Acute effects of thyroid hormone analogs on sodium currents in neonatal rat myocytes.
We previously reported that T3(3,3',5-triiodo-L-thyronine) acutely increases sodium currents (INa) in neonatal rat myocytes. Here we compare the effects of several thyroid hormone analogs, including T4(3,3',5,5'-tetraiodo-L-thyronine), rT3(3,3',5'-triiodo-L-thyronine), D-T3(3,3',5-triiodo-D-thyronine), 3,5-T2(3,5-diiodo-L-thyronine), DIT (3,5-diiodo-L-tyrosine), MIT (3-monoiodo-L-tyrosine), tetrac (3,3',5,5'-tetraiodo-thyroacetic acid), triac (3, 3',5-triiodo-thyroacetic acid), and tyrosine, on INa in cultured neonatal rat myocytes (n ranged from 9 to 28 for each comparison). T4, T3, 3,5-T2, and DIT (10 n m) all increased current density relative to control to a similar degree: to 1.22+/-0.2, 1.21+/-0.03, 1.16+/-0.02 and 1.16+/-0.03, respectively, P<0.05. In contrast, thyroid hormone analogs with an altered side group of the inner iodophenyl ring, including tetrac, triac, and D-T3, had no effect on INa nor did rT3, MIT or tyrosine. Pretreatment with rT3 inhibited the effects of T4, T3, 3,5-T2, and DIT. Conversely, the dose-dependent inhibitory effect of amiodarone, an iodinated benzofuran derivative that antagonizes thyroid hormone actions, on INa was blocked when myocytes were pretreated with T3(100 n m, n=3), suggesting an interaction of T3 with amiodarone. The enhancement of INa by T3 and 3, 5-T2 could not be blocked by propranolol, suggesting that the effects are not mediated through beta -adrenergic signaling pathways. In conclusion, the present results suggest that the acute effects of thyroid hormone and analogs on cardiac INa are mediated by a non-genomic thyroid hormone receptor with a unique structure-activity relationship.


Robotic retroperitoneal lower para-aortic lymphadenectomy in cervical carcinoma: first report on the technique used in 5 patients.
Retroperitoneal para-aortic laparoscopic lymphadenectomy is a technically challenging operation. The robotic Da Vinci system might be valuable in this operation due to a steady three-dimensional visualization, instrumentation with articulating tips, and an adaptive downscaling of the surgeons movements (without tremor). To the best of our knowledge, this is the first report on robotic retroperitoneal para-aortic lymphadenectomy in patients with gynecologic cancer. We report on the technique and operative results of the robotic retroperitoneal lower para-aortic lymphadenectomy using the Da Vinci Surgical System. Five patients with cervical carcinoma stage IIb-IIb were included. Technically the procedure was easier to perform than with the classical retroperitoneal laparoscopic approach. However using the Da Vinci Surgical System it is important to tilt the patient slightly to the left to avoid collision between the left arm of the patient and the robotic arms, and to place the endoscopic robotic arm between the 2 arms used for dissection. Finally, we experienced that using a 30 degrees scope is advantageous for the dissection of the paracaval nodes. None of the patients had evidence of para-aortic metastases on preoperatively staging, including Positron Emission Tomography - Computed Tomography (PET-CT). One of the patients had positive para-aortic lymph nodes. Here we report on the surgical technique used in our first 5 patients undergoing retroperitoneal para-aortic lymphadenectomy using the robotic Da Vinci system. It is important to adapt the surgical technique using the Da Vinci Surgical System compared with the classical laparoscopic technique.


Neurotrophin in obstetrics and gynaecology.
Since Rita Levi Montalcini and Stanley Cohen received Nobel Prize for their pioneering work on nerve growth factor (NGF), its role in female reproductive system has been reinforced in last two decades. The neurotrophins (NT) including nerve growth factor (NGF) are a family of related growth factors and their respective receptor tyrosine kinases that are of major importance in the regulation of neuronal survival and differentiation. While role of NGF in mast cell-mediated egg implantation and inhibition of rejection were primary concern at their time, in the ovary NGF can help in the differentiation process by which ovarian follicles become responsive to gonadotrophins. They help in follicular maturation, steroid secretion and ovulation in the ovary, by inducing the FSH receptor (FSHR). Due to the pleiotropism, NGF is mandatory for the success of pregnancy, while progesterone helping to maintain local levels of NGF in utero. In endometriosisi and polycystic ovarian disease it has major role to play. An autocrine role of NGF in breast cancer and epithelial ovarian cancer (EOC) is evident now. Thus its study will infuse new insight in diseases of both obstetrics and gynaecology.


Prolactin signaling and Stat5: going their own separate ways?
Miyoshi et al. compared the role of the prolactin receptor (PrlR) and its downstream mediator, the signal transducer and activator of transcription 5 (Stat5), in mammary epithelial cells in vivo by studying PrlR-/- and Stat5ab-/- mouse mammary epithelial transplants during pregnancy. At first glance, the two mutant epithelia appear to have similar defects in the differentiation of the alveolar epithelium. However, a closer examination by Miyoshi et al. revealed defects in the epithelial architecture of the smallest ducts of Stat5ab-/- transplants not apparent in the PrlR-/- transplants, suggesting that Stat5 is more than a simple mediator of PrlR action.


A Japanese 4-year-old with protracted phonological development: the challenge of coronals.
This study examines the phonology of a Japanese four-year-old with mildly protracted phonological development (PPD) as a contribution to a special crosslinguistic issue presenting individual profiles in PPD within the framework of constraint-based nonlinear phonology. Although the child's word structure and vowels were well-established, certain consonant classes presented challenges. Coronal anterior obstruents often showed posteriorization (backing): dorsal stops replaced coronal stops, and with some exceptions, alveolopalatal affricates replaced anterior fricatives and affricates. The feature [+continuant] was also not yet established: palatal and bilabial fricatives and /h/ were either deleted or replaced with glottal stop; and non-anterior affricates replaced coronal fricatives. If affricates are analyzed as a sequence of [-continuant]-[+continuant], they were possible transitional elements from non-continuants to continuants. The profile culminates with suggestions for intervention based on the nonlinear phonological analysis, consistent with other papers in this special issue.


Assessing olfaction following pediatric traumatic brain injury.
A brief procedure for screening the olfactory function in elementary-age children was developed in the present investigation When the performance of pediatric patients with mild traumatic brain injury (TBI) was compared with that of a matched sample with severe TBI, the severe TBI sample was one and one-half times as likely to exhibit an impaired sense of smell of formal testing (p<0 05) Subsequent analyses demonstrated that patients with olfactory deficits were three times as likely to manifest executive dysfunction as reported by their parents on a behavior rating scale In contrast to formal testing, individual interview revealed that TBI subjects and their parents were seldom aware of olfactory deficits Thus, formal testing of olfaction following pediatric head trauma should not be deferred.


The Effect of Cold Plasma Pretreatment on Water-Suspended Herbs Measured in the Content of Bioactive Compounds, Antioxidant Activity, Volatile Compounds and Microbial Count of Final Extracts.
Cold plasma is a new technology of promising potential to use as a part of technological extraction lines constructed to implement green chemistry solutions or simply to reduce resources in solvent-based extraction lines. The present study was undertaken to verify the effect of nitrogen cold plasma pre-treatment conducted for 8 min (20 kHz) on the content of antioxidants, antioxidant activity, the profile of volatile compounds, microbial count, pH and color measured in herb extracts (12 herbs: Echinacea purpurea; Salvia officinalis; Urtica dioica; Polygonum aviculare; Vaccinium myrtillus; Taraxacum officinale; Hypericum perforatum; Achillea millefolium; Sanguisorba officinalis; Leonurus cardiaca; Ballota nigra; Andrographis paniculata) obtained with its usage. The surface morphology of extracted herbs was examined as well. Herbs used for extraction were ground and suspended in water before cold plasma treatment, which is a novel approach not studied before. Most plasma-treated extracts were characterized by a higher content of polyphenols (11 out of 12). Content of flavonoids and anthocyanins increased in four extracts and in the case of anthocyanins was significantly higher in comparison to control (up to 77%). The antioxidant activity measured at least by one method (ABTS, DPPH, FRAP) was also higher in nine plasma-treated solutions. Moreover, plasma decreased total aerobic bacteria, affected the color and increased pH of the extracts. The surface structure of the plant material after the extraction process was significantly damaged, which probably led to a higher extraction yield of bioactive compounds and in consequence to the higher antioxidant activity of extracts obtained with the cold plasma treatment.


Osteonecrosis of the hip in renal transplant recipients. Changes in functional status and magnetic resonance imaging findings over three years in three hundred five patients.
to conduct a retrospective study of the appearance and course of magnetic resonance imaging abnormalities in avascular osteonecrosis of the femoral head in renal transplant recipients and of potential relations between these abnormalities and the functional outcome. among 305 renal transplant recipients, patients with pain in the hips or knees underwent radiographs and magnetic resonance imaging studies of the hips and, if appropriate, of the knees. The mean time interval between these studies and transplantation was 8.9 months. The outcome was evaluated based on the Lequesne index and findings from a repeat magnetic resonance imaging study after a mean follow-up of 33 months since transplantation. The criteria developed by Mitchell et al. were used to diagnose osteonecrosis on magnetic resonance images. The size of the necrotic area was estimated using the tracing paper method as < 25%, 25-50%, > 50% of the surface of the femoral head. Eleven patients were treated by elimination of weight-bearing and conservative treatments and 15 underwent core decompression (radiographic stage I or II). Fourteen patients (4.5%) developed osteonecrosis of the femoral head, which was bilateral in 12 patients and unilateral in two: thus, the total number of hips with osteonecrosis was 26. The first magnetic resonance imaging study disclosed a crescent-shaped area of low signal intensity in 25 cases, most of which were mild in severity as assessed on radiographs (Arlet and Ficat stage I or II). Extensive necrosis was found in most cases at the first evaluation (> 25% in 15 cases and > 50% in eight). The surface of the necrotic area (as assessed irrespective of the treatment used) remained unchanged in 20 cases and decreased in six. In half the cases the hyperintense signal from the sequestrum converted to a hypointense signal after a mean follow-up of 39 years. A poor functional outcome (Lequesne's index > 7 or total hip arthroplasty) was seen in 61.5% of cases, irrespective of the treatment used. Avascular osteonecrosis of the femoral head precipitated by corticosteroid therapy in renal transplant recipients occurred in 4.5% of patients immediately involved a large segment of the epiphysis, and usually remained stable over time, although a decrease in the size of the lesion was seen in a few cases. Overall, the functional prognosis was poor, with a Lequesne's index greater than 7 or total hip arthroplasty in two thirds of cases after three years' follow-up. The incidence of avascular osteonecrosis of the hip in renal transplant recipients has decreased since 1980, when cyclosporin was introduced and doses of corticosteroids used to treat rejection episodes were diminished.


Introduction to biological rhythms: A brief history of chronobiology and its relevance to parasite immunology.
Almost every living organism on earth is exposed to a fluctuating environment, for example, light:dark cycles, food availability and seasonal photoperiods. Most species have therefore evolved internal timing mechanisms allowing them to anticipate these rhythmic environmental changes, obtaining a survival advantage. Circadian (24 h) rhythms, in particular, regulate multiple aspects of physiology, including sleep/wake activity, feeding rhythms and immune function. Recent studies have identified circadian rhythms in symptoms of parasite infections, rhythms in parasite schizogony and evidence that certain parasites can manipulate host rhythms. Furthermore, efficacy of anti-parasite medications can also be modulated by timing of drug administration. Understanding the interactions between host rhythms, parasite rhythms and disease severity is crucial to fully understand how to combat infections and reduce pathology. The aim of this review is, therefore, to provide an introduction to the field of biological rhythms, give a brief history of chronobiology research and discuss the relevance of biological rhythms to parasite immunology.


[Deformities of the feet after Volkmann's ischemia in the lower limb (author's transl)].
The authors have observed 11 cases of Volkmann's ischemia in the lower limb. The main deformity was of equinus. 10 patients were operated on. In 8 cases, arthrolysis was performed with good results in 7 cases. In 2 cases an ankle arthrodesis was done with one good result and one secondary amputation. The surgical technique of the arthrolysis is described. In most of the cases, tendon lengthenings, capsulotomy and fixation with an external fixator was required. This device was tolerated and it is concluded that it is worthwhile in severe ischaemic syndrome and that arthrolysis is preferred to arthrodesis.


Effectiveness of amendments on the spread and phytotoxicity of contaminants in metal-arsenic polluted soil.
A metal-arsenic polluted soil from sulphide-mine waste was treated, in all possible combinations, with two different amounts of marble sludge (98% CaCO3), compost (41% organic carbon), and Byferrox (70% Fe). Lixiviate and pore water from each treated and untreated soil were analysed, and lettuce-seed bioassays were performed. None of the treatments decreased the electrical conductivity of lixiviates or the concentrations of all pollutants found in both solutions. Marble sludge and compost increased the pH values and decreased the zinc, cadmium, copper, and lead concentrations in both solutions while increasing the arsenic concentrations in the lixiviates. Byferrox did not alter the physicochemical parameters or the concentrations of zinc, cadmium, copper, or lead in either solution but significantly decreased the arsenic concentrations in pore water. Compared with the Byferrox treatment, the mixture of marble sludge and Byferrox decreased redox potential values, increasing the arsenic concentrations in both solutions and the electrical conductivity of the pore water. All lixiviates were highly phytotoxic and seeds did not germinate. Pore-water phytotoxicity was related to electrical conductivity values and heavy-metal concentrations. The combination of marble sludge and compost was most effective at diminishing toxicity in lettuce. The soils treated with Byferrox, alone or mixed with marble sludge or compost, were the most phytotoxic.


Cure of malignant lymphoma in dogs with peripheral blood stem cell transplantation.
Twelve dogs with spontaneous malignant lymphoma in chemotherapy-induced remission were treated with total-body irradiation (TBI) and transplantation of autologous peripheral blood mononuclear cells collected following chemotherapy-induced expansion of the stem cell pool. Four animals (33%) died of transplant-related complications, five (41%) relapsed, and three (25%) are long-term disease-free survivors. Recovery to 1000 white cells/mm3 occurred by day 16 and dogs no longer required platelet transfusions by day 37. With the exception of delayed platelet recovery these results are virtually identical to those previously reported using autologous bone marrow transplantation for canine lymphoma. This study therefore suggests that autologous peripheral blood mononuclear cells collected following chemotherapy-induced expansion of the stem cell pool may offer a realistic alternative to autologous marrow transplantation in patients with malignant lymphoma for whom autologous marrow is not available.


Folding of Trp-cage mini protein using temperature and biasing potential replica-exchange molecular dynamics simulations.
The folding process of the 20 residue Trp-cage mini-protein was investigated using standard temperature replica exchange molecular dynamics (T-RexMD) simulation and a biasing potential RexMD (BP-RexMD) method. In contrast to several conventional molecular dynamics simulations, both RexMD methods sampled conformations close to the native structure after 10-20 ns simulation time as the dominant conformational states. In contrast, to T-RexMD involving 16 replicas the BP-RexMD method achieved very similar sampling results with only five replicas. The result indicates that the BP-RexMD method is well suited to study folding processes of proteins at a significantly smaller computational cost, compared to T-RexMD. Both RexMD methods sampled not only similar final states but also agreed on the sampling of intermediate conformations during Trp-cage folding. The analysis of the sampled potential energy contributions indicated that Trp-cage folding is favored by both van der Waals and to a lesser degree electrostatic contributions. Folding does not introduce any significant sterical strain as reflected by similar energy distributions of bonded energy terms (bond length, bond angle and dihedral angle) of folded and unfolded Trp-cage structures.


Modified nasopharyngeal tube for upper airway obstruction.
A modified nasopharyngeal tube is described that does not add airway dead space and resistance, is well tolerated, highly successful, and allows simultaneous use of oxygen prongs. This potentially reduces the need for surgical intervention to relieve high upper airway obstruction from Pierre-Robin syndrome and other causes.


Evidence-based practice in a military intensive care unit family visitation.
The dissatisfaction of family members with a restrictive visiting policy in a combined intensive care and step-down unit provides an opportunity for staff to develop better ways to meet the needs of patients and their families. A review of the evidence-based practice (EBP) literature as the measure of significance indicated that less restrictive visitation policies enhance patient and family satisfaction and offer many physiologic and psychological benefits to the patient. The purpose of this study was to determine whether a less restrictive visitation policy could be implemented in the adult critical care department of a naval medical center. Staff was educated on the use of EBP, specifically the Iowa-based model, and a less restrictive visitation policy was developed and implemented. Evaluation of the postintervention survey findings revealed higher patient and family satisfaction. The findings from this EBP project suggest that a more open visitation policy is feasible in adult critical care units, with an increase in overall satisfaction of patients and their families with regard to their stay in the intensive care unit.


Time-resolved angiography with stochastic trajectories for dynamic contrast-enhanced MRI in head and neck cancer: Are pharmacokinetic parameters affected?
To investigate the effects of different time-resolved angiography with stochastic trajectories (TWIST) k-space undersampling schemes on calculated pharmacokinetic dynamic contrast-enhanced (DCE) vascular parameters. A digital perfusion phantom was employed to simulate effects of TWIST on characteristics of signal changes in DCE. Furthermore, DCE-MRI was acquired without undersampling in a group of patients with head and neck squamous cell carcinoma and used to simulate a range of TWIST schemes. Errors were calculated as differences between reference and TWIST-simulated DCE parameters. Parametrical error maps were used to display the averaged results from all tumors. For a relatively wide range of undersampling schemes, errors in pharmacokinetic parameters due to TWIST were under 10% for the volume transfer constant, Ktrans, and total extracellular extravascular space volume, Ve. TWIST induced errors in the total blood plasma volume, Vp, were the largest observed, and these were inversely dependent on the area of the fully sampled k-space. The magnitudes of errors were not correlated with Ktrans, Vp and weakly correlated with Ve. The authors demonstrated methods to validate and optimize k-space view-sharing techniques for pharmacokinetic DCE studies using a range of clinically relevant spatial and temporal patient derived data. The authors found a range of undersampling patterns for which the TWIST sequence can be reliably used in pharmacokinetic DCE-MRI. The parameter maps created in the study can help to make a decision between temporal and spatial resolution demands and the quality of enhancement curve characterization.


[Initiation of treatment in Parkinson disease].
Initiating treatment in a patient with Parkinson's disease requires consideration of age, degree of disease activity, and consequences of long-term treatment. In young patients, albeit dopaminergic agonists or selegiline are possible alternatives, they will never be as effective as L-dopa, and they can be used only initially in very mild cases and for a short period of time. Long-acting L-dopa is probably better after titration with standard preparations. Potential neuroprotection by selegiline has not been confirmed so far, but it acts as a mild anti-Parkinsonian. In patients over 60, it is recommended not to use anticholinergic or dopaminergic agonists, but to start with a low dose of L-dopa and increase it by a maximum of 125 mg every 7 to 10 days. Clozapine can be very useful against psychosis.


[Effects of oxidized low-density lipoprotein on cholesterol efflux in 3T3-L1 cells].
To explore whether oxidized low-density lipoprotein (ox-LDL) can stimulate the cholesterol efflux in fully differentiated 3T3-L1 cells and the possible mechanism. Fully differentiated 3T3-L1 cells were incubated in the medium containing various concentrations of ox-LDL ( 0 to 50 microg/mL) for 8 or 24 hours. 22(R)-Hydroxycholesterol (10 micromol/L) was exposed to preconditioned adipocytes with 25 microg/mL ox-LDL for 24 hours. Reverse transcription polymerase chain reaction (RT-PCR) was used to evaluate ATP binding cassette transporter A1 (ABCA1), scavenger receptor class B type I (SR-BI), and liver X receptor alpha (LXRalpha) mRNA expression. Cholesterol efflux mediated by apolipoprotein A-I (apoA-I) was determined using liquid scintillator. Low levels (12.5-25 microg/mL) of ox-LDL could increase cholesterol efflux via the enhancement of ABCA1 pathway and SR-BI expression, whereas the higher concentration (50 microg/mL) could not. In adipocytes preincubated with 25 microg/mL ox-LDL for 24 hours, 22(R)-hydroxycholesterol could increase ABCA1 and LXRalpha mRNA and apoA-I-mediated cholesterol efflux, but had no effect on the SR-BI mRNA expression. Low levels of ox-LDL may enhance the LXRalpha-ABCA1-apoA-I pathway in adipocytes, up-regulate SR-BI mRNA expression, and then increase the cholesterol efflux. This new effect of ox-LDL will not only make contribution to cholesterol homeostasis in adipocytes, but also be potentially atheroprotective.


Testing the effects of nutrient deficiencies on behavioral performance.
The association between specific nutrient deficiencies and poor performance on behavioral tests has been documented for several nutrients. The determination of causality, however, remains elusive. This paper presents the essential criteria for a valid test of causality. Findings from experimental studies in which a nutritional treatment was randomly allocated can be summarized in a statistical statement about the probability that the nutrient treatment caused the behavioral response. Criteria for assessing the internal validity of these studies are examined in terms of whether alleviation of a nutrient deficiency did or did not produce a detectable behavioral response. The plausibility of such a causal inference is dependent on its congruency with known or theorized biological and behavioral mechanisms. External validity describes the extent to which inferences from internally valid studies may be applicable to other populations or circumstances. In addition to these scientific considerations, some of the ethical issues of nutrient-treatment trials are also discussed. All of these considerations provide a better basis for judging whether public health action would be worthwhile than do observed associations that could actually be due to other causes.


Lingual (Not Palatine) Tonsillolith: Case Report.
The lingual tonsil (LT), located at the base of the tongue posterior to the circumvallate papillae, consists of aggregates of lymphoid tissue separated by a median glossoepiglottic ligament that splits the LT into right and left halves. Tonsillar tissue on either side of the ligament exhibits discrete round nodules that project upward. Each prominence is covered by nonkeratinized epithelium and has a central crypt formed by an invagination of the overlying epithelium. Ducts of adjacent mucous glands empty into the crypt, serving as a flushing mechanism to cleanse the crypt. A thin fibrous connective tissue capsule isolates the LT from the underlying tongue musculature. Lingual tonsillar tissue tends to regress with aging. Hypertrophy and pathologic changes of the LT can develop and cause subjective symptomatology. Patient complaints include sore throats, dysphagia, globus sensation, dyspnea, obstructive sleep apnea, dysgeusia, halitosis, and otalgia. Tonsilloliths in the palatine tonsil are often reported, but the LT also can develop a tonsillolith. Only 1 report of LT tonsilloliths was found in the English-language dental literature. Because of its literary rarity, this report presents a case of an incidental finding of a lingual tonsillolith. Diagnostic skills are sharpened when such cases are brought to the attention of the profession.


Transcatheter PFO closure with GORE(®) septal occluder: early and mid-term clinical results.
Transcatheter closure of patent foramen ovale (PFO) is a widespread procedure. However the "quest" for the ideal device is still ongoing. Here we present the procedural and early results of transcatheter closure of PFO with the GORE® Septal Occluder. Three Italian centers participated in a registry and collected data from 122 consecutive patients undergoing PFO closure by using GSO device. Indication for closure was previous stroke or transient cerebral ischemia in 110 and migraine in 12 subjects. The procedure was successful in all patients. The procedure was performed under general anesthesia, fluoroscopic, and trans-esophageal echocardiographic imaging in 80 subjects while it was performed with local anesthesia, fluoroscopic, and intracardiac echocardiographic monitoring in 42 subjects. Twenty patients received a 20 mm device, 70 patients received a 25 mm device, and 32 received a 30 mm device. Procedure and fluoroscopy times were 30 ± 20 and 5 ± 4 min, respectively. In three cases, the implanted device was retrieved because of unsatisfactory position. Four subjects (2.5%) experienced vascular complications. During a median follow-up of 9 months (range 1-18 months) seven patients experienced atrial arrhythmias and four of them required medical treatment. At six months follow-up, at chest X-ray in two cases there was evidence of fracture of two wires of the device. Devices were stable and no treatment was required. Moderate residual shunting was found in two patients at 6- and 12-months follow-up. No other complication occurred. GORE® Septal Occluder is an easy, safe, and effective device in closing PFO.


Antifungal activity change of Streptomyces rimosus MY02 mediated by confront culture with other microorganism.
Streptomyces rimosus can produce antibacterial and antifungal antibiotics, which have important applications in medicine and agriculture. Seventy-nine microbial strains were employed to assay interaction between S. rimosus MY02 and different fungi, actinomyces, and bacteria when confront cultured on solid media. The results showed that the presence of a microorganism might affect the activity of another one. When S. rimosus MY02 confront cultured with other microorganisms, the inductive effect might be positive or negative. In this study, fungi showed to be effective elicitors, with a highest inductivity rate of 90.1%, and all of fungi showed positive induction behavior. Followed by bacteria with 59.6% of the tested bacterial strains showing positive inductivity, and the highest inductivity was 54.9%. Only six actinomyces (counting for 40% of the tested actinomyces strains) showed positive inductivity, and the highest induction rate of the strain NK413 was 34.1%. We also found that growth of most of bacteria or actinomyces which showed negative inductivity were similar or better than that of the strain MY02. However, the growth status of the strains was not positive related to inducing ability directly.


Unfair offers, unfair offenders? Fairness considerations in incarcerated individuals with and without psychopathy.
Offenders with psychopathy have often committed crimes violating social norms, which may suggest a biased moral reasoning in psychopathy. Yet, as findings on utilitarian decisions remain conflicting, the current study investigated different aspects of fairness considerations in offenders with psychopathy, offenders without psychopathy and healthy individuals (N = 18/14/18, respectively). Unfair offers in a modified Ultimatum Game (UG) were paired with different unselected alternatives, thereby establishing the context of a proposal, and made under opposing intentionality constraints (intentional vs. unintentional). As in previous studies, unfair offers were most often rejected when the alternative was fair and when the offer was made intentionally. Importantly, however, offenders with psychopathy demonstrated a similar rejection pattern to that of healthy individuals, i.e., taking the unselected alternative into account. In contrast, delinquents without psychopathy did not adjust their decision behavior to the alternatives to an offer, suggesting stronger impairments in social decision-making. Crucially, the mechanisms and processes underlying rejection decisions might differ, particularly with regard to cognitive vs. emotional competencies. While preserved cognitive perspective-taking could drive seemingly intact decision patterns in psychopathy, emotional empathy is likely to be compromised.


The lysosome as a command-and-control center for cellular metabolism.
Lysosomes are membrane-bound organelles found in every eukaryotic cell. They are widely known as terminal catabolic stations that rid cells of waste products and scavenge metabolic building blocks that sustain essential biosynthetic reactions during starvation. In recent years, this classical view has been dramatically expanded by the discovery of new roles of the lysosome in nutrient sensing, transcriptional regulation, and metabolic homeostasis. These discoveries have elevated the lysosome to a decision-making center involved in the control of cellular growth and survival. Here we review these recently discovered properties of the lysosome, with a focus on how lysosomal signaling pathways respond to external and internal cues and how they ultimately enable metabolic homeostasis and cellular adaptation.


Efficient Transient Expression of Plasmid DNA Using Poly (2-(N,N-Dimethylamino) Ethyl Methacrylate) in Plant Cells.
Nanomaterials have been widely studied for their potential to become the new generation of nanocarriers in gene transfection, yet it remains still difficult to apply them efficiently and succinctly to plant cells. Poly (2-(N,N-dimethylamino) ethyl methacrylate) (PDMAEMA), which possesses temperature and pH dual-sensitivity, has largely been applied in animal cells, but it is rarely involved in plant cells. As a proof of concept, PDMAEMA as a gene carrier is incubated with plasmid GFP (pGFP) to explore its transfection ability in plants, and cationic polymer polyethylenimine (PEI) is used as a control. pGFP was efficiently condensed into the nanostructure by electrostatic interactions at an N/P (amino group from cationic polymers/phosphate group from plasmid DNA (pDNA)) ratio of 15; after complexation into nanocarriers, pGFP was protected from endonuclease degradation according to the DNase I digestion assay. After incubation with protoplasts and leaves, GFP was observed with confocal microscopy in plant cells. Western blot experiments confirmed GFP expression at the protein level. Toxicity assay showed PDMAEMA had a lower toxicity than PEI. These results showed that transient expression of pGFP was readily achieved in Arabidopsis thaliana and Nicotiana benthamiana. Notably, PDMAEMA showed lower cytotoxicity than PEI upon incubation with Nicotiana benthamiana leaves. PDMAEMA exhibited great potency for DNA delivery in plant cells. This work provides us with new ideas of more concise and more effective methods for plant transformation.


The Evolving Role of Allogeneic Stem Cell Transplant in the Era of Molecularly Targeted Agents.
Allogeneic stem cell transplantation (allo-SCT) is an increasingly important treatment strategy in fit adults with acute myeloid leukemia (AML). Increased donor availability and a steady reduction in transplant-related mortality (TRM) over the last 2 decades have transformed access to the curative potential of allo-SCT. The identification of patients with AML in first complete remission who will benefit from allo-SCT requires a dynamic assessment of the risk of disease relapse and TRM. Increased accuracy in predicting both relapse risk and transplant toxicity has allowed recommendations for allo-SCT to become increasingly personalized. Notwithstanding its now central position in the treatment algorithm of patients with AML, there, however, has been little progress in reducing the main cause of transplant failure, which remains disease relapse. Novel molecularly targeted therapies have the potential to augment the curative potential of nontransplant therapies, and this may influence the proportion of newly diagnosed fit patients deemed to be allomandatory. At the same time, the ability of such therapies to improve transplant outcomes, either by reducing TRM or the risk of relapse, has the potential to further embed allo-SCT as a key therapeutic modality in AML.


Disruption of L-histidine decarboxylase reduces airway eosinophilia but not hyperresponsiveness.
Histamine has a variety of airway actions and is considered to be an important mediator in asthma. This study examined the role of endogenous histamine in allergic airway eosinophil recruitment and hyperresponsiveness using L-histidine decarboxylase gene knockout mice. Histamine levels of the airways in L-histidine decarboxylase knockout mice were largely diminished compared with wild-type mice. Inhalation challenge with ovalbumin (OVA) in OVA-sensitized wild-type mice caused eosinophil accumulation in the lung as well as airway hyperresponsiveness to methacholine 3 days after the challenge. The eosinophil recruitment was significantly reduced in the knockout mice. In the bone marrow, the proliferation of eosinophils was enhanced after OVA challenge in the wild-type mice; however, the proliferation was significantly reduced in the knockout mice. The induction of P-selectin in the lung after OVA challenge was also inhibited in the knockout mice. In contrast, airway hyperresponsiveness was not suppressed in the knockout mice. These results suggest that endogenous histamine is involved in the accumulation of eosinophils into the airways after allergic challenge, possibly acting in the bone marrow and producing P-selectin in the airways. Furthermore, allergen-induced airway hyperresponsiveness appeared to occur independently of airway eosinophilia in our present model.


Designed folding of pseudopeptides: the transformation of a configurationally driven preorganization into a stereoselective multicomponent macrocyclization reaction.
The efficient synthesis of large-ring pseudopeptidic macrocycles through a multicomponent [2+2] reductive amination reaction is described. The reaction was entirely governed by the structural information contained in the corresponding open-chain pseudopeptidic bis(amidoamine) precursors, which have a rigid (R,R)-cyclohexane-1,2-diamine moiety. A remarkable match/mismatch relationship between the configurations of the chiral centers of the cyclic diamine and those of the peptidic frame was observed. The macrocyclic tetraimine intermediates have been studied in detail by NMR spectroscopy, circular dichroism (CD), and molecular modeling, and the results support the appropriate preorganization induced by the match combination of the chiral centers. We have also synthesized the corresponding open-chain bis(imine) model compounds. The structural studies (NMR spectroscopy, CD, modeling) of these systems showed an intrinsically lower reactivity of the mismatch combination, even when the product of the reaction was acyclic. In addition, a synergistic effect between the two chiral substructures for the correct folding of the molecules was observed. Finally, X-ray analysis of the HCl salt of one of the macrocycles showed an interesting pattern; the macrocyclic rings stack in columnar aggregates leaving large interstitial channels filled with water-solvated chloride anions.


Maternal Mood and Perception of Infant Temperament at Three Months Predict Depressive Symptoms Scores in Mothers of Preterm Infants at Six Months.
Postpartum depression is more prevalent in mothers and fathers of preterm infants compared to parents of full-term infants and may have long-term detrimental consequences for parental mental health and child development. The temperamental profile of an infant has been postulated as one of the important factors associated with parental depressiveness in the first months postpartum. This study aimed to examine the longitudinal relationship between depressive symptoms and perceived infant temperament at 3 months corrected age, and depressive symptoms at 6 months corrected age among mothers and fathers of infants born preterm. We assessed 59 families with infants born before the 34th gestational week using the Edinburgh Postnatal Depression Scale (EDPS) and the Infant Behavior Questionnaire-Revised. We found that mothers' scores on EPDS and infants' Orienting/regulation at 3 months corrected age predicted mothers' EPDS scores at 6 months corrected age. In particular, higher depressive scores were related to higher depressive symptoms at 6 months corrected age, whereas higher infant Orienting/regulation was related to lower depressive symptoms at 6 months corrected age. Due to the low internal consistency of EPDS at 6 months for fathers, we were unable to conduct similar analyses for fathers. Our results point to the importance of considering both early indices of maternal mood as well as mother-reported measures of preterm infant temperament in the attempts to predict levels of maternal depressiveness in later months of an infant's life. Further studies are urgently needed in order to better understand the associations between depressiveness and infant temperament in fathers, and with more consideration for the severity of the effects of infant prematurity.


'It's different from my culture; they're very different': Providing community-based, 'culturally competent' palliative care for South Asian people in the UK.
This article investigates the challenges faced by those trying to develop 'culturally competent' palliative care for South Asian cancer patients in Luton, UK. It discusses the findings of a phenomenological study of service providers' attitudes to and experiences of caring for South Asian patients. Ten semi-structured in-depth interviews were carried out with a range of staff who work in home and community-based palliative care settings, including nurses, community liaison personnel and representatives of non-statutory organisations. The authors begin by considering how these service providers construct ideas of cultural difference and how these relate to philosophies of palliative care. They then examine attempts to deal with cultural diversity in everyday practice, focusing in particular on the social context of care in the home. The paper considers the ways in which staff attempt to incorporate the cultural needs of patients, family, kin and community. Rather than criticising current working practices, the authors highlight the complexity of delivering culturally competent services from the perspective of those working directly with patients. In doing so, they contribute to ongoing debates about the development of anti-discriminatory practice in health and social care.


Victimization and Exposure to Pro-Self-Harm and Pro-Suicide Websites: A Cross-National Study.
The study of websites displaying methods of both physical self-harm and suicide has become an important aspect of deliberate self-injury and suicide research. However, little is known about contextual factors related to entering such sites. Using data from 3,567 respondents aged 15-30 in the US, UK, Germany, and Finland, we found that experiences of victimization are associated with entering pro-self-harm sites and pro-suicide sites. Also, the victimization context had relevance, as online victimization was particularly related to pro-self-harm behavior. The findings suggest a need to organize more specific online support for the victims of violence and online aggression.


Survivors of acute lymphoblastic leukemia and body mass changes.
Obesity is a rapidly growing challenge that has now reached epidemic proportions. Along with malnutrition, it causes increasing morbidity and mortality in the general population. Survivors of pediatric leukemia are at increased risk of developing adverse body mass changes. Despite many studies, mechanisms of regulation of fat tissue metabolism are still poorly understood. The present article reviews the data from studies of leukemia survivors in the context of basic science studies and reports of nutritional situation in Europe published between 1994 and 2009. As regulation of appetite and energy balance is very complex, environmental, biochemical and genetic factors are presented. Fat mass and obesity associated gene (FTO) has recently been found to contribute to the risk of obesity. The possible role of this gene as well as late consequences of body mass changes are discussed. Both underweight and overweight leukemia survivors need to be monitored for ongoing health consequences of abnormal BMI. Parameters of metabolic syndrome should be included as routine assessments in outpatient clinics taking care of childhood leukemia survivors.


Corrigendum.
Svoboda SJ, Owens BD, Harvey TM, Tarwater PM, Brechue WF, Cameron KL. The association between serum biomarkers of collagen turnover and subsequent anterior cruciate ligament rupture. Am J Sports Med 2016;44(7):1687-1693. (Original DOI: 10.1177/0363546516640515)In the above article, the affiliation for Travis M. Harvey was incorrectly listed. The correct affiliation is United States Special Operations Command, MacDill Air Force Base, Florida, USA.


Relationship of the Pelvic-Trochanteric Index with greater trochanteric pain syndrome.
This study aimed to correlate a higher Pelvic-Trochanteric Index (PTI) with an increased varus of the femoral neck with greater trochanteric pain syndrome (GTPS). The secondary objective was to check whether the pelvic width changes with age. A prospective study was conducted to compare female patients diagnosed with GTPS (case group) with asymptomatic female participants (control group) from March 2011 to June 2017. On an anteroposterior pelvic radiograph, lines were drawn by two radiologists, and the PTI (ratio of the distance between the greater trochanters and distance between the iliac crests) was defined and the femoral neck-shaft angle was measured. Data collected based on radiographs of 182 female patients (cases) and 150 female participants (controls) showed that the mean PTI was 1.09 (SD=0.01) in the case group and 1.07 (SD=0.01) in the control group (p<0.05), regardless of age. The distance between iliac crests increased with age (p<0.05) in symptomatic and asymptomatic individuals. It was also found that the mean femoral neck-shaft angle was 130.6° (SD=0.59) and progression of the varus angulation occurred with age in both groups, with a significance level of 5%. The PTI was higher in patients with GTPS. The femoral neck-shaft angle does not differ between individuals with and without GTPS; however, it does decrease with age. The pelvic width tends to increase with aging in symptomatic or asymptomatic individuals; therefore, the increase in the pelvic width and decrease in the femoral neck-shaft angle can be interpreted as normal in aging women, which could alter the biomechanics of the hips and pelvis.


A novel jaspine B-ceramide hybrid modulates sphingolipid metabolism.
A new sphingolipid hybrid molecule was designed to assemble, within a tail-to-tail double-chain structure, the ceramide hydrophilic moiety and the tetrahydrofuran pharmacophore of jaspine B, a natural product known to interfere with sphingolipid metabolism. This compound was prepared through acylation of sphingosine with a jaspine B derivative bearing a COOH group in the terminal position of the aliphatic backbone. This new hybrid molecule was evaluated for its capacities to affect melanoma cell viability and sphingolipid metabolism. While retaining the cytotoxicity of ceramide itself, this compound was shown to lower the sphingomyelin cellular levels and significantly enhance the production of sphingosine-1-phosphate, thus representing a novel sphingolipid metabolism modulator.


Case challenges in shoulder surgery: what would you do?
The management of complex shoulder issues was discussed in an interactive case presentation session. Patient scenarios discussed included reoperation of a rotator cuff repair with a subscapularis tear; uncemented hemiarthroplasty presenting with pain and osteolysis; severe osteoarthritis with all nonoperative options exhausted; rheumatoid arthritis with pain and diminished function; and significant pain, limited motion, and weakness in an active patient.


Electrophysiological Changes Related to Childhood Trauma in Patients with Major Depressive Disorder: An Event-related Potential Study.
Childhood trauma is the most important environmental factor for several psychiatric disorders. Depressed patients with childhood trauma appear to have severe symptoms that frequently recur. This study investigated whether depressed patients with childhood trauma showed attenuated Nogo event-related potentials (ERPs) and source activity during response-inhibition tasks. Forty-four patients patients with major depressive disorder (MDD) were instructed to perform a Go/Nogo task during electroencephalography. Sensors and source activities of N2 and P3 of the Nogo ERPs were analyzed. The participants' clinical symptoms were assessed using the Childhood Trauma Questionnaire (CTQ), Beck Depression Inventory, State-Trait Anxiety Inventory, Barratt Impulsivity Scale, and Affective Lability Scale. The participants were divided into two groups (low and high), based on their total CTQ scores. MDD subjects with high CTQ scores showed significantly decreased Nogo P3 amplitudes at the frontal, frontocentral, central, and parietal electrodes than those with low CTQ scores (all p < 0.01). In Nogo P3, the source activities of the right cuneus, right posterior cingulate cortex, right precuneus, left supramarginal gyrus, and left lingual gyrus were significantly lower in the high CTQ group than in the low one (all p < 0.01). There were significant negative correlations between the total CTQ scores and the Nogo P3 amplitudes in the frontocentral (p = 0.03) and parietal regions (p = 0.02), which showed lower source activity in the Nogo P3 condition. Depressed patients with severe childhood trauma showed different Nogo-ERP characteristics, which might reflect inhibitory failure and dysfunction in related brain regions.


Micro-Computed Tomography Detection of Gold Nanoparticle-Labelled Mesenchymal Stem Cells in the Rat Subretinal Layer.
Mesenchymal stem cells are widely used in many pre-clinical and clinical settings. Despite advances in molecular technology; the migration and homing activities of these cells in in vivo systems are not well understood. Labelling mesenchymal stem cells with gold nanoparticles has no cytotoxic effect and may offer suitable indications for stem cell tracking. Here, we report a simple protocol to label mesenchymal stem cells using 80 nm gold nanoparticles. Once the cells and particles were incubated together for 24 h, the labelled products were injected into the rat subretinal layer. Micro-computed tomography was then conducted on the 15th and 30th day post-injection to track the movement of these cells, as visualized by an area of hyperdensity from the coronal section images of the rat head. In addition, we confirmed the cellular uptake of the gold nanoparticles by the mesenchymal stem cells using transmission electron microscopy. As opposed to other methods, the current protocol provides a simple, less labour-intensive and more efficient labelling mechanism for real-time cell tracking. Finally, we discuss the potential manipulations of gold nanoparticles in stem cells for cell replacement and cancer therapy in ocular disorders or diseases.


Glutamate receptor ionotropic, kainate 1 serves as a novel tumor suppressor of colorectal carcinoma and predicts clinical prognosis.
Colorectal cancer (CRC) is one of the most malignant cancers worldwide. However, the mechanisms of initiation and development of CRC are still largely unclear. The present study aimed to investigate the biological function and prognosis of glutamate receptor ionotropic, kainate 1 (GRIK1) in CRC. GRIK1 expression levels were analyzed in tissue microarrays containing 80 primary CRC samples using immunohistochemistry (IHC). The association between GRIK1 expression levels, clinicopathological factors and the prognosis was also investigated using Spearman's correlation analysis and Kaplan-Meier analysis, respectively. After genetic knockdown or overexpression of GRIK1, invasion/migration assays, proliferation assay, soft agar/colony formation assays, western blotting, reverse transcription-quantitative PCR and tumor xenograft models were used to investigate the function of GRIK1 both in vitro in two CRC cell lines, HCT116 and SW620, and in vivo. The results revealed that the expression levels of GRIK1 were significantly downregulated in CRC samples. Furthermore, IHC analysis indicated that the downregulated expression levels of GRIK1 were significantly associated with lymph node status and tumor size. In addition, patients with CRC with low GRIK1 expression levels demonstrated a consistently poor overall survival. The overexpression of GRIK1 inhibited the proliferation, colony formation, migration, invasion and epithelial-mesenchymal transition of HCT116 cells in vitro. In contrast, the genetic knockdown of GRIK1 promoted the proliferative, colony forming, migratory and invasive abilities of SW620 cells in vitro. Moreover, the overexpression of GRIK1 inhibited tumor growth, and liver and lung metastasis of CRC in vivo. In conclusion, the findings of the present study suggested that GRIK1 may serve as a tumor suppressor in CRC, and upregulated expression levels of GRIK1 may predict an improved prognosis for patients with CRC.


The hydrolytic water molecule in trypsin, revealed by time-resolved Laue crystallography.
Crystals of bovine trypsin were acylated at the reactive residue, serine 195, to form the transiently stable p-guanidinobenzoate. Hydrolysis of this species was triggered in the crystals by a jump in pH. The hydrolysis was monitored by three-dimensional Laue crystallography, resulting in three x-ray diffraction structures, all from the same crystal and each representing approximately 5 seconds of x-ray exposure. The structures were analyzed at a nominal resolution of 1.8 angstroms and were of sufficient quality to reproduce subtle features in the electron-density maps for each of the structures. Comparison of the structures before and after the pH jump reveals that a water molecule has positioned itself to attack the acyl group in the initial step of the hydrolysis of this transient intermediate.


Pioneers in Psychopharmacology.
In pursuing the history of any field, even one in which many of the main exponents are still alive, it can be very difficult to establish facts and priorities. Detailed scrutiny of the events leading to the recognition of the antidepressant effects of iproniazid, in which Nathan Kline was involved, may fail to establish the exact sequence of events or the sources of inspiration for a discovery (Healy, 1997). Quite apart from the 'facts' behind the antidepressant story, Kline's role in the story beautifully illustrates one of the sayings of Francis Galton, to the effect that in history the driving force may not lie with the first discoverer of a new scientific fact, but rather with the individual who was the first to persuade the world of the importance of a particular discovery. This maxim applies with some force to the three individuals who have been honoured by the CINP in 1998 for their pioneering roles in psychopharmacology - Pierre Deniker, Joel Elkes and Heinz Lehmann whose contributions to the field have included original research and also key initiatives to capture the central ground of academic and public opinion for the new science. They have been science makers rather than just scientists.


Control of glucose- and NaCl-induced biofilm formation by rbf in Staphylococcus aureus.
Both Staphylococcus aureus and S. epidermidis are capable of forming biofilm on biomaterials. We used Tn917 mutagenesis to identify a gene, rbf, affecting biofilm formation in S. aureus NCTC8325-4. Sequencing revealed that Rbf contained a consensus region signature of the AraC/XylS family of regulators, suggesting that Rbf is a transcriptional regulator. Insertional duplication inactivation of the rbf gene confirmed that the gene was involved in biofilm formation on polystyrene and glass. Phenotypic analysis of the wild type and the mutant suggested that the rbf gene mediates the biofilm formation of S. aureus at the multicellular aggregation stage rather than at initial attachment. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis demonstrated that the mutation resulted in the loss of an approximately 190-kDa protein. Biofilm production by the mutant could be restored by complementation with a 2.5-kb DNA fragment containing the rbf gene. The rbf-specific mutation affected the induction of biofilm formation by glucose and a high concentration of NaCl but not by ethanol. The mutation did not affect the transcription of the ica genes previously shown to be required for biofilm formation. Taken together, our results suggest that the rbf gene is involved in the regulation of the multicellular aggregation step of S. aureus biofilm formation in response to glucose and salt and that this regulation may be mediated through the 190-kDa protein.


A controlled comparison of fluoxetine and amitriptyline in depressed out-patients.
Fluoxetine, a selective serotonin uptake inhibitor (mean dose 73 mg each morning) was compared with amitriptyline (mean dose 122 mg at night) in a double-blind study of 64 depressed out-patients. Fifty patients completed the 6-week trial. The drugs did not differ with respect to psychiatrists' ratings, but amitriptyline was slightly superior with respect to patients' ratings. The amitriptyline-treated group had complaints of dry mouth and dizziness on standing; the fluoxetine-treated group of sleep disturbances, nausea, and headaches.


Natal and neonatal teeth: a clinical and histological study.
Nine thousand and six hundred infants delivered in a maternity hospital were examined for the prevalence of natal and neonatal teeth. The prevalence among this group was noted. The teeth were the normal primary incisors that had erupted prematurely. The crown was normal in shape and size with very little root formation. The histological features were that of an immature tooth.


[Parapneumonic pleural effusion, pleural empyema: medical and surgical aspects].
The following are essential for prophylaxis and treatment of empyema: antibiotic therapy for pneumonia, based on susceptibility results; early detection of parapneumonic effusions (decubitus radiograph, sonography); immediate diagnostic thoracocentesis if a parapneumonic effusion is large, increasing despite antibiotic therapy, if it is associated with clinical deterioration or if empyema is suspected; assessment of the stage of parapneumonic effusion or empyema (clinical signs, sonography, CT, laboratory parameters); immediate therapeutic thoracocentesis of frank empyema, in loculated empyema fibrinolytic agents may be used; early surgical intervention if conservative management fails; complete thoracoscopic decortication, if necessary open thoracotomy to assure complete reexpansion of the lung.


Conservation analysis of large biochemical networks.
Large biochemical networks pose a unique challenge from the point of view of evaluating conservation laws. The computational problem in most cases exceeds the capability of available software tools, often resulting in inaccurate computation of the number and form of conserved cycles. Such errors have profound effects on subsequent calculations, particularly in the evaluation of the Jacobian which is a critical quantity in many other calculations. The goal of this paper is to outline a new algorithm that is computationally efficient and robust at extracting the correct conservation laws for very large biochemical networks. We show that our algorithm can perform the conservation analysis of large biochemical networks, and can evaluate the correct conserved cycles when compared with other similar software tools. Biochemical simulators such as Jarnac and COPASI are successful at extracting only a subset of the conservation laws that our algorithm can. This is illustrated with examples for some large networks which show the advantages of our method.


Correlation Between Doppler Ultrasound Blood Flow Parameters and Angiogenesis and Proliferation Activity in Breast Cancer.
BACKGROUND The aim of this study was to assess the correlation between Doppler ultrasound blood flow parameters and angiogenesis and proliferation activity in breast cancer. MATERIAL AND METHODS We enrolled breast cancer patients (n=55) and benign tumor patients (n=40) from Tengzhou Central People's Hospital from Mar 2014 to Dec 2016. Doppler ultrasound examination was conducted to determine blood flow parameters, and immunohistochemistry (IHC) experiments were performed to determine the protein expression of angiogenesis genes, cell proliferation genes, and tumor-suppressor genes. RESULTS Compared with benign tumors, the maximum velocity (Vmax) and resistance index (RI) were significantly different in I-II stage and III-IV stage breast cancer (P<0.01 and P<0.001, respectively). IHC assay showed that VEDGF165, NRP-1, SphK1, CD31, YAP, CTGF, and Gli2 proteins expressions were significantly higher in breast cancer patients (P<0.01 and P<0.001, respectively). PTEN and MFN2 protein expressions of breast cancer patients were significantly lower (P<0.01 or P<0.001, respectively) compared with those of benign tumor patients. VEDGF165, NRP-1, SphK1, CD31, YAP, CTGF, and Gli2 proteins expressions were positively correlated with Vmax and negatively correlated with RI in breast cancer. PTEN and MFN2 protein expressions were negative correlated with Vmax and positively correlated with RI in breast cancer patients. CONCLUSIONS Decreased RI and increased Vmax are correlated with angiogenesis, proliferation, and tumor suppression in breast cancer.


Dermal absorption of benzo[a]pyrene into human skin from soil: Effect of artificial weathering, concentration, and exposure duration.
In vitro assessments of 14C-benzo[a]pyrene (BaP) absorption through human epidermis were conducted with the sub-63-μm fraction of four test soils containing different amounts of organic and black carbon. Soils were artificially weathered for eight weeks and applied to epidermis at nominal BaP concentrations of 3 and 10 mg/kg for 8 or 24 h. Experiments were also conducted at 24 h with unweathered soils and with BaP deposited onto skin from acetone at a comparable chemical load. For the weathered soils, absorption was independent of the amount of organic or black carbon, the mass in the receptor fluid was proportional to exposure duration but independent of concentration, and the mass recovered in the skin after washing was proportional to concentration and independent of exposure time. Results from the weathered and unweathered soils were similar except for the mass recovered in the washed skin, which was lower for the weathered soil only at the higher concentration. We hypothesize that chemical concentrations exceeded the BaP sorption capacity accessible within the artificial weathering timeframe for all soils tested, and that BaP mass in the washed skin was dominated by particles that were not removed by washing. Fluxes into and through skin from soils were lower by an order of magnitude than from acetone-deposited BaP.


Richer milk for sons but more milk for daughters: Sex-biased investment during lactation varies with maternal life history in rhesus macaques.
Lactation represents the greatest postnatal energetic expenditure for human and non-human primate females, and the ability to sustain the costs of lactation is influenced by a mother's physical condition. This is especially true for young mothers that initiate reproduction shortly after adolescence. These mothers have fewer bodily reserves available for lactation and face tradeoffs between reproduction and their own growth. Milk synthesis among captive rhesus macaques (Macaca mulatta) was investigated at the California National Primate Research Center from 2005 to 2007 (N = 114). Rhesus macaques produced low energy density milk typical of the primate order, but there was substantial individual variation among mothers in both milk energy density and yield. As a consequence, the available milk energy (AME), the product of milk energy density and milk yield, to support infant growth, development, and activity, varied tenfold among mothers. Primiparous mothers (N = 40) had fewer bodily resources, as measured by mass and body mass index, available for lactation than did multiparous mothers (N = 74) and showed poorer lactational performance. Mothers of sons produced milk of higher energy density, especially primiparous mothers, but lower milk yield, such that AME was the same for sons and daughters. Although AME from the mother was the same for sons and daughters, there was significant sexual dimorphism in infant mass. These data indicate that selection has likely favored sex-specific regulation of growth and development that is not necessarily contingent on greater maternal investment.


Dispersive liquid-liquid microextraction for the determination of three cytokinin compounds in fruits and vegetables by liquid chromatography with time-of-flight mass spectrometry.
The paper presents a novel approach for the determination of three cytokinin compounds, thidiazuron (TDZ), 1,3-diphenylurea (1,3-DPU) and forchlorfenuron (CPPU), in fruit and vegetables samples using liquid chromatography with electrospray ionization and time-of-flight mass spectrometry (LC-ESI-TOFMS). Analytes were extracted from the sample matrix with ethanol, and the extract, after dilution with water, was submitted to dispersive liquid-liquid microextraction (DLLME). Once acetonitrile and 1,2-dichloroethane had been selected as extraction and disperser solvents, respectively, the influence of the following experimental parameters was studied using a Plackett-Burman design: volume of extraction and disperser solvents, sample mass and time and speed of centrifugation. The best analytical conditions were 250 µL 1,2-dichloroethane, 1.5 mL acetonitrile, 5 g sample mass, and centrifugation at 3000 rpm for 3 min. The optimized method provided DLs in the range 0.02-0.05 ng g(-1), depending on the compound. Satisfactory recovery values between 89 and 106% were obtained for spiked samples (kiwifruit, watermelon, grape and tomato) in the 0.2-1.0 ng g(-1) concentration range, depending on the compound. None of the target analytes was detected in any of the samples analyzed.


Group-specific differentiation of Rhizobium from clover species by PCR amplification of 23S rDNA sequences.
Two 20-bp primers that provide group-specific detection of Rhizobium spp. by polymerase chain reaction (PCR) have been used to differentiate strains that belong to different effectiveness groups within the Rhizobium-Trifolium cross-inoculation group. The target for DNA amplification was a 370-bp fragment of the 23S rDNA region. Analysis of additional root-nodule forming, as well as root-associated bacterial species by PCR-primer assay revealed that variability within this 20-bp segment of the 23S rDNA region may be widespread and provide an effective identification tool. Our data suggest that strains of Rhizobium isolated from the perennial clover Trifolium semipilosum may be phylogenetically more closely related to Rhizobium etli.


An open source delineation and hierarchical classification of UK retail agglomerations.
Town centres and high streets typically form the social and commercial cores of UK cities and towns, yet, there is no uniform definition of what a town centre or high street is. In this study the spatial delineations of retail agglomerations are generated using open-source data for England, Wales, Scotland and Northern Ireland. The extent and boundaries of these physical retail areas are identified based on the density and connectivity patterns of individual retail units over space. A high resolution hexagonal grid is superimposed over spatial clusters of retail points and a network-based algorithm used to identify mutually exclusive tracts. Agglomerations are then pruned and fine-tuned according to a series of heuristic rules. Our retail agglomerations represent local commerce areas with shopping amenities and are assigned to a hierarchical classification ranking from the largest Regional Centres, Major Town Centres and Town Centres, down to Small Local Centres and Retail Parks. The classification into one of eleven hierarchies is based on a combination of relative rank in the local area and absolute size of retail units within the area. These retail agglomeration boundaries, hierarchical classification and lookups form an open-source spatial data product available for wide use and research implementation.


Delivery of traditional hospital services to patients at home.
The high cost of traditional inpatient care, advances in the delivery of depot antibiotics and narcotics, and the demands of patients for realistic alternatives to frequent hospitalisation have led to programs for the provision of acute hospital care in the home. We review the progress of overseas hospital-in-the-home programs and the issues that such service delivery has raised for clinicians and administrators. The potential application in Australia is examined and priorities for preparative research are suggested. It seems inevitable that for a select number of conditions in a select group of patients, home hospital services will become a reality in this country.


PX-12 inhibits the growth of A549 lung cancer cells via G2/M phase arrest and ROS-dependent apoptosis.
PX-12 (1-methylpropyl 2-imidazolyl disulfide) is an inhibitor of thioredoxin (Trx-1), which has antitumor effects. However, little is known about the toxicological effect of PX-12 on cancer cells. We investigated the anti-growth effects of PX-12 on A549 lung cancer cells in relation to reactive oxygen species (ROS) and glutathione (GSH) levels. Based on MTT assays, PX-12 inhibited the growth of A549 cells with an IC50 of approximately 20 µM at 72 h. DNA flow cytometric analysis indicated that PX-12 significantly induced the G2/M phase arrest of the cell cycle in A549 cells. This agent also induced apoptotic cell death, as demonstrated by Annexin V-FITC staining cells and the loss of mitochondrial membrane potential MMP (∆ψm). In addition, the administration of Bax siRNA attenuated PX-12-induced A549 cell death. All the tested caspase inhibitors, especially Z-VAD significantly prevented apoptosis induced by PX-12. With respect to ROS and GSH levels, PX-12 increased ROS levels including O2(•)- in A549 cells and induced GSH depletion. N-acetyl cysteine (NAC) markedly reduced ROS levels in PX-12-treated A549 cells. NAC also prevented apoptotic cell death and GSH depletion induced by PX-12. This is the first report to show that PX-12 inhibits the growth of A549 cells via G2/M phase arrest, and Bax-mediated and ROS-dependent apoptosis.


Application of a paraplegic gait orthosis in thoracolumbar spinal cord injury.
Paraplegic gait orthosis has been shown to help paraplegic patients stand and walk, although this method cannot be individualized for patients with different spinal cord injuries and functional recovery of the lower extremities. There is, however, a great need to develop individualized paraplegic orthosis to improve overall quality of life for paraplegic patients. In the present study, 36 spinal cord (below T4) injury patients were equally and randomly divided into control and observation groups. The control group received systematic rehabilitation training, including maintenance of joint range of motion, residual muscle strength training, standing training, balance training, and functional electrical stimulation. The observation group received an individualized paraplegic locomotion brace and functional training according to the various spinal cord injury levels and muscle strength based on comprehensive systematic rehabilitation training. After 3 months of rehabilitation training, the observation group achieved therapeutic locomotion in 8 cases, family-based locomotion in 7 cases, and community-based locomotion in 3 cases. However, locomotion was not achieved in any of the control group patients. These findings suggest that individualized paraplegic braces significantly improve activity of daily living and locomotion in patients with thoracolumbar spinal cord injury.


Roles of p300 and cyclic adenosine monophosphate response element binding protein in high glucose-induced hypoxia-inducible factor 1α inactivation under hypoxic conditions.
Given the high prevalence of diabetes and burn injuries worldwide, it is essential to dissect the underlying mechanism of delayed burn wound healing in diabetes patients, especially the high glucose-induced hypoxia-inducible factor 1 (HIF-1)-mediated transcription defects. Human umbilical vein endothelial cells were cultured with low or high concentrations of glucose. HIF-1α-induced vascular endothelial growth factor (VEGF) transcription was measured by luciferase assay. Immunofluorescence staining was carried out to visualize cyclic adenosine monophosphate response element binding protein (CREB) localization. Immunoprecipitation was carried out to characterize the association between HIF-1α/p300/CREB. To test whether p300, CREB or p300+CREB co-overexpression was sufficient to rescue the HIF-1-mediated transcription defect after high glucose exposure, p300, CREB or p300+CREB co-overexpression were engineered, and VEGF expression was quantified. Finally, in vitro angiogenesis assay was carried out to test whether the high glucose-induced angiogenesis defect is rescuable by p300 and CREB co-overexpression. Chronic high glucose treatment resulted in impaired HIF-1-induced VEGF transcription and CREB exclusion from the nucleus. P300 or CREB overexpression alone cannot rescue high glucose-induced HIF-1α transcription defects. In contrast, co-overexpression of p300 and CREB dramatically ameliorated high glucose-induced impairment of HIF-1-mediated VEGF transcription, as well as in vitro angiogenesis. Finally, we showed that co-overexpression of p300 and CREB rectifies the dissociation of HIF-1α-p300-CREB protein complex in chronic high glucose-treated cells. Both p300 and CREB are required for the function integrity of HIF-1α transcription machinery and subsequent angiogenesis, suggesting future studies to improve burn wound healing might be directed to optimization of the interaction between p300, CREB and HIF-1α.


Clinical quality improvement: eliminating unplanned extubation in the CCU.
This article aims to explore coronary care unit (CCU) extubation structures, processes and outcomes. There were 13 unplanned-extubation cases (UE) among 251 intubated patients (5.2 per cent) in a cardiologist-led CCU in 2008. Seven did not require re-intubation, implying possible earlier extubation. A quality improvement project was undertaken with a goal to eliminate CCU UE within 12 months. Using the clinical practice improvement (CPI) method, the most significant root causes were missing sedation/analgesia protocol, no ventilator weaning protocol and absent respiratory therapist during the CCU morning rounds. Non-physician directed sedation/analgesia and ventilation weaning protocols were created and put on trial in Plan-Do-Study-Act cycles before formal implementation. Arrangements were made to allocate a respiratory therapist to the CCU daily for morning rounds. For 12 months after fully implementing the interventions, UE incidence dropped from 5.2 per cent to 0.9 per cent (p = 0.006). There were no adverse outcomes, re-intubation and/or readmission to CCU within 48 hours. Through a multi-disciplinary CPI approach, adopting non-physician directed protocols has successfully streamlined and improved airway management in mechanically ventilated patients in a cardiologist-led CCU. There is little published data on improving intubated patient care in cardiologist-led CCUs. Previous studies centered on intensive care units managed by critical care specialists.


A flow cytometric procedure for the quantification of cell adhesion in complex mixtures of cells.
We present a simple non-radioactive cytometry-based assay that permits the simultaneous quantitation of cell adhesion of distinct subsets of cells contained in a mixture without any previous fractionation. The procedure is simple and highly reproducible and has the advantage of confining the quantitation of cell adhesion to live cells only. This new approach is based on counting the absolute number of cells. This is done by adding known numbers of distinguishable beads to the cell suspension and counting beads and cells in a cytometer. Quantitation of adhesion is accomplished by counting each subpopulation of cells before and after the adhesive process. To illustrate this methodology we determined adhesion of Ramos cells to monolayers of endothelial cells and its inhibition by specific antibodies. Also, we determined adhesion to endothelial cells of B lymphocytes and subsets of T lymphocytes present in a preparation of unfractionated human mononuclear cells. The results presented here demonstrate that the new assay has the required properties to be used in the quantitation of cell adhesion.


[Hyperkeratotic Kaposi sarcoma with leg lymphoedema after prolonged corticosteroid therapy for SLE. Case report and review of the literature].
Kaposi sarcoma (KS) is a malignant vascular neoplasia with a viral etiology, characterized by development of multiple hyperpigmentate lesions, primarily at cutaneous level with associated edema and ulcerations, but frequently involving also the mucous membranes and/or visceral organs. In this study, we describe (in the light of the relevant literature) the clinical case of an elderly (78 yrs-old) woman, who developed red-blues multiple hyperkeratotic nodules in the right leg and foot with marked lymphoedema, blushing and pain, after a long period of a low-dose corticosteroid therapy for LES (at least 10 years of continuous treatment). The diagnosis of KS was made on the basis of histologic findings. The patient HLA-typing showed the haplotypes HLA-A2-10, -B21-35, -Bw4-6, -Cw4 and HLA-DR11-13 (some of which are known to predispose to LES, but not to KS). The KS, first described by Moritz Kaposi in 1872, has been a very rare pathology until the 80s, afterwards its frequency has steadly increased, favored by immunosuppressive therapy for autoimmune diseases or tranplants and by immunodepression of AIDS. Concerning the pathogenesis, it is crucial the role of HHV-8 of the herpesvirus family (found in the lesions and in the circulating cells of all KS patients), for which a prevailing sexual transmission is postulated. General physicians and specialists of internal medicine and angiology should know this disease, which can be undiagnosed because of the low incidence in the general population and the consequent poor knowledge of this vascular neoplastic disease, which is now reported with increasing frequency.


Externalization and internalization of (Na+ + K+)-ATPase in rat heart during different phases of sepsis.
Changes in the distribution of (Na+ + K+)-ATPase in two subcellular fractions, the sarcolemma and the light vesicle, of rat heart during sepsis were studied. Sepsis was induced by cecal ligation and puncture (CLP). The alpha-subunit of (Na+ + K+)-ATPase was photoaffinity labeled with [alpha-32P]8-N3ATP. The results show that septic rat heart exhibits hyperdynamic (hypermetabolic) phase during early (9 hr post-CLP), followed by hypodynamic (hypometabolic) phase during late (18 hr post-CLP) sepsis. Marker enzyme and beta-adrenergic receptor assays depict that the light vesicle fraction is the intracellular site of surface receptor. The incorporation of the photolabel into the alpha-subunit (M(r) = 98,000) of the (Na+ + K+)-ATPase in sarcolemmal fraction was increased by 60% (P < 0.01) during early sepsis, but was decreased by 63% (P < 0.01) during late sepsis. In contrast, the binding of 98,000-M(r) peptide in light vesicles was decreased by 40% (P < 0.01) in early sepsis, but was increased by 102% (P < 0.01) during late sepsis. The ouabain-sensitive (Na+ + K+)-ATPase activity was increased by 31% (P < 0.05) during the early sepsis, but was decreased by 32% (P < 0.01) during late sepsis in the sarcolemmal fraction; while in the light vesicle fraction, the (Na+ + K+)-ATPase activity was decreased by 21% (P < 0.01) during early sepsis, but was increased by 47% (P < 0.01) during the late phase of sepsis. The yield of membrane proteins for each specific fraction remained unchanged for control, early sepsis, and late sepsis.(ABSTRACT TRUNCATED AT 250 WORDS)


A successful pregnancy and delivery after resectoscopic surgery for early invasive endometrial cancer.
Among young women, the incidence of uterine corpus cancer is increasing. Most young women can not preserve fertility because simple total hysterectomy with bilateral salpingo-oophorectomy is the standard method for early endometrial cancer so far. We present a case of early endometrial adenocarcinoma which succeeded in pregnancy and delivery after resectoscopic surgery. Following a circumferential resection of the lesion including the mucosa and muscle layer under resectoscopic guidance, the patient became pregnant by means of in vitro fertilization-embyo transfer with hormone replenishment. She underwent cesarean section at 33 weeks and five days of gestation and had a healthy baby. Resectscopic surgery can help to preserve fertility among young women who have early invasive endometrial cancer.


Ischemic demyelination.
White matter lesions representing ischemic demyelination have evolved in terms of our understanding of their pathogenesis and potential clinical significance. Low density lesions on CT brain scan, most commonly seen in the periventricular region, also frequently seen in the centrum semiovale, have been termed 'leukoaraiosis'. In the past years, it was not uncommon at all to hear the term 'Binswanger's disease' used in an attempt to define the neurological sequelae of such lesions. Further refinement came with the advent of magnetic resonance imaging (MRI) brain scan which is particularly sensitive to such white matter areas of increased signal intensity, which tend to be seen particularly well on T2-weighted and fluid attenuation inversion recovery (FLAIR) scans. The major challenge has been to correlate the clinical attributes with such relatively frequent findings in the elderly population. Recent studies have looked at lesion load in a fashion analogous to that seen with multiple sclerosis. A particularly relevant clinical model for white matter disease is cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) which combines the potential components of small vessel disease, resulting in progressive neurological deficit, with a common association with migraine which can also be associated with white matter lesions. However, the most common pathogenic factor associated with the microangiopathy, which appears to be at the heart of ischemic demyelination, continues to be hypertension. How well we are able to tie in the various pathological mechanisms associated with this end organ damage of the brain will determine how well we can arrive at effective interventions for a common contributor to neurological deficits in the elderly.


Structure-activity relationship for enhancement of paracellular permeability across Caco-2 cell monolayers by 3-alkylamido-2-alkoxypropylphosphocholines.
Paracellular permeability enhancers have been used to improve the oral bioavailability of hydrophilic drugs; however, the mechanism of action of many enhancers is poorly understood. In this study, highly potent enhancers of paracellular permeability were identified in the 3-alkylamido-2-alkoxypropylphosphocholine series, and a structure-activity relationship was developed for enhancement of paracellular permeability across Caco-2 cell monolayers. Compounds with short (<5 carbons) hydrocarbon chains at both C-2 and C-3 were generally inactive. The potency exhibited a parabolic relationship with respect to the chain length at either C-2 or C-3. Linear molecules (i.e., compounds with a short hydrocarbon chain at C-2 or C-3 and a long hydrocarbon chain on C-3 or C-2, respectively) were more potent than the corresponding branched molecules with the same carbon load. The efficacy of 3-alkylamido-2-alkoxypropylphosphocholines as enhancers of paracellular permeability was not dependent on their existence in micellar form or their ability to alter the fluidity of cell membrane. Previously, a correlation between the potency of alkylphosphocholines as enhancers of paracellular permeability and the inhibitors of phospholipase C (PLC) was established in Madine Darby canine kidney (MDCK) cell monolayers. The potencies of selected 3-alkylamido-2-alkoxypropylphosphocholines as inhibitors of PLC and enhancers of paracellular permeability fit well into this correlation. Therefore, phosphocholines are likely to increase paracellular permeability by modulating the signal transduction pathway initiated by a PLC-catalyzed reaction rather than by physically altering the cell membrane.


Response of the bacterial community associated with a cosmopolitan marine diatom to crude oil shows a preference for the biodegradation of aromatic hydrocarbons.
Emerging evidence shows that hydrocarbonoclastic bacteria (HCB) may be commonly found associated with phytoplankton in the ocean, but the ecology of these bacteria and how they respond to crude oil remains poorly understood. Here, we used a natural diatom-bacterial assemblage to investigate the diversity and response of HCB associated with a cosmopolitan marine diatom, Skeletonema costatum, to crude oil. Pyrosequencing analysis and qPCR revealed a dramatic transition in the diatom-associated bacterial community, defined initially by a short-lived bloom of Methylophaga (putative oil degraders) that was subsequently succeeded by distinct groups of HCB (Marinobacter, Polycyclovorans, Arenibacter, Parvibaculum, Roseobacter clade), including putative novel phyla, as well as other groups with previously unqualified oil-degrading potential. Interestingly, these oil-enriched organisms contributed to the apparent and exclusive biodegradation of substituted and non-substituted polycyclic aromatic hydrocarbons (PAHs), thereby suggesting that the HCB community associated with the diatom is tuned to specializing in the degradation of PAHs. Furthermore, the formation of marine oil snow (MOS) in oil-amended incubations was consistent with its formation during the Deepwater Horizon oil spill. This work highlights the phycosphere of phytoplankton as an underexplored biotope in the ocean where HCB may contribute importantly to the biodegradation of hydrocarbon contaminants in marine surface waters.


Expanding the PA applicant pool.
The PA profession has experienced a decline in the applicant pool and the actual number of PA students in training programs. This comes at a time when demand for PAs has increased dramatically. Basic questions facing the profession regarding this critical issue include: What is the current situation facing the most PA programs? Who are the individuals seeking to become PAs? What are the vi able options for the future? How can individual PAs impact the applicant pool, attracting and retaining qualified students? PA leadership must address these questions immediately. All Pas must take an active role in recruiting more students.


Criteria for the ergonomic evaluation of work chairs.
On the basis of a critical overview of specialised ergonomics literature and of national and international standards on the subjects, this paper outlines the main ergonomic requirements and characteristics for work chairs. The main ergonomic requirements for work chairs are the following: the chair should not be the source or cause of accidents. Adaptability: the chair's dimensions and control features should be such that they meet the anthropometric characteristics of at least 90% of the potential users. Comfort: the chair should be physiologically comfortable for the user. To this end, the following are all important features: seat-plane and backrest contours, backrest height and inclination adjustability, padding and covering materials that allow the body to breath. Practicality: the chair, and in particular the control features, should be practical and easy to control use. Durability: the chair should offer good wear and durability of its components and controls. Suitability for the job: the chair should be appropriately designed for the intended type of job and working environment. For each of these requirements single parameters are considered and for each parameter specific qualitative and/or quantitative data are given in order to class each single item as: "not acceptable", "acceptable" or "good", as regards standards and regulations, anthropometric parameters and intended uses. Criteria are given for a concise assessment of each of the six main requirements and for a comprehensive assessment of the "ergonomic quality" of the work chair.


Extracellular nucleotides elicit cytosolic free calcium oscillations in Arabidopsis.
Extracellular ATP induces a rise in the level of cytosolic free calcium ([Ca(2+)](cyt)) in plant cells. To expand our knowledge about the function of extracellular nucleotides in plants, the effects of several nucleotide analogs and pharmacological agents on [Ca(2+)](cyt) changes were studied using transgenic Arabidopsis (Arabidopsis thaliana) expressing aequorin or the fluorescence resonance energy transfer-based Ca(2+) sensor Yellow Cameleon 3.6. Exogenously applied CTP caused elevations in [Ca(2+)](cyt) that displayed distinct time- and dose-dependent kinetics compared with the purine nucleotides ATP and GTP. The inhibitory effects of antagonists of mammalian P2 receptors and calcium influx inhibitors on nucleotide-induced [Ca(2+)](cyt) elevations were distinct between CTP and purine nucleotides. These results suggest that distinct recognition systems may exist for the respective types of nucleotides. Interestingly, a mutant lacking the heterotrimeric G protein Gβ-subunit exhibited a remarkably higher [Ca(2+)](cyt) elevation in response to all tested nucleotides in comparison with the wild type. These data suggest a role for Gβ in negatively regulating extracellular nucleotide signaling and point to an important role for heterotrimeric G proteins in modulating the cellular effects of extracellular nucleotides. The addition of extracellular nucleotides induced multiple temporal [Ca(2+)](cyt) oscillations, which could be localized to specific root cells. The oscillations were attenuated by a vesicle-trafficking inhibitor, indicating that the oscillations likely require ATP release via exocytotic secretion. The results reveal new molecular details concerning extracellular nucleotide signaling in plants and the importance of fine control of extracellular nucleotide levels to mediate specific plant cell responses.


Evaluation of Triggered Electromyogram Monitoring during Insertion of Percutaneous Pedicle Screws.
percutaneous pedicle screw (PPS) fixation has been widely used in minimally invasive spine stabilization. Triggered electromyogram (TrEMG) monitoring is performed to prevent PPS misplacement, but is not widely accepted. We have newly developed an insulating tap device to minimize the misplacement of PPS. TrEMG was measurable in insulation tap devices in 31 cases, and in non-insulating tap devices in 27 cases. Fluoroscopy was used to insert 194 PPS and 154 PPS, respectively. Based on the Rampersaud classification of postoperative computed tomography, we classified PPS insertion into four categories (Grade A as no violation, Grade D as more than 4 mm perforation). Grade A was noted in 168 PPSs (86.6%) and Grade B to D in 26 PPSs in the insulation tap device group, and Grade A was noted in 129 PPSs (83.8%) and Grade B to D in 25 PPSs in the non-insulating tap device group, respectively. At a cutoff value of 11 mA, the sensitivity was 41.4% and the specificity was 98.2%. The sensitivity and specificity of the non-insulating tap device were 4.0% and 99.2%, respectively. The insulation treatment of the tap device has improved the sensitivity of TrEMG. TrEMG using the insulating tap device is one of the methods for safe PPS insertion.


In situ identification and quantification of protein-hydrolyzing ruminal bacteria associated with the digestion of barley and corn grain.
In this study, BODIPY FL DQ™ casein staining combined with fluorescence in situ hybridization (FISH) was used to detect and identify protein-hydrolyzing bacteria within biofilms that produced active cell-surface-associated serine- and metallo-proteases during the ruminal digestion of barley and corn grain in cows fed barley-based diets at 2 different levels. A doublet coccoid bacterial morphotype associated with barley and corn grain particles fluoresced after BODIPY FL DQ™ casein staining. Bacteria with this morphotype accounted for 3%-10% of the total bacteria attached to surface of cereal grain particles, possibly indicative of an important role in the hydrolysis of the protein matrix within the endosperm. However, the identity of these predominant proteolytic bacteria could not be determined using FISH. Quantitative FISH revealed that known proteolytic species, Prevotella ruminicola, Ruminobacter amylophilus, and Butyrivibrio fibrisolvens, were attached to particles of various cultivars of barley grain and corn, confirming their role in the proteolysis of cereal grains. Differences in chemical composition among different barley cultivars did not affect the composition of proteolytic bacterial populations. However, the concentrate level in the basal diet did have an impact on the relative abundance of proteolytic bacteria and thus possibly their overall contribution to the proteolysis of cereal grains.


p21ras supports the survival of chick embryonic motor neurones.
Various trophic factors present in muscle extract can promote the survival of cultured motor neurones. However, little is known about the signal transduction pathways used in these cells. The proto-oncogene product p21ras has been shown to play an important role in proliferative and differentiative signalling pathways. We report here that cytoplasmic introduction of its oncogenic form, p21ras(G12V), fully supports the in vitro survival of chick embryonic motor neurones. The proto-oncogenic form of p21ras also showed a dose-dependent survival effect, while a C-terminally truncated counterpart of p21ras(G12V) was ineffective. These results suggest an involvement of p21ras in signal transduction pathways leading to motor neurone survival and may be of relevance for the development of therapeutic strategies for motor neurone disease.


Leishmania Sexual Reproductive Strategies as Resolved through Computational Methods Designed for Aneuploid Genomes.
A cryptic sexual reproductive cycle in Leishmania has been inferred through population genetic studies revealing the presence of hybrid genotypes in natural isolates, with attempts made to decipher sexual strategies by studying complex chromosomal inheritance patterns. A more informative approach is to study the products of controlled, laboratory-based experiments where known strains or species are crossed in the sand fly vector to generate hybrid progeny. These hybrids can be subsequently studied through high resolution sequencing technologies and software suites such as PAINT that disclose inheritance patterns including ploidies, parental chromosome contributions and recombinations, all of which can inform the sexual strategy. In this work, we discuss the computational methods in PAINT that can be used to interpret the sexual strategies adopted specifically by aneuploid organisms and summarize how PAINT has been applied to the analysis of experimental hybrids to reveal meiosis-like sexual recombination in Leishmania.


Tailored Fabrication of Transferable and Hollow Weblike Titanium Dioxide Structures.
The preparation of weblike titanium dioxide thin films by atomic layer deposition on cellulose biotemplates is reported. The method produces a TiO2 web, which is flexible and transferable from the deposition substrate to that of the end application. Removal of the cellulose template by calcination converts the amorphous titania to crystalline anatase and gives the structure a hollow morphology. The TiO2 webs are thoroughly characterized using electron microscopy, X-ray diffraction, and X-ray photoelectron spectroscopy to give new insight into manufacturing of porous titanium dioxide structures by means of template-based methods. Functionality and integrity of the TiO2 hollow weblike thin films were successfully confirmed by applying them as electrodes in dye-sensitized solar cells.


Life course vaccination and healthy aging.
The authors notice the low vaccine coverage rate among European citizens and inventory the multiple reasons leading to the non-use of preventable infectious diseases vaccines in adults whose mortality consequences represent an important and unexpected burden of diseases. These facts are in close relation with the disruption of vaccine recommendations after the childhood vaccine program, the poor literacy knowledge concerning vaccines among the general population, but also unfortunately among physicians and other health care workers. Popular beliefs, fear of side-effects, fear of needles facilitated the constitution of active non-vaccine groups which conduct to the reappearance in non-vaccinated adults and with dramatic consequences of preventable childhood infectious diseases. This careful analysis of the current preventable infectious disease vaccine coverage in old adults leads to propose a life course vaccine programme including adult vaccinations as part of healthy aging as well as old adults' vaccine guidelines integrated in health prevention programs.


Blood pressure levels in the elderly with or without nutritional intervention.
Blood pressure (BP) examination and urine analyses for the assessment of dietary Na, K, and protein intakes were carried out according to the standardized methods for the World Health Organization Cardiovascular Diseases and Alimentary Comparison Study in aged people with or without a longlasting nutritional intervention. Nutritional intervention to reduce salt intake and increase K and protein intakes was effective for BP reduction even in aged people over 65 years.


The role of proton pump inhibitor therapy in the management of eosinophilic esophagitis.
Eosinophilic esophagitis (EoE) is a chronic esophageal disease characterized by a Th2 inflammatory response triggered by food/environmental allergens. Solid data confirm that up to half of patients with suspected EoE achieve complete remission on proton pump inhibitors (PPI) therapy. This disease phenotype is currently labelled as PPI-responsive esophageal eosinophilia (PPI-REE). Albeit initially believed to represent gastro-esophageal reflux disease (GERD), evolving evidence has underscored that PPI-REE and EoE show a significant overlap regarding clinic, endoscopic, histologic, Th2 immune-mediated inflammation and gene expression features. Moreover, PPI therapy can effectively reverse Th2 inflammation and the EoE transcriptome expression in PPI-REE patients. Therefore, EoE and PPI-REE likely represent a common allergic disorder, where PPI therapy should be considered a short- and long-term therapeutic asset, along with diet and topical steroids.