Percutaneous vertebroplasty.
This review, aimed at current practitioners of vertebroplasty, highlights recent changes in patient work-up and procedural techniques that have streamlined the authors' clinical practice. Preprocedural work-up, including history, physical examination, and adjunctive imaging techniques, are discussed. Technical details are reviewed, including types of equipment, techniques of needle placement, and utility of venography. Postprocedural issues are noted, including risk of subsequent fracture after vertebroplasty, long-term outcome of cement in the vertebral body, and utility of prophylactic vertebroplasty. Finally, the current state of evidence in support of the efficacy of vertebroplasty are discussed, with particular attention to the need for ongoing clinical trials.


Analysis of MicroRNA-18a Expression in Multiple Sclerosis Patients.
In multiple sclerosis (MS), the immune system acts against myelin lesions of the central nervous system, destroying neuronal fibers resulting in signal transmission disturbances in the nervous system. MicroRNAs play important roles in the post-transcriptional regulation of gene expression and in the regulation of disease activity and its response to treatment. The goal of this study was to determine the role of miR-18a-5p by comparing its expression in MS patients and healthy subjects. RNA was isolated from blood samples of 32 MS patients and 32 healthy individuals, and miR-18a-5p expression was determined by real-time polymerase chain reaction (real-time PCR). miR-18a-5p expression was significantly less in MS patients than in healthy subjects. The reduction of miR-18a-5p expression may be via pathway signaling. Altered signaling plays an important role in MS pathogenesis and the miR-18a-5p expression profile in blood cells can be described as a prognostic biomarker and identifier of high-risk individuals in MS.


Transition pathways in complex systems: Application of the finite-temperature string method to the alanine dipeptide.
The finite-temperature string method proposed by E, et al. [W. E, W. Ren, and E. Vanden-Eijnden, Phys. Rev. B 66, 052301 (2002)] is a very effective way of identifying transition mechanisms and transition rates between metastable states in systems with complex energy landscapes. In this paper, we discuss the theoretical background and algorithmic details of the finite-temperature string method, as well as the application to the study of isomerization reaction of the alanine dipeptide, both in vacuum and in explicit solvent. We demonstrate that the method allows us to identify directly the isocommittor surfaces, which are approximated by hyperplanes, in the region of configuration space where the most probable transition trajectories are concentrated. These results are verified subsequently by computing directly the committor distribution on the hyperplanes that define the transition state region.


From psychosis to Wernicke encephalopathy: a case of hunger strike in prison.
Wernicke encephalopathy (WE) is a neuropsychiatric condition associated with thiamine deficiency that includes a triad of mental status changes, ophthalmoplegia, and ataxia. Worsening WE may lead to Korsakoff syndrome(KS), in which cognitive impairments such as confabulation and memory deficits and also psychiatric symptoms may occur. Diagnosis of Wernicke-Korsakoff syndrome can be complicated in many cases. We present the case of a prisoner who commenced a hunger strike and developed WE. The preceding factors were associated with his oral intake refusal, which originated from his mental disorder with psychotic content. We discuss the clinical and treatment concerns for this complicated condition.


Can a numerically stable subgrid-scale model for turbulent flow computation be ideally accurate?: a preliminary theoretical study for the Gaussian filtered Navier-Stokes equations.
This paper introduces a candidate for the origin of the numerical instabilities in large eddy simulation repeatedly observed in academic and practical industrial flow computations. Without resorting to any subgrid-scale modeling, but based on a simple assumption regarding the streamwise component of flow velocity, it is shown theoretically that in a channel-flow computation, the application of the Gaussian filtering to the incompressible Navier-Stokes equations yields a numerically unstable term, a cross-derivative term, which is similar to one appearing in the Gaussian filtered Vlasov equation derived by Klimas [J. Comput. Phys. 68, 202 (1987)] and also to one derived recently by Kobayashi and Shimomura [Phys. Fluids 15, L29 (2003)] from the tensor-diffusivity subgrid-scale term in a dynamic mixed model. The present result predicts that not only the numerical methods and the subgrid-scale models employed but also only the applied filtering process can be a seed of this numerical instability. An investigation concerning the relationship between the turbulent energy scattering and the unstable term shows that the instability of the term does not necessarily represent the backscatter of kinetic energy which has been considered a possible origin of numerical instabilities in large eddy simulation. The present findings raise the question whether a numerically stable subgrid-scale model can be ideally accurate.


Spatiotemporal characteristics of the pharyngeal event-related potential in healthy subjects and older patients with oropharyngeal dysfunction.
Oropharyngeal dysphagia (OD) is a highly prevalent symptom in older people. Appropriate oropharyngeal sensory feedback is essential for safe and efficient swallowing. However, pharyngeal sensitivity decreases with advancing age and could play a fundamental role in the physiopathology of swallowing dysfunction associated with aging. We aimed to characterize pharyngeal sensitivity and cortical response to a pharyngeal electrical stimulus in healthy volunteers (HV) and older patients with and without OD. Eight young HV, eight older HV without OD, and 14 older patients with OD were studied by electroencephalography through 32 scalp electrodes. Pharyngeal event-related potentials (ERP) were assessed following electrical stimulation of the pharynx. Sensory and tolerance thresholds to the electrical stimulus and latency, amplitude, and scalp current density of each ERP component were analyzed and compared. An ERP source localization study was also performed using the sLORETA software. Older participants (with and without OD) presented an increased sensory threshold to pharyngeal electrical stimulation (10.2 ± 1.7 mA and 11.5 ± 1.9 mA respectively), compared with young HV (6.0 ± 1.2 mA). The cortical activation of older HV in response to pharyngeal electrical stimulus was reduced compared with young HV (N2 amplitude: 0.22 ± 0.79 vs -3.10 ± 0.59, P<.05). Older patients with OD also presented disturbances to the pharyngo-cortical connection together with disrupted pattern of cortical activation. Older people present a decline in pharyngeal sensory function, more severe in older patients with OD. This sensory impairment might be a critical pathophysiological element and a potential target for treatment of swallowing dysfunction in older patients.


Enteroenteroanastomosis near adjacent ileocecal valve in infants.
To investigate the feasibility and the effectiveness of ileoileostomy in the region adjacent to the ileocecal valve, which can retain the ileocecal valve in infants. This is a retrospective review of 48 patients who underwent ileoileostomy in the region adjacent to the ileocecal valve (group 1) and 34 patients who underwent ileocecal resections and ileotransversanastomosis (group 2). Patients were monitored for the time to flatus, resumption of eating, length of hospital stay after surgery, serum total bile acid, vitamin B12 and postoperative complications. The time to flatus, time until resumption of eating and post-operative length of hospital stay showed no statistically significant differences between the two groups. Serum total bile acid and vitamin B12 were not significantly different between the two groups at post-operative day 1 and day 3, but were significantly decreased at 1 wk after operation in group 2. None of the patients died or suffered from stomal leak in these two groups. However, the incidence of diarrhea, intestinal infection, disturbance of acid-base balance and water-electrolytes in group 1 was lower than in group 2. Ileoileostomy in the region adjacent to the ileocecal valve is safe and results in fewer complications than ileotransversanastomosis in infants.


Late-gestation treatment of pregnant cows with trenbolone acetate does not increase subsequent growth of heifer calves.
Fifty crossbred cows (38 multiparous and 12 nulliparous) were used to evaluate in utero androgenization of heifer calves with trenbolone acetate. Three 200-mg trenbolone acetate (Finaplix-H) implants were implanted in the ear of treated cows (n = 24) on d 214 +/- 11 of gestation; the remaining animals (n = 26) were used as controls. Cows' rate of gain, serum levels of trenbolone acetate, gestation length, degree of dystocia, percentage bred back, days until conception, and 24-h milk production were evaluated. Fourteen-day weigh periods until parturition indicated that trenbolone acetate-treated dams had an increased (P < .05) average daily gain (1.05 +/- .1 kg) compared with control cows (.55 +/- .1 kg). Serum concentrations of trenbolone acetate were higher (P < .01) in treated cows with a peak at 9 d after implantation and returned to basal concentrations by d 77. Treatment did not affect degree of dystocia among all cows (P > .05) but seemed to increase (P < .01) the incidence of dystocia in nulliparous cows compared with nulliparous control cows. Gestation length and subsequent fertility were not affected by treatment (P > .05). Similarly, there was no difference in 24-h milk production (P > .05) between treated and control cows. Calf birth weight, phenotypic measurements at birth, vigor, average daily gain, carcass characteristics, and heifer reproductive tract and ovarian weights did not differ with treatment (P > .05). These data showed that late-gestation treatment with 600 mg of trenbolone acetate significantly increased weight gain of dams without demonstrating any androgenizing effects on the growth or physical characteristics of heifer calves.


New generation high performance in situ polarized 3He system for time-of-flight beam at spallation sources.
Modern spallation neutron sources generate high intensity neutron beams with a broad wavelength band applied to exploring new nano- and meso-scale materials from a few atomic monolayers thick to complicated prototype device-like systems with multiple buried interfaces. The availability of high performance neutron polarizers and analyzers in neutron scattering experiments is vital for understanding magnetism in systems with novel functionalities. We report the development of a new generation of the in situ polarized 3He neutron polarization analyzer for the Magnetism Reflectometer at the Spallation Neutron Source at Oak Ridge National Laboratory. With a new optical layout and laser system, the 3He polarization reached and maintained 84% as compared to 76% in the first-generation system. The polarization improvement allows achieving the transmission function varying from 50% to 15% for the polarized neutron beam with the wavelength band of 2-9 Angstroms. This achievement brings a new class of experiments with optimal performance in sensitivity to very small magnetic moments in nano systems and opens up the horizon for its applications.


Denaturant-dependent folding of bovine pancreatic trypsin inhibitor mutants with two intact disulfide bonds.
The equilibrium and kinetic behavior of the guanidine hydrochloride (Gdn-HCl) induced unfolding/refolding of four bovine pancreatic trypsin inhibitor (BPTI) mutants was examined by using ultraviolet difference spectroscopy. In three of the mutants, we replaced the buried 30-51 disulfide bond with alanine at position 51 and valine (Val30/Ala51), alanine (Ala30/Ala51), or threonine (Thr30/Ala51) at position 30. For the fourth mutant, the solvent-exposed 14-38 disulfide was substituted by a pair of alanines (Ala14/Ala38). All mutants retained the 5-55 disulfide. Experiments were performed under oxidizing conditions; thus, both the unfolded and folded forms retained two native disulfide bonds. Equilibrium experiments demonstrated that all four mutants were destabilized relative to wild-type BPTI. However, the stability of the 30-51 mutants increased with the hydrophobicity of the residue substituted at position 30. Kinetic experiments showed that all four mutants contained two minor slow refolding phases with characteristics of proline isomerization. The specific behavior of the phases depended on the location of the disulfide bonds. The major unfolding/refolding phase for each of the 30-51 mutants was more than an order of magnitude slower than for Ala14/Ala38 or for BPTI in which the 14-38 disulfide bond was specifically reduced and blocked with iodoacetamide [Jullien, M., & Baldwin, R. L. (1981) J. Mol. Biol. 145, 265-280]. Since this effect is independent of the stability of the protein, it is consistent with a model in which the proper docking of the interior residues of the protein is the rate-limiting step in the folding of these mutants.


The dental educator. An endangered species.
The dental educator is increasingly an endangered species. Part of the problem rests with the failure of dental educators themselves to convey to new graduates and to seasoned colleagues the variety, excitement and realities of reasonable income and fringe benefits associated with an academic career. Each of us in dental education must make a daily effort to convey this information through personal experience to our potential junior and new senior colleagues. Loan forgiveness protocols and unique training programs for those who choose to pursue full-time academic careers require collaborative financing from all of us in the profession, from our state and federal governments, and, ideally, from private industrial resources as well. The use of new educational technologies to relieve some of the more repetitive and burdensome aspects of education and to free the time of dental educators for more discussion in small groups, for problem-solving discussions, and for one-on-one interaction is imperative. If the current, clear and frightening decrease in the number of dental educators is ignored or even inadvertently fostered through ignorance or inaction, the entire profession will suffer directly. Practitioners, educators, industry and our government must cooperate in an intense and immediate effort to reverse this trend.


Characterization of epidemic Neisseria meningitidis serogroup C strains in several Brazilian states.
Epidemic strains of the Neisseria meningitidis C:2b:P1.3 electrophoretic type 11 complex were responsible for an outbreak in Curitiba, Parana State, Brazil, from 1990 to 1991. Strains of this complex were also isolated in other Brazilian states and were responsible for a meningococcal disease epidemic in São Paulo State in 1990. Serotyping both with monoclonal antibodies and by multilocus enzyme electrophoresis was useful for typing these epidemic strains related to the increased incidence of meningococcal disease. The genetic similarity of members of the electrophoretic type 11 complex was confirmed by the ribotyping method by using EcoRI or ClaI endonuclease restriction enzymes.


Hepatitis C associated chronic liver disease in renal transplant recipients.
Infection with Hepatitis C Virus (HCV) is emerging as a major cause of morbidity and mortality in renal transplant recipients. We studied three hundred and forty stable renal transplant recipients on follow-up in our transplant clinic. Anti-HCV, tested by second generation ELISA, was positive in 185 patients (54%) of whom 52 (28%) had evidence of chronic liver disease. Six of the study patients were positive for anti-HCV and hepatitis B surface antigen. Twenty-three patients consented to undergo liver biopsy of whom eight had normal histology or fatty changes. Five patients had chronic non-specific hepatitis; four each had chronic lobular and chronic active hepatitis (CAH) and two had CAH with cirrhosis. All 15 patients with significant abnormalities on liver histology had elevated serum transaminase levels. Repeat liver biopsies were performed in seven patients after a mean period of 23.8 months following the first biopsy which showed worsening of the disease in four while three retained the same pattern. These results suggest that the prevalence of anti-HCV in our renal transplant recipients is high and that these patients have a high prevalence of chronic liver disease associated with major changes on liver histology. It is therefore recommended that caution is exercised while considering transplantation in patients who are anti-HCV positive.


Crystal structure of glucooligosaccharide oxidase from Acremonium strictum: a novel flavinylation of 6-S-cysteinyl, 8alpha-N1-histidyl FAD.
Glucooligosaccharide oxidase from Acremonium strictum has been screened for potential applications in oligosaccharide acid production and alternative carbohydrate detection, because it catalyzes the oxidation of glucose, maltose, lactose, cellobiose and cello- and maltooligosaccharides. We report the crystal structures of the enzyme and of its complex with an inhibitor, 5-amino-5-deoxy- cellobiono-1,5-lactam at 1.55- and 1.98-A resolution, respectively. Unexpectedly, the protein structure demonstrates the first known double attachment flavinylation, 6-S-cysteinyl, 8alpha-N1-histidyl FAD. The FAD cofactor is cross-linked to the enzyme via the C(6) atom and the 8alpha-methyl group of the isoalloxazine ring with Cys(130) and His(70), respectively. This sugar oxidase possesses an open carbohydrate-binding groove, allowing the accommodation of higher oligosaccharides. The complex structure suggests that this enzyme may prefer a beta-d-glucosyl residue at the reducing end with the conserved Tyr(429) acting as a general base to abstract the OH(1) proton in concert with the H(1) hydride transfer to the flavin N(5). Finally, a detailed comparison illustrates the structural conservation as well as the divergence between this protein and its related flavoenzymes.


Transsynaptic Long-Term Potentiation in the Hippocampus of Behaving Mice.
Long-term potentiation (LTP) is an experimental procedure that shares certain mechanisms with neuronal learning and memory processes and represents a well-known example of synaptic plasticity. LTP consists of an increase of the synaptic response to a control stimulus following the presentation of a high-frequency stimulation (HFS) train to an afferent pathway. This technique is studied mostly in the hippocampus due to the latter's high susceptibility and its laminar nature which facilitates the location of defined synapses. Although most preceding studies have been performed in vitro, we have developed an experimental approach to carry out these experiments in alert behaving animals. The main goal of this study was to confirm the existence of synaptic changes in strength in synapses that are post-synaptic to the one presented with the HFS. We recorded field excitatory post-synaptic potentials (fEPSPs) evoked in five hippocampal synapses, from both hemispheres, of adult male mice. HFS was presented to the perforant pathway (PP). We characterized input/output curves, paired-pulse stimulation, and LTP of these synapses. We also performed depth-profile recordings to determine differences in fEPSP latencies. Collected data indicate that the five selected synapses have similar basic electrophysiological properties, a fact that enables an easier comparison of LTP characteristics. Importantly, we observed the presence of significant LTP in the contralateral CA1 (cCA1) area following the control stimulation of non-HFS-activated pathways. These results indicate that LTP appears as a physiological process present in synapses located far away from the HFS-stimulated afferent pathway.


An ID-like current that is downregulated by Ca2+ modulates information coding at CA3-CA3 synapses in the rat hippocampus.
Voltage-gated K+ channels localised on presynaptic nerve terminals control information coding by modulating presynaptic firing and synaptic efficacy in target neurones. We found that at CA3-CA3 connections in hippocampal slice cultures, a fast-activating, slowly inactivating K+ conductance similar to the so-called delay current (ID) is responsible for the delayed appearance of the first spike upon membrane depolarisation, for action potential repolarisation and for modulation of transmitter release. The ID-like current was downregulated by intracellular Ca2+, as indicated by the increased delay in the appearance of the first action potential following either the block of Ca2+ flux through voltage-dependent Ca2+ channels with Cd2+ or replacement of the bathing solution with one devoid of Ca2+. In both cases, this effect was reversed by blocking this conductance with a low concentration of 4-aminopyridine (4-AP, 10-50 muM). Application of 4-AP shortened the delay to the first spike generation, prevented the effect of Cd2+ and increased the spike duration. The earlier appearance of the first action potential was also observed in the presence of dendrotoxin-1 (100 nM). In voltage-clamp experiments larger currents were recorded in the absence of extracellular Ca2+, thus confirming the downregulation of the ID-like current by Ca2+ due to the positive shift of its inactivation. Spike broadening was associated with an enhancement of synaptic efficacy in target neurones, as assessed by the increase in EPSC amplitude and in the percentage of successes. Moreover, in the presence of 4-AP, EPSCs appeared with a longer latency and were more scattered. This conductance is therefore crucial for setting the timing and strength of synaptic transmission at CA3-CA3 connections. It is conceivable that switching off ID by increasing intracellular Ca2+ following activity-dependent processes may facilitate network synchronisation and crosstalk between CA3 pyramidal cells, leading to seizure activity.


Template Synthesis, Metalation, and Self-Assembly of Protic Gold(I)/(NHC)2 Tectons Driven by Metallophilic Interactions.
A new protocol for the synthesis of protic bis(N-heterocyclic carbene) complexes of Au(I) by a stepwise metal-controlled coupling of isocyanide and propargylamine is described. They are used as tectons for the construction of supramolecular architectures through metalation and self-assembly. Notably a unique polymeric chain of Cu(I) with alternate Au(I) /bis(imidazolate) bridging scaffolds and strong unsupported Cu(I) -Cu(I) interactions has been generated, as well as a 28-metal-atoms cluster containing a nanopiece of Cu2 O trapped by peripheral Au(I) /bis(imidazolate) moieties.


Identification of a deep-branching thermophilic clade sheds light on early bacterial evolution.
It has been proposed that early bacteria, or even the last universal common ancestor of all cells, were thermophilic. However, research on the origin and evolution of thermophily is hampered by the difficulties associated with the isolation of deep-branching thermophilic microorganisms in pure culture. Here, we isolate a deep-branching thermophilic bacterium from a deep-sea hydrothermal vent, using a two-step cultivation strategy ("Subtraction-Suboptimal", StS) designed to isolate rare organisms. The bacterium, which we name Zhurongbacter thermophilus 3DAC, is a sulfur-reducing heterotroph that is phylogenetically related to Coprothermobacterota and other thermophilic bacterial groups, forming a clade that seems to represent a major, early-diverging bacterial lineage. The ancestor of this clade might be a thermophilic, strictly anaerobic, motile, hydrogen-dependent, and mixotrophic bacterium. Thus, our study provides insights into the early evolution of thermophilic bacteria.


Individual movements and contact patterns in a Canadian long-term care facility.
Contact networks of individuals in healthcare facilities are poorly understood, largely due to the lack of spatio-temporal movement data. A better understanding of such networks of interactions can help improve disease control strategies for nosocomial outbreaks. We sought to determine the spatio-temporal patterns of interactions between individuals using movement data collected in the largest veterans long-term care facility in Canada. We processed close-range contact data generated by the exchange of ultra-low-power radio signals, in a prescribed proximity, between wireless sensors worn by the participants over a two-week period. Statistical analyses of contact and movement data were conducted. We found a clear dichotomy in the contact network and movement patterns between residents and healthcare workers (HCWs) in this facility. Overall, residents tend to have significantly more distinct contacts with the mean of 17.3 (s.d. 3.6) contacts, versus 3.5 (s.d. 2.3) for HCWs (p-value < 10-12), for a longer duration of time (with mean contact duration of 8 minutes for resident-resident pair versus 4.6 minutes for HCW-resident pair) while being less mobile than HCWs. Analysis of movement data and clustering coefficient of the hourly aggregated network indicates that the contact network is loosely connected (mean clustering coefficient: 0.25, interquartile range 0-0.40), while being highly structured. Our findings bring quantitative insights regarding the contact network and movements in a long-term care facility, which are highly relevant to infer direct human-to-human and indirect (i.e., via the environment) disease transmission processes. This data-driven quantification is essential for validating disease dynamic models, as well as decision analytic methods to inform control strategies for nosocomial infections.


Effects of Riot Control Training on Systemic Microvascular Reactivity and Capillary Density.
The main aim of the present study is to evaluate the effects of strenuous exercise, related to special military training for riot control, on systemic microvascular endothelial function and skin capillary density. Endothelium-dependent microvascular reactivity was evaluated in the forearm skin of healthy military trainees (age 23.4 ± 2.3 yr; n = 15) using laser speckle contrast imaging coupled with cutaneous acetylcholine (ACh) iontophoresis and post-occlusive reactive hyperemia (PORH). Functional capillary density was assessed using high-resolution, intra-vital color microscopy in the dorsum of the middle phalanx. Capillary recruitment (capillary reserve) was evaluated using PORH. Microcirculatory tests were performed before and after a 5-wk special military training for riot control. Microvascular endothelium-dependent vasodilatory responses were markedly and significantly reduced after training, compared with values obtained before training. The peak values of microvascular conductance obtained during iontophoresis of ACh or PORH before training (0.84 ± 0.22 and 0.94 ± 0.72 APU/mmHg, respectively) were markedly reduced after training (0.47 ± 0.11 and 0.71 ± 0.14 APU/mmHg; p < 0.0001 and p = 0.0037, respectively). Endothelium-dependent capillary recruitment was significantly reduced after training (before 101 ± 9 and after 95 ± 8 capillaries/mm2; p = 0.0007). The present study showed that a 5-wk strenuous military training, performed in unfavorable climatic conditions, induces marked systemic microvascular dysfunction, mainly characterized by reduced endothelium-dependent microvascular vasodilation and blunted capillary recruitment.


Dissociation of chicken blastoderm for examination of apoptosis and necrosis by flow cytometry.
We describe a method of isolating blastodermal cells for characterization through flow cytometry. Particular attention was placed on cell viability and integrity issues faced by conventional protocols. The method allowed us to examine mechanisms behind cellular death. Our protocol was optimized by the spatial resolution of the ImageStream multispectral imaging flow cytometer. Overall, the technique provides both quantitative and qualitative information on blastodermal cells. The methodology was applied to the current biological problem in which prolonged (14 d) versus short-term (4 d) layer egg storage reduces embryo viability. Data were obtained between 3 egg storage treatments (unstored, 4 d, and 14 d); the data were analyzed by the PROC MIXED model procedure of SAS at P < or = 0.05 and least squares means separated by the PDIFF procedure of SAS. The results showed that egg storage increases the rate of cell death by both apoptosis and necrosis. Importantly, our study showed higher percentages of necrosis and late apoptosis in long-term versus short-term stored eggs. The percentage of live cells decreased significantly when eggs were stored for 14 d (71.42 + or - 3.36%) compared with eggs stored for 4 d (83.58 + or - 2.15%). The percentage of early apoptotic cells was not significantly different between the 2 treatments. The percentage of necrotic cells and late apoptotic-necrotic cells was higher in eggs stored for 14 d (16.75 + or - 1.73%; 7.36 + or - 1.53%) versus eggs stored for 4 d (3.56 + or - 1.64%; 2.31 + or - 1.52%), respectively. This could negatively affect embryo survival because of the potential effect that necrosis has on surrounding tissue integrity. The technique will be particularly relevant in studies requiring single cells from chicken blastoderms or as a basis to characterize genes that regulate apoptosis in avian species.


Breaking bad news and personality assessment.
Breaking bad news to seriously ill patients is an especially difficult and important part of patient education and counseling. Guidelines for breaking bad news have been previously presented, but this is the first report to address the personality of the patient in deciding how to break had news. A case study of a patient diagnosed with amyotrophic lateral sclerosis is presented. A psychiatric consultation assisted in assessing the patient's personality and thus preparing the medical staff for breaking the bad news to him. The patient was assessed as having an obsessive-compulsive personality, and consequently the staff was instructed to concentrate on facts and not on feelings when breaking the bad news to him. The patient coped adaptively with this procedure, as did the staff. This case report illustrates that personality assessment may be of benefit in breaking bad news to seriously ill patients. It remains to be seen whether this procedure can be successfully generalized to other patients and settings as well as to other domains of patient education and counseling, and if so--whether this will also prove to be cost-effective.


Distribution of IgG subclasses in a biopsy specimen showing membranous nephropathy with anti-glomerular basement membrane glomerulonephritis: an uncharacteristically good outcome with corticosteroid therapy.
Few occurrences of anti-glomerular basement membrane glomerulonephritis superimposed on membranous nephropathy have been reported; most reported cases began as membranous nephropathy. Little is known about the etiology, pathogenesis, or immunoglobulin G subclasses in glomerular basement membrane deposits in these combined cases. The authors report the case of an elderly patient with apparently simultaneous onset of both membranous nephropathy and anti-glomerular basement membrane glomerulonephritis who had an excellent outcome with only pulse corticosteroid therapy. Successive renal biopsy specimens showed occurrence and disappearance of immunoglobulin G4 deposits in the glomerular basement membrane. Immunoglobulin G subclass analysis was important in recognizing membranous nephropathy underlying the anti-glomerular basement membrane disease.


Health perceptions among older urban American Indians.
There is a dearth of empirically based accounts dealing with health from the perspective of older American Indians. Some have even referred to these individuals as a "forgotten population." The purpose of the present investigation was to explore the phenomenon of health among urbanized members of this vulnerable population. More specifically, the study focused on how these individuals perceived their health and how they managed their health problems. Using the grounded theory method, discoveries indicated that these older adults constructed their ideas of health by observing signs of illness, incorporating the ideas of others, and evaluating getting around. Moreover, their health ideas often reflected a biomedical perspective. The data analysis also revealed factors in the historical and contemporary context that had salient consequences for these individuals' health beliefs and practices. Research implications include future studies of the complex factors that have consequences for health beliefs and practices, as well as a critical examination of the underlying social conditions that relate to health among these older American Indians.


Role of Vasopressin Receptor 2 and 3 in ACTH-Secreting Tumors and their Potential Therapeutic Implications.
We investigated the expression of vasopressin receptor 2 and 3 on corticotrophin tumor cells, their role in regulating ACTH secretion, and their potential therapeutic implications. We retrospectively assessed 52 hospitalized patients with pathologically confirmed ACTH-secreting tumors. The expression of vasopressin receptor 2 and 3 was explored via qualitative and quantitative immunohistochemistry analyses. The role of vasopressin receptors in regulating ACTH secretion was further studied in the AtT-20 cell line. Among 50 cases of pituitary corticotrophin adenoma, 31 were vasopressin receptor 2 positive, 38 were vasopressin receptor 3 positive, and 24 were both vasopressin receptor 2 and 3 positive. Two patients with ectopic ACTH syndrome were vasopressin receptor 3 positive, and one was also vasopressin receptor 2 positive. In 12 patients who underwent bilateral inferior petrosal sinus sampling before surgery, the central ACTH increment ratio after desmopressin stimulation was correlated with vasopressin receptor 2 but not with vasopressin receptor 3 staining intensity. In an in vitro study, the expression of both vasopressin receptor 2 and 3 on AtT-20 cells was confirmed. The vasopressin receptor 2 antagonist Tolvaptan inhibited desmopressin-induced ACTH secretion in a dose-dependent manner. Both vasopressin receptor 2 and 3 are expressed in ACTH-secreting tumors. Vasopressin receptor 2 rather than vasopressin receptor 3 is the primary receptor that seems to mediate the ACTH response in corticotrophin tumors. A vasopressin receptor 2 antagonist can inhibit ACTH secretion induced by desmopressin in AtT-20 cells.


A recommended guideline for the development of mHealth Apps.
Mobile Health or mHealth applications cope with medical or health issues supported by smartphones. Being a part of great importance in healthcare, mHealth apps are able to improve both the quality of medical services and the safety of the patients. It is regarded to be a new field with great prospect that attracts the interest of the stakeholders and the developers, above all. Of all the entities involved, developers have to face many challenges classified in four pillars: the regulation framework, the market, the technical issues and society. This paper aims to describe the role of the developers in the mHealth apps' market, the barriers they deal with and also, the impact of their work in the mobile healthcare domain. In our viewpoint, we propose a guideline with all of the developers' requirements for the buildup of mHealth apps. The methodology followed includes a Boolean search strategy used in academic libraries (PubMed, IEEE Xplore, JMIR, The Cochrane Library) and search engines additionally (Google and Google Scholar), aiming to identify the developers' perspective. Our research from October until December of 2014 led us to academic papers referring to the various demands that developers have to confront. The major outcome of our research is the general acknowledgement of the dominant role that developers own in the mHealth apps' process. Mobile technology allies multiple groups such as users, patients, providers of medical services, software developers, governments and even, non-governmental organizations. In particular, the developers' perspective involves the legal boundaries, the side of the market, the technological requirements (programming, devices, designing) and the moral aspects, as well. Developers should define the purposes of their apps-either diagnostic or therapeutic-and gain the confidence of the users in order to dominate the market, yet comply with the regulations.


Optic nerve involvement in viral spread in herpes simplex virus type 1 retinitis.
Colchicine was used to block fast axonal transport of the optic nerve of the uninjected eye after uniocular anterior chamber inoculation of herpes simplex virus type 1 (HSV-1). The results of these experiments suggest that second-wave virus is transported to the retina of the uninjected contralateral eye through the optic nerve of the uninjected eye, since intravitreal treatment with colchicine reduced both the viral titer and prevalence of animals with histopathologic evidence of retinitis. The chemical block to viral entry provided by colchicine was both dose- and time-dependent, with administration of colchicine that was timed to interfere with the second viral wave being the most effective. Colchicine did not appear to be directly inhibitory to viral replication or toxic to the virus, and colchicine did not cause clinical or microscopic evidence of retinal inflammation. Intravitreal injection of colchicine did not alter the timing or recovery of the first wave of virus.


Measurement of glucagon in human plasma by enzyme immunoassay.
In order to investigate the validity of an enzyme immunoassay for glucagon, the glucagon levels of human plasma were determined by both enzyme immunoassay (EIA) and radioimmunoassay (RIA). After a glucose load, plasma glucagon measured by both EIA and RIA fell in 12 normal subjects. The glucagon levels measured by both assays during glucose tolerance test showed good agreement in a group of 10 patients. After arginine infusion, plasma glucagon increased in 6 normal subjects and 3 patients and glucagon values measured by EIA correlated well with those by RIA. The present study demonstrates correlation between glucagon levels measured by RIA and EIA and indicates the usefulness of EIA for determining glucagon in human plasma.


[Comparison of effects of hydroxyethylstarch (HES 200/0.5) administered pre- and postoperatively in vascular surgery with dextran 40 (60) (author's transl)].
In a randomised study comprising 16 patients undergoing vascular surgery of the lower extremities blood replacement was performed after preinfusion of either 500 ml 10% hydroxyethylstarch (LMW-HES) or 10% dextran 40 (followed by dextran 60 intraoperatively). After infusion of 500 ml within 30 min preoperatively there was a significant rise in PCWP, PAP, RAP and CI accompanied by an increase in blood volume and colloid osmotic pressure, whereas hematocrit fell. No difference between the two plasmasubstitutres was found, prolonged infusion of HES, however, caused a lesser rise in cardiac pressures and blood volume. Overloading of the circulation could be ruled out by ECG, Frank-Starling curves, blood gases, observation of total pulmonary vascular resistance and vascular filtration pressure. The modified haemodilution technique suggested, using preoperative priming without blood drainage and subsequent dilution by blood replacement up to a total amount of 1,500 ml by HES or dextran thus seems to be free of risks and may be recommended. For monitoring purposes during prolonged operations not only filling pressures should serve as a guideline, determination of blood volume and fluid balance being imperative.


Emergent properties and trends of a new class of carbon nanocomposites: graphene nanoribbons encapsulated in a carbon nanotube.
Using density functional theory calculations, we show that recently synthesized carbon nanocomposites of graphene nanoribbons encapsulated in a carbon nanotube (GNR@CNT) possess rich emergent electronic and magnetic properties that offer new functionality and tunability and display systematic trends that are sensitive to the matchup of constitutive GNRs and CNTs. The encapsulation of H-passivated GNRs in metallic armchair CNTs always leads to a metallic complex while those in semiconducting zigzag CNTs can be either metallic or semiconducting depending on the chirality of GNRs. In particular, the complex of armchair GNRs in a zigzag CNT exhibits an oscillating electronic band gap with changing GNR width and a well-separated spatial distribution of electrons and holes localized in the CNT and GNR components, respectively. When bare large zigzag GNRs are encapsulated in an armchair CNT, the resulting complex shows strong structural stability and enhanced magnetism and, most interestingly, such GNR@CNT configurations can be tuned to be metallic or semiconducting depending on relative bond position and magnetic order. These results offer key insights for understanding and predicting emergent properties of GNR@CNT, which establish a roadmap for guiding design and synthesis of specific nanocomposite configurations with tailor-made properties for nanoelectronic, photovoltaic and spintronic applications.


Pathophysiology of rhinitis. 1. Assessment of the sources of protein in methacholine-induced nasal secretions.
Nasal provocation tests with normal saline and methacholine (MC) were performed in 25 atopic and 27 nonatopic subjects in an effort to assess the sources of protein in induced airway secretions. Nasal lavages obtained at baseline and after provocation were analyzed for albumin, total protein, secretory IgA (sIgA), and total IgA. Compared with baseline levels or saline provocation, MC provocation increased the secretion of albumin (p less than 0.025), total protein (p less than 0.001), sIgA (p less than 0.025), and total IgA (p less than 0.025), but did not significantly affect the relative proportions of albumin-to-total protein (albumin percent) or sIgA-to-total IgA (sIgA/total IgA ratio). Nasal pretreatment with atropine significantly inhibited MC-induced secretion of all 4 proteins, again without affecting the albumin percent or the sIgA/total IgA ratio. Because MC is known to stimulate atropine-inhibitable secretion of glandular products, these data suggest that sIgA and albumin may accompany glandular secretions. Immunohistochemical analyses of nasal turbinates confirmed that secretory component was found only on serous cells within submucous glands. Thus, it appears that cholinergic stimulation may regulate sIgA secretion and thereby participate in local nasal (and possibly respiratory tract) immunity.


Sequential deletion of all the polyketide synthase and nonribosomal peptide synthetase biosynthetic gene clusters and a 900-kb subtelomeric sequence of the linear chromosome of Streptomyces coelicolor.
Streptomyces coelicolor, with its 8 667 507-bp linear chromosome, is the genetically most studied Streptomyces species and is an excellent model for studying antibiotic production and cell differentiation. Here, we report construction of S. coelicolor derivatives containing sequential deletions of all the 10 polyketide synthase (PKS) and nonribosomal peptide synthetase (NRPS) biosynthetic gene clusters and a 900-kb subtelomeric sequence (total c. 1.22 Mb, 14% of the genome). No obvious differences in growth rates and sporulation of the strains were found. An artificially circularized S. coelicolor genome with deletions of total c. 1.6 Mb segments (840-kb for the left and 761-kb for the right arm of the linear chromosome) was obtained. The actinorhodin biosynthetic gene cluster could be overexpressed in some of the constructed strains.


Confining isolated chromophores for highly efficient blue phosphorescence.
High-efficiency blue phosphorescence emission is essential for organic optoelectronic applications. However, synthesizing heavy-atom-free organic systems having high triplet energy levels and suppressed non-radiative transitions-key requirements for efficient blue phosphorescence-has proved difficult. Here we demonstrate a simple chemical strategy for achieving high-performance blue phosphors, based on confining isolated chromophores in ionic crystals. Formation of high-density ionic bonds between the cations of ionic crystals and the carboxylic acid groups of the chromophores leads to a segregated molecular arrangement with negligible inter-chromophore interactions. We show that tunable phosphorescence from blue to deep blue with a maximum phosphorescence efficiency of 96.5% can be achieved by varying the charged chromophores and their counterions. Moreover, these phosphorescent materials enable rapid, high-throughput data encryption, fingerprint identification and afterglow display. This work will facilitate the design of high-efficiency blue organic phosphors and extend the domain of organic phosphorescence to new applications.


Comparison of inertial records during anticipatory postural adjustments obtained with devices of different masses.
Step initiation involves anticipatory postural adjustments (APAs) that can be measured using inertial measurement units (IMUs) such as accelerometers. However, previous research has shown heterogeneity in terms of the population studied, sensors used, and methods employed. Validity against gold standard measurements was only found in some studies, and the weight of the sensors varied from 10 to 110 g. The weight of the device is a crucial factor to consider when assessing APAs, as APAs exhibit significantly lower magnitudes and are characterized by discrete oscillations in acceleration paths. This study aims to validate the performance of a commercially available ultra-light sensor weighing only 5.6 g compared to a 168-g smartphone for measuring APAs during step initiation, using a video capture kinematics system as the gold standard. The hypothesis is that APA oscillation measurements obtained with the ultra-light sensor will exhibit greater similarity to those acquired using video capture than those obtained using a smartphone. Twenty subjects were evaluated using a commercial lightweight MetaMotionC accelerometer, a smartphone and a system of cameras-kinematics with a reflective marker on lumbar vertebrae. The subjects initiated 10 trials of gait after a randomized command from the experimenter and APA variables were extracted: APAonset, APAamp, PEAKtime. A repeated measures ANOVA with post-hoc test analyzed the effect of device on APA measurements. Bland-Altman plots were used to evaluate agreement between MetaMotionC, smartphone, and kinematics measurements. Pearson's correlation coefficients were used to assess device correlation. Percentage error was calculated for each inertial sensor against kinematics. A paired Student's t-test compared th devices percentage error. The study found no significant difference in temporal variables APAonset and PEAKtime between MetaMotionC, smartphone, and kinematic instruments, but a significant difference for variable APAamp, with MetaMotionC yielding smaller measurements. The MetaMotionC had a near-perfect correlation with kinematic data in APAonset and APAamp, while the smartphone had a very large correlation in APAamp and a near-perfect correlation in APAonset and PEAKtime. Bland-Altman plots showed non-significant bias between smartphone and kinematics for all variables, while there was a significant bias between MetaMotionC and kinematics for APAamp. The percentage of relative error was not significantly different between the smartphone and MetaMotionC. The temporal analysis can be assessed using ultralight sensors and smartphones, as MetaMotionC and smartphone-based measurements have been found to be valid compared to kinematics. However, caution should be exercised when using ultralight sensors for amplitude measurements, as additional research is necessary to determine their effectiveness in this regard.


Light microscopical and fluorescence histochemical observations on the endocrinological activity of human pulmonary neoplasia.
Light microscopical histochemical methods known to demonstrate the hormone storage granules of the hypophyseal ACTH/MSH cells were applied to study 14 oat cell carcinomas of human lung with special reference to assessment of the applicability of these techniques in the detection of the reported endocrinological activity of these tumors. Lead-hematoxylin, masked metachromasia and PAS reactions gave negative results for hormone storage granules in all cases studied. Argyrophilic granules were found in two tumors. The above methods, thus, were interpreted to be far too insensitive to be applicable for the demonstration of endocrinological activity. Fluorescence histochemical demonstration of the NH2-terminal tryptophyl-peptides, shown to be present in the hormone storage granules of the hypophyseal ACTH/MSH cells, yeilded positive results in three of the five studied cases. Two of these positive cases were found to have a pronounced adrenal hyperplasia. Conclusion was drawn that the used fluorescence histochemical technique for the demonstration of the NH2-terminal tryptophyl-peptides might offer new possibilities in the diagnosis of obscure human lung tumors, and it might be a valuable aid in the demonstration of the endocrinological activity in general.


[In vivo siRNA delivery to tumor cells and its application to cancer gene therapy].
RNA interference (RNAi) is a posttranscriptional gene-silencing event in which short double-stranded RNA (siRNA) degrades target mRNA. Because of its potent and highly specific gene-silencing effect, RNAi is expected to be used in the treatment of various diseases. Cancer is one of the major targets of RNAi-based therapy, because silencing oncogenes or other genes contributing to tumor progression can be target genes for RNAi. The delivery of RNAi effector to target cells is one of the key factors determining therapeutic efficacy, because gene silencing is limited to cells reached by RNAi effectors. Tumor cell lines stably expressing reporter genes were confirmed to be effective in sensitively and quantitatively evaluating RNAi effects in tumor cells in vitro and in vivo. Quantitative analyses of the gene-silencing effect revealed that short-hairpin RNA expressing plasmid DNA (pshRNA) has more durable effects than siRNA. Intratumoral injection of RNAi effectors was effective in suppressing target gene expression in tumor cells, and silencing of beta-catenin or hypoxia-inducible factor-1alpha (HIF-1alpha) significantly inhibited tumor growth. RNAi effectors were successfully delivered to tumor cells colonizing the liver through the vascular route. We found that tumor-bearing liver showed elevated HIF-1alpha expression in the cells, and the silencing of the expression in normal liver cells is also effective in inhibiting metastatic tumor growth. These results indicate the possibility of RNAi-based cancer therapy.


Biochemical markers of bone turnover associated with calcium supplementation in children with juvenile rheumatoid arthritis: results of a double-blind, placebo-controlled intervention trial.
To determine the effects of calcium supplementation on bone physiology in corticosteroid-free children with juvenile rheumatoid arthritis (JRA) by measuring serum and urinary bone-related hormones, minerals, and markers of bone formation and resorption. In this double-blind trial, patients were randomized to receive daily oral supplementation with 1,000 mg of calcium and 400 IU of vitamin D or with placebo and 400 IU of vitamin D for 24 months. The effect of calcium supplementation on bone physiology was determined periodically using markers of bone turnover. One hundred ninety-eight patients met the inclusion criteria and were followed up in the study. At baseline, there were no differences in markers of bone turnover between the groups. Patients with < or = 4 joints with active disease had higher serum levels of calcium and parathyroid hormone (PTH). Calcium-treated patients with < or =4 joints with active disease had lower levels of osteocalcin (OC). At followup, levels of 1,25-dihydroxyvitamin D3, PTH, OC, and urine phosphorus were lower in the group receiving calcium supplementation. Hypercalciuria, as determined by the urinary calcium-to-creatinine ratio, was not noted in 24-hour urine studies. Levels of markers of bone physiology were significantly decreased in children with JRA receiving calcium supplementation. The physiologic changes were noted as early as 12 months into calcium supplementation. The hypercalciuria noted on spot testing of the urinary calcium-to-creatinine ratio was not demonstrated on further evaluation, nor did it lead to renal pathology. These findings suggest that the calcium supplementation met physiologic needs and caused an increased calcium loss in urine.


Ku86 modulates DNA topoisomerase I-mediated radiosensitization, but not cytotoxicity, in mammalian cells.
Ku86 is an integral component of the nonhomologous end-joining (NHEJ) pathway of cellular double-strand break repair. In the current study, we investigated the role of Ku86 in DNA topoisomerase I-mediated radiosensitization induced by camptothecin in mammalian cells. Interestingly, as examined by clonogenic survival assay, a 30-minute camptothecin treatment induced significantly higher levels of radiosensitization in the Ku86-deficient Chinese hamster ovary xrs-6 cells than in the hamster Ku86-complemented xrs-6+hamKu86 cells, albeit exhibiting similar drug toxicity in these two cell lines. To confirm these findings, similar studies were conducted in two pairs of transfectant sublines established from the Ku86-deficient Chinese hamster lung fibroblast XR-V15B cells. Compared with the vector-alone sublines, radiation resistance was restored in the human Ku86-complemented sublines without alteration of cell cycle distributions. Again, significantly higher levels of camptothecin-induced radiosensitization were observed in the vector-alone sublines than in the Ku86-complemented XR-V15B sublines. In contrast, camptothecin treatments, ranging from 0.5 to 24 hours, induced similar cytotoxicities in both vector-alone and Ku86-complemented sublines. Because neither the DNA-damaging etoposide and cisplatin nor the tubulin-binder vinblastine induced enhanced levels of radiosensitization in the Ku86-deficient cells, Ku86 seems to uniquely affect topoisomerase I-mediated radiosensitization induced by camptothecin. Furthermore, cotreatment with DNA replication inhibitor aphidicolin abolished both camptothecin-induced cytotoxicity and radiosensitization in the vector-alone, as well as the Ku86-complemented subline cells, indicating both events are initiated by replication-dependent topoisomerase I-mediated DNA damages. Taken together, our data show a novel role of Ku86 in modulating topoisomerase I-mediated radiosensitization, but not cytotoxicity, in mammalian cells.


Concentration of pig slurry by evaporation: anaerobic digestion as the key process.
Nutrient redistribution between areas with a structural pig slurry surplus and those with a shortage, is limited by the high cost of transportation and spreading, due to the high water content in slurry (more than 90%) and its relative low nutrient concentration. Water can be removed from slurry by evaporation, through the application of waste heat from a power plant or from other processes. Apart from obtaining a concentrate with an obviously higher nutrient concentration than the original slurry, another objective is to obtain clean water as condensate. The objective of this work was to study the batch vacuum evaporation of pig slurry liquid fraction, to evaluate the economic feasibility and to evaluate condensate quality as a function of both pH (4, 5 and 6) and pig slurry type (fresh slurry and anaerobically digested slurry). Results showed that condensate characteristics (ammonia nitrogen, VFA, COD) were strongly dependent on these variables. Previous anaerobic digestion presented clear advantages: it provided a fraction of the required energy and it removed organic matter, preventing its volatilisation in the evaporation process and providing higher quality condensates. These advantages make the combined treatment strategy economically more feasible than the evaporation process alone.


Vaginal and cervical atresia in a cynomolgus macaque.
A female cynomolgus monkey presented clinically with a caudal abdominal mass noted on a prestudy physical examination. No other clinical abnormalities were noted. An ultrasound examination revealed a mass approximately 2 cm in diameter, which contained fluid with a granular "free-floating" appearance. Within a month the mass enlarged and was visible from external examination. Exploratory laparotomy revealed a mass encompassing the uterus, both ovaries, bladder, and rectum. The animal was euthanized under anesthesia, and the mass was removed, examined, and submitted for histopathology. A diagnosis of vaginal and cervical atresia was made. To the author's knowledge, this is the first description of vaginal and cervical atresia in a laboratory nonhuman primate.


Human neutrophil elastase in temporal (giant cell) arteritis: plasma and immunohistochemical studies.
Few enzymes are able to attack the internal elastic lamina, which is destroyed in temporal arteritis (TA). Because human neutrophil elastase (HNE) is one of these, its role in the pathogenesis of TA was examined in patients undergoing temporal artery biopsy for suspected TA. Over a 6 month period, 33 patients undergoing temporal artery biopsy were prospectively included in the study. TA was diagnosed in 15 patients; 9 of them had positive temporal artery biopsy. The other 18 patients made up the non-TA group. Nineteen healthy age matched subjects (mean age 74 +/- 9 yrs) served as controls. Levels of plasma HNE bound to alpha1-antitrypsin (pHNE-alpha1AT) were measured by ELISA. The presence of HNE in the temporal artery wall of 7 TA and 7 non-TA patients was evaluated immunohistochemically. Age, neutrophil counts, and erythrocyte sedimentation rates were similar in TA and non-TA patients. The mean pHNE-alpha1AT concentration in the TA group (84 +/- 20 microg/l) was significantly higher (p < 0.001) than in the non-TA group (51 +/- 26 microg/l) or in healthy controls (52 +/- 23 microg/l). The diagnostic sensitivity of pHNE-alpha1AT > 50 microg/l was 100%. Immunohistochemistry detected no HNE within the temporal artery wall of any patient. High levels of pHNE-alpha1AT were associated with TA. Our preliminary results indicate this could be a diagnostic marker for TA. Further studies are needed to confirm its reliability. Because HNE was not detected locally, no conclusions can be drawn as to its pathogenic role in TA.


Percutaneous Coil Embolization for the Treatment of a Giant Brachial Artery Pseudoaneurym in a Child.
Brachial artery pseudoaneurysm is a rare phenomenon. When a diagnosis of brachial artery pseudoaneurysm is established, early and appropriate treatment should be performed as soon as possible to prevent possible complications, such as hemorrhage, rupture, and upper limb and finger losses. Open surgical repair is usually the cornerstone of treatment; however, we here report a case of giant brachial pseudoaneurysm in a 2-year-old girl, which was successfully treated with percutaneous coil embolization.


Correlations of vascular architecture and angiogenesis with pituitary adenoma histotype.
Vascular endothelial growth factor (VEGF) is a potent angiogenic factor in solid tumors. However, its role in angiogenesis in pituitary adenoma is controversial. Angiogenesis in solid tumors including pituitary adenoma is commonly evaluated by microvascular density (MVD). Here, we evaluated MVD and the role of VEGF in vascular architecture in 51 pituitary adenomas (24 nonfunctioning, 13 prolactin-secreting, 10 growth hormone-secreting, 3 adrenocorticotropic hormone-secreting, and 1 thyroid-stimulating hormone-secreting). Paraffin sections were stained with CD34 and VEGF. MVD and vascular architecture parameters (vessel area, diameter, perimeter, and roundness) were evaluated in CD34-stained sections. Immunohistochemistry showed 27/51 tumors (53%) were VEGF-positive. There were no significant differences in MVD, any vascular parameter, or adenoma volume between VEGF-positive and VEGF-negative tumors. VEGF mRNA expression was significantly higher in VEGF-positive tumors. There were no significant correlations between VEGF mRNA expression and MVD or vascular parameters. However, vessel diameter and perimeter were significantly larger in prolactin-secreting than nonfunctioning and growth hormone-secreting macroadenomas. The difference in vessel diameter was observed among both VEGF-positive and all adenomas (micro- and macroadenoma). Thus, VEGF may have limited roles in the development of vascular architecture and tumor angiogenesis in pituitary adenomas, but the differences in vessel architecture by histotype (i.e., larger vessel diameter and perimeter in prolactin-secreting adenomas) suggest the hormonal regulation of vessel architecture rather than angiogenesis.


Regulatory systemic effect of postsurgical polychromatic light (480-3400 nm) irradiation of breast cancer patients on the proliferation of tumor and normal cells in vitro.
The aim of this work was to study the effect of phototherapy (PT) with percutaneous exposures to polychromatic visible and IR light (pVIS + pIR) on breast cancer (BC) patients at the early postmastectomy period, on the growth-promoting (GP) properties of their blood serum, by evaluating its capability to support proliferation of normal and tumor human cells in vitro. After mastectomy, one group of patients was treated daily for 1 week on the sacral area with pVIS + pIR light (480-3400 nm, 40 mW/cm(2), 95% polarization, 24 J/cm(2)). The second group used as a control was sham irradiated. Blood serum samples collected before surgery, and 1 and 8 days after surgery, were added (2.5%) into nutrition media for cells instead of 10% of fetal calf serum. Cell targets were cultures of human fibroblasts (FBs), keratinocytes (KCs), three lines of the human BC cells (BT-474, HBL-100, Hs 578T) and cells of human epidermoid carcinoma (A-431). Cell number was evaluated by staining cell nuclei with crystal violet and a spectrometric assay of the extracted dye. The day after mastectomy there were no significant changes in the GP activity of sera. After a 7-day PT course, an increase of this activity was recorded for normal FBs and KCs by 18% and 24%, respectively, in comparison with presurgical levels. GP activity of the same patients' sera for all tumor cells, BT-474, HBL-100, Hs 578T and A-431, decreased by 32%, 17%, 11%, and 7% respectively. As a result, enhancement of proliferation of KCs and FBs and inhibition of proliferation of tumor cells was seen. The results suggest an effect at the systemic level where pVIS + pIR light may stimulate growth of human skin cells and simultaneously downregulate the proliferation of tumor cells, including BC cells. This argues in favor of the oncological safety of PT for BC patients postsurgically.


Going beyond exposure to local news media: an information-processing examination of public perceptions of food safety.
The relationship between local news media and public perceptions of food safety was examined in a statewide telephone survey (n = 524). The theoretical framework of the study was based on a review of the social and psychological factors that affect public concerns about food safety, the relationship between mass communication and risk perception, and the thesis of information-processing strategies and its impact on learning from the news. The results show that information-processing strategies substantially mediated the relationship between local news media and public perceptions of food safety, with elaborative processing being more influential than active reflection in people's learning from the news media. Attention to local television had an independent effect, after demographics, awareness of food safety problems, and perceived safety of local food supply were statistically controlled. Other important predictors included gender, education, ethnicity, and perceived safety of local food supply.


New druggable targets in the Ras pathway?
Ras proteins are key elements in the regulation of cellular proliferation, differentiation and survival. Mutational activation of Ras or of components of its effector pathways are detected in one-third of human cancers and are essential for the genesis and maintenance of the tumoral phenotype. Research efforts have been dedicated to the development of therapeutic agents that inhibit aberrant Ras signals and, subsequently, tumor progression. However, many of these initiatives have proven less successful than expected. This review summarizes the current status of developments in Ras research, the challenges that have arisen during preclinical and clinical stages, and how novel approaches to targeting Ras pathways have introduced new strategies toward the development of antitumoral agents that are alternative or complementary to those currently in use. These new approaches would be aimed at disrupting key protein-protein interactions that are essential for the conveyance of Ras aberrant signals or would be directed against new proteins recently demonstrated to be critical participants in Ras-regulated pathways.


Association between Obstructive Sleep Apnea and Intracranial Artery Calcification Stratified by Gender and Body Mass Index: A Hospital-Based Observational Study.
Background and Objectives Obstructive sleep apnea (OSA) is an independent risk factor for stroke. Furthermore, intracranial arterial calcification (IAC) has been validated as a marker for subclinical cerebrovascular disease. However, the relationship between OSA with IAC was less studied compared with its established association with coronary artery calcification (CAC). In this study, we aimed to investigate the association between the severity of OSA and the degree of IAC in hospitalized patients without pre-existing cardiovascular disease. Methods This hospital-based observational study was conducted from June 1, 2017, to May 1, 2019. In total, 901 consecutive patients who underwent head computed tomography (CT) scans and portable sleep monitoring were included. Based on the apnea-hypopnea index (AHI), patients were divided into four OSA severity groups (normal: AHI <5/h; mild: 5≤ AHI <15/h; moderate: 15≤ AHI <30/h; severe: AHI ≥30/h). Associations of OSA with IAC scores were assessed by using multivariate logistic regression analysis. Results Of the 901 patients, 484 (53.7%) were men; the mean (SD) age was 66.1 (10.0) years. The non-OSA group included 207 (23.0%) patients; mild OSA, 209 (23.2%); moderate OSA, 235 (26.1%); and severe OSA, 169 (18.8%). Mean IAC scores were higher in the severe OSA group compared with non, mild, and moderate OSA groups (4.79 vs. 2.58; 4.79 vs. 2.94; 4.79 vs. 3.39, p<0.001). Multivariate analysis adjusted for confounding factors revealed that only severe OSA was associated with a higher IAC score (odds ratio [OR] 1.65; 95% confidence interval [CI], 1.43-1.91; p<0.001). In stratified analyses by BMI, among participants with a BMI <25kg/m2, the positive association between AHI values and IAC scores was found in the moderate OSA group (OR, 1.23; 95% CI 1.05, 1.43, p=0.01) and severe OSA group (OR, 1.96; 95% CI 1.55, 2.48, p<0.001). When stratified by gender, in women, the positive association was found in moderate OSA group (adjusted OR=1.21, 95% CI: 1.02-1.51, p=0.016) and severe OSA group (adjusted OR=1.76, 95% CI: 1.36-2.25, p<0.001). For the men group, a positive association between IAC scores and AHI was only observed in the severe OSA group. Discussion These findings suggest that OSA, in particular severe OSA (AHI ≥ 30), is independently associated with higher IAC scores. Women and no-obesity individuals appeared more susceptible to adverse OSA-related subclinical cerebrovascular disease as measured by IAC scores.


Nonmosaic Trisomy 19p13.3p13.2 Resulting from a Rare Unbalanced t(Y;19)(q12;p13.2) Translocation in a Patient with Pachygyria and Polymicrogyria.
Nonmosaic trisomy involving 19p13.3p13.2 is a very uncommon abnormality. At present, only 12 cases with this genetic condition have been reported in the literature. However, the size of the trisomic fragment is heterogeneous and thus, the clinical spectrum is variable. Herein, we report the clinical and cytogenetic characterization of a 5-year-old boy with nonmosaic trisomy 19p13.3p13.2 (7.38 Mb), generated by a derivative Y chromosome resulting from a de novo unbalanced translocation t(Y;19)(q12;p13.2). We demonstrated the integrity of the euchromatic regions in the abnormal Y chromosome to confirm the pure trisomy 19p. Our patient shares some clinical features described in other reported patients with pure trisomy 19p, such as craniofacial anomalies, developmental delay, and heart defects. Different to previous reports, our case exhibits frontal pachygyria and polymicrogyria. These additional features contribute to further delineate the clinical spectrum of trisomy 19p13.3p13.2.


The genetic architecture of water-soluble protein content and its genetic relationship to total protein content in soybean.
Water-soluble protein content (WSPC) is a critical factor in both soybean protein quality and functionality. However, the underlying genetic determinants are unclear. Here, we used 219 soybean accessions and 152 recombinant inbred lines genotyped with high-density markers and phenotyped in multi-environments to dissect the genetic architectures of WSPC and protein content (PC) using single- and multi-locus genome-wide association studies. In the result, a total of 32 significant loci, including 10 novel loci, significantly associated with WSPC and PC across multi-environments were identified, which were subsequently validated by linkage mapping. Among these loci, only four exhibited pleiotropic effects for PC and WSPC, explaining the low correlation coefficient between the two traits. The largest-effect WSPC-specific loci, GqWSPC8, was stably identified across all six environments and tagged to a linkage disequilibrium block comprising two promising candidate genes AAP8 and 2 S albumin, which might contribute to the high level of WSPC in some soybean varieties. In addition, two genes, Glyma.13G123500 and Glyma.13G194400 with relatively high expression levels at seed development stage compared with other tissues were regarded as promising candidates associated with the PC and WSPC, respectively. Our results provide new insights into the genetic basis of WSPC affecting soybean protein quality and yield.


Case Report: Systemic lupus erythematous associated with thrombotic thrombocytopenic purpura, a diagnostic challenge.
Thrombotic thrombocytopenic purpura (TTP) is an uncommon microangiopathic disease and sometimes is associated with systemic lupus erythematous (SLE). However, this probable causal relationship has not been completely proven. The diagnostic differentiation of both diseases is difficult in the first instance because they share similar characteristics that may overlap. We present a case of a 32-year-old woman with antecedents of epileptic seizures since she was 12 years old. The patient was admitted to the emergency room with a clinical picture of headaches, fever, paleness in the skin and mucosa, confused state, paresthesia, and transient spasticity of the extremities. The laboratory results revealed direct Coombs negative hemolytic anemia, severe thrombocytopenia, significant elevation of lactate dehydrogenase, and presence of schistocytes ++ in the peripheral film. In addition, positive antinuclear antibodies and positive anti-native DNA in titers of 1/320 and 1/160, respectively, were found. Urinalysis showed that serum creatinine was in normal range. Because of limited hospital resources, ADAMTS13 was not evaluated. However, based on clinical, hematological, and biochemical findings, we concluded that it was a case of TTP associated with SLE and indicated treatment with plasmapheresis and methylprednisolone pulses, obtaining a satisfactory response (normalization of biomarker levels, health condition) after the second session of plasmapheresis. Diagnosis of both SLE and TTP is often difficult to achieve; however, adequate correlation of clinical manifestations and laboratory tests, along with the help of partial therapeutic interventions, may lead to good clinical response.


Reconstruction of delayed scleral flap melting with bovine pericardium after trabeculectomy with mitomycin C.
Aim: To present a challenging case of hypotony after trabeculectomy and its treatment. Case description: A 22-year-old woman with juvenile glaucoma underwent a conventional trabeculectomy with mitomycin C on the right eye (OD). In the immediate postoperative period, we observed a hyperfiltration bleb with hypotony refractory to conservative measures leading to hypotony maculopathy. A surgical revision with scleral flap resuture and conjunctival graft was performed with a satisfactory result and resolution of hypotony maculopathy. After two years, the patient complained of low visual acuity (VA) of the OD. During examination, we observed a fine and avascular bleb with Seidel and visualization of the underlying uveal tissue, an intraocular pressure (IOP) of 5 mmHg, and chorioretinal folds. A new revision of the trabeculectomy was performed. During the procedure, it was not possible to identify the scleral flap, so the fistula was closed with a patch of collagenous membrane derived from bovine pericardium (Tutopatch® graft). A good clinical evolution occurred. After 2 months, IOP was 15 mmHg without Seidel or changes in the fundus and VA was 20/20. After 8 months of follow-up, the IOP remains stable without further complaints. Conclusion: This case illustrates the difficulties faced in the management of a common complication of trabeculectomy and highlights some of the options available for its treatment. There are few reports of scleral melting after trabeculectomy. However, trauma and scleral necrosis associated with mitomycin are listed as the main causes. The use of a scleral patch derived from bovine pericardium allows effective suturing and closure of the aqueous leak.


Viewing oxidative stress through the lens of oxidative signalling rather than damage.
Concepts of the roles of reactive oxygen species (ROS) in plants and animals have shifted in recent years from focusing on oxidative damage effects to the current view of ROS as universal signalling metabolites. Rather than having two opposing activities, i.e. damage and signalling, the emerging concept is that all types of oxidative modification/damage are involved in signalling, not least in the induction of repair processes. Examining the multifaceted roles of ROS as crucial cellular signals, we highlight as an example the loss of photosystem II function called photoinhibition, where photoprotection has classically been conflated with oxidative damage.


Quantal density functional theory of the hydrogen molecule.
In this paper we perform a quantal density functional theory (Q-DFT) study of the hydrogen molecule in its ground state. In common with traditional Kohn-Sham density functional theory, Q-DFT transforms the interacting system as described by Schrodinger theory, to one of noninteracting fermions--the S system--such that the equivalent density, total energy, and ionization potential are obtained. The Q-DFT description of the S system is in terms of "classical" fields and their quantal sources that are quantum-mechanical expectations of Hermitian operators taken with respect to the interacting and S system wave functions. The sources, and hence the fields, are separately representative of all the many-body effects the S system must account for, viz. electron correlations due to the Pauli exclusion principle, Coulomb repulsion, and correlation-kinetic effects. The local electron-interaction potential energy of each model fermion is the work done to move it in the force of a conservative effective field that is the sum of the individual fields. The Hartree, Pauli, Coulomb, and correlation-kinetic energy components of the total energy are also expressed in virial form in terms of the corresponding fields. The highest occupied eigenvalue of the S system is the negative of the ionization potential energy. The Q-DFT analysis of the hydrogen molecule is performed employing the highly accurate correlated wave function of Kolos and Roothaan.


A Case of Prostatic Metastasis from Intrahepatic Cholangiocarcinoma: An Extremely Rare Event.
The second most frequent primary carcinoma of the liver to emerge is intrahepatic cholangiocarcinoma (ICC), which is thought to be an incurable, rapidly proliferating tumor with a dismal prognosis. ICC is typically found at an advanced stage and is physiologically hostile. Regional lymph nodes and liver metastases are frequent tumor metastatic sites for ICC and serve as indicators of tumor recurrence. ICC metastasizing to the male urogenital tract has only seldom been documented. Typically, lymph vessels serve as the primary pathway for disseminating tumor cells. The high fatality rate associated with ICC and the rapid spread of the disease may be caused by this lymphatic route. The only curative therapeutic approach for treating these tumors is surgical removal. We report a case of prostatic metastasis from ICC.


[Comparison of activity of fosfomycin, oxacillin and penicillin G against staphylococci and micrococci (author's transl)].
The in vitro sensitivity against fosfomycin, oxacillin and penicillin G was tested in 65 Staphylococcus aureus strains, 71 coagulase negative staphylococci and 46 micrococci. Fosfomycin was very effective against staphylococci. Cross resistance with simultaneously tested penicillins could not be demonstrated. Fosfomycin was only partially effective against micrococci for which penicillin G was most effective.


Phosphatidylglycerol is implicated in divisome formation and metabolic processes of cyanobacteria.
Phosphatidylglycerol is an essential phospholipid for photosynthesis and other cellular processes. We investigated the role of phosphatidylglycerol in cell division and metabolism in a phophatidylglycerol-auxotrophic strain of Synechococcus PCC7942. Here we show that phosphatidylglycerol is essential for the photosynthetic electron transfer and for the oligomerisation of the photosynthetic complexes, notably, we revealed that this lipid is important for non-linear electron transport. Furthermore, we demonstrate that phosphatidylglycerol starvation elevated the expressions of proteins of nitrogen and carbon metabolism. Moreover, we show that phosphatidylglycerol-deficient cells changed the morphology, became elongated, the FtsZ ring did not assemble correctly, and subsequently the division was hindered. However, supplementation with phosphatidylglycerol restored the ring-like structure at the mid-cell region and the normal cell size, demonstrating the phosphatidylglycerol is needed for normal septum formation. Taken together, central roles of phosphatidylglycerol were revealed; it is implicated in the photosynthetic activity, the metabolism and the fission of bacteria.


[Is resistance to antibiotics changing? Development of resistance of Enterobactericeae from specimens 1977-1980].
The results of sensitivity testing from the last 4 years of the enterobacteria isolates have been evaluated for ampicillin, cephalothin, gentamicin, and trimethoprim-sulfamethoxazole. There was a remarkable decrease of cephalothin resistant E. coli, proteus mirabilis, and klebsiella strains. The number of strains resistant to ampicillin was only decreased in the case of proteins mirabilis. The resistance frequency to gentamicin was unchanged. In contrast, an increasing number of resistant strains of E. coli and proteins mirabilis was observed with regard to trimethoprim-sulfamethoxazole.


A kiosk survey of perception, attitudes and knowledge (PAK) of Australians concerning microbes, antibiotics, probiotics and hygiene.
To obtain a baseline of public perception, attitudes and knowledge (PAK) of Australians about microbes, antibiotics and hygiene like hand washing and use of probiotics. Using a kiosk-based survey method at the American Museum of Natural History (AMNH), we remotely assayed PAK of Australians through their interaction with the kiosk. The surveys we used had five and seven multiple answer questions and were analysed using standard comparative approaches. We also made comparisons based on gender and on age group for many of the questions. Our analyses indicate that there is a lack of general understanding of the role of microbes in everyday life among Australians. In addition, we detected some basic misunderstandings about antibiotics. While 80% of the respondents identified penicillin as an antibiotic, up to 30% of the respondents wrongly identified aspirin, Tylenol, valium and Benadryl as antibiotics. We also detected a general lack of knowledge about hand washing hygiene and probiotic use. Our results from around 700 Australian respondents can serve as a baseline for further PAK assessment of Australians. PAK of Australians with respect to microbes and hand washing hygiene is poor therefore public education is needed. This study should stimulate a better roadmap for public education about microbes, antibiotics, probiotics and hygiene. SO WHAT?: With the recent spread of SARS-Cov2 and the ensuing Covid19 pandemic and the continuing rise in antimicrobial resistance, the need for assessment PAK of microbes and infectious disease has become acute.


Psychological problems of aging.
The increasing number of older persons in the United States is having far-reaching economic, social, political and psychological effects. Patients over 60 make up more than a fourth of current admissions to California's state mental hospitals. Biological, personal, cultural and economic problems are present in each elderly person and must be considered in the treatment of such individuals. Neurotic reactions are much more frequent that the psychoses, and these may be treated by the same therapeutic tools utilized with younger persons. Not all the psychoses in the aged group are such as to necessitate mental hospital care. Many of the patients could be cared for in suitable nursing homes. An adequate mental hygiene program, maintenance of physical health, opportunities for work, and the development of hobby and recreation centers may help ward off many of the difficult problems that the aged now present.


Episodic dyscontrol: a controlled replication.
The authors describe previous research in which the syndrome of episodic dyscontrol is delineated and a majority of patients treated successfully with diphenyldantoin (Dilantin). This original research was uncontrolled because of an ethical dilemma: to withhold active treatment for violent outbursts might result in damage to people or property. The present study undertakes a controlled replication of this original research employing sequential analysis in a double blind discontinuation trial such that no patient was denied active treatment any longer than absolutely necessary. Results indicate a clear superiority for Dilantin over placebo when both were added to a psychotherapeutic treatment regimen for violent behavior. Conclusions based on these results are discussed and suggestions for future research offered.


Surgical site infection in elderly patients with hip fractures, silver-coated versus regular dressings: a randomised prospective trial.
Surgical site infection (SSI) after hip fracture surgery is a well-known complication with serious consequences for both the patient and the medical system. Silver ion treatment is considered an effective antibacterial agent, however, the use of silver dressing (SD) in the primary prevention of SSIs is controversial. The aims of this study were to compare SD with regular dressing (RD) in the prevention of SSI in elderly patients undergoing surgery for hip fractures, and to compare costs. A matched group of 55 patients with hip fractures undergoing surgery with dynamic hip screw, cephalomedullary nail or hemiarthroplasty were randomised to either SD or RD groups. The dressings were applied in the operating theatre, and the patients were followed for one week for clinical signs of infection (discharge, erythema and fever). The RDs were replaced daily. The SDs were not removed for 5-7 days and kept moist. Skin swabs were taken from the wound surface on postoperative day 5-7 for bacterial skin colonisation. The SD (n=31) and RD (n=24) groups were similar in age, sex and comorbidities. Infection signs were seen in two (2/31, 6.4%) of the SD patients compared with 2 (2/24, 8.3%) RD patients (p=1.0). Skin colonisation by bacteria at postoperative day 5-7 was tested in 27 patients: it was higher in the SD group (positive skin swab, 12/19, 63.2%) compared to the RD group (4/8, 50%, p=0.67). The use of SD added ~US$5 (UK ~£3.19) per patient. The use of SD was associated with higher costs than RD, but not superior in preventing SSIs in elderly patients undergoing hemiarthroplasty or fixation of hip fractures. SD was also not effective in reducing bacterial skin colonisation following hip fracture and surgery.


Lumbar laminectomy alone or with instrumented or noninstrumented arthrodesis in degenerative lumbar spinal stenosis. Patient selection, costs, and surgical outcomes.
A prospective, multicenter observational study. 1) Identify correlates of the decision to perform arthrodesis in patients undergoing laminectomy for lumbar spinal stenosis. 2) Compare symptoms, walking capacity, and satisfaction 6 and 24 months after laminectomy alone and laminectomy with noninstrumented and with instrumented arthrodesis. Few prospective studies have compared outcomes of laminectomy alone or laminectomy with noninstrumented or with instrumented arthrodesis in patients with degenerative lumbar spinal stenosis. There is uncertainty regarding the optimal use of arthrodesis and instrumentation. Two hundred seventy--two patients undergoing--surgery for degenerative lumbar stenosis by eight surgeons at four centers were included in the study cohort. Of these, 37 had noninstrumented and 41 had instrumented arthrodesis. Logistic regression identified factors associated with arthrodesis. The principal outcomes-health status, walking capacity, back and leg pain, and satisfaction with surgery-were assessed 6 and 24 months postoperatively with univariate and multivariate techniques. Outcomes also were assessed in a restricted cohort of patients with at least 5 mm spondylolisthesis and/or 15 degrees scoliosis. Hospital costs were obtained from a computerized hospital cost accounting system. The major predictor of the decision to perform arthrodesis was the individual surgeon (P = 0.0001). Noninstrumented arthrodesis was associated with superior relief of low back pain at 6 months (P = 0.004) and 24 months (P = 0.01). This difference persisted in multivariate analyses, with borderline statistical significance. There were no significant differences in the other outcomes across treatment groups. Mean hospital costs of laminectomy alone and noninstrumented and instrumented arthrodesis were $12,615, $18,495, and $25,914, respectively (P = 0.0001). Findings were limited by the small number of participating surgeons, modest sample size that produced P values of borderline significance, and nonrandomized design. With these caveats in mind, the authors conclude: (1) The individual surgeon was a more important correlate of the decision to perform arthrodesis than clinical variables such as spondylolisthesis. (2) Noninstrumented arthrodesis resulted in superior relief of back pain after 6 and 24 months. (3) Instrumented arthrodesis was the most costly option. These results highlight the need for randomized controlled trials and cost effectiveness analyses of lumbar arthrodesis and instrumentation in patients with degenerative lumbar spinal stenosis.


Ultraviolet-B activates components of the systemin signaling pathway in Lycopersicon peruvianum suspension-cultured cells.
Among the early responses of Lycopersicon peruvianum suspension-cultured cells to the polypeptide wound signal systemin are the alkalinization of the culture medium and the activation of a 48-kDa mitogen-activated protein kinase (MAPK). Here, we report that both responses are induced in the cells by exposure to ultraviolet-B (UV-B) radiation. Suramin, an inhibitor of systemin receptor function, strongly inhibited the UV-B-induced medium alkalinization and MAPK activity. The UV-B response was also reduced when cells were initially treated with systemin or the systemin antagonist Ala-17-systemin, which competitively inhibits binding of systemin to the systemin receptor. Cells that were initially treated with either UV-B or systemin exhibited a strongly reduced response to a subsequent elicitation with systemin. The desensitization was transient, reaching a maximum at 30-60 min after the initial treatment. Several hours later, depending on the initial UV-B dose or systemin concentration, the cells regained their initial responsiveness. When cells were irradiated with low doses of UV-B and subsequently treated with systemin, the UV-B response reached levels higher than the response without UV-B treatment. The data provide evidence for an involvement of the systemin receptor and/or systemin-responsive signaling elements in the UV-B response.


Prognosis and conditional disease-free survival among patients with ovarian cancer.
Traditional disease-free survival (DFS) does not reflect changes in prognosis over time. Conditional DFS accounts for elapsed time since achieving remission and may provide more relevant prognostic information for patients and clinicians. This study aimed to estimate conditional DFS among patients with ovarian cancer and to evaluate the impact of patient characteristics. Patients were recruited as part of the Hormones and Ovarian Cancer Prediction case-control study and were included in the current study if they had achieved remission after a diagnosis of cancer of the ovary, fallopian tube, or peritoneum (N = 404). Demographic and lifestyle information was collected at enrollment; disease, treatment, and outcome information was abstracted from medical records. DFS was calculated using the Kaplan-Meier method. Conditional DFS estimates were computed using cumulative DFS estimates. Median DFS was 2.54 years (range, 0.03-9.96 years) and 3-year DFS was 48.2%. The probability of surviving an additional 3 years without recurrence, conditioned on having already survived 1, 2, 3, 4, and 5 years after remission, was 63.8%, 80.5%, 90.4%, 97.0%, and 97.7%, respectively. Initial differences in 3-year DFS at time of remission between age, stage, histology, and grade groups decreased over time. DFS estimates for patients with ovarian cancer improved dramatically over time, in particular among those with poorer initial prognoses. Conditional DFS is a more relevant measure of prognosis for patients with ovarian cancer who have already achieved a period of remission, and time elapsed since remission should be taken into account when making follow-up care decisions.


Auditory event-related brain potentials in children with specific language impairment.
Event-related brain potentials evoked by tone and speech stimuli were recorded in ten children with specific language impairment and a control group. The patient group showed prolonged P3 latencies in both tasks compared with the controls and smaller P3 amplitude in the speech task. There were no group differences concerning the N1-P2 components. The findings indicate that the children with language impairment showed signs of deficient late-stage auditory perceptual processing whereas the earlier sensory stages as indexed by the N1 were no different from the controls. The results are further discussed within the framework of context updating in working memory.


Using wavelet denoising and mathematical morphology in the segmentation technique applied to blood cells images.
Accurate image segmentation is used in medical diagnosis since this technique is a noninvasive pre-processing step for biomedical treatment. In this work we present an efficient segmentation method for medical image analysis. In particular, with this method blood cells can be segmented. For that, we combine the wavelet transform with morphological operations. Moreover, the wavelet thresholding technique is used to eliminate the noise and prepare the image for suitable segmentation. In wavelet denoising we determine the best wavelet that shows a segmentation with the largest area in the cell. We study different wavelet families and we conclude that the wavelet db1 is the best and it can serve for posterior works on blood pathologies. The proposed method generates goods results when it is applied on several images. Finally, the proposed algorithm made in MatLab environment is verified for a selected blood cells.


Analysis of Sera of Recipients with Allograft Rejection Indicates That Keratin 1 Is the Target of Anti-Endothelial Antibodies.
Anti-endothelial cell antibodies (AECAs) are usually directed against the surface antigens on the vascular endothelial cells. Clinical studies suggest a pathogenic role for nonhuman leukocyte antigen in antibody-mediated rejection; however, the antigens on the donor vascular endothelium that serve as the first-line targets for an immune response during allograft rejection have not been fully identified. Here, we used immunoprecipitation and mass spectrometry to identify antigens from the sera of kidney transplant recipients who were experiencing antibody-mediated rejection. Keratin 1 (KRT1) was identified as a novel antigenic target expressed on endothelial cells. To validate our finding, we produced recombinant proteins representing the three most common alleles of KRT1. The serum used for immunoprecipitation showed a strong reaction to KRT1 recombinants in western blot and ELISA. In the kidney transplant cohort, more AECA-positive recipients than AECA-negative recipients had KRT1 antibodies (32.2% versus 11.9%, p = 0.002). Sera from 255 renal recipients were tested by ELISA. Of the 77 recipients with deteriorating graft function (serum creatinine > 120 μmol/L), 23 had anti-KRT1 antibodies. KRT1-IgG positivity was, therefore, associated with a higher risk of kidney transplant rejection (29.9% (23/77) versus 16.9% (30/178), p = 0.0187). A better understanding of this antigenic target will improve long-term allograft survival.


Support not stigma needed.
Sam Foster, Chief Nurse, Oxford University Hospitals, reflects on how nurses' mental health problems are viewed by colleagues and responded to by the NHS and nursing's regulatory body.


Near-Infrared II Hemicyanine Dye with Large Stokes Shift Designed by TICT Regulation for Boosting Imaging-Guided Photothermal Therapy.
The serious threat that cancer poses to human health highlights the significance of early detection and effective treatment. The integration of fluorescence diagnosis and photothermal therapy in NIR-II has gained attention due to its high sensitivity, fast response, and noninvasiveness. Fluorescence, produced by the radiative relaxation process of electrons in a molecule, and photothermal, generated by the nonradiative relaxation process of electrons in a molecule, are competing photophysical processes. Hence, it is a challenge for the molecule to balance between the properties of fluorescence and photothermal. In this study, a NIR-II hemicyanine with TICT character is designed to obtain molecules with both better fluorescence and photothermal properties, utilizing positively charged pyridine salt and triphenylamine as electron acceptor and donor, respectively, and oxole as the conjugated π-bridge. HCY-995, one of the synthesized compounds, has a quantum yield of 0.09%, photothermal conversion efficiency of 54.90%, and a significant Stoke shift of 232 nm, which makes it appropriate for the integration of photothermal therapy and high-resolution imaging. This study provides new insights into the development of NIR-II molecules with fluorescent and photothermal integrated properties.


Spectral karyotyping of fresh, non-inseminated oocytes.
The object of this study was to determine the mechanisms producing aneuploidy in female meiosis I by analysing the whole chromosome complement of human non-inseminated and unfertilized fresh oocytes. For this purpose, 131 fresh oocytes were obtained from 16 oocyte donors (24-48 years old). These oocytes were fixed immediately after retrieval and 47 good quality metaphases from 13 donors were analysed by spectral karyotyping to identify all 23 chromosome types. The data was divided into two maternal age groups, 24-34 (n = 31) and > or = 35 years (n = 16). More non-disjunction (13 and 25%), unbalanced predivision (10 and 44%, P < 0.01) and balanced predivision (6 and 62%, P < 0.001) events were found in the older group of oocytes. There was an increase in balanced predivision with decreasing chromosome size (P < 0.001). The present results are the first obtained in fresh oocytes where all chromosomes were specifically identified, and support previous theories that predivision of chromatids is a major factor causing aneuploidy. Previous reports with inseminated, non-fertilized oocytes fixed > or = 24 h after retrieval suffered from artefactual predivision of chromatids triggered by in-vitro ageing of oocytes.


Dispersion of fibrin using cationic detergent.
By treating fibrin with cationic detergent in a medium containing 5M urea, a fibrincationic detergent complex was formed. The complex was soluble in distilled water, and was observed to be in a dispersed state by electron microscopy. The complex was precipitated and resolubilized in the presence of salt. This behavior of the complex was due to adsorption of the salt anions onto the complex. When an aqueous solution of the complex was incubated with fresh serum, the complex soon aggregated and then was converted into a firm clot which was not soluble in distilled water.