Appendiceal involvement as a skip lesion in ulcerative colitis.
Despite the frequency of ulcerative colitis (UC), and numerous studies related to this disease, controversy remains regarding its distribution patterns. It is generally believed that UC starts in the rectum and progresses proximally in continuity to involve cecum along with appendix in 50% of all cases. However, recent endoscopic and histological studies suggest that UC can occur as a discontinuous process. Furthermore, the few existing studies specifically addressing appendiceal histology in UC are divided over whether ulcerative appendicitis (UA) may be seen without cecal involvement (i.e., as a "skip lesion"). To study the appendiceal pathology in UC, and in particular the frequency of UA as a "skip lesion," we retrospectively evaluated 39 proctocolectomy specimens containing appendices removed for UC. Six cases (17%) had obliterated appendices; appendiceal and cecal histologies of the remaining 33 cases were divided into (a) active disease, (b) quiescent disease, or (c) nonspecific or normal histology. Twenty of 39 appendices (51%) showed active disease, four (10%) had quiescent disease, and nine (23%) were either normal or nonspecifically inflamed. After exclusion of one case for inadequate cecal sampling, comparison of cecal and appendiceal histologies showed concordance in 16 cases and discordance in the remaining 16. Of these discordant cases, six had greater disease activity in the cecum and 10 had greater activity in the appendix. Of these latter 10 cases, six showed normal or nonspecific cecal histology associated with active UA. Thus, "skip lesions" of the appendix were detected in 15% of the UC specimens examined.


Responses of thoracic interneurons to tactile stimulation in cockroach, Periplaneta americana.
Recent findings indicate that cockroaches escape in response to tactile stimulation as well as they do in response to the classic wind puff stimulus. The thoracic interneurons that receive inputs from ventral giant interneurons also respond to tactile stimulation and, therefore, represent a potential site of convergence between wind and tactile stimulation, as well as other sensory modalities. In this article, we characterize the tactile response of these interneurons, which are referred to as type-A thoracic interneurons (TIAs). In response to tactile stimulation of the body cuticle, TIAs typically respond with a short latency biphasic depolarization which often passes threshold for action potentials. The biphasic response is not typical of responses to wind stimulation nor of tactile stimulation of the antennae. It is also not seen in tactile responses of thoracic interneurons that are not part of the TIA group. The responses of individual TIAs to stimulation of various body locations were mapped. The left-right directional properties of TIAs are consistent with their responses to wind puffs from various different directions. Cells that respond equally well to wind from the left and right side also respond equally well to tactile stimuli on the left and right side of the animal's body. In contrast, cells that are biased to wind on one side are also biased to tactile stimulation on the same side. In general, tactile responses directed at body cuticle are phasic rather than tonic, occurring both when the tactile stimulator is depressed and released. The response reflects stimulus strength and follows repeated stimulation quite well. However, the first phase of the biphasic response is more robust during high-frequency stimulation than the second phase. TIAs also respond to antennal stimulation. However, here the response characteristics are complicated by the fact that movement of either antenna evokes descending activity in both left and right thoracic connectives. The data suggest that the TIAs make up a multimodal site of sensory convergence that is capable of generating an oriented escape turn in response to any one of several sensory cues.


Inflammation modulates the expression of the intestinal mucins MUC2 and MUC4 in gastric tumors.
Infection of gastric mucosa by Helicobacter pylori induces an inflammatory response with increased levels of proinflammatory cytokines. Among them, tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta and IL-6 induce the activation of signaling pathways that regulate genes expression, such as MUC2 and MUC4 intestinal mucins ectopically detected in gastric tumors. This study evaluated if the predominant inflammatory cell type correlates with MUC2 and MUC4 expression in human intestinal gastric tumors (n=78). In addition, we analyzed the regulatory effects of the associated inflammatory signaling pathways on their expression in gastric cancer cell lines, and in a mouse model with hyperactivated STAT3 signaling pathway. Tumors with predominant lymphoplasmocytic infiltrate (chronic inflammation), presented higher levels of MUC2 and were more differentiated than tumors with predominant polymorphonuclear infiltrate (acute inflammation). These differences can be attributed to specific cytokines, because TNF-alpha and IL-1beta induced MUC2 but no MUC4 expression in gastric cancer cell lines. The two groups of tumors expressed similar levels of MUC4 that correlated with the expression of STAT3 transcription factor, implicated in the activation of genes through the IL-6 pathway. In gastric tissues from gp130(+/+), gp130(Y757F/Y757F) and gp130(Y757F/Y757F) Stat3(-/+) mice, Muc2 was not detected, whereas Muc4 was found in the gastric tumors developed in the gp130(Y757F/Y757F) mice, with hyperactivated STAT3. These data indicate that the signaling pathways associated with the inflammatory response can modulate the expression of MUC2 and MUC4 intestinal mucin genes, in human and mouse gastric tumors.


Organizational configuration of hospitals succeeding in attracting and retaining nurses.
This paper contrasts structural and managerial characteristics of low- and high-turnover hospitals, and describes the organizational configuration of attractive hospitals. In countries facing nurse shortages and turnover, some hospitals succeed in recruiting and retaining nurses. In Magnet Hospitals, managerial practices and environmental characteristics increase nurses' job satisfaction and their commitment to the organization, which in turn decreases nurse turnover. Such an approach suggests that organizations are best understood as clusters of interconnected structures and practices, i.e. organizational configurations rather than entities whose components can be understood in isolation. From a sample of 12 hospitals whose nurse turnover was studied for 1 year, structural and organizational features of hospitals in the first and fourth quartiles, i.e. attractive (turnover <3.1%) vs. conventional (turnover >11.8%) were contrasted. A questionnaire, including perceptions of health-related factors, job demands, stressors, work schedules, organizational climate, and work adjustments antecedent to turnover, was received from 401 nurses working in attractive hospitals (response rate = 53.8%) and 774 nurses in conventional hospitals (response rate = 54.5%). Structural characteristics did not differentiate attractive and conventional hospitals, but employee perceptions towards the organization differed strikingly. Differences were observed for risk exposure, emotional demands, role ambiguity and conflicts, work-family conflicts, effort-reward imbalance and the meaning of work, all in favour of attractive hospitals (P < 0.001). Relationships with nursing management, work ability and satisfaction with working time, handover shifts and schedules were also better in attractive hospitals (P < 0.001). Job satisfaction and commitment were higher in attractive hospitals, whereas burnout and intention to leave were lower (P < 0.001). Organizational characteristics are key factors in nurse attraction and retention. Nurses face difficulties in their work situations, but some hospitals are perceived as healthy organizations. The concept of attractive institutions could serve as a catalyst for improvement in nurses' work environments in Europe.


Genetic diversity and population structure of Plasmodium falciparum in the Philippines.
In the Philippines, malaria morbidity and mortality have decreased since the 1990s by effective malaria control. Several epidemiological surveys have been performed in the country, but the characteristics of the Plasmodium falciparum populations are not yet fully understood. In this study, the genetic structure of P. falciparum populations in the Philippines was examined. Population genetic analyses based on polymorphisms of 10 microsatellite loci of the parasite were conducted on 92 isolates from three provinces (Kalinga, Palawan, and Davao del Norte) with different malaria endemicity. The levels of genetic diversity and the effective population sizes of P. falciparum in the Philippines were similar to those reported in the mainland of Southeast Asia or South America. In the low malaria transmission area (Kalinga), there was a low level of genetic diversity and a strong linkage disequilibrium (LD) when the single-clone haplotype (SCH) was used in the multilocus LD analysis, while in the high malaria transmission areas (Palawan and Davao del Norte), there was a high level of genetic diversity and a weak LD when SCH was used in the multilocus LD analysis. On the other hand, when the unique haplotypes were used in the multilocus LD analysis, no significant LD was observed in the Kalinga and the Palawan populations. The Kalinga and the Palawan populations were, therefore, estimated to have an epidemic population structure. The three populations were moderately differentiated from each other. In each area, the level of genetic diversity correlates with the local malaria endemicity. These findings confirm that population genetic analyses using microsatellite loci are a useful tool for evaluating malaria endemicity.


Texas Scottish Rite Hospital rod instrumentation for thoracic and lumbar spine trauma.
The authors present their experience with 28 patients who had incurred unstable thoracic or lumbar spine fractures and who were intraoperatively stabilized with the Texas Scottish Rite Hospital (TSRH) universal instrumentation system. These patients were treated over a 1-year period and reflect an evolving insight into the treatment of thoracic and lumbar spine trauma with universal instrumentation. The TSRH instrumentation system appears equivalent to the more established Cotrel-Dubousset system in most respects. The construct design of the TSRH system facilitates the safe application of a rigid spinal implant. No cases of instability or pseudoarthrosis were observed during an average follow-up period of 9 months, (minimum 3 months). As the surgical treatment plan evolved, shorter and more compact constructs were increasingly utilized. There were no cases of instrumentation failure, regardless of the number of spinal levels fused or the number of levels instrumented. The value of using short rods when possible is emphasized: they may decrease the incidence of delayed instability and discomfort related to loosening at the hook/bone interface compared to that observed when long-rod systems are used in association with short spine fusions causing a fusion/instrumentation mismatch.


RGS19 regulates Wnt-beta-catenin signaling through inactivation of Galpha(o).
The Wnt-beta-catenin pathway controls numerous cellular processes, including differentiation, cell-fate decisions and dorsal-ventral polarity in the developing embryo. Heterotrimeric G-proteins are essential for Wnt signaling, and regulator of G-protein signaling (RGS) proteins are known to act at the level of G-proteins. The functional role of RGS proteins in the Wnt-beta-catenin pathway was investigated in mouse F9 embryonic teratocarcinoma cells. RGS protein expression was investigated at the mRNA level, and each RGS protein identified was overexpressed and tested for the ability to regulate the canonical Wnt pathway. Expression of RGS19 specifically was found to attenuate Wnt-responsive gene transcription in a time- and dose-dependent manner, to block cytosolic beta-catenin accumulation and Dishevelled3 (Dvl3) phosphorylation in response to Wnt3a and to inhibit Wnt-induced formation of primitive endoderm (PE). Overexpression of a constitutively active mutant of Galpha(o) rescued the inhibition of Lef-Tcf-sensitive gene transcription caused by RGS19. By contrast, expression of RGS19 did not inhibit activation of Lef-Tcf gene transcription when induced in response to Dvl3 expression. However, knockdown of RGS19 by siRNA suppressed canonical Wnt signaling, suggesting a complex role for RGS19 in regulating the ability of Wnt3a to signal to the level of beta-catenin and gene transcription.


Proteins of the mammalian mitotic spindle: phosphorylation/dephosphorylation of MAP-4 during mitosis.
The phosphoprotein composition of isolated CHO spindles was analyzed using the MPM-1 and MPM-2 antibodies, which are reactive with a phosphorylated epitope enriched in mitotic cells and present on the centrosome, kinetochores, midbody and fibers of the mitotic spindle. Several high molecular weight phosphorylated spindle proteins were detected on immunoblots, including species of 410 x 10(3) Mr, 350 x 10(3) Mr, a 230-240 X 10(3) Mr doublet, 210 x 10(3) Mr and 120 x 10(3) Mr. The temporal and spatial distribution of the MPM-reactive phosphoproteins was determined by examining spindle structures isolated from cells at various stages of mitosis. The susceptibility of the staining pattern to extraction with salt, a procedure known to remove most microtubule-associated proteins (MAPs), was also examined. The phosphorylated 210 x 10(3) Mr species was identified as MAP-4 and localized to the spindle fibers using (1) a polyclonal antibody raised against this species, that reacted with known MAPs, and (2) established MAP-4 antibodies that reacted with the spindle 210 x 10(3) Mr MPM-reactive proteins. The comparative immunoblot and immunofluorescence analysis establishes a cycle of phosphorylation/dephosphorylation of MAP-4 upon entry and exit from mitosis. Regarding the other MPM-reactive proteins, comparative immunofluorescence staining and immunoblot analysis of isolated spindle samples before and after salt extraction indicate that they may be constituents of the centrosome, kinetochores or midbody, but their definitive identification awaits the production of monospecific antibodies.


New insights into pathways that determine the link between infection and thrombosis.
Severe infection is often linked to prothrombotic events. Indeed, haemostatic abnormalities are encountered in most cases of infection, ranging from an increase in sensitive markers for coagulation activation or insignificant laboratory changes to gross activation of coagulation that may result in localised thrombotic complications or disseminated intravascular coagulation. Systemic inflammation as a consequence of infection results in activation of coagulation, due to tissue factor-mediated thrombin generation, down-regulation of physiological anticoagulant mechanisms, and inhibition of fibrinolysis. Pro-inflammatory cytokines, immune cells and the endothelium form the interface on which differential effects on the coagulation and fibrinolysis pathways may ensue. Conversely, activation of the coagulation system may importantly affect inflammatory responses by direct and indirect mechanisms. Apart from the general coagulation response to inflammation associated with severe infection, specific infections may cause distinct features, such as haemorrhagic fever or thrombotic microangiopathy.


First Report of Sclerotinia Blight of Peanut Caused by Sclerotinia minor in Arkansas.
In September, 2013, symptoms similar to Sclerotinia blight caused by Sclerotinia minor were observed on Runner peanut (cv. FloRun 107) in a commercial field near Pocahontas, Arkansas, in Randolph County (2). Blighted plants with wilted leaves were observed in several small (30 × 30 cm) clustered foci located near the end of a 20-ha, furrow-irrigated field. Peanut stems within the lower canopy of symptomatic plants had straw-colored lesions, with white fluffy mycelium and small (<2.0 mm diam.), black, irregularly shaped sclerotia. Stems on plants with severe symptoms were shredded in appearance, with small black sclerotia inside the stem tissue (2). Final disease incidence near harvest in mid-October was less than 1% of the field. Sclerotinia blight symptoms were also observed in 2013 on Runner (cvs. FloRun 107, Georgia 09B, and Florida 07) and Spanish peanut (cvs. OLin and OL06) research plots near Newport, AR, in Jackson County. Disease incidence among cultivars in these research plots was <1% for all cultivars except FloRun 107, which had a disease incidence of 2.6% for a 849.8 m2 plot. Isolations from surface-disinfected leaves on potato dextrose agar (PDA) consistently yielded white, fluffy mycelia with small (0.5 to 2.0 mm diam.), black, irregularly shaped sclerotia typical of S. minor (2). Six-week-old peanut plants (cv. FloRun 107) growing in pots were used to test pathogenicity. Each plant was inoculated by placing an agar plug (5 mm diam.), collected from the edge of an actively growing S. minor culture, on the main peanut stem. Plants (n = 5) were incubated for 8 days in a humidity chamber where temperatures ranged from 24 to 30°C and relative humidity remained >95%. Characteristic symptoms of Sclerotia blight were observed on all inoculated peanut plants whereas none of the plants (n = 3) inoculated with sterile PDA agar plugs expressed symptoms. Pathogenicity tests were repeated on peanut cvs. Flavor Runner 458 and Georgia 09B with similar results. S. minor was consistently isolated from symptomatic tissue on PDA, fulfilling Koch's postulates. To our knowledge, this is the first report of S. minor on peanut or any host in Arkansas or the Mid-South region. The two peanut fields with Sclerotinia blight had a history of soybean production, and S. minor may have gone undetected on soybean or one of many host weed species (1). Since S. minor is a major economic pathogen of peanut, commonly causing yield losses of 10% (2), it will likely be a significant factor in Arkansas and Mid-South peanut production. References: (1) M. S. Melzer et al. Can. J. Plant Pathol. 19:272, 1997. (2) D. M. Porter and H. A. Melouk. Sclerotinia blight. Page 34 in: Compendium of Peanut Diseases, 2nd ed. N. Kokalis-Burelle et al., eds. The American Phytopathological Society, St. Paul, MN, 1997.


Farnesol-like endogenous sesquiterpenoids in vertebrates: the probable but overlooked functional "inbrome" anti-aging counterpart of juvenile hormone of insects?
Literature on the question whether the juvenile stage of vertebrates is hormonally regulated is scarce. It seems to be intuitively assumed that this stage of development is automated, and does not require any specific hormone(s). Such reasoning mimics the state of affairs in insects until it was shown that surgical removal of a tiny pair of glands in the head, the corpora allata, ended larval life and initiated metamorphosis. Decades later, the responsible hormone was found and named "juvenile hormone" (JH) because when present, it makes a larva molt into another larval stage. JH is a simple ester of farnesol, a sesquiterpenoid present in all eukaryotes. Whereas vertebrates do not have an anatomical counterpart of the corpora allata, their tissues do contain farnesol-like sesquiterpenoids (FLS). Some display typical JH activity when tested in appropriate insect bioassays. Some FLS are intermediates in the biosynthetic pathway of cholesterol, a compound that insects and nematodes (=Ecdysozoa) cannot synthesize by themselves. They ingest it as a vitamin. Until a recent (2014) reexamination of the basic principle underlying insect metamorphosis, it had been completely overlooked that the Ca(2+)-pump (SERCA) blocker thapsigargin is a sesquiterpenoid that mimics the absence of JH in inducing apoptosis. In our opinion, being in the juvenile state is primarily controlled by endogenous FLS that participate in controlling the activity of Ca(2+)-ATPases in the sarco(endo)plasmic reticulum (SERCAs), not only in insects but in all eukaryotes. Understanding the control mechanisms of being in the juvenile state may boost research not only in developmental biology in general, but also in diseases that develop after the juvenile stage, e.g., Alzheimer's disease. It may also help to better understand some of the causes of obesity, a syndrome that holometabolous last larval insects severely suffer from, and for which they found a very drastic but efficient solution, namely metamorphosis.


Anillin: a pivotal organizer of the cytokinetic machinery.
Cytokinesis is a dynamic and plastic process involving the co-ordinated regulation of many components. Accordingly, many proteins, including the putative scaffold protein anillin, localize to the cleavage furrow and are required for cytokinesis, but how they function together is poorly understood. Anillin can bind to numerous other furrow components, including F-actin, septins and myosin II, but its molecular functions are unclear. Recent data suggest that anillin participates in a previously unrecognized Rho-dependent pathway that can promote the association of anillin with the plasma membrane, septins, myosin II and microtubules. Studies using the inhibitor of F-actin assembly, Lat A (Latrunculin A), have revealed that these associations occur independently of F-actin; indeed they appear to be stabilized by the loss of F-actin. This pathway may explain previously described requirements for anillin in maintaining stable furrow positioning and for forming a stable midbody, and supports the notion that anillin is a central organizer at the hub of the cytokinetic machinery.


Cell dispersal methods for increasing yield from animal tissues.
An improved method for increasing cell yield from animal tissues is described. The current technique differs from the classical, primarily in that the tissues were perfused with trypsin in situ and cell dispersal was completed by trypsinization either at 4 or 37 C but without prior mincing of the tissue. Increased yields of 75% were obtained. Mechanical damage to tissue by mincing was presumed to be the greatest single source of injury to cells. The adoption of the trypsin perfusion technique reduced the number of animals needed to prepare an equivalent quantity of tissue culture.


Estimation of pathogenic potential of an environmental Pseudomonas aeruginosa isolate using comparative genomics.
The isolation and sequencing of new strains of Pseudomonas aeruginosa created an extensive dataset of closed genomes. Many of the publicly available genomes are only used in their original publication while additional in silico information, based on comparison to previously published genomes, is not being explored. In this study, we defined and investigated the genome of the environmental isolate P. aeruginosa KRP1 and compared it to more than 100 publicly available closed P. aeruginosa genomes. By using different genomic island prediction programs, we could identify a total of 17 genomic islands and 8 genomic islets, marking the majority of the accessory genome that covers ~ 12% of the total genome. Based on intra-strain comparisons, we are able to predict the pathogenic potential of this environmental isolate. It shares a substantial amount of genomic information with the highly virulent PSE9 and LESB58 strains. For both of these, the increased virulence has been directly linked to their accessory genome before. Hence, the integrated use of previously published data can help to minimize expensive and time consuming wetlab work to determine the pathogenetic potential.


Candida albicans, the opportunist. A cellular and molecular perspective.
Candida albicans causes the majority of opportunistic fungal infections. The yeast's commensualistic relationship with humans enables it, when environmental conditions are favorable, to multiply and replace much of the normal flora. Virulence factors of C. albicans, enabling the organism to adhere to and penetrate host tissues, involve specific molecular interactions between the cells of the fungus and the host. Localized disease, such as oral candidiasis, onychomycosis, and vaginitis, results. These infections are usually limited to surfaces of the host, and can be quickly and successfully controlled by the use of one of the available antifungal agents. Candida albicans infections typically become systemic and life threatening when the host is immunocompromised. Depending on the immune defect in the host, one of the spectrum of Candida diseases can develop. If successful treatment of these patients is to be achieved, modulation of the immune deficit, as well as the use of an appropriate antifungal drug, must become a routine part of therapeutic interventions.


Molecular imaging coupled to pattern recognition distinguishes response to temozolomide in preclinical glioblastoma.
Non-invasive monitoring of response to treatment of glioblastoma (GB) is nowadays carried out using MRI. MRS and MR spectroscopic imaging (MRSI) constitute promising tools for this undertaking. A temozolomide (TMZ) protocol was optimized for GL261 GB. Sixty-three mice were studied by MRI/MRS/MRSI. The spectroscopic information was used for the classification of control brain and untreated and responding GB, and validated against post-mortem immunostainings in selected animals. A classification system was developed, based on the MRSI-sampled metabolome of normal brain parenchyma, untreated and responding GB, with a 93% accuracy. Classification of an independent test set yielded a balanced error rate of 6% or less. Classifications correlated well both with tumor volume changes detected by MRI after two TMZ cycles and with the histopathological data: a significant decrease (p < 0.05) in the proliferation and mitotic rates and a 4.6-fold increase in the apoptotic rate. A surrogate response biomarker based on the linear combination of 12 spectral features has been found in the MRS/MRSI pattern of treated tumors, allowing the non-invasive classification of growing and responding GL261 GB. The methodology described can be applied to preclinical treatment efficacy studies to test new antitumoral drugs, and begets translational potential for early response detection in clinical studies.


Dog Population & Dog Sheltering Trends in the United States of America.
Dog management in the United States has evolved considerably over the last 40 years. This review analyzes available data from the last 30 to 40 years to identify national and local trends. In 1973, The Humane Society of the US (The HSUS) estimated that about 13.5 million animals (64 dogs and cats per 1000 people) were euthanized in the US (about 20% of the pet population) and about 25% of the dog population was still roaming the streets. Intake and euthanasia numbers (national and state level) declined rapidly in the 1970s due to a number of factors, including the implementation of shelter sterilization policies, changes in sterilization practices by private veterinarians and the passage of local ordinances implementing differential licensing fees for intact and sterilized pets. By the mid-1980s, shelter intake had declined by about 50% (The HSUS estimated 7.6⁻10 million animals euthanized in 1985). Data collected by PetPoint over the past eight years indicate that adoptions increased in the last decade and may have become an additional driver affecting recent euthanasia declines across the US. We suspect that sterilizations, now part of the standard veterinary care, and the level of control of pet dogs exercised by pet owners (roaming dogs are now mostly absent in many US communities) played an important part in the cultural shift in the US, in which a larger proportion of families now regard their pet dogs as "family members".


Acrylic microspheres in vivo. II. The effect in rat of L-asparaginase given in microparticles of polyacrylamide.
L-Asparaginase was immobilized in spherical microparticles of polyacrylamide. Particles of three different sizes, mean diameter 0.34, 18 and 36 micron, respectively, were used. The Michaelis constant Km, for L-asparaginase, immobilized in small particles (0.34 micron), is virtually the same as in solution. L-Asparaginase in microparticles was also more stable than free enzyme after storage for 140 days at +4 and +37 degrees C. After an i.v. injection of 200 I.U./kg into rat, the plasma L-asparagine fell to very low values (less than 10 nmol/ml), but was normalized again after 4 to 5 days with both the native and immobilized enzymes. After an i.p. injection of 1000 I.U./kg into rats, the microparticles containing L-asparaginase lowered the plasma L-asparagine level for a substantially longer period of time than L-asparaginase in free solution. Normal L-asparagine level was thus reached on day 14 after the injection with immobilized enzyme. However, L-asparaginase activity was still present in the abdominal lymph nodes after this period of time.


Chronic exposure to high glucose and impairment of K(+)-channel function in perifused rat pancreatic islets.
Prolonged exposure to high glucose levels impairs the ability of pancreatic islets to secrete insulin as a response to that stimulus. Because glucose, like other insulin secretagogues, elicits insulin secretion by inhibiting the ATP-sensitive K+ channels, in this study, we investigated the effect of prolonged (24-h) exposure of rat pancreatic islets to high (16.7 mM) glucose concentration on 86Rb efflux (used as a tracer for K+). The data obtained indicate that islets exposed to high glucose concentration have impaired function of the glucose-sensitive K+ channel, this phenomenon is temporarily related to a defective response of glucose-induced insulin release, and these alterations are reversible.


Somatostatin release from dispersed hypothalamic cells: effects of diabetes.
We examined the release of growth hormone-release inhibiting factor (somatostatin) from dispersed hypothalamic cells obtained from mature diabetic rodents and normal age-matched controls, in an attempt to demonstrate a possible hypothalamic defect which might underlie some of the reported abnormalities in somatotrophic function in diabetes mellitus. Insulinopoenic diabetes was induced by either streptozotocin or alloxan. Somatostatin release from cells from diabetic rats was diminished both basally and after stimulation by membrane depolarisation. Stimulated release was calcium dependent in cells from both normal and diabetic animals. The defect was present in both streptozotocin and alloxan induced diabetes. We also compared hypothalamic somatostatin release from cells obtained from obese hyperinsulinaemic C57 BL/Ks db/db diabetic mice and non diabetic lean litter mates (db/-). Despite longstanding marked hyperglycaemia, no significant alteration in somatostatin release was apparent. Likewise, starvation of rats for 5 days did not result in significant diminution of somatostatin release. These observations document a defect in hypothalamic somatostatin release in experimentally induced insulinopoenic diabetes, which is not apparent in the db/db mouse, suggesting that glucose per se is not responsible. Rather than the anticipated increase in hypothalamic somatostatin release in insulinopoenic diabetes, a reduction in release was observed. These observations are compatible with the hypothesis that increased hypothalamic somatostatin release is not responsible for abnormal growth hormone secretion in this model.


A psychologically rich life: Beyond happiness and meaning.
Psychological science has typically conceptualized a good life in terms of either hedonic or eudaimonic well-being. We propose that psychological richness is another, neglected aspect of what people consider a good life. Unlike happy or meaningful lives, psychologically rich lives are best characterized by a variety of interesting and perspective-changing experiences. We present empirical evidence that happiness, meaning, and psychological richness are related but distinct and desirable aspects of a good life, with unique causes and correlates. In doing so, we show that a nontrivial number of people around the world report they would choose a psychologically rich life at the expense of a happy or meaningful life, and that approximately a third say that undoing their life's biggest regret would have made their lives psychologically richer. Furthermore, we propose that the predictors of a psychologically rich life are different from those of a happy life or a meaningful life, and report evidence suggesting that people leading psychologically rich lives tend to be more curious, think more holistically, and lean more politically liberal. Together, this work moves us beyond the dichotomy of hedonic versus eudaimonic well-being, and lays the foundation for the study of psychological richness as another dimension of a good life. (PsycInfo Database Record (c) 2022 APA, all rights reserved).


Optimizing Treatment for Elderly Patients With Newly Diagnosed Multiple Myeloma: A Personalized Approach.
The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors' suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology, to patients seen in their own clinical practice. An 84-year-old woman presented with bone pain and lytic bone lesions in April 2010. Diagnosis of multiple myeloma was based on the presence of an immunoglobulin G lambda serum M protein (4,784 mg/dL) and confirmed by the findings of bone marrow plasma cell infiltration, with t(11;14) chromosomal abnormality detected by fluorescence in situ hybridization analysis. The patient's medical history was significant for hypertension; she had an Eastern Cooperative Oncology Group performance status of 1, International Staging System (ISS) stage of 1, and Durie-Salmon stage of IIIA. In May 2010, the patient was enrolled in a randomized phase III trial comparing different lenalidomide-based treatments and received induction with lenalidomide plus dexamethasone (nine cycles) followed by lenalidomide maintenance. The patient started treatment with lenalidomide 25 mg per day for 21 days and reduced-dose dexamethasone 20 mg per week per protocol because of age. Induction was well tolerated; no relevant complications occurred, except for grade 1 fatigue and grade 1 diarrhea. Best response was partial response. In March 2011, she started maintenance with lenalidomide 10 mg per day. A dose reduction of lenalidomide 5 mg per day was required because of grade 2 diarrhea. In July 2015, the patient experienced relapse, with painful collapse of L3 vertebral body.


Evaluation of the in vitro Function of Platelet Concentrates from Pooled Buffy Coats or Apheresis.
Platelet concentrates play an important role in transfusion medicine. Their short lifespan and lack of robustness require efforts to ensure adequate product quality. In this study, we compared the in vitro quality of the main concentrate types, pooled platelet concentrate (PPC) from whole blood donations, and platelet concentrate from single-donor apheresis (APC). Twenty PPCs and 20 APCs prepared in plasma were analyzed on days 2, 4, and 7 of storage. Variables related to metabolism, degranulation, platelet aggregation, P-selectin expression, and annexin V binding were analyzed. Morphology was assessed by transmission electron microscopy of ultrathin sections. A microfluidic device was applied to test the effects of shear stress on platelet function. The metabolic parameters indicated stable storage conditions throughout the 7-day period. The resting discoid form was the prevailing morphology on days 2 and 4 in the PPCs and APCs. Chemokine release and receptor shedding of soluble P-selectin and soluble CD40L equally increased in PPCs and APCs. Aggregation responses to ADP and collagen were heterogeneous, with marked losses in collagen responsiveness on day 4 in individual concentrates. Baseline expression of P-selectin in PPCs and APCs was low, and inducibility of P-selectin was well preserved until day 4. Under shear stress, equal adhesiveness and stability were found with platelets from PPCs and APCs. Platelets from PPCs and APCs showed similar in vitro function and stability parameters. However, platelet concentrates presented a high variability and individual concentrates an impaired functional capability. Identifying the factors contributing to this would help increase product reliability.


Evaluation of a patient with left ventricular assist device dysfunction.
With the increasing number of LVAD recipients due to lack of donor availability and use of an LVAD as destination therapy, there will be a significant proportion of this population presenting with device related complications. Initial evaluation should be with TEE because conduit obstruction would be a significant complication, among others. As observed in this case report, it is sometimes difficult to noninvasively detect device malfunction, and even surgical exploration left questions unanswered. Echocardiography has been the principal modality used so far to assess the LVAD cannulas. More reliance on Doppler velocities and establishment of a normal range of values and flow profiles of the inflow and outflow cannulas are necessary. Baseline echocardiographic studies could be used for future comparisons. Fluoroscopy and selective angiography have also been reported to be helpful. We would also recommend measuring LV hemodynamics, which have not been previously described, as an additional mode of evaluation of this emerging problem. This case report demonstrates the need for additional noninvasive modalities for diagnosis of ventricular assist device malfunction.


Choosing the right substrate.
Carbohydrate and fatty acids are major energetic substrates, although amino acid oxidation also permits ATP synthesis. Among several major metabolic differences between lipids and carbohydrate (activation, transport, effect of insulin, etc.), two are of particular importance when considering energy metabolism of critically ill patients: the yield of ATP synthesis and the response to uncoupling. (I) Oxidative phosphorylation yield is higher when NADH is the electron donor (three coupling sites: complex 1, 3 and 4) as compared to FADH2 (two coupling sites: complex 3 and 4). Since the ratio NADH/FADH2 is higher for glycolysis as compared to beta-oxidation, the stoichiometry of ATP synthesis to oxygen consumption is also higher. Lipid oxidation provides more ATP than carbohydrate, but it requires more oxygen per mole of ATP synthesized. (II) The ratio of NADH oxidation versus FADH, oxidation depends on the proton motive force, and lowering proton motive force by uncoupling favours FADH2 oxidation, i.e. lipids versus carbohydrate. In conclusion, lipid oxidation provides a high rate of ATP synthesis even during a mild uncoupling state, but at a high rate of oxygen consumption. If oxygen availability is limited, the major metabolic adaptation to increase the efficiency is represented by a switch from lipid oxidation to glucose oxidation.


[Integral bread development with soybean, chia, linseed, and folic acid as a functional food for women].
Six bread formulations were developed, using different proportions of whole-wheat flour, chia seeds and flaxseed flour. All of our formulations were added with folic acid. Sensorial and texture evaluations were performed, showing good acceptance of the products. Proximal chemical analysis was carried out; in addition, the following parameters were determined: calcium, phosphorus, total dietary fiber, folic acid, water hydration capacity, Glucose Dialysis Retardation Index (GDRI) and fatty acids. The results obtained showed higher protein levels in the developed breads (23.23-30.24 (g/100g dry matter) as compared to a control (21.00% of proteins in bread elaborated without chia or flaxseed). Furthermore, the breads contained 10.07-12.15 of lipids (g/100g dry matter) (linoleic acid: 2.43-4.05%; linolenic acid: 1.12-4.46 %; oleic acid: 2.93-6.13 %), GDRI values were between 89.1 and 98.1 % and folic acid was in the range 699.44 - 991.3 (microg/100g dry matter). The same parameters were determined in the chia seed and in the flaxseed flour. It was concluded that; due to their high levels of protein, insaturated fatty acids (omega-3 and omega-6), dietary fiber and folic acid, these breads have a high nutritional value, so they could have special benefits for woman.


Convergence of developmental mutants into a single tomato model system: 'Micro-Tom' as an effective toolkit for plant development research.
The tomato (Solanum lycopersicum L.) plant is both an economically important food crop and an ideal dicot model to investigate various physiological phenomena not possible in Arabidopsis thaliana. Due to the great diversity of tomato cultivars used by the research community, it is often difficult to reliably compare phenotypes. The lack of tomato developmental mutants in a single genetic background prevents the stacking of mutations to facilitate analysis of double and multiple mutants, often required for elucidating developmental pathways. We took advantage of the small size and rapid life cycle of the tomato cultivar Micro-Tom (MT) to create near-isogenic lines (NILs) by introgressing a suite of hormonal and photomorphogenetic mutations (altered sensitivity or endogenous levels of auxin, ethylene, abscisic acid, gibberellin, brassinosteroid, and light response) into this genetic background. To demonstrate the usefulness of this collection, we compared developmental traits between the produced NILs. All expected mutant phenotypes were expressed in the NILs. We also created NILs harboring the wild type alleles for dwarf, self-pruning and uniform fruit, which are mutations characteristic of MT. This amplified both the applications of the mutant collection presented here and of MT as a genetic model system. The community resource presented here is a useful toolkit for plant research, particularly for future studies in plant development, which will require the simultaneous observation of the effect of various hormones, signaling pathways and crosstalk.


Hierarchical Aligned Cluster Analysis for Temporal Clustering of Human Motion.
Temporal segmentation of human motion into plausible motion primitives is central to understanding and building computational models of human motion. Several issues contribute to the challenge of discovering motion primitives: the exponential nature of all possible movement combinations, the variability in the temporal scale of human actions, and the complexity of representing articulated motion. We pose the problem of learning motion primitives as one of temporal clustering, and derive an unsupervised hierarchical bottom-up framework called hierarchical aligned cluster analysis (HACA). HACA finds a partition of a given multidimensional time series into m disjoint segments such that each segment belongs to one of k clusters. HACA combines kernel k-means with the generalized dynamic time alignment kernel to cluster time series data. Moreover, it provides a natural framework to find a low-dimensional embedding for time series. HACA is efficiently optimized with a coordinate descent strategy and dynamic programming. Experimental results on motion capture and video data demonstrate the effectiveness of HACA for segmenting complex motions and as a visualization tool. We also compare the performance of HACA to state-of-the-art algorithms for temporal clustering on data of a honey bee dance. The HACA code is available online.


Mechanisms involved in the antiinflammatory effect of propolis extract.
Propolis is a natural product produced by the honey bee. The extract contains amino acids, flavanoids, terpenes and cinnamic acid derivatives. In various in vitro models propolis extract was shown to inhibit platelet aggregation and to inhibit eicosanoid synthesis, suggesting that it might have potent antiinflammatory properties. A 13% aqueous extract was tested orally in three dose levels (1, 5 and 10 ml/kg) on the carrageenan rat paw oedema model and on adjuvant-induced arthritis in rats. In both models, the extract showed potent dose-related antiinflammatory activity, which compared well with that of diclofenac (as a reference standard). The extract was then tested on an isolated sensitized guinea pig lung preparation to study its effect on the release of prostaglandins, leukotrienes and histamine. It is concluded that propolis extract has potent antiinflammatory properties in vivo. Its activity can be well correlated with its effects on the release of various mediators of inflammation.


Adult cellular rhabdomyoma of the heart: a report of 3 cases.
We present 3 adults with cardiac rhabdomyomas, 2 in the atria and 1 in the right ventricle. One atrial tumor was discovered incidentally, and 1 resulted in supraventricular tachycardia. The ventricular lesion caused ventricular tachycardia. Compared with congenital rhabdomyomas, the tumors are relatively cellular, the cells are smaller, there are few spider cells, and there is evidence of cell proliferation. Two of the 3 tumors demonstrated spindling in contrast to adult rhabdomyomas of the head and neck. Although surgical excision was possible in all patients, long-term follow-up will be required to determine the true biologic behavior of these neoplasms.


Staging presymptomatic type 1 diabetes: a scientific statement of JDRF, the Endocrine Society, and the American Diabetes Association.
Insights from prospective, longitudinal studies of individuals at risk for developing type 1 diabetes have demonstrated that the disease is a continuum that progresses sequentially at variable but predictable rates through distinct identifiable stages prior to the onset of symptoms. Stage 1 is defined as the presence of β-cell autoimmunity as evidenced by the presence of two or more islet autoantibodies with normoglycemia and is presymptomatic, stage 2 as the presence of β-cell autoimmunity with dysglycemia and is presymptomatic, and stage 3 as onset of symptomatic disease. Adoption of this staging classification provides a standardized taxonomy for type 1 diabetes and will aid the development of therapies and the design of clinical trials to prevent symptomatic disease, promote precision medicine, and provide a framework for an optimized benefit/risk ratio that will impact regulatory approval, reimbursement, and adoption of interventions in the early stages of type 1 diabetes to prevent symptomatic disease.


[A project to improve the "do not resuscitation" consent completeness rate for terminal cancer patients].
Signed do-not-resuscitate (DNR) consent is the essential first step for terminal cancer patients to choose palliative care and a quality marker of terminal care. DNR consent completeness helps deliver correct information, ensure consent legal validity, reduce medical disputes, and protect patient and family rights. The DNR consent completeness rate during May and June 2005 was only 33.9% in our hospital. Reasons indicated for this low rate included: (1) lack of a standard operating procedure for DNR consent; (2) multiple DNR consent versions; (3) lack of DNR-related education; and (4) lack of monitoring procedures. Our team developed a project to resolve these problems and improve terminal care quality. The goal of this project was to increase the rate of DNR consent completeness from 33.9% to 80%. The plan, implemented between August and December 2009, included the following components: (1) establish standard guidelines for DNR consent; (2) simplify and unify DNR consent procedures; (3) provide DNR education for hospital staff; and (4) establish a DNR consent monitoring system. The DNR consent completeness rate rose from 33.9% to 90%. The goal of this project was thus achieved. This project effectively improved the DNR consent completeness rate at our hospital. The project ensured patients a good death and enhanced terminal care quality and patient satisfaction. Our experience may provide a reference to help other hospitals increase DNR their consent completeness rates.


[Apathetic hyperthyroidism with heart failure in an elderly patient with Plummer's disease].
We report a case of apathetic hyperthyroidism associated with unrecognized slowly growing functional thyroid adenoma (Plummer's disease), atrial fibrillation and heart failure. An 81-year-old woman with worsening thyroid dysfunction was admitted to our hospital for the treatment of heart failure. The patient had developed heart failure associated with chronic atrial fibrillation at 76 years of age, and one year later was found to have asymptomatic hyperthyroidism. Anti-thyroid autoantibodies were negative, but thyroid echography showed a 32-mm tumor devoid of internal blood flow in the left lower lobe. Free thyroxine 4 (FT4) decreased from 3.30 to 2.60 ng/dl without treatment. The patient was diagnosed with transient thyroiditis and was followed-up without treatment. However, a repeat thyroid echography showed growth of the tumor to 41 mm in 4 years. Thyroid scintigraphy showed uptake that matched the thyroid mass. Based on these findings, the established diagnosis was Plummer's disease complicated with heart failure. The patient was treated with anti-thyroid drugs, which resulted in improvement of FT4 and reduced the severity of heart failure. In this rare case of an elderly patient, Plummer's disease was associated with a slowly-growing functional thyroid adenoma, apathetic hyperthyroidism, repeated episodes of atrial fibrillation and heart failure. Since symptoms of thyrotoxicosis are likely to be missed in the elderly, it is necessary to include hyperthyroidism in the pathoetiology of heart failure and atrial fibrillation in this population.


t-SNARE protein conformations patterned by the lipid microenvironment.
The spatial distribution of the target (t-)SNARE proteins (syntaxin and SNAP-25) on the plasma membrane has been extensively characterized. However, the protein conformations and interactions of the two t-SNAREs in situ remain poorly defined. By using super-resolution optical techniques and fluorescence lifetime imaging microscopy, we observed that within the t-SNARE clusters syntaxin and SNAP-25 molecules interact, forming two distinct conformations of the t-SNARE binary intermediate. These are spatially segregated on the plasma membrane with each cluster exhibiting predominantly one of the two conformations, representing the two- and three-helical forms previously observed in vitro. We sought to explain why these two t-SNARE intermediate conformations exist in spatially distinct clusters on the plasma membrane. By disrupting plasma membrane lipid order, we found that all of the t-SNARE clusters now adopted a single conformational state corresponding to the three helical t-SNARE intermediates. Together, our results define spatially distinct t-SNARE intermediate states on the plasma membrane and how the conformation adopted can be patterned by the underlying lipid environment.


Stapedectomy modified by the application of fibrin tissue adhesive.
Certain failures of the stapes operation are caused by loosening of the crimped metal loop on the long process of the incus, atrophy or necrosis of the lenticular process, erosion of the long process with the prosthesis causing injury to the labyrinth, erosion of the incudostapedial joint with upward rotation of the long process, and dislocation of the prosthesis. To reduce the occurrences of these failures following stapes removal, we close the oval window by gluing a fascia graft into place with fibrin tissue adhesive. A ceramic strut with a cup on its upper end that fits the lenticular process is glued between the fascia graft and the lenticular process. This method does not cause bone necrosis or blood circulation disturbances. The hearing results are the same or better than those reported for other stapes procedures.


[The effect of ecdysterone on experimental arrhythmias and changes in the hemodynamics and myocardial contractility induced by coronary artery occlusion].
In acute animal experiments it was shown that phytoecdizon ecdisteron (ecdisten) in some animals eliminates arrhythmia caused by the ligation of the descending branch of the left coronary artery and prevents the development of fibrillation and also corrects the hemodynamic parameters and the structure of the heart contractility, prevents the development of arrhythmias induced by aconitine and calcium chloride. The mechanism of the antiarrhythmic action is related to the membrane stabilizing effect and the improvement of the hemodynamic parameters and the heart contractility is due to an increase of the adaptative possibilities of the myocardium.


[Quality assurance of medical information in the internet--challenges for a seal of approval in gynecology].
The Internet offers a vast amount of medical information for laymen and experts. Many sites focus on gynecology and obstetrics. The multitude of information and lacking structure make it difficult to retrieve high-quality information and to distinguish them from dubious ones. Many projects were started to solve these challenges. Criteria for assessing medical information on the internet were published by several authors. Some information providers comply to such standards voluntary to show their quality standards. There are scientific councils who assess individual sits. The Concerted Action on Health Information Systems (Aktions forum Gesundheits informations systeme AFGIS) was founded by the German Federal Ministry of Health to coordinate existing activities. The knowledge of experts is essential to describe and rate internet resources. The cooperation of the scientific medical societies in Germany should be an aim to make a quality seal for information on gynecology and obstetrics possible.


Long Non-Coding RNA Expression Profiles for the Characterization of Different Bladder Cancer Grade.
Bladder cancer (BC) is one of the most frequent urologic tumors worldwide. However, long non-coding RNA(lncRNA) expression profiles in BC progression remain unclear. This study aimed to explore lncRNA expression profiles in different grades of bladder cancer and normal urothelium tissues. We performed high-throughput sequencing in BC tissues of different grade and obtained the expression profiles of its lncRNAs. Then, aberrantly expressed lncRNAs were validated by quantitative reverse transcription polymerase chain reaction (RT-PCR). Gene Ontology (GO) and pathway analyses were used to investigate the potential function of these lncRNAs. Co-expresson network was constructed to explore the relationship between lncRNAs and target mRNAs. We identified 252 aberrantly expressed lncRNAs in high-grade BC while compared to low-grade BC, and 269 lncRNAs in high-grade BC while compared to normal urothelium. Notably, we found 33 overlapped lncRNAs. Subsequently, 7 lncRNAs were selected from the overlapped part and confirmed by RT-PCR. GO and pathway analyses showed that these dysregulated lncRNAs participated in cell migration, cell adhesion, as well as Ras signaling pathway. Co-expression network and The Cancer Genome Atlas (TCGA) data showed LUCAT1 and CCNB1 had positive relationship in regulating the progress of bladder cancer. Our findings revealed the significant role of lncRNAs in the development process of bladder cancer.


Reverse-transcriptase loop-mediated isothermal amplification as a rapid screening/monitoring tool for Salmonella enterica detection in liquid whole eggs.
Reverse-transcriptase loop-mediated isothermal amplification (RT-LAMP) is a novel molecular detection method that is specific, fast, and simple. It is based on reverse transcription followed by DNA amplification using the Bst DNA polymerase large fragment requiring one temperature and a simple waterbath, without the need for any expensive equipment. Detection is by turbidity or agarose gel electrophoresis. Our objective was to apply this LAMP-based technology to rapidly and sensitively detect Salmonella enterica serovar Enteritidis in liquid whole eggs (LWEs) within 1 d. LWE were inoculated with S. Enteritidis and stomached in tetrathionate broth (TTB), and spread-plated on Xylose lysine tergitol 4 agar either immediately or after 6, 12, or 16-h enrichment. RNA was extracted from 5-mL TTB and the RT-LAMP assay was carried out using invA primers. After 16 and 12-h enrichment, improved Salmonella detection up to 10⁰ to 10¹ and 10⁴ CFU/25 mL LWE, respectively was obtained. Without enrichment, Salmonella could be detected at 10⁷ CFU/25 mL; however, after 6-h enrichment a 1-log improvement to 10⁶ CFU/25 mL was obtained. This RT-LAMP assay appears to be suitable as a potential screening/monitoring tool for Salmonella enterica from LWE products in routine settings with results obtainable within 24-h, which is significantly faster than traditional cultural assays.


HIV Testing as a Standard of Care for Men Who Have Sex With Men: Patient and Provider Perspectives.
In 2006, the Centers for Disease Control and Prevention (CDC) revised its HIV testing recommendations in health care settings. Current guidelines recommend that all patients aged 13 to 64 years be screened for HIV as part of routine medical care. Additionally, the CDC recommends that persons at high risk for HIV infection should be screened for HIV at least annually. Primary care providers in clinical settings are seen as important providers of HIV prevention services and will be critical to expand HIV testing rates, particularly among populations such as men who have sex with men (MSM). This article reports on results from a multifaceted study that combined qualitative and quantitative methods and targeted both MSM and primary care providers. Through a quantitative survey with 709 MSM in Wisconsin, we explored the relationship between having a primary care provider, risk behavior, and HIV testing patterns. In the qualitative portion of the study, we conducted structured interviews with 7 clinic medical directors to explore the acceptability and feasibility of increased HIV testing in clinical setting strategy among primary care providers. Consistent with previous research, the results of this study indicate that primary care providers can play a significant role in encouraging and facilitating annual routine testing as a standard of care for high-risk MSM. This article offers policy and practice recommendations based on these findings.


Laser Effects on the Prevention and Treatment of Dentinal Hypersensitivity: A Systematic Review.
Introduction: Dentinal hypersensitivity (DH) is an acute intensive tooth pain which can lead to dental annoyances during eating and drinking. Stimulating exposed dentinal tubules by either kind of thermal, tactile, chemical and/or osmotic stimuli is believed to be the cause of this pain. It is hypothesized that dentinal tubules' orifice occlusion (DOO) can help relieve such dental irritations. Thus, this systematic review was conducted to evaluate the effectiveness of laser application as a prevention and treatment modality on DH reduction. Methods: Electronic databases (MEDLINE, SCOPUS) were searched among randomized clinical trials from January 2007 to December 2016. The extraction of data and quality assessments were carried out by different independent observers. Results: A total of 499 items were found of which3 9 relevant articles were extracted. The profound findings proved lasers' effectiveness as a treatment of DH. Although some of the researches reported no significant difference between laser and other desensitizing agents, most of the studies suggested that better results (both rapid and long-lasting) were obtained in combined modalities. Furthermore, the preventive role of this new technology has been emphasized as well. Nd-YAG (neodymium-doped yttrium aluminum garnet) and diode lasers reduce DH after bleaching. Lasers can also protect cervical restorations from DH due to tubular occlusion. Moreover, it is suggested to apply lasers in relief of DH following scaling and root planning. Nevertheless, a few researchers dispute its beneficence as a result of placebo effect. Conclusion: The results obtained from several studies in the present review revealed that the application of lasers is effective not only in terms of treatment of DH, but also in the prevention of this intensive tooth pain. Among various types of lasers, the application of Nd:YAG laser has shown the best results in DH treatment.


[Possible uses for callus distraction. Bridging bone defects and bone lengthening in leg length inequality].
Representation of the possibilities of callus distraction for bridging bone defects on the basis of four typical cases successfully treated with this procedure. The filling of large diaphyseal bone defects through the use of callus distraction is reliable, relatively simple to carry out, and in most cases can be done on an outpatient basis. After prior osteotomy, a segment of the remaining bone is forced, millimeterwise, into the defect zone. As a result of continuous distraction of the callus forning in the osteotomy, tubular bone with weight-bearing capability is formed, and the patient is spared the defect resulting at the donor site when an autologous bone graft is taken, or the implantation of exogenous material. The same principle is employed for leg lengthening, and also permits simultaneous compensation of axis malalignment.


[Agricultural and nutritional importance of legumes].
The main ecophysiologic, agronomic and economic feature of legume plants is the development of tubercles and nodules in their apical system. Nodule formation occurs in most legume species provided a compatible type of Rhizobium bacteria is present in the soil. Nitrogen fixation in nodules renders these plants independent of nitrogen fertilizers, the most expensive of all goods in modern cereal agriculture. Considering that soils may get enriched in nitrogen through fixation in nodules and the decomposition of foliage when the aerial parts of legume plants are used as green fertilizers, only through the inclusion of legume crops within planned harvest schemes, it would be possible to achieve success in large scale production strategies. Legume crops are extensively produced in temperate climates areas in which, in addition to their use in animal nutrition, yields of 18 kg per person per year are obtained. In contrast, in the Third World countries located in tropical areas, legume production is scarce, with annual yields of 9 kg per person per year. Currently, it is proposed that the energy and protein intake should match that of the developed countries 40 years ago (i.e. 3000 Kcal and 70 g protein per day); for this, it would be necessary to have an average availability of 60 g of legume seeds per person per day. Therefore, the production of legume seeds should be increased. In addition, research aimed to study and exploit the agronomic potential of this rich botanical family should be strengthened through the formation of interdisciplinary groups.


The Use of CRISPR/Cas9 Gene Editing to Confirm Congenic Contaminations in Host-Pathogen Interaction Studies.
Murine models of Salmonella enterica serovar Typhimurium infection are one of the commonest tools to study host-pathogen interactions during bacterial infections. Critically, the outcome of S. Typhimurium infection is impacted by the genetic background of the mouse strain used, with macrophages from C57BL/6 and BALB/c mice lacking the capacity to control intracellular bacterial replication. For this reason, the use of congenic strains, which mix the genetic backgrounds of naturally protected mouse strains with those of susceptible strains, has the capacity to significantly alter results and interpretation of S. Typhimurium infection studies. Here, we describe how macrophage knockout cell lines generated by CRISPR/Cas9 gene editing can help determine the contribution of background contaminations in the phenotypes of primary macrophages from congenic mice, on the outcome of S. Typhimurium infection studies. Our own experience illustrates how the CRISPR/Cas9 technology can be used to complement pre-existing knockout models, and shows that there is great merit in performing concurrent studies with both genetic models, to exclude unanticipated side-effects on host-pathogen interactions.


Fitness Inference from Short-Read Data: Within-Host Evolution of a Reassortant H5N1 Influenza Virus.
We present a method to infer the role of selection acting during the within-host evolution of the influenza virus from short-read genome sequence data. Linkage disequilibrium between loci is accounted for by treating short-read sequences as noisy multilocus emissions from an underlying model of haplotype evolution. A hierarchical model-selection procedure is used to infer the underlying fitness landscape of the virus insofar as that landscape is explored by the viral population. In a first application of our method, we analyze data from an evolutionary experiment describing the growth of a reassortant H5N1 virus in ferrets. Across two sets of replica experiments we infer multiple alleles to be under selection, including variants associated with receptor binding specificity, glycosylation, and with the increased transmissibility of the virus. We identify epistasis as an important component of the within-host fitness landscape, and show that adaptation can proceed through multiple genetic pathways.


Modulating the growth of chemically deposited ZnO nanowires and the formation of nitrogen- and hydrogen-related defects using pH adjustment.
ZnO nanowires (NWs) grown by chemical bath deposition (CBD) have received great interest for nanoscale engineering devices, but their formation in aqueous solution containing many impurities needs to be carefully addressed. In particular, the pH of the CBD solution and its effect on the formation mechanisms of ZnO NWs and of nitrogen- and hydrogen-related defects in their center are still unexplored. By adjusting its value in a low- and high-pH region, we show the latent evolution of the morphological and optical properties of ZnO NWs, as well as the modulated incorporation of nitrogen- and hydrogen-related defects in their center using Raman and cathodoluminescence spectroscopy. The increase in pH is related to the increase in the oxygen chemical potential (μ O), for which the formation energy of hydrogen in bond-centered sites (HBC) and VZn-NO-H defect complexes is found to be unchanged, whereas the formation energy of zinc vacancy (VZn) and zinc vacancy-hydrogen (VZn-nH) complexes steadily decreases as shown from density-functional theory calculations. Revealing that these VZn-related defects are energetically favorable to form as μ O is increased, ZnO NWs grown in the high-pH region are found to exhibit a higher density of VZn-nH defect complexes than ZnO NWs grown in the low-pH region. Annealing at 450 °C under an oxygen atmosphere helps tuning the optical properties of ZnO NWs by reducing the density of HBC and VZn-related defects, while activating the formation of VZn-NO-H defect complexes. These findings show the influence of pH on the nature of Zn(ii) species, the electrostatic interactions between these species and ZnO NW surfaces, and the formation energy of the involved defects. They emphasize the crucial role of the pH of the CBD solution and open new possibilities for simultaneously engineering the morphology of ZnO NWs and the formation of nitrogen- and hydrogen-related defects.


Phosphorylation and calcium binding properties of an Arabidopsis GF14 brain protein homolog.
Arabidopsis GF14 omega was originally described because of its apparent association with a DNA-protein complex; it is a member of the 14-3-3 kinase regulatory protein family that is conserved throughout eukaryotes. Here, we demonstrated that recombinant GF14 omega is expressed in Escherichia coli as a dimer. Blot binding and electrophoretic mobility shift analyses indicated that GF14 omega binds calcium. Equilibrium dialysis further demonstrated that GF14 omega binds an equimolar amount of calcium with an apparent binding constant of 5.5 x 10(4) M-1 under physiological conditions. The C-terminal domain, which contains a potential EF hand motif, is responsible for the calcium binding. The C-terminal domain also cross-reacted with the anti-GF14 omega monoclonal antibody. In addition, GF14 omega is phosphorylated by Arabidopsis protein kinase activity at a serine residue(s) in vitro. Therefore, GF14 omega protein has biochemical properties consistent with potential signaling roles in plants. The presence of a potential EF hand-like motif in the highly conserved C terminus of 14-3-3 proteins together with the calcium-dependent multiple functions attributed to the 14-3-3 proteins indicate that the C terminus EF hand is a common functional element of this family of proteins.


Immunoproteasomes as a novel antiviral mechanism in rhinovirus-infected airways.
Rhinovirus (RV) infection is involved in acute exacerbations of asthma and chronic obstructive pulmonary disease (COPD). RV primarily infects upper and lower airway epithelium. Immunoproteasomes (IP) are proteolytic machineries with multiple functions including the regulation of MHC class I antigen processing during viral infection. However, the role of IP in RV infection has not been explored. We sought to investigate the expression and function of IP during airway RV infection. Primary human tracheobronchial epithelial (HTBE) cells were cultured at air-liquid interface (ALI) and treated with RV16, RV1B, or interferon (IFN)-λ in the absence or presence of an IP inhibitor (ONX-0914). IP gene (i.e. LMP2) deficient mouse tracheal epithelial cells (mTECs) were cultured for the mechanistic studies. LMP2-deficient mouse model was used to define the in vivo role of IP in RV infection. IP subunits LMP2 and LMP7, antiviral genes MX1 and OAS1 and viral load were measured. Both RV16 and RV1B significantly increased the expression of LMP2 and LMP7 mRNA and proteins, and IFN-λ mRNA in HTBE cells. ONX-0914 down-regulated MX1 and OAS1, and increased RV16 load in HTBE cells. LMP2-deficient mTECs showed a significant increase in RV1B load compared with the wild-type (WT) cells. LMP2-deficient (compared with WT) mice increased viral load and neutrophils in bronchoalveolar lavage (BAL) fluid after 24 h of RV1B infection. Mechanistically, IFN-λ induction by RV infection contributed to LMP2 and LMP7 up-regulation in HTBE cells. Our data suggest that IP are induced during airway RV infection, which in turn may serve as an antiviral and anti-inflammatory mechanism.


Long-term functional outcome after type A3 spinal fractures: operative versus non-operative treatment.
The authors retrospectively studied, by questionnaires, the long-term (5 years) functional outcome after operative (posterior instrumentation: 38 cases) and non-operative treatment (25 cases) for type A3 spinal fractures (Comprehensive Classification) without neurological deficit. A possible bias of this study was the fact that the operative group included 60% A3.2 and A3.3 fractures, versus only 12% in the nonoperative group. Two disease-specific questionnaires were used: the Visual Analogue Scale Spine Score and the Roland-Morris Disability Questionnaire. At follow-up the mean VAS scores were 82.6 and 80.8 in the operatively and non-operatively treated group, respectively; the difference was not significant. The mean RMDQ scores were 3.3 and 3.1 in the operatively and non-operatively treated groups, respectively; again the difference was not significant. Functional outcome appeared to be equally good five years after operative or non-operative treatment of type A3 "burst" fractures.


Knowledge, attitudes and practice of healthcare ethics and law among doctors and nurses in Barbados.
The aim of the study is to assess the knowledge, attitudes and practices among healthcare professionals in Barbados in relation to healthcare ethics and law in an attempt to assist in guiding their professional conduct and aid in curriculum development. A self-administered structured questionnaire about knowledge of healthcare ethics, law and the role of an Ethics Committee in the healthcare system was devised, tested and distributed to all levels of staff at the Queen Elizabeth Hospital in Barbados (a tertiary care teaching hospital) during April and May 2003. The paper analyses 159 responses from doctors and nurses comprising junior doctors, consultants, staff nurses and sisters-in-charge. The frequency with which the respondents encountered ethical or legal problems varied widely from 'daily' to 'yearly'. 52% of senior medical staff and 20% of senior nursing staff knew little of the law pertinent to their work. 11% of the doctors did not know the contents of the Hippocratic Oath whilst a quarter of nurses did not know the Nurses Code. Nuremberg Code and Helsinki Code were known only to a few individuals. 29% of doctors and 37% of nurses had no knowledge of an existing hospital ethics committee. Physicians had a stronger opinion than nurses regarding practice of ethics such as adherence to patients' wishes, confidentiality, paternalism, consent for procedures and treating violent/non-compliant patients (p = 0.01) CONCLUSION: The study highlights the need to identify professionals in the workforce who appear to be indifferent to ethical and legal issues, to devise means to sensitize them to these issues and appropriately training them.


Lack of direct inhibition of insulin secretion by exogenous insulin in the canine pancreas.
To test whether insulin secretion is self-regulatory, canine pancreata were isolated and perfused in vitro and were infused with 0.3, 0.6, or 1.2 mU/ml exogenous insulin. Basal and arginine-stimulated concentrations of C-peptide, glucagon, and somatostatin were measured. There were no significant differences between basal secretion nor the increment of arginine-stimulated secretion for each respective hormone at each exogenous insulin concentration. The second preparation studied was a vascularly isolated, yet innervated, in situ perfused pancreas. Exogenous insulin (1 mU/kg per min) was infused "systemically"; the pancreas received no insulin. Endogenous pancreatic insulin and C-peptide secretion was suppressed, while pancreatic glucagon secretion increased during systemic insulin infusion. No changes in pancreatic hormone secretion occurred after the sympathetic nerves were sectioned. These results suggest that exogenous insulin does not directly suppress the B cell, but can suppress insulin secretion through an indirect neurally mediated, insulin-dependent nerve mechanism.


The development of pain in young pigs associated with castration and attempts to prevent castration-induced behavioral changes.
Four experiments were conducted to examine the development of castration-induced behavioral changes, the effects of castration age on pig weight gain, and the efficacy of common analgesics for use in castrated pigs. In Exp. 1, behavioral changes associated with castration of pigs at 1, 5, 10, 15, or 20 d of age were evaluated. Castration caused measurable changes (reduced suckling, reduced standing, and increased lying times, P < .05) in the behavior of young pigs compared with that of intact pigs at all ages tested. Effects of age and interactions between age and castration treatment were not significant (P > .10) for any behaviors evaluated. In Exp. 2, the performance of pigs castrated at 1 d of age was compared with the performance of those castrated on d 14 and female littermates. Birth weights, weaning weights, and mortality were recorded. Pigs that were castrated on d 14 were heavier (P = .05) at weaning and had a higher (P < .05) weight gain during lactation compared to pigs castrated on d 1 of age. Pig mortality was similar among the treatments. In Exp. 3 and 4, the efficacies of pain-reducing drugs (non-narcotic analgesics) were evaluated for effectiveness in reducing castration-induced behavioral changes in 8-wk-old pigs. Although castration reduced (P < .05) feeding time and weight gain, neither aspirin nor butorphanol influenced behavioral changes associated with castration. We conclude that pigs show similar behavioral changes (and probably pain perception) when castrated from 1 to 20 d of age. However, pig performance data favored castration at 14 d rather than at 1 d of age.(ABSTRACT TRUNCATED AT 250 WORDS)


The prognostic significance of frequency and morphology of premature ventricular complexes during ambulatory holter monitoring.
Multiform premature ventricular complexes (PVCs) are associated with an adverse prognosis in patients with structural heart disease. Very frequent PVCs are associated with ventricular dysfunction. Our hypothesis is that multiform PVCs confer an adverse prognosis in the general population. We performed a retrospective cohort study of patients ≥18 years old referred to our institution for 24-hour ambulatory Holter monitoring between July 1, 2008 and December 31, 2009. Holters without PVCs or with more frequent ectopy (couplets, triplets, or nonsustained ventricular tachycardia) were excluded. Clinical and adverse event (AE) data ("major adverse cardiovascular event" or new/worsening heart failure) were gathered from chart review. Data was analyzed by PVC frequency (rare, occasional, or frequent) and pattern (uniform or multiform). A total of 222 patients (43% male, mean age: 55 ± 16 years) were evaluated (median follow-up 2.3 years [IQR: 2.0-2.6]). Median frequency was 2 PVCs per hour (IQR: 1-13). Multiform PVCs were noted in 48%. Patients with multiform PVCs were older, and had a higher prevalence of comorbidities. Thirty-nine AE were noted. Patients with an AE were younger, had a higher prevalence of HTN, diabetes, CAD, CHF, and previous MI. The multiform group had a higher incidence of AE (28%) compared to the uniform group (8%) (P < 0.001). Increasing PVC frequency was associated with a higher incidence of AE (8% vs 24% vs 35%, respectively). In Cox regression analyses, the multiform pattern but not frequency predicted AE. Multiform PVCs were associated with a 4-fold increase in AE in patients referred for ambulatory Holter monitoring.


Cross-reaction of immune sera from patients with rickettsial diseases.
Rickettsia rickettsii and Rickettsia conorii are the causative agents of two common and serious diseases, Rocky Mountain spotted fever and Mediterranean spotted fever, respectively. In patients naturally infected with either of these organisms, antibodies are produced which cross-react with antigens of the other so extensively that diagnostic tests usually cannot identify the causative agents. The results of this study indicate that serodiagnostic tests with antigen from one of these two organisms could be used to detect antibodies in patients with either of the two rickettsial diseases.


Minireview: Androgen metabolism in castration-resistant prostate cancer.
The decades-old terminology of androgen independence has been replaced in recent years with castration-resistant prostate cancer. Biological and clinical evidence have together conspired to support the use of this revised terminology by demonstrating that in the vast majority of cases tumors are neither truly depleted of androgens, nor are they free of the requirement for androgens to sustain growth and progression. Abiraterone acetate, an androgen synthesis inhibitor, and enzalutamide, a potent androgen receptor antagonist, both exploit the continued requirement for androgens. A central question, given the therapeutic gains enabled by further suppression of the androgen axis with these newer agents, is whether there may be additional clinical benefit gained by moving the goal posts of androgen suppression even further. The answer lies in part with the mechanisms utilized by tumors that enable resistance to these therapies. The aims of this review were to give a broad outline of steroidogenesis in prostate cancer and to highlight recent developments in understanding resistance to hormonal therapies.


Prevalence and characteristics of subclinical giant cell arteritis in polymyalgia rheumatica.
The main objective of this study was to analyse the prevalence and characteristics of subclinical GCA in patients with PMR. This was a cross-sectional multicentre international study of consecutive patients with newly diagnosed PMR without symptoms or signs suggestive of GCA. All patients underwent ultrasound of the temporal superficial, common carotid, subclavian and axillary arteries. Patients with halo signs in at least one examined artery were considered to have subclinical GCA. The clinical, demographic and laboratory characteristics of the PMR group without subclinical vasculitis were compared with to with subclinical GCA, and the pattern of vessel involvement was compared with that of a classical single-centre GCA cohort. We included 346 PMR patients, 267 (77.2%) without subclinical GCA and 79 (22.8%) with subclinical GCA. The PMR patients with subclinical GCA were significantly older, had a longer duration of morning stiffness and more frequently reported hip pain than PMR without subclinical GCA. PMR with subclinical GCA showed a predominant extracranial large vessel pattern of vasculitic involvement compared with classical GCA, where the cranial phenotype predominated. The patients with PMR in the classical GCA group showed a pattern of vessel involvement similar to classical GCA without PMR but different from PMR with subclinical involvement. More than a fifth of the pure PMR patients had ultrasound findings consistent with subclinical GCA. This specific subset of patients showed a predilection for extracranial artery involvement. The optimal screening strategy to assess the presence of vasculitis in PMR remains to be determined.


Quantitative Assessment of Age-dependent Changes in Porphyrins from Fluorescence Images of Ultraviolet Photography by Image Processing.
Skin is the first line of defense against harmful external environmental factors. Skin flora living on the skin surface impact skin health and skin disease. Bacteria, form part of the unique and complex skin micro-ecological system. For example, Propionibacterium acnes (P. acnes) is a member of the anaerobic organisms and is involved in the induction of skin acne. It produces porphyrins that absorb ultraviolet light and emit red fluorescence in response. As a result, fluorescence surveillance of the skin can be important in both the diagnosis of skin acne and the evaluation of therapeutic effects. Many different measurement methods for single skin biophysical properties have been reported.. This study focused on the age-dependent changes in porphyrins for normal skin, and developed a novel algorithm to evaluate porphyrins using the fluorescence images by image processing quantitatively. An extraction algorithm was proposed for the segmentation of porphyrin fluorescence images in OpenCV. The algorithm consisted primarily of preprocessing, conversion from RGB color space to HSV color space, and classification of fluorescence. There are 3595 healthy Japanese aged 16-85 years enrolled in the study and fluorescence images were acquired from their cheek sites under 375 nm UV-LED excitation. Age-related fluorescence variation was conducted applying the algorithm implemented. A new extraction algorithm has been proposed with fluorescence image input and three indexes output, including the number of fluorescence, area of fluorescence, and mean intensity of fluorescence. Proposed algorithm was verified by three parameters, the accuracy, sensitivity, and precision, which refer to the ability of algorithm to detect the number of fluorescence correctly and repeatedly. The verification results were 71%, 72%, and 88% respectively, taking a validly fundamental step for skin health record and analysis. Furthermore, large-scale fluorescence image segmentation results revealed that similar trends were coming out for all three indexes in cheek as people get older. All the fluorescence number, area and mean intensity arrived at the highest at 30 years old and fell off since then. The number, area, and fluorescence intensity of porphyrins can be extracted well from fluorescence images with the proposed algorithm in the study, which has the potential to aid in thediagnosis of skin acne and predict skin conditions as an assisted tool. It is implicated that fluorescence status is influenced by age, which rises to the peak around 30 years old for normal cheek's skin.


A systematic review on physical therapy interventions for patients with binge eating disorder.
Since a distorted body experience and a sedentary lifestyle are central in the course of binge eating disorder (BED), physical therapy might be an interesting add-on treatment. The aim of this study was to systematically review randomised controlled trials (RCTs) evaluating physical therapy on binge eating and physical and mental health in BED patients. EMBASE, PsycINFO, PubMed, Cumulative Index to Nursing and Allied Health Literature, Physiotherapy Evidence Database and Cochrane Library were searched from their inception until 15 August 2012 for relevant RCTs comparing physical therapy with a placebo condition, control intervention or standard care. Three RCTs involving 211 female community patients (age range: 25-63 years) met all selection criteria. Review data demonstrate that aerobic and yoga exercises reduce the number of binges and the body mass index (BMI) of BED patients. Aerobic exercise also reduces depressive symptoms. Only combining cognitive behavioural therapy (CBT) with aerobic exercise and not CBT alone reduces BMI. Combining aerobic exercise with CBT is more effective in reducing depressive symptoms than CBT alone. The limited number of available studies and the heterogeneity of the interventions limit overall conclusions and highlight the need for further research. Because of severe co-morbid psychiatric and physical conditions, binge eating disorder is one of the most difficult psychiatric conditions to treat. Both yoga and aerobic exercise have shown promise in reducing binge eating pathology and weight. Combining aerobic exercise with cognitive behavioural therapy seems more effective in reducing depressive symptoms than cognitive behavioural therapy alone.


[Effect of ftorafur and 5-fluorouracil on the chromosomes of human tumor cell cultures].
The effect of two antitumour drugs, ftorafur (Ft) and 5-fluorouracil (5-FU) on chromosomes of human tumour cells (strain CA-1) was studied in vitro. Since no data on the karyotype of this tumour strain had been published, the chromosome set of the model was investigated at first. Significant quantitative and structural divergence from the normal human male karyotype were observed. Steam line cells contained 47-49 chromosomes, including 9 permanent markers. No Y-chromosome was revealed. Ft and 5-FU hardly injured the chromosomes of CA-1 cells; the level of aberrant metaphases reached 94%. Chromatid deletions and gaps formed the major part of drug-induced cytogenetic abnormalities.


Marinobufagenin regulates permeability and gene expression of brain endothelial cells.
Marinobufagenin (MBG) is a cardiotonic steroid that increases in the circulation in preeclampsia. Preeclampsia and eclampsia are associated with cerebral edema. Therefore, we examined the effects of MBG on human brain microvascular endothelial cells (HBMEC) in vitro. MBG enhanced the permeability of HBMEC monolayers at 1-, 10-, and 100-nM doses, but had no effect at 0.1 nM. Agilent Human Gene Expression microarrays were utilized in these studies. MBG treatment (10 nM for 12 h) downregulated concentrations of the soluble VEGFR transcript sFLT by 59% but did not alter those of FLTv3 mRNA (determined by quantitative PCR). When treated and control HBMEC transcriptomes were interrogated on microarrays, 1,069 genes appeared to be regulated by MBG. Quantitative RT-PCR confirmed that MBG treatment upregulated ENKUR mRNA concentrations by 57%. Its protein product interacts with calmodulin and calcium channel proteins. MBG treatment downregulated several genes whose protein products are involved in cell adhesion (ITGA2B, FERMT1, CLDN16, and TMEM207) and cell signaling (GRIN2C, SLC8A1, and ESR1). The level of downregulation ranged from 22 to 66%. Altogether, MBG actively enhanced the permeability of HBMEC monolayers while downregulating genes involved in adhesion. MBG treatment had variable effects on ENKUR, GRIN2C, and SLC8A1 genes, all associated with calcium transport. These studies provide the basis for future investigations of MBG actions in normal physiology and disease.


Cost-effectiveness of risk-based low-dose computed tomography screening for lung cancer in Switzerland.
Throughout Europe, computed tomography (CT) screening for lung cancer is in a phase of clinical implementation or reimbursement evaluation. To efficiently select individuals for screening, the use of lung cancer risk models has been suggested, but their incremental (cost-)effectiveness relative to eligibility based on pack-year criteria has not been thoroughly evaluated for a European setting. We evaluate the cost-effectiveness of pack-year and risk-based screening (PLCOm2012 model-based) strategies for Switzerland, which aided in informing the recommendations of the Swiss Cancer Screening Committee (CSC). We use the MISCAN (MIcrosimulation SCreening ANalysis)-Lung model to estimate benefits and harms of screening among individuals born 1940 to 1979 in Switzerland. We evaluate 1512 strategies, differing in the age ranges employed for screening, the screening interval and the strictness of the smoking requirements. We estimate risk-based strategies to be more cost-effective than pack-year-based screening strategies. The most efficient strategy compliant with CSC recommendations is biennial screening for ever-smokers aged 55 to 80 with a 1.6% PLCOm2012 risk. Relative to no screening this strategy is estimated to reduce lung cancer mortality by 11.0%, with estimated costs per Quality-Adjusted Life-Year (QALY) gained of €19 341, and a €1.990 billion 15-year budget impact. Biennial screening ages 55 to 80 for those with 20 pack-years shows a lower mortality reduction (10.5%) and higher cost per QALY gained (€20 869). Despite model uncertainties, our estimates suggest there may be cost-effective screening policies for Switzerland. Risk-based biennial screening ages 55 to 80 for those with ≥1.6% PLCOm2012 risk conforms to CSC recommendations and is estimated to be more efficient than pack-year-based alternatives.


Forces required to initiate membrane tether extrusion from cell surface depend on cell type but not on the surface molecule.
When a cell adhered to another cell or substratum via surface proteins is forced to detach, lipid membrane tethers are often extruded from the cell surface before the protein bond dissociates. For example, during the inflammatory reaction leukocytes roll on the surface of activated endothelial cells. The rolling adhesion is mediated by interactions of selectins with their ligands, e.g., P-selectin glycoprotein ligand (PSGL)-1, which extrudes membrane tethers from the surfaces of both leukocytes and endothelial cells. Membrane tether extrusion has been suggested to regulate leukocyte rolling. Here we examine several factors that may affect forces required to initiate membrane tethers, or initial tether force. It was found that initial tether forces were similar regardless of the presence or absence of the cytoplasmic tail of P-selectin and regardless of whether the tethers were extruded via binding to PSGL-1 or Fcy receptors. Initial tether forces were found to depend on the cell types tested and were greatly reduced by treatment of latrunculin A, which inhibits actin polymerization. These data provide additional insights to the control of membrane tether extrusion, which should be taken into account when cellular functions such as rolling where tether extrusion plays a regulatory role are compared using different cell types expressing the same molecule.


Will opposites attract? Similarities and differences in students' perceptions of the stereotype profiles of other health and social care professional groups.
The extent to which health and social care (HSC) students hold stereotypical views of other HSC professional groups is of great potential importance to team working in health care. This paper explores students' perceptions of different HSC professional groups at the beginning of their university programmes. Findings are presented from an analysis of baseline data collected as part of the New Generation Project longitudinal cohort study which is assessing the impact of interprofessional education over time on a range of variables including stereotyping. Questionnaires were administered to a cohort of over 1200 students from 10 different HSC professional groups entering their first year of university. Stereotypes were measured using a tool adapted from Barnes et al. (2000) designed to elicit stereotype ratings on a range of nine characteristics. The findings confirm that students arrive at university with an established and consistent set of stereotypes about other health and social care professional groups. Stereotypical profiles were compiled for each professional group indicating the distinctive characteristics of the groups as well as the similarities and differences between groups.Midwives, social workers and nurses were rated most highly on interpersonal skills and on being a team player whilst doctors were rated most highly on academic ability. Doctors, midwives and social workers were perceived as having the strongest leadership role, whilst doctors were also rated most highly on decision making. All professions were rated highly on confidence and professional competence and, with the exception of social workers, on practical skills. A comparison of profiles for each professional group reveals that, for example, pharmacists and doctors were perceived as having very similar characteristics as were social workers, midwives and nurses. However, the profiles of nurses and doctors were perceived to be very different. The implications of these similarities and differences are discussed in terms of their potential impact on interprofessional interactions, role boundaries and team working.


Positively selected autologous blood CD34+ cells and unseparated peripheral blood progenitor cells mediate identical hematopoietic engraftment after high-dose VP16, ifosfamide, carboplatin, and epirubicin.
To investigate the feasibility of peripheral blood CD34+ cell selection and to analyze CD34+ cell-mediated engraftment after high-dose chemotherapy, we performed a phase I/II trial in 21 patients with advanced malignancies. The rationale for the selection of CD34+ cells from peripheral blood progenitor cell (PBPC) collections is based on the observation that contaminating tumor cells can be depleted approximately 3 logs using this procedure. CD34+ cells from chemotherapy+granulocyte colony-stimulating factor-mobilized PBPCs were positively selected with an avidin-biotin immunoadsorption column (CEPRATE SC system). One leukapheresis product with a median number of 2.8 x 10(6) CD34+ cells/kg was labeled with a biotinylated anti-CD34 monoclonal antibody and subsequently processed over the column. The yield of selected CD34+ cells was 73% +/- 24.6%. The purity of the CD34+ cell fraction was 61.4% +/- 19.7%. CD34+ cells were shown to represent predominantly committed progenitors coexpressing CD33, CD38, and HLA-DR molecules (lin+). They gave rise to myeloid as well as erythroid and multilineage colonies in vitro. In addition, positively selected CD34+ cells also comprised early hematopoietic progenitor cells, as shown by the presence of CD34+/lin- cells. Transfusion of positively selected CD34+ cells (2.5 x 10(6) CD34+/kg; range, 0.45 to 5.1) after high-dose VP16 (1,500 mg/m2), ifosfamide (12 g/m2), carboplatin (750 mg/m2), and epirubicin (150 mg/m2) (VIC-E) in 15 patients resulted in a rapid and stable engraftment of hematopoiesis without any adverse events. As compared with 13 historical control patients reconstituted with a comparable number of unseparated PBPCs, time to neutrophil and platelet recovery was identical in both groups (absolute neutrophil count > 500/microL, day + 12; platelet count > 50,000/microL, day + 15). These data indicate that autologous peripheral blood CD34+ cells and unseparated PBPCs mediate identical reconstitution of hematopoiesis after high-dose VIC-E chemotherapy. Because positive selection of CD34+ cells from mobilized blood results in a median 403-fold depletion of T cells, allogeneic CD34+ cells from mobilized blood should be investigated as an alternative to bone marrow cells for allotransplantation.


Pigmented choroid plexus papilloma.
A pigmented choroid plexus papilloma was found in the left lateral ventricle of a 15-year-old white boy with a 10-year history of seizures. Grossly the lesion appeared finely lobular, orangish brown, rubbery, gritty, and friable. Microscopic examination revealed delicate papillary formations reminiscent of normal choroid plexus, with simple cuboidal to columnar epithelium overlying fibrovascular cores. Light- and electron-microscopic studies demonstrated that the neoplastic cell pigment consisted of both neuromelanin and lipofuscin. To our knowledge, this is the first reported case of neuromelanin pigmentation within a choroid plexus papilloma.