The Tel-Abl (ETV6-Abl) tyrosine kinase, product of complex (9;12) translocations in human leukemia, induces distinct myeloproliferative disease in mice.
Several patients with clinical features of chronic myeloid leukemia (CML) have fusion of the TEL (ETV6) gene on 12p13 with ABL on 9q34 and express a chimeric Tel-Abl protein that contains the same portion of the Abl tyrosine kinase fused to Tel, an Ets family transcription factor, rather than Bcr. In a murine retroviral bone marrow transduction-transplantation model, a Tel (exon 1-5)-Abl fusion protein induced 2 distinct illnesses: a CML-like myeloproliferative disease very similar to that induced by Bcr-Abl but with increased latency and a novel syndrome characterized by small-bowel myeloid cell infiltration and necrosis, increased circulating endotoxin and tumor necrosis factor alpha levels, and fulminant hepatic and renal failure. Induction of both diseases required the Tel pointed homology oligomerization domain and Abl tyrosine kinase activity. Myeloid cells from mice with both diseases expressed Tel-Abl protein. CML-like disease induced by Tel-Abl and Bcr-Abl was polyclonal and originated from cells with multilineage (myeloid, erythroid, and B- and T-lymphoid) repopulating ability and the capacity to generate day-12 spleen colonies in secondary transplantations. In contrast to findings with Bcr-Abl, however, neither Tel-Abl-induced disease could be adoptively transferred to irradiated secondary recipient syngeneic mice. These results show that Tel-Abl has leukemogenic properties from distinct from those of Bcr-Abl and may act in a different bone marrow progenitor.


Cx43- and Smad-Mediated TGF-β/ BMP Signaling Pathway Promotes Cartilage Differentiation of Bone Marrow Mesenchymal Stem Cells and Inhibits Osteoblast Differentiation.
The aim of this study was to investigate the influence of Cx43- and Smad-mediated TGF-β/BMP signaling pathway on the differentiation of bone marrow mesenchymal stem cells (BMSCs) into cartilage and inhibition of ossification. BMSCs of Wistar rats were cultured and assigned into 5 groups for transfection with adenoviruses. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting were employed to detect mRNA and protein expressions of target genes. The condition of cartilage and ossification were measured by a series of staining methods. Subcutaneous injection of mesenchymal stem cells (MSCs) into nude rats was performed. After transfection, compared to the AdGFP group, the corresponding target mRNAs were overexpressed in the AdBMP2, AdSmad1, AdCx43 + AdSmad1 and AdCx43 + AdSmad1 + AdBMP2 groups, and overexpression of BMP2 at the mRNA and protein expression was observed in the AdSmad1 and AdCx43 + AdSmad1 groups. The mRNA expressions of aggrecan (ACAN) and collagen type II alpha 1 (Col2a1), the glycosaminoglycan content of the extracellular matrix and the expression of type II collagen, Col2a1, osteopontin (OPN) and osteocalcin (OC) were higher in the AdBMP2, AdSmad1, AdCx43 + AdSmad1 and AdCx43 + AdSmad1 + AdBMP2 groups than in the AdGFP group; alkaline phosphatase (ALP) activity and mRNA and protein expressions of Runx2 were also higher in these groups than in the AdGFP group. Heterotopic osteogenesis tests demonstrated evident cartilage differentiation ability in the AdCx43 + AdSmad1 + AdBMP2 groups. In comparison, the AdCx43 + AdSmad1 and AdSmad1 groups exhibited weaker cartilage differentiation abilities. Cx43 and Smad1 promote BMP-induced cartilage differentiation of BMSCs and inhibit osteoblast differentiation, which provide a new strategy for cartilage tissue engineering using exogenous Cx43 and Smad1.


Transcriptional and translational control of glucose-stimulated (pro)insulin biosynthesis.
Islets of Langerhans were isolated from the pancreata of fed or 48-h-fasted Wistar rats. The islets were incubated with either [3H]leucine of [3H]uridine. Inhibition of RNA synthesis by actinomycin D or by alpha-amanitin for 4 h had no influence on the (pro)insulin biosynthesis of isolated islets of fed rats. The (pro)insulin biosynthesis was not inhibited after two days incubation of islets of fed rats with alpha-amanitin either. Incorporation of labelled uridine into total RNA for 3 h was stimulated by glucose in islets of fasted, but not of fed rats. Therefore, it was concluded that transcriptional control does not participate, even for longer periods than believed previously, in acute regulation of (pro)insulin biosynthesis of islets isolated fed rats. Despite the strong and preferential stimulation of (pro)insulin biosynthesis of islets of fed rats by glucose the radioactivity of the [3H]uridine-labelled polysomes active in proinsulin synthesis remained unchanged. To interprete these experimental data we suggest that glucose triggers the transformation of a translationally inactive form of pre-proinsulin mRNA to a translationally active form.


The frequency of homozygous deletion of a developmentally regulated Vh gene (Humhv3005) is increased in patients with chronic idiopathic thrombocytopenic purpura.
Little is known of the genetic factors that may contribute to the development of chronic idiopathic thrombocytopenic purpura (cITP). We have previously shown that a developmentally regulated Vh gene (Humhv3005) is absent in 10/41 (24%) of patients with systemic lupus erythematosus while it is absent in only 7/88 (8%) of normal controls. This finding suggests that a homozygous deletion of an Ig variable (V) gene may alter the immune system and thus predispose the host to an autoimmune disorder. We have analyzed the same gene in 44 patients with cITP and found that Humhv3005 and like genes were absent in a higher percentage of patients (14 of 44, 31.8%) than they were absent in either normals (7/88, 8%, p = 0.002) or thrombocytopenic patients without cITP (6/53, 11.3%, p = 0.042); the hv3005 deletion frequency in the latter group did not differ from that in normals (P = 0.74). These data suggest that deletions of Humhv3005 and/or highly homologous Vh genes may predispose individuals to the development of cITP, and may contribute toward production of pathogenic antiplatelet antibodies.


Identification and molecular characterization of porcine kobuvirus in U. S. swine.
Porcine kobuvirus has been associated with piglet diarrhea in Asia and Europe, but there are no reports of its presence in the U.S. swine farms. We screened intestinal contents from 114 diarrheic pigs and fecal samples from 46 apparently healthy pigs to determine the presence of kobuvirus by reverse transcription-polymerase chain reaction using 3D (RNA polymerase) region primers (amplicon size 216 bp). The samples from ill pigs came from 15 different U.S. states, while those from healthy pigs were obtained from three different farms in Minnesota. Twenty-five (21.9 %) pigs with diarrhea and ten (21.7 %) healthy pigs were positive for kobuvirus. All strains from diarrheic pigs were further typed by means of VP1 region primers (amplicon size 811 bp). Phylogenetic analysis revealed that all porcine kobuvirus strains had 93.1-96.5 % nucleotide identity with NLD45 strain from the Netherlands and BRA24 strain from Brazil in the 3D region. In the VP1 region, only 86.7-88.5 % homology was found with the T247 strain from Japan and 85.8-87.4 % homology with WUH1 strain from China. All 25 kobuvirus positive pigs had mixed infection with transmissible gastroenteritis virus and/or rotavirus (groups A, B, or C). Pigs less than 4 weeks of age showed higher prevalence of kobuvirus than the older pigs. The results of this preliminary study indicate that porcine kobuvirus is present in both healthy and diarrheic pigs in the U.S. and that further studies are needed to determine its role in gastrointestinal infections of pigs.


Geraniol-mediated osteoarthritis improvement by down-regulating PI3K/Akt/NF-κB and MAPK signals: In vivo and in vitro studies.
Osteoarthritis (OA) is a degenerative disease that has received increasing attention among the elderly. Its clinical manifestation is primarily long-term joint pain. Evidence for the pharmacological effects of geraniol in various diseases is accumulating. However, whether geraniol has a therapeutic effect against OA remains to be determined. In this study, we discussed the anti-inflammatory effects of geraniol in IL-1β-induced chondrocytes and the anti-cartilage degradation effects in a mouse model of destabilization of the medial meniscus (DMM). In cell experiments, we found that the treatment of geraniol inhibited the expression of IL-1β-induced PGE2, NO, COX-2, iNOS, TNF-α and IL-6 by western blot, qRT-PCR and immunofluorescence staining. Besides, geraniol inhibited the expression of MMP-9 and ADAMTS-5, and reversed the degradation of aggrecan and type II collagen. Mechanistically, we revealed that geraniol suppressed IL-1β-stimulated PI3K/Akt/NF-κB and MAPK activation. Importantly, we have found in animal experiments that oral treatment of geraniol was beneficial in protecting articular cartilage from degradation. Overall, these data indicated that geraniol may have the potential to be developed as an effective treatment for OA.


Moderators and Predictors of Response to Eating Disorder Risk Factor Reduction Programs in Collegiate Female Athletes.
The primary aim of this paper was to investigate moderators and predictors of response to two programs designed to reduce eating disorder risk factors in collegiate female athletes. This study served as an ancillary study to a parent trial that investigated the feasibility of an athlete modified cognitive dissonance-based program (AM-DBP) and an athlete modified healthy weight intervention program (AM-HWI). 157 female collegiate athletes were randomized to either the AM-DBP or the AM-HWI program. Participants completed surveys at baseline, post-intervention, 6 weeks, and 1 year. After classifying sports as either lean or non-lean, we investigated if sport type acted as a moderator of program response to AM-DBP and AM-HWI using ANOVAs. Next, we examined whether baseline thin-ideal internalization, weight concern, shape concern, bulimic pathology, dietary restraint, and negative affect acted as predictors of changes in bulimic pathology using linear regression models. Athletes in non-lean sports who received AM-DBP showed more improvement in negative affect versus non-lean sport athletes in AM-HWI. Higher baseline scores of bulimic pathology predicted greater response in bulimic pathology to both programs at 6-weeks. In contrast, athletes with higher dietary restraint and negative affect baseline scores showed decreased response to both interventions at 6-weeks. Finally, athletes with higher baseline shape concern showed a decreased response to the AM-HWI intervention at the post intervention time point. Results from the present study indicate that lean/non-lean sport may not play a strong role in determining response to efficacious programs. Further, factors such as pre-existing bulimic pathology, dietary restraint, negative affect, and shape concern may affect general response to intervention versus specific responses to specific interventions.


POPULATION GENETICS OF INTRAGAMETOPHYTIC SELFING.
Intragametophytic selfing is a mode of reproduction occurring in homosporous ferns where two gametes from the same haploid gametophyte form a completely homozygous sporophyte. The inbreeding equilibrium is derived for a population with partial intragametophytic selfing, selfing, and outcrossing. Procedures for directly estimating the extent of intragametophytic selfing and selfing using parent-offspring data are given. The conditions for a stable polymorphism from a heterozygous-advantage fitness model are more restrictive for partial intragametophytic selfing than for selfing. The rate of decay of gametic disequilibrium is slower for partial intragametophytic selfing than for selfing. Based on these findings, one would predict that plants with intragametophytic selfing would have less polymorphism for loci with a heterozygous advantage and more gametic disequilibrium between neutral loci than is expected for populations with an equivalent amount of selfing. Data from several studies are consistent with these predictions.


Are emotionally attached companion animal caregivers conscientious and neurotic? Factors that affect the human-companion animal relationship.
Few studies have examined how personality traits may be related to the amounts and types of attachments humans have toward companion animals (pets). In this study, 1,098 companion animal guardians (owners) completed a survey that included the Big Five Inventory, the Lexington Attachment to Pets Scale, and the Pet Attachment Questionnaire. Each participant chose whether he or she identified as a Cat Person, Dog Person, Both, or Neither. Results indicated that neuroticism, conscientiousness, choosing a dog as a favorite pet, and identifying as a Cat Person, Dog Person, or Both predicted affection for a pet. Conscientiousness, extraversion, and openness decreased avoidant attachment to pets, and neuroticism increased anxious attachment to pets. Both dogs and cats could benefit from pet owners who are conscientious, and there may be some benefits of neuroticism in pet owners. The findings of this study will advance understanding of the human-animal bond. As this understanding increases, measurements of human attachment and personality may be useful for the development of tools that could assist shelter employees and veterinarians in counseling people about pet ownership.


Respiratory muscle performance with stretch-shortening cycle manoeuvres: maximal inspiratory pressure-flow curves.
To test the hypothesis that the maximal inspiratory muscle (IM) performance, as assessed by the maximal IM pressure-flow relationship, is enhanced with the stretch-shortening cycle (SSC). Maximal inspiratory flow-pressure curves were measured in 12 healthy volunteers (35 +/- 6 years) during maximal single efforts through a range of graded resistors (4-, 6-, and 8-mm diameter orifices), against an occluded airway, and with a minimal load (wide-open resistor). Maximal inspiratory efforts were initiated at a volume near residual lung volume (RV). The subjects exhaled to RV using slow (S) or fast (F) manoeuvres. With the S manoeuvre, they exhaled slowly to RV and held the breath at RV for about 4 s prior to maximal inspiration. With the F manoeuvre, they exhaled rapidly to RV and immediately inhaled maximally without a post-expiratory hold; a strategy designed to enhance inspiratory pressure via the SSC. The maximal inspiratory pressure-flow relationship was linear with the S and F manoeuvres (r2 = 0.88 for S and r2 = 0.88 for F manoeuvre, P < 0.0005 in all subjects). With the F manoeuvre, the pressure-flow relationship shifted to the right in a parallel fashion and the calculated maximal power increased by approximately 10% (P < 0.05) over that calculated with the S manoeuvre. The maximal inspiratory pressure-flow capacity can be enhanced with SSC manoeuvres in a manner analogous to increases in the force-velocity relationship with SSC reported for skeletal muscles.


Unusual dyslipoproteinemia in a patient with primary systemic amyloidosis and nephrotic syndrome. Role of excessive cholesterol synthesis.
We describe a patient with primary systemic amyloidosis, nephrotic syndrome and unusual dyslipoproteinemia. Levels of plasma cholesterol greater than 2,000 mg/dl and triglycerides greater than 3,000 mg/dl were observed. As much as 70% of the plasma cholesterol separated into abnormal very-low-density lipoprotein (VLDL) with cholesterol ester/triglyceride weight ratio of 0.7-1.0. Intermediate-density lipoprotein (IDL) and low-density lipoprotein (LDL) were also elevated, and high-density lipoprotein (HDL) was low. Both LDL and HDL were triglyceride rich. Neither IDL nor LDL was detected after in vitro lipolysis of VLDL triglycerides (95%); hence, IDL and LDL were most probably secreted directly from liver cells. Treatment by weekly plasma exchange was instituted, and the progression of the amyloidosis was slowed. Endogenous cholesterol synthesis, estimated from increments of plasma cholesterol after exchange, was greater than 2,000 mg/dl. We conclude that the unusual dyslipoproteinemia observed in this patient represents a special type of nephrotic syndrome with remarkably enhanced endogenous cholesterol production.


Passive acoustic observations of tide height in the Iroise Sea using ambient noise.
Considering a broadband motionless source in a waveguide with a depth that varies with time, the time-frequency representation of the acoustic intensity shows a striation pattern than can be explained using the depth-frequency waveguide invariant. This phenomenon is used here to describe acoustic data recorded in the Iroise Sea, where intense tides occur. The originality of this study is that the acoustic data consist of only ambient noise. The best hypothesis is that these striations are created by distant marine traffic in the Bay of Brest, and the results suggest that tide height can be monitored using long-term passive acoustics.


Time-Dependent Extension of the Long-Range Corrected Density Functional Based Tight-Binding Method.
We present a consistent linear response formulation of the density functional based tight-binding method for long-range corrected exchange-correlation functionals (LC-DFTB). Besides a detailed account of derivation and implementation of the method, we also test the new scheme on a variety of systems considered to be problematic for conventional local/semilocal time-dependent density functional theory (TD-DFT). To this class belong the optical properties of polyacenes and nucleobases, as well as charge transfer excited states in molecular dimers. We find that the approximate LC-DFTB method exhibits the same general trends and similar accuracy as range-separated DFT methods at significantly reduced computational cost. The scheme should be especially useful in the determination of the electronic excited states of very large molecules, for which conventional TD-DFT is supposed to fail due to a multitude of artificial low energy states.


Virtual assessment of stereoscopic viewing of digital breast tomosynthesis projection images.
Digital breast tomosynthesis (DBT) acquires a series of projection images from different angles as an x-ray source rotates around the breast. Such imaging geometry lends DBT naturally to stereoscopic viewing as two projection images with a reasonable separation angle can easily form a stereo pair. This simulation study assessed the efficacy of stereo viewing of DBT projection images. Three-dimensional computational breast phantoms with realistically shaped synthetic lesions were scanned by three simulated DBT systems. The projection images were combined into a sequence of stereo pairs and presented to a stereomatching-based model observer for deciding lesion presence. Signal-to-noise ratio was estimated, and the detection performance with stack viewing of reconstructed slices was the benchmark. We have shown that: (1) stereo viewing of projection images may underperform stack viewing of reconstructed slices for current DBT geometries; (2) DBT geometries may impact the efficacy of the two viewing modes differently: narrow-arc and wide-arc geometries may be better for stereo viewing and stack viewing, respectively; (3) the efficacy of stereo viewing may be more robust than stack viewing to reductions in dose. While in principle stereo viewing is potentially effective for visualizing DBT data, effective stereo viewing may require specifically optimized DBT image acquisition.


[The problem of acquired aplastic anaemia].
PURE RED CELL APLASIA: Designated by the acronym PRCA or the term erythroblastopenia, pure red cell aplasia is characterised by severe anaemia with reticulocytopenia. It may occur in acute form induced by infectious agents, following drug toxicity or transplantation of allogeneic haematopoietic cells, associated with autoimmune haemolytic anaemia. The chronic form is rarely constitutional but can be acquired and is usually associated with blood or idiopathic diseases. IMMUNOLOGICAL INHIBITION OF ERYTHROPOIESIS: Among the mechanisms responsible for PRCA is immunological erythropoiesis inhibition. This may be of lymphocyte T cell origin or due to the presence of antibodies in the patient's serum. Although observations of PRCA with presence of neutralising antierythropoietin antibodies in patient's serum have multiplied over the past 5 years, they still remain extremely rare. From a therapeutic point of view, they require withdrawal of epoetin and often the administration of immunosuppressors and transfusion for symptomatic treatment. GROWTH FACTORS: The role of growth factors in restoring aplastic anaemia appears to be only partial, at random and temporary.


Osteogenesis and angiogenesis in regenerating bone during transverse distraction: quantitative evaluation using a canine model.
For some patients with a bone defect, curved deformity, or small diameter bone, transverse distraction might be better indicated than bone transport or lengthening. However, detailed quantitative evaluation of osteogenesis or angiogenesis during transverse distraction by creating a well-controlled animal model has not been done. We established a transverse distraction model of the canine tibia. A rectangular cortex was separated for a distraction fragment. Seven days after the operation, 0.5-mm distraction was applied twice daily for 14 days. After a 28-day consolidation period, the animals were sacrificed. Quantitative evaluations of the rates of mineralization and the increases of bone mineral density indicated faster mineralization and earlier corticalization of the regenerating bone in the initial stage of the consolidation period. The average blood vessel volume ratio in the distraction area was more than three times greater than in the intact contralateral tibiae. We hypothesized that adequate preservation of the marrow arteries and stability of the distraction site throughout an experimental period could induce this faster osteogenesis. Our results indicated that the transverse distraction technique was feasible. The transverse distraction technique could be indicated for patients with small-diameter bones or with massive bone defects.


Halothane sensitizes the guinea-pig heart to pharmacological IKr blockade: comparison with urethane anesthesia.
Potential utility of halothane-anesthetized guinea pigs for detecting drug-induced repolarization delay was analyzed in comparison with urethane-anesthesia (n = 4 for both groups). Basal QT interval was significantly greater under halothane-anesthesia than urethane-anesthesia (192 +/- 7 vs 132 +/- 5 ms, respectively), whereas the reverse was true for the heart rate (190 +/- 7 vs 248 +/- 11 beats/min, respectively). The typical I(Kr)-blocker dl-sotalol (0.1 to 3 mg/kg, i.v.) induced dose-related bradycardia and QT interval prolongation under each anesthesia. The extent of maximum prolongation in the QT interval was greater under halothane-anesthesia than urethane-anesthesia (+101 +/- 15 vs +49 +/- 3 ms, respectively), whereas that of peak change in the heart rate was smaller under the former than the latter (-49 +/- 8 vs -63 +/- 5 beats/min, respectively). Pretreatment of the animals under urethane-anesthesia with the selective I(Ks) blocker chromanol 293B (n = 6) increased the extent of the dl-sotalol-induced QT interval prolongation to +57 +/- 8 ms, which was only 0.56 times of that under the halothane-anesthesia, whereas the pretreatment increased the peak change in the heart rate to -76 +/- 12 ms. These results indicate that the halothane-anesthesia may effectively sensitize the guinea-pig heart to pharmacological I(Kr) blockade.


Cellular transporters for zinc.
Nutritionally essential metals such as zinc are moved into and out of cells by a series of transport proteins or transporters. Their tri-fold purpose is to procure zinc from the environment, to protect cells against zinc toxicity, and maintain ample supplies of zinc for metabolic purposes. Two families of zinc transporters are known: the ZIP family that imports zinc and the ZnT family that functions in releasing zinc or sequestering zinc internally.


Primary amebic meningoencephalitis--Georgia, 2002.
In early September 2002, the Georgia Division of Public Health and CDC were notified about a fatal case of primary amebic meningoencephalitis (PAM) caused by Naegleria fowleri in a boy aged 11 years who had recently swum in a local river. This report summarizes the case investigation. In response to this case, the district health department recommended that local community authorities advise persons to avoid swimming in this river during periods of high temperature and low water depth.


Temporal evolution of sample entropy in thermal lens system.
The photothermal phenomenon resulting in thermal lens formation in liquid media involves complex molecular dynamics responsible for temperature and refractive index variation. As a thermodynamic system, the entropy of the medium also changes. In this paper, the time series and phase portrait analysis of the thermal lens signal is carried out to understand the molecular dynamics. The study reveals the increase in complexity, disorder, and antipersistance nature through fractal dimension, sample entropy, and Hurst exponent, respectively. The analysis of the signal on segmentation reveals the evolution of sample entropy and the stochastic nature of the system with time. The phase portrait analysis also is in support of these observations. Thus, the study suggests that the temporal evolution of sample entropy is similar to the temperature-dependent refractive index.


Redescription of Neocamallanus singhi (Nematoda: Camallanidae) with a note on related species.
The present paper deals with the redescription of the nematode Neocamallanus singhi Ali, 1957 based on specimens collected from the fish, Channa striata from Burdwan, West Bengal, India. Comparative study of this species with other related forms described from freshwater fishes of India and Pakistan indicates that Neocamallanus bengalensis Soota et Chaturvedi, 1971 and N. ophicephali Rehana et Bilquees, 1972 are synonyms of N. singhi.


Time-dependent fiber bundles with local load sharing. II. General Weibull fibers.
Fiber bundle models (FBMs) are useful tools in understanding failure processes in a variety of material systems. While the fibers and load sharing assumptions are easily described, FBM analysis is typically difficult. Monte Carlo methods are also hampered by the severe computational demands of large bundle sizes, which overwhelm just as behavior relevant to real materials starts to emerge. For large size scales, interest continues in idealized FBMs that assume either equal load sharing (ELS) or local load sharing (LLS) among fibers, rules that reflect features of real load redistribution in elastic lattices. The present work focuses on a one-dimensional bundle of N fibers under LLS where life consumption in a fiber follows a power law in its load, with exponent rho , and integrated over time. This life consumption function is further embodied in a functional form resulting in a Weibull distribution for lifetime under constant fiber stress and with Weibull exponent, beta. Thus the failure rate of a fiber depends on its past load history, except for beta=1 . We develop asymptotic results validated by Monte Carlo simulation using a computational algorithm developed in our previous work [Phys. Rev. E 63, 021507 (2001)] that greatly increases the size, N , of treatable bundles (e.g., 10(6) fibers in 10(3) realizations). In particular, our algorithm is O(N ln N) in contrast with former algorithms which were O(N2) making this investigation possible. Regimes are found for (beta,rho) pairs that yield contrasting behavior for large N. For rho>1 and large N, brittle weakest volume behavior emerges in terms of characteristic elements (groupings of fibers) derived from critical cluster formation, and the lifetime eventually goes to zero as N-->infinity , unlike ELS, which yields a finite limiting mean. For 1/2<or=rho<or=1 , however, LLS has remarkably similar behavior to ELS (appearing to be virtually identical for rho=1 ) with an asymptotic Gaussian lifetime distribution and a finite limiting mean for large N. The coefficient of variation follows a power law in increasing N but, except for rho=1, the value of the negative exponent is clearly less than 1/2 unlike in ELS bundles where the exponent remains 1/2 for 1/2<rho<or=1. For sufficiently small values 0<rho1, a transition occurs, depending on beta , whereby LLS bundle lifetimes become dominated by a few long-lived fibers. Thus the bundle lifetime appears to approximately follow an extreme-value distribution for the longest lived of a parallel group of independent elements, which applies exactly to rho=0. The lower the value of beta , the higher the transition value of rho , below which such extreme-value behavior occurs. No evidence was found for limiting Gaussian behavior for rho>1 but with 0<beta(rho+1)<1, as might be conjectured from quasistatic bundle models where beta(rho+1) mimics the Weibull exponent for fiber strength.


Analysis of p16 expression and allelic imbalance / loss of heterozygosity of 9p21 in cutaneous squamous cell carcinomas.
Deletions of the short arm of chromosome 9 have been reported in different types of malignancies. This chromosomal region contains a number of known tumour suppressor genes, including the p16INK4A (CDKN2A), p15INK4B and MTAP tumour suppressor genes located at 9p21. In this study twenty-two paraffin embedded invasive cutaneous SCC were examined for allelic imbalance/ loss of heterozygosity (AI/LOH) of the 9p region (in particular 9p21), and for p16 protein expression. DNA was isolated from microdissected sections of normal and tumour cells and analysed for AI/LOH by using six fluorescently labelled microsatellite markers that map to the 9p region. P16 protein expression was examined by immunohistochemistry. At each of the six microsatellite markers the majority of SCC analysed showed AI/LOH. Overall both AI/LOH within the CDKN2A locus and absence of p16 protein expression were frequent among the cutaneous SCC analysed, suggesting that p16 inactivation may play a role in cutaneous SCC development. The majority of the SCC analysed also had AI/LOH of the marker within the MTAP gene, and at markers flanking the CDKN2A gene; thus further investigation as to a possible role for these genes in the development of cutaneous SCC is warranted.


Indicators of perceived useful dementia care assistive technology: Caregivers' perspectives.
The study aims to investigate the caregivers' context-specific perceived usefulness of available assistive technology (AT) devices and the professionals' perspectives on the usefulness indicators of AT devices for home-dwelling individuals with mild-to-moderate dementia. A total of 72 caregivers completed a questionnaire rating 82 AT devices with a high-perceived usefulness (HPU) or low-perceived usefulness (LPU). A total of 21 experts rated 10 usefulness indicators of these devices. We compared the mean of each indicator between the HPU and LPU groups. Most caregivers, who are generally amenable to using AT devices, thought they were useful for helping to care for home-dwelling older adults with mild-to-moderate dementia. The level of perceived usefulness from the experts' perspectives depends on specific design indicators (e.g. familiarity) and the context in which the AT is used (e.g. in everyday life or in emergencies). Indicators for HPU devices were: allows selective accident prevention, has an intuitive interface, is familiar, offers ease of use and simplifies activities. LPU devices featured client prompting. There were no significant differences between HPU and LPU devices with indicators of: is automated, informs caregiver, preserves privacy and preserves autonomy. Safety issues were considered important, and sometimes overshadowed ethical dilemmas, such as privacy and autonomy concern. The present study provides insight into how caregivers perceived the usefulness of AT devices, and how that varied with context. Indicators of devices perceived as useful can serve as guidelines for modifying existing devices and designing new devices. Future application could also incorporate the points of view from the persons with dementia.


Psychological Distress amid Change: Role Disruption in Girls during the Adolescent Transition.
The present study investigates the underlying cognitive, social, and behavioral tendencies that may explain why some girls are more likely to perceive the adolescent transition as disrupting and difficult, otherwise characterized as role disruption. It was hypothesized that individual differences in rumination, rejection sensitivity, peer problems, and pubertal status would contribute to why some girls perceived more role disruption during the transition from childhood to adolescence, and that girls who reported more role disruption would be at increased risk for subsequent depression. N = 188 girls (Mage = 11.70 years) reported on their level of pubertal development, rumination, rejection sensitivity, peer problems, and depressive symptoms at three time points approximately 4 months apart. Structural equation modeling results suggested that baseline levels of rumination and angry rejection sensitivity explained perceptions of role disruption at Time 2 more than overall levels of pubertal development, and that greater role disruption predicted subsequent depressive symptoms at Time 3. These findings highlight the importance of individual tendencies in understanding who will find early adolescence challenging.


Kidney Dendritic Cells Become Pathogenic during Crescentic Glomerulonephritis with Proteinuria.
It is unclear why kidney dendritic cells attenuate some models of kidney disease but aggravate others. Kidney dendritic cells ameliorate the early phase of nonaccelerated nephrotoxic nephritis, a murine model of crescentic glomerulonephritis, but their effect on the later phase is unknown. Here, we report that kidney dendritic cells at later stages of nephrotoxic nephritis expressed higher levels of costimulatory molecules but lower levels of the cosuppressor molecule ICOS-L and started production of IL-12/23p40 and TNF-α. Furthermore, we noted that kidney dendritic cells captured more filterable antigen in proteinuric mice at late time points of nephrotoxic nephritis and started to capture molecules that were too large for filtration by a healthy kidney. They presented filtered antigen to Th cells, which responded by producing the proinflammatory cytokines IL-2, IFN-γ, TNF-α, IL-6, and IL-17. Notably, production of the suppressive cytokine IL-10 further increased in late nephrotoxic nephritis. Depletion of kidney dendritic cells at a late stage attenuated nephrotoxic nephritis, in contrast to the exacerbation observed with depletion at an early stage, indicating that their acquired proinflammatory phenotype adversely affected disease. These findings indicate that the intrarenal inflammatory microenvironment determines how kidney dendritic cells affect nephritis. In addition, proteinuria may harm the kidney by providing dendritic cells with more antigens to stimulate potentially pathogenic Th cells.


Assessment of the external validity of a predictive score for blood transfusion in liver surgery.
Perioperative bleeding is a predictor of morbidity following liver resection. The transfusion-related score (TRS), which is derived from five variables (cirrhosis, preoperative haemoglobin level, tumour size, vena cava exposure and associated extraliver surgical procedure), has been proposed to predict the likelihood of transfusion in liver resection. The purpose of this observational study was to evaluate the external validity of the TRS. In a retrospective, monocentre, observational cohort study of patients undergoing elective liver resection surgery, data for transfused and non-transfused patients were compared by univariate analysis. The TRS was calculated for each patient. The frequency of transfusion was calculated for each score level. The accuracy of the TRS was evaluated using the area under the receiver operator characteristic curve (AUC). A total of 205 patients submitted to liver resection were included. Of these, 48 (23.4%) patients received a blood transfusion. There was no significant difference between transfused and non-transfused patients in age, American Society of Anesthesiologists (ASA) score or cirrhosis. The AUC for the TRS was 0.68 (95% confidence interval 0.59-0.77). Among TRS items, only vena cava exposure and associated surgical procedures were significantly associated with risk for transfusion. In the present population, the TRS appeared to serve as a weak predictor of perioperative transfusion. This study confirms that the external validity of the transfusion predictive score should be subject to further investigation before it can be implemented in clinical use.


Acid-catalyzed ring-opening reactions of a cyclopropanated 3-aza-2-oxabicyclo[2.2.1]hept-5-ene with alcohols.
The acid-catalyzed ring-opening reactions of a cyclopropanated 3-aza-2-oxabicylic alkene using alcohol nucleophiles were investigated. Although this acid-catalyzed ring-opening reaction did not cleave the cyclopropane unit as planned, this represent the first examples of ring-openings of cyclopropanated 3-aza-2-oxabicyclo[2.2.1]alkenes that lead to the cleavage of the C-O bond instead of the N-O bond. Different acid catalysts were tested and it was found that pyridinium toluenesulfonate in methanol gave the best yields in the ring-opening reactions. The scope of the reaction was successfully expanded to include primary, secondary, and tertiary alcohol nucleophiles. Through X-ray crystallography, the stereochemistry of the product was determined which confirmed an SN2-like mechanism to form the ring-opened product.


Symptomatic hyperlipasemia after cardiopulmonary bypass: implications for enteral nutritional support.
The incidence of pancreatitis after cardiopulmonary bypass is reported as < 0.1%. We report a milder form of pancreatitis characterized by hyperlipasemia and early intolerance to enteral nutrition without overt signs of clinical pancreatitis. A retrospective study was conducted in 72 patients who had received tube feeding. A statistically (p = 0.01) greater incidence of symptomatic hyperlipasemia was noted in post-cardiopulmonary bypass (PCPB) patients (42%, 5 of 12) than in non-PCPB patients (0%, 0 of 60). Four of the 5 PCPB patients who developed symptomatic hyperlipasemia received tube feeding into the stomach or duodenum before onset of their symptoms. The overall incidence of PCPB symptomatic hyperlipasemia during the study period was 1.3% (5 of 375). A prospective study was then carried out in 54 PCPB patients. Five patients became critically ill, and 4 of these developed symptomatic hyperlipasemia. Three of the 4 patients had received tube feeding into the stomach or duodenum before the onset of symptoms. In all cases, the symptoms of tube-feeding intolerance were mild and resolved with termination of feeding. This study suggests that critically ill cardiopulmonary bypass patients may be more susceptible to developing symptomatic hyperlipasemia, which is characterized by early intolerance to enteral nutritional support.


Reproductive performance of sows inseminated with semen doses stored for up to seven days in long-term extender in a field condition.
This study aimed to evaluate the reproductive performance of sows inseminated with semen doses preserved at 15-18 °C for up to seven days in long-term extender (Duragen®). Parity one (PO1) to PO7 sows were randomly assigned to the following groups: AI1-3 (n=190), insemination with semen doses stored between one and three days; and AI5-7 (n=124), insemination with semen doses stored between five and seven days. Sows were submitted to estrus detection twice a day. Post-cervical insemination according to weaning-to-estrus interval was performed. The farrowing rate (FR) did not differ between the groups (AI1-3=83.2%; AI5-7=82.2%; p>0.05) nor did the total number of piglets born (TPB; AI1-3=14.2±0.3; AI5-7=14.5±0.3; p>0.05). Considering the semen dose most likely responsible for fertilization according to its storage time (1, 2-3, 5, and 6-7 days), the FR (72.7%, 87.8%, 85.7%, and 79%, respectively) and TPB (14.4, 14.0, 14.9, and 13.5, respectively) were similar among the groups (p>0.05). In conclusion, the use of semen doses extended with long-term extender stored for up to seven days did not impair the reproductive performance of sows. Therefore, it's using could optimize production efficiency and logistics of semen dose deliveries to sow farms.


Portable flat-panel detector for low-dose imaging in a pediatric intensive care unit: comparison with an asymmetric film-screen system.
We sought to evaluate the diagnostic performance of a portable indirect flat-panel detector for low-dose imaging as compared with an asymmetric film-screen system in a pediatric intensive care unit. A total of 120 neonates underwent chest radiographs using a portable flat-panel detector (digital speed 800) and an asymmetric film-screen system (400 speed). Four readers evaluated the detection of 11 anatomic and 5 pathologic landmarks and 4 support devices. Statistical analysis was performed using repeated analysis of variance. The level of statistical significance was P = 0.05. The detection of 4 anatomic/4 pathologic landmarks and 2 support devices was significantly better using the flat-panel detector as compared with the asymmetric film-screen system (P < 0.05). Another 8 anatomic and one pathologic landmarks were detected equally well or slightly better with the flat-panel detector (P > 0.05). The portable flat-panel detector offers the potential of a 50% dose reduction with equal or significantly better detection of clinically important structures.


Salt Enhances Disease Resistance and Suppresses Cell Death in Ceramide Kinase Mutants.
Sphingolipids act as structural components of cellular membranes and as signals in a variety of plant developmental processes and defense responses, including programmed cell death. Recent studies have uncovered an interplay between abiotic or biotic stress and programmed cell death. In a previous study, we characterized an Arabidopsis (Arabidopsis thaliana) cell-death mutant, accelerated cell death5 (acd5), which accumulates ceramides and exhibits spontaneous cell death late in development. In this work, we report that salt (NaCl) treatment inhibits cell death in the acd5 mutant and prevents the accumulation of sphingolipids. Exogenous application of abscisic acid (ABA) and the salicylic acid (SA) analog benzothiadiazole demonstrated that the effect of NaCl was partly dependent on the antagonistic interaction between endogenous SA and ABA. However, the use of mutants deficient in the ABA pathway suggested that the intact ABA pathway may not be required for this effect. Furthermore, pretreatment with salt enhanced the resistance response to biotic stress, and this enhanced resistance did not involve the pathogen-associated molecular pattern-triggered immune response. Taken together, our findings indicate that salt inhibits sphingolipid accumulation and cell death in acd5 mutants partly via a mechanism that depends on SA and ABA antagonistic interaction, and enhances disease resistance independent of pattern-triggered immune responses.


Exploring the costs and outcomes of sexually transmitted infection (STI) screening interventions targeting men in football club settings: preliminary cost-consequence analysis of the SPORTSMART pilot randomised controlled trial.
The objective of this study was to compare the costs and outcomes of two sexually transmitted infection (STI) screening interventions targeted at men in football club settings in England, including screening promoted by team captains. A comparison of costs and outcomes was undertaken alongside a pilot cluster randomised control trial involving three trial arms: (1) captain-led and poster STI screening promotion; (2) sexual health advisor-led and poster STI screening promotion and (3) poster-only STI screening promotion (control/comparator). For all study arms, resource use and cost data were collected prospectively. There was considerable variation in uptake rates between clubs, but results were broadly comparable across study arms with 50% of men accepting the screening offer in the captain-led arm, 67% in the sexual health advisor-led arm and 61% in the poster-only control arm. The overall costs associated with the intervention arms were similar. The average cost per player tested was comparable, with the average cost per player tested for the captain-led promotion estimated to be £88.99 compared with £88.33 for the sexual health advisor-led promotion and £81.87 for the poster-only (control) arm. Costs and outcomes were similar across intervention arms. The target sample size was not achieved, and we found a greater than anticipated variability between clubs in the acceptability of screening, which limited our ability to estimate acceptability for intervention arms. Further evidence is needed about the public health benefits associated with screening interventions in non-clinical settings so that their cost-effectiveness can be fully evaluated.


[The application of chorioallantois membranes of chicken embryos for the virulence determination of Nocardia asteroides (author's transl)].
The pathogenicity of Nocardia asteroides and other strains of different Nocardia species against chicken embryos was investigated. The strains were inoculated on the chorioallantois membrane of embryonated eggs and the resulting lesions were judged. 55 Nocardia asteroides strains and some strains of the species N. brasiliensis, N. leishmanii, N. caviae, N. (Actinomadura) madurae, N. caprae, N. rubra, N. pellegrini, N. corallina and N. polychromogenes were studied. 47 strains of the species N. asteroides were pathogenic, 2 apathogenic and 6 strains showed doubtful results. All the investigated 5 strains of the species N. brasiliensis, N. leishmanii, N. caviae and N. (Actinomadura) madurae, provoked typical lesions on the chorioallantois membrane. The other investigated strains were apathogenic. With this, described test it is possible to distinguish between pathogenic and apathogenic Nocardia strains, which is indeed important for the diagnosis of Nocardia infection.


Ginsenoside Rg3 suppresses the proliferation of prostate cancer cell line PC3 through ROS-induced cell cycle arrest.
To investigate the potential antitumor effects of ginsenoside Rg3 in prostate cancer cells, the androgen-insensitive prostate cancer cell line PC3 was cultured and incubated with ginsenoside Rg3 in vitro. Cell number counts, cell proliferation assays and senescence-associated β-galactosidase (SA-β-gal) staining were performed to evaluate cell proliferation. The results demonstrated that ginsenoside Rg3 led to cell proliferation arrest; ginsenoside Rg3 decreased the number of cells and increased the positive SA-β-gal staining rate in PC3 cells. Cell cycle analysis by flow cytometry revealed that ginsenoside Rg3 interfered with the G1/S transition in PC3 cells. The mechanism involved in ginsenoside Rg3-induced cell proliferation arrest was then further investigated. This indicated that the level of reactive oxygen species (ROS) in PC3 cells was upregulated by ginsenoside Rg3 treatment. Furthermore, pretreatment with N-acetyl-L-cysteine, a scavenger of ROS, was able to reverse the effects on cell number and cell cycle arrest induced by ginsenoside Rg3 in PC3 cells. These results indicate that ginsenoside Rg3 exhibits anticancer effects on prostate cancer cells through ROS-mediated arrest of the cell cycle.


DNA sequence recognition by an isopropyl substituted thiazole polyamide.
We have used DNA footprinting and fluorescence melting experiments to study the sequence-specific binding of a novel minor groove binding ligand (thiazotropsin A), containing an isopropyl substituted thiazole polyamide, to DNA. In one fragment, which contains every tetranucleotide sequence, sub-micromolar concentrations of the ligand generate a single footprint at the sequence ACTAGT. This sequence preference is confirmed in melting experiments with fluorescently labelled oligonucleotides. Experiments with DNA fragments that contain variants of this sequence suggest that the ligand also binds, with slightly lower affinity, to sequences of the type XCYRGZ, where X is any base except C, and Z is any base except G.


Endogenous tachykinins in antigen-induced acute bronchial responses of guinea pigs.
Because tachykinins (TKs) cause severe bronchoconstriction in humans and animals, this study was carried out to examine whether depletion of TKs can prevent or ameliorate antigen-induced immediate bronchial constriction. Forty-five guinea pigs were randomly divided into six groups: control, antigen challenge, TK depletion + antigen challenge, ganglionic (Ggl) blockade, Ggl blockade + antigen challenge, and TK depletion + Ggl blockade + antigen challenge. Control animals received no treatment. Animals of all antigen challenge groups were sensitized with ovalbumin 10 days before the study. TK depletion was performed via 5-day pretreatment of capsaicin, which began 11 days before the study. On the day of the study, pulmonary resistance (RI), dynamic compliance (Cdyn), and breathing patterns were measured for 15 min just before (baseline) and for 30 min after intravenous injection of either saline (control) or ovalbumin (antigen challenge). In controls, saline injection did not produce any significant change within 30 min, whereas antigen challenge significantly increased RL at 4-15 min and significantly decreased Cdyn at 6-15 min, suggesting antigen-induced bronchoconstriction. Following TK depletion, antigen challenge produced pulmonary changes similar to those without depletion. Ggl blockade reduced RL and breathing frequency, and increased Cdyn and tidal volume; the blockade, however, did not significantly alter (in terms of % baseline) antigen challenge-induced changes in RL, Cdyn, or breathing patterns. These results suggest that TKs and reflexes via Ggl do not appear to be important contributing factors for antigen-induced immediate bronchial constriction in this animal model.


Diagnosing postpartum depression: can we do better?
The purpose of this study was to evaluate the efficacy of the Edinburgh Postnatal Depression Scale versus routine clinical evaluation to detect postpartum depression among a low-income inner-city population and to evaluate risk factors associated with a positive score on the Edinburgh Postnatal Depression Scale. On the basis of the day of the month, all English-speaking patients who were seen for their postpartum visit were assigned either to routine clinical evaluation for postpartum depression or routine clinical evaluation plus the use of the 10-question Edinburgh Postnatal Depression Scale. During the 7-week study period, 72 women participated in the study: 35 women in the routine evaluation group and 37 women in the Edinburgh Postnatal Depression Scale group. Women who completed the Edinburgh Postnatal Depression Scale were significantly more likely than those in the routine evaluation group to be identified as being at risk for depression: 11 of 37 women (30%) versus 0 of 35 women (P <.001). A failed attempt at breast-feeding was associated with an increased risk of a score of > or =10 on the Edinburgh Postnatal Depression Scale (relative risk, 3.78; 95% CI, 1.03-13.89). The Edinburgh Postnatal Depression Scale appears to be a valuable and efficient tool for the identification of patients who are at risk for postpartum depression.


IRF5 is associated with adverse postoperative prognosis of patients with non-metastatic clear cell renal cell carcinoma.
IRF5 is one member of IRFs family, and is critical for host immunity and cell response. In the present study, we sought to search the clinical and prognostic value of IFR5 in patients with non-metastatic ccRCC. IRF5 proved to be an adverse independent prognostic factor for overall survival (p < 0.001) and recurrence free survival (p = 0.002). The newly built nomograms could give better prediction for overall survival and recurrence free survival in ccRCC patients. We included 264 individuals who were diagnosed with non-metastatic clear cell renal cell carcinoma in the present study. Immunohistochemistry staining was performed on tissue microarrays to evaluate the IRF5 expression. χ2 test, Fisher's exact test, t test, Kaplan-Meier method and Cox proportional hazard model were applied to evaluate the prognostic value of IRF5. Two nomograms were constructed to predict clinical outcomes for ccRCC patients after surgery. IRF5 was an adverse independent prognostic factor for both overall survival and recurrence free survival in patients with non-metastatic ccRCC.


The future regulation of artificial intelligence systems in healthcare services and medical research in the European Union.
Despite its promising future, the application of artificial intelligence (AI) and automated decision-making in healthcare services and medical research faces several legal and ethical hurdles. The European Union (EU) is tackling these issues with the existing legal framework and drafting new regulations, such as the proposed AI Act. The EU General Data Protection Regulation (GDPR) partly regulates AI systems, with rules on processing personal data and protecting data subjects against solely automated decision-making. In healthcare services, (automated) decisions are made more frequently and rapidly. However, medical research focuses on innovation and efficacy, with less direct decisions on individuals. Therefore, the GDPR's restrictions on solely automated decision-making apply mainly to healthcare services, and the rights of patients and research participants may significantly differ. The proposed AI Act introduced a risk-based approach to AI systems based on the principles of ethical AI. We analysed the complex connection between the GDPR and AI Act, highlighting the main issues and finding ways to harmonise the principles of data protection and ethical AI. The proposed AI Act may complement the GDPR in healthcare services and medical research. Although several years may pass before the AI Act comes into force, many of its goals will be realised before that.


What happens to the brain in weightlessness? A first approach by EEG tomography.
Basic changes in environmental conditions are fundamental to understanding brain cortical mechanisms. Several studies have reported impairment of central nervous processes during weightlessness. There is ongoing debate as to whether these impairments are attributable to primary physiological effects or secondary psychological effects of the weightlessness environment. This study evaluates the physiological effects of changed gravity conditions on brain cortical activity. In a first experiment, EEG activity of seven participants was recorded at normal, increased and zero gravity during a parabolic flight. Additionally an EEG under normal gravity conditions preflight was recorded. In a second experiment, 24 participants were exposed to a supine, seated and 9 degree head-down tilt position while EEG was recorded. Data were analysed using low resolution brain electromagnetic tomography (LORETA). Beta-2 EEG activity (18-35 Hz) was found to be increased in the right superior frontal gyrus under normal gravity conditions inflight. By exposure to weightlessness a distinct inhibition of this activity within the same areas could be noticed. As the tilt experiment showed changes in the left inferior temporal gyrus in supine and tilted positions we conclude that the observed changes under weightlessness are not explainable by hemodynamic changes but rather reflect emotional processes related to the experience of weightlessness. These findings suggest that weightlessness has a major impact on electro cortical activity and may affect central nervous and adaptation processes.


Left ventricular systolic function in myocardial infarction survivors treated with primary angioplasty, thrombolysis of angioplasty preceded by thrombolysis.
Acute myocardial infarction (AMI) may be treated with thrombolysis, primary angioplasty or a combination of both methods. Preservation of left ventricular systolic function is an important goal of treatment. To assess whether the mode of treatment of AMI influences left ventricular systolic function measured 6 months after AMI. In a group of 108 patients who survived AMI, an echocardiographic examination was performed 6 months afterwards. Ejection fraction, wall motion score index, asynergy area index, infarcted wall motion score index and apical segments motion score index were measured. Patients were divided into three groups: those treated with thrombolysis only, treated with angioplasty or those who underwent angioplasty preceded by thrombolysis. Global left ventricular systolic function was similar in all three groups. Compared to the two remaining groups, the group treated with combined therapy had significantly worse indexes of infarcted wall motion score and apical segments motion score. This group also included a significantly higher number of patients with akinetic or dyskinetic apical segments. Echocardiographic examination of global left ventricular systolic function in MI survivors performed 6 months after AMI, reveals similar values regardless of the method used for AMI treatment. However, segmental systolic function in the area of infarcted wall and apical segments is significantly more altered in patients treated with angioplasty preceded by thrombolysis than in other analysed patients.


The estrogen receptor gene: promoter organization and expression.
The estrogen receptor (ER) is a ligand-activated transcription factor and a member of a large family of nuclear hormone receptors. As a mediator of estrogen hormone action, the ER is involved in many important physiological processes. ER gene expression has been demonstrated to be restricted to certain tissues and under complex hormonal control. However, the molecular mechanisms involved have remained largely unknown. Due to this lack of knowledge an investigation was undertaken to characterize the promoter organization of ER gene and investigate its expression. Approximately 3 kb of the 5' flanking region of the human ER (hER) gene was isolated and sequenced. By performing RT-PCR and RACE experiments it was shown that the hER gene is transcribed from three different promoters. Transcription of the hER gene from these promoters yields three different mRNA isoforms with unique 5' untranslated regions (5'UTRs), but identical coding regions. The expression pattern of the hER mRNA isoforms was investigated by RT-PCR. Both the A- and B-mRNA isoforms were found to be expressed in breast and uterus, whereas expression of the C-transcript was predominantly detected in liver. In bone cells only expression of the B-mRNA could be detected. The steady-state levels of the A- and B-transcripts in normal breast and uterus were quantified and compared with the hER mRNA levels in established cancer cell lines derived from the same tissues. This demonstrated approximately equal levels of the two transcripts in normal tissues whereas the A-mRNA was the most abundant isoform in the cancer cell lines investigated. Approximately 4.5 kb of the 5' flanking region of the rat ER (rER) gene were sequenced. Sequence analysis and PCR experiments suggested that the promoter organization of the rat and human ER genes is only partially conserved which might indicate species-specific differences in the regulation of ER expression. In conclusion, this work suggests tissue-specific alternative promoter usage as a mechanism in the regulation of human and rat ER gene expression.


Bifurcated Rhodaelectro-catalyzed C-H Activation for the Synthesis of Pyrroles and Lactones.
While electrocatalyzed alkyne annulations of arenes represent a powerful strategy for the assembly of heteroaromatic motives, electrochemical C(sp2)-H activations of alkenes remain scarce. Herein, a strategy for the rhodaelectro-catalyzed functionalization of enamides is presented for the efficient construction of pyrroles using electricity as a sustainable oxidant. Moreover, the tuning of the solvent system allowed a fascinating switch in chemoselectivity, which is not possible with traditionally used chemical oxidants, giving rise to lactone architectures. The rhoda-electrocatalysis features a broad scope as well as high regio- and chemoselectivities.


Seed coat metabolite profiling of cowpea (Vigna unguiculata L. Walp.) accessions from Ghana using UPLC-PDA-QTOF-MS and chemometrics.
Cowpea (Vigna unguiculata L. Walp.) is an important grain legume in Africa exhibiting high morpho-genetic diversity. However, not much information exists on the phytochemical profiles of its hulls. This study explored the metabolite profiles of seed-coats from thirteen cowpea accessions of varying phenotypes using UPLC-QTOF-MS and chemometric analysis. A total of 34 secondary metabolites were identified, which comprised phenolic acids, flavonoids, anthocyanins, sphingolipids and fatty acids. Quantification of selected phenolic compounds revealed marked variations among the cowpea accessions. The chemical profiles of the test accessions were distinguished by multivariate analysis, and the results revealed a marked influence of seed-coat pigmentation on the observed differences in their metabolite profiles. Moreover, delphinidin (traces to 2257.6 µg/g), catechin glucoside (traces to 2840.6 µg/g), catechin (traces to 2089.2 µg/g) and epicatechin (26.3 to 3222.7 µg/g) contributed to the segregation amongst the studied samples. The concentrations of the discriminant metabolites were greater in the dark seeded cowpeas compared to their lighter seeded counterparts. The findings represent a useful contribution to the literature on cowpea seed coat metabolites, and also reveal their potential for use in the development of food and pharmaceutical products.


Accumulation of infectious mutants in stocks during the propagation of fiber-modified recombinant adenoviruses.
In infected cells, replication errors during viral proliferation generate mutations in adenoviruses (Ads), and the mutant Ads proliferate and evolve in the intracellular environment. Genetically fiber-modified recombinant Ads (rAd variants) were generated, by modification of the fiber gene, for therapeutic applications in host cells that lack or express reduced levels of the Coxsackievirus and adenovirus receptor. To assess the genetic modifications of rAd variants that might induce the instability of Ad virions, we examined the frequencies of mutants that accumulated in propagated stocks. Seven of 41 lines of Ad variants generated mutants in the stocks and all mutants were infectious. Moreover, all the mutations occurred in the modified region that had been added at the 3' end of the fiber gene. Our results show that some genetic modifications at the carboxyl terminus of Ad fiber protein lead to the instability of Ad virions.


Circumferential strain in the wall of the common carotid artery: comparing displacement-encoded and cine MRI in volunteers.
The walls of conduit arteries undergo cyclic stretching from the periodic fluctuation of arterial pressure. Atherosclerotic lesions have been shown to localize to regions of excessive stretching of the arterial wall. We employed a displacement encoding with stimulated echoes (DENSE) sequence to image the motion of the common carotid artery wall and map the two-dimensional (2D) circumferential strain. The sequence utilizes a fully-balanced steady-state free-precession (SSFP) readout with 0.60 mm in-plane resolution. Preliminary results in volunteers at 1.5T (N = 4) and 3.0T (N = 17) are compared to measurements of the lumen circumference from cine images. The agreement between the two independent measurements at both field strengths (P < or = 0.001) supports the use of DENSE as a means to map the pulsatile strain in the carotid artery wall.


Functional hyposplenia after allogeneic bone marrow transplantation is detected by epinephrine stimulation test and splenic ultrasonography.
Splenic function was evaluated after subcutaneous epinephrine injection (0.5 mg/m2) in 15 bone marrow transplant (BMT) recipients, 10 healthy volunteers and 5 healthy asplenic men. Healthy volunteers and BMT recipients with minor primary induction chemotherapy (mRx) showed similar rise in platelet (plt) and neutrophil granulocyte (PMN) counts and similar contraction of spleen. Patients with intensive primary induction chemotherapy (MRx), however, had significantly smaller spleens and spleen contraction (p less than 0.02) and no plt increase (p less than 0.05) when compared with healthy volunteers. 2 patients with MRx even exhibited a decrement of plt count after epinephrine, similar to that observed in all 5 healthy asplenic subjects tested. Our results suggest that mRx and conditioning for BMT including total body irradiation (TBI) does not alter the splenic function, but that the combination of MRx and conditioning regimen including TBI may cause functional hyposplenism, sensitively revealed by reduction in plt count after epinephrine stimulation.


Addressing the potential risks associated with ephedra use: a review of recent efforts.
The appropriate amount of oversight for dietary supplements has been a subject of debate for over a decade. This debate has come to a head recently with herbal ephedra, which may be associated with adverse events including heart attack, stroke, seizure, and death. This article reviews and puts into context recent findings on the safety concerns related to ephedra, based primarily on adverse event reports. It presents the response from industry and the FDA in light of this evidence, and describes additional steps taken by other groups who believe that more restrictive action is required. The article concludes by observing the lack of explicit, shared criteria for determining whether a supplement is unsafe, and pointing out ways in which the experience with ephedra can be used constructively to address that problem.


Influence of Calcium Ions on the Thermal Characteristics of α-amylase from Thermophilic Anoxybacillus sp. GXS-BL.
α-Amylases are starch-degrading enzymes and used widely, the study on thermostability of α-amylase is a central requirement for its application in life science and biotechnology. In this article, our motivation is to study how the effect of Ca2+ ions on the structure and thermal characterization of α-amylase (AGXA) from thermophilic Anoxybacillus sp.GXS-BL. α-Amylase activity was assayed with soluble starch as the substrate, and the amount of sugar released was determined by DNS method. For AGXA with calcium ions and without calcium ions, optimum temperature (Topt), half-inactivation temperature (T50) and thermal inactivation (halflife, t1/2) was evaluated. The thermal denaturation of the enzymes was determined by DSC and CD methods. 3D structure of AGXA was homology modeled with α-amylase (5A2A) as the template. With calcium ions, the values of Topt, T50, t1/2, Tm and ΔH in AGXA were significantly higher than those of AGXA without calcium ions, showing calcium ions had stabilizing effects on α-amylase structure with the increased temperature. Based on DSC measurements AGXA underwent thermal denaturation by adopting two-state irreversible unfolding processes. Based on the CD spectra, AGXA without calcium ions exhibited two transition states upon unfolding, including α- helical contents increasing, and the transition from α-helices to β-sheet structures, which was obviously different in AGXA with Ca2+ ions, and up to 4 Ca2+ ions were located on the inter-domain or intra-domain regions according to the modeling structure. These results reveal that Ca2+ ions have pronounced influences on the thermostability of AGXA structure.


Fundamentals of microfluidics for high school students with no prior knowledge of fluid mechanics.
Three microfluidics-based laboratory exercises were developed and implemented in a high school science classroom setting. The first exercise demonstrated ways in which flows are characterized, including viscosity, turbulence, shear stress, reversibility, compressibility, and hydrodynamic resistance. Students characterized flows in poly(dimethylsiloxane) microfluidic devices in the other two exercises, where they observed the mixing characteristics of laminar flows, and conservation of volumetric flow rate for incompressible flows. In surveys, the students self-reported increased knowledge of microfluidics, and an improved attitude toward science and nanotechnology.


Endovascular treatment of wide-neck intracranial bifurcation aneurysms with 'Y'-configuration, double Neuroform® stents-assisted coiling technique: Experience in a single center.
Background Intracranial wide-neck aneurysms at the arterial bifurcations, especially in the aneurysms where the bifurcating branches emanate directly from the base of the aneurysm, have been particularly difficult on which to perform endovascular treatment. The 'Y'-configuration, double stent-assisted coil embolization is an option for the treatment of these difficult aneurysms, allowing the closure of the aneurysm, preserving the parent arteries. Material and methods In a nine-year period, 546 intracranial aneurysms in 493 patients were treated at our center by endovascular approach. We have reviewed the medical records and arteriographies from November 2007 to January 2017 of 45 patients who were treated using 'Y'-configuration double Neuroform® stent-assisted coil embolization. Results All patients were successfully treated. The location of the aneurysms were: middle cerebral artery (MCA) 20 (44.4%), anterior communicating artery (AComA) 17 (37.7%), basilar four (8.9%), internal carotid artery (ICA) bifurcation three (6.6%) and posterior communicating artery (PComA) one (2.2%). The mRS at hospital discharge was: mRS 0: 42 (93.3%), mRS 1: 1 (2.2%), mRS 2: 1 (2.2%) and mRS 5: 1 (2.2%). The Modified Raymond-Roy Occlusion Classification, in the control at six months, was: Class I: 41 (91.1%), Class II: 2 (4.4%), Class IIIa: 1 (2.2%) and Class IIIb: 1 (2.2%). Forty-four (97.8%) patients had a good outcome (mRS < 2) at six months. One (2.2%) patient had a poor outcome (mRS > 2) at six months that was due to sequelae of SAH. There was no mortality at six months. Conclusions This technique is safe and effective for the endovascular treatment of difficult wide-neck bifurcation aneurysms, allowing the stable closure of the aneurysm, preserving the parent arteries.


Human rabies: a descriptive observation of 21 children in Kinshasa, the Democratic Republic of Congo.
Human rabies has recently emerged as a significant public health threat in Kinshasa, Democratic Republic of Congo (DRC). However, there is little epidemiological information on human rabies especially in children. We performed at Pediatrics Department of General Reference hospital of Kinshasa between December 2008 and July 2009, a retrospective study to assess the incidence and to describe their clinical aspects and outcome. A total of 21 cases were observed, rather three cases per month. There were 12 boys (57·1%) and 9 girls (42·9%). Biting animal was found to be dog in all cases (100%). The dog was not immunized in all of cases. On admission, all patients (100%) showed furious rabies manifestations. Only two (9·5%) had their wounds treated and received an anti-rabies vaccine (ARV) after the bite incident. Two (9·5%) patients received rabies immunoglobulin (RIG). The case-fatality rate was 100%. The disease emerges as a new major public health problem because of a lack of knowledge regarding rabies risk, the poor management of dog bites. Preventative vaccination for rabies should be recommended in the population of Kinshasa, area at high risk to contract rabies, particularly in children.


Substitutions in the active site of chloramphenicol acetyltransferase: role of a conserved aspartate.
The role of conserved Asp-199 in chloramphenicol acetyltransferase (CAT) has been investigated by site-directed mutagenesis. Substitution of Asp-199 by alanine results in a thermolabile mutant enzyme (Ala-199 CAT) with reduced kcat(13-fold) but similar Km values to wild type CAT. Replacement by asparagine gives rise to a thermostable mutant enzyme (Asn-199 CAT) with much reduced kcat(1500-fold). Furthermore, Asn-199 CAT shows anomalous inactivation kinetics with the affinity reagent 3-(bromo-acetyl)chloramphenicol. These results favor a structural role for Asp-199 rather than a catalytic one, in keeping with crystallographic evidence for involvement of Asp-199 in a tight salt bridge with Arg-18. Replacement of Arg-18 by valine results in a mutant enzyme (Val-18 CAT) with similar properties to Ala-199 CAT. The catalytic imidazole of His-19 appears to be conformationally constrained by hydrogen bonding between N1-H and the carbonyl oxygen of the same residue and by ring stacking with Tyr-25.


Anthropogenic impact and lead pollution throughout the Holocene in Southern Iberia.
Present day lead pollution is an environmental hazard of global proportions. A correct determination of natural lead levels is very important in order to evaluate anthropogenic lead contributions. In this paper, the anthropogenic signature of early metallurgy in Southern Iberia during the Holocene, more specifically during the Late Prehistory, was assessed by mean of a multiproxy approach: comparison of atmospheric lead pollution, fire regimes, deforestation, mass sediment transport, and archeological data. Although the onset of metallurgy in Southern Iberia is a matter of controversy, here we show the oldest lead pollution record from Western Europe in a continuous paleoenvironmental sequence, which suggests clear lead pollution caused by metallurgical activities since ~3900 cal BP (Early Bronze Age). This lead pollution was especially important during Late Bronze and Early Iron ages. At the same time, since ~4000 cal BP, an increase in fire activity is observed in this area, which is also coupled with deforestation and increased erosion rates. This study also shows that the lead pollution record locally reached near present-day values many times in the past, suggesting intensive use and manipulation of lead during those periods in this area.


Scintimetric assessment of synovitis activity during treatment with disease modifying antirheumatic drugs.
In a double blind trial of 36 patients with rheumatoid arthritis a new scintimetric method was applied to three comparable patient groups before and after eight months' treatment with levamisole, penicillamine, or azathioprine. Technetium-99m pyrophosphate scintigraphy of both hands was performed on a gammacamera with a computer attached, immediately after the administration of the tracer. The uptake ratio of each proximal interphalangeal (PIP) joint and the mid-half of the adjacent proximal phalanx was calculated from the activity counted for one minute. A scintimetric index was expressed as the sum of eight uptake ratios. This index was higher for each of the three patient groups before start of treatment than that for 10 age matched controls. After eight months of treatment the index, the number of PIP joints with clinical signs of synovitis, and the total circumference of the PIP joints decreased in the penicillamine and azathioprine groups. The scintimetric method reliably reflected local synovitis activity and its changes but, like grip strength and PIP circumference, was not a representative measure of the overall activity of the disease.


Alzheimer's disease: the downside of a highly evolved parietal lobe?
Clinical grade Alzheimer's disease (AD) is only described in humans. Recent imaging studies in early AD patients showed that the parietal areas display the most prominent metabolic impairments. So far, neuroimaging studies have not been able to explain why the medial parietal regions possess this hub characteristic in AD. Paleoneurological and neuroanatomical studies suggest that our species, Homo sapiens, has a unique and derived organization of the parietal areas, which are involved in higher cognitive functions. Combining evidence from neuroimaging, paleontology, and comparative anatomy, we suggest that the vulnerability of the parietal lobe to neurodegenerative processes may be associated with the origin of our species. The species-specific parietal morphology in modern humans largely influenced the brain spatial organization, and it involved changes in vascularization and energy management, which may underlie the sensitivity of these areas to metabolic impairment. Metabolic constraints and anatomical evolutionary changes in the medial parietal regions of modern humans may be important in early AD onset. Taking into account the species-specific adaptations of the modern human parietal areas and their association with AD, we hypothesize that AD can be the evolutionary drawback of the specialized structure of our parietal lobes. The cognitive advantage is associated with increased sensitivity to neurodegenerative processes which, being limited to the post-reproductive period, have a minor effect on the overall genetic fitness. The changes of energy requirements associated with form and size variations at the parietal areas may support the hypothesis of AD as a metabolic syndrome.


Novel polycarbo-substituted alkyl (thieno[3,2-c]quinoline)-2-carboxylates: synthesis and cytotoxicity studies.
Direct one-pot base-promoted conjugate addition-elimination of 6,8-dibromo-4-chloroquinoline-3-carbaldehyde with methyl mercaptoacetate and subsequent cyclization afforded methyl [(6,8-dibromothieno[3,2-c]quinoline)]-2-carboxylate. The latter undergoes Suzuki-Miyaura cross-coupling with arylboronic acids to yield exclusively the corresponding alkyl [(6,8-diarylthieno[3,2-c]quinoline)]-2-carboxylates,. The cytotoxicity of the prepared compounds was evaluated against the human breast cancer cell line MCF-7 using the MTT assay. The effects of compounds 2, 3c and 4d on cell kinetics were further determined using the xCELLigence Real Time Cell Analysis (RTCA) system. In both the MTT assay and Real Time Cell Analysis, the compounds inhibited cancer cell growth in a dose- and time-dependent manner. Furthermore, on the basis of the calculated LC50 values, the compounds compared favourably with nocodazole, a well-established anticancer drug.


Neutrality, compensation, and negative selection during evolution of B-cell development transcriptomes.
B cells develop in the mammalian bone marrow through a sequence of precursor stages, which can be ordered by the recombination status of their immunoglobulin loci. This developmental pathway is functionally similar between mice and man. However, whether this similarity is based on usage of the same genes is unknown. We show that large-scale gene expression patterns differ substantially between human and mouse B-cell development. Among 644 genes which were differentially expressed in 4 early stages of human B-cell development, only 48, 86, and 75 genes could be identified, which are upregulated in both human and mouse pre-BI, large pre-BII, and small pre-BII cells, respectively. A comparison of mouse B- and T-cell development reveals that gene expression patterns of early murine B- and T-cell precursors are most similar, whereas in more differentiated precursors, human and mouse B cells have a more similar gene expression profile. We conclude that large-scale differences in gene expression patterns between human and mouse B-cell precursors may stem from either selective neutrality or compensatory evolution, whereas the few similarities may stem from negative selection. Gene expression patterns are shaped by ontogenic relationships in early and by functional specialization in later stages of development.


Pretreatment Source Location and Functional Connectivity Network Correlated With Therapy Response in Childhood Absence Epilepsy: A Magnetoencephalography Study.
Objective: This study aims to investigate the differences between antiepileptic drug (AED) responders and nonresponders among patients with childhood absence epilepsy (CAE) using magnetoencephalography (MEG) and to additionally evaluate whether the neuromagnetic signals of the brain neurons were correlated with the response to therapy. Methods: Twenty-four drug-naïve patients were subjected to MEG under six frequency bandwidths during ictal periods. The source location and functional connectivity were analyzed using accumulated source imaging and correlation analysis, respectively. All patients were treated with appropriate AED, at least 1 year after their MEG recordings, their outcome was assessed, and they were consequently divided into responders and nonresponders. Results: The source location of the nonresponders was mainly in the frontal cortex at a frequency range of 8-12 and 30-80 Hz, especially 8-12 Hz, while the source location of the nonresponders was mostly in the medial frontal cortex, which was chosen as the region of interest. The nonresponders showed strong positive local frontal connections and deficient anterior and posterior connections at 80-250 Hz. Conclusion: The frontal cortex and especially the medial frontal cortex at α band might be relevant to AED-nonresponsive CAE patients. The local frontal positive epileptic network at 80-250 Hz in our study might further reveal underlying cerebral abnormalities even before treatment in CAE patients, which could cause them to be nonresponsive to AED. One single mechanism cannot explain AED resistance; the nonresponders may represent a subgroup of CAE who is refractory to several antiepileptic drugs.


Preliminary analyses of Hebrew verbal fluency measures.
Hebrew language versions of phonemic and semantic fluency were administered to samples of normal control participants and individuals who had been hospitalized for 24 hr following a head injury. For the control sample, verbal fluency tasks were normally distributed and significantly correlated with education. The head injury sample's word generation was significantly lesser than that of the control's and not at all related to educational attainment. The findings provide evidence for the use of Hebrew fluency measures for clinical assessment and the need for collection of normative data across education levels.


Round window electrode insertion potentiates retention in the scala tympani.
The round window membrane (RWM)-intentioned approach is superior to the traditional bony cochleostomy (BC) approach in obtaining electrode placement within the scala tympani (ST). Cochlear implant outcome is influenced by several factors, including optimal placement and retention of the electrode array within the ST. The present study aimed to assess whether the RWM route is superior to a traditional BC for placement and retention of the electrode array in the ST. This was a prospective consecutive non-randomized comparison study. All patients were implanted with the Advanced Bionics 1J electrode array. The RWM approach (n = 32) was compared with a traditional BC group (n = 33). The outcome measure was the electrode position as judged within the scalar chambers at four points along the basal turn using postoperative computed tomography (CT). When the mean position scores were compared, the RWM-intentioned group had significantly more electrodes directed towards the ST compartment than the BC group (p < 0.001). The RWM electrodes achieved 94% ST retention compared with 64% for the BC group (p < 0.05). All electrodes stayed in the ST in the RWM group, whereas in the BC group 9% crossed from the ST to the scala vestibuli.


Calcium Propionate Supplementation Has Minor Effects on Major Ruminal Bacterial Community Composition of Early Lactation Dairy Cows.
Calcium propionate is one kind of good source for preventing and treating hypocalcemia and ketosis for dairy cows in early lactation. However, little is known about the effects of different feeding levels of calcium propionate on the ruminal bacterial community of early lactation dairy cows. This study aimed to explore the effects of different calcium propionate feeding levels on the ruminal fermentation and bacterial community composition of early lactation dairy cows. Twenty-four multiparous cows were randomly allocated into control (CON), low calcium propionate (LCaP), medium calcium propionate (MCaP), and high calcium propionate (HCaP) groups with six cows per group after calving. The CON group cows were fed the normal total mixed ration (TMR), and the cows of the LCaP, MCaP, and HCaP groups were fed TMR supplemented with 200, 350, and 500 g/day calcium propionate for 35 days after calving, respectively. The rumen fermentation parameters were measured every week, and the ruminal bacterial community composition of the last week was analyzed by 16S rRNA gene sequencing. Under the same diet, the rumen pH showed no difference among the four groups, but the content of microbial crude protein (MCP) and ammonia nitrogen quadratically decreased and linearly increased with calcium propionate supplementation, respectively. The feeding of calcium propionate linearly increased the concentrations of total volatile fatty acid (VFA), acetate, propionate, butyrate, iso-valerate, and valerate in the rumen. In all the treatment groups, Bacteroidetes, Firmicutes, and Proteobacteria were the dominant phyla, and Prevotella_1 and Succiniclasticum were the dominant genera in the rumen. Compared with the CON group, the addition of calcium propionate to the early lactation dairy cows quadratically improved the alpha diversity index of Chao1 estimator and observed species, but had little effect on the relative abundance of the major bacterial at phyla and genera level. These results suggested different levels of calcium propionate supplementation improved the rumen fermentation and the ruminal bacterial diversity but had little impact on the major ruminal bacterial community composition of dairy cows in early lactation.


BDNF Influence on Adult Terminal Axon Sprouting after Partial Deafferentation.
BDNF is a neurotrophin family member implicated in many different neuronal functions, from neuronal survival during development to synaptic plasticity associated with processes of learning and memory. Its presence in the oculomotor system has previously been demonstrated, as it regulates afferent composition of extraocular motoneurons and their firing pattern. Moreover, BDNF expression increases after extraocular motoneuron partial deafferentation, in parallel with terminal axon sprouting from the remaining axons. To elucidate whether BDNF could play an active role in this process, we performed partial deafferentation of the medial rectus motoneurons through transection of one of the two main afferents, that is, the ascending tract of Deiters, and injected BDNF into the motoneuron target muscle, the medial rectus. Furthermore, to check whether BDNF could stimulate axon sprouting without lesions, we performed the same experiment without any lesions. Axon terminal sprouting was assessed by calretinin immunostaining, which specifically labels the remaining afferent system on medial rectus motoneurons, the abducens internuclear neurons. The results presented herein show that exogenous BDNF stimulated terminal axon growth, allowing the total recovery of synaptic coverage around the motoneuron somata. Moreover, calretinin staining in the neuropil exceeded that present in the control situation. Thus, BDNF could also stimulate axonal sprouting in the neuropil of intact animals. These results point to an active role of BDNF in plastic adaptations that take place after partial deafferentation.


Reconsideration of Plant Morphological Traits: From a Structure-Based Perspective to a Function-Based Evolutionary Perspective.
This opinion article proposes a novel alignment of traits in plant morphogenesis from a function-based evolutionary perspective. As a member species of the ecosystem on Earth, we human beings view our neighbor organisms from our own sensing system. We tend to distinguish forms and structures (i.e., "morphological traits") mainly through vision. Traditionally, a plant was considered to be consisted of three parts, i.e., the shoot, the leaves, and the root. Based on such a "structure-based perspective," evolutionary analyses or comparisons across species were made on particular parts or their derived structures. So far no conceptual framework has been established to incorporate the morphological traits of all three land plant phyta, i.e., bryophyta, pteridophyta and spermatophyta, for evolutionary developmental analysis. Using the tenets of the recently proposed concept of sexual reproduction cycle, the major morphological traits of land plants can be aligned into five categories from a function-based evolutionary perspective. From this perspective, and the resulting alignment, a new conceptual framework emerges, called "Plant Morphogenesis 123." This framework views a plant as a colony of integrated plant developmental units that are each produced via one life cycle. This view provided an alternative perspective for evolutionary developmental investigation in plants.


Effect of nifedipine on skin prick tests.
The immediate skin test due to interaction between allergen and mast cell bound IgE is one of the cornerstones in the clinical allergy workup. The release of histamine and other mediators from basophils and mast cells depends on the influx of Ca2+ into these cells when stimulated. The aim of this study was to evaluate the effect of common therapeutic doses of nifedipine (NFD), one of the calcium channel blockers, on the allergen skin tests. We prick tested 23 grass sensitive individuals with 7 different grass pollens at three times: at basal conditions (T0), 30 min. after having taken 20 mg of NFD s. l. (T1), and 17 of them after a week of receiving twice a day 20 mg of a NFD retard form (T2). The wheal surface obtained for each substance (allergen, histamine) at T0 was considered as basal value and compared with the one obtained at T1 and T2 for the same substance by the Wilcoxon's test. We found a significant increase in the wheal surfaces, both with allergen and histamine, at T1 and T2. In contrast to what could be expected, common therapeutic doses of NFD produce a discrete but statistically significant increase of the PT. Factors such as arteriolar vasodilation could be implicated. The increase of the allergen prick test and the increase of the histamine prick test both at T1 and T2 were not statistically different. Therefore, we do not think it necessary to stop NFD before allergen skin testing.


Hepatitis B virus infection seromarkers among college freshmen and their immune responses to different vaccination policies of hepatitis B vaccine.
College students are one of the susceptible population of Hepatitis B virus (HBV) infection. We aim to delineate HBV infection seromarkers among college freshmen and to evaluate immunological response of vaccination immunization for hepatitis B vaccine (HepB). A simple random sampling method was adopted to select subjects and who met the "inclusion and exclusion criteria" and who with history of vaccination were selected as the observation objects. HBsAg and anti-HBs levels were detected before revaccination. Subjects with negative anti-HBs before immunization were inoculated with 20 ug HepB according to the 0-1-6 procedure and those with weak positive anti-HBs before immunization were inoculated with 1-dose 20 ug HepB. Anti-HBs levels were detected after HepB booster. Combined with the results of anti-HBs, their immune response to HepB and influencing factors in freshmen were investigated. Anti-HBs before immunization was negative and ≥10 m IU/ml after immunization was considered positive conversion; anti-HBs before immunization was weak positive and anti-HBs≥100 m IU/ml after immunization was also considered positive conversion. A total of 10645 freshmen were included. The total rate of HBsAg carriers was 0.6% (63/10645), and the strong positive rate of anti-HBs was 16.1% (1706/10645), the weak positive rate was 14.4% (1526/10645).1286 freshmen were vaccinated with HepB and completed the questionnaire survey. About 79.0% (154/195) of freshmen's anti-HBs turned strong positive after receiving 1-dose HepB and 100.0% (1091/1091) turned positive after receiving 3-doses HepB. The Geometrical Mean Titer (GMT) of anti-HBs was significantly influenced by gender, registration and the immunization doses of HepB. The HBsAg carrying rate and anti-HBs positive rate of college freshmen were low, and the HepB has a good effect on the immunity of college freshmen. Increasing the immunization rate of HepB is very important for the prevention and control of hepatitis B.


Knowledge of toxoplasmosis among doctors and nurses who provide prenatal care in an endemic region.
Congenital toxoplasmosis is a potentially severe infection and its prevention is most often based on serological screening in pregnant women. Many cases could be prevented by simple precautions during pregnancy. Aiming to assess the knowledge about toxoplasmosis among professionals working in antenatal care in a high prevalent region, a questionnaire was administered to 118 obstetric nurses and physicians attending at primary care units and hospitals. The questionnaire was self-completed and included questions on diagnosis, clinical issues, and prevention. Only 44% of total answers were corrected. Lower scores were observed among those with over 10 years of graduation, working in primary care units, and nurses. Errors were mainly observed in questions of prevention and diagnosis. As congenital toxoplasmosis is a mother-to-child (MTC) transmitted disease, early diagnosis and treatment can prevent serious and irreversible fetal damage. Thus, doctors and nurses who provide prenatal care must be appropriately trained on prophylactic, diagnostic, and clinical aspects of toxoplasmosis. The authors suggest that measures should be taken for continuing education regarding toxoplasmosis in pregnancy.


Surgical treatment of post-infarction ventricular septal rupture.
The authors describe their series of 9 patients operated upon for post-infarction rupture of the ventricular septum. Two patients operated upon earlier than 6 weeks following the rupture died. Of the 7 patients operated upon 6 weeks after the diagnosis of rupture 1 died. The risk of operative intervention is determined not only by the time between rupture and surgery, but also by the magnitude of rupture and the extent of the myocardial infarction, as well as the functional state of the residual myocardium.


Novel pathogenic COX20 variants causing dysarthria, ataxia, and sensory neuropathy.
COX20/FAM36A encodes a mitochondrial complex IV assembly factor important for COX2 activation. Only one homozygous COX20 missense mutation has been previously described in two separate consanguineous families. We report four subjects with features that include childhood hypotonia, areflexia, ataxia, dysarthria, dystonia, and sensory neuropathy. Exome sequencing in all four subjects identified the same novel COX20 variants. One variant affected the splice donor site of intron-one (c.41A>G), while the other variant (c.157+3G>C) affected the splice donor site of intron-two. cDNA and protein analysis indicated that no full-length cDNA or protein was generated. These subjects expand the phenotype associated with COX20 deficiency.


[Value of MS associated factors for test procedures in multiple sclerosis: 2. Angers' MS-induced substance in the LAI test].
Attempts to find test systems specific for multiple sclerosis are directed to the investigation of MS-associated factors in serum. Basing on the methods of the adherence of antigen-reactive leukocytes, the MSRM (MS-related material) a substance conditioned by the disease was derived from blood of MS-patients and applied in the leukocyte adherence-inhibition (LAI)-test. The mean values in the LAI-test showed a significant difference between MS, the other neurological diseases (OND) and the normals. For the limiting value mean NK +/- 2 s a positive LAI-effect resulted in 58% of the intermittent and in 43% of the chronic-progredient cases of MS, yet also in 11% of the OND. The fact that the rate of detection is lower than that reported by Angers, could depend on factors caused by the method used or by anomalies of immune regulation in MS (including the so-called blocking factors in serum). The results received with LAI-test applying the MSRM don't allow any definite diagnostical assessment specific for MS.


Strain-induced magnetic moment enhancement in frustrated antiferromagnet Cs2CuBr4.
The structure and magnetic properties are studied in co-doped Cs2-x K x CuBr4-x Cl x and pressurized Cs2CuBr4 samples. No structural phase transition is found with doping concentration x ⩽ 0.1 and pre-compression pressure up to 4.5 GPa. The maximum susceptibility temperature T max of the zero-field-cooling (ZFC) susceptibility curves decreases slightly with increasing doping concentration and pre-compression pressure, indicating only small changes in the exchange coupling constants. However, an unusual enhancement of the magnetic moment deduced from the ZFC susceptibility is observed in both series samples. A maximum increase of 40% is obtained in Cs1.9K0.1CuBr3.9Cl0.1 sample. The magnetic moment increases almost linearly with decreasing Δ, i.e., defined as the wavenumber difference between the short- and long-bond stretching modes of the CuBr4 2- tetrahedra in the Raman spectra. The effect is likely due to the recovery of the Cu-3d orbital magnetic moments by strain-induced suppression of Jahn-Teller distortion in CuBr4 2- tetrahedra.