leaf flavonoids protect bovine mammary epithelial cells from hydrogen peroxide-induced oxidative stress in vitro.
Bovine mammary epithelial cells (BMECs) of high-producing dairy cows are subject to constant oxidative stress as a result of high metabolic rate and physiological adaptation to intensive farming. Moringa (Moringa oleifera) leaf has been proposed to have the antioxidant potential in scavenging free radicals due to the presence of flavonoids. In this study, we investigated the cytoprotective effects of moringa leaf flavonoids in alleviating oxidative stress in BMECs in vitro. Oxidative stress was established by exposing isolated BMECs to H2 O2 for 2 hr. Doses of moringa leaf flavonoids were evaluated by treating BMECs for 12 hr. The optimal concentrations of H2 O2 and moringa leaf flavonoids were 500 μmol/L and 1.0 mg/ml, respectively. The results showed that moringa leaf flavonoids increased the activities of superoxide dismutase, catalase, and glutathione peroxidase; and reduced malondialdehyde activity and intracellular accumulation of reactive oxygen species (ROS) in the H2 O2 -induced oxidative stress system. A Hoechst33258 staining assay revealed that moringa leaf flavonoids decreased the apoptosis rate in BMECs, while leaving membrane integrity and nucleolar morphology unchanged. We concluded that moringa leaf flavonoids have the antioxidant capacity to effectively reduce oxidative stress in BMECs.


Decoupling of female host plant preference and offspring performance in relative specialist and generalist butterflies.
The preference-performance hypothesis posits that the host plant range of plant-feeding insects is ultimately limited by larval costs associated with feeding on multiple resources, and that female egg-laying preferences evolve in response to these costs. The trade-off of either using few host plant species and being a strong competitor on them due to effective utilization or using a wide host plant range but being a poor competitor is further predicted to result in host plant specialization. This follows under the hypothesis that both females and offspring are ultimately favoured by utilizing only the most suitable host(s). We develop an experimental approach to identify such trade-offs, i.e. larval costs associated with being a host generalist, and apply a suite of experiments to two sympatric and syntopic populations of the closely related butterflies Pieris napi and Pieris rapae. These butterflies show variation in their level of host specialization, which allowed comparisons between more and less specialized species and between families within species. Our results show that, first, the link between female host preference and offspring performance was not significantly stronger in the specialist compared to the generalist species. Second, the offspring of the host plant specialist did not outperform the offspring of the generalist on the former's most preferred host plant species. Finally, the more generalized species, or families within species, did not show higher survival or consistently higher growth rates than the specialists on the less preferred plants. Thus, the preference and performance traits appear to evolve as largely separated units.


Proteomic landscape of the primary somatosensory cortex upon sensory deprivation.
Experience-dependent plasticity (EDP) powerfully shapes neural circuits by inducing long-lasting molecular changes in the brain. Molecular mechanisms of EDP have been traditionally studied by identifying single or small subsets of targets along the biochemical pathways that link synaptic receptors to nuclear processes. Recent technological advances in large-scale analysis of gene transcription and translation now allow systematic observation of thousands of molecules simultaneously. Here we employed label-free quantitative mass spectrometry to address experience-dependent changes in the proteome after sensory deprivation of the primary somatosensory cortex. Cortical column- and layer-specific tissue samples were collected from control animals, with all whiskers intact, and animals whose C-row whiskers were bilaterally plucked for 11-14 days. Thirty-three samples from cortical layers (L) 2/3 and L4 spanning across control, deprived, and first- and second-order spared columns yielded at least 10 000 peptides mapping to ∼5000 protein groups. Of these, 4676 were identified with high confidence, and >3000 were found in all samples. This comprehensive database provides a snapshot of the proteome after whisker deprivation, a protocol that has been widely used to unravel the synaptic, cellular, and network mechanisms of EDP. Complementing the recently made available transcriptome for identical experimental conditions (see the accompanying article by Kole et al.), the database can be used to (i) mine novel targets whose translation is modulated by sensory organ use, (ii) cross-validate experimental protocols from the same developmental time point, and (iii) statistically map the molecular pathways of cortical plasticity at a columnar and laminar resolution.


Personnel and participant experiences of a residential weight-loss program. A qualitative study.
Residential weight-loss programs aim to help persons with obesity lose weight and maintain a long-term healthy lifestyle. Knowledge is needed on the different actors' perceptions and experiences from such programs. The aim of this study was to describe how personnel argued for and perceived a residential weight-loss program, to investigate how the participants experienced the program, and to contrast these perspectives. This qualitative study took place in an 18-week residential weight-loss program. Exercise, diet, and personal development were the main components in the program. Data was collected through participant observation and individual and focus group interviews with participants and personnel. Program personnel characterized persons with obesity in specific terms, and these formed the basis of the educational aims, teaching principles, and content of the program. According to personnel, persons with obesity typically had problems acknowledging their own resources, lived unstructured lives, had a distorted relationship to food, experienced a range of social problems and featured a lack of personal insight. Program participants reported enthusiasm about their experiences of exercise and appreciated measures of success with the exercise program. They had, however, very different experiences regarding the usefulness and appropriateness of the parts of the program focused on social and personal development. Some felt that weight loss required an engagement with personal development while others viewed it as unnecessary and inappropriate. The reliance in personnel accounts on particular characteristics of persons with obesity as a rationale for the program might lead to stigmatizing and stereotyping. Program activities focused on social and personal development need to be better understood by participants if they are to be viewed as helpful. To achieve this personnel must carefully consider how these parts of the program are communicated and conducted.


Actin reorganization contributes to loss of cell adhesion in pemphigus vulgaris.
In the human autoimmune blistering skin disease pemphigus vulgaris autoantibodies (PV-IgG), which are mainly directed against keratinocyte cell adhesion molecules desmoglein (Dsg) 3 and Dsg1, cause keratinocyte cell dissociation (acantholysis). Recent studies reported that loss of keratinocyte cell adhesion was accompanied by profound alterations of the actin cytoskeleton. Nevertheless, the relevance of actin reorganization in this process is unclear at present. In this study, we provide evidence for an important role of actin reorganization in pemphigus pathogenesis. In parallel to loss of cell adhesion and fragmentation of Dsg3 staining along cell borders, PV-IgG treatment resulted in striking changes in actin cytoskeleton organization. Moreover, in experiments using fluorescence recovery after photobleaching (FRAP), PV-IgG were detected to interfere with actin dynamics. Therefore, we investigated whether pharmacological manipulation of actin polymerization modulates pathogenic effects of PV-IgG. Pharmacological stabilization of actin filaments via jasplakinolide significantly blocked cell dissociation and Dsg3 fragmentation, whereas cytochalasin D-induced actin depolymerization strongly enhanced pathogenic effects of PV-IgG. To substantiate these findings, we studied whether the protective effects of Rho GTPases, which are potent regulators of the actin cytoskeleton and were shown to be involved in pemphigus pathogenesis, were dependent on modulation of actin dynamics. Cytotoxic necrotizing factor-1 (CNF-1)-mediated activation of Rho-GTPases enhanced the cortical junction-associated actin belt and blunted PV-IgG-induced cell dissociation. However, when actin polymerization was blocked under these conditions via addition of latrunculin B, the protective effects of CNF-1 were abrogated. Taken together, these experiments indicate that reorganization of cortical actin filaments is a critical step in PV-IgG-induced keratinocyte dissociation.


Oral Pyogenic Granuloma: A Narrative Review.
Pyogenic granuloma (PG) is a benign vascular lesion found predominantly in the oral cavity. Characterized by rapid growth and propensity to bleed, PG presents diagnostic challenges due to its similarity and alarming proliferation. This narrative review synthesizes current knowledge on the epidemiology, etiopathogenesis, clinical manifestations, and management of oral PG, with emphasis on recent advances in diagnostic and therapeutic approaches. The epidemiology of the injury is meticulously analyzed, revealing a higher incidence in women and a wide range of ages of onset. It delves into the etiopathogenesis, highlighting the uncertainty surrounding the exact causal factors, although historical attributions suggest an infectious origin. It exhaustively analyzes the clinical and histopathological aspects of oral PG, offering information on its various presentations and the importance of an accurate diagnosis to guide effective treatment. It details treatment strategies, emphasizing the personalized approach based on individual patient characteristics. This comprehensive review consolidates current knowledge on oral PG, highlighting the need for further research to clarify its pathogenesis and optimize treatment protocols.


The waterpipe: time for action.
The waterpipe, known in many cultures under different shapes and names (e.g. hookah, shisha, narghile), is a centuries-old tobacco use method that is witnessing a world-wide surge in popularity. This popularity is most noticeable among youths, and is surpassing cigarette smoking among this group in some societies. Many factors may have contributed to the recent waterpipe spread, including the introduction of sweetened/flavored waterpipe tobacco (known as Maassel), its reduced-harm perception, the thriving café culture, mass media and the internet. The passage of smoke through water on its way to the smoker underlies much of the common misperception that waterpipe use is less harmful than cigarettes. The health/addictive profile of waterpipe compared to cigarettes is largely unresearched and is likely to be influenced by the properties of smoke, duration and frequency of use, type of tobacco used, volume of smoke inhaled and the contribution of charcoal. However, the accumulation of evidence about the harmful and addictive potential of waterpipe use is outpacing the public health response to this health risk. A timely public health and policy action is needed in order to curb the emerging waterpipe smoking epidemic.


An erroneous opinion on a cause of death in a forensic autopsy: a case report.
The quality of autopsies is always questioned in courts, especially in developing countries. Wrong decisions or misjudgments are undesirable in medicine, but they are very dangerous in forensic medicine. If a wrong opinion is given, either a culprit can be acquitted or an innocent person can be sentenced. Therefore, an expert opinion is always required before the announcement of a judgment. To highlight the problem of accuracy in determining the cause of death in forensic autopsy. A 19- year old young adult male (Mr E), who had a history of alcohol abuse, was brought to a hospital casualty department by police, on an allegation of theft. He was unconscious and died within two hours of arrival. A post-mortem report was requested by a private attorney for an expert opinion. A post-mortem examination was conducted and multiple superficial injuries were recorded on his body. Head injury was given as a cause of death. The author seeks to critically analyze the post-mortem findings in relation to the cause and manner of death. An erroneous opinion was reached regarding cause and manner of death in this autopsy report.


A comparative study of the effect of ultrasound and electrostimulation on wound healing in rats.
A comparative study has been carried out to investigate the effects of electrical stimulation and ultrasound on wound healing. Eighty-four female rats were divided into four groups depending on the treatment received. The first group was given electrical stimulation of 300 microA direct current, 30 minutes daily, starting with negative polarity and then changed after 3 days of treatment. Group 2 received sham electrostimulation treatment. The third group received 0.1 W/cm2 pulsed ultrasound using the moving applicator technique for 5 minutes a day. Group 4 received sham ultrasound treatment. A total of 7 days of treatment was given to all groups. Histopathologic and biochemical analyses on the fourth and seventh days and wound breaking strength on the twenty-fifth day were performed for all groups. By accelerating the inflammatory phase, electrical stimulation had progressed the proliferative phase of wound healing earlier than ultrasound had done. Both electrical stimulation and ultrasound have positive effects on proliferative phases, but electrical stimulation was superior to ultrasound at the maturation phase. There was no difference between the two experimental groups on the mast cell reduction effect. Although ultrasound treatment may seem to be efficient in terms of time, when the effects of electrical stimulation and ultrasound on wound healing with the methods employed in our study are considered, it is concluded that electrical stimulation is a means of treatment superior to ultrasound in wound healing.


Two distinct loci confer resistance to acycloguanosine in herpes simplex virus type 1.
Two distinct loci that confer resistance to acycloguanosine (acyclo-Guo) in herpes simplex virus types 1 have been identified. The first locus is the gene for the virus-specific thymidine kinase (TK). Mutations that decrease TK activity also render the virus resistant to acyclo-Guo, and the level of resistance corresponds to the decrease in TK activity. acyclo-Guo resistance due to defective TK expression is recessive to the wild-type phenotype, acyclo-Guo-sensitive (ACGs). We term this locus ACGr-TK. The second locus is defined by the properties of a mutant, PAAr5, which is resistant to acyclo-Guo and to phosphonoacetic acid (PAA) yet exhibits wild-type TK activity. The acyclo-Guo-resistant locus in PAAr5 is separable from ACGr-TK mutations by recombination. Moreover, PAAr5 and ACGr-TK mutants can complement each other, producing drug-sensitive gene products which result in growth inhibition in the presence of acyclo-Guo. The acyclo-Guo resistance conferred by PAAr5 behaves as though it were codominant with the wild-type phenotype. This second acyclo-Guo-resistance locus is closely linked to the mutation specifying resistance to PAA. Resistance to PAA is thought to result from mutations in the gene for viral DNA polymerase. Thus, the close linkage of the ACGr and PAAr loci suggest that resistance to both drugs is specified by a mutant DNA polymerase. We term this second locus ACGr-PAA.


For uninsured cancer patients, outpatient charges can be costly, putting treatments out of reach.
Reimbursement information for public and private payers has long been available. However, information about charges—the amounts that providers request before payments are negotiated—has been scarce, particularly for outpatient care. Using the new Medicare Provider Utilization and Payment Data Public Use File and other sources, we evaluated physician charges, reimbursements by Medicare and large private health plans, and expected patient cost sharing for outpatient oncology care. In 2012 the average Medicare reimbursement for chemotherapy was 39.6 percent of charges; for private insurance, the share was 55.7 percent. Uninsured patients faced potential prices for chemotherapy that were 2-43 times as much as the total Medicare-allowed amount and 2-5 times as much as the private insurance-allowed amount. Charges for outpatient chemotherapy and office visits were substantially higher than insurer-reimbursed amounts, which is consistent with previous evidence about hospital charges. The charges for outpatient services underscore the pressure that the current system places on the people who are least able to pay. Encouraging rational pricing for health care services will be an important step toward ensuring access to care for everyone.


Changes in suicide and non-suicidal self-injury ideation and the moderating role of specific emotions over the course of dialectical behavior therapy.
Dialectical behavior therapy (DBT) targets suicidal behavior and non-suicidal self-injury (NSSI) as well as urges/ideation to engage in these behaviors. However, it remains unclear which specific suicidal ideation (SI) and NSSI ideation domains (i.e., frequency, worst intensity, average intensity, perceived likelihood of future ideation, and duration of ideation), if any, are impacted, and whether specific emotions moderate these effects. 73 individuals with borderline personality disorder (BPD), enrolled in six months of DBT, completed interviews of suicide and NSSI ideation and self-report measures of specific emotions at baseline, mid-treatment, and post-treatment. Generalized estimation equations revealed that all domains of suicidal ideation decreased over the course of DBT, but for NSSI domains, only ideation intensity decreased. Higher levels of shame/guilt predicted less, and higher fear predicted more, reduction in SI and NSSI ideation frequency. Higher shame/guilt also predicted more reduction in worst SI intensity. Higher sadness predicted greater reductions in SI intensity and duration, but less reductions in the perceived likelihood of future NSSI ideation. These findings suggest that DBT effectively reduces several facets of SI, but more work is required to target NSSI ideation. Results also suggest that targeting shame/guilt may be important to reducing SI and NSSI ideation.


Optogenetic excitation of cholinergic inputs to hippocampus primes future contextual fear associations.
Learning about context is essential for appropriate behavioral strategies, but important contingencies may not arise during initial learning. A variant of contextual fear conditioning, context pre-exposure facilitation, allows us to directly test the relationship between novelty-induced acetylcholine release and later contextual associability. We demonstrate that optogenetically-enhanced acetylcholine during initial contextual exploration leads to stronger fear after subsequent pairing with shock, suggesting that novelty-induced acetylcholine release primes future contextual associations.


Seasonal origin of the thermal maxima at the Holocene and the last interglacial.
Proxy reconstructions from marine sediment cores indicate peak temperatures in the first half of the last and current interglacial periods (the thermal maxima of the Holocene epoch, 10,000 to 6,000 years ago, and the last interglacial period, 128,000 to 123,000 years ago) that arguably exceed modern warmth1-3. By contrast, climate models simulate monotonic warming throughout both periods4-7. This substantial model-data discrepancy undermines confidence in both proxy reconstructions and climate models, and inhibits a mechanistic understanding of recent climate change. Here we show that previous global reconstructions of temperature in the Holocene1-3 and the last interglacial period8 reflect the evolution of seasonal, rather than annual, temperatures and we develop a method of transforming them to mean annual temperatures. We further demonstrate that global mean annual sea surface temperatures have been steadily increasing since the start of the Holocene (about 12,000 years ago), first in response to retreating ice sheets (12 to 6.5 thousand years ago), and then as a result of rising greenhouse gas concentrations (0.25 ± 0.21 degrees Celsius over the past 6,500 years or so). However, mean annual temperatures during the last interglacial period were stable and warmer than estimates of temperatures during the Holocene, and we attribute this to the near-constant greenhouse gas levels and the reduced extent of ice sheets. We therefore argue that the climate of the Holocene differed from that of the last interglacial period in two ways: first, larger remnant glacial ice sheets acted to cool the early Holocene, and second, rising greenhouse gas levels in the late Holocene warmed the planet. Furthermore, our reconstructions demonstrate that the modern global temperature has exceeded annual levels over the past 12,000 years and probably approaches the warmth of the last interglacial period (128,000 to 115,000 years ago).


Self-organizing potential field network: a new optimization algorithm.
This paper presents a novel optimization algorithm called self-organizing potential field network (SOPFN). The SOPFN algorithm is derived from the idea of the vector potential field. In the proposed network, the neuron with the best weight is considered as the target with the attractive force, while the neuron with the worst weight is considered as the obstacle with the repulsive force. The competitive and cooperative behaviors of SOPFN provide a remarkable ability to escape from the local optimum. Simulations were performed, compared, and analyzed on eight benchmark functions. The results presented illustrate that the SOPFN algorithm achieves a significant performance improvement on multimodal problems compared with other evolutionary optimization algorithms.


Silent and apparent cerebral ischemia after percutaneous transfemoral aortic valve implantation: a diffusion-weighted magnetic resonance imaging study.
The risk of stroke after transfemoral aortic valve implantation (TAVI) due to dislodgement and subsequent embolization of debris from aortic arch atheroma or from the calcified valve itself ranges between 2% and 10%. The rate of clinically silent cerebral ischemia is unknown but may be even higher. Thirty-two patients who underwent TAVI with the use of a balloon-expandable (n=22) or self-expandable (n=10) stent valve prosthesis were included in this descriptive study and compared with a historical control group of 21 patients undergoing open surgical aortic valve replacement. Periprocedural apparent and silent cerebral ischemia was assessed by neurological testing and serial cerebral diffusion-weighted magnetic resonance imaging at baseline, at 3.4 (2.5 to 4.4) days after the procedure, and at 3 months. TAVI was successful in all patients. After the procedure, new foci of restricted diffusion on cerebral diffusion-weighted magnetic resonance imaging were found in 27 of 32 TAVI patients (84%) and were more frequent than after open surgery (10 of 21 patients [48%]; P=0.011). These lesions were usually multiple (1 to 19 per patient) and dispersed in both hemispheres in a pattern suggesting cerebral embolization. Volumes of these lesions were significantly smaller after TAVI than after surgery (77 [59 to 94] versus 224 [111 to 338] mm(3); P<0.001). There were neither measurable impairments of neurocognitive function nor apparent neurological events during the in-hospital period among TAVI patients, but there was 1 stroke (5%) in the surgical patient group. On 3-month follow-up diffusion-weighted magnetic resonance imaging, there were no new foci of restricted diffusion, and there was no residual signal change associated with the majority (80%) of the foci detected in the periprocedural period. Clinically silent new foci of restricted diffusion on cerebral magnetic resonance imaging were detected in almost all patients (84%) undergoing TAVI. Although typically multiple, these foci were not associated with apparent neurological events or measurable deterioration of neurocognitive function during 3-month follow-up. Further work needs to be directed to determine the clinical significance of these findings in a larger patient population.


Ultraviolet photometer observations of the saturnian system.
Several interesting cloud and atmospheric features of the Saturn system have been observed by the long-wavelength channel of the two-channel ultraviolet photometer aboard the Pioneer Saturn spacecraft. Reported are observations of the most obvious features, including a Titan-associated cloud, a ring cloud, and the variation of atmospheric emission across Saturn's disk. The long-wavelength data for Titan suggest that a cloud of atomic hydrogen extends at least 5 Saturn radii along its orbit and about 1.5 Saturn radii vertically. A ring cloud, thought to be atomic hydrogen, has also been observed by the long-wavelength channel of the photometer; it shows significant enhancement in the vicinity of the B ring. Finally, spatially resolved observations of Saturn's disk show significant latitudinal variation. Possible explanations of the variation include aurora or limb brightening.


[Expression of human tissue plasminogen activator by recombinant cell lines from various animals].
A number of recombinant cell lines which produce human tissue plasminogen activator (tPA) was obtained using different hosts--mouse, rat, hamster, simian and human cell lines. All types of recombinant lines secreted active r-tPA into conditioned medium. A slight difference between molecular weights of secreted variants of r-tPA was mediated by the different mechanisms of protein modification. Treatment of some recombinant cell lines with different substances resulted in increased levels of r-tPA production.


Ontogenic development of drug-metabolizing enzymes in male chicken liver.
The ontogenic study of the hepatic biotransformation enzymes revealed the early development of both oxidative and conjugative enzymes in male chickens ranging in age from 3 to 12 weeks. Although the rate of microsomal cytochrome P450 reactions progressively increased during the first 9 weeks, it decreased thereafter. Furthermore, the proteins revealed by the antibodies to anti-cytochrome P450 1A2, 2B4, 2C7, and 3A4 appeared to be constitutively expressed. Hepatic monooxygenases were characterized by different developmental patterns. The demethylase activities increased progressively up to 9 weeks, then they declined, in 12 weeks reaching the activity level observed in 3-week-old chickens. In contrast, alkoxyresorufin O-dealkylases and benzopyrene hydroxylase activities continued to increase with age. Significant variability was noted for aniline hydroxylase. Among conjugation enzymes, UDP-glucuronyltransferase towards p-nitrophenol and isoniazid N-acetyltransferase activities increased with the age of the fowl, but with different profiles. Concerning glutathione S-transferase accepting 1-chloro-2,4-dinitrobenzene or 1,2-dichloro-4-nitrobenzene, the chickens aged from 3 to 9 weeks were less well developed in this enzyme than 12-week-old ones.


Prediction of hospital readmission for heart failure: development of a simple risk score based on administrative data
OBJECTIVES: The purpose of this study was to develop a convenient and inexpensive method for identifying and individual's risk for hospital readmission for congestive heart failure (CHF) using information derived exclusively from administrative data sources and available at the time of an index hospital discharge. BACKGROUND: Rates of readmission are higher after hospitalization for CHF. The significant determinants of rehospitalization are debated. METHODS: Administrative information on all 1995 hospital discharges in New York State which were assigned International Classification of Diseases--9--Clinical Modification codes indicative of CHF in the principal diagnosis position were obtained. The following were compared among hospital survivors who did and did not experience readmission: demographics, comorbid illness, hospital type and location, processes of care, length of stay and hospital charges. RESULTS: A total of 42,731 black or white patients were identified. The subgroup of 9,112 (21.3%) who were readmitted were distinguished by a greater proportion of blacks, a higher prevalence of Medicare and Medicaid insurance, more comorbid illnesses and the use of telemetry monitoring during their index hospitalization. Patients treated at rural hospitals, those discharged to skilled nursing facilities and those having echocardiograms or cardiac catheterization were less likely to be readmitted. Using multiple regression methods, a simple methodology was devised that segregated patients into low, intermediate and high risk for readmission. CONCLUSIONS: Patient characteristics, hospital features, processes of care and clinical outcomes may be used to estimate the risk of hospital readmission for CHF. However, some of the variation in rehospitalization risk remains unexplained and may be the result of discretionary behavior by physicians and patients.


Spatial interactions between subsurface bacterial colonies in a model system: a territory model describing the inhibition of Listeria monocytogenes by a nisin-producing lactic acid bacterium.
The effect of spatial separation on interactions between subsurface bacterial colonies was tested using a model system: the inhibition of Listeria monocytogenes by nisin-producing and nisin-non-producing Lactococcus lactis subsp. lactis. Separation distance was controlled by altering the number of inoculum organisms within the agar. Mean separation distance was calculated by determining the mean volume available to each cell at the start of the experiment. Inhibition was assessed by comparing the growth of L. monocytogenes in pure culture with its growth in the presence of Lac. lactis subsp. lactis. Increasing the distance between colonies resulted in an exponential decrease in inhibition. When L. monocytogenes and Lac. lactis subsp. lactis colonies were within 100 microns of each other, the increase in cell numbers per L. monocytogenes colony was only 0.6 c.f.u. (which indicated some cells had become non-viable). This was a log reduction of 3.5 compared to the pure culture control. A separation distance of 1000 microns resulted in a L. monocytogenes colony growth increment of 2.5 x 10(2) c.f.u. per colony, a log reduction of 3.0 compared to the control. Increasing the separation distance to 3000 microns resulted in a L. monocytogenes colony growth increment of 1.3 x 10(6) c.f.u. per colony, a log reduction of 0.9 compared to the control. The effects of nisin and acidity were investigated by using a nisin-non-producing strain of Lac. lactis subsp. lactis and by buffering the medium. Data were obtained for the effect of separation on inhibition, as well as competition between colonies of the same species. The inhibition was mathematically described in terms of a simplified 'territory' model of immobilized bacterial growth. There was a strong qualitative agreement between the mathematical model and the experimental data. It was concluded that the phenomenon of propinquity is of important consideration when modeling and predicting microbial growth within solid food systems.


[The state of children in the early period after adenectomy].
Sixty-three children, aged 3 to 12, were examined after adenotomy made with general anesthesia. The parameters of central hemodynamics and of cardiointervalography describing the state of the vegetative nervous system as well as the postoperative clinical course were analyzed in children after adenotomy. A high sympathoadrenal activity with a trend to reduction was noted in children immediately after adenotomy. The psycho-emotional state and the postoperative pain severity got back to the normal values within 1 postoperative hour.


Satisfaction of 30 402 callers to a medical helpline of the Emergency Medical Services Copenhagen: a retrospective cohort study.
To keep healthcare systems sustainable for future demands, many countries are developing a centralised telephone line for out-of-hours primary care services. To increase the quality of such services, more information is needed on factors that influence caller satisfaction. The aim of this study was to identify demographic and call-related characteristics that are associated with the patient satisfaction of callers to a medical helpline in Denmark. Retrospective cohort study on patient registry data and questionnaire results. Non-emergency medical helpline in the Capital Region of Denmark. A random sample of 30 402 callers to the medical helpline between May 2016 and May 2018. Responses of a satisfaction questionnaire were linked to demographic and call-related dispatch data. Associations between the characteristics were analysed with multivariable logistic regression analysis with satisfaction as the dependent variable. A subgroup analysis was performed on callers for children aged between 0 and 4 years. Of the 30 402 analysed callers, 73.0% were satisfied with the medical helpline. Satisfaction was associated with calling for a somatic injury (OR: 1.96, 95% CI: 1.72 to 2.23), receiving a face-to-face consultation (OR: 2.27, 95% CI: 2.04 to 2.50) and a waiting time less than 10 min (OR: 1.82, 95% CI: 1.56 to 2.08). Callers for a 0-year to 4-year-old patient were more likely to be satisfied when they called for a somatic illness or received a telephone consultation, compared with the rest of the population (p<0.0001). Callers were in general satisfied with the medical helpline. Satisfaction was associated with reason for encounter, triage response and waiting time. People calling for 0-year to 4-year-old patients were, compared with the rest of the population, more frequently satisfied when they called for a somatic illness or received a telephone consultation.


Cell free Microcystis aeruginosa spent medium affects Daphnia magna survival and stress response.
Primary consumers in freshwater ecosystems, such as the zooplankton organism Daphnia magna, are highly affected by cyanobacteria, both as they may use it as a food source but also by cyanobacterial metabolites present in the water. Here, we investigate the impacts of cyanobacterial metabolites focussing on the environmental realistic scenario of the naturally released mixture without crushing cyanobacterial cells or their uptake as food. Therefore, D. magna were exposed to two concentrations of cell free cyanobacterial spent medium from Microcystis aeruginosa PCC 7806 to represent higher and lower ecologically-relevant concentrations of cyanobacterial metabolites. Including microcystin-LR, 11 metabolites have been detected of which 5 were quantified. Hypothesising concentration and time dependent negative impact, survival, gene expression marking digestion and metabolism, oxidative stress response, cell cycle and molting as well as activities of detoxification and antioxidant enzymes were followed for 7 days. D. magna suffered from oxidative stress as both catalase and glutathione S-transferase enzyme activities significantly decreased, suggesting enzyme exhaustibility after 3 and 7 days. Moreover, gene-expressions of the 4 stress markers (glutathione S-transferase, glutathione peroxidase, catalase and thioredoxin) were merely downregulated after 7 days of exposure. Energy allocation (expression of glyceraldehyde-3-phosphate dehydrogenase) was increased after 3 days but decreased as well after 7 days exposure. Cell cycle was impacted time dependently but differently by the two concentrations, along with an increasing downregulation of myosin heavy chain responsible for cell arrangement and muscular movements. Deregulation of nuclear hormone receptor genes indicate that D. magna hormonal steering including molting seemed impaired despite no detection of microviridin J in the extracts. As a consequence of all those responses and presumably of more than investigated molecular and physiological changes, D. magna survival was impaired over time, in a concentration dependent manner. Our results confirm that besides microcystin-LR, other secondary metabolites contribute to negative impact on D. magna survival and stress response.


Effective treatment for mental disorders in children and adolescents.
As pressure increases for the demonstration of effective treatment for children with mental disorders, it is essential that the field has an understanding of the evidence base. To address this aim, the authors searched the published literature for effective interventions for children and adolescents and organized this review as follows: (1) prevention; (2) traditional forms of treatment, namely outpatient therapy, partial hospitalization, inpatient treatment, and psychopharmacology; (3) intensive comprehensive community-based interventions including case management, home-based treatment, therapeutic foster care, and therapeutic group homes; (4) crisis and support services; and (5) treatment for two prevalent disorders, major depressive disorder and attention-deficit hyperactivity disorder. Strong evidence was found for the treatment of attention-deficit hyperactivity disorder, depression, anxiety, and disruptive behavior disorders. Guidance from the field relevant to moving the evidence-based interventions into real-world clinical practice and further strengthening the research base will also need to address change in policy and clinical training.


Dried blood spots collected on filter paper: an international resource for the diagnosis and genetic characterization of human immunodeficiency virus type-1.
The collection of dried blood spots (DBS) on filter paper provides a powerful approach for the development of large-scale, population-based screening programs. DBS methods are particularly valuable in developing countries and isolated rural regions where resources are limited. Large numbers of field specimens can be economically collected and shipped to centralized reference laboratories for genetic and (or) serological analysis. Alternatively, the dried blood can be stored and used as an archival resource to rapidly establish the frequency and distribution of newly recognized mutations, confirm patient identity or track the origins and emergence of newly identified pathogens. In this report, we describe how PCR-based technologies are beginning to interface with international screening programmes for the diagnosis and genetic characterization of human immunodeficiency virus type 1 (HIV-1). In particular, we review recent progress using DBS specimens to resolve the HIV-1 infection status of neonates, monitor the genetic evolution of HIV-1 during early infancy and establish a sentinel surveillance system for the systematic monitoring of HIV-1 genetic variation in Asia.


Cerium(IV) ammonium nitrate mediated 5-endo-dig cyclization of α-amino allenylphosphonates to spirodienones.
α-Amino allenylphosphonates were treated with cerium(iv) ammonium nitrate under various conditions to form spirodienones in good to excellent yields. The 5-endo-dig cyclization proceeds through the formation of a key iminium intermediate. A comprehensive study on the nature of the solvent used for this reaction was undertaken resulting in the formation of three types of spirodienone scaffolds.


First experience of high-intensity focused ultrasound combined with transcatheter arterial embolization as local control for hepatoblastoma.
The purpose of this study was to assess the effectiveness of high-intensity focused ultrasound (HIFU) combined with transarterial chemoembolization (TACE) in treating pediatric hepatoblastoma. Twelve patients with initially unresectable hepatoblastoma were enrolled in the study. All patients received chemotherapy, TACE, and HIFU ablation. Follow-up materials were obtained in all patients. The tumor response, survival rate, and complications were analyzed. Complete ablation was achieved in 10 patients (83.3%), and the alpha-fetoprotein level was also decreased to normal in these patients. The mean follow-up time was 13.3 ± 1.8 months (range, 2-25 months). At the end of follow-up, two patients died from tumor progression, the other 10 patients were alive. One patient was found to have lung metastasis after HIFU and had an operation to remove the lesion. The median survival time was 14 months, and the 1- and 2-year survival rates were 91.7% and 83.3%, respectively. Complications included fever, transient impairment of hepatic function, and mild malformation of ribs. HIFU combined with TACE is a safe and promising method with a low rate of severe complications. As a noninvasive approach, it may provide a novel local therapy for patients with unresectable hepatoblastoma.


The effects of competition and implicit power motive on men's testosterone, emotion recognition, and aggression.
A contribution to a special issue on Hormones and Human Competition. We investigated the effects of competition on men's testosterone levels and assessed whether androgen reactivity was associated with subsequent emotion recognition and reactive and proactive aggression. We also explored whether personalized power (p Power) moderated these relationships. In Study 1, 84 males competed on a number tracing task and interpreted emotions from facial expressions. In Study 2, 72 males competed on the same task and were assessed on proactive and reactive aggression. In both studies, contrary to the biosocial model of status (Mazur, 1985), winners' testosterone levels decreased significantly while losers' levels increased, albeit not significantly. Personalized power moderated the effect of competition outcome on testosterone change in both studies. Using the aggregate sample, we found that the effect of decreased testosterone levels among winners (compared to losers) was significant for individuals low in p Power but not for those with medium or high p Power. Testosterone change was positively related to emotion recognition, but unrelated to either aggression subtype. The testosterone-mediated relationship between winning and losing and emotion recognition was moderated by p Power. In addition, p Power moderated the direct (i.e., non-testosterone mediated) path between competition outcome and emotion recognition and both types of aggression: high p-Power winners were more accurate at deciphering others' emotions than high p-Power losers. Finally, among high p-Power men, winners aggressed more proactively than losers, whereas losers aggressed more reactively than winners. Collectively, these studies highlight the importance of implicit power motivation in modulating hormonal, cognitive, and behavioral outcomes arising from human competition.


Lack of correlation between arterial and venous beta-adrenergic receptor sensitivity.
The regulation of vascular beta-adrenoceptor responses in humans has been studied in vivo in both arteries and veins. Because venous responses can be studied less invasively than arterial responses, they are an attractive substitute for the measurement of arterial responses, provided that venous responses are representative of responses in resistance arteries. However, although venous, particularly hand vein response, has been extensively studied, arterial and venous beta-adrenergic sensitivities, in the same individuals, have not been compared. Measures of venous and arterial beta-adrenergic sensitivities were compared in 10 healthy normotensive subjects. Forearm blood flow, after administration of increasing doses of isoproterenol into the brachial artery, was measured by strain-gauge plethysmography and was used for determination of arterial beta-adrenoceptor sensitivity, expressed as the IP500 (the dose of isoproterenol resulting in a fivefold [500%] increase in baseline forearm blood flow). Venous sensitivity to isoproterenol, expressed as the IP15 (the dose of isoproterenol resulting in 15% venodilation), was measured in a dorsal hand vein using the linear variable differential transformer. Administration of isoproterenol into the hand vein and brachial artery resulted in venodilation and increased forearm blood flow, respectively. However, there was no correlation between the measures of venous (log IP15) and arterial (log IP500) measures of vascular beta-adrenergic sensitivity (r = -.12, P = .74). We conclude that since arterial and venous sensitivities to isoproterenol in healthy white men did not correlate, venous and arterial beta-adrenergic responses are regulated differently and that studies examining vascular beta-adrenoceptor sensitivity would most appropriately be performed in a vessel representative of the vascular bed of interest.


The Nell-1 growth factor stimulates bone formation by purified human perivascular cells.
The search for novel sources of stem cells other than bone marrow mesenchymal stem cells (MSCs) for bone regeneration and repair has been a critical endeavor. We previously established an effective protocol to homogeneously purify human pericytes from multiple fetal and adult tissues, including adipose, bone marrow, skeletal muscle, and pancreas, and identified pericytes as a primitive origin of human MSCs. In the present study, we further characterized the osteogenic potential of purified human pericytes combined with a novel osteoinductive growth factor, Nell-1. Purified pericytes grown on either standard culture ware or human cancellous bone chip (hCBC) scaffolds exhibited robust osteogenic differentiation in vitro. Using a nude mouse muscle pouch model, pericytes formed significant new bone in vivo as compared to scaffold alone (hCBC). Moreover, Nell-1 significantly increased pericyte osteogenic differentiation, both in vitro and in vivo. Interestingly, Nell-1 significantly induced pericyte proliferation and was observed to have pro-angiogenic effects, both in vitro and in vivo. These studies suggest that pericytes are a potential new cell source for future efforts in skeletal regenerative medicine, and that Nell-1 is a candidate growth factor able to induce pericyte osteogenic differentiation.


[Use of system of radiation and hygienic certification of territories for ensuring supervision of radiation safety of the population at the regional level].
In article the experience of Department of Federal Service for Supervision of Consumer Rights Protection and Human Welfare in St. Petersburg, related with performing of radiation and hygienic certification of the organizations and territories is considered. The annual assessment of individual and collective risks of emergence of stochastic effects for the population and the personnel of radiation objects shows the significance of radiation and hygienic certification for hygienic justification of the measures directed on a decrease in radiation exposure of the population from technogenic, natural and medical sources of ionizing radiation. The long-term analysis of the structure and dynamics of annual individual and collective effective doses of radiation of the population within the framework of radiation and hygienic certification and the Universal state system for control and accounting for individual doses of radiation of citizens allows to estimate efficiency of address target programs for the solution of actual problems of radiation safety at the regional level.


Frontiers of Deep-Red Emission of Mn4+ Ions with Ruddlesden-Popper Perovskites.
It is well-known that the chemical composition of the host material significantly affects the spectroscopic performance of transition metal ions. However, it is worth noting that also the structure and symmetry of crystallographic sites play significant roles in transition metal ion luminescence. In this study, we demonstrate three perovskite structures of strontium titanate forming so-called Ruddlesden-Popper phases doped with Mn4+ ions. The observed reduction in the average Ti4+-O2- distance in the series SrTiO3-Sr2TiO4-Sr3Ti2O7 allowed for a record-breaking shift in the spectral position of Mn4+ emission band with a maximum of around 734 nm and led to an improvement of the already impressive thermometric performance of SrTiO3:Mn4+ in ratiometric and lifetime-based approaches. This research encourages a further search for structures that, with the help of the developed correlations between structural and optical properties, could lead to the discovery of phosphors beyond the limits established so far.


Evolutionary origin of cAMP-based chemoattraction in the social amoebae.
Phenotypic novelties can arise if integrated developmental pathways are expressed at new developmental stages and then recruited to serve new functions. We analyze the origin of a novel developmental trait of Dictyostelid amoebae: the evolution of cAMP as a developmental chemoattractant. We show that cAMP's role of attracting starving amoebae arose through recruitment of a pathway that originally evolved to coordinate fruiting body morphogenesis. Orthologues of the high-affinity cAMP receptor (cAR), cAR1, were identified in a selection of species that span the Dictyostelid phylogeny. The cAR1 orthologue from the basal species Dictyostelium minutum restored aggregation and development when expressed in an aggregation-defective mutant of the derived species Dictyostelium discoideum that lacks high-affinity cARs, thus demonstrating that the D. minutum cAR is a fully functional cAR. cAR1 orthologues from basal species are expressed during fruiting body formation, and only this process, and not aggregation, was disrupted by abrogation of cAR1 function. This is in contrast to derived species, where cAR1 is also expressed during aggregation and critically regulates this process. Our data show that coordination of fruiting body formation is the ancestral function of extracellular cAMP signaling, whereas its derived role in aggregation evolved by recruitment of a preexisting pathway to an earlier stage of development. This most likely occurred by addition of distal cis-regulatory regions to existing cAMP signaling genes.


Decontamination Strategies Used for AFB Culture Significantly Reduce the Viability of Mycobacterium abscessus Complex in Sputum Samples from Patients with Cystic Fibrosis.
Nontuberculous mycobacteria are important respiratory pathogens in patients with cystic fibrosis (CF). For diagnosis, international guidelines recommend culture of sputum that has been decontaminated via chemical treatment. Fifty-six sputum samples from 32 patients known to be previously colonized or infected with NTM were subdivided, and the aliquots were subjected to six different decontamination strategies, followed by quantitative culture for NTM. Thirty sputum samples contained Mycobacterium abscessus complex (MABSC) and 11 contained Mycobacterium avium complex (MAC). Decontamination strategies included treatment with N-acetyl L-cysteine with 2% sodium hydroxide (NALC-NaOH), 4% NaOH, 1% chlorhexidine, 0.5 N sulfuric acid, 5% oxalic acid, double decontamination with NALC-NaOH, followed by 5% oxalic acid, and saline (0.85%) as a control. The samples were also cultured directly with no treatment. Treatment with NALC-NaOH resulted in an average reduction in colony count of 87% for MABSC when compared with direct culture. NaOH at 4% caused a 98.3% average reduction in colony count. All treatments that included NaOH resulted in colony counts that were statistically lower than those obtained from direct culture or the saline-treated control (p < 0.05). Standard treatments using sulfuric or oxalic acids were less deleterious, but still resulted in an average reduction in colony count of at least 30%. The viability of MAC was much less affected by most decontamination treatments. In conclusion, the viability of MABSC was severely compromised by standard decontamination regimens. This supports recent evidence showing that optimal recovery of MABSC is achieved by culture on an appropriate selective agar without decontamination of sputum samples.


Sequential high-intensity focused ultrasound treatment combined with chemotherapy for inoperable pancreatic cancer: a retrospective analysis for prognostic factors and survival outcomes.
To evaluate the effect of HIFU (High-Intensity Focused Ultrasound) therapy on the survival and prognosis of patients with inoperable pancreatic cancer, and the clinical application of serological prognostic indicators. We retrospectively analyzed the clinicopathological features, laboratory tests and follow-ups of 192 patients. Among the patients, 57 were treated with HIFU prior to chemotherapy (HIFU-priority), and 135 patients received chemotherapy followed by HIFU (HIFU-second). Univariate and multivariate Cox regression analysis was used to determine the prognostic value of tumor inflammation-related serological markers. A nomogram model was established based on the identified prognostic factors. Univariate analysis showed that receiving the treatment regimen in HIFU-priority was a significant protective factor for overall survival (OS, p < 0.001). Tumor stage, high C-reactive protein (CRP), high gamma-glutamyl transferase(γGT) high carbohydrate antigen 125 (CA125), high neutrophil-to-lymphocyte ratio (NLR), high lymphocyte-to-monocyte ratio (LMR) and liver metastasis were significant risk factors for poor prognosis (p < 0.05). CRP combined with normal tumor marker CA125 (CRP + CA125) was associated with longer OS (p = 0.005). Multivariate analysis shows that HIFU-priority is a protective factor for OS (Hazard Ratio, HR: 0.38; 95% confidence interval(CI): 0.25-0.57), tumor stage (HR: 1.61; 95% CI: 1.12-2.31), CRP + CA125 (HR: 1.46; 95% CI: 1.02-2.08) and γGT (HR: 1.44; 95% CI: 1.04-1.98) are risk factors for OS and serve as independent prognostic factors in the nomogram. Early application of HIFU treatment improves the OS of patients with inoperable pancreatic cancer. CRP + CA125 and γGT are independent prognostic factors.


Expression of OVCA1, a candidate tumor suppressor, is reduced in tumors and inhibits growth of ovarian cancer cells.
Loss of all or part of one copy of chromosome 17p is very common in ovarian and breast tumors. OVCA1 is a candidate tumor suppressor gene mapping to a highly conserved region on chromosome 17p13.3 that shows frequent loss of heterozygosity in breast and ovarian carcinomas. Western blot analysis of extracts prepared from breast and ovarian carcinomas revealed reduced expression of OVCA1 compared with extracts from normal epithelial cells from these tissues. Subcellular localization studies indicate that OVCA1 is localized to punctate bodies scattered throughout the cell but is primarily clustered around the nucleus. Attempts to create cell lines that stably expressed OVCA1 from the cytomegalovirus promoter were generally unsuccessful in a variety of different cell lines. This reduction of colony formation was quantified in the ovarian cancer cell line A2780, where it was demonstrated that cells transfected with plasmids expressing OVCA1 had a 50-60% reduction in colony number as compared with appropriate controls, and only a few of these clones expressed OVCA1, albeit at low levels. The clones that expressed exogenous OVCA1 were found to have dramatically reduced rates of proliferation. Reduced growth rates correlated with an increased proportion of the cells in the G1 fraction of the cell cycle compared with the parental cell line and decreased levels of cyclin D1. The low levels of cyclin D1 appeared to be caused by an accelerated rate of cyclin D1 degradation. Overexpression of cyclin D1 was able to override OVCA1's suppression of clonal outgrowth. These results suggest that slight alterations in the level of OVCA1, such as would occur after reduction of chromosome 17p13.13 to hemizygosity, may result in cell cycle deregulation and promote tumorigenesis.


Bilateral Vocal Cord Immobility After Chemoradiotherapy For Nasopharyngeal Carcinoma.
Post chemoradiation vocal cord immobility is a rare complication and this maybe life threatening when patients present with severe aspiration and recurrent pneumonia or even worse if they have an upper airway obstruction. We report a case of nasopharyngeal carcinoma patient whom after receiving curative concurrent chemoradiotherapy, presented with episodes of shortness of breath and aspiration pneumonia finally diagnosed with bilateral vocal cord immobility. She had no evidence of tumour recurrence.


Social representations of female sex workers about their sexuality.
To know the social representations of female sex workers about their sexuality. Qualitative study based on the Theory of Social Representations. Thirty-nine women from a health region of Alto Sertão Produtivo Baiano - Brazil agreed to participate. For the production of empirical data, the techniques of Free Word Association and in-depth interviews were used. The answers were analyzed based on Constellation Target Content Analysis and Semantic Content Analysis. Two thematic categories emerged: "negative representation of sexuality"; "my pleasure is the money". Therefore, the theme sexuality and meanings derived from the social representations elaborated by the sex workers about sexuality, based on their experiences and daily life, showed that the work involved a negative representation of sexuality when associated with sexual satisfaction with the client, in addition to the allusion to sex as a source of income. The social representations about sexuality constructed by sex workers are linked to the feeling of denial of pleasure and obtaining money for subsistence. Reflecting on sexuality points out ways to rethink the care to be provided for a stigmatized and vulnerable group.


Six-year follow-up of untreated T1 carcinoma of prostate.
The management of T1 carcinoma of prostate remains controversial and the critical role of histopathology is often underestimated. A retrospective review was conducted on 27 cases of T1 prostate carcinoma diagnosed between 1980 and 1992, all of which were managed on a surveillance programme. Pathological material of 24 cases was available for re-examination by a single histopathologist without prior knowledge of the originally assigned grade. Gleason's scoring system was used in the current review. Twenty-two (81.5%) were T1a and 5 (18.5%) T1b. Mean duration of follow-up was 77.3 months (1.0 to 159.0) and median age was 72.0 years (61.0 to 84.0). Twenty-five (92.6%) were originally graded as well differentiated, 1 (3.7%) was moderately differentiated and 1 (3.7%) was poorly differentiated. Three of the well-differentiated tumours were upstaged because of tumour volume. On review, differences in grading were noted in 13 cases (54.2%) and 11 (45.8%) were, as a consequence, upstaged. Progression was recorded in 5 cases (18.5%). Mean disease-free interval was 47.6 months (7.0 to 75.0) and mean serum PSA at progression was 34.2 ug/l (2.3 to 62.5). Four responded to delayed therapy. Mortality was recorded in 13 cases (48.1%) but cancer-specific mortality was only 7.7% (1/13). Mean age at death was 78.1 years. The importance of accurate grading and staging cannot be overemphasized given its pivotal role in subsequent management. The impact of age is also apparent and surveillance appears a reasonable option for those with limited life expectancy after diagnosis.


Echinodorus macrophyllus: Acute toxicological evaluation of hydroxycinnamoyl derivatives from SF1 subfractions.
Echinodorus macrophyllus (Kunth.) Micheli (Alismataceae), known as chapéu-de-couro in Brazil, is popularly used to treat inflammatory diseases. We have previously demonstrated a significant reduction in the acute inflammation for the aqueous extract of E. macrophyllus (AEEm) and its ethanolic fraction (Fr20) and described that hydroxycinnamoyl derivatives present in SF1 (Fr20 subfraction) showed higher anti-inflammatory properties by mechanisms that include a reduction of TNF-α, IL-1β, CKCL1/KC, LTB4, and PGE2 levels in exudate. This work describes the acute toxicological effect of SF1 subfraction on SW mice treated orally for five days in the air pouch model by evaluating the hematological and biochemical determinations on the blood samples; the relative organ weight and its histopathological analysis; the liver genotoxicity assessment and the activity of liver enzymes from xenobiotic metabolism. Fr20 was earlier fractionated on the Sephadex LH-20 column, yielding mainly four subfractions, including SF1. The SF1 toxicity was evaluated in mice challenged with carrageenan on the air pouch inflammation model and orally treated for five days. The body weight was monitored daily, and the organs were weighed after the euthanasia. Hematological and biochemical determinations were carried out using specific commercial kits and following the protocols provided by the manufacturers. The organs were fixed, sectioned, processed for hematoxylin and eosin staining, and analyzed by light microscopy. Genotoxicity assessment was performed by the alkaline single-cell gel electrophoresis. Livers were processed for ethoxyresorufin-O-deethylase (EROD) and Glutathione S-transferase (GST) assays. SF1 exhibited low toxicity, as no significant discrepancy was observed in the relative weight of the body organs of mice. Moreover, the daily treatment with SF1 did not alter the number and percentage of red blood cells or hemoglobin concentration in the blood. The treatment with SF1 did not affect the creatinine concentration, but the 25 mg/kg dose reduced the plasma urea level and uric acid, suggesting its use in treating acute renal failure. The parameters analyzed did not present biochemical alterations indicative of liver disease. Regarding serum triglyceride and cholesterol levels, a significant decrease was detected in both parameters in mice treated with SF1. In addition, the histopathological analysis showed that inflammatory focus in the livers seemed more relevant in the control groups than in those treated. There were no significant changes in the renal or splenic tissues of animals treated with SF1. Treatment with SF1 also does not have a genotoxic effect on liver cells. Treatment with SF1 showed no toxicity in mice at doses equivalent to those recommended for humans, which provides evidence of the safety of the therapeutic use of this subfraction.


A national resident survey about the current state of venous education in vascular surgery training programs.
The objective of this study was to characterize U.S. vascular surgery trainees' perceptions, case numbers, and attitudes toward venous disease education, as well as their intent to incorporate it into future practice. These data will provide us with a current snapshot of postgraduate venous education from a resident's perspective. Institutional Review Board approval was obtained. A 13-question survey was created and distributed to all vascular surgery residents in the United States by SurveyMonkey. Formal electronic distribution remained deidentified as the surveys were e-mailed to residents from the Association of Program Directors in Vascular Surgery. Of 464 vascular surgery trainees queried, 104 (22%) responded to the survey. The majority of responders (80%) were between 25 and 34 years of age, 60% were male, and 72% were white; 91% reported that they were in an academic training program, and 57% were enrolled in an integrated vascular surgery residency program. Postgraduate years (PGYs) of training among respondents were well represented: PGY 1, 14%; PGY 2, 8%; PGY 3, 14%; PGY 4, 12%; PGY 5, 9%; PGY 6, 18%; and PGY 7, 25%. Vascular resident training experience with venous disease revealed the following: 63% performed <10 inferior vena cava stents, 64% performed <10 vein stripping/ligation procedures, and 50% performed <10 iliac stents; 92% of responders reported having performed <10 venous bypasses during their training. Experience with endothermal ablations was slightly better, with 74% of responders reporting having performed up to 20 cases. Case volumes for endothermal ablation, vein stripping/ligation, inferior vena cava stenting, and iliac stenting increased progressively by clinical training year among integrated vascular residents (P ≤ .02) but were relatively stable for classic 5 + 2 vascular fellows (P ≥ .67). Integrated residents reported having received more didactic venous education than the 5 + 2 vascular surgery fellows (P = .01). There were no differences in overall reported venous procedure volumes between groups (P ≥ .28). The majority of trainees (82%) acknowledged that treating venous disease is part of a standard vascular surgery practice, and many (75%) indicated a desire to have increased venous training. Despite this, 59% of responders reported plans to dedicate <25% of their future vascular surgery practice to venous disease. In this national survey-based study of vascular surgery trainees, we demonstrate a perceived weakness in venous disease case volumes and didactic education in residency. This training deficit is apparent in both integrated (0 + 5) and traditional (5 + 2) training pathways. Our data suggest that expansion of the venous disease curriculum with clear training standards is warranted and that trainees would welcome such a change.


Full left ventricle quantification via deep multitask relationships learning.
Cardiac left ventricle (LV) quantification is among the most clinically important tasks for identification and diagnosis of cardiac disease. However, it is still a task of great challenge due to the high variability of cardiac structure across subjects and the complexity of temporal dynamics of cardiac sequences. Full quantification, i.e., to simultaneously quantify all LV indices including two areas (cavity and myocardium), six regional wall thicknesses (RWT), three LV dimensions, and one phase (Diastole or Systole), is even more challenging since the ambiguous correlations existing among these indices may impinge upon the convergence and generalization of the learning procedure. In this paper, we propose a deep multitask relationship learning network (DMTRL) for full LV quantification. The proposed DMTRL first obtains expressive and robust cardiac representations with a deep convolution neural network (CNN); then models the temporal dynamics of cardiac sequences effectively with two parallel recurrent neural network (RNN) modules. After that, it estimates the three types of LV indices under a Bayesian framework that is capable of learning multitask relationships automatically, and estimates the cardiac phase with a softmax classifier. The CNN representation, RNN temporal modeling, Bayesian multitask relationship learning, and softmax classifier establish an effective and integrated network which can be learned in an end-to-end manner. The obtained task covariance matrix captures the correlations existing among these indices, therefore leads to accurate estimation of LV indices and cardiac phase. Experiments on MR sequences of 145 subjects show that DMTRL achieves high accurate prediction, with average mean absolute error of 180 mm2, 1.39 mm, 2.51 mm for areas, RWT, dimensions and error rate of 8.2% for the phase classification. This endows our method a great potential in comprehensive clinical assessment of global, regional and dynamic cardiac function.


[Considerations on malnutrition in Central America with special reference to Costa Rica].
This paper analyzes aspects relevant to the nutritional situation in Costa Rica and to a lesser extent the rest of Central America. The nutritional problems have been dealt in a realistic way trying to avoid magnification of the situation. The available data show that calorie-protein malnutrition, anemia and goiter are the problems that, in that order, should receive attention in public health planning. Deficient maternal education and infection of the child play a preponderant role in the etiology of calorie-protein malnutrition and anemia. Analyses presented here show the convenience to revise periodically the criteria used to characterize the nutritional status, in order to adequately plan health actions. Also, the necessity to carry out basic and applied research in the field is emphasized. The future of the nutritional situation is uncertain for the majority of the Central American countries. However, some demographic indicators reveal that nations such as Costa Rica probably will reach an adequate nutrition in a not too distant future.


Extensive experience of disease control with gefitinib and the role of prognostic markers.
Traditionally, the efficacy of an anticancer agent has been measured by response rate. With the development of biological molecular-targeted agents, which have a different mechanism of action from conventional agents, it may be appropriate to consider alternative criteria that reflect the positive effect of these biological agents on disease control, palliation, symptom improvement and quality of life. One such targeted agent is the orally active epidermal growth factor receptor tyrosine kinase inhibitor gefitinib ("Iressa", ZD1839). This article reviews the clinical experience of patients with advanced/metastatic non-small-cell lung cancer, who have received gefitinib as part of a clinical trial or through the "Iressa" Expanded Access Programme. Disease-control rates of approximately 50% were observed in some Expanded Access Programme series, comparable with results obtained from Phase II trials. Symptom improvement was also reported. Information that will help identify those patients most likely to respond to treatment will become increasingly important. Therefore, the possible role of prognostic markers and the relationship between epidermal growth factor receptor status and response to gefitinib has been investigated. No clear association between epidermal growth factor receptor expression and response was observed. Future studies of other biomarkers in the epidermal growth factor receptor pathway should help to identify which patients are likely to benefit most from gefitinib.


Comparison of Pain Tolerance between Opioid Dependent Patients on Methadone Maintenance Therapy (MMT) and Opioid Naive Individuals.
This study compared pain sensitivity among opioid dependent patients on methadone maintenance therapy (MMT) and opioid naive subjects. The three hundred participants comprised 152 opioid naive subjects and 148 opioid dependent patients. Opioid naive subjects had not taken any opioids including morphine and methadone to their best knowledge and were presumed so after two consecutive negative urine screenings for drugs. All opioid dependent patients were stabilized in treatment, defined as having been enrolled in the program for more than one month with no change of methadone dosage over the past one month. Excluded from the study were individuals with chronic or ongoing acute pain and individuals with a history of analgesics ingestion within 3 d before the cold pressor test (CPT). Pain tolerance to CPT was evaluated at 0 h, and at 2, 4, 8, 12, and 24 h post-methadone dose. Patients exhibited a significantly shorter mean pain tolerance time of 34.17 s (95% CI 24.86, 43.49) versus 61.36 (52.23, 70.48) [p < 0.001] compared with opioid naive subjects. Time-dependent mean pain tolerance was also significantly different when naive subjects were compared to patients (p = 0.016). This study revealed hyperalgesia amongst patients on MMT, as manifested by their quicker hand withdrawal. The complaints of pain in this population should not be underestimated and the pain should be evaluated seriously and managed aggressively.


A chitin-binding domain in a marine bacterial chitinase and other microbial chitinases: implications for the ecology and evolution of 1,4-beta-glycanases.
To examine the ecology and evolution of microbial chitinases, especially the chitin-binding domain, one of the chitinase genes (chiA) from the marine bacterium Vibrio harveyi was analysed. The deduced amino acid sequence of ChiA is not very similar overall to other proteins, except for two regions, the putative catalytic and chitin-binding domains. Among all bacterial chitinases sequenced to date, there is no relationship between percentage similarity of catalytic domains and chitin-binding domains in pairwise comparisons, suggesting that these two domains have evolved separately. The chitin-binding domain appears to be evolutionarily conserved among many bacterial chitinases and is also somewhat similar to cellulose-binding domains found in microbial cellulases and xylanases. To investigate the role of the chitin-binding domain, clones producing versions of ChiA with or without this domain were examined. One version with the domain (ChiA1) bound to and hydrolysed chitin, whereas a truncated ChiA without the putative chitin-binding domain (ChiA2) did not bind to chitin, but it could hydrolyse chitin, although not as well. ChiA1 diffused more slowly in agarose containing colloidal chitin than ChiA2, but diffusion of the two proteins in agarose without colloidal chitin was similar. These results indicate that the chitin-binding domain helps determine the movement of chitinase along N-acetylglucosamine strands and within environments containing chitin.


[Stimulus dependent sodium channel blockade in node of Ranvier membranes by the quaternary antiarrhythmic N-propyl ajmaline (neogiluritmal)].
The blocking action of neo-gilurytmal (NG), a quaternary derivative of aimalin, on sodium channels was studied in the voltage-clamped node of Ranvier. NG exerted no action on the resting membrane unless the repetitive pulsing was turned on. A series of repetitive depolarizing pulses of short duration (5 ms) produced the accumulating "stimulus-dependent" blockade of sodium channels. The rate and degree of the blockade increased with the increasing of pulse voltage even over the potential range where all the sodium channels were open. Recovery from the blockade occurred within several tens of minutes. Unlike the repetitive pulsing, long-lasting (1 s) depolarization of the membrane produced only a slight increase in the blockade of sodium channels. Elimination of sodium inactivation by aconitine prevented the blocking action of NG. The results of the experiments indicate that NG blocks only the open sodium channels with intact inactivation gate.


Carbon nanotube fiber microelectrodes show a higher resistance to dopamine fouling.
We have compared the properties and resistance to DA fouling of a carbon nanotube fiber (CNTF) microelectrode to a traditional carbon fiber (CF) microelectrode. These two materials show comparable electrochemical activities for outer-sphere and inner-sphere redox reactions. Although the CNTF might have a higher intrinsic RC constant, thus limiting its high-frequency behavior, the CNTF shows a significantly higher durability than the CF in terms of electrode stability. During constant oxidation of 100 μM DA, the signal measured by the CNTF microelectrode shows a 2-h window over which no decrease in current is observed. Under the same conditions, the current obtained at the CF microelectrode decreases by almost 50%. A model of the fouling process, assuming the formation of growing patches of insulator on the surface, has been compared to the data. This model is found to be in good agreement with our results and indicates a growth rate of the patches in the 0.1-2 nm s(-1) range.


Effect of ablation of capsaicin-sensitive neurons on gastric protection by honey and sucralfate.
Accumulating evidence indicates that capsaicin-sensitive afferent neurons play a pivotal role in acute gastroprotection by liberating vasodilator substances. The mechanism of gastric protection by honey and sucralfate has been shown to be mediated through the vasodilator nitric oxide and cytoprotective sulphydryl-sensitive pathways in the stomach. The aim of the present study was to investigate the role of capsaicin-sensitive afferent neurons in the protective mechanism of honey and sucralfate against ethanol-induced gastric lesions. Ablation of capsaicin-sensitive afferent neurons was carried out by treating rats with neurotoxic doses of capsaicin (50 + 50 mg/kg subcutaneously over 2 consecutive days). The control groups received equal volumes of the vehicle (10% ethanol + 10% Tween 80 + 80% normal saline). The non-protein sulphydryl level was determined spectrophotometrically. Afferent sensory nerve ablation significantly aggravated ethanol-induced gastric lesions and caused a greater depletion of non-protein sulphydryl levels. Pretreatment with honey (0.078-0.625 g/kg, orally) or sucralfate (0.062-0.250 g/kg, orally) 30 min before administration of the ethanol prevented ethanol-induced gastric lesions and the depletion of non-protein sulphydryls in vehicle-treated rats. However, honey failed to afford protection or reverse non-protein sulphydryl depletion, while sucralfate was effective in the capsaicin-treated animals. The protective effect of sucralfate was lost in both groups following pretreatment with indomethacin (10 mg/kg, subcutaneously), while honey-induced protection was unaffected. These results suggest that the gastric protection by honey is solely dependent on the presence of intact afferent sensory neurons, whereas sucralfate-induced gastroprotection is mediated through the afferent sensory neuron and prostaglandin systems. It seems that the non-protein sulphydryl level is affected by the ablation of sensory neurons and plays an important regulatory role in gastric protection.


Aging of cultured retinal pigment epithelial cells: oxidative reactions, lipofuscin formation and blue light damage.
This report reviews our experimental work on cultured retinal pigment epithelial (RPE) cells, fed native or UV-irradiated photoreceptor outer segments (POS). We showed that significantly more lipofuscin (LF) was formed in cells cultured in 40% oxygen than in cells cultured in 8% oxygen, indicating an involvement of oxidative mechanisms in LF formation. The antioxidants alpha-tocopherol, lycopene, zeaxanthin and lutein significantly reduced LF formation. RPE cells high in melanin content exhibited significantly less formation of LF than cells low in or devoid of melanin, suggesting that melanin acts as an effective antioxidant. The phagocytic capacity of LF-loaded RPE cells was significantly reduced compared to that of unloaded control cells, indicating that LF-loaded RPE cells may be unable to serve the photoreceptors sufficiently regarding phagocytosis of shed outer segment tips. Blue light irradiation destabilized lysosomal membranes in LF-loaded RPE cells and significantly reduced the viability of such cells compared to unloaded, irradiated control cells. These results may be of significance in relation to the development of age-related macular degeneration (AMD).


Neurogenic cholinergic prejunctional inhibition of sympathetic beta adrenergic relaxation in the canine coronary artery.
Electrical stimulation of isolated canine coronary arteries causes release of norepinephrine and subsequent relaxation by activation of beta adrenoceptors. The purpose of the present study was to determine if this beta adrenergic relaxation was influenced by a concomitant release of acetylcholine. Rings of epicardial coronary arteries of the dog were studied in organ chambers filled with physiological salt solution. The tetrodotoxin-sensitive, beta adrenergically mediated relaxation induced by electrical stimulation was studied during contractions evoked by prostaglandin F2 alpha. The relaxation to low-frequency stimulation was inhibited and augmented, respectively, by acetylcholine and atropine, suggesting that release of acetylcholine may modulate the beta adrenergic response to sympathetic nerve stimulation. The relaxation caused by high-frequency stimulation was not affected by atropine or removal of the endothelium, indicating that endogenously released acetylcholine does not act directly on the smooth muscle or initiate an endothelium-dependent vasodilator response. In superfused strips of coronary artery preincubated in [3H]norepinephrine, acetylcholine depressed the stimulated overflow of [3H]norepinephrine, indicating prejunctional cholinergic receptors on adrenergic nerve endings. Atropine augmented the overflow, suggesting that endogenous acetylcholine, released during stimulation, inhibits the release of norepinephrine. These observations suggest that prejunctional inhibition of norepinephrine release, which limits the sympathetic beta adrenergic relaxation of the smooth muscle, is the primary neurogenic cholinergic effect in canine epicardial coronary arteries.


Correction of erroneously packed protein's side chains in the NMR structure based on ab initio chemical shift calculations.
In this work, protein side chain (1)H chemical shifts are used as probes to detect and correct side-chain packing errors in protein's NMR structures through structural refinement. By applying the automated fragmentation quantum mechanics/molecular mechanics (AF-QM/MM) method for ab initio calculation of chemical shifts, incorrect side chain packing was detected in the NMR structures of the Pin1 WW domain. The NMR structure is then refined by using molecular dynamics simulation and the polarized protein-specific charge (PPC) model. The computationally refined structure of the Pin1 WW domain is in excellent agreement with the corresponding X-ray structure. In particular, the use of the PPC model yields a more accurate structure than that using the standard (nonpolarizable) force field. For comparison, some of the widely used empirical models for chemical shift calculations are unable to correctly describe the relationship between the particular proton chemical shift and protein structures. The AF-QM/MM method can be used as a powerful tool for protein NMR structure validation and structural flaw detection.


Genetic and physical mapping of the mouse Ulnaless locus.
The mouse Ulnaless locus is a semidominant mutation which displays defects in patterning along the proximal-distal and anterior-posterior axes of all four limbs. The first Ulnaless homozygotes have been generated, and they display a similar, though slightly more severe, limb phenotype than the heterozygotes. To create a refined genetic map of the Ulnaless region using molecular markers, four backcrosses segregating Ulnaless were established. A 0.4-cM interval containing the Ulnaless locus has been defined on mouse chromosome 2, which has identified Ulnaless as a possible allele of a Hoxd cluster gene(s). With this genetic map as a framework, a physical map of the Ulnaless region has been completed. Yeast artificial chromosomes covering this region have been isolated and ordered into a 2 Mb contig. Therefore, the region that must contain the Ulnaless locus has been defined and cloned, which will be invaluable for the identification of the molecular nature of the Ulnaless mutation.


Toxicity of anthrax toxin is influenced by receptor expression.
Anthrax toxin protective antigen (PA) binds to its cellular receptor, and seven subunits self-associate to form a heptameric ring that mediates the cytoplasmic entry of lethal factor or edema factor. The influence of receptor type on susceptibility to anthrax toxin components was examined using Chinese hamster ovary (CHO) cells expressing the human form of one of two PA receptors: TEM8 or CMG2. Unexpectedly, PA alone, previously believed to only mediate entry of lethal factor or edema factor, was found to be toxic to CHO-TEM8 cells; cells treated with PA alone displayed reduced cell growth and decreased metabolic activity. PA-treated cells swelled and became permeable to membrane-excluded dye, suggesting that PA formed cell surface pores on CHO-TEM8 cells. While CHO-CMG2 cells were not killed by wild-type PA, they were susceptible to the PA variant, F427A. Receptor expression also conferred differences in susceptibility to edema factor.


Correlation between the stimulation of human neutrophil function by monoclonal antibody and by colony-stimulating factor.
Purified human neutrophils from 48 individuals were tested for their capacity to kill antibody-coated target cells in vitro in the absence or presence of stimulating agents. The agents used to stimulate cytotoxic capacity were the monoclonal antibody (MAb) WEM-G1, colony-stimulating factor (CSF-alpha), or mononuclear cell supernatant (MNC-SN). There existed an heterogeneity among the neutrophils of different individuals in the capacity to kill target cells both in the unstimulated ("resting") or the stimulated state. A positive correlation was found between the ability of neutrophils to kill in the "resting" state and their capacity to be stimulated by MAb WEM-G1, CSF-alpha, or MNC-SN. Furthermore, a strong positive correlation in the ability of neutrophils to be stimulated by the MAb WEM-G1 and either CSF-alpha (r = .76) or MNC-SN (r = .68), as well as between CSF-alpha and MNC-SN (r = .79) was demonstrated. No correlation was seen, however, between stimulation of neutrophil function in vitro and total blood leukocyte counts, neutrophil counts, monocyte counts, or intensity of binding of MAb WEM-G1. The observation that neutrophils respond to a similar extent to different types of stimulators, -such as cytokines (CSF-alpha and MNC-SN) and MAb, suggests that these two factors may be operating through a common mechanism and the degree of stimulation may reflect an intrinsic responsiveness of neutrophils that differs among individuals. Our results also suggest a potential clinical use of WEM-G1 in measuring neutrophil functional capacity in vitro and predicting the capacity to respond to CSF-like cytokines.


Evaluation of a Parchment Document, the 13th Century Incorporation Charter for the City of Krakow, Poland, for Microbial Hazards.
The literature of environmental microbiology broadly discusses issues associated with microbial hazards in archives, but these publications are mainly devoted to paper documents. There are few articles on historical parchment documents, which used to be very important for the development of literature and the art of writing. These studies present a broad spectrum of methods for the assessment of biodeterioration hazards of the parchment document in question. They are based on both conventional microbiological methods and advanced techniques of molecular biology. Here, a qualitative analysis was conducted, based on genetic identification of bacteria and fungi present on the document as well as denaturing gradient gel electrophoresis profiling and examining the destructive potential of isolated microbes. Moreover, the study involved a quantitative and qualitative microbiological assessment of the indoor air in the room where the parchment was kept. The microbes with the highest destructive potential that were isolated from the investigated item were Bacillus cereus and Acinetobacter lwoffii bacteria and Penicillium chrysogenum,Chaetomium globosum, and Trichoderma longibrachiatum fungi. The presence of the B. cereuss train was particularly interesting since, under appropriate conditions, it leads to complete parchment degradation within several days.


A computational simulated control system for a high-force pneumatic muscle actuator: system definition and application as an augmented orthosis.
High-force pneumatic muscle actuators (PMAs) are used for force assistance with minimal displacement applications. However, poor control due to dynamic nonlinearities has limited PMA applications. A simulated control system is developed consisting of: (1) a controller relating an input position angle to an output proportional pressure regulator voltage, (2) a phenomenological model of the PMA with an internal dynamic force loop (system time constant information), (3) a physical model of a human sit-to-stand task and (4) an external position angle feed-back loop. The results indicate that PMA assistance regarding the human sit-to-stand task is feasible within a specified PMA operational pressure range.


Nucleus replacement technologies.
Nucleus replacement offers a less invasive alternative to traditional fusion or total disc replacement techniques in the treatment of symptomatic lumbar degenerative disc disease (DDD). The authors discuss the classification of nucleus replacement devices as well as their potential indications. The authors review the history and evolution of nucleus replacement devices emphasizing several that are actively in US Investigational Device Exemption pilot feasibility trials. Nucleus replacement devices can be functionally categorized as elastomeric and mechanical. A classification scheme is discussed. Nucleus replacement remains investigational, but early clinical results have been encouraging. Further clinical investigation with well-designed prospective, randomized pivotal trials is needed to determine the efficacy of nucleus replacement in the treatment of lumbar DDD, as well as its ideal indications.


Carbon monoxide reverses the metabolic adaptation of microglia cells to an inflammatory stimulus.
Microglia fulfill important immunological functions in the brain by responding to pathological stresses and modulating their activities according to pro- or anti-inflammatory stimuli. Recent evidence indicates that changes in metabolism accompany the switch in microglia activation state, favoring glycolysis over oxidative phosphorylation when cells exhibit a pro-inflammatory phenotype. Carbon monoxide (CO), a byproduct of heme breakdown by heme oxygenase, exerts anti-inflammatory action and affects mitochondrial function in cells and tissues. In the present study, we analyzed the metabolic profile of BV2 and primary mouse microglia exposed to the CO-releasing molecules CORM-401 and CORM-A1 and investigated whether CO affects the metabolic adaptation of cells to the inflammatory stimulus lipopolysaccharide (LPS). Microglia respiration and glycolysis were measured using an Extracellular Flux Analyzer to provide a real-time bioenergetic assessment, and biochemical parameters were evaluated to define the metabolic status of the cells under normal or inflammatory conditions. We show that CO prevents LPS-induced depression of microglia respiration and reduction in ATP levels while altering the early expression of inflammatory markers, suggesting the metabolic changes induced by CO are associated with control of inflammation. CO alone affects microglia respiration depending on the concentration, as low levels increase oxygen consumption while higher amounts inhibit respiration. Increased oxygen consumption was attributed to an uncoupling activity observed in cells, at the molecular level (respiratory complex activities) and during challenge with LPS. Thus, application of CO is a potential countermeasure to reverse the metabolic changes that occur during microglia inflammation and in turn modulate their inflammatory profile.


Measurement of the charge properties of articular cartilage by an electrokinetic method.
The charge structure of the surface of articular cartilage determines its interactions with the macromolecules and cells of synovial fluid. It may thereby be important to the physiological function and pathological degeneration of the tissue. To determine whether the electrokinetic properties of the surface differ from those of the bulk tissue, we measured the streaming potential generated by the flow of electrolyte over the surface of a cartilage plug mounted in a chamber built for that purpose. We then calculated the effective surface charge density. In nonfibrillated cartilage from the human femoral head, the surface charge density, 0.037+/-0.004 Cm(-2) (mean+/-SD), was approximately half that measured at the surface of slices cut from the middle and deep zones. In addition, the surface charge density fell relatively little at low pH; this is consistent with a higher proportion of strongly acidic groups. The variations in surface charge density were found to be similar to those in total fixed charge density in the slices by the tracer cation method. Therefore, no evidence exists that the actual surface differs in composition from the immediately underlying matrix. The addition of synovial fluid (0.0025 ml/ml) to the superfusing solution reduced the surface charge density by 25+/-9% (n=5), and we attributed this to the binding of synovial-fluid macromolecules.


What provides cerebral reserve?
The cerebral reserve hypothesis is a heuristic concept used to explain apparent protection from the onset of cerebral disease and/or cognitive decline in old age. A significant obstacle when investigating the reserve hypothesis is the absence of baseline data with which to compare current cognitive status. We tested the influence of three hypothesized proxies of reserve (education, head size and occupational attainment [OCC]) in 92 volunteers born in 1921, whose cognitive function was measured at age 11 and 79 years, and who underwent brain MRI. The association between each proxy and old age cognitive function was tested, adjusting for variance contributed by childhood mental ability and detrimental age-related pathological changes measured using MRI. The results showed that education and OCC, but not total intracranial volume (TICV), contribute to cerebral reserve and help retain cognitive function in old age. Education was found to contribute between 5 and 6% of the variance found in old age memory function but was found to have no significant association with reasoning abilities. OCC was found to contribute around 5% of the variance found in old age memory function and between 6 and 8% of the variance found in old age reasoning abilities. We conclude that the intellectual challenges experienced during life, such as education and occupation, accumulate reserve and allow cognitive function to be maintained in old age.