Increased structural connectivity of the medial forebrain bundle in schizophrenia spectrum disorders is associated with delusions of paranoid threat and grandiosity.
In many cases delusions in schizophrenia spectrum disorders (SSD) are driven by strong emotions such as feelings of paranoia or grandiosity. We refer to these extreme emotional experiences as psychotic affectivity. We hypothesized that increased structural connectivity of the supero-lateral medial forebrain bundle (slMFB), a major tract of the reward system, is associated with delusional psychotic affectivity. Forty-six patients with SSD and 44 healthy controls (HC) underwent diffusion weighted magnetic resonance imaging (DW-MRI)-scans. The slMFB and a comparison tract (corticospinal tract) were reconstructed using diffusion tensor imaging (DTI)-based tractography. Fractional anisotropy (FA) was sampled across the tracts. We used a mixed-model analyses of variance controlling for age and gender to compare FA of bilateral slMFB between SSD-patients and HC. Correlations of FA of bilateral slMFB and the PANSS-positive item delusions were calculated. In addition, FA was compared between three clinically homogeneous SSD-subgroups in terms of psychotic affectivity (severe, mild and no PA, sPA, mPA, nPA) and HC. FA of the slMFB did not differ between all SSD-patients and HC. In SSD-patients there was a positive correlation between delusions and FA in bilateral slMFB. Likewise, SSD-subgroups of psychotic affectivity and HC differed significantly in FA of the slMFB. Results were driven by higher FA in the right slMFB in sPA as compared to nPA and to HC. There was no significant effect for the comparison tract. In conclusion, increased structural connectivity of the slMFB may underlie delusional experiences of paranoia and grandiosity in SSD.


Mammary gland development and tumorigenesis in estrogen receptor knockout mice.
Estrogens are important for the development of the mammary gland and strongly associated with oncogenesis in this tissue. The biological effects of estrogens are mediated through the estrogen receptor (ER), a member of the nuclear receptor superfamily. The estrogen/ER signaling pathway plays a central role in mammary gland development, regulating the expression and activity of other growth factors and their receptors. The generation of the ER knockout (ERKO) mouse has made it possible to directly understand the contribution of ER in mammary development and has provided an unique opportunity to study estrogen action in carcinogenesis. A mammary oncogene (Wnt-1) was introduced into the ERKO background to determine if the absence of the ER would affect the development of tumors induced by oncogenic stimulation. The development, hyperplasia, and tumorigenesis in mammary glands from the ERKO/Wnt-1 mouse line are described. These studies provide the impetus to evaluate the effect of other oncogenes in mammary tumorigenesis in the absence of estrogen/ER signaling.


Harnessing tactile waves to measure skin-to-skin interactions.
Skin-to-skin touch is an essential form of tactile interaction, yet there is no known method to quantify how we touch our own skin or someone else's skin. Skin-to-skin touch is particularly challenging to measure objectively, since interposing an instrumented sheet, no matter how thin and flexible, between the interacting skins is not an option. To fill this gap, we explored a technique that takes advantage of the propagation of vibrations from the locus of touch to pick up a signal that contains information about skin-to-skin tactile interactions. These "tactile waves" were measured by an accelerometer sensor placed on the touching finger. Applied pressure and speed had a direct influence on measured signal power when the target of touch was the self or another person. The measurements were insensitive to changes in the location of the sensor relative to the target. Our study suggests that this method has potential for probing behaviour during skin-to-skin tactile interactions and could be a valuable technique to study social touch, self-touch, and motor control. The method is non-invasive, easy to commission, inexpensive, and robust.


Minimally invasive esophagectomy for cancer.
Since 1992, various combinations of thoracoscopy (VATS), laparoscopy or hand-assisted thoracolaparoscopy have been used for 'minimally invasive' cancer esophagectomy (MIE). Despite widespread current use, indications and potential benefits of the many technical approaches remain controversial. A systematic literature search was conducted until June 2007. Out of 128 publications, 46 original series (1932 patients) met the inclusion criteria and were analyzed for surgical and oncological outcome. No prospective controlled study has compared any MIE technique to another or to open surgery. Most publications are retrospective series of highly selected patients, mostly excluding high-risk patients and locally advanced (T3) tumors. Altogether, the overall conversion rate was 5.9%, mortality 2.9% and morbidity 46%, many papers reporting only major complications. Overall, rates for pulmonary complications were 22%, leakage 8.8% and vocal cord palsy 7.1%. Fifteen tracheo-bronchial injuries or fistulas (1% of all VATS cases) were reported. Laparoscopy and VATS were combined in 11 series (609 patients, 4.7% conversions, 2.4% mortality). VATS combined with (mini)-laparotomy was reported in 14 papers (743 patients, 6.3% conversions, 2.4% mortality). Laparoscopy combined with right thoracotomy was reported in four papers (147 patients, 5.4% conversions, 2% mortality). Laparoscopic transhiatal resections were reported in 17 papers (433 patients, 7% conversions, 4.6% mortality). Overall morbidity rates for these four approaches were 43%, 47.6%, 51.6% and 46%, respectively. Data on oncological outcome are scarce. Lymph node retrieval (median of all series: 14 nodes, range 5-62) was mostly inferior to open surgery standards and follow-up too short to draw definitive conclusions regarding long-term survival. Based on the available literature, the morbidity and mortality of MIE is substantial and not inferior to radical open esophagectomy in experienced centers. Many different operative techniques for MIE have been reported without obvious superiority for any of them. The term 'minimally invasive' is not supported by hitherto reported results. Selection bias and huge variability in extent of resection and lymphadenectomy impair comparisons of different MIE techniques. Oncological outcome of MIE remains largely unknown by lack of good quality data and selection bias. MIE remains an investigational and still evolving treatment for invasive cancer.


Association between chlorpropamide-alcohol flushing and fast acetylator phenotype in type I and type II diabetes.
Different prevalences of chlorpropamide alcohol flushing (CPAF) have been reported by different authors in either type I or type II diabetics or in normal subjects and this could be due to different methodological approaches or to different criteria of evaluation of CPAF. Previous studies in small series of patients have also suggested the existence of an association between type I diabetes and the fast acetylator phenotype (AP). The first aim of this study was to find reliable criteria for the assessment of CPAF. The second was to evaluate the prevalence of CPAF and of AP in a large series of type I and type II diabetics; and the third was to evaluate possible associations of CPAF and AP. AP and CPAF were evaluated separately in 256 diabetics (110 with type I and 146 with type II diabetes) and in 183 diabetics (74 with type I and 109 with type II diabetes), respectively. In 156 of these subjects, the two markers were evaluated together. The occurrence of CPAF was studied by subjective and objective assessment and by thermographic recording; CPAF was quantified by the differential value of skin temperature increase [delta T(C-P)] and by the value of differential speed of ascent, expressed in angle-degrees [delta a(C-P)], after treatment with placebo and with chlorpropamide. The fast AP was more frequent in type I than in type II diabetics, was not related to family history of diabetes, sex of the patients, age at onset and duration of diabetes or metabolic control. The most reliable assessment of CPAF was represented by thermographic recording of speed of ascent of skin temperature. CPAF was more frequent in females than in males, more frequent in diabetics than in healthy controls, similarly frequent in type I and in type II diabetes and showed no relationship with family history of diabetes, age at onset, duration of diabetes or metabolic control. An association between fast AP and CPAF was found in type II, but not in type I diabetics: fast acetylators were more frequently CPAF-positive, while slow acetylators were more frequently CPAF-negative. In addition, a linear relationship was found between rate of acetylation and speed of ascent of facial skin temperature after chlorpropamide and alcohol in type II diabetics, not in type I diabetics. The meaning of this association is not clear and deserves further investigations.


The chemical activities of the Viking biology experiments and the arguments for the presence of superoxides, peroxides, gamma-Fe2O3 and carbon suboxide polymer in the Martian soil.
The evolution of N2, Ar, O2, and CO2 from Martian soil as a function of humidity in the Gas Exchange Experiment are correlated with the mean level of water vapor in the Martian atmosphere. All but O2 are associated with desorption. The evolution of oxygen is consistent with the presence of alkaline earth and alkali metal superoxides; and their peroxides and the gamma-Fe2O3 in the soil can account for the generation of radioactive gas in the Labeled Release Experiment. The slower evolution of CO2 from both the Gas Exchange Experiment and the Labeled Release Experiment are associated with the direct oxidation of organics by gamma-Fe2O3. The Pyrolytic Release Experiment's second peak may be carbon suboxide as demonstrated by laboratory experiments. A necessary condition is that the polymer exists in the Martian soil. We ascribe the activity of the surface samples to the reaction of Martian particulates with an anhydrous CO2 atmosphere activated by uv and ionizing radiations. The surface particles are ultimately altered by exposure to small but significant amounts of water at the sites. From the working model, we have predicted the peculiar nature of the chemical entities and demonstrated that the model is justified by laboratory data. The final confirmation of this model will entail a return to Mars, but the nature and implications of this chemistry for the Martian surface is predicted to reveal even more about Mars with further simulations in the laboratory.


Immunotoxicity of petroleum hydrocarbons and microplastics alone or in combination to a bivalve species: Synergic impacts and potential toxication mechanisms.
Both the frequent occurrence of accidental petroleum spills and the ubiquitous presence of microplastics (MPs) in the sea may pose severe threats to marine species. However, the immunotoxic impacts of these two types of pollutants and the underlying toxication mechanisms still remain largely unknown in sessile filter-feeding bivalve mollusks. Therefore, the impacts of exposure to petroleum hydrocarbons and MPs alone or in combination on the total count, cell type composition, and phagocytic activity of hemocytes were investigated in the blood clam, Tegillarca granosa. In addition, the intracellular ROS content, cell viability, degree of DNA damage, and expression levels of genes from immune-, apoptosis-, and immunotoxicity-related pathways were analyzed to reveal the potential toxication mechanisms. The results demonstrated that exposure to petroleum hydrocarbons and MPs alone or in combination at environmentally realistic concentrations could exert significant immunotoxic impacts on the blood clam, which may be caused by alterations in a series of physiological and molecular processes. In addition, the immunotoxicity of petroleum hydrocarbons could be significantly aggravated by the copresence of MPs, which suggests that coexposure to these two pollutants deserves closer attention.


Brave new world revisited: Focus on nanomedicine.
Nanomedicine is at a crossroads: with relatively few success stories in terms of clinical translation despite more and more research on increasingly sophisticated nanomaterials, it is important to consider whether we are on the right track. Indeed, it is crucial that we address the fact that while considerable efforts are being made to overcome barriers to translation from the bench to the clinic, scientists are still struggling to decipher fundamental aspects of nanomaterial interactions with biological systems. We believe that a key to the successful adoption of nanomedicines in oncology and beyond lies in a deeper understanding of underlying biological processes and in decoding interactions between engineered nanomaterials and biological systems. Here we provide an overview of progress in nanomedicine during the past 5 years.


Azethoxyl nitroxide spin labels. ESR studies involving thiourea crystals, model membrane systems and chromatophores, and chemical reduction with ascorbate and dithiothreitol.
Trans- and cis-azethoxyl nitroxides 1, 2, 3 and 4 can be trapped in the cavities of thiourea crystals. The presence of a single gauche conformation on either side of the pyrrolidine ring within the crystals was indicated by the ESR spectra. Rotation about the long molecular axis then corresponds approximately to y-axis motion of the nitroxide moiety. Proxyl nitroxides in which the nitroxide group is located on the penultimate carbon of long chain lipids can also be trapped and were shown to adopt the azethoxyl conformation in the thiourea crystals. The measured deltaA values (A parallel to - A perpendicular) of oriented egg lecithin multilayers containing trans- and cis-azethoxyl nitroxides 1 and 2 were quite small, consistent with the unique orientation of the nitroxide principal axes with respect to the long axis of the molecule. The deltaA values for a series of lipids bearing a label near the terminus of the chain were very similar to that of 1, showing that the azethoxyl conformation is likely the predominant one in these labels in orienting systems. Computer simulations of the ESR spectra of 1 and 2 in egg lecithin vesicles provided values for molecular orientation and motion parameters consistent with those expected from a consideration of molecular models in the extended (all trans) conformation. Azethoxyl nitroxides have also proven useful in the investigation of motion restricted (boundary) lipid in a lipid-protein system. Thus, the values (69 +/- 10%) for the amount of boundary lipid in the chromatophore membranes from Rhodopseudomonas sphaeroides as determined using trans- 2 and cis- 2 are in good agreement with values using 16-doxylstearic acid (64 +/- 3%). The fact that all three labels show about the same fraction of boundary lipid in this system indicates that the lipid binding sites are relatively insensitive to the geometry of the lipid chain. Also, both 1 and 2 appear to be able to detect a third lipid environment not seen with the doxyl fatty acid. The apparent fluidity of this component lies between that of boundary and bilayer lipid. The unique orientation of the nitroxide principal axes with respect to the long molecular axis in azethoxyl nitroxides 1 and 2 allows detection of hindrance to rotation about the long molecular axis, in contrast to the analogous doxyl and proxyl fatty acids. Comparative reduction studies using ascorbate and dithiothreitol indicate that azethoxyl nitroxides are slightly more resistant toward reduction than proxyl nitroxides and much more resistant than doxyl nitroxides.


Enchondromas in children: imaging appearance with pathological correlation.
Enchondromas are benign lesions that may present with nonspecific features on imaging in children. Correlation of histology with imaging findings is often required to make the final diagnosis of a benign lesion. The aim of this study was to review imaging and pathological findings of enchondromas in children. Imaging examinations of 12 enchondromas in 11 patients (median age 14 years) were retrospectively reviewed. Imaging evaluation included an assessment of lesion size, relationship to the growth plate, mineralization, matrix and periosteal reaction, intrinsic MR signal characteristics, and intraosseous and soft-tissue edema. Pathological findings were reviewed. Lesions were located in the phalanx in 33% (4 out of 12), metacarpal in 25% (3 out of 12), femur in 33% (4 out of 12) and tibia in 8% cases (1 out of 12). The mean size was 28 mm (range, 11-70 mm). Matrix mineralization in a typical "rings-and-arcs" pattern was observed in 20% of the lesions with available radiographs/CT (2 out of 10). Lesions were expansive with endosteal scalloping in 75% of cases (9 out 12) and contacted the growth plate in 50% of cases (6 out of 12). All enchondromas in which MR imaging was available (5 out of 5) demonstrated typical cartilaginous matrix of lobules of high T2 signal, low T1 signal, and peripheral enhancement. Enchondromas in children are relatively large lesions, with frequent endosteal scalloping and rare matrix mineralization.


Use of preputial skin for the release of burn contractures in children.
Contractures are frequent sequelae of burn injuries. Progressive worsening of contractures with limitation of joint movement is common in children. The results of release procedures in 10 male Chinese children using their own preputial skin obtained from circumcision were reviewed. This technique yields reliable results and is well accepted by the parents.


Prevention of neuropathic pain in an animal model of spare nerve injury following oral immunization with recombinant adenovirus serotype 5-mediated NR2B gene transfer.
Spinal N-methyl-D-aspartate receptor 2B subunit (NR2B)-increased expression plays an important role in the facilitation and maintenance of the persistent pain state due to peripheral nerve injury. A vaccination strategy to reduce the expression of brain protein is feasible and may have therapeutic potential for neurological disorders. Thus, we investigated the effect of oral immunization with recombinant adenovirus serotype 5-mediated NR2B gene transfer (rAd5/NR2B) for the modulation of neuropathic pain. After peroral administration of the rAd5/NR2B vaccine, transgene NR2B expression persisted for at least a week and was associated with the induction of high serum titers of NR2B-specific antibodies. Following the occurrence of mechanical allodynia due to peripheral nerve injury, NR2B-specific antibodies could pass the blood-brain barrier, transport and subsequently bind to the spinal NR2B protein. The humoral immunoresponse results in the strong antiallodynia in the spared nerve injury animal model. These data proved the feasibility of oral immunization with rAd5/NR2B for the prevention of neuropathic pain.


[Prevention of thrombosis with physical therapy in trauma surgery. Possibilities and value of individual measures].
Patients in traumatology need additional physiotherapy to prevent deep vein thrombosis. There is still a 4% risk of deep vein thrombosis in outpatients receiving already low molecular weight heparin prophylaxis [9]. However, there are no prospective studies with a high number of patients to prove effectiveness of the presented physiotherapeutic tools, even if the hypothesis "achieving physiological-like conditions" sounds positive and some authors postulate that physiotherapy would be equal to drug prophylaxis of deep vein thrombosis.


Prevalence and diversity of Clostridium botulinum types A, B, E and F in honey produced in the Nordic countries.
A total of 294 honey samples produced in Denmark, Norway and Sweden were studied for the presence of Clostridium botulinum types A, B, E and F by using a multiplex-PCR method. The samples consisted of honeycombs taken directly from beehives, and extracted honey representing several hives or apiaries. The prevalence of C. botulinum showed a significant variation between Denmark, Norway and Sweden, the proportions of positive samples being 26%, 10% and 2%, respectively. The major serotype detected was type B. When analysed with pulsed-field gel electrophoresis (PFGE) using restriction enzyme SacII, the 24 strains isolated produced eight different PFGE patterns. At a similarity level of 95%, four clusters were produced, three of which contained 20 of the 24 analysed strains. One of the clusters included isolates from both Denmark and Norway.


Infants ask for help when they know they don't know.
Uncertainty monitoring is a core property of metacognition, allowing individuals to adapt their decision-making strategies depending on the state of their knowledge. Although it has been argued that other animals share these metacognitive abilities, only humans seem to possess the ability to explicitly communicate their own uncertainty to others. It remains unknown whether this capacity is present early in development, or whether it emerges later with the ability to verbally report one's own mental states. Here, using a nonverbal memory-monitoring paradigm, we show that 20-month-olds can monitor and report their own uncertainty. Infants had to remember the location of a hidden toy before pointing to indicate where they wanted to recover it. In an experimental group, infants were given the possibility to ask for help through nonverbal communication when they had forgotten the toy location. Compared with a control group in which infants had no other option but to decide by themselves, infants given the opportunity to ask for help used this option strategically to improve their performance. Asking for help was used selectively to avoid making errors and to decline difficult choices. These results demonstrate that infants are able to successfully monitor their own uncertainty and share this information with others to fulfill their goals.


Comparative sequence analysis of the phytochrome C gene and its upstream region in allohexaploid wheat reveals new data on the evolution of its three constituent genomes.
Bread wheat is an allohexaploid with genome composition AABBDD. Phytochrome C is a gene involved in photomorphogenesis that has been used extensively for phylogenetic analyses. In wheat, the PhyC genes are single copy in each of the three homoeologous genomes and map to orthologous positions on the long arms of the group 5 chromosomes. Comparative sequence analysis of the three homoeologous copies of the wheat PhyC gene and of some 5 kb of upstream region has demonstrated a high level of conservation of PhyC, but frequent interruption of the upstream regions by the insertion of retroelements and other repeats. One of the repeats in the region under investigation appeared to have inserted before the divergence of the diploid wheat genomes, but was degraded to the extent that similarity between the A and D copies could only be observed at the amino acid level. Evidence was found for the differential presence of a foldback element and a miniature inverted-repeat transposable element (MITE) 5' to PhyC in different wheat cultivars. The latter may represent the first example of an active MITE family in the wheat genome. Several conserved non-coding sequences were also identified that may represent functional regulatory elements. The level of sequence divergence (Ks) between the three wheat PhyC homoeologs suggests that the divergence of the diploid wheat ancestors occurred some 6.9 Mya, which is considerably earlier than the previously estimated 2.5-4.5 Mya. Ka/Ks ratios were <0.15 indicating that all three homoeologs are under purifying selection and presumably represent functional PhyC genes. RT-PCR confirmed expression of the A, B and D copies. The discrepancy in evolutionary age of the wheat genomes estimated using sequences from different parts of the genome may reflect a mosaic origin of some of the Triticeae genomes.


Genetic polymorphism of alpha-lactalbumin gene in riverine buffalo.
Alpha-lactalbumin (alpha-LA) is a major whey protein found in milk. Polymorphs of alpha-LA gene are reported to be significantly associated with milk production and constituent traits. Therefore, the present study was undertaken to detect polymorphism in alpha-LA at the genic level and to explore allelic variability at this locus. A total of 196 animals, belonging to four breeds of riverine buffalo viz. Bhadwari, Mehsana, Surti and Murrah were included under the present investigation. Two fragments i.e. 133 bp (Exon 1) and 159 bp (Exon 2) of alpha-LA gene were amplified by polymerase chain reaction and subsequently, single strand confirmation polymorphism (SSCP) study was carried out to identify different allelic pattern and genotypes of the animal included in the study. Both fragment of alpha-LA gene was found to be polymorphic in all the four breeds of riverine buffalo. Number of genotypes and allele varied breed to breed for both the fragments. In case of 133 bp fragment, four alleles A, B, C and D were found among different breeds of buffalo whereas in 159 bp fragment, five alleles namely A, B, C, D and E was found in different breeds. Nucleotide sequence data of different alleles showed the presence of both silent as well as functional mutation leading to variability in polypeptide chain.


Orthognathic surgery treatment injuries reported to the Danish Patient Compensation Association: A 25-year retrospective observational study.
The aim of this study was to describe and classify indemnity claims of treatment injuries in orthognathic surgery received by the Danish Patient Compensation Association (DPCA) during a 25-year time span from 1993 to 2018 in order to illustrate the wide scope of treatment injuries, patient's complaints, suffering, and compensation. All indemnity claims associated with orthognathic surgery were reviewed accessing the DPCA database including osteotomies performed in association with orthodontic treatment only, thus excluding access osteotomies for tumor surgery, osseodistraction cases, etc. RESULTS: A total of 237 indemnity claims were received for injury associated with orthognathic surgery, including anesthesia. One-hundred sixteen claims (49 %) were approved and patients accordingly compensated with a total of 23.2 million, average 200.000 Danish kroner per patient. In US dollars, 3.5 million, and 30 thousand, respectively. Most claims (45.5 %) were associated with neurological issues, neurosensory disturbances of all kinds including pain and loss of neural function. Others were associated with airway, breathing and circulation (2.1 %), temporomandibular joint issues (8.9 %), jaw malposition (9.3 %), malocclusion (11.0 %), facial issues (6.8 %), dental issues (10.5 %), and miscellaneous (5.9 %), as sole complaint or in concert. Data from the Danish Health Data Authority allowed a calculation of the indemnity claims rate covering the time frame 2005-2008 being indeed very low, 1.8 % out of 10,955 orthognathic surgeries. Treatment injuries do occur to the misfortune of patients and surgeons alike. The low rate of indemnity claims indicates an underreporting when compared to known rates of complications. It is the surgeon's responsibility that potential benefits of surgery outweigh the risk of complications, be they treatment errors or known shortcomings of procedures. Established criteria for admission to orthognathic surgery would be advisable and most probably reduce the number patients operated on marginal indication and hence treatment injuries in this group.


Critical considerations in the assessment of health and environmental risks - what we have learned from the nuclear experience.
The radiological experience has produced some sophisticated approaches to estimating the environmental risks of anthropogenic chemicals, based on well-validated models for both health effects and exposure assessment. As to exposure assessment, site- and situation-specific data must be acquired for quantitative predictions. However, the requirements for quantitative estimation are often overlooked, even with the radiological models. Metabolism or other chemical processes, also, may more profoundly alter a chemical contaminant than they would a radioelement. Suitably developed models provide useful guidance in deciding what kinds of data to get and how extensive particular data bases need to be.


Transarterial chemoembolization for advanced hepatocellular carcinoma without macrovascular invasion or extrahepatic metastasis: analysis of factors prognostic of clinical outcomes.
To evaluate the safety and efficacy of TACE and factors predicting survival in patients with advanced hepatocellular carcinoma (HCC) without macrovascular invasion (MVI) or extrahepatic spread (EHS). This single-center retrospective study included 236 treatment-naïve patients who underwent TACE as first-line treatment for advanced HCC without MVI or EHS between January 2007 and December 2021. Following TACE, the median overall survival (OS) was 24 months. Multivariate Cox regression analyses revealed that tumor number ≥4 (risk point: 3), maximal tumor size >10 cm (risk point: 2), Child-Pugh class B (risk point: 2), alpha-fetoprotein (AFP) concentration ≥400 ng/mL (risk point: 2), and presence of HCC rupture (risk point: 2) were risk factors significantly associated with OS. The expected median OS among patients with <2, 2-4, and 5-9 risk points were 72, 29, and 12 months respectively. The major complication rates were significantly lower in patients with maximal tumor size ≤10 cm than in those with maximal tumor size >10 cm (4% [5/138] vs 21% [21/98], p = 0.001). TACE may be safe and effective in selected patients with advanced HCC without MVI or EHS, with a median OS of 24 months. Patients with limited tumor burden, compensated liver function, absence of HCC rupture, and favorable biologic markers may benefit the most from TACE. TACE is not recommended for patients with huge HCCs (>10 cm) because of its high rate of major complications (21%).


The effect of carbon supply on allocation to allelochemicals and caterpillar consumption of peppermint.
The carbon supply of peppermint plants was manipulated by growing clonal propagules under three carbon dioxide regimes (350, 500 and 650 μl l-1). Feeding by fourth instar caterpillars of Spodoptera eridania increased with elevated CO2 hostplant regime, as well as with low leaf nitrogen content and by a high proportion of leaf volatile terpenoids. Leaf weight increased significantly with the increased carbon supply, but the amount of nitrogen per leaf did not change. The amount of volatile leaf mono-and sesquiterpenes increased proportionately with total leaf dry weight and hence was not influenced by CO2 supply. These results are consistent with ecological hypotheses which assume that allocation to defense is closely regulated and not sensitive to carbon supply per se.


New library buildings: Bracken Library, Queen's University, Kingston, Ontario, Canada.
A brief sketch is given of the past history and present functions of the Bracken Library. Architectural and decorative features of the new library are described.


Role of space station instruments for improving tropical carbon flux estimates using atmospheric data.
The tropics is the nexus for many of the remaining gaps in our knowledge of environmental science, including the carbon cycle and atmospheric chemistry, with dire consequences for our ability to describe the Earth system response to a warming world. Difficulties associated with accessibility, coordinated funding models and economic instabilities preclude the establishment of a dense pan-tropical ground-based atmospheric measurement network that would otherwise help to describe the evolving state of tropical ecosystems and the associated biosphere-atmosphere fluxes on decadal timescales. The growing number of relevant sensors aboard sun-synchronous polar orbiters provide invaluable information over the remote tropics, but a large fraction of the data collected along their orbits is from higher latitudes. The International Space Station (ISS), which is in a low-inclination, precessing orbit, has already demonstrated value as a proving ground for Earth observing atmospheric sensors and as a testbed for new technology. Because low-inclination orbits spend more time collecting data over the tropics, we argue that the ISS and its successors, offer key opportunities to host new Earth-observing atmospheric sensors that can lead to a step change in our understanding of tropical carbon fluxes.


Testing for hepatitis B virus in patients with chronic urticaria and angioedema.
Serologic markers of hepatitis B virus (HBV) infection were sought in serum from 85 (75%) of 114 consecutive patients with chronic urticaria and angioedema (CUA). Markers of HBV infection were detected in 15 (17.6%) patients. Of these 13 (15.3%) were found to have anti-hepatitis B surface antibody (anti-HBs) and 2 (2.4%) had hepatitis B surface antigen (HBsAg). The frequency of current and previous HBV infection is thus several times greater than that reported in the general population. No patient was found to have anti-HBs and HBsAg detectable in the same sample of blood. A diagnosis of chronic persistent hepatitis was established in the two patients with HBsAg in their circulation. The possibility that CUA was causally related to HBV infection in these two cases, as well as those with anti-HBs, was considered and it was suggested that further exploration of the relationship between CUA and HBV infection is warranted.


Chronic rapamycin pretreatment modulates arginase/inducible nitric oxide synthase balance attenuating aging-dependent susceptibility to Trypanosoma cruzi infection and acute myocarditis.
Considering the efficacy of rapamycin in increasing lifespan and healthspan, attenuating the aging-dependent immunological decline, we compared the evolution of Trypanosoma cruzi infection and acute myocarditis in young and elderly mice untreated and chronically treated with this drug. Five groups were investigated: young uninfected and infected, elderly uninfected and infected with Trypanosoma cruzi untreated and treated with rapamycin (4 mg/kg every 3 days) from the 8th to the 96th week of age. Seven days after the last treatment, elderly mice were inoculated with T. cruzi. Young animals were infected at 8-weeks-old. Untreated elderly mice exhibited increase parasitemia, parasite load and myocarditis, which were associated to down-regulation in IL-2, IL-6, IFN-γ, TNF, anti-T. cruzi immunoglobulin G (IgG) total, IgG1 and IgG2a plasma levels, inducible nitric oxide synthase (iNOS) gene expression and nitric oxide (NO) cardiac production, as well as upregulation in Arginase-1 gene expression and arginase activity compared to young animals. These parameters were improved in rapamycin-pretreated elderly mice, which exhibited a better parasitological control, reduced heart inflammation and microstructural damage. These responses were associated with a better balance between Th1 and Th2 effectors similar to that observed in young animals, including an improved activation of Th1 cytokines and the iNOS pathway that positively regulates NO biosynthesis, contradicting the predominant activation of the arginase pathway in untreated elderly animals. Thus, our findings suggest that chronic pretreatment with rapamycin can attenuate immunosenescence in mice, contributing to prolong parasite resistance and attenuate acute myocarditis in elderly host challenged by T. cruzi.


Effects of Electroacupuncture on Metabolic Changes in Motor Cortex and Striatum of 6-Hydroxydopamine-Induced Parkinsonian Rats.
To explore the possible underlying mechanism by investigating the effect of electroacupuncture (EA) treatment on the primary motor cortex and striatum in a unilateral 6-hydroxydopamine (6-OHDA) induced rat Parkinson's disease (PD) model. Male Sprague-Dawley rats were randomly divided into sham group (n=16), model group (n=14), and EA group (n=14). EA stimulation at Dazhui (GV 14) and Baihui (GV20) was applied to PD rats in the EA group for 4 weeks. Behavioral tests were conducted to evaluate the effectiveness of EA treatment. Metabolites were detected by 7.0 T proton nuclear magnetic resonance. Following 4 weeks of EA treatment in PD model rats, the abnormal behavioral impairment induced by 6-OHDA was alleviated. In monitoring changes in metabolic activity, ratios of myoinositol/creatine (Cr) and N-acetyl aspartate (NAA)/Cr in the primary motor cortex were significantly lower at the injected side than the non-injected side in PD rats (P=0.024 and 0.020). The ratios of glutamate + glutamine (Glx)/Cr and NAA/Cr in the striatum were higher and lower, respectively, at the injected side than the non-injected side (P=0.046 and 0.008). EA treatment restored the balance of metabolic activity in the primary motor cortex and striatum. In addition, the taurine/Cr ratio and Glx/Cr ratio were elevated in the striatum of PD model rats compared to sham-lesioned rats (P=0.026 and 0.000). EA treatment alleviated the excessive glutamatergic transmission by down-regulating the striatal Glx/Cr ratio (P=0.001). The Glx/Cr ratio was negatively correlated with floor plane spontaneous locomotion in PD rats (P=0.027 and P=0.0007). EA treatment is able to normalize the metabolic balance in the primary motor cortex and striatum of PD rats, which may contribute to its therapeutic effect on motor deficits. The striatal Glx/Cr ratio may serve as a potential indicator of PD and a therapeutic target of EA treatment.


Gene transfer in magnetic bacteria: transposon mutagenesis and cloning of genomic DNA fragments required for magnetosome synthesis.
Broad-host-range IncP and IncQ plasmids have been transferred to the aerobic magnetic bacterium Aquaspirillum sp. strain AMB-1. Conjugal matings with Escherichia coli S17-1 allowed high-frequency transfer of the RK2 derivative pRK415 (4.5 x 10(-3) transconjugant per recipient cell) and the RSF1010 derivative pKT230 (3.0 x 10(-3) transconjugant per recipient). These plasmids successfully formed autonomous replicons in transconjugants and could be isolated and transformed back into E. coli, illustrating their potential as shuttle vectors. A mobilizable plasmid containing transposon Tn5 was transferred to Aquaspirillum sp. strain AMB-1 and also to the obligately microaerophilic magnetic bacterium Aquaspirillum magnetotacticum MS-1. Five nonmagnetic kanamycin-resistant mutants of Aquaspirillum sp. strain AMB-1 in which Tn5 was shown to be integrated into the chromosome were obtained. Different genomic fragments containing the mutagenized regions were cloned into E. coli. Two genomic fragments were restriction mapped, and the site of Tn5 insertion was determined. They were shown to be identical, although derived from independent transposon insertions. One of these clones was found to hybridize strongly to regions of the A. magnetotacticum MS-1 chromosome. This is the first report of gene transfer in a magnetic bacterium.


Cortisol mediated suppression of salmonid lymphocyte responses in vitro.
The suppressive activity of cortisol on the in vitro induction of coho salmon (Oncorhynchus kisutch) B cell activation was examined. Suppression was observed with splenic and pronephric (anterior kidney) derived lymphocytes. The kinetics of cortisol-induced suppression revealed distinct differences in the sensitivity of splenic and pronephric lymphocytes. Pronephric lymphocytes were only sensitive to cortisol early in the induction of the antibody response, whereas the splenic cells were sensitive to cortisol throughout the culture period. Addition of supernatants from antigen stimulated pronephric cultures completely restored the ability of pronephric lymphocytes to produce an antibody response, suggesting that this glucocorticoid-suppression may be mediated by inhibition of lymphokine production.


Monte Carlo assessment of soil moisture effect on high-energy thermal neutron capture gamma-ray by 14N.
Among many conventional techniques, nuclear techniques have shown to be faster, more reliable, and more effective in detecting explosives. In the present work, neutrons from a 5 Ci Am-Be neutron source being in water tank are captured by elements of soil and landmine (TNT), namely (14)N, H, C, and O. The prompt capture gamma-ray spectrum taken by a NaI (Tl) scintillation detector indicates the characteristic photo peaks of the elements in soil and landmine. In the high-energy region of the gamma-ray spectrum, besides 10.829 MeV of (15)N, single escape (SE) and double escape (DE) peaks are unmistakable photo peaks, which make the detection of concealed explosive possible. The soil has the property of moderating neutrons as well as diffusing the thermal neutron flux. Among many elements in soil, silicon is more abundant and (29)Si emits 10.607 MeV prompt capture gamma-ray, which makes 10.829 MeV detection difficult. The Monte Carlo simulation was used to adjust source-target-detector distances and soil moisture content to yield the best result. Therefore, we applied MCNP4C for configuration very close to reality of a hidden landmine in soil.


Computational modelling of embryonic stem-cell fate control.
The maintenance of pluripotency in embryonic stem cells (ESCs), its loss during lineage specification or its re-induction to generate induced pluripotent stem cells are central topics in stem cell biology. To uncover the molecular basis and the design principles of pluripotency control, a multitude of experimental, but also an increasing number of computational, studies have been published. Here, we consider recent reports that apply computational or mathematical modelling approaches to describe the regulatory processes that underlie cell fate decisions in mouse ESCs. We summarise the principles, the strengths and potentials but also the limitations of different computational strategies.


Immunological basis for susceptibility and resistance to pulmonary blastomycosis in mouse strains.
The immunological basis for a >10-fold resistance of outbred CD-1 mice compared to inbred BALB/c mice to pulmonary blastomycosis was investigated. Bronchoalveolar macrophages (BAM) from CD-1 mice killed yeast cells of Blastomyces dermatitidis (Bd) by 25% and this increased to 59% when activated by IFN-gamma. In contrast, BAM from BALB/c mice lacked significant killing (5%) of Bd but could be activated by IFN-gamma for enhanced killing (19%). Peritoneal macrophages (PM) from CD-1 mice had significant fungicidal activity for Bd (43%) and this increased to 63% with IFN-gamma treatment. By contrast, PM from BALB/c mice did not significantly kill Bd (14%) but were activated by IFN-gamma for significant killing (24%). Fungicidal activity of peripheral blood polymorphonuclear neutrophils (PMN) from CD-1 (87%) was greater than that of BALB/c (75%) (P<0.05). Macrophage inflammatory protein-1alpha (MIP-1alpha) production by BAM from BALB/c was significantly less than that from CD-1 in response to co-culture with Bd. IFN-gamma production by CD-1 spleen cells in response to concanavalin A (Con A, 1microg/ml) was 8-fold greater than that by BALB/c spleen cells. In contrast, BAM and PM from BALB/c mice in co-culture with Bd secreted several-fold more TNFalpha than BAM or PM from CD-1 mice. IL-2 production by BALB/c spleen cells in response to Con A was 3- to 4-fold greater than that by CD-1 spleen cells. Depressed IL-2 production by Con A stimulated CD-1 spleen cells correlated with depressed proliferative responses. Resistance of CD-1 mice to pulmonary blastomycosis correlates with enhanced fungicidal activity of BAM, PM, PMN, and IFN-gamma production by Con A stimulated spleen cells, compared to BALB/c mice. Consistent with the in vitro enhancement of effector cell function by IFN-gamma, in vivo therapy with IFN-gamma significantly (P<0.0001) improved survival of BALB/c mice with pulmonary blastomycosis.


Rituximab in children with steroid sensitive nephrotic syndrome: in quest of the optimal regimen.
Rituximab has emerged as an effective and important therapy in children with complicated frequently relapsing and steroid-dependent nephrotic syndrome to induce long-term disease remission and avoid steroid toxicities. The optimal rituximab regimen is not totally well defined, and there are many varying practices worldwide. We will in this review describe how patient factors, rituximab dose, and use of maintenance immunosuppression affect treatment outcomes. Specifically, low-dose rituximab without concomitant immunosuppression is associated with shorter relapse-free duration while other regimens have comparable outcomes. Patients with more severe disease generally have worse response to rituximab. Although rituximab appears to be generally safe, there are growing concerns of chronic hypogammaglobulinemia and impaired immunity especially in young children. Reliable prognostications and biomarkers for guiding subsequent treatments to avoid excessive treatments are yet to be identified. In this review, we will outline the, as we see it, best approach of rituximab in childhood steroid sensitive nephrotic syndrome at the present state of knowledge.


Peste des petits ruminants has been widely present in southern India since, if not before, the late 1980s.
Because previous authorities had suggested that small ruminants were playing a part in the dissemination of rinderpest, and a rinderpest-eradication campaign was about to begin, it was necessary to make precise virus identifications from a number of small-ruminant "rinderpest" outbreaks. When this was done using a database created from passive disease reports, we found that epidemics-reportedly due to rinderpest-were in fact due to peste des petits ruminants (PPRs). Although such cases had been common in India for a number of years, earlier clinical and laboratory reports no longer should be regarded as definitive. PPR outbreaks have been frequent in recent years. Further, we suggest that PPR is not a recent invader of India.


A Comparison of Health Plan- and Provider-Delivered Chronic Care Management Models on Patient Clinical Outcomes.
The real world implementation of chronic care management model varies greatly. One aspect of this variation is the delivery mode. Two contrasting strategies include provider-delivered care management (PDCM) and health plan-delivered care management (HPDCM). We aimed to compare the effectiveness of PDCM vs. HPDCM on improving clinical outcomes for patients with chronic diseases. We used a quasi-experimental two-group pre-post design using the difference-in-differences method. Commercially insured patients, with any of the five chronic diseases-congestive heart failure, chronic obstructive pulmonary disease, coronary heart disease, diabetes, or asthma, who were outreached to and engaged in either PDCM or HPDCM were included in the study. Outreached patients were those who received an attempted or actual contact for enrollment in care management; and engaged patients were those who had one or more care management sessions/encounters with a care manager. Effectiveness measures included blood pressure, low density lipoprotein (LDL), weight loss, and hemoglobin A1c (for diabetic patients only). Primary endpoints were evaluated in the first year of follow-up. A total of 4,000 patients were clustered in 165 practices (31 in PDCM and 134 in HPDCM). The PDCM approach demonstrated a statistically significant improvement in the proportion of outreached patients whose LDL was under control: the proportion of patients with LDL < 100 mg/dL increased by 3 % for the PDCM group (95 % CI: 1 % to 6 %) and 1 % for the HPDCM group (95 % CI: -2 % to 5 %). However, the 2 % difference in these improvements was not statistically significant (95 % CI: -2 % to 6 %). The HPDCM approach showed 3 % [95 % CI: 2 % to 6 %] improvement in overall diabetes care among outreached patients and significant reduction in obesity rates compared to PDCM (4 %, 95 % CI: 0.3 % to 8 %). Both care management delivery modes may be viable options for improving care for patients with chronic diseases. In this commercially insured population, neither PDCM nor HPDCM resulted in substantial improvement in patients' clinical indicators in the first year. Different care management strategies within the provider-delivered programs need further investigation.


Application of nanomaterials in sample preparation.
Nanotechnology is one of the most important trends in material science. Due to the ultra-small size, nanomaterials possess unique physical and chemical properties. In this review, we summarized and discussed the recent applications of different nanomaterials, including metallic nanoparticles, metal organic frameworks (MOFs) materials, carbonaceous nanomaterials and siliceous nanoparticles, in sample preparation techniques.


Pulmonary hypertension. Its association with hepatic cirrhosis and iron accumulation.
A 62-year-old white woman was found to have pulmonary hypertension; a short time later hepatic insufficiency developed. At the time of autopsy, hepatic cirrhosis, "primary" pulmonary hypertension, and evidence of increased iron absorption and storage were found. Pulmonary hypertension is an unusual complication of portal hypertension that is being reported increasingly often.


An ESI-MS method for characterization of native and modified oligonucleotides used for RNA interference and other biological applications.
RNA interference (RNAi) has become a powerful tool for investigating gene function, and, in addition, shows potential for the development of therapeutic agents. RNAi can be triggered in a variety of eukaryotic cells using small interfering RNA (siRNA), their double-stranded precursors (double-stranded RNA) and short hairpin precursors (shRNA). Here, we describe a protocol for analyzing these RNAs and their modifications using electrospray ionization mass spectrometry (ESI-MS). This protocol involves the desalting of nucleic acids using ammonium acetate precipitation, followed by characterization using ESI-MS. This protocol has been chiefly used for analyzing siRNAs and their chemical modifications, but it has also been used and can be applied to the analysis of a wide range of native and modified oligonucleotides. This protocol provides accurate information on molecular weight for a range of nucleic acids and can be completed in less than a day.


Chagas disease screening among HIV-positive Latin American immigrants: an emerging problem.
Chagas disease (CD) is an emergent disease in Europe that can behave as an opportunistic infection in HIV positive patients. The objective of this study was to evaluate the implementation of a CD screening programme in an HIV unit. An immunochromatography (ICT) of Trypanosoma cruzi was performed as a screening tool in HIV-positive patients born in CD endemic countries. ELISA and IFAT were used to confirm the diagnosis. A total of 155 patients, 116 males and 38 females, were included. Mean age was 36.9 years (± 8.4) and mean length of stay in Spain at the screening was 7.1 years (± 4.7). T. cruzi ICT was positive in four cases (2.6%), being confirmed (by ELISA and IFAT) in three of those (1.9%). Factors associated with confirmed positive T.cruzi serology were: Bolivia origin (p=0.016), Bolivia or Argentina origin (p=0.002), Southern Cone origin (p=0.015), rural origin (p=0.023), previously living in an adobe-made (p=0.001) or thatch-roofed house (p<0.0001), having a previous CD test (p=0.015), previous knowledge about CD (p=0.019), about vector (p=0.009) or recorded seeing vectors at home (p=0.012). Units dealing with HIV patients from endemic areas of American trypanosomiasis should implement CD screening protocols. Interviews of patients coming from endemic areas should include CD epidemiological questions.


A new surgical technique for short bowel syndrome.
Short bowel syndrome (SBS) is a severe intestinal disease that causes malabsorption. Long-term parental nutrition therapy induces infection and liver failure. For the surgical management of intestinal rehabilitation, the intestinal loop lengthening method and serial transverse enteroplasty (STEP) method have been reported, although their effects have proven limited. We herein report a new surgical technique, Saeki-Spiral-Shark (3S) method for SBS using biomimetics of shark intestine. In the 3S method, a spiral valve is formed inside the intestine by external sutures. Using a 25 cm length intestinal organ model, we performed both the 3S method and STEP procedure. We then compared the length and fluid passage times of the subsequently formed intestine. After the 3S method was performed, the length of the intestinal model changed to 22 cm, and after the STEP procedure, that was elongated to 30 cm. Although the water passage times did not change markedly, the semi-digestive nutritional supplement passage time slowed down in the model with the 3S method. There was slight leakage in the STEP procedure model. The 3S method is a unique method of treating SBS based on biomimetics. This procedure does not require an incision of the intestine, which thereby enabling clean and less-invasive surgery. We plan to conduct animal experiments in the future.


Protective effect of metabotropic glutamate mGluR5 receptor elimination in a 6-hydroxydopamine model of Parkinson's disease.
Pharmacologic or genetic blockade of metabotropic glutamate mGlu5 receptors (mGluR5) has been shown to attenuate parkinsonian motor deficits and protect nigrostriatal neurons from damage in the acute MPTP model of Parkinson's disease (PD), suggesting that therapeutically targeting the mGluR5 receptor may offer a novel approach to improving motor symptoms and/or slowing neurodegeneration in PD. This study further explored the neuroprotective potential of targeting mGluR5 receptors. We examined the behavioral and neurochemical effects of receptor elimination on toxicity induced by intra-striatal application of 6-hydroxydopamine (6-OHDA), thought to represent a comparatively progressive model of PD. mGluR5 knockout (KO) mice and wild-type (WT) littermates received unilateral 6-OHDA infusions. Reflecting the imbalance expected following unilateral infusion, WT but not KO mice demonstrated predominantly ipsilateral forepaw use and robust ipsilateral amphetamine-induced rotation. Further, performance on the vertical pole descent task was profoundly impaired in WT mice, while KO mice completed the task significantly faster. Consistent with the behavioral observations, neurochemical analyses of striatal dopamine depletion showed significantly diminished severity in KO mice with only 64% of striatal dopamine lost, compared to 92% in WT mice. The absence of brain mGluR5 receptors in living KO mice was verified using positron emission tomography (PET). Our findings substantiate the key role of mGluR5 receptors in animal models of PD, strengthening the rationale for the development of mGluR5 antagonists for their neuroprotective, as well as symptomatic, benefit.


Families Affected by Huntington's Disease Report Difficulties in Communication, Emotional Involvement, and Problem Solving.
Family functioning in Huntington's disease (HD) is known from previous studies to be adversely affected. However, which aspects of family functioning are disrupted is unknown, limiting the empirical basis around which to create supportive interventions. The aim of the current study was to assess family functioning in HD families. We assessed family functioning in 61 participants (38 HD gene-expanded participants and 23 family members) using the McMaster Family Assessment Device (FAD; Epstein, Baldwin and Bishop, 1983), which provides scores for seven domains of functioning: Problem Solving; Communication; Affective Involvement; Affective Responsiveness; Behavior Control; Roles; and General Family Functioning. The most commonly reported disrupted domain for HD participants was Affective Involvement, which was reported by 39.5% of HD participants, followed closely by General Family Functioning (36.8%). For family members, the most commonly reported dysfunctional domains were Affective Involvement and Communication (both 52.2%). Furthermore, symptomatic HD participants reported more disruption to Problem Solving than pre-symptomatic HD participants. In terms of agreement between pre-symptomatic and symptomatic HD participants and their family members, all domains showed moderate to very good agreement. However, on average, family members rated Communication as more disrupted than their HD affected family member. These findings highlight the need to target areas of emotional engagement, communication skills and problem solving in family interventions in HD.


Changing incidence of orthopedic surgery in rheumatic disease: contributing factors.
Rheumatic diseases are multisystem conditions that predominantly affect the musculoskeletal system, leading to soft tissue and articular damage. Historically, medical therapy was able to slow, but not prevent, erosion and joint destruction, resulting in the frequent need for orthopedic procedures to maintain function and minimize pain. However, the widespread use of disease-modifying anti-rheumatic drugs (DMARDs) and biologic therapy over the last twenty years has resulted in a dramatic decrease in the incidence of musculoskeletal damage and impairment among these patients. This review will discuss changing patterns of orthopedic surgery among patients with rheumatic diseases, focusing on rheumatoid arthritis and systemic lupus erythematosus.


Development, survivorship and reproduction of Eretmocerus sp. nr furuhashii (Hymenoptera: Aphelinidae) parasitizing Bemisia tabaci (Hemiptera: Aleyrodidae) on glabrous and non-glabrous host plants.
The developmental, survivorship and reproductive biology of Eretmocerus sp. nr furuhashii Rose & Zolnerowich parasitizing Bemisia tabaci (Gennadius) biotype B on tomato, cucumber, eggplant and collard at 26+/-0.5 degrees C was studied. The mean longevity ranged from 6.5 days on tomato to 8.1 days on collard. The mean lifetime fecundities on tomato, cucumber, eggplant and collard were 35.4, 37.3, 41.4 and 46.4 eggs, whereas the mean lifetime fertility was 20.2, 22.7, 28.3 and 33.6 offspring, respectively. Developmental time was longest on cucumber (17.1 days) and shortest on collard (15.9 days). Survival rates varied significantly across host plants. Sex ratio (female symbol:male symbol) varied from 1.71 to 1.93 across the four hosts. The intrinsic rate of increase (rm) was highest (0.157) on collard and lowest on tomato (0.133). Mean generation time (R0) ranged from 14.7 to 20.9 days. All the data demonstrated that the reproductive success and overall performance of E. sp. nr furuhashii increased as the density of leaf hairs declined. As leaf hairs play a key role in determining efficacy, it is unlikely that effective biological control of B. tabaci using E. sp. nr furuhashii will be achieved on non-glabrous crop varieties.


Aryl hydrocarbon receptor-microRNA-212/132 axis in human breast cancer suppresses metastasis by targeting SOX4.
MicroRNAs (miRNAs) are a class of short non-coding RNAs that pave a new avenue for understanding immune responses and cancer progression. Although the miRNAs are involved in breast cancer development, their axis with the transcription factors that show therapeutic potential in breast cancer is largely unknown. Previous studies showed anti-metastatic roles of agonist-activated aryl hydrocarbon receptor (Ahr) in various breast cancer cell lines. Recently, we demonstrated that agonist-activated Ahr induced a highly conserved miRNA cluster, named miR-212/132, in murine cellular immune compartment. Therefore, current study was performed to examine if this miRNA cluster mediates the anti-metastatic properties of Ahr agonists. The expression of miR-212/132 cluster and coding genes were examined by real-time PCR, and the protein levels were detected by western blot. The 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and 3,3'-diindolylmethane (DIM) were used to activate Ahr in MDA-MB-231 and T47D breast cancer cells. Chromatin immunoprecipitation (ChIP) assay was used to identify the binding site(s) for Ahr on miR-212/132 promoter. For prediction of potentially target gene of the miRNA cluster, bioinformatics analysis was carried out, and to test targeting, luciferase activity was quantified. Besides, biological effects of Ahr-miR-212/132 axis were examined in vitro by cell migration, expansion and invasion, and examined in vivo by orthotopic model of spontaneous metastasis. The miR-212/132 cluster was transcriptionally activated in MDA-MB-231 and T47D cells by TCDD and DIM, and this activation was regulated by Ahr. A reciprocal correlation was identified between Ahr agonists-induced miR-212/132 and the pro-metastatic SRY-related HMG-box4 (SOX4), and a new specific binding sites for miR-212/132 were identified on the untranslated region (3'UTR) of SOX4. Interestingly, miR-212/132 over-expression showed direct anti-migration, anti-expansion and anti-invasion properties, and an inhibition of the miRNA cluster mitigated the anti-invasive properties of TCDD and DIM. Further in vivo studies demonstrated that the Ahr-miR-212/132-SOX4 module was induced by Ahr activation. Taken together, the findings provide the first evidences of the synergistic anti-metastatic properties of miR-212/132 cluster through suppression of SOX4. Also, current study suggest a new miRNA-based mechanism elucidating the anti-metastatic properties of Ahr agonists, suggesting possibility of using miR-212/132 to control metastasis in breast cancer patients.


Solidification of self-emulsifying drug delivery systems (SEDDS): Impact on storage stability of a therapeutic protein.
Four solidification methods for self-emulsifying drug delivery systems (SEDDS) were compared to evaluate the impact of solidification on storage stability of an incorporated protein. Papain was loaded in SEDDS via hydrophobic ion pairing (HIP). Liquid SEDDS (l-SEDDS) were either solidified by adsorption to solid excipients such as magnesium-aluminometasilicate via wet granulation (ssilica-SEDDS) and carbohydrates via lyophilisation (scarbo-SEDDS) or by incorporation of high-melting PEG-surfactants (sPEG-SEDDS) and triglycerides (soil-SEDDS) in SEDDS preconcentrates. L- and s-SEDDS were compared regarding intrinsic emulsion properties, solid-state form of papain, enzyme stability and activity during storage. HIP with deoxycholate showed a precipitation efficiency of 82% and papain maintained 90% of its initial activity. Incorporated papain was present in an amorphous state, confirming a molecular dispersion in all preconcentrates. In comparison to l-SEDDS each solidification method investigated improved the storage stability of incorporated papain. Neither precipitation nor phase separation was observed for s-SEDDS. sPEG-SEDDS demonstrated with 87.8% the highest enzymatic activity and displayed according to the following rank order: sPEG-SEDDS > soil-SEDDS > ssilica-SEDDS > scarbo-SEDDS > l-SEDDS the highest remaining papain activity after 30 days of storage. This work clearly demonstrates that solidified SEDDS can provide a significantly improved storage stability for therapeutic proteins compared to corresponding liquid formulations.


Flow microfluorometric DNA content measurements of tissue culture cells and peripheral lymphocytes.
The difference in DNA content of peripheral lymphocytes from normal males, normal females, and an individual with a 48 (xxxy) chromosome constitution was determined by rapid flow microfluorometric techniques. A similar comparison was performed using tissue culture fibroblasts derived from an individual with a 49 (xxxxy) chromosome constitution and WI-38 cells as a normal control. Less than 60 min were required to isolate the lymphocytes, to stain the cells fluorescently, and to measure the increased DNA content. The measured increase in DNA content is consistent with chromosome DNA analyses and chromosome length measurements.


Response by the neurotensin systems of the basal ganglia to cocaine treatment.
Multiple administrations of high doses of cocaine had profound effects on the neurotensin (NT) systems of the basal ganglia. Approximately 200-300% increases in striatal content of neurotensin-like immunoreactivity (NTLI) were observed 1-8 h following five doses of 30 mg/kg per dose of cocaine. The effect subsided by 48 h after treatment. Significant changes in striatal NTLI levels were not observed after a single dose of this stimulant. The nigral NT systems appeared to be even more sensitive to cocaine administration. Compared to striatal changes, increases in nigral NTLI content were greater (as much as 455% of control), required lower cocaine doses (20 mg/kg per dose), lasted longer (still elevated to 200% of control after 48 h) and were significant following a single cocaine exposure. The response of the striatal NT systems to cocaine appeared to be mediated principally by dopamine D-1 receptors, while both D-1 and D-2 receptors contributed to the response by the nigral NT projections. Specific dopamine, but not serotonin, uptake blockers caused increases in striatal and nigral NTLI concentrations similar to that seen with cocaine treatments, suggesting that interference with the dopamine uptake carrier complex by cocaine was responsible for its actions on extrapyramidal NT systems.


Castration-resistant metastatic prostate cancer: current status and treatment possibilities.
Prostate cancer (PCa) is the most common cancer in the male population in Western countries, second to skin cancer. Hormonal therapy allows long-lasting and effective control of cancer-related symptoms in advanced stages; however, in almost all patients with metastatic PCa the disease will progress when it becomes castration-resistant (CRPC). Chemotherapy with docetaxel was a turning point in CRPC, as, for the first time, it resulted in an increased survival time in comparison with mitoxantrone and prednisone. Combination therapy with docetaxel and prednisone is the first-line treatment of choice. Once the cancer has progressed, there is no clear alternative, although some new agents have shown promise in the treatment of this type of cancer. This review will provide an overview of the current status of CRPC, including clinical status, prognosis, firstline treatment and new second-line treatment options.


Laxity and flexibility of the ankle following reconstruction with the Chrisman-Snook procedure.
The effect of reconstruction of the anterior talofibular ligament with the Chrisman-Snook procedure on neutral zone laxity (anterior-posterior displacement at low loads) and flexibility (a measure of the nonlinear load-displacement response) of the ankle was investigated in vitro during the anterior drawer test. Neutral zone laxity was defined as the magnitude of anterior-posterior displacement of the ankle joint at +/- 2.5 N of applied load. The flexibility parameter was defined as the slope of a line between the natural logarithm of the anterior load applied to the ankle and the resulting displacement. After reconstruction with the Chrisman-Snook procedure, the values for neutral zone laxity of the ankle were significantly less than normal at 0 degree of plantar flexion, whereas the flexibility values were significantly greater than normal. This study revealed that, after the Chrisman-Snook procedure, values for ankle flexibility are not restored to normal even if those for neutral zone laxity are reduced to less than normal. The findings suggest that this nonanatomical reconstruction procedure does not reproduce normal kinematics of the ankle joint. This may help explain some of the adverse clinical reports associated with the Chrisman-Snook reconstruction procedure.


Predictive factors of lower calyceal stone clearance after extracorporeal shockwave lithotripsy (ESWL): the impact of radiological anatomy.
This study was carried out to determine whether or not there is a significant relationship between the radiologic anatomy of the lower calyx, as seen on preoperative intravenous urography (IVU), and the outcome of stone clearance after extracorporeal shockwave lithotripsy (ESWL) for lower renal calyceal stones. Between June 1998 and April 2007, 112 patients with a solitary lower renal calyceal stone measuring 20 mm or less in size were enrolled in this retrospective study. Pretreatment IVU was reviewed for measuring the anatomical predictors, such as lower pole infundibular length, infundibular width (IW) and infundibulopelvic angle, while the stone location and size were determined on plain abdominal X-ray. All patients were treated with ESWL using a Siemens Lithostar Plus lithotriptor and were followed-up for the outcome of stone clearance 3 months after ESWL with plain abdominal X-ray films and ultrasonography. Three months after ESWL, only 49 (43.7%) patients were stone-free. Under multivariate analysis with logistic regression, smaller stone size (10 mm or less, p = 0.005) and greater IW (4 mm or more, p = 0.029) were significant favourable predictors for better stone clearance. In addition to the influence of stone size, lower pole anatomy, especially IW, has a significant impact on stone clearance for lower calyceal stone after ESWL.


Peripheral Intravenous Catheter Complications in Hospitalized Cats: An Observational Pilot Study.
There is little information about complications associated with peripheral catheter use in cats. The primary objective of this study was to determine the main reason for catheter removal in cats hospitalized in the Intensive Care Unit at a university teaching hospital. The secondary objective was to describe catheter-associated complications in cats hospitalized. All feline patients with peripheral intravenous catheters admitted to the Intensive Care Unit between June and August 2017 were prospectively enrolled in this study. All catheters were evaluated at least 3 times a day per institutional Intensive Care Unit protocol. The catheters were monitored throughout the cat's hospitalization period for development of complications, including occlusion, phlebitis and extravasation. Data collected included patient signalment, reason for hospitalization, catheter size and location, number of hours the catheter remained in place, reason for removal and if the catheter was replaced once removed. Thirty-four cats were enrolled in the study, and a total of 42 catheters were placed in those cats. Median peripheral IV catheter duration was 23.8 hours (interquartile range [IQR] 13.8-41.3 hours). The most frequent reason for catheter removal was patient discharge from the hospital (24/42, 57.1%). Overall catheter complication rate was 21.4% (9/42). Complications observed included phlebitis, extravasation, patient removal, occlusion, and edema formation. The results of this study conclude that the majority of peripheral IV catheters in cats are removed due to discharge from hospitalization. More studies with a larger population of cats are needed to see if there is a relationship between length of indwelling catheterization and risk of catheter-associated complications.


Increased expression of Abeta degrading enzyme IDE in the cortex of transgenic mice with Alzheimer's disease-like neuropathology.
Expression levels of amyloid beta (Abeta)-degrading enzymes, insulin degrading enzyme (IDE) and neprilysin (NEP), were examined in transgenic mice with Alzheimer's disease-like neuropathology. After the development of first Abeta plaques in transgenic mice brain, cortical mRNA and protein levels of IDE were significantly up-regulated in the transgenic mice compared to their non-transgenic littermates. Up-regulation of IDE mRNA-levels occurred in parallel with increased Abeta40 and Abeta42 production. Additionally, a significant positive correlation was observed between protein levels of IDE and full-length amyloid precursor protein (APP) in the cerebral cortex. mRNA and protein levels of NEP were also nominally up-regulated in Tg mice compared to controls. These data may reflect up-regulation of the IDE and possibly of NEP expression in response to the Abeta accumulation.


Trimethyltin-induced differential expression of PAR subtypes in reactive astrocytes of the rat hippocampus.
Thrombin, its main inhibitor (protease nexin-1) and its related receptors (protease-activated receptors, PAR-1,-2, -3, -4) were studied in rat hippocampus following administration of trimethyltin (TMT), a neurotoxin inducing neuronal degeneration and reactive gliosis. Reverse transcriptase-polymerase chain reaction (RT-PCR) and immunohistochemistry revealed that while expression of prothrombin and protease nexin-1 did not change significantly in TMT-treated hippocampi, PARs (in particular PAR-1 and to a lesser extent PAR-2 and PAR-3) were upregulated in reactive astrocytes, suggesting their involvement in neurodegeneration and in the consequent response of the nervous tissue.


A logic model framework for community nutrition education.
Logic models are a practical method for systematically collecting impact data for community nutrition efforts, such as the Food Stamp Nutrition Education program. This report describes the process used to develop and test the Community Nutrition Education Logic Model and the results of a pilot study to determine whether national evaluation data could be captured without losing flexibility of programming and evaluation at the state level. The objectives were to develop an evaluation framework based on the Logic Model to include dietary quality, food safety, food security, and shopping behavior/food resource management and to develop a training mechanism for use. The portability feature of the model should allow application to a variety of community education programs.


The characterization of a mammalian DNA structure-specific endonuclease.
The repair of some types of DNA double-strand breaks is thought to proceed through DNA flap structure intermediates. A DNA flap is a bifurcated structure composed of double-stranded DNA and a displaced single-strand. To identify DNA flap cleaving activities in mammalian nuclear extracts, we created an assay utilizing a synthetic DNA flap substrate. This assay has allowed the first purification of a mammalian DNA structure-specific nuclease. The enzyme described here, flap endonuclease-1 (FEN-1), cleaves DNA flap strands that terminate with a 5' single-stranded end. As expected for an enzyme which functions in double-strand break repair flap resolution, FEN-1 cleavage is flap strand-specific and independent of flap strand length. Furthermore, efficient flap cleavage requires the presence of the entire flap structure. Substrates missing one strand are not cleaved by FEN-1. Other branch structures, including Holliday junctions, are also not cleaved by FEN-1. In addition to endonuclease activity, FEN-1 has a 5'-3' exonuclease activity which is specific for double-stranded DNA. The endo- and exonuclease activities of FEN-1 are discussed in the context of DNA replication, recombination and repair.


Extracting regulatory modules from gene expression data by sequential pattern mining.
Identifying a regulatory module (RM), a bi-set of co-regulated genes and co-regulating conditions (or samples), has been an important challenge in functional genomics and bioinformatics. Given a microarray gene-expression matrix, biclustering has been the most common method for extracting RMs. Among biclustering methods, order-preserving biclustering by a sequential pattern mining technique has native advantage over the conventional biclustering approaches since it preserves the order of genes (or conditions) according to the magnitude of the expression value. However, previous sequential pattern mining-based biclustering has several weak points in that they can easily be computationally intractable in the real-size of microarray data and sensitive to inherent noise in the expression value. In this paper, we propose a novel sequential pattern mining algorithm that is scalable in the size of microarray data and robust with respect to noise. When applied to the microarray data of yeast, the proposed algorithm successfully found long order-preserving patterns, which are biologically significant but cannot be found in randomly shuffled data. The resulting patterns are well enriched to known annotations and are consistent with known biological knowledge. Furthermore, RMs as well as inter-module relations were inferred from the biologically significant patterns. Our approach for identifying RMs could be valuable for systematically revealing the mechanism of gene regulation at a genome-wide level.


Automated and robust extraction of genomic DNA from various leftover blood samples.
With the development of genomic technologies, the isolation of genomic DNA (gDNA) from clinical samples is increasingly required for clinical diagnostics and research studies. In this study, we explored the potential of utilizing various leftover blood samples obtained from routine clinical tests as a viable source of gDNA. Using an automated method with optimized pre-treatments, we obtained gDNA from seven types of clinical leftover blood, with average yields of gDNA ranging from 3.11 ± 0.45 to 22.45 ± 4.83 μg. Additionally, we investigated the impact of storage conditions on gDNA recovery, resulting in yields of 8.62-68.08 μg when extracting gDNA from EDTA leftover blood samples stored at 4 °C for up to 13 weeks or -80 °C for up to 78 weeks. Furthermore, we successfully obtained sequenceable gDNA from both Serum Separator Tube and EDTA Tube using a 96-well format extraction, with yields ranging from 0.61 to 71.29 μg and 3.94-215.98 μg, respectively. Our findings demonstrate the feasibility of using automated high-throughput platforms for gDNA extraction from various clinical leftover blood samples with the proper pre-treatments.


Higher soil organic carbon sequestration potential at a rehabilitated mangrove comprised of Aegiceras corniculatum compared to Kandelia obovata.
The present study compared the ecosystem organic carbon (OC) stocks and soil OC sources between two 12-year-old monospecific mangrove sites comprised of different species (Kandelia obovata in tree form and Aegiceras corniculatum in shrub form). We tested whether the carbon sequestration performance following rehabilitation varied with plantation of species in different forms and whether mangrove vegetation sequestrate OC more rapidly than soil pool. The results showed that mangrove rehabilitation increased the ecosystem OC stock relative to that of a non-vegetated bare flat. The accumulation of soil carbon was accompanied by increased soil total nitrogen contents and decreased δ13C values of soil OC, indicating that the increases in OC and TN contents were a function of accumulation of 13C-depleted mangrove materials in the soil. The sequestrated OC over the 12 years was considerably less in soil than in biomass at each mangrove site, suggesting that mangrove vegetation contributes more rapidly than the soil to ecosystem OC sequestration following rehabilitation before the vegetation has reached maturity. Compilation of the carbon stocks from worldwide rehabilitated mangrove forests with various ages further supports this finding. The K. obovata site had an apparently higher biomass OC stock but less OC in the soil than those at the A. corniculatum site. There was a higher standing leaf litter stock on the forest floor and more mangrove materials incorporated into the top 15 cm soil at the A. corniculatum site. These results suggested that the two rehabilitated mangrove sites had different development trajectories of both biomass and soil OC sequestration. Moreover, the performance of ecosystem carbon sequestration was related to plantation of different mangrove species. These carbon sequestration feature of rehabilitated mangrove forests therefore deserve attention in future rehabilitation programs to promote carbon sequestration performance.


A comparison of the hemodynamic effects of prenalterol and isoprenaline in patients with complete heart block.
Prenalterol is a new beta-adrenergic agonist which stimulates mainly beta 1-receptors, in contrast to isoprenaline which stimulates both beta 1- and beta 2-receptors. We studied the hemodynamic effects of prenalterol and isoprenaline in seven patients with complete heart block and idioventricular escape rhythm due to ischemic heart disease. Isoprenaline was given as a continuous infusion at two increasing doses (1.7 micrograms/min and 3.4 micrograms/min each given for 30 min). After the second dose of isoprenaline the cardiac index was increased from 2.27 +/- 0.06 to 3.61 +/- 0.60 1/min/m2, heart rate was increased from 34.1 +/- 1.2 to 50.4 +/- 3.1 beats/min and mean blood pressure was decreased by 12.4 mm Hg. Mean pulmonary artery pressure was increased by 2 mm Hg. Prenalterol was given as two i.v. bolus injections of 3.5 mg and 7.0 mg at 15-min intervals. The first dose of prenalterol increased the cardiac index from 2.22 +/- 0.10 to 2.42 +/- 0.12 and heart rate from 37.0 +/- 1.8 to 40.1 +/- 1.7. Mean blood pressure and mean pulmonary artery pressure were unchanged. The second dose of prenalterol did not change the hemodynamic variables significantly compared to the changes after the first dose. We conclude that isoprenaline is preferable to prenalterol for treatment of complete heart block.


Temporal variations in scale cortisol indicate consistent local-and broad-scale constraints in a wild marine teleost fish.
Environmental changes can alter the nursery function of coastal areas through their impact on juveniles' growth and survival rates, an effect mediated by individuals' chronic stress response. Fish chronic stress can be quantified using scale cortisol but no study has yet been quantified the spatio-temporal variations in scale cortisol and its relationship with growth in wild nurseries. We collected wild sea bass juveniles (Dicentrarchus labrax, four years, three nurseries) and found that scale cortisol levels increased consistently with age and across cohorts in 2019 and 2020 probably due to greater stress history in older fish and/or heatwaves that occurred in summers of 2018 and 2019. Growth was impaired in fish with high scale cortisol in 2019 and 2020, confirming the usefulness of scale cortisol as a biomarker of broad and local constraints in wild fish; longer time series will enable us to identify environmental factors underpinning these temporal variations.


A comparison of central brain (cerebrospinal and extracellular fluids) and peripheral blood kinetics of phenytoin after intravenous phenytoin and fosphenytoin.
Phenytoin (PHT) is a first-line drug in the treatment of status epilepticus. However, the parenteral PHT formulation is associated with administration difficulties and therefore fosphenytoin (FosPHT), a PHT pro-drug, has been developed. As the peripheral (blood) and central (cerebrospinal fluid [CSF] and brain extracellular fluid [ECF]) kinetic inter-relationship of PHT after i.v. FosPHT administration is unknown we sought to ascertain the relationship and to compare it to that of i.v. PHT. A freely behaving rat model, which allows for the concurrent and temporal sampling of blood (jugular vein), CSF (cisterna magna) and brain ECF (frontal cortex and hippocampus), was used. PHT and FosPHT were administered by i.v. infusion and blood, CSF and microdialysate samples collected at timed intervals up to 6 hours. The pharmacokinetic parameters in plasma of PHT after PHT and FosPHT (30 and 60 mg/kg) administration were indistinguishable. The PHT plasma free fraction (free/total concentration ratio) was 0.25-0.31 and 0.26-0.31 for PHT and FosPHT, respectively. Mean PHT Tmax values for CSF were 9-13 minutes. The equivalent values in the frontal cortex and hippocampal ECF were 29-34 minutes. Cmax values increased dose-dependently and were independent of whether PHT or FosPHT was administered. Furthermore the kinetic profiles of PHT for the frontal cortex and hippocampus were indistinguishable suggesting that PHT distribution in the brain is not brain region specific. Thus, overall, the central and peripheral kinetics of PHT are indistinguishable after PHT and FosPHT.


Effects of dietary supplementation with fish oil, lard, or coconut oil on oxytocinase activity in the testis of mice.
Oxytocin (OT), locally synthesized in the testis, is involved in androgen biosynthesis. The use of polyunsaturated fatty acids (e.g., fish oil) in the diet may improve the fertilizing ability in mammals. Cystinyl aminopeptidase (oxytocinase) activity plays a major role regulating the functional status of OT. Sex steroids and the type of the fatty acid used in the diet modify aminopeptidase activities in serum. In the present study, the authors compared the effect of a fish oil supplemented diet with two other diets supplemented with saturated oils (lard and coconut) on oxytocinase activity in the testis of mice. The enzymatic activity was determined fluorometrically using cystinyl-beta-naphthylamide as substrate. The results demonstrated higher levels of oxytocinase activity in mice fed the diet supplemented with fish oil than in those that were fed diets containing lard or coconut oils. The testicular functions in which OT is involved may be attenuated by the use of fish oil in the diet.


Evaluation of protective efficacy of CC-2 formulation against topical lethal dose of T-2 toxin in mice.
T-2 toxin is the type-A trichothecene and a common contaminant of food and cereals, produced by Fusarium species. T-2 toxin easily penetrates skin due to its lipophilic nature and causes skin irritation and blisters in humans. Physical protection of the skin and airway is the only proven effective method of protection. To date, no chemical antidotes are available to prevent T-2 induced lethality. In the present study, we evaluated the protective efficacy of 20% N,N'-dichloro-bis(2,4,6-trichlorophenyl) urea (CC-2) formulation against lethal topical exposure dose of T-2 toxin in mice. None of the animals exposed to only T-2 toxin at lethal dose of 2 and 4 LD50 (11.8 and 23.76 mg/kg body weight) survived beyond 36 and 16 h, respectively. CC-2 application at 5 and 15 min post-exposure protected mice 100% from lethality at 2 LD50. Survival rate was 100% and 50% at 4LD50 dose if CC-2 was applied dermally within 5 and 15 min post-exposure. Recovery profile of surviving animals after 2LD50 T-2 toxin exposure at 1, 3, 7, and 14 days was assessed in terms of hepatic GSH, lipid peroxidation, serum ALP, ALT and AST. Hepatic lipid peroxidation significantly increased in all groups exposed to T-2 toxin by 3 day but normalized by day 7. A delayed GSH depletion was noted in surviving animals on day 7 but recovered by day 14. ALT and AST levels were elevated in all CC-2 protected mice on day 1 and normalized by day 3. ALP level decreased till day 7 in all protected groups. The biochemical variables recovered to control values by 14th day. GC-MS analysis after in vitro interaction of CC-2 formulation with T-2 toxin had shown that nearly 86% of T-2 toxin is decontaminated in 5 min but 8-10% of T-2 toxin was still present even after 60 min of interaction. Results of our study suggest that CC-2 may be an effective dermal decontaminant against lethal topical exposure of T-2 toxin.


Autoradiographic localization of binding sites for follicle stimulating hormone (FSH) in the boar testis.
The tubular localization of binding sites for 125I-FSH is demonstrated in vitro by the autoradiography on frozen sections of boar-testis. The uniform distribution of silver grains throughout the seminiferous epithelium suggests the presence of receptors for FSH also in the adluminal compartment. Similar results have been obtained using rat testis.


Proteome studies on liver tissue in a phenobarbital-induced rat model.
Many drugs may affect the activity of cytochrome P450 (CYP), which is a major source of adverse drug interactions (ADR). Phenobarbital (PB) is the typical inducer of cytochrome P450. The aim of our study was to determine the changes in the cytosolic proteins expression in rat liver at a protein level following induction of cytochrome P450. Firstly, we made a phenobarbital-induced cytochrome P450 rat model. The total cytosolic proteins were then extracted from rat liver tissue and separated by 2-D gel electrophoresis (2-DE). Differentially expressed spots were identified by MALDI-TOF/TOF tandem mass spectrometry followed by database searching. Eight differentially expressed proteins were identified and these proteins were found to be involved in protein degradation, oxidative stress, energy metabolism, biotransformation, and the synthesis of quinolinic acid (QUIN). These findings should provide useful information for research into the regulation of cytochrome P450 gene expression, drug metabolism and drug interaction.


Can tropical seaweeds reduce herbivory by growing at night? Diel patterns of growth, nitrogen content, herbivory, and chemical versus morphological defenses.
Tropical seaweeds in the genus Halimeda reduce losses to grazing by capitalizing on diel patterns of herbivore activity. These seaweeds produce new, more herbivoresusceptible growth at night when herbivorous reef fishes are inactive. Plant portions more than 48 h old are low in food value, well defended morphologically (calcified and high in ash content), and relatively resistant to herbivory. Younger plant portions represent 3-4.5 times the food value (nitrogen or organic content) of older portions but are only moderately more susceptible to herbivores due to their high concentrations of the terpenoid feeding deterrents halimedatrial and halimedatetraacetate. Halimedatrial significantly deters grazing by both parrotfishes (Scaridae) and surgeonfishes (Acanthuridae) and occurs in high concentrations (2-4.5% of plant ash-free dry mass) in plant portions that are 4-12 h old, intermediate concentrations (0.3-2.3%) in portions that are 16-26 h old, and low concentrations (0.3%) in older plant portions. The related compound halimedatetraacetate is absent from the youngest plant portions, shows a rapid increase in concentration (from 0 to 1%) in plant material that is approximately 16 h old, and then rapidly declines to low levels (0.1 to 0.2%) in older plant portions. Thus, newly produced tissues are nutritionally valuable but contain high concentrations of defensive chemicals. As these tissues age, morphological defenses increase, the tissue becomes less valuable as a food for herbivores, and chemical defenses decrease. Additionally, new growth of Halimeda remains unpigmented until just before sunrise. Thus, the valuable, nitrogen-containing molecules associated with photosynthesis are not placed in the new, and more herbivore susceptible, growth until lights is available and they can start producing income for the plant.Experiments in a coral-reef microcosm, where diel patterns of light and water chemistry could be altered, indicated that Halimeda's growth pattern is cued by the timing of light-dark cycles rather than by co-occurring diel changes in water chemistry. Although the growth patterns of Halimeda seem unusual, similar patterns appear to occur in numerous other seaweeds and in microalgae such as diatoms and dinoflagellates.


Author Correction: Artificial Intelligence based Models for Screening of Hematologic Malignancies using Cell Population Data.
An amendment to this paper has been published and can be accessed via a link at the top of the paper.


Expression dynamics of CXCL12 and CXCR4 during the progression of mycosis fungoides.
Mycosis fungoides (MF) classically presents from patch stage to plaque stage over a number of years and finally progresses to tumour stage with nodal or visceral involvement. The mechanism of progression remains incompletely elucidated. Chemokines and their receptors are known to be involved in disease mechanisms, with CXCL12 and CXCR4 playing a critical role in carcinogenesis, invasion and cancer cell migration in various carcinomas. To investigate the expression of CXCL12 and CXCR4 in different cutaneous stages of MF. Formalin-fixed, paraffin-embedded skin samples from 40 patients with MF (21 patch stage, 10 plaque stage, nine tumour stage) and 30 non-neoplastic control skin samples were analysed. CXCL12 and CXCR4 were assessed by quantitative reverse-transcription polymerase chain reaction and immunohistochemical staining. The expression level of mRNA for CXCL12 in plaque-stage MF was significantly higher than in control skin (P = 0.0035), or patch-stage (P = 0.0108) or tumour-stage disease (P = 0.0089). The CXCR4 mRNA expression level in plaque-stage disease was significantly higher than in control skin (P = 0.0090) or patch-stage disease (P = 0.0387). CXCL12- and CXCR4-positive cell rates in patch-stage and plaque-stage MF were significantly higher than those in control skin (P < 0.0001). CXCL12- and CXCR4-positive cell rates in tumour-stage MF were significantly lower than those in patch- and plaque-stage disease (P = 0.0274 and P = 0.0492, respectively). Our data suggest that neoplastic T cells in MF are exposed to the microenvironment, given the abundance of CXCL12 during its progression, and also that neoplastic T cells express CXCR4, especially in the pretumour stage. We reveal that the CXCL12-CXCR4 axis plays a critical role in MF progression.


The influence of hydrogen on plasticity in pure iron-theory and experiment.
Tensile stress relaxation is combined with transmission electron microscopy to reveal dramatic changes in dislocation structure and sub structure in pure α-Fe as a result of the effects of dissolved hydrogen. We find that hydrogen charged specimens after plastic deformation display a very characteristic pattern of trailing dipoles and prismatic loops which are absent in uncharged pure metal. We explain these observations by use of a new self consistent kinetic Monte Carlo model, which in fact was initially used to predict the now observed microstructure. The results of this combined theory and experimental study is to shed light on the fundamental mechanism of hydrogen enhanced localised plasticity.


Tooth-derived stem cells integrated biomaterials for bone and dental tissue engineering.
Recent years have seen the emergence of tissue engineering strategies as a means to overcome some of the limits of conventional medical treatment. A biomaterial with tailored physio-chemical characteristics is used in this sophisticated method to transport stem cells and growth factors/bioactive substances, or to attract local endogenous cells, enabling new tissue formation. Biomaterials might serve as a biomimetic structure inspired by the natural milieu, assisting the cells in establishing their natural relationships. Such a method would benefit from having ready access to an abundant reservoir of stem cells with strong tissue regeneration capacity, in addition to using biological compatible material to promote new tissue creation. Teeth may have a plethora of self-renewing, multipotent mesenchymal stem cell (MSC) populations. Recent advancements and promising directions for cell transplantation and homing techniques using dental MSCs for tissue regeneration are discussed in this review paper. Overall, this research paints a picture of the present landscape of new approaches to using tooth-derived MSCs in conjunction with biomaterials and bioactive substances for tissue regeneration.


Experimental regional myocardial ischaemia and myocardial uptake of potassium analogues; intercomparison of 42K, 86Rb and 201Tl.
The uptake of 42K, 86Rb and 201Tl by non-ischaemic and ischaemic myocardium was determined in rats with coronary artery ligature lasting 10, 30, 60 and 120 min, and in control rats without ischaemia. Whereas the myocardial concentration of 201Tl and 42K in control rats was similar and higher than that of 86Rb, 201Tl was superior to the other two radionuclides due to its significantly higher accumulation in non-ischaemic myocardium and the higher ratio of non-ischaemic to ischaemic radioactivity. The 86Rb accumulation in non-ischaemic myocardium and non-ischaemic/ischaemic ratio began to decrease from its maximum at 10 min. 201Tl, 42K and 86Rb blood levels in intact animals decreased rapidly after intravenous injection to low and nearly stabilized values at 5 min. Na+K+-ATPase activity in the ischaemic myocardium was high in the acutely ischaemic myocardium and decreased to below control levels after 4 h of ischaemia; changes in activity could not influence the low uptake of potassium analogues in fresh ischaemic myocardium.


Effects of an 8-session behavioral parent training group for parents of children with ADHD on child impairment and parenting confidence.
This study examined the feasibility and effectiveness of a behavioral parent training (BPT) group intervention implemented in an outpatient mental health setting in reducing child impairments and increasing parenting confidence in managing child behavior. Parents of 241 children with ADHD participated in the eight-session parent group program, completing the Impairment Rating Scale (IRS) and a measure of parenting confidence at the first and last session. Parents reported improvements in child behavior across all domains of the IRS, with the largest improvements in terms of overall impairment, parent-child relationship, and impact of child behavior on the family. Parents also reported increased confidence in managing their child's behavior. These findings suggest that brief BPT group programs administered to a diverse range of attendees in a typical outpatient setting result in improvements in functional impairments comparable with those produced in controlled studies, as well as improved parenting confidence.