Indole-3-acetic acid improves postharvest biological control of blue mold rot of apple by Cryptococcus laurentii.
Cryptococcus laurentii is a well-known postharvest biocontrol yeast; however, it cannot provide satisfactory levels of decay control when used alone. Here, we evaluated the effects of indole-3-acetic acid (IAA), a plant growth regulator, on the biocontrol efficacy of the yeast antagonist C. laurentii against blue mold rot caused by Penicillium expansum in apple fruit. Results showed that the addition of IAA at 20 microg/ml to suspensions of C. laurentii greatly enhanced inhibition of mold rot in apple wounds compared with that observed with C. laurentii alone. The addition of IAA at 20 microg/ml or lower did not influence the population growth of C. laurentii in wounds, but adverse effects were seen on C. laurentii when the concentration of IAA was increased to 200 microg/ml or above in vitro and in vivo. P. expansum infection in apple wounds was not inhibited when the pathogen was inoculated into the fruit wounds within 2 h after application of IAA; however, infection was reduced when inoculated more than 12 h after IAA application. Treatment of wounds with IAA at 20 microg/ml 24 h before pathogen inoculation resulted in significant inhibition of P. expansum spore germination and host infection. Application of IAA at 20 microg/ml also reduced P. expansum infection when it was applied 48 h before pathogen inoculation in the intact fruit. Thus, IAA could reinforce the biocontrol efficacy of C. laurentii in inhibiting blue mold of apple fruit by induction of the natural resistance of the fruit.


Depressed thyroid function following paediatric cardiopulmonary bypass: association with interleukin-6 release?
Cellular activation with release of cytokines such as interleukin-6 (IL-6) occurs during cardiopulmonary bypass. IL-6 regulates a number of physiologic processes, and a possible role of IL-6 was recently postulated in the pathogenesis of changes in serum thyroid hormone concentrations in patients with nonthyroidal illness. The perioperative concentrations of triiodothyronine (T3) and IL-6 were determined in ten children undergoing open-heart surgery. Significant fall in T3 concentration was found postoperatively, while IL-6 increased significantly, peaking 2 hours postoperatively. The total accumulated IL-6 level 2 hours postoperatively was correlated to postoperative T3 concentration. A significant inverse correlation was found between T3 levels 24 and 48 hours postoperatively and total accumulated IL-6, and also between the percentage decrease in T3 concentrations and total accumulated IL-6. IL-6 release thus correlated inversely to T3 levels after cardiopulmonary bypass.


High sensitivity detection of cancer in vivo using a dual-controlled activation fluorescent imaging probe based on H-dimer formation and pH activation.
The key to improving the sensitivity of in vivo molecular imaging is to increase the target-to-background signal ratio (TBR). Optical imaging has a distinct advantage over other molecular imaging methods in that the fluorescent signal can be activated at the target thus reducing background signal. Previously, we found that H-dimer formation quenches fluorescence of xanthene fluorophores, and among these, TAMRA had the highest quenching ratio. Another approach to lowering background signal is to employ pH activation based on the photon-induced electron transfer (PeT) theory. We hypothesized that combining these two strategies could lead to greater quenching capacity than was possible with either probe alone. A pH-sensitive fluorophore, pHrodo or TAMRA was conjugated to the cancer targeting molecules, avidin (Av) and trastuzumab (Tra). As expected, both pHrodo and TAMRA formed H-dimers when conjugated to avidin or antibody and the dimerization resulted in efficient fluorescence quenching. In addition, pHrodo conjugated probes showed pH-dependent fluorescence activation. When the probes were used in an in vivo animal model, fluorescence endoscopy with Av-pHrodo depicted tumors with high TBR 1 h and 2 h after injection. Av-TAMRA also visualized tumors 1 h and 2 h after the injection, however, TBR was lower due to the background signal from non-specific binding 1 h after the injection as well as background fluorescence from the unbound agent. Thus, we demonstrate that a dual-controlled activatable optical probe based on the combination of H-dimer formation and pH activation can achieve high TBR at early time points during in vivo molecular imaging.


Fast iterative reconstruction of differential phase contrast X-ray tomograms.
Differential phase-contrast is a recent technique in the context of X-ray imaging. In order to reduce the specimen's exposure time, we propose a new iterative algorithm that can achieve the same quality as FBP-type methods, while using substantially fewer angular views. Our approach is based on 1) a novel spline-based discretization of the forward model and 2) an iterative reconstruction algorithm using the alternating direction method of multipliers. Our experimental results on real data suggest that the method allows to reduce the number of required views by at least a factor of four.


Diagnosis of middle cerebral artery stenosis by transcranial color-coded real-time sonography.
This study was performed to determine the usefulness of transcranial color-coded real-time sonography (TCCS) in detecting stenosis in the horizontal portion of the middle cerebral artery (MCA). Using TCCS and the incident angle correction technique, we measured the peak-systolic flow velocity in bilateral MCAs in 45 consecutive patients in whom cerebral angiography was carried out within 1 week before or after TCCS. Three patients had a stenosis of 75% or greater and four had a unilateral occlusion of the extracranial internal carotid artery (ICA) (the ICS and ICO groups, respectively). Eight patients had a stenosis of 50% or greater (one bilateral and seven unilateral) (the M1S group). Four patients had unilateral distal occlusion of the horizontal portion of the MCA (the M1O group). Twenty-six patients had no significant extra- or intracranial stenosis on the ipsilateral or contralateral side (the control group). Mean peak-systolic flow velocity on the affected side was 83.0 +/- 20.8 cm/s in the ICS group, 59.8 +/- 23.2 cm/s in the ICO group, and 62.3 +/- 33.7 cm/s in the M1O group. In the control group, the mean peak-systolic flow velocity was 116.0 +/- 31.5 cm/s. In the M1S group, however, the mean peak-systolic flow velocity (334.2 +/- 35.7 cm/s) on the affected side always exceeded 180 cm/s (mean value +/- 2 SD in the control group), and was significantly higher than that in the other groups. The mean peak-systolic flow velocity in the M1S group increased with the grade of stenosis. The M1S group members could easily be distinguished from the other group members by their peak-systolic flow velocity in excess of 180 cm/s. Measurement of the peak-systolic flow velocity of the MCA by TCCS may help to identify a significant stenosis in the horizontal portion of the MCA.


Irradiation reduces interstitial fluid transport and increases the collagen content in tumors.
We have shown that the interstitial diffusion of large molecules is significantly hindered in tumors with high collagen levels. Because large therapeutic agents (e.g., monoclonal antibodies and viral vectors) will be combined with radiation or chemotherapy, it is significant to determine how cytotoxic therapies modify the transport and composition of the interstitial space in tumors. To test the hypothesis that radiation alters tumor interstitial transport, we measured tumor hydraulic conductivity (K) and hyaluronan and collagen type I levels after irradiation. K and the quantification of interstitial matrix components were determined in sections of s.c. implants of the human colon adenocarcinoma LS174T. K was measured on days 1 and 5 after 10 Gy of irradiation or on day 5 after 30 Gy of irradiation. Compared with control tumors, K decreased by approximately 12-fold after 10 or 30 Gy of irradiation on day 5. At 24 h after irradiation with 10 Gy, the decrease in K was not significant. Five days after 10 and 30 Gy of irradiation, the decrease in K was associated with significantly higher levels of collagen type I. The collagen type I content was not changed 24 h after irradiation with 10 Gy. Irradiation did not significantly increase hyaluronan levels in LS174T tumors. After irradiation, the decrease in K and increase in collagen type I levels could significantly hinder the convective movement and diffusion of large therapeutic agents in tumors.


Growth hormone induces low-density lipoprotein clearance but not bile acid synthesis in humans.
Growth hormone (GH) induces hepatic low-density lipoprotein (LDL) receptors and lowers plasma cholesterol. We characterized the influence of GH treatment on plasma LDL clearance in normal humans and investigated the relative role of LDL receptor (LDLR) activity and stimulation of bile acid synthesis in subjects with different LDLR expression. Plasma clearance of autologous 125I-LDL was measured before and during 3 weeks of treatment with GH (0.1 IU/kg per day) in 9 healthy young males. Plasma LDL cholesterol was reduced by 13% and the fractional catabolic rate of LDL increased by 27%. More marked changes were seen in a patient with hypopituitarism substituted with GH (0.07 IU/kg per day) for 3 months. In a second study, GH dose-dependently reduced LDL cholesterol and increased Lp(a) levels in 3 groups of males: younger and elderly healthy subjects and heterozygous familial hypercholesterolemia (FH). No effect on bile acid synthesis measured by the plasma marker 7alpha-hydroxy-4-cholesten-3-one was observed. In an LDLR-deficient FH homozygote, LDL cholesterol was not affected by GH. GH treatment reduces plasma LDL cholesterol by inducing LDL clearance. In humans, LDLR expression is a prerequisite for this effect, whereas it is not related to stimulation of bile acid synthesis.


Regulation of the small regulatory RNA MicA by ribonuclease III: a target-dependent pathway.
MicA is a trans-encoded small non-coding RNA, which downregulates porin-expression in stationary-phase. In this work, we focus on the role of endoribonucleases III and E on Salmonella typhimurium sRNA MicA regulation. RNase III is shown to regulate MicA in a target-coupled way, while RNase E is responsible for the control of free MicA levels in the cell. We purified both Salmonella enzymes and demonstrated that in vitro RNase III is only active over MicA when in complex with its targets (whether ompA or lamB mRNAs). In vivo, MicA is demonstrated to be cleaved by RNase III in a coupled way with ompA mRNA. On the other hand, RNase E is able to cleave unpaired MicA and does not show a marked dependence on its 5' phosphorylation state. The main conclusion of this work is the existence of two independent pathways for MicA turnover. Each pathway involves a distinct endoribonuclease, having a different role in the context of the fine-tuned regulation of porin levels. Cleavage of MicA by RNase III in a target-dependent fashion, with the concomitant decay of the mRNA target, strongly resembles the eukaryotic RNAi system, where RNase III-like enzymes play a pivotal role.


Positron emission tomography in oncology.
Positron emission tomography (PET) scans use positrons, positively charged particles, to detect metabolic and chemical changes in the body. Although the clinical applications of this technology still are evolving, PET scans are being used to detect cancer and evaluate neurologic disorders, heart muscle function, and response to treatment. In oncology, PET scans may be used to determine biopsy location, stage disease, diagnose cancer recurrence, and discern malignant from benign conditions. PET scans also have led to the incidental diagnosis of cancer. This article reviews patient preparation and PET scan procedures and includes a patient information sheet on PET scanning. Oncology nurses need to be well informed about new technologies used in cancer care, such as PET scans, to better educate and prepare patients to undergo these tests.


alpha vbeta 6 Integrin promotes the invasion of morphoeic basal cell carcinoma through stromal modulation.
Basal cell carcinoma (BCC) is the most prevalent cancer in the Western world and its incidence is increasing. The pathogenesis of BCC involves deregulated Sonic hedgehog signaling, leading to activation of the Gli transcription factors. Most BCCs have a nodular growth pattern, and are indolent, slow-growing, and considered "low-risk" lesions. In contrast, the "high-risk" morphoeic variant, which causes significant morbidity, has an infiltrative growth pattern, and is so-called because of its densely fibrous stroma. As alpha v beta 6 is capable of promoting both carcinoma invasion and fibrosis, we examined the expression of this integrin in BCCs and found that the morphoeic type showed significantly higher alpha v beta 6 expression than the nodular type (P = 0.0009). In order to examine the function of alpha v beta 6, we transfected the transcription factors Gli1 or Gli2 into NTERT, human keratinocytes to generate a BCC model. These cells expressed alpha v beta 6 and were invasive, although inhibition of alpha v beta 6 had no direct effect on cell invasion. However, the cells showed alpha v beta 6-dependent activation of transforming growth factor-beta1, which induced transdifferentiation of human fibroblasts into myofibroblasts. Paracrine secretion of hepatocyte growth factor/scatter factor by these myofibroblasts promoted c-Met-dependent tumor invasion in both Transwell and three-dimensional organotypic assays. These experimental in vitro findings were confirmed using human clinical samples in which we showed that the stroma of morphoeic BCC is myofibroblast-rich compared with nodular BCC (P = 0.0036), that myofibroblasts express hepatocyte growth factor/scatter factor, and that morphoeic BCCs are strongly c-Met-positive. These data suggest that alpha v beta 6-dependent transforming growth factor-beta1 activation induces both the infiltrative growth pattern and fibrotic stroma so characteristic of morphoeic BCC.


Metal content of ephedra-containing dietary supplements and select botanicals.
The metal content of dietary supplements, including 13 ephedra-containing supplements, was studied. Samples of botanicals (black cohosh, echinacea, goldenseal, kava kava, milk thistle, saw palmetto, Synephrine, and valerian root), ephedra-containing dietary supplements (Amp II, EPH 833, Ephedra, Ephedra 1000, Hydroxycut, Metabolife 356, Metabolift, Ripped Fuel, Ripped Fuel Extreme, Ripped Fuel [ma huang-free], Stacker 2 [two lots], Super Stinger, Virgin Earth, Xenadrine RFA-1 [two lots], Yellow Jacket), and nonprescription reference agents (NoDoz and Primatene) were digested in acid, reacidified, and then spiked with internal standards. Metals were quantified using Environmental Protection Agency quality assurance and quality-control standards 6020 and 200.8. Forty-seven metals were analyzed by inductively coupled plasma-mass spectrometry, with subpart-per-trillion detection limits. All metals detected were in concentrations below toxic levels or physiological limit levels for the daily doses specified by the products' labeling. Metals found in highest concentrations among all the supplements sampled were sodium, magnesium, calcium, potassium, aluminum, iron, titanium, mercury, strontium, lead, barium, and silver. Of the 27 supplements analyzed, those with the lowest metal concentrations were mostly single-ingredient botanical supplements, while multiple-component, ephedra-containing dietary supplements generally had higher metal concentrations. Significant lot-to-lot variations were found for two ephedra-containing dietary supplements. None of 47 metals was found in highly toxic amounts in 23 brands of dietary supplements and two nonprescription reference preparations.


Myoglobin-CO substate structures and dynamics: multidimensional vibrational echoes and molecular dynamics simulations.
Spectrally resolved infrared stimulated vibrational echo data were obtained for sperm whale carbonmonoxymyoglobin (MbCO) at 300 K. The measured dephasing dynamics of the CO ligand are in agreement with dephasing dynamics calculated with molecular dynamics (MD) simulations for MbCO with the residue histidine-64 (His64) having its imidazole epsilon nitrogen protonated (N(epsilon)-H). The two conformational substate structures B(epsilon) and R(epsilon) observed in the MD simulations are assigned to the spectroscopic A(1) and A(3) conformational substates of MbCO, respectively, based on the agreement between the experimentally measured and calculated dephasing dynamics for these substates. In the A(1) substate, the N(epsilon)-H proton and N(delta) of His64 are approximately equidistant from the CO ligand, while in the A(3) substate, the N(epsilon)-H of His64 is oriented toward the CO, and the N(delta) is on the surface of the protein. The MD simulations show that dynamics of His64 represent the major source of vibrational dephasing of the CO ligand in the A(3) state on both femtosecond and picosecond time scales. Dephasing in the A(1) state is controlled by His64 on femtosecond time scales, and by the rest of the protein and the water solvent on longer time scales.


Anaemia in infancy in rural Bangladesh: contribution of iron deficiency, infections and poor feeding practices.
Few data exist on the aetiology of anaemia and Fe deficiency (ID) during early infancy in South Asia. The present study aimed to determine the contribution of ID, infections and feeding practices to anaemia in Bangladeshi infants aged 6-11 months. Baseline data from 1600 infants recruited into a cluster-randomised trial testing the effectiveness of micronutrient powder sales by frontline health workers on the prevalence of anaemia were used. Multivariate logistic regression was used to identify risk factors for anaemia and ID, and population attributable fractions (PAF) were computed to estimate the proportion of anaemia that might be prevented by the elimination of individual risk factors. It was found that 68 % of the infants were anaemic, 56 % were Fe deficient, and one-third had evidence of subclinical infections. The prevalence of anaemia and ID increased rapidly, until 8-9 months of age, while that of subclinical infections was constant. ID (adjusted OR (AOR) 2·6-5·0; P< 0·001) and subclinical infections (AOR 1·4-1·5; P< 0·01) were major risk factors for anaemia, in addition to age and male sex. Similarly, subclinical infections, age and male sex were significant risk factors for ID. Previous-day consumption of Fe-rich foods was very low and not associated with anaemia or ID. The PAF of anaemia attributable to ID was 67 % (95 % CI 62, 71) and that of subclinical infections was 16 % (95 % CI 11, 20). These results suggest that a multipronged strategy that combines improvements in dietary Fe intake alongside infection control strategies is needed to prevent anaemia during infancy in Bangladesh.


Is bone formation induced by high-frequency mechanical signals modulated by muscle activity?
Bone formation and resorption are sensitive to both external loads arising from gravitational loading as well to internal loads generated by muscular activity. The question as to which of the two sources provides the dominant stimulus for bone homeostasis and new bone accretion is arguably tied to the specific type of activity and anatomical site but it is often assumed that, because of their purportedly greater magnitude, muscle loads modulate changes in bone morphology. High-frequency mechanical signals may provide benefits at low- (<1g) and high- (>1g) acceleration magnitudes. While the mechanisms by which cells perceive high-frequency signals are largely unknown, higher magnitude vibrations can cause large muscle loads and may therefore be sensed by pathways similar to those associated with exercise. Here, we review experimental data to examine whether vibrations applied at very low magnitudes may be sensed directly by transmittance of the signal through the skeleton or whether muscle activity modulates, and perhaps amplifies, the externally applied mechanical stimulus. Current data indicate that the anabolic and anti-catabolic effects of whole body vibrations on the skeleton are unlikely to require muscular activity to become effective. Even high-frequency signals that induce bone matrix deformations of far less than five microstrain can promote bone formation in the absence of muscular activity. This independence of cells on large strains suggests that mechanical interventions can be designed that are both safe and effective.


Why Are We Distracted by Social Media? Distraction Situations and Strategies, Reasons for Distraction, and Individual Differences.
Social media is a major source of distraction and thus can hinder users from successfully fulfilling certain tasks by tempting them to use social media instead. However, an understanding of why users get distracted by social media is still lacking. We examine the phenomenon of social media distraction by identifying reasons for, situations of, and strategies against social media distraction. The method adopted is a quantitative online survey (N = 329) with a demographically diverse sample. The results reveal two reasons for social media distraction: social (e.g., staying connected and being available) and task-related distraction (e.g., not wanting to pursue a task). We find individual differences in these reasons for distraction. For social distraction, affiliation motive and fear of missing out (FoMO) are significant predictors, while for task-related distraction, self-regulatory capabilities (self-control, problematic social media use) and FoMO are significant predictors. Additionally, typical distraction situations are non-interactive situations (e.g., watching movies, facing unpleasant tasks). Strategies used to reduce distractions mostly involved reducing external distractions (e.g., silencing the device). This paper contributes to the understanding of social media use by revealing insights into social media distraction from the user perspective.


Neuprex XOMA Corp.
XOMA is developing Neuprex, an injectable recombinant protein fragment (rBPI-21) of the naturally-occurring bactericidal/permeability increasing (BPI) protein, for serious infections and infectious complications of trauma and surgery. Neuprex is the most advanced compound from XOMA's BPI platform. Neuprex is planning to commence a clinical trial for at least one additional indication in 1998 [293193]. Meningococcemia The lead indication for Neuprex is meningococcemia, for which phase III trials are expected to be completed in the second half of 1998 [275644]. In June 1998, Neuprex received Orphan Drug designation from the FDA for the treatment of severe meningococcal disease. XOMA is preparing components of a BLA to be submitted to the FDA as soon as the ongoing phase III trial is complete [290059]. In an open-label pilot study in 26 patients, completed in 1996, the mortality rate was 3.8% (one death) compared with 22% (12 deaths in 55 patients) of patients treated at the same medical centers from the previous two years [264164]. A 200-patient phase III trial, testing Neuprex in children with severe meningococcemia, is being carried out in the UK and North America. An independent Data Safety Monitoring Board recommended continuation of the trial following an interim analysis of the data [264164]. Post hepatectomy A phase II trial in partial hepatectomy patients has stopped enrollment at 35 patients (due to the slow rate; XOMA intends to make progress in other hepatic studies). Data from the first interim safety analysis, on twelve patients (low-dose group), suggested that patients receiving Neuprex spent less time on respirator, in the ICU and in the hospital [282257]. Antibiotic-resistant infections In vitro studies have shown that rBPI-21 can make resistant bacteria more antibiotic-susceptible and enhance the potency of a broad range of traditional antibiotics. Hence, XOMA has commenced studies to examine Neuprex in situations where infections may be resistant to antibiotics. A 21-patient open-label trial of Neuprex as an adjuvant to antibiotics in the treatment of severe intra-abdominal infections has been completed. The results showed a consistent, dose-related improvement in patient outcome as measured by time to improvement and time to fever-free status, but few resistant bacterial strains were found in this study and none that were resistant to all three antibiotics used in the study [282257]. In November 1997, XOMA began a clinical trial evaluating Neuprex as an adjunctive therapy with conventional antibiotics in bacterial lung infections in cystic fibrosis (CF) patients. A second study site was added in January 1998. The pilot study will enroll up to 24 CF patients hospitalized for acute bacterial exacerbations [264398]. Post-hemorrhagic trauma The company is initiating a phase III clinical trial to evaluate Neuprex as a treatment to prevent infections and infectious complications in patients suffering from hemorrhagic trauma [268444]. A 401-patient, phase II hemorrhagic trauma trial showed a positive overall benefit in patients receiving Neuprex versus placebo [282257]. A follow-on study in 169 patients confirmed the original dosing regimen [282257]. Bactericidal/permeability increasing protein platform BPI is a human host-defense protein discovered in 1978 by Drs Peter Elsbach & Gerrold Weiss, at New York University (NYU) Medical School. BPI occurs in neutrophils. XOMA scientists have discovered three active areas (functional domains) within the N-terminal fragment of human BPI (the amino-terminal 199 amino acid fragment). Many peptides, derived from these domains, have been identified and characterized. Five classes of bioactivity have been shown: antifungal, antibacterial, endotoxin-neutralizing, heparinneutralizing and anti-angiogenic [282257]. XOMA has succeeded in producing recombinant versions of BPI proteins but has also modified them to fine-tune their function and improve their pharmacodynamic profile [162407,183566, 184024]. XOMA is New York University's exclusive licensee for patents relating to human therapeutic and diagnostic uses of rBPI. XOMA has also built a broad patent position related to its own work with BPI [282257]. In addition, in July 1998, XOMA licensed all of Incyte's BPI-related intellectual property, adding seven patents to XOMA's portfolio, which now includes worldwide rights to all existing BPI patents [293193].


STING modulates iron metabolism to promote liver injury and inflammation in acute immune hepatitis.
The pathogenesis of Autoimmune Hepatitis (AIH) is closely associated with perturbations in iron ion metabolism, during which Stimulator of Interferon Genes (STING) plays an important role. However, the precise regulatory mechanism remains elusive. In this study, we investigated the relationship between iron dysregulation and STING activation in Concanavalin A (ConA)-induced AIH liver injury. STING knockout (STING-/-) mice and AAV (Adeno-Associated virus)-Sting1-RNAi-treated mice were involved and subjected in AIH. We observed that increased iron dysregulation was linked with STING activation, but this effect was effectively reversed by the administration of iron chelating agent Desferoxamine (DFO) and the antioxidant Ferrostatin-1 (Fer-1). Notably, the iron transport protein Transferrin (TF) and Transferrin Receptor (TfR) exhibited significant accumulation in AIH along with upregulated expression of ferritin protein. Additionally, the deficiency of STING reduced hepatic iron accumulation, mitigated oxidative stress, and attenuated macrophage activation during ConA treatment. Furthermore, liver-specific knockdown of STING using AAV-Sting1-RNAi significantly ameliorated liver iron dysregulation and oxidative stress response induced by Kupffer cells (KCs). KC-derived STING exacerbates liver damage severity in AIH through promoting disturbances in hepatic iron ion metabolism as well as oxidative stress response. These findings provide valuable insights into the pathogenesis of AIH and may pave the way for potential therapeutic strategies targeting STING and iron metabolism in the future.


Adrenalectomy-induced potentiation of morphine analgesia: reversal by prednisolone.
Effects of adrenalectomy (ADX) on analgesic potency and morphine (MOR) content after SC administration of 3.5 or 7 mg/kg of MOR, and effects of prednisolone (PRED) on the ADX-induced effects were studied. ADX significantly potentiated MOR analgesia at both MOR doses, and PRED reversed the ADX-induced potentiation of MOR analgesia, ADX did not affect MOR content in brain and plasma after 3.5 mg/kg MOR, but significantly increased MOR content in brain and plasma after 7 mg/kg MOR, and PRED reversed the ADX-induced increase in the MOR content. Although the analgesic potency of 3.5 mg/kg MOR in ADX group was equipotent with those of 7 mg/kg MOR in sham-operated and PRED-treated ADX groups, MOR content in the former group was significantly lower than those in the latter two groups. These results suggest that ADX potentiates MOR analgesia through both mechanisms of the increased MOR content and the increased sensitivity to MOR, and that the lack of glucocorticoids participates in both of these ADX-induced effects.


Flat-panel-detector chest radiography: effect of tube voltage on image quality.
To compare the visibility of anatomic structures in direct-detector chest radiographs acquired with different tube voltages at equal effective doses to the patient. The study protocol was approved by the institutional internal review board, and written informed consent was obtained from all patients. Posteroanterior chest radiographs of 48 consecutively selected patients were obtained at 90, 121, and 150 kVp by using a flat-panel-detector unit that was based on cesium iodide technology and automated exposure control. Monte Carlo simulations were used to verify that the effective dose for all kilovoltage settings was equal. Five radiologists subjectively and independently rated the delineation of anatomic structures on hard-copy images by using a five-point scale. They also ranked image quality in a blinded side-by-side comparison. Average ranking scores were compared by using one-way analysis of variance with repeated measures. Data were analyzed for the entire patient group and for two patient subgroups that were formed according to body mass index (BMI). The visibility scores of most anatomic structures were significantly superior with the 90-kVp images (mean score, 3.11), followed by the 121-kVp (mean score, 2.95) and 150-kVp images (mean score, 2.80). Differences did not reach significance (P > .05) only for the delineation of the peripheral vessels, the heart contours, and the carina. This was also true for the subgroup of patients (n = 24) with a BMI greater than and the subgroup of patients (n = 24) with a BMI less than the mean BMI (26.9 kg/m(2)). At side-by-side comparison, the readers rated 90-kVp images as having superior image quality in the majority of image triplets; the percentage of 90-kVp images rated as "first choice" ranged from 60% (29 of 48 patients) to 90% (43 of 48 patients), with a median of 88% (42 of 48 patients), among the readers. Delineation of most anatomic structures and overall image quality were ranked superior in digital radiographs acquired with lower kilovoltage at a constant effective patient dose.


Coexistence of ehrlichiae of the phagocytophila group with Borrelia burgdorferi in Ixodes ricinus from Southern Germany.
Human granulocytic ehrlichiosis (HGE) is an emerging infectious disease recognized in the Western hemisphere. HGE is well known to occur in North America, but records from outside the United States are sparse. The great majority of data from Europe are restricted to seroprevalence studies and molecular biological detection of granulocytic ehrlichiae (GE) in ticks and mammals, but include defined cases from Slovenia. They argue for the existence of this disease in many parts of Europe. In the present study, 510 Ixodes ricinus ticks collected in five different regions of Southern Germany were investigated for the presence of GE and Borrelia burgdorferi sensu lato using polymerase chain reaction. In all, 8 (1.6%) of the 492 ticks that could be evaluated (193 females, 208 males, and 91 nymphs) contained GE and 178 (36.2%) B. burgdorferi s.l.. Four of these ticks were infected with both pathogens. Interestingly, all ehrlichia-infected ticks were adults and all were collected in the English Garden, a recreational park area located in the city of Munich. Sequencing of the 16S rDNA (bp 1 1101) of four of the GE showed 100% sequence identity to each other and greater than 99.9% identity with the published sequence of the HGE agent. The four GE differed in respect to other hitherto described GE by a nucleotide exchange at position 336. These results show that GE that are closely related to the HGE agent are present in Southern Germany, and that coinfection with B. burgdorferi is common in GE-infected ticks. However, in contrast to B. burgdorferi which is endemic everywhere in Southern Germany, the distribution of GE seems to be focal.


[Local growth factors for breast cancer: general review and potential value for clinician].
The discovery of a panel of peptides produced by normal and cancerous cells and capable of stimulating cell growth in an autocrine and paracrine fashion has been witnessed in recent years. This article focusses on the local growth factors thought to play a role in the biology of breast cancer and reviews which growth factors' receptors have been associated with prognosis of primary breast cancer. The potential of those growth factors for the development of new anticancer treatment strategies is also briefly discussed.


Treponema pallidum in nerve fibres.
Ultrathin sections of a rabbit scrotal syphiloma were examined by electron microscopy. Treponemes were observed in the endo-, peri-, and epineurium of the nerve fibre. The significance of these findings, in that infection may be transmitted via the nerve fibres and pain reduced by damage to the afferent fibres, are discussed.


Cellulose acetate beads activate the complement system but inactivate the anaphylatoxins generated.
The generation of anaphylatoxins, particularly C5a, is important in extracorporeal circulation therapies such as granulocyte/monocyte apheresis, which activates the complement system and elevates C5a levels. However, no side effects of granulocyte/monocyte apheresis using cellulose acetate beads have been reported. To investigate the mechanism of complement activation, we prepared plasma from cellulose acetate bead-treated blood (P-CAB) and compared it with zymosan-activated plasma (ZAP). Anaphylaxis activity was measured by skin test, and the activity of carboxypeptidase, which inactivates C5a, was measured by colorimetric assay. Pro-carboxypeptidase R and neutrophil elastase concentrations were measured by enzyme-linked immunosorbent assay. Although C5a was generated in P-CAB, the anaphylaxis activity of P-CAB was lower than that of ZAP. Carboxypeptidase activity and pro-carboxypeptidase R levels were suppressed in P-CAB, but not in ZAP. Furthermore, neutrophil elastase levels increased in P-CAB. The decreases in carboxypeptidase activity and inactivation of anaphylatoxin were inhibited by a neutrophil elastase inhibitor. These results suggest that cellulose acetate beads initiate the activation of carboxypeptidase R via elastase release, thereby inducing the inactivation of anaphylatoxin.


Analysis of peripheral blood lymphocyte subsets in critical patients at ICU admission: A preliminary investigation of their role in the prediction of sepsis during ICU stay.
A better knowledge of factors predicting the development of sepsis in patients hospitalized in intensive care unit (ICU) might help deploy more targeted preventive and therapeutic strategies. In addition to the known clinical and demographic predictors of septic syndromes, in this study, we investigated whether measuring T and B lymphocyte subsets upon admission in the ICU may help individualize the prediction of ensuing sepsis during ICU stay. Between May 2015 and December 2016, we performed a prospective cohort study evaluating peripheral blood lymphocyte T-CD4+ (T-helper cells), T-CD8+ (cytotoxic T-cells), T-CD56 + (natural killer cells), and T-CD19+ (B-lymphocytes), using flow cytometry on blood samples collected 2 days after admission in the ICU. We enrolled 176 patients, 65.3% males, with mean age of 61.1 ± 15.4 years. At univariate analyses, higher percentages of CD19 B-cells were significantly associated with ensuing sepsis (20.5% (15.7-27.7)% vs 16.9% (11.3-22)%, P = 0.0001), whereas median interquartile range (IQR) proportions of CD4 T-cells (41.2% (33.4-50.6)% vs 40% (35-47)%, P = 0.5), CD8 T-cells (21.1% (15.8-28.2)% vs 19.6% (14.6-25.1)%, P = 0.2) and CD56 T-cells (1.7% (0.9-3.1)% vs 1.45% (0.7-2.3)%, P = 0.4) did not reveal any significant association. An unexpected, highly significant inverse correlation of CD8 T-cells and CD19 B-cells proportions, however, was observed, suggesting that patients with lower CD19 and higher CD8 proportions might be somehow protected from ensuing sepsis. We therefore studied the ability of the CD8/CD19 ratio to predict ensuing sepsis in our sample. In final models of multivariate logistic regression, the following independent associations were found: previous antibiotic exposure (odds ratio (OR): 3.8 (95% confidence interval (CI): 1.35-10.87), P = 0.01), isolation of at least one multi-drug resistant organism at any time during ICU stay (OR: 8.4 (95% CI: 3.47-20.6), P < 0.0001), decreasing age (OR: 0.9 (95% CI: 0.93-0.99), P = 0.02) and a CD8/CD19 ratio >2.2 (OR: 10.3 (95% CI: 1.91-55.36), P = 0.007). Our data provide preliminary evidence that immune characterization of critically ill patients on ICU admission may help personalize the prediction of ensuing sepsis during their ICU stay. Further polycentric evaluation of the true potential of this new tool is warranted.


Immunotherapy strategies for spinal cord injury.
Regeneration in the central nervous system (CNS) of adult mammalian after traumatic injury is limited, which often causes permanent functional motor and sensory loss. After spinal cord injury (SCI), the lack of regeneration is mainly attributed to the presence of a hostile microenvironment, glial scarring, and cavitation. Besides, inflammation has also been proved to play a crucial role in secondary degeneration following SCI. The more prominent treatment strategies in experimental models focus mainly on drugs and cell therapies, however, only a few strategies applied in clinical studies and therapies still have only limited effects on the repair of SCI. Recently, the interests in immunotherapy strategies for CNS are increasing in number and breadth. Immunotherapy strategies have made good progresses in treating many CNS degenerative disorders, such as Alzheimer's disease (AD), Parkinson's disease (PD), stroke, and multiple sclerosis (MS). However, the strategies begin to be considered to the treatment of SCI and other neurological disorders in recent years. Besides anti-inflamatory therapy, immunization with protein vaccines and DNA vaccines has emerged as a novel therapy strategy because of the simplicity of preparation and application. An inflammatory response followed by spinal cord injury, and is controled by specific signaling molecules, such as some cytokines playing a crucial role. As a result, appropriate immunoregulation, the expression of pro-inflammatory cytokines and anti-inflammatory cytokines may be an effective therapy strategy for earlier injury of spinal cord. In addition, myelinassociated inhibitors (MAIs) in the injured spinal cord, such as Nogo, myelin-associated glycoprotein (MAG) and oligodendrocyte- myelin glycoprotein (OMgp) are known to prevent axonal regeneration through their co-receptors, and to trigger demyelinating autoimmunity through T cell-mediated harmful autoimmune response. The antagonism of the MAIs through vaccinating with protein or DNA vaccines targeting Nogo, MAG, OMgp, and their co-receptors, may be an effective strategy for the treatment of SCI. However, immunotherapy such as anti-inflammtory therapy or vaccine targeting MAIs or their receptors, accompanied with the potential in risking autoimmune diseases. As a result, in order to optimize the anti-inflammtory therapy and design of protein or DNA vaccines for their use in the future clinical application, we need to further understand the possible mechanisms of neuroprotective immunity. This review presents recent advances in the development of immunotherapy strategies for the treatment of axonal degeneration and demyelination, and improvement of motor function after SCI.


Chromosome 11 loss from thymic lymphomas induced in heterozygous Trp53 mice by phenolphthalein.
C57BL/6 p53 (+/-) N5 mice heterozygous for a null p53 allele were given phenolphthalein to learn more about mechanisms of carcinogenesis and to evaluate the p53-deficient mouse as a tool for identifying potential human carcinogens. DNA samples isolated from 10 phenolphthalein-induced thymic lymphomas were analyzed for loss of heterozygosity (LOH) at the Trp53 locus and simple sequence length polymorphic (SSLP) loci. The initial screening revealed remarkable results from only chromosome 11. Allelotyping at approximately five centiMorgan intervals, we found SSLP heterozygosity for C57BL/6 and 129Sv over much of chromosome 11. In the tumors, treatment-related LOH was apparent on chromosome 11 at each of the 28 informative loci examined. The strain-specific polymorphism lost from individual tumors allowed us to deduce the distribution of alleles along the length of the maternal and paternal chromosomes 11. The allelic patterns indicate that mitotic homologous recombination occurred during embryogenesis if breeding protocols were carried out as described. The mitotic recombination observed may be attributable to p53 haploinsufficiency for normal suppression of mitotic recombination.


Expression of 5-HT3 receptors in the rat gastrointestinal tract.
Functional effects mediated via the 5-hydroxytryptamine3 receptor (5-HT3R) can be elicited from both extrinsic and intrinsic neurons innervating the gastrointestinal (GI) tract. Clinically, 5-HT3 antagonists are important in the treatment of emesis and have been used for the treatment of symptoms in functional bowel disease. The aim of the present study was to elucidate the cellular sites of 5-HT3R expression in the rat GI tract using immunohistochemistry. Immunohistochemistry was performed in fixed cryostat sections and whole mounts of stomach and intestine of fasted rats, using an affinity-purified antibody directed to a 19-amino acid sequence of the cytoplasmic loop of the 5-HT3R. 5-HT3R immunoreactivity was localized to numerous neurons of the myenteric and submucosal plexus, concentrated primarily near the neuronal plasma membrane, and to fibers in the circular and longitudinal muscles, submucosa, and mucosa. 5-HT3R immunoreactivity was also expressed by interstitial cells of Cajal and a few endocrine cells. Numerous 5-HT3R-positive myenteric neurons were cholinergic, and few neurons coexpressed VIP or SP immunoreactivity. Fibers immunoreactive for 5-HT3R in the duodenal but not ileal mucosa were markedly reduced by subdiaphragmatic vagotomy or chemical denervation of vagal afferents. These findings indicate that 5-HT3Rs are expressed by distinct cells in the GI tract, including functionally distinct classes of neurons, interstitial cells of Cajal, and endocrine cells. The effects of serotonin mediated by 5-HT3Rs involve the activation of neuronal and nonneuronal pathways.


Chloroplast DNA sequence of the green alga Oedogonium cardiacum (Chlorophyceae): unique genome architecture, derived characters shared with the Chaetophorales and novel genes acquired through horizontal transfer.
To gain insight into the branching order of the five main lineages currently recognized in the green algal class Chlorophyceae and to expand our understanding of chloroplast genome evolution, we have undertaken the sequencing of chloroplast DNA (cpDNA) from representative taxa. The complete cpDNA sequences previously reported for Chlamydomonas (Chlamydomonadales), Scenedesmus (Sphaeropleales), and Stigeoclonium (Chaetophorales) revealed tremendous variability in their architecture, the retention of only few ancestral gene clusters, and derived clusters shared by Chlamydomonas and Scenedesmus. Unexpectedly, our recent phylogenies inferred from these cpDNAs and the partial sequences of three other chlorophycean cpDNAs disclosed two major clades, one uniting the Chlamydomonadales and Sphaeropleales (CS clade) and the other uniting the Oedogoniales, Chaetophorales and Chaetopeltidales (OCC clade). Although molecular signatures provided strong support for this dichotomy and for the branching of the Oedogoniales as the earliest-diverging lineage of the OCC clade, more data are required to validate these phylogenies. We describe here the complete cpDNA sequence of Oedogonium cardiacum (Oedogoniales). Like its three chlorophycean homologues, the 196,547-bp Oedogonium chloroplast genome displays a distinctive architecture. This genome is one of the most compact among photosynthetic chlorophytes. It has an atypical quadripartite structure, is intron-rich (17 group I and 4 group II introns), and displays 99 different conserved genes and four long open reading frames (ORFs), three of which are clustered in the spacious inverted repeat of 35,493 bp. Intriguingly, two of these ORFs (int and dpoB) revealed high similarities to genes not usually found in cpDNA. At the gene content and gene order levels, the Oedogonium genome most closely resembles its Stigeoclonium counterpart. Characters shared by these chlorophyceans but missing in members of the CS clade include the retention of psaM, rpl32 and trnL(caa), the loss of petA, the disruption of three ancestral clusters and the presence of five derived gene clusters. The Oedogonium chloroplast genome disclosed additional characters that bolster the evidence for a close alliance between the Oedogoniales and Chaetophorales. Our unprecedented finding of int and dpoB in this cpDNA provides a clear example that novel genes were acquired by the chloroplast genome through horizontal transfers, possibly from a mitochondrial genome donor.


The giant serotonergic neuron of Aplysia: a multi-targeted nerve cell.
We have examined the various classes of cells that can be innervated by the giant cerebral neuron (GCN), an identified serotonergic cell that functions in arousal and maintenance of feeding behavior. We have found that this single neuron innervates a remarkable variety of postsynaptic targets by means of varicosities bearing active zones. The neuron's presynaptic terminals were identified by electron microscopic radioautography after intrasomatic injection of a tritiated amino sugar precursor of membrane glycoproteins; these are moved to nerve endings by fast axonal transport. In addition to endings on buccal muscle, we have found that GCN forms appositions with the morphological characteristics of synapses on axonal processes and cell bodies of neurons in the buccal ganglion and, unexpectedly, it forms appositions most often with glial cells which form the lining of intraganglionic hemal sinuses. Thus, GCN, through contacts on a variety of postsynaptic targets, has the potential of mediating several different functions, each of which is usually associated with a specific specialized type of neuron. In random electron micrographs, approximately 14% of GCN's varicosities had membrane specializations presumed to be the sites where transmitter is released. In these sections, GCN's active zones were quite small, 0.25 micrometer or approximately five vesicle diameters long. One of GCN's terminals was reconstructed completely from a series of thin sections. It had a single, flat ovoid active zone with an area of 17 micrometers2. We suggest that active zones often are overlooked in random sections of monoaminergic terminals because they are small.


The uncemented isoelastic/isotitan total hip arthroplasty. A 10-15 years follow-up with bone mineral density evaluation.
The present study analyses the long-term outcome of isoelastic hip prostheses and their influence on the extent of periprosthetic bone remodeling. Ninety-two patients (102 hips) with Isoelastic/Isotitan uncemented total hip arthroplasty were evaluated after an average of 13.4 years. The average age of patients at surgery was 42.5 years. The clinical outcome was assessed based on the Harris hip score, complications and thigh pain. Bone mineral density (BMD) of the proximal femur in the seven Gruen zones was evaluated by dual-energy X-ray absorptiometry (DEXA) scans with the contralateral hip serving as a control. The average Harris hip score at the most recent follow-up was 72 points, with 72 hips (70%) rating completely pain free. Eight stems required revision whereas none of the cups showed any evidence of loosening. The change in the mean BMD values between the femora on the operated side and the contralateral femora averaged 15% for all zones Although the isoelastic stems are no longer used owing to their high loosening rate, it appears that this prosthesis preserved periprosthetic bone better than reported for cemented or uncemented metallic implants. Besides, the provision of a titanium coating on the isoelastic stem, comparable to that on the RM cup, would presumably have improved its long-term fixation by encouraging bony ongrowth.


Dysmenorrhoea: Can Medicinal Cannabis Bring New Hope for a Collective Group of Women Suffering in Pain, Globally?
Dysmenorrhoea effects up to 90% of women of reproductive age, with medical management options including over-the-counter analgesia or hormonal contraception. There has been a recent surge in medicinal cannabis research and its analgesic properties. This paper aims to critically investigate the current research of medicinal cannabis for pain relief and to discuss its potential application to treat dysmenorrhoea. Relevant keywords, including medicinal cannabis, pain, cannabinoids, tetrahydrocannabinol, dysmenorrhoea, and clinical trial, have been searched in the PubMed, EMBASE, MEDLINE, Google Scholar, Cochrane Library (Wiley) databases and a clinical trial website (clinicaltrials.gov). To identify the relevant studies for this paper, 84 papers were reviewed and 20 were discarded as irrelevant. This review critically evaluated cannabis-based medicines and their mechanism and properties in relation to pain relief. It also tabulated all clinical trials carried out investigating medicinal cannabis for pain relief and highlighted the side effects. In addition, the safety and toxicology of medicinal cannabis and barriers to use are highlighted. Two-thirds of the clinical trials summarised confirmed positive analgesic outcomes, with major side effects reported as nausea, drowsiness, and dry mouth. In conclusion, medicinal cannabis has promising applications in the management of dysmenorrhoea. The global medical cannabis market size was valued at USD 11.0 billion in 2021 and is expected to expand at a compound annual growth rate (CAGR) of 21.06% from 2022 to 2030. This will encourage academic as well as the pharmaceutical and medical device industries to study the application of medical cannabis in unmet clinical disorders.


Generation of confluent cardiomyocyte monolayers derived from embryonic stem cells in suspension: a cell source for new therapies and screening strategies.
Cellular cardiomyoplasty is evolving as a new strategy to treat cardiac diseases. A prerequisite is a reliable source of pure cardiomyocytes, which could also help in the exploitation of recent advances in genomics and drug screening. Our goal was to establish a robust lab-scale process for the generation of embryonic stem (ES)-cell-derived cardiomyocytes in suspension. A 71 ES cell clone carrying a construct consisting of the alpha-cardiac myosin heavy chain (alphaMHC) promoter driving the neomycin resistance gene was used for antibiotic-driven cardiomyocyte enrichment. Rotating suspension culture was established to initiate embryoid body (EB) formation. To track growth and differentiation kinetics, cell count and flow cytometry for SSEA-I, E-cadherin (stem-cell marker)and sarcomeric myosin (cardiomyocytes marker) was performed. Oct4 expression was measured via real time (RT)-PCR. Cultures comprising 2.5-8 x 10(6) differentiating FS cells/mL were obtained after 9 days in rotating suspension. Upon G418 addition,vigorous contracting spheres, termed cardiac bodies (CB), developed. These cultures consisted of about 2.1 x 10(5) enriched cardiomyocytes/mL after 6- 10 days of selection. Suspensions comprising 90- 95%viable single cells were generated using an improved dissociation method. Seeding of cardiomyocytes with 7 x 10(4) cell/cm(2) resulted in a homogeneous monolayer of synchronously contracting cells. Myocyte specific immunohistochemistry indicated purity of > 99%. We have established a reliable lab-scale protocol to generate cultures of highly enriched cardiomyocytes in suspension. This will facilitate development of larger-scale processes for stem-cell based cardiomyocyte supply. An improved method is provided to derive vital suspensions of cardiomyocytes, which could be utilized for transplantation as well as for drug screening purposes.


Levels of HBx, VEGF, and CEACAM1 in HBV-related hepatocellular carcinoma and their correlation with cancer prognosis.
Hepatitis B virus X protein (HBx), vascular endothelial growth factor (VEGF) and carcinoembryonic antigen related cell adhesion molecule 1 (CEACAM1), are related to HBV associated hepatocellular carcinoma (HCC). This study recruited HCC patients and employed the SMMC-7721 and L02 liver cell lines, to analyze the expression levels of HBx, VEGF and CEACAM1 in liver cancer and their correlation with the cancer prognosis. HBV-related HCC patients were recruited from our hospital. Immunohistochemistry (IHC) and Western blotting assay were used to detect the expression of HBx, VEGF and CEACAM1 in liver tissues. Multi-variant analysis and the correlation analysis between HBx, VEGF, CEACAM1 expression and clinical/pathological features of HCC were performed by using the Cox regression analysis. In HBV-related HCC tissues, positive expression rates of HBx, CEACAM1, and VEGF, were 80%, 50%, and 65%, respectively. In HBx-positive group, positive rate for CEACAM1 and VEGF were 56.25% and 75%, while in HBx-negative group such figures were 75% and 25% (p<0.05). HCC cells had lower expression of CEACAM1 and higher VEGF levels compared to normal hepatocytes. Those HCC cells transfected with HBx had even lower CEACAM1 and higher VEGF levels compared to un-transfected cells. HBx was negatively correlated with CEACAM1 and positively correlated with VEGF. Expressions of these three factors were all independent risk factors as they were correlated with lesion size, venous infiltration, metastasis, and capsule. HBx, VEGF and CEACAM1 were widely expressed in HBV-related HCC. HBx may facilitate occurrence and progression of HBV-related HCC via down-regulating CEACAM1 and up-regulating VEGF.


Ubiquitin-specific peptidase 20 regulates Rad17 stability, checkpoint kinase 1 phosphorylation and DNA repair by homologous recombination.
Rad17 is a subunit of the Rad9-Hus1-Rad1 clamp loader complex, which is required for Chk1 activation after DNA damage. Rad17 has been shown to be regulated by the ubiquitin-proteasome system. We have identified a deubiquitylase, USP20 that is required for Rad17 protein stability in the steady-state and post DNA damage. We demonstrate that USP20 and Rad17 interact, and that this interaction is enhanced by UV exposure. We show that USP20 regulation of Rad17 is at the protein level in a proteasome-dependent manner. USP20 depletion results in poor activation of Chk1 protein by phosphorylation, consistent with Rad17 role in ATR-mediated phosphorylation of Chk1. Similar to other DNA repair proteins, USP20 is phosphorylated post DNA damage, and its depletion sensitizes cancer cells to damaging agents that form blocks ahead of the replication forks. Similar to Chk1 and Rad17, which enhance recombinational repair of collapsed replication forks, we demonstrate that USP20 depletion impairs DNA double strand break repair by homologous recombination. Together, our data establish a new function of USP20 in genome maintenance and DNA repair.


Cyclic nucleotide signaling mechanisms in trypanosomes: possible targets for therapeutic agents.
Trypanosome infections cause several major human diseases, including sleeping sickness and Chagas disease, which affect millions of people in Africa and South America, respectively. Although adenosine 3',5'-monophosphate (cAMP) signaling and regulation have been widely studied in mammalian systems, and these pathways provide targets for the treatment of numerous pathologies, a molecular understanding of cAMP signaling in trypanosomes remains incomplete. Recent studies in these parasites, however, have revealed diverse families of adenylyl cyclase and phosphodiesterase that regulate cAMP concentrations. Importantly, these enzymes differ pharmacologically and biochemically from their mammalian counterparts. In this review, we discuss recent developments, emerging ideas, and gaps in knowledge in this area of research, highlighting aspects of enzymes in the cAMP signaling pathway that may be good targets for antitrypanosomal drug therapy.


TIR1/AFB-Aux/IAA auxin perception mediates rapid cell wall acidification and growth of Arabidopsis hypocotyls.
Despite being composed of immobile cells, plants reorient along directional stimuli. The hormone auxin is redistributed in stimulated organs leading to differential growth and bending. Auxin application triggers rapid cell wall acidification and elongation of aerial organs of plants, but the molecular players mediating these effects are still controversial. Here we use genetically-encoded pH and auxin signaling sensors, pharmacological and genetic manipulations available for Arabidopsis etiolated hypocotyls to clarify how auxin is perceived and the downstream growth executed. We show that auxin-induced acidification occurs by local activation of H+-ATPases, which in the context of gravity response is restricted to the lower organ side. This auxin-stimulated acidification and growth require TIR1/AFB-Aux/IAA nuclear auxin perception. In addition, auxin-induced gene transcription and specifically SAUR proteins are crucial downstream mediators of this growth. Our study provides strong experimental support for the acid growth theory and clarified the contribution of the upstream auxin perception mechanisms.


Transplantation of clinical-grade human neural stem cells reduces neuroinflammation, prolongs survival and delays disease progression in the SOD1 rats.
Stem cells are emerging as a therapeutic option for incurable diseases, such as Amyotrophic Lateral Sclerosis (ALS). However, critical issues are related to their origin as well as to the need to deepen our knowledge of the therapeutic actions exerted by these cells. Here, we investigate the therapeutic potential of clinical-grade human neural stem cells (hNSCs) that have been successfully used in a recently concluded phase I clinical trial for ALS patients (NCT01640067). The hNSCs were transplanted bilaterally into the anterior horns of the lumbar spinal cord (four grafts each, segments L3-L4) of superoxide dismutase 1 G93A transgenic rats (SOD1 rats) at the symptomatic stage. Controls included untreated SOD1 rats (CTRL) and those treated with HBSS (HBSS). Motor symptoms and histological hallmarks of the disease were evaluated at three progressive time points: 15 and 40 days after transplant (DAT), and end stage. Animals were treated by transient immunosuppression (for 15 days, starting at time of transplantation). Under these conditions, hNSCs integrated extensively within the cord, differentiated into neural phenotypes and migrated rostro-caudally, up to 3.77 ± 0.63 cm from the injection site. The transplanted cells delayed decreases in body weight and deterioration of motor performance in the SOD1 rats. At 40DAT, the anterior horns at L3-L4 revealed a higher density of motoneurons and fewer activated astroglial and microglial cells. Accordingly, the overall survival of transplanted rats was significantly enhanced with no rejection of hNSCs observed. We demonstrated that the beneficial effects observed after stem cell transplantation arises from multiple events that counteract several aspects of the disease, a crucial feature for multifactorial diseases, such as ALS. The combination of therapeutic approaches that target different pathogenic mechanisms of the disorder, including pharmacology, molecular therapy and cell transplantation, will increase the chances of a clinically successful therapy for ALS.


Medical and nursing students' knowledge and attitudes toward violence against women in India.
The purpose of this study was to explore the knowledge and attitudes towards violence against women among fourth (final) year baccalaureate nursing students and fifth (final) year medical students from two distinct educational institutions in India. Data were collected from 440 students using two questionnaires: the Student Exposure to Woman Abuse Questionnaire (SEWAQ), and the Inventory of Beliefs about Wife Beating (IBWB). Results were analysed based on gender, profession, and educational institution. Nursing students believed that they had received more classroom preparation and practical skills to better prepare them to assist abused clients than male and female medical students. Only 38% of the participants believed that they had acquired classroom knowledge on woman abuse through their respective educational programs, whereas 43% thought they had practical skills to care for victims. All participants were sympathetic toward abuse victims, but demonstrated varying attitudes about the justification for abuse against women, help given to victims, punishment of the offender and the effect of woman abuse. Female medical students believed more strongly than males and nursing students that wives do not gain from being beaten. Congruent with existing literature, the study demonstrated that health care students in India do not receive sufficient training, practical skills and classroom knowledge to effectively manage abuse against women.


Relationship of salivary adipocytokines, diet quality, physical activity, and nutrition status in adult Emirati females in United Arab Emirates.
The United Arab Emirates (UAE) ranks as the fifth most obese country with increasing cardio-metabolic risks. In this paper, relationships of salivary adipocytokines (markers of cardio-metabolic syndrome), diet quality and physical activity in 90 normal-weight, overweight and obese (30 subjects in each group) Emirati adult females were investigated. A cross-sectional research design was adopted. Anthropometric measurements, diet quality and physical activity questionnaires were administered. Overnight fasting saliva was collected to determine levels of adiponectin, interleukin-10 (IL-10) and tumor necrosis factor-alpha (TNF-α). Salivary adiponectin was significantly lower, while TNF-α was higher in obese than normal-weight subjects. IL-10 displayed a lower trend in obese subjects. Though diet quality and physical activity did not exhibit significant differences among the three groups, better diet quality and higher physical activity level were reported among normal-weight subjects. Salivary TNF-α correlated positively with body mass index (BMI) (r = 0.37; p < 0.001) and waist circumference (r = 0.31; p < 0.001), while adiponectin correlated negatively with BMI (r = -0.28; p < 0.05). IL-10 showed negative trend in correlation with obesity measures. Correlations were not observed between diet quality and physical activity with salivary adipocytokines. Interestingly, a significant negative correlation emerged between diet quality and neck circumference (r = -0.24; p < 0.05). Our findings demonstrate that salivary adipocytokines correlate with obesity measures and can serve as convenient adjunct method in predicting cardio-metabolic risks in the population.


Foster Care Dynamics and System Science: Implications for Research and Policy.
Although system is a word frequently invoked in discussions of foster care policy and practice, there have been few if any attempts by child welfare researchers to understand the ways in which the foster care system is a system. As a consequence, insights from system science have yet to be applied in meaningful ways to the problem of making foster care systems more effective. In this study, we draw on population biology to organize a study of admissions and discharges to foster care over a 15-year period. We are interested specifically in whether resource constraints, which are conceptualized here as the number of beds, lead to a coupling of admissions and discharges within congregate care. The results, which are descriptive in nature, are consistent with theory that ties admissions and discharges together because of a resource constraint. From the data, it is clear that the underlying system exerts an important constraint on what are normally viewed as individual-level decisions. Our discussion calls on extending efforts to understand the role of system science in studies of child welfare systems, with a particular emphasis on the role of feedback as a causal influence.


Microbiological and meteorological analysis of two Australian dust storms in April 2009.
Dust is an important source of bioaerosols including bacteria. In this study, the microbiology and meteorology of specific dust storms in Australia were investigated. The samples were collected from two dust events in April 2009 that were characterised by intense cold fronts that entrained dust from the highly erodible and drought-stricken Mallee and Riverina regions of Victoria and central NSW. In the first storm, the dust travelled eastward over Canberra and Sydney, and in the second storm, the dust travelled east/southeastward over Canberra and Melbourne. Rain fell on both cities during the second dust storm. Dust and rain samples were collected, cultured, and the composition compared using polymerase chain reaction denaturing gradient gel electrophoresis (PCR-DGGE). Multiple bands were evident on DGGE indicative of a diverse microflora, and identification of several bands confirmed the presence of multiple genera and species representing three phyla. Numerous bands represented Bacillus species, and these were present in multiple dust samples collected from both Canberra and Melbourne. Interestingly, the microflora present in rain samples collected in Canberra during the second dust storm was quite different and the DGGE banding patterns from these samples clustered separately to most dust samples collected at the same time. Identification of several DGGE bands and PCR products from these rain samples indicated the presence of Pseudomonas species. These results indicate that Australian dust and rain have a diverse microflora and highlights the contribution of dust events to the distribution of microbes in the environment.


Analysis of growth of multicellular tumour spheroids by mathematical models.
We wished to determine the applicability of previously proposed deterministic mathematical models to description of growth of multicellular tumour spheroids. The models were placed into three general classes: empirical, functional and structural. From these classes, 17 models were applied systematically to growth curves of multicellular tumour spheroids used as paradigms of prevascular and microregional tumour growth. The spheroid growth curves were determined with uniquely high density of measurements and high precision. The theoretical growth curves obtained from the models were fitted by the weighted least-squares method to the 15 measured growth curves, each corresponding to a different cell line. The classical growth models such as von Bertalanffy, logistic and Gompertz were considered as nested within more general models. Our results demonstrate that most models fitted the data fairly well and that criteria other than statistical had to be used for final selection. The Gompertz, the autostimulation and the simple spheroid models were the most appropriate for spheroid growth in the empirical, functional and structural classes of models, respectively. We also showed that some models (e.g. logistic, von Bertalanffy) were clearly inadequate. Thus, contrary to the widely held belief, the sigmoid character of a three or more parameter growth function is not sufficient for adequate fits.


Food Consumer Behavior and Salmonella Exposure Self-Perception in the Central Region of Mexico.
In Mexico, there is limited information regarding food consumer behaviors at home. The knowledge of food consumption and food handling practices can help to determine more realistically the exposure to different hazards, such as Salmonella spp. on the population. The main goal of this study was to characterize the food consumption habits of five food groups (fruits and vegetables, fresh meat, dairy products, processed meat products, and seafood), food handling practices, and Salmonella exposure self-perception of the population of the central region of Mexico using an online survey. A total of 1,199 surveys were analyzed. The group of fruits and vegetables is the most consumed and one of the most related to the consumer self-perception of suffering from salmonellosis. Mexican consumers regularly use refrigeration as the principal food storage method for the five food groups (42.2% to 90.8%), and generally, they store the products between 2 and 3 days (26.5% to 38.1%). A total of 86.4% of consumers reported that they always wash their hands prior to food preparation. A total of 16.9% and 13.0% use the same cutting board and knife, respectively, to cut more than one product without applying sanitization. Men, people between 20 and 24 years, and people between 60 and 64 years, had the highest risk food handling practices at home. Finally, age (P < 0.0001), education level (P = 0.0004), and suffering from gastrointestinal diseases (P = 0.0005) showed significant effects with self-perception of having salmonellosis. PRACTICAL APPLICATION: Data presented in this study could be used in future risk and exposure assessment research to evaluate the public health risk from the consumption of contaminated food. In addition, it could be used by government agencies to design education campaigns in food safety area.


Key visual features for rapid categorization of animals in natural scenes.
In speeded categorization tasks, decisions could be based on diagnostic target features or they may need the activation of complete representations of the object. Depending on task requirements, the priming of feature detectors through top-down expectation might lower the threshold of selective units or speed up the rate of information accumulation. In the present paper, 40 subjects performed a rapid go/no-go animal/non-animal categorization task with 400 briefly flashed natural scenes to study how performance depends on physical scene characteristics, target configuration, and the presence or absence of diagnostic animal features. Performance was evaluated both in terms of accuracy and speed and d' curves were plotted as a function of reaction time (RT). Such d' curves give an estimation of the processing dynamics for studied features and characteristics over the entire subject population. Global image characteristics such as color and brightness do not critically influence categorization speed, although they slightly influence accuracy. Global critical factors include the presence of a canonical animal posture and animal/background size ratio suggesting the role of coarse global form. Performance was best for both accuracy and speed, when the animal was in a typical posture and when it occupied about 20-30% of the image. The presence of diagnostic animal features was another critical factor. Performance was significantly impaired both in accuracy (drop 3.3-7.5%) and speed (median RT increase 7-16 ms) when diagnostic animal parts (eyes, mouth, and limbs) were missing. Such animal features were shown to influence performance very early when only 15-25% of the response had been produced. In agreement with other experimental and modeling studies, our results support fast diagnostic recognition of animals based on key intermediate features and priming based on the subject's expertise.


Performance Evaluation of Porous Graphene as Filter Media for the Removal of Pharmaceutical/Emerging Contaminants from Water and Wastewater.
Graphene and its counterparts have been widely used for the removal of contaminants from (waste)water but with limited success for the removal of pharmaceutical contaminants. Driven by this need, this study reports, for the first time, the removal of pharmaceuticals from real contaminated water samples using porous graphene (PG) as a filter-based column. This work systematically evaluates the performance of PG as a filter medium for the removal of widely consumed pharmaceutical/emerging contaminants (ECs) such as atenolol, carbamazepine, ciprofloxacin, diclofenac, gemfibrozil and ibuprofen. Several factors were investigated in these column studies, including different reactive layer configurations, bed packing heights (5-45 mm), filter sizes (inner diameter 18-40 mm), adsorbent dosages (100-500 mg-PG) and water bodies (distilled water, greywater, and actual effluent wastewater). Sustainable synthesis of PG was carried out followed by its use as a filter medium for the removal of pharmaceuticals at high concentrations (10.5 ± 0.5 mg/L) and trace concentrations (1 mg/L). These findings revealed that the double-layered PG-sand column outperformed a PG single-layered configuration for the removal of most of the ECs. The removal efficiency of ECs from their solutions was improved by increasing PG dosages and filter bed height and size. Although the treatment of mixed pharmaceutical solutions from different water bodies was affected by the negative interference caused by competing water compounds, the treatment of ECs-contaminated greywater was not severely affected. Our findings suggest that PG, as a highly efficient filter medium, could be used for the removal of emerging pharmaceutical contaminants from water and wastewater.


Development and characterization of mucoadhesive buccal gels containing lipid nanoparticles of ibuprofen.
The lipid nanoparticles, namely Nanostructured Lipid Carriers (NLC), as drug delivery systems have been investigated for several years. One of the delivery routes for which these carriers can be applied is buccal administration. However, the liquid dispersions of lipid nanoparticles can be rapidly removed from oral cavity by saliva. Thus, the development of a system that allows increased retention time on the mucosa is necessary. For this reason, the development of mucoadhesive preparations for buccal administration of lipid nanoparticles becomes important. Hydrogels prepared with mucoadhesive polymers (Carbopol® 980 and polycarbophil) constitute a promising option. The aim of this work was to develop mucoadhesive buccal hydrogels with NLC, using ibuprofen as a model drug. The obtained results showed that the developed NLC dispersions presented particles in the nanometric size range, with low polydispersity index values and efficient ability for the entrapment of the model drug. Moreover, the incorporation of NLC in hydrogels of mucoadhesive polymers resulted in preparations with desirable rheological features as well as texture (firmness and adhesiveness) and mucoadhesive properties, which could benefit the therapeutic efficacy, by increasing the residence time and easiness for topical application in the buccal mucosa. Additionally, the developed preparations exhibited sustained drug release as intended for these systems.


Physicians' and pharmacists' information provision and patients' psychological distress.
Providing information related to medication has many benefits for patients. However, patients' conflicting perceptions about medical information provided by physicians and pharmacists may be associated with their psychological distress regarding treatment and medication. This study investigated associations between patients' perceptions of agreement between physicians and pharmacists about medical information and improvements in their psychological distress. It also clarified the specific relationships of their perceptions with psychological distress. A cross-sectional survey was conducted in Japanese community pharmacy settings. Pharmacists approached 1,500 patients visiting community pharmacies and provided them with questionnaire packages. Patients completed the questionnaires at home and returned them to the researchers by mail. Multivariate logistic regression analysis and signal detection analysis were conducted to examine associations of patients' perceptions of information agreement with improvement in psychological distress. Measures of improvement in worry and anxiety about disease, improvement in worry and anxiety about medication, and improvement in depressive mood were used to assess alleviation of psychological distress. A total of 645 patients returned the questionnaires; 628 contributed to the data. Multivariate logistic regression analyses clarified that patients' perceptions of agreement in information regarding need for medication, methods for adverse drug reaction reduction, adverse drug reaction symptoms, coping with forgetting to take medication, and advice for daily life were significantly associated with improvements in psychological distress. Furthermore, signal detection analysis showed that several combinations of patients' perceptions of agreement between physicians and pharmacists about specific medical information were also significantly associated with improvement in psychological distress. Consistent information provision by physicians and pharmacists could contribute to decreased psychological distress in patients, and consequently to adherence to treatment and taking medication.


A 3D digital reconstruction of the components of the gas exchange tissue of the lung of the muscovy duck, Cairina moschata.
To elucidate the shape, size, and spatial arrangement and association of the terminal respiratory units of the avian lung, a three-dimensional (3D) computer-aided voxel reconstruction was generated from serial plastic sections of the lung of the adult muscovy duck, Cairina moschata. The air capillaries (ACs) are rather rotund structures that interconnect via short, narrow passageways, and the blood capillaries (BCs) comprise proliferative segments of rather uniform dimensions. The ACs and BCs anastomose profusely and closely intertwine with each other, forming a complex network. The two sets of respiratory units are, however, absolutely not mirror images of each other, as has been claimed by some investigators. Historically, the terms 'air capillaries' and 'blood capillaries' were derived from observations that the exchange tissue of the avian lung mainly consisted of a network of minuscule air- and vascular units. The entrenched notion that the ACs are straight (non-branching), blind-ending tubules that project outwards from the parabronchial lumen and that the BCs are direct tubules that run inwards parallel to and in contact with the ACs is overly simplistic, misleading and incorrect. The exact architectural properties of the respiratory units of the avian lung need to be documented and applied in formulating reliable physiological models. A few ostensibly isolated ACs were identified. The mechanism through which such units form and their functional significance, if any, are currently unclear.


Picogram per liter level determination of estrogens in natural waters and waterworks by a fully automated on-line solid-phase extraction-liquid chromatography-electrospray tandem mass spectrometry method.
The present work describes a novel, fully automated method, based on on-line solid-phase extraction-liquid chromatography-electrospray tandem mass spectrometry (SPE-LC-ESI-MS-MS), which allows the unequivocal identification and quantification of the most environmentally relevant estrogens (estradiol, estrone, estriol, estradiol-17-glucuronide, estradiol-17-acetate, estrone-3-sulfate, ethynyl estradiol, diethylstilbestrol) in natural and treated waters at levels well below those of concern (limits of quantification between 0.02 and 1.02 ng/L). The method is highly precise, with relative standard deviations varying between 1.43 and 3.89%, and accurate (recovery percentages >74 %). This method was used to track the presence and fate of the target compounds in a waterworks and to evaluate the removal efficiency of the treatment processes applied. Only estrone and estrone-3-sulfate were detected in the river water used as source (at 0.68 and 0.33 ng/L, respectively). After progressive removal through the various treatment steps, none of them were detected in the finished drinking water. In addition to selectivity, sensitivity, repeatability, and automation (up to 15 samples plus 6 calibration solutions and 1 blank can be analyzed unattended), this technique offers fairly high throughput (analysis time per sample is 60 min), low time and solvent consumption, and ease of use.


The prescription rate of antibacterial agents in dogs in Norway - geographical patterns and trends during the period 2004-2008.
The aim of the present study was to describe the prescription rate and patterns of antibacterial agents in the Norwegian dog population in relation to time and place during 2004-2008. Prescription data were collected from the Norwegian prescription database (NorPD), whereas an estimate of the dog population was obtained from the Norwegian Kennel Club (NKK). Maps of the geographical prescription rate patterns were generated in the software ArcGIS 9.2. This study indicates an increased usage of antibacterial agents in dogs in Norway during the study period in which antibacterial agents for systemic use and especially the combination amoxicillin and clavulanic acid accounted for the major part. Among antibacterial agents defined as critically important for human medicine, an increase was observed in the prescription rate of quinolones. The geographical prescription rate patterns were stable during the study period, which indicated that the identified increase in usage of antimicrobial agents occurred all over the country, but that there were regional differences in the prescribing behaviour. Prescription data from the NorPD of antibacterial agents to dogs can be used as a basis to perform a risk-based sampling approach to detect emerging antimicrobial resistance in the dog population.


Cep55 regulates embryonic growth and development by promoting Akt stability in zebrafish.
CEP55 was initially described as a centrosome- and midbody-associated protein and a key mediator of cytokinesis. More recently, it has been implicated in PI3K/AKT pathway activation via an interaction with the catalytic subunit of PI3K. However, its role in embryonic development is unknown. Here we describe a cep55 nonsense mutant zebrafish with which we can study the in vivo physiologic role of Cep55. Homozygous mutants underwent extensive apoptosis by 24 hours postfertilization (hpf) concomitant with cell cycle defects, and heterozygous carriers were indistinguishable from their wild-type siblings. A similar phenotype was also observed in zebrafish injected with a cep55 morpholino, suggesting the mutant is a cep55 loss-of-function model. Further analysis revealed that Akt was destabilized in the homozygous mutants, which partially phenocopied Akt1 and Akt2 knockdown. Expression of either constitutively activated PIK3CA or AKT1 could partially rescue the homozygous mutants. Consistent with a role for Cep55 in regulation of Akt stability, treatment with proteasome inhibitor, MG132, partially rescued the homozygous mutants. Taken together, these results provide the first description of Cep55 in development and underline the importance of Cep55 in the regulation of Pi3k/Akt pathway and in particular Akt stability.


Radiographic analysis of diabetic midfoot charcot neuroarthropathy with and without midfoot ulceration.
The aim of this study was to evaluate weight-bearing radiographs in patients with and without foot ulcers diagnosed with midfoot Charcot neuroarthropathy (CN) secondary to diabetes mellitus. One hundred fourteen patients with midfoot CN (50 with foot ulcers and 64 without ulcers) were identified and included in this study. Nine radiographic measurements were made (7 in the sagittal plane and 2 in the transverse plane). CN patients with foot ulcers had significantly greater deformity when assessing the lateral-talar first metatarsal angle, calcaneal pitch, cuboid height, medial column height, calcaneal-fifth metatarsal angle, talar declination, and lateral tibiotalar angle. Two measurements in the transverse plane (hindfoot-forefoot angle and AP talar first metatarsal angle) were not significantly different between the 2 groups. Of patients with foot ulcers, 24% had a lateral talar first metatarsal angle of less than -27 degrees and 80% had a negative cuboid height. Sagittal plane deformities were more likely to be associated with foot ulceration in patients with CN than transverse plane deformities. Lateral column involvement was associated with a worse prognosis than medial column involvement, thus we believe progressive deformity of the lateral column should be monitored closely to prevent foot ulceration. Lateral column involvement could be identified by a decrease in the cuboid height, decreased calcaneal pitch, and decreased lateral calcaneal fifth metatarsal angle. This study can assist physicians in stratifying the risk for both ulceration and need for surgery in patients with CN based on reproducible radiographic measurements. Level III, comparative series.


Round Robin Study: Molecular Simulation of Thermodynamic Properties from Models with Internal Degrees of Freedom.
Thermodynamic properties are often modeled by classical force fields which describe the interactions on the atomistic scale. Molecular simulations are used for retrieving thermodynamic data from such models, and many simulation techniques and computer codes are available for that purpose. In the present round robin study, the following fundamental question is addressed: Will different user groups working with different simulation codes obtain coinciding results within the statistical uncertainty of their data? A set of 24 simple simulation tasks is defined and solved by five user groups working with eight molecular simulation codes: DL_POLY, GROMACS, IMC, LAMMPS, ms2, NAMD, Tinker, and TOWHEE. Each task consists of the definition of (1) a pure fluid that is described by a force field and (2) the conditions under which that property is to be determined. The fluids are four simple alkanes: ethane, propane, n-butane, and iso-butane. All force fields consider internal degrees of freedom: OPLS, TraPPE, and a modified OPLS version with bond stretching vibrations. Density and potential energy are determined as a function of temperature and pressure on a grid which is specified such that all states are liquid. The user groups worked independently and reported their results to a central instance. The full set of results was disclosed to all user groups only at the end of the study. During the study, the central instance gave only qualitative feedback. The results reveal the challenges of carrying out molecular simulations. Several iterations were needed to eliminate gross errors. For most simulation tasks, the remaining deviations between the results of the different groups are acceptable from a practical standpoint, but they are often outside of the statistical errors of the individual simulation data. However, there are also cases where the deviations are unacceptable. This study highlights similarities between computer experiments and laboratory experiments, which are both subject not only to statistical error but also to systematic error.


Radiographic evaluation of the modified Bristow procedure for recurrent anterior dislocation of the shoulder.
Concerning the radiological evaluation of the modified Bristow procedure in the operative treatment of recurrent anterior dislocation of the shoulder, several aspects are of importance. In the first place, the position of the coracoid transplant and the screw used to fix it with should be underneath the equator of the humeral head and within 1 cm of the glenoid rim. Secondly, bony union appears to take place in most instances in which the screw has enough length to reach the posterior cortex of the scapular neck. However, when the screw is too short, in most cases a fibrous union develops. These features can be demonstrated on three routine radiological examinations: the anatomical anterior-posterior view, the axial projection with internally rotated humerus and the axial view with the arm in external rotation.


[Modifying effect of ionizing radiation on the transmembrane transport of sodium ions in Ehrlich carcinoma tumor cells].
The effect of a local X-irradiation on the transmembrane transfer of Na ions and activity of Na-K ATPase in Ehrlich ascites tumor cells has been investigated. Irradiation with doses of 0.05 and 0.15 C/kg are shown to change natrium ion transport. This effect is absent at a dose of 0.08 C/kg. A change in the rate of active transport correlates to some extent with the disturbance in Na-K ATPase occurring at the same radiation doses.


Function and regulation of plant invertases: sweet sensations.
The disaccharide sucrose and the cleavage products glucose and fructose are the central molecules for carbohydrate translocation, metabolism and sensing in higher plants. Invertases mediate the hydrolytic cleavage of sucrose into the hexose monomers. Plants possess three types of invertases, which are located in the apoplast, the cytoplasm and the vacuole, respectively. It has become evident that extracellular and vacuolar invertase isoenzymes are key metabolic enzymes that are involved in various aspects of the plant life cycle and the response of the plant to environmental stimuli because their substrates and reaction products are both nutrients and signal molecules. Invertases, alone or in combination with plant hormones, can regulate many aspects of the growth and development of plants from gene expression to long-distance nutrient allocation and are involved in regulating carbohydrate partitioning, developmental processes, hormone responses and biotic and abiotic interactions.


Do patient-specific guides improve coronal alignment in total knee arthroplasty?
Coronal alignment may impact clinical outcome and survivorship in TKA. Patient-specific instrumentation has been developed to restore mechanical or kinematic axis and potentially reduce component malpositioning. Although it is clear these instruments add cost, it is unclear whether they improve alignment. We determined whether the mean coronal alignment after TKA performed with conventional versus patient-specific instrumentation better restored the mechanical and kinematic axes and whether there were more outliers with one of the two methods. We retrospectively evaluated 150 primary TKAs performed for osteoarthritis: Group 1 (n = 50) conventional instrumentation; Group 2 (n = 50) patient-specific instrumentation restoring the mechanical axis; Group 3 (n = 50) patient-specific instrumentation restoring the kinematic axis, and measured femorotibial angle, hip-knee-ankle angle, and the zone of the mechanical axis from scout CT images taken 0 to 6 weeks postoperatively. The mean femorotibial angle differed between the groups: Group 1 had the greatest varus mean alignment and most varus outliers. The mean hip-knee angle was similar between Groups 1 and 2, with Group 3 having greater valgus mean alignment and the most valgus outliers. For the zone of the mechanical axis, Groups 1 and 2 had similar percentages of outliers (40% versus 32%), whereas Group 3 had a greater number of outliers (64%) that were valgus. TKAs with patient-specific instrumentation restoring the mechanical axis had a similar number of outliers as conventional instrumentation with both groups having more varus outliers than TKAs with patient-specific instrumentation restoring kinematic axis, which had more valgus outliers. Therefore, additional studies are needed to determine whether patient-specific instrumentation improves clinical function or patient satisfaction and whether their routine use can be justified in primary TKA. Level III, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.


Basketball players' experience of dental injury and awareness about mouthguard in China.
The objective of the present study was to describe the occurrence of orofacial, particularly dental injuries in basketball, and to survey the athletes' awareness concerning the use of mouthguards during basketball training and competition. A pilot questionnaire was designed and tested with basketball players. Two hundred and thirty-six male athletes were surveyed. Seventy-seven players were professional players. Exactly 80.6% professionals and 37.7% semi-professional athletes had an experience of oral soft tissue laceration and dental injuries in basketball practice. The difference between the two groups is significant. The incidence of dental and oral injuries was related to the length of training time. About 59% of the athletes ranked the risk of orofacial and dental injury in basketball as medium. Although the awareness of mouthguards among the basketball players was very high (80.1%), only one of them had used the custom-made mouthguard. Most of the athletes gained the knowledge about mouthguards from foreign players (33.5%), media (24.8%) and teammates/classmates (24.3%). The influence of dentists was very weak. Athletes should be informed about the high risk of oral injuries when participating in contact sports. Dentists should play a more significant role in the program of promoting mouthguard use to prevent the occurrence of oral injury in sport participation.


Racial Differences in Breastfeeding on the Mississippi Gulf Coast: Making Sense of a Promotion-Prevalence Paradox with Cross-Sectional Data.
Breastfeeding is less prevalent among African American women than their white peers. Moreover, breastfeeding rates in the South lag behind those in other regions of the U.S. Consequently, various efforts have been undertaken to promote breastfeeding among groups for which this practice is less common. This study examines African American and white racial disparities concerning (1) exposure to breastfeeding promotional information and (2) reported prevalence of breastfeeding in primary social networks. The survey combines a randomly selected sample of adults representative of the population and a non-random oversample of African Americans in a predominantly rural tri-county area on the Mississippi Gulf Coast. An initial wave of 2019 Mississippi REACH Social Climate Survey data collected under the auspices of the CDC-funded REACH program (Mississippi's Healthy Families, Mothers, and Babies Initiative; 2018-2023) is used to examine racial disparities in these two key outcomes for Mississippians in Hancock, Harrison, and Jackson counties. The results show that African American respondents are more likely to be exposed to breastfeeding promotional messages than their white counterparts. However, the reported prevalence of breastfeeding in African American respondents' primary social networks is significantly lower than that indicated by their white peers. These paradoxical results underscore the limitations of promotional efforts alone to foster breastfeeding. While breastfeeding promotion is important, the reduction of racial disparities in this practice likely requires a multi-pronged effort that involves structural breastfeeding supports (e.g., lactation spaces, peer networking groups, and pro-breastfeeding employment policies and workplaces). This study provides a promising model of innovative methodological approaches to the study of breastfeeding while underscoring the complex nature of racial disparities in lactation prevalence.


Enzymatic synthesis of [3'-O-methyl-(3)H]malvidin-3-glucoside from petunidin-3-glucoside.
Malvidin-3-glucoside has been labeled by enzymatic synthesis in a single-step experiment. Catechol-O-methyl transferase catalyzed the B-ring methylation of petunidin-3-glucoside, and S-Adenosyl-L-[methyl-(3)H] methionine was the methyl donor. Solid phase extraction and preparative high-performance liquid chromatography were necessary to separate [3'-O-methyl-(3)H]malvidin-3-glucoside from an isomer and the starting material. The specific activity was 2.2 Ci mmol(-1), and the yield of incorporation was 1.1%. A possible application of the labeled material is the study of anthocyanin reactions in complex mixtures such as red wine where products are difficult to isolate and analyze.