Expression of the receptor MPL and proliferative effects of its ligand thrombopoietin on human leukemia cells.
Thrombopoietin (TPO) is a recently characterized growth and differentiation factor for megakaryocytes and platelets exerting its effects via the receptor MPL. We examined the expression of MPR on the cell surface of a panel of 43 myelomonocytic, erythroid and megakaryocytic leukemia cell lines and 21 primary acute myeloid leukemia (AML) cases by flow cytometry. With few exceptions MPL was found on all 32 erythroid/megakaryocytic cell lines and on all 11 growth factor-dependent myelomonocytic cell lines, albeit at variable percentages and intensities per cell population (with a 10% cut-off level for positivity still 30/43 cell lines scored as MPL positive). The majority of the primary AML samples (including all seven M6/M7 cases) expressed the MPL protein regardless of the morphological and immunological subtype (13/21 cases had >10% MPL-positive cells). Recombinant TPO overexpressed in hamster cells induced a mitogenic response in seven cell lines (one growth factor-independent and six factor-dependent lines) and in 3/21 AML specimens (two AML M2, one AML M7) as measured by 3H-thymidine incorporation. Expression of MPL clearly did not correlate with response to TPO. For further detailed studies of the interaction of TPO with other cytokines we used the AML M7-derived M-07e cells as an informative indicator cell line for which both murine and human TPO acted as a very potent mitogen in a dose-dependent fashion (3- to 11-fold proliferation increase relative to medium alone). This growth factor-dependent cell line which is normally cultured in conditioned medium containing several cytokines could be grown in long-term culture supplemented only with TPO. Co-incubation of M-07e with various cytokines and TPO showed additive proliferative effects for interleukin-3 (IL-3) and granulocyte-macrophage colony-stimulating factor (GM-CSF) and synergistic responses for stem cell factor (SCF), interferon (IFN)-alpha, and to a lesser extent for IFN-gamma and tumor necrosis factor (TNF)-alpha. Erythropoietin (EPO), IL-1, IL-6, IL-11 and leukemia inhibitory factor (LIF), know as megakaryocytic maturation-inducing molecules, were not substantially effective, neither singly nor in combination with TPO, with regard to cell growth. Transforming growth factor (TGF)-beta1 antagonized the inductive effect of TPO on M-07e cell growth. Addition of TPO to cultures of megakaryocytic cell lines failed to significantly alter the ploidy distribution and the differentiation marker immunoprofile of the cells indicating a lack of maturation-inducing effects in this model system. In summary, TPO represents an efficient in vitro potentiator of megakaryocytic leukemia proliferation of at least some primary cases or cell lines. While TPO seems to be the major physiological regulator of megakaryocytopoiesis, the present data suggest also some proliferative effects on certain leukemia cells, apparently on non-megakaryocytic leukemia cells as well, thus assigning to TPO a possible pathobiological role in leukemogenesis which would be of clinical relevance. Our data show that the response to TPO is not restricted to cells committed to the megakaryocytic differentiation pathway as we could demonstrate TPO-responsive megakaryocytic and non-megakaryocytic cell lines; thus, these cell lines represent powerful tools in such analyses. Consequently, this new cytokine needs to be properly examined so we can get a clear understanding of the clinical possibilities and dangers.


Immediate postoperative enteral feeding decreases weight loss and improves wound healing after abdominal surgery in rats.
To determine the effect of immediate vs. delayed (72 hrs) postoperative enteral feeding on weight loss and wound healing after experimental abdominal surgery. Prospective, randomized, controlled study. Laboratory of a large university-affiliated medical school. Seventeen male Sprague-Dawley rats, each weighing 350 to 400 g. Four-centimeter longitudinal midabdominal incisions were made and gastroduodenal feeding tubes were inserted in the animals. The abdominal wound was closed in two layers. Immediately after closure, animals were randomized to receive immediate enteral feeding (early-fed group) with a peptide-based enteral formula or 5% dextrose in water at 4 mL/hr. Seventy-two hours after surgery, the 5% dextrose in water group was switched to the peptide formula (late-fed group). Animals were weighed daily. On postoperative day 5, the strength of the abdominal wound was determined using a balloon-bursting pressure technique. Blood was also obtained for measurement of insulin growth factor 1 concentrations. Mucosal protein content of the small bowel was measured. Total body weight loss was less in the early-fed group (26 +/- 4 vs. 46 +/- 5 g/5 days) and wound strength was increased in the early-fed group compared with the late-fed group (6 +/- 0.4 vs. 2.9 +/- 0.8 kPa; 45 +/- 3 vs. 22 +/- 6 mm Hg). There were no differences between groups for circulating insulin growth factor 1 concentrations or small intestinal mucosal protein concentrations. Immediate postoperative enteral feeding results in decreased weight loss and improved wound healing after abdominal surgery in rats.


Three-dimensional simulation of the nasoalveolar cleft defect.
This study describes the planning process for a three-dimensional (3D) model of a nasoalveolar bone graft in patients with unilateral cleft lip and palate. A 3D reconstruction of the alveolar cleft based on cone-beam computed tomography was performed in 10 patients. Graft models were planned using a 3D planning software (iPlan ENT 3.0, Brainlab, Feldkirchen, Germany) and printed using a 3D printer (Objet30 Pro, Objet Ltd., Rehovot, Israel). A reproducible, step-by-step planning method was established, which is manual rather than automatic. Still, the 3D visualization and a life-size graft template could be useful during secondary alveolar osteoplasty.


Alcohol levels in killed drivers and pedestrians on Irish roads 2003-2005: a national study.
No official data are provided in Ireland to indicate what proportion of the deaths on Irish roads have alcohol as a contributory factor. The aim of this study was to identify the blood alcohol concentration (BAC) in fatally injured drivers and pedestrians in Ireland. An Garda Síochána (The Irish police) gather data on all fatal road crashes and individual paper files are kept on each crash. The authors examined all such files for deaths in 2003-2005. Of the 611 drivers fatally injured, 184 (30.1%) were over the BAC legal limit (80 mg/100 ml). BACs were available for only 397 (64.9%) of drivers. Of the 397 drivers who had their BACs recorded, 184 (46.3%) had a BAC over the legal limit of 80 mg/100 ml and 220 (55.4%) had BACs 20 mg/100 ml or higher. Fatally injured drivers with BACs 20 mg/100 ml or greater were more likely to be male (88.6%/o, p<0.01). Alcohol-related crashes were more likely to occur on week end nights. Pedestrian alcohol consumption was considered to be a contributory factor in 50 (24.4%) of the pedestrian deaths with 22 (10.7%) of the pedestrians having alcohol levels exceeding 240 mgl/100 ml. This study confirms that alcohol is a significant factor in road deaths. Further targeted action including a reduction in the legal limit is required.


Effect of hypotensive anesthesia on cognitive functions. A comparison of esmolol and remifentanil during tympanoplasty.
To compare the effects of esmolol and remifentanil, used as adjuncts for induced hypotension on surgical conditions and short-term cognitive functions, during tympanoplasty. The study was conducted in Hacettepe University, School of Medicine, Ankara, Turkey between January 2005 and December 2006 following Institutional Ethical Committee approval, 40 ASA I-II patients, between 18 and 60 years of age were included in this study. With the induction of anesthesia, for group E, an esmolol infusion of 50-250 ug.kg-1.min-1 was titrated, following a bolus of 0.5 mgxkg-1; for group R, a remifentanil infusion of 0.2-0.5 ugxkg-1xmin-1 was titrated; to achieve a mean blood pressure (BP) of 55-65 mm Hg. Arterial BP were recorded continuously throughout the operation. Mini Mental State Test (MMS) was performed at the preoperative 30th minute (MMSP), postoperative 30th minute (MMS30), 60th minute (MMS60) and 24th hour (MMS24). Surgical field was evaluated by the blinded surgeon, using a 6 point category scale. Patient demographics were similar in both groups. Sustained controlled hypotension was sufficient in all of the groups throughout surgery. Surgical field scores were lower in group R (p<0.05), although the scores were </=2 in both groups, which was regarded as adequate for tympanoplasty. Four patients in group R (20%) and one patient in group E (5%) showed cognitive function decline between MMSP and MMS30. Within both groups, there were statistically significant differences between MMS60 and MMSP, MMS24 and MMSP, MMS60 and MMS30, MMS24 and MMS30, but the results were similar between the groups. Remifentanil or esmolol provided adequate induced hypotension and similar operating conditions and their effects on cognitive functions in the short postoperative period are similar for tympanoplasty.


In vitro and in vivo activity of meropenem and sulbactam against a multidrug-resistant Acinetobacter baumannii strain.
The potential therapeutic role of meropenem combined with sulbactam against a clinical endemic isolate of multidrug-resistant Acinetobacter baumannii, Ab-153, was investigated. The antimicrobial susceptibility of Ab-153 to various drugs was studied by the agar dilution method and Etest strips. The antibacterial activity of meropenem and sulbactam were investigated by a time-kill study in vitro and further examined for therapeutic efficacy in vivo in a murine model. In the time-kill study, at a concentration of 0.5 x MIC (4 mg/L) of meropenem, 1 x MIC (8 mg/L) of sulbactam and both in combination, only the combination demonstrated bactericidal effects and there was at least a 5 log(10) reduction in bacterial colony counts after 48 h, compared with either drug alone. BALB/c mice infected with 2.1-2.6 x 10(7) cfu of Ab-153 were treated with 20 mg/kg meropenem every 8 h, 40 mg/kg sulbactam every 8 h or both in combination. The survival rate of mice in the combination group was significantly higher than that in the meropenem-treated or sulbactam-treated group (87% versus 35%, P = 0.0004; 87% versus 30%, P = 0.0002). Meropenem in conjunction with sulbactam can exhibit more potent antimicrobial activity against Ab-153 than meropenem or sulbactam alone.


Dorsomorphin stimulates neurite outgrowth in PC12 cells via activation of a protein kinase A-dependent MEK-ERK1/2 signaling pathway.
In this study, we investigated the effect of dorsomorphin, a selective inhibitor of bone morphogenetic protein (BMP) signaling, on rat PC12 pheochromocytoma cell differentiation. PC12 cells can be induced to differentiate into neuron-like cells possessing elongated neurites by nerve growth factor, BMP2, and other inducers. Cells were incubated with BMP2 and/or dorsomorphin, and the extent of neurite outgrowth was evaluated. Unexpectedly, BMP2-mediated neuritogenesis was not inhibited by co-treatment with dorsomorphin. We also found that treatment with dorsomorphin alone, but not another BMP signaling inhibitor, LDN-193189, induced neurite outgrowth in PC12 cells. To further understand the mechanism of action of dorsomorphin, the effects of this drug on intracellular signaling were investigated using the following signaling inhibitors: the ERK kinase (MEK) inhibitor U0126; the tropomyosin-related kinase A inhibitor GW441756; and the protein kinase A (PKA) inhibitor H89. Dorsomorphin induced rapid and sustained ERK1/2 activation; however, dorsomorphin-mediated ERK1/2 activation and neuritogenesis were robustly inhibited in the presence of U0126 or H89, but not GW441756. These findings suggest that dorsomorphin has the potential to induce neuritogenesis in PC12 cells, a response that requires the activation of PKA-dependent MEK-ERK1/2 signaling.


Corneal ulceration associated with naturally occurring canine herpesvirus-1 infection in two adult dogs.
An 8-year-old Labrador Retriever with diabetes mellitus in which bilateral phacoemulsification had been performed 3 weeks earlier was evaluated for acute onset of blepharospasm, and a 7-year-old Miniature Schnauzer with chronic immune-mediated thrombocytopenia was reevaluated for keratoconjunctivitis sicca that had been diagnosed 4 weeks earlier. Dendritic corneal ulcerations were detected in both dogs. Canine herpesvirus-1 (CHV-1) was isolated from corneal swab specimens obtained during the initial evaluation of each dog and during recheck examinations performed until the ulcerations were healed. Canine herpesvirus-1 serum neutralization titers were detected in both dogs. Results of virus isolation from oropharyngeal and genital swab specimens were negative for both dogs. The isolated viruses were identified as CHV-1 via immunofluorescence, transmission electron microscopy, PCR assay, and gene sequencing. Negative controls for PCR assay and virus isolation included conjunctival swab specimens from 50 dogs without extraocular disease and corneal swab specimens from 50 dogs with corneal ulcers, respectively. Lesions resolved in both dogs after topical administration of idoxuridine or trifluridine and discontinuation of topically administered immunosuppressive medications. To the authors' knowledge, this is the first report of corneal ulcerations associated with naturally occurring CHV-1 infection and may represent local ocular recrudescence of latent CHV-1 infection. The viruses isolated were identified as CHV-1, and the morphology, antigenicity, and genotype were similar to those for CHV-1 isolates obtained from a puppy that died from systemic CHV-1 infection.


Continuous microwave-assisted isoflavone extraction system: design and performance evaluation.
The purpose of this research was to design, test, and optimize a continuous microwave extraction method using temperature and residence time during and after microwave exposure as optimizing parameters for extraction of major isoflavones (genistin, genistein, daidzin, and daidzein) from soy flour. The extraction yield of four isoflavones at different heating temperatures (55 and 73 degrees C) and extraction times (0, 4, 8, 12, and 16 min) were investigated and compared with yields provided by a conventional solvent extraction method. The microwave prototype consisted of multiple, commercially available, batch-type, house-hold microwave units placed on top of each other in series to impart a continuous operation. The optimum parameters for microwave-assisted extraction of isoflavones were 73 degrees C for 8 min using a 3:1 ethanol-to soy flour ratio. At these parameters, the total yield of isoflavones extracted doubled, while the amount of oil extracted was 12%. Continuous microwave-assisted solvent extraction is a viable method for extraction of soybean isoflavones at relatively short residence times and high throughput.


A Comparison between the Perturbed-Chain Statistical Associating Fluid Theory Equation of State and Machine Learning Modeling Approaches in Asphaltene Onset Pressure and Bubble Point Pressure Prediction during Gas Injection.
Predicting asphaltene onset pressure (AOP) and bubble point pressure (Pb) is essential for optimization of gas injection for enhanced oil recovery. Pressure-Volume-Temperature or PVT studies along with equations of state (EoSs) are widely used to predict AOP and Pb. However, PVT experiments are costly and time-consuming. The perturbed-chain statistical associating fluid theory or PC-SAFT is a sophisticated EoS used for prediction of the AOP and Pb. However, this method is computationally complex and has high data requirements. Hence, developing precise and reliable smart models for prediction of the AOP and Pb is inevitable. In this paper, we used machine learning (ML) methods to develop predictive tools for the estimation of the AOP and Pb using experimental data (AOP data set: 170 samples; Pb data set: 146 samples). Extra trees (ET), support vector machine (SVM), decision tree, and k-nearest neighbors ML methods were used. Reservoir temperature, reservoir pressure, SARA fraction, API gravity, gas-oil ratio, fluid molecular weight, monophasic composition, and composition of gas injection are considered as input data. The ET (R 2: 0.793, RMSE: 7.5) and the SVM models (R 2: 0.988, RMSE: 0.76) attained more reliable results for estimation of the AOP and Pb, respectively. Generally, the accuracy of the PC-SAFT model is higher than that of the AI/ML models. However, our results confirm that the AI/ML approach is an acceptable alternative for the PC-SAFT model when we face lack of data and/or complex mathematical equations. The developed smart models are accurate and fast and produce reliable results with lower data requirements.


Evidence from cancer intervention and biomarker studies and the development of biochemical markers.
Evidence from intervention trials with vitamins E and C and beta-carotene are reviewed as well as evidence from trials that have used intermediate endpoints with a special emphasis on biomarkers of cancer of the colorectum. The methodologic issues that require resolution before a second generation of clinical trials are launched to assess the efficacy of these antioxidants in the prevention of cancer are identified. Specific concerns regarding the validation of pathologic biomarkers of cancer and biochemical markers of mechanism of action for the antioxidants are discussed. Cellular proliferation indexes in the colon are used as an example of pathologic biomarkers for cancer and the measurement of plasma and tissue malondialdehyde concentrations is used as an example of problems with the development of biochemical markers of oxidative stress that can be used in prevention trials. The use of DNA oxidation products as promising biomarkers is also discussed.


Efficient introduction of plasmid DNA into Trypanosoma brucei and transcription of a transfected chimeric gene.
Electroporation induces efficient transient transfection of Trypanosoma brucei, and the introduced DNA can be transcribed into RNA. When we delivered a high-voltage electric pulse to cells mixed with radiolabeled pBR322, approximately equal to 15% of the plasmid DNA was taken up by the parasites. When transfecting DNA contained a segment of T. brucei ribosomal DNA that included the 5' end of the rRNA gene, the introduced plasmid directed expression of RNA; this RNA expression was shown both by dot blots and by S1 nuclease protection assays carried out under conditions specific for probe hybridization to RNA. In the absence of the ribosomal region, analogous transcription did not occur. We optimized this trypanosomal expression system with regard to electric shock strength, concentration of input DNA, and incubation time after electric shock. This technique enabling specific trypanosome DNA expression in vivo should facilitate the molecular analysis of T. brucei gene expression.


Drug-Drug Interactions With Cyclosporine in the Anti-Hepatitis C Viral PrOD Combination Regimen of Paritaprevir/Ritonavir-Ombitasvir and Dasabuvir in Organ Transplant Recipients With Severe Hepatic Fibrosis or Cirrhosis.
The clinical guidelines suggest that the dosing of cyclosporine (CsA), during combination therapy with paritaprevir/ritonavir-ombitasvir and dasabuvir (PrOD), would be only one-fifth of the pre-PrOD total daily dose to be administered once daily. However, this dosing may not be applicable to all patients depending on their clinical condition. This study focuses on the pharmacokinetic dynamics of PrOD with CsA in Asian organ transplant recipients with severe liver fibrosis or cirrhosis who undergo concurrent treatment with PrOD treatment and CsA. The efficacy and safety of PrOD treatment was also evaluated. Data from 7 patients obtained between January 2017 and September 2017 were retrospectively analyzed. Determinations of the blood concentrations of CsA were made, whether used as a single treatment or in combination therapy with PrOD. The combination regimen compared with CsA administered alone resulted in a 4.53-fold and 5.52-fold increase in the area under the concentration-time curve from time 0-12 hours (AUC0-12 h) of CsA on days 1 and 15, respectively. In addition, the maximal concentration, time to maximum concentration, and terminal phase elimination half-life (t1/2) of CsA were increased during the combined treatment of PrOD and CsA. The authors proposed reducing the CsA dosage during PrOD treatment to one-seventh of that of the pre-PrOD treatment of the total daily dose to maintain target CsA levels. All patients achieved sustained virologic responses at week 12. There were no episodes of serious adverse events or graft rejections observed. Although the combination with PrOD significantly affects the pharmacokinetics of CsA, it is effective and safe with regular monitoring of the CsA blood concentrations and appropriate CsA dose adjustment.


[Pharmacology and classification of cyclooxygenase inhibitors].
The discovery of at least two cyclooxygenase (COX) isoenzymes had two major consequences: i) to give a new impetus to the research on lipid metabolism, giving rise to the crystallization of these peculiar membrane enzymes, the characterization of their active sites and their gene regulation, and the identification of new metabolic pathways; ii) the development of new NSAIDs aimed to have an improved safety profile, the coxibs. These drugs are defined by their COX-2 selectivity which is supported by a negligible inhibitory potency on platelet COX-1 in vitro and ex vivo after oral intake of maximal therapeutic doses. However, the coxibs marketed in France (celecoxib, rofecoxib, parecoxib) are not equivalent in terms of selectivity and some drugs developed by pharmaceutical companies (etoricoxib, lumiracoxib) will be even more selective for COX-2. These "new" coxibs are the final step in the theory of COX-2 selectivity and they will probably be helpful to better define the limitations of the therapeutic concept based on a selective inhibition of this iso-enzyme.


[Risk of overtreatment: not to be neglected. The example of antiepileptic drugs].
Overtreatment (unnecessary treatment, excessive drug dosages, unjustified polypharmacy) alters the risk-benefit ratio. Its prevention requires the recognition of the situations and the understanding of the mechanisms leading to it. The pharmacological treatment of epilepsy exposes to such a risk and serves as an example for its detection and correction.


Reciprocal inhibition and corticospinal transmission in the arm and leg in patients with autosomal dominant pure spastic paraparesis (ADPSP).
The pathophysiological mechanisms underlying the development of spasticity are not clear, but the excitability of the disynaptic reciprocal inhibitory pathway is affected in many patients with spasticity of different origin. Patients with genetically identified autosomal dominant pure spastic paraparesis (ADPSP) develop spasticity and paresis in the legs, but usually have no symptoms in the arms. Comparison of the spinal and supraspinal control of the legs and arms in these patients may therefore provide valuable information about the pathophysiology of spasticity. In the present study, we tested the hypothesis that one of the pathophysiological mechanisms of spasticity in these patients is abnormal corticospinal transmission and that this may lead to decreased reciprocal inhibition. Ten patients and 15 healthy age-matched control subjects were investigated. The patients were all spastic in the legs (with hyperactive tendon reflexes, increased muscle tone and Babinski sign), but had no neurological symptoms in the arms (except for one patient). Disynaptic reciprocal Ia inhibition of flexor carpi radialis (FCR) and soleus (SOL) motoneurons was measured (as the depression of the background FCR and SOL EMG activity and as the short latency inhibition of the FCR and SOL H-reflex evoked by radial and peroneal nerve stimulation). In addition, the latency of motor evoked potentials (MEPs) in the FCR muscle and the tibialis anterior (TA) muscle was measured. In the patients, the mean reciprocal inhibition was normal in the arms, while it was significantly decreased in the leg compared with the healthy subjects. In the patients, the average latency of MEPs in the FCR muscle was normal, while the latency to the MEP in TA muscle was significantly longer than that found in healthy subjects. Four patients, however, differed from the other patients by having significant reciprocal inhibition in the leg and a significantly shorter latency of TA MEPs than found in the other patients. The six patients without reciprocal inhibition in the leg instead had significant short latency facilitation of the SOL H-reflex and a longer TA MEP latency than seen in the healthy subjects and in the four patients with retained reciprocal inhibition. These findings support the hypothesis that disynaptic reciprocal inhibition and short latency facilitation are involved in the development of spasticity and, furthermore, they suggest a positive correlation between impairment of corticospinal transmission and decrease of reciprocal inhibition/appearance of reciprocal facilitation.


Salivary IL-17A, IL-17F, and TNF-α Are Associated with Disease Advancement in Patients with Oral and Oropharyngeal Cancer.
Delayed diagnosis of oral cavity and oropharyngeal cancer is associated with a poor prognosis. Despite progress in systemic therapy and radiotherapy, there has only been a slight improvement in the five-year survival rate. A non-invasive diagnostic method that consists of an assessment of specific proteins in saliva samples may significantly facilitate assessment of treatment results in patients diagnosed with oral and oropharyngeal cancer. The aim of this study was to assess the levels of IL-17 and TNF-α in the saliva of patients with oral and oropharyngeal cancer. The study was conducted prior to treatment in patients hospitalized in the Frederic Chopin Provincial Specialist Hospital No. 1 in Rzeszów, Poland. Saliva samples were collected from subjects on an empty stomach. Cytokine concentrations in the saliva were measured with ELISA and Luminex Multiplex Assays. The higher salivary concentrations of IL-17A, IL-17F, and TNF-α were significantly associated with disease advancement. Lower levels of IL-17A were associated with colonization of the oral cavity with aerobic bacteria. On the other hand, higher concentration of TNF-α was observed in patients with positive aerobic culture of oral swabs. Our results suggest that IL-17A, IL-17F, and TNF-α measured in the saliva may be a potential biomarker for cancer of the oral cavity and oropharynx.


Microgravity induces pelvic bone loss through osteoclastic activity, osteocytic osteolysis, and osteoblastic cell cycle inhibition by CDKN1a/p21.
Bone is a dynamically remodeled tissue that requires gravity-mediated mechanical stimulation for maintenance of mineral content and structure. Homeostasis in bone occurs through a balance in the activities and signaling of osteoclasts, osteoblasts, and osteocytes, as well as proliferation and differentiation of their stem cell progenitors. Microgravity and unloading are known to cause osteoclast-mediated bone resorption; however, we hypothesize that osteocytic osteolysis, and cell cycle arrest during osteogenesis may also contribute to bone loss in space. To test this possibility, we exposed 16-week-old female C57BL/6J mice (n = 8) to microgravity for 15-days on the STS-131 space shuttle mission. Analysis of the pelvis by µCT shows decreases in bone volume fraction (BV/TV) of 6.29%, and bone thickness of 11.91%. TRAP-positive osteoclast-covered trabecular bone surfaces also increased in microgravity by 170% (p = 0.004), indicating osteoclastic bone degeneration. High-resolution X-ray nanoCT studies revealed signs of lacunar osteolysis, including increases in cross-sectional area (+17%, p = 0.022), perimeter (+14%, p = 0.008), and canalicular diameter (+6%, p = 0.037). Expression of matrix metalloproteinases (MMP) 1, 3, and 10 in bone, as measured by RT-qPCR, was also up-regulated in microgravity (+12.94, +2.98 and +16.85 fold respectively, p<0.01), with MMP10 localized to osteocytes, and consistent with induction of osteocytic osteolysis. Furthermore, expression of CDKN1a/p21 in bone increased 3.31 fold (p<0.01), and was localized to osteoblasts, possibly inhibiting the cell cycle during tissue regeneration as well as conferring apoptosis resistance to these cells. Finally the apoptosis inducer Trp53 was down-regulated by -1.54 fold (p<0.01), possibly associated with the quiescent survival-promoting function of CDKN1a/p21. In conclusion, our findings identify the pelvic and femoral region of the mouse skeleton as an active site of rapid bone loss in microgravity, and indicate that this loss is not limited to osteoclastic degradation. Therefore, this study offers new evidence for microgravity-induced osteocytic osteolysis, and CDKN1a/p21-mediated osteogenic cell cycle arrest.


A healthy lifestyle index is associated with reduced risk of colorectal adenomatous polyps among non-users of non-steroidal anti-inflammatory drugs.
In a Columbia, South Carolina-based case-control study, we developed a healthy lifestyle index from five modifiable lifestyle factors (smoking, alcohol intake, physical activity, diet, and body mass index), and examined the association between this lifestyle index and the risk of colorectal adenomatous polyps (adenoma). Participants were recruited from a local endoscopy center and completed questionnaires related to lifestyle behaviors prior to colonoscopy. We scored responses on each of five lifestyle factors as unhealthy (0 point) or healthy (1 point) based on current evidence and recommendations. We added the five scores to produce a combined lifestyle index for each participant ranging from 0 (least healthy) to 5 (healthiest), which was dichotomized into unhealthy (0-2) and healthy (3-5) lifestyle scores. We used logistic regression to calculate odds ratios (OR) and 95% confidence intervals (CI) for adenoma with adjustment for multiple covariates. We identified 47 adenoma cases and 91 controls. In the main analyses, there was a statistically nonsignificant inverse association between the dichotomous (OR 0.54; 95% CI 0.22, 1.29) and continuous (OR 0.75; 95% CI 0.51, 1.10) lifestyle index and adenoma. Odds of adenoma were significantly modified by the use of non-steroidal anti-inflammatory drugs (NSAIDs) (p(interaction) = 0.04). For participants who reported no use of NSAIDs, those in the healthy lifestyle category had a 72% lower odds of adenoma as compared to those in the unhealthy category (OR 0.28; 95% CI 0.08, 0.98), whereas a one-unit increase in the index significantly reduced odds of adenoma by 53% (OR 0.47; 95% CI 0.26, 0.88). Although these findings should be interpreted cautiously given our small sample size, our results suggest that higher scores from this index are associated with reduced odds of adenomas, especially in non-users of NSAIDs. Lifestyle interventions are required to test this approach as a strategy to prevent colorectal adenomatous polyps.


Spectral radiance of the carbon arc between 2500 a and 1900 a.
The absolute intensity of the carbon arc in the region from 2500 A to 1900 A was measured by comparing it with the intensity of a mercury high-pressure lamp (UV Standard) and a deuterium discharge lamp, both of which had been calibrated before by means of the synchrotron radiation. The intensity of the carbon arc was found to be considerably higher than given in earlier papers. The rms error of the results is less than 10%.


Adamantane in Drug Delivery Systems and Surface Recognition.
The adamantane moiety is widely applied in design and synthesis of new drug delivery systems and in surface recognition studies. This review focuses on liposomes, cyclodextrins, and dendrimers based on or incorporating adamantane derivatives. Our recent concept of adamantane as an anchor in the lipid bilayer of liposomes has promising applications in the field of targeted drug delivery and surface recognition. The results reported here encourage the development of novel adamantane-based structures and self-assembled supramolecular systems for basic chemical investigations as well as for biomedical application.


Analysis of Bacterial Communities in White Clover Seeds via High-Throughput Sequencing of 16S rRNA Gene.
White clover widely cultivated in China is one of the most important perennial leguminous forages in temperate and subtropical regions. There is a large quantity of white clover seeds imported into China each year for demands of high-quality grass seeds. Seedborne diseases may cause significant economic losses. DNA sequencing technologies allow for the direct estimation of microbial community diversity, avoiding culture-based biases. Therefore, we used 16S rRNA gene sequencing to investigate the bacterial communities in white clover seeds collected from four different countries. The results showed that a total of 484,715 clean reads were obtained for further subsequent analysis. In total, 341, 340, 382, and 297 operational taxonomic units were obtained at 3% distance cutoff in DB, MB, TB, and XB samples, respectively. The richness indexes revealed that TB sample from Argentina had the highest bacterial richness in four samples. Our results demonstrated that Proteobacteria was the dominant phyla in MB, TB, and XB; however, Bacteroidetes was the dominant phyla in DB. The dominant genus of DB was Prevotella (11.9%), while Sphingomonas was the major genus of MB (46.9%), TB (55.08%), and XB (47.2%) samples. These results provide useful information for seedborne diseases and transmission of bacteria from seed to seedling.


Crestal bone loss around submerged and non-submerged implants during the osseointegration phase with different healing abutment designs: a randomized prospective clinical study.
To evaluate peri-implant crestal bone loss during the osseointegration period, comparing submerged and non-submerged implants with healing abutments of different design. A total of 90 Avinent® dental implants (Avinent Implant System, Barcelona, Spain) were placed in 90 patients. All were sited in the posterior mandibular zone to replace teeth 3.6 or 4.6. Patients were divided randomly into three groups: submerged (n = 30), non-submerged with anatomical healing abutment (n = 30), and non-submerged with esthetic healing abutment (n = 30). Peri-implant crestal bone loss was evaluated in intraoral radiographs taken at baseline, 1, and 3 months after implant placement. Peri-implant crestal bone loss at the end of the (3-month) osseointegration period was lowest in the submerged group (0.11 ± 0.14 mm), followed by the esthetic non-submerged group (0.15 ± 0.06 mm), but without statistically significant difference between these groups (P = 0.234). The greatest bone loss was produced in the non-submerged group with anatomical healing abutments (0.37 ± 0.12 mm), with significant differences between this group and the other two (P < 0.001). On the basis of these findings, bone resorption during the osseointegration period using the non-submerged technique varied significantly depending on the morphology of the healing abutment used. The non-submerged technique with an esthetic healing post-produced an equally predictable outcome compared with the submerged technique.


Experimental and Numerical Study on Interface Bond Strength and Anchorage Performance of Steel Bars within Prefabricated Concrete.
This study investigates the interface bond strength and anchorage performance of steel bars within prefabricated concrete. Twenty-two specimens were designed and manufactured to study the interface bond behavior of deformed and plain steel bars under a larger cover thickness. Diameter of steel bars, strength grade of concrete, and anchorage length were considered influential factors. The finite element method (ABAQUS) was used for the validation of experimental results. The interface bond's failure mechanism and the anchorage length in the prefabricated concrete under different concrete strength levels were explored and compared to national and international codes. A suitable value of the basic anchoring length for the prefabricated structure was recommended. The results show that the interface bond strength of prefabricated bridge members is directly proportional to the strength grade of the concrete, inversely proportional to the reinforcement diameter, and less related to anchorage length. The effect of the cover thickness of the surrounding concrete is negligible. Conversely, the bearing capacity of prefabricated bridge members depends on the strength of the concrete, the diameter of the steel bar, and the anchorage length. Furthermore, it is concluded that the mechanical bond strength accounts for 88% of the bond strength within prefabricated concrete.


Relationship between perceived body weight and body mass index based on self- reported height and weight among university students: a cross-sectional study in seven European countries.
Despite low rates of obesity, many university students perceive themselves as overweight, especially women. This is of concern, because inappropriate weight perceptions can lead to unhealthy behaviours including eating disorders. We used the database from the Cross National Student Health Survey (CNSHS), consisting of 5,900 records of university students from Bulgaria, Denmark, Germany, Lithuania, Poland, Spain and Turkey to analyse differences in perceived weight status based on the question: "Do you consider yourself much too thin, a little too thin, just right, a little too fat or much too fat?". The association between perceived weight and body mass index (BMI) calculated from self-reported weight and height was assessed with generalized non-parametric regression in R library gam. Although the majority of students reported a normal BMI (72-84% of males, 65-83% of females), only 32% to 68% of students considered their weight "just right". Around 20% of females with BMI of 20 kg/m2 considered themselves "a little too fat" or "too fat", and the percentages increased to 60% for a BMI of 22.5 kg/m2. Male students rarely felt "a little too fat" or "too fat" below BMI of 22.5 kg/m2, but most felt too thin with a BMI of 20 kg/m2. Weight ideals are rather uniform across the European countries, with female students being more likely to perceive themselves as "too fat" at a normal BMI, while male students being more likely to perceive themselves as "too thin". Programs to prevent unhealthy behaviours to achieve ill-advised weight ideals may benefit students.


[Evaluation problems of anti-natalist policies].
"This study is a brief overview of the main problems hindering the measurement of the impact of family planning programmes on fertility. A brief description of several evaluation methods commonly resorted to is presented. A number of theoretical, conceptual and methodological difficulties pertaining to these methods are then scrutinized. Special attention is devoted to various concepts of potential fertility and...their effect on the measurement of the demographic impact of a programme. Likewise, problems encountered in attempts to disentangle the effect of programme factors from the effects of social change on fertility are also examined. The reliability of the results obtained with these methods is affected by these problems, but these results remain, despite some weaknesses, useful approximations of the demographic impact of anti-natalist population policies." The primary geographical focus is on developing countries. (SUMMARY IN ENG)


[Occupational health risk assessment for organic solvent in the major posts of printing industry].
Objective: To evaluate the occupational health risk of organic solvents in major posts of printing industry, and to provide technical reference to take targeted risk control measures. Methods: In January 2021, the contact ratio method was used to assess the occupational health risk of organic solvents in the major posts of 84 printing enterprises in Shantou, and Monte Carto method was used to estimate the probability distribution of risk levels in the majorpostsin January 2021. Results: The highest probability of risk assessment in printing and membranecovering post is Level 4 (high risk) , which are 76.2% and 67.6% respectively; the highest probability of simulation evaluation result in oil blending, dispensing and cleaning post is Level 3 (medium risk) ; and the simulation evaluation result in glueing post are mostly Level 3 (medium risk) and Level 4 (high risk) , the probability of which are 45.7% and 54.3% respectively. Conclusion: The occupational health risk of organic solvents in the major posts is generally middle-high risk level, and then the occupational health risk control of organic solvents in major posts of printing industry should be strengthened.


Comparison of iliofemoral and femorofemoral crossover bypass in the treatment of unilateral iliac arterial occlusive disease.
Between 1981 and 1988, 74 synthetic crossover bypass grafts were inserted for unilateral iliac arterial occlusive disease. In 32 patients the bypass procedure was iliofemoral and in 42 femorofemoral. The cumulative patency rate at a mean of 2.7 years was 79 per cent in both groups. There was no significant difference in either postoperative mortality rate or duration of hospital stay. Iliofemoral bypass may offer significant advantages over the femorofemoral approach. In particular it avoids a groin incision in the donor limb, leaving the common femoral artery intact for subsequent angioplasty or reconstruction should proximal stenotic disease develop in the donor iliac vessel.


Oral lactoferrin administration does not impact the diversity or composition of the infant gut microbiota in a Peruvian cohort.
Previous studies have suggested that oral lactoferrin enhances diversity in the gut microbiota in infants while inhibiting the growth of opportunistic pathogens. However, the effect of lactoferrin on infant gut microbiota over time has yet to be thoroughly studied. Our study suggests that lactoferrin oral treatment in infants aged 12-18 months does not affect gut microbiome diversity and composition over time. To our knowledge, this is the first study to report the effect of lactoferrin on infant gut microbiome composition over time and helps elucidate its impact on infant health and its therapeutic potential.


[Tumor lysis syndrome after the administration of corticosteroids in an adolescent without confirmed neoplastic disease. Case Reports].
Tumor lysis syndrome is a potentially lethal complication and constitutes with infections the most frequent oncological emergency. In children, this condition can be secondary to neoplastic diseases, with corticosteroids being a triggering factor. This paper presents the case of an adolescent patient, without known or obvious neoplasms, who developed a tumor lysis syndrome after the administration of corticosteroids due to suspected respiratory infection. The clinical presentation and differential diagnoses are discussed. Special focus is placed on the administration of corticosteroids in clinical conditions with weak scientific evidence. The use of systemic corticosteroids in acute respiratory infections should be evaluated in the clinical context and only indicated in situations with proven effectiveness.


Psychosocial aspects of antepartum hospitalization.
High-risk pregnant women who undergo antepartum hospitalization experience significant stress. Nurses play an important role in helping these pregnant women adapt to their high-risk status and cope effectively with hospitalization. This article identifies the stressors imposed by antepartum hospitalization and discusses nursing interventions to reduce the impact of those stressors.


Low rate of venous thromboembolism after craniotomy for brain tumor using multimodality prophylaxis.
Venous thromboembolism (VTE) is the most frequent complication following craniotomy for brain tumors. At Brigham and Women's Hospital, VTE after craniotomy for brain tumor is the leading cause of deep vein thrombosis (DVT) and pulmonary embolism (PE) among patients hospitalized for conditions other than VTE. To minimize VTE among patients undergoing craniotomy for brain tumor. Randomized, prospective, double-blind clinical trial. Brigham and Women's Hospital. One hundred fifty patients undergoing craniotomy for brain tumor randomized to enoxaparin, 40 mg/d, vs heparin, 5,000 U bid, with all patients receiving graduated compression stockings and intermittent pneumatic compression. The rate of DVT detected by venous ultrasonography prior to hospital discharge. Symptomatic DVT or PE developed in none of the patients. The overall rate of asymptomatic VTE was 9.3%, with no significant difference in the rates between the two prophylaxis groups. Ten of the 14 patients identified with VTE had thrombus limited to the deep veins of the calf. Enoxaparin, 40 mg/d, or unfractionated heparin, 5,000 U bid, in combination with graduated compression stockings, intermittent pneumatic compression, and predischarge surveillance venous ultrasonography of the legs, resulted in 150 consecutive patients without symptomatic VTE. The low 9.3% frequency of asymptomatic VTE comprised mostly isolated calf DVT. Therefore, this comprehensive, multimodality approach to VTE prophylaxis achieved excellent efficacy and safety.


Human Genetic Host Factors and Its Role in the Pathogenesis of Chikungunya Virus Infection.
Chikungunya virus (CHIKV) is an alphavirus from the Togaviridae family that causes acute arthropathy in humans. It is an arthropod-borne virus transmitted initially by the Aedes (Ae) aegypti and after 2006's epidemic in La Reunion by Ae albopictus due to an adaptive mutation of alanine for valine in the position 226 of the E1 glycoprotein genome (A226V). The first isolated cases of CHIKV were reported in Tanzania, however since its arrival to the Western Hemisphere in 2013, the infection became a pandemic. After a mosquito bite from an infected viremic patient the virus replicates eliciting viremia, fever, rash, myalgia, arthralgia, and arthritis. After the acute phase, CHIKV infection can progress to a chronic stage where rheumatic symptoms can last for several months to years. Although there is a great number of studies on the pathogenesis of CHIKV infection not only in humans but also in animal models, there still gaps in the proper understanding of the disease. To this date, it is unknown why a percentage of patients do not develop clinical symptoms despite having been exposed to the virus and developing an adaptive immune response. Also, controversy stills exist on the pathogenesis of chronic joint symptoms. It is known that host immune response to an infectious disease is reflected on patient's symptoms. At the same time, it is now well-established that host genetic variation is an important component of the varied onset, severity, and outcome of infectious disease. It is essential to understand the interaction between the aetiological agent and the host to know the chronic sequelae of the disease. The present review summarizes the current findings on human host genetics and its relationship with immune response in CHIKV infection.


Urinary tract infection in patients with chronic kidney disease under conservative treatment.
to assess the prevalence and associated risk factors for urinary tract infection in patients with chronic kidney disease under conservative treatment and identify the microorganisms isolated in the urine of these patients and the staging of chronic kidney disease. a cross-sectional, analytical study carried out at the Conservative Treatment Outpatient Clinic of a university hospital in the city of São Paulo. the prevalence of urinary tract infection is 22%. The risk factors Diabetes Mellitus, hypertension, heart disease, neoplasms and thyroid and autoimmune diseases stand out in the infected group (p < 0.001). Most of the microorganisms found in urine cultures (87.9%) were Gram-negative, being Escherichia coli (50.70%), followed by Klebsiella pneumoniae (23.1%) and Enterococcus spp. (9.7%). the findings of this investigation reveal the intrinsic association between risk factors and microorganisms for the development of urinary tract infection.


Pseudomorphy, surface alloys and the role of elementary clusters on the domain orientations in the Cu/Al13Co4(100) system.
We have used the pseudo-tenfold surface of the orthorhombic Al(13)Co(4) crystal as a template for the adsorption of Cu thin films of various thicknesses deposited at different temperatures. This study has been carried out by means of low energy electron diffraction (LEED), scanning tunnelling microscopy (STM), x-ray photoelectron spectroscopy (XPS) and x-ray photoelectron diffraction (XPD). From 300 to 573 K, Cu adatoms grow pseudomorphically up to one monolayer. At 300 K, the β-Al(Cu, Co) phase appears for coverages greater than one monolayer. For higher temperature deposition, the β-Al(Cu, Co) phase further transforms into the γ-Al(4)Cu(9) phase. Both β and γ phases grow as two (110) domains rotated by 72° ± 1° from each other. Instead of following the substrate symmetry, it is the orientations of the bipentagonal motifs present on the clean Al(13)Co(4)(100) surface that dictate the growth orientation of these domains. The initial bulk composition and structural complexity of the substrate have a minor role in the formation of the γ-Al(4)Cu(9) phase as long as the amount of Al and the Cu film thickness reach a critical stoichiometry.


Re-Evaluation of the Taxonomy of Talaromyces minioluteus.
Talaromyces minioluteus belongs to the section Trachyspermi, has a worldwide distribution and has been found on various substrates, especially on various (stored) food commodities and indoor environments. This species is phenotypically and phylogenetically closely related to T. chongqingensis and T. minnesotensis. The phylogenetic and morphological analyses of 37 strains previously identified as T. chongqingensis, T. minnesotensis and T. minioluteus revealed that this clade incudes eight species: the accepted species T. chongqingensis, T. minnesotensis and T. minioluteus, the newly proposed species T. calidominioluteus, T. africanus and T. germanicus, and the new combinations T. gaditanus (basionym Penicillium gaditanum) and T. samsonii (basionym Penicillium samsonii). In this study, we give insight of the phylogenetic relationships and provide detailed descriptions of the species belonging to this clade. Macromorphological features, especially colony growth rates, texture and conidial colors on agar media, are important characters for phenotypic differentiation between species.


Outcome of gastric cancer surgery in elderly patients.
The aim of the study was to review cases of gastric cancers in elderly adults (70 years of age and older), and compare demographic, clinical, pathologic features and outcomes of surgical treatment with younger patients (below 70 years of age). The analysis included 3431 patients treated for gastric cancer between 1977 and 1998 at eight university surgical centers cooperating for the Polish Gastric Cancer Study Group (PGCSG). Patients were analyzed retrospectively according to data obtained from standardized forms and divided into two groups: group I--patients 70 years of age and over, group II--younger patients. There were no significant differences between these two groups in clinical symptoms at the time of diagnosis and tumor advancement. The incidence of the intestinal type according to Lauren (55.9% vs. 43.9%;p<0.05) and distally-located cancers (40.8% vs. 31.3%; p<0.05) was higher in group I. Total gastrectomies and extended lymph node dissection were performed more often in younger patients. There were no significant differences in postoperative complications between both groups, except the higher incidence of abdominal abscesses in the younger group. The overall 5-year survival was 24% and 35% for group I and II, respectively (p<0.05), and increased to 35% and 53% after radical resections, respectively. However, there were no statistically significant differences in stage-specific survival between both groups. Surgical resection is the method of choice in the treatment of gastric cancer. Age of the patients is not a contraindication to surgical treatment of gastric cancer.


Variation of HMGB1 expression in breast cancer.
The amount of steroid hormone receptor proteins does not always correlate with the response of breast cancers to endocrine therapy. This may partly be due to the fact that binding of the estrogen receptor (ER) to estrogen responsive elements (ERE) of its target genes is mediated by additional cellular proteins. One of these is the high mobility group protein HMGB1, known to interact with ER thus dramatically increasing its binding to ERE. This is the first report analysing the expression patterns of HMGB1 in breast cancer cells. Northern blot analyses of the 1.4 kb and the 2.4 kb transcripts of HMGB1 in 13 breast cancer samples revealed a strong intertumoural variation by a factor of 8.5 and 14.5, respectively. This variation may contribute to the different response, of estrogen receptor-positive breast tumours to endocrine therapy, making HMGB1 a marker of considerable clinical interest.


Impact of spinal Anaesthesia versus general Anaesthesia on the incidence of surgical site infections after knee or hip arthroplasty: A meta-analysis.
Postoperative Surgical Site Infections (SSIs) pose significant challenges to recovery after joint arthroplasty. This systematic review and meta-analysis aim to compare the incidence of SSIs after knee or hip arthroplasty under Spinal Anaesthesia (SA) versus general anaesthesia (GA). We conducted the systematic review and meta-analysis following the PRISMA guidelines, analysing data from 15 studies selected from PubMed, Embase, Web of Science, and Cochrane Library up to May 16, 2023. The analysis included studies comparing SSIs incidence in patients aged 18 years and above who underwent knee or hip arthroplasty under SA or GA. Quality assessment was performed using the Cochrane Collaboration's risk of bias tool. The effect size was calculated using random or fixed-effects models based on the observed heterogeneity. We assessed the heterogeneity between studies and conducted a sensitivity analysis. Of 1651 initially identified studies, 15 articles encompassing 353 169 patients were included in the final analysis. A total of 156 405 patients were under SA, while 196 764 received GA. The studies demonstrated substantial heterogeneity (p = 0.007, I2 = 53.7%), resulting in a random-effects model being employed. Patients receiving SA showed a 23% lower likelihood of developing SSIs postoperatively compared to GA patients (OR: 0.77, 95% CI: 0.70-0.86, p < 0.001). Sub-group analysis further confirmed these findings regardless of the type of joint arthroplasty. This meta-analysis indicated a significantly lower incidence of SSIs following knee or hip arthroplasty under SA compared to GA. Despite observed heterogeneity, the results underscore the potential benefit of SA over GA in orthopaedic surgeries to reduce the risk of SSIs.


Building Extraction Based on an Optimized Stacked Sparse Autoencoder of Structure and Training Samples Using LIDAR DSM and Optical Images.
In this paper, a building extraction method is proposed based on a stacked sparse autoencoder with an optimized structure and training samples. Building extraction plays an important role in urban construction and planning. However, some negative effects will reduce the accuracy of extraction, such as exceeding resolution, bad correction and terrain influence. Data collected by multiple sensors, as light detection and ranging (LIDAR), optical sensor etc., are used to improve the extraction. Using digital surface model (DSM) obtained from LIDAR data and optical images, traditional method can improve the extraction effect to a certain extent, but there are some defects in feature extraction. Since stacked sparse autoencoder (SSAE) neural network can learn the essential characteristics of the data in depth, SSAE was employed to extract buildings from the combined DSM data and optical image. A better setting strategy of SSAE network structure is given, and an idea of setting the number and proportion of training samples for better training of SSAE was presented. The optical data and DSM were combined as input of the optimized SSAE, and after training by an optimized samples, the appropriate network structure can extract buildings with great accuracy and has good robustness.


Directing Differentiation of Pluripotent Stem Cells Toward Retinal Pigment Epithelium Lineage.
Development of efficient and reproducible conditions for directed differentiation of pluripotent stem cells into specific cell types is important not only to understand early human development but also to enable more practical applications, such as in vitro disease modeling, drug discovery, and cell therapies. The differentiation of stem cells to retinal pigment epithelium (RPE) in particular holds promise as a source of cells for therapeutic replacement in age-related macular degeneration. Here we show development of an efficient method for deriving homogeneous RPE populations in a period of 45 days using an adherent, monolayer system and defined xeno-free media and matrices. The method utilizes sequential inhibition and activation of the Activin and bone morphogenetic protein signaling pathways and can be applied to both human embryonic stem cells and induced pluripotent stem cells as the starting population. In addition, we use whole genome transcript analysis to characterize cells at different stages of differentiation that provides further understanding of the developmental dynamics and fate specification of RPE. We show that with the described method, RPE develop through stages consistent with their formation during embryonic development. This characterization- together with the absence of steps involving embryoid bodies, three-dimensional culture, or manual dissections, which are common features of other protocols-makes this process very attractive for use in research as well as for clinical applications. Stem Cells Translational Medicine 2017;6:490-501.


Transcriptional regulation of the human establishment of cohesion 1 homolog 2 gene.
Transcriptional regulation of human establishment of cohesion 1 homolog 2 (ESCO2), the causative gene of Roberts syndrome, was investigated. Deletion and mutation analyses of the ESCO2 promoter indicated that the selenocysteine tRNA-activating factor (Staf) binding site (SBS) is an essential element for transcriptional activation of ESCO2. Electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (ChIP) assay revealed that the zinc finger protein 143 (ZNF143), a human homolog of Xenopus Staf, bound to the ESCO2 promoter. The ACTACAN submotif, adjacent to SBS, also contributed to transcriptional activation of ESCO2. EMSA indicated that the ACTACAN submotif was not involved in binding of ZNF143 to SBS. S phase-specific expression of the ESCO2 gene was confirmed by real-time reverse transcriptase-polymerase chain reaction (RT-PCR), but EMSA revealed binding of ZNF143 to SBS in G1/S and G2/M phases. These results demonstrated that SBS functioned as the basal transcriptional activator of the S phase-specific gene ESCO2, but other mechanisms are required for cell cycle-dependent expression.


Preparation of multiparticulate vaginal tablet using glyceryl monooleate for sustained progesterone delivery.
Most of the sustained release vaginal formulations are in the form of bioadhesive gels and tablets. Though proved efficient, their presence in the vagina for a longer time as a bulk produces discomfort and interference with body functioning including sexual activities. Hence, they lack complete patient compliance. In this study, multiparticulate vaginal tablets were prepared by utilizing progesterone (PRO) loaded dry powder precursor of cubic phase (DPPCP) of glyceryl monooleate (GMO). DPPCP were obtained by spray drying GMO with magnesium trisilicate (MTS) and have presented PRO sustained release in simulated vaginal fluid (SVF) for 14 hours. The effect of hydrophilic and hydrophobic tableting excipients on compression, phase, bioadhesion and drug release properties of prepared tablets was evaluated. The effervescent hydrophilic tablet (EHT) prepared with hydrophilic excipients showed rapid disintegration but, diminished sustaining ability owing to transformation into lamellar phase whereas the multiparticulate hydrophobic tablet (MHT) obtained from hydrophobic excipients presented both rapid disintegration and sustained release in SVF by virtue of cubic phase retention. During bioadhesivity testing, fast disintegration of MHT with formation of uniform and viscous bioadhesive layer on cow mucosa was observed even with a small volume of SVF. As MHT may not produce discomfort and interference, it will be preferred over bioadhesive gel or tablet.


Cigarette smoking among Asian American and Pacific Islander college students: implications for college health promotion.
Asian Americans (AA) and Pacific Islanders (PI) are an understudied population for health and tobacco use, which is alarming for a fast growing U.S. population. Research in smoking among AA and PI college students is limited, despite 50% of AA and 20% of PI having obtained a college degree. A cross-sectional tobacco survey was administered in a large racially diverse Southern California university (N = 490) that examined smoking behavior, psychosocial, and perceptual factors related to smoking among AA and PI compared with Caucasians. Overall, 19% of participants were smokers. The prevalence of current smoking by race was 26% PI, 19% AA, and 17% Caucasian. AA and PI are light, infrequent smokers who smoke mainly for social reasons and in social locations. Most AA and PI made quit attempts and reported intention to quit smoking. Low to moderate risk perceptions for addiction, disease and difficulty in quitting were observed. Social norms center on family influences, therefore it is recommended that cessation approaches target cigarette smoking norms within this social environment to increase perceptual risks of smoking. Smoking cessation should be placed in college health outreach programs based on culturally tailored approaches for AA and PI that target their unique smoking characteristics.


Chemopreventive Potential of Myrtenal against Nitrosamine-Initiated, Radiation-Promoted Rat Bladder Carcinogenesis.
The present study was undertaken to evaluate the chemopreventive activity of myrtenal, a natural monoterpene, against bladder carcinoma in rats induced with N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN) and promoted with γ-ionizing radiation (γ-IRR) as well as to assess the involvement of inflammation, apoptosis and oxidative damage in tumor development. Histopathological examination of rat bladder revealed the presence of noninvasive papillary transitional cell carcinoma (Grade 2) in sections from BBN group indicating the credibility of the applied carcinogenesis model. Myrtenal treatment caused improvement in urinary bladder mucosa with cells more likely in Grade 1. Administration of myrtenal to BBN-treated rats exhibited downregulation in the expressions of COX-2, NF-kB and STAT-3 associated with suppression of inflammatory cytokines levels of TNF-α and IL-6 as well as biomarkers of oxidative damage (MDA & NO). In addition, myrtenal treatment caused a significant increase in caspase-3 activity and Bax/Bcl-2 ratio. Data obtained suggested that the anti-inflammatory effect and the induction of apoptosis contributed largely to the beneficial antitumor effects of myrtenal in rats with BBN/γ-IRR-induced bladder carcinoma. Present findings, in addition to benefits described in other pathologies, indicated myrtenal as a potential adjuvant natural compound for the prevention of tumor progression of bladder cancer.


[Two patients with a non-palpable, subcutaneously implanted contraceptive].
Two women, 33 and 31 years of age, were referred to a surgeon for the removal of a previously implanted hormonal contraceptive after the general practitioner had attempted this without success. However, no foreign body could be detected in either patient by surgery, echography and MRI and by X-ray, echography and MRI, respectively. They were then referred to a gynaecologist. In the first patient, a low level of etonogestrel confirmed that there was no contraceptive in her body. Subcutaneous contraceptives are sometimes implanted incorrectly. If the rod is not palpable at the site of insertion, then the etonogestrel level should be determined first of all. If the hormone level indicates that a rod is indeed present, then echography or MRI may be considered to localise it before resorting to surgical exploration. Many problems can be prevented by proper implantation.


Ionic regulation of the binding of DL-2-amino-7-phosphono-[4,5-3H]heptanoic acid to synaptosome-enriched homogenates of rat cerebral cortex.
The ionic requirements of the site labelled by DL-2-amino-7-phosphono-[4,5-3H]heptanoic acid ([3H]DL-2AP7) in synaptosome-enriched homogenates of rat cerebral cortex were examined using radioligand binding methodology. Binding of [3H]DL-2AP7 was increased by calcium and chloride ions by an apparently non-competitive mechanism. The actions of ions on specific binding displayed similarities to the effects of ions on DL-[3H]2-amino-4-phosphonobutyric acid and Cl-/Ca2+-dependent L-[3H]glutamate ([3H]Glu) binding sites but were more consistent with the Glu-C binding site.


The prevalence of Molar-Incisor Hypomineralisation (MIH) in Wainuiomata children.
The aim of this study was to determine the prevalence of Molar-Incisor Hypomineralisation (MIH) in Wainuiomata children and describe differences in prevalence among Māori, Pacific Island and New Zealand European ethnic groups. Cross-sectional survey of developmental defects of enamel in a random sample of children attending primary school in Wainuiomata, Wellington. Study information and consent forms were sent to 850 7-to-10-year-old schoolchildren. Using the modified Developmental Defects of Enamel index, a single paediatric dentist examined students in the classroom. Dental caries experience was recorded as decayed, missing or filled primary and permanent teeth. Examinations were conducted on 522 children (participation rate 61.4%). The mean age of the children was 8.2 years (range 7 to 10 years). MIH prevalence was 14.9%. The prevalence ofhypomineralisation ofany tooth was 15.3%, and that for hypoplasia was 4.0%. There was no statistically significant ethnic difference in MIH prevalence. The mean DMFT was 0.16 (SD, 0.54) in those without a developmental defect, 0.54 (SD, 1.12) in those with hypomineralisation and 1.85 (SD, 1.85) in those with hypoplasia (p < 0.01). Approximately one in seven Wainuiomata children have MIH. Ethnicity is not a modifying factor in the occurrence of developmental defects of enamel. The presence of hypomineralisation and/or hypoplasia was associated with significantly greater caries experience in the permanent dentition.


Inherited defects in the complement system.
The complement system plays an essential role in both innate and adaptive immune responses. Any dysregulation in this system can disturb normal host defense and alter inflammatory response leading to both infections and autoimmune diseases. The complement system can be activated through three different pathways. Inherited complement deficiencies have been described for all complement components and their regulators. Despite being rare diseases, complement deficiencies are often severe, with a frequent onset during childhood. We provide an overview of clinical disorders related to these disorders and describe current diagnostic strategies required for their comprehensive characterization and management.


Informed consent and the history of inclusion of women in clinical research.
The purposes of this paper are to (a) discuss the troubled history of informed consent for research on women and its ramifications for women's participation in clinical trials; (b) interrogate current informed consent practices as to their accountability and justice in the treatment of women; and (c) recommend to nurse researchers and clinical nurses ways of improving the practice of informed consent in research with women.


San Antonio breast cancer symposium--32nd annual meeting.
The 32nd San Antonio Breast Cancer Symposium, held in San Antonio, TX, USA, included topics covering etiology, epidemiology and tumor immunotherapy in the field of breast cancer therapy. This conference report discusses epigenetics and the PI3K/Akt/mTOR pathway in breast tumorigenesis.


Complete Genome Sequence of a GII.17 Norovirus Isolated from a Rhesus Monkey in China.
The previously silent GII.17 norovirus was found to be the predominant genotype causing major epidemics in China in the 2014-2015 winter epidemic season. We report here the complete genomic sequence of a GII.17 norovirus (mky/GII.17/KM1509/CHN/2015) that infected rhesus monkeys at a monkey farm in southwestern China.


Carcinoma in situ associated with superficial bladder tumor.
In a sample of 306 patients with superficial bladder tumors (Ta, Tl), 48 were affected by associated carcinoma in situ (TIS). We included 40 of them in a random program with Mitomycin C or Adriamycin, administered endovesically. We found that those patients with associated TIS whose progression rate had increased to 37.1% compared to 8.8% in the original series (p less than 0.01), had a worse prognosis. Besides, 10 of them required radical cystectomy. With this chemotherapy program, we achieved a high rate of complete response (70%), but its duration was limited by a recurrence rate of 42.9%, with a time free of disease of 26.2 months. In the whole group, the survival rate free of disease was 77.5%, with an average follow-up of 37.3 months. On the other hand, we found extravesical recurrences not only in the prostatic urethra (13; 32.5%) but also at the end of the ureter (3; 7.5%).


Are we becoming more alike? Comparison of substance use in Australia and the United States as seen in the 1995, 1998, 2001 and 2004 national household surveys.
This paper reports the results of the 1995, 1998, 2001 and 2004 Australian and US household surveys, with emphasis on changes since 2001. The US survey data were recalculated to match age groups in the Australian data. Statistically significant changes are reported. Differences in prevalence of use by gender within age group were tested for significance. The past-year use of 'any illicit drug', cannabis, cocaine, tranquillisers and injecting drugs decreased between 2001 and 2004 in Australia, but remained stable for all these drugs except ecstasy between 2002 and 2004 in the United States. The use of hallucinogens decreased in both countries. Alcohol and use of many illicit drugs by teenage girls in both countries increased to rates similar to or higher than boys, and teens in both countries reported binge and heavy drinking in the past month. Australians in their 20s had the highest rates of use, but in the United States, past-year use of many drugs was highest among teenagers. More treatment services are needed, particularly for people dependent upon non-opiate drugs. The changes in acceptability of use of different drugs and their perceived availability are related to changes in prevalence rates. Even with the similarities in levels of use, there are differences in patterns of use and preferences for certain drugs in each country, and geographic proximity to drug sources is a factor.


Insulin-stimulated release of D-chiro-inositol-containing inositolphosphoglycan mediator correlates with insulin sensitivity in women with polycystic ovary syndrome.
Some actions of insulin are mediated by inositolphosphoglycan (IPG) mediators. Deficient release of a putative D-chiro-inositol-containing (DCI) IPG mediator may contribute to insulin resistance in women with polycystic ovary syndrome (PCOS). Previously, we demonstrated that oral DCI supplementation improved ovulation and metabolic parameters in women with PCOS. However, whether oral DCI mediates an increase in the release of the DCI-IPG mediator and an improvement in insulin sensitivity in women with PCOS is unknown. We conducted a randomized controlled trial of DCI supplementation vs placebo in 11 women with PCOS who were assessed at 2 time points 6 weeks apart. Plasma DCI, DCI-IPG release during oral glucose tolerance test (AUC(DCI-IPG)), and insulin sensitivity (S(i)) by frequently sampled intravenous glucose tolerance test were assessed at baseline and end of study. The study was terminated early because of a sudden unavailability of the study drug. However, in all subjects without regard to treatment assignment, there was a positive correlation between the change in AUC(DCI-IPG)/AUC(insulin) ratio and the change in S(i) during the 6-week period (r = 0.69, P = .02), which remained significant after adjustment for body mass index (P = .022) and after further adjustment for body mass index and treatment allocation (P = .0261). This suggests that, in women with PCOS, increased glucose-stimulated DCI-IPG release is significantly correlated with improved insulin sensitivity. The significant relationship between DCI-IPG release and insulin sensitivity suggests that the DCI-IPG mediator may be a target for therapeutic interventions in PCOS.


Ablation threshold and ablation mechanism transition of polyoxymethylene irradiated by CO2 laser.
Polyoxymethylene (POM) decomposes gradually as it is heated up by the irradiation of CO2 laser; the long-chain molecules of POM are broken into short chains, which leads to the lowering of the melting point and the critical temperature of the ablation products. When the product temperature is above the melting point, ablation comes up in the way of vaporization; when the product temperature is higher than the critical temperature, all liquid products are transformed into gas instantly and the ablation mechanism is changed. The laser fluence at which significant ablation is observed is defined as the ablation threshold, and the fluence corresponding to the ablation mechanism changing is denoted as the flyover threshold. In this paper, random pyrolysis is adopted to describe the pyrolytic decomposition of POM, and consequently, the components of the pyrolysis products under different pyrolysis rates are acquired. The Group Contribution method is used to count the thermodynamic properties of the pyrolysis products, and the melting point and the critical temperature of the product mixture are obtained by the Mixing Law. The Knudsen layer relationship is employed to evaluate the ablation mass removal when the product temperature is below the critical temperature. The gas dynamics conservation laws associated with the Jouguet condition are used to calculate the mass removal when the product temperature is higher than the critical temperature. Based on the model, a set of simulations for various laser intensities and lengths are carried out to generalize the relationships between the thresholds and the laser parameters. Besides the ablated mass areal density, which fits the experimental data quite well, the ablation temperature, pyrolysis rate, and product components are also discussed for a better understanding of the ablation mechanism of POM.


"HEALTH FOR ALL". THE MEDICAL SYSTEM IN WALLACHIA UNDER PROTOMEDICUS NICOLAE GUSSI 1848-1859.
The main objective of this study is to provide an overview of the evolution of the medical system in Wallachia between 1840 and 1860 and the very important role of physician Nicolae Gussi (1802-1869), protomedicus of Wallachia between 1840 and 1859, to transform medicine into a modern public service, accessible to the entire population. Particularly, we will refer to the medical reform project of 1853, which Gussi implemented during the time he headed the medical-sanitary administration. We will insist on the details of the project because it was designed to create a network of county hospitals that would improve the health of the population and, in the medium and long term, would reduce mortality and increase life expectancy. Another dimension of the study aims at the tenure of physicians in county hospitals and describes the medical services they provided to patients, particularly from the poor population.


Differential effects of intrastriatal neurotensin(1-13) and neurotensin(8-13) on striatal dopamine and pallidal GABA release. A dual-probe microdialysis study in the awake rat.
In the present dual-probe microdialysis study the effects of intrastriatal perfusion with the tridecapeptide neurotensin(1-13) [NT(1-13)] and its active fragment NT(8-13) on striatopallidal GABA and striatal dopamine release were investigated. The modulatory action of NT(1-13) on D2 receptor-mediated inhibition of striatal and pallidal GABA release was also studied. Both intrastriatal NT(1-13) (100 nM) and NT(8-13) (100 nM) increased striatal (139 and 149% respectively) and pallidal (130 and 164%) GABA release, and this effect was antagonized by intrastriatal perfusion with the neurotensin receptor antagonist SR48692 (100 nM). A similar increase (155%) in striatal dopamine release was observed following intrastriatal NT(1-13) (100 nM), but not NT(8-13) (100 and 500 nM). However, at the highest concentration studied (1 microM) NT(8-13) was associated with a rapid increase (130%) in striatal dopamine release. In a second study intrastriatal NT(1-13) (10 nM) counteracted the inhibition of striatal and pallidal GABA release induced by pergolide (500 and 1500 nM). The inhibitory action of the D2 agonist was restored when SR48692 (100 nM) was added to the perfusion medium. These results suggest that in the neostriatum the neurotensin receptor located postsynaptically on the striatopallidal GABA neurons seems to differ from the neurotensin receptor located on dopaminergic terminals, as indicated by the relative lack of effect of NT(8-13) on striatal dopamine release. Furthermore, the ability of NT(1-13) to counteract the pergolide-induced inhibition of both striatal and pallidal GABA release strengthens the evidence for antagonistic receptor-receptor interaction between postsynaptic striatal neurotensin and D2 receptors located on striatopallidal GABA neurons.


Continuation high schools: youth at risk for drug abuse.
Students at alternative high schools may be at substantial risk for drug abuse. The present article provides a general overview of the drug use-related context of continuation high schools in southern California. A total of 144 students and ninety-six staff were interviewed from twenty continuation high schools. The interview data revealed that continuation school students show high levels of substance use. However, only 20 percent of the students report that they received any drug abuse prevention programming. Also, students at continuation high schools aspired to a productive life after high school including continued education. Thus, these youth may still be amenable to preventive educational interventions which deter them from drug use and help them to fulfill their future goals.


One-Step Synthesis of SnO2/Carbon Nanotube Nanonests Composites by Direct Current Arc-Discharge Plasma and Its Application in Lithium-Ion Batteries.
Tin dioxide (SnO2)-based materials, as anode materials for lithium-ion batteries (LIBs), have been attracting growing research attention due to the high theoretical specific capacity. However, the complex synthesis process of chemical methods and the pollution of chemical reagents limit its commercialization. The new material synthesis method is of great significance for expanding the application of SnO2-based materials. In this study, the SnO2/carbon nanotube nanonests (SnO2/CNT NNs) composites are synthesized in one step by direct current (DC) arc-discharge plasma; compared with conventional methods, the plasma synthesis achieves a uniform load of SnO2 nanoparticles on the surfaces of CNTs while constructing the CNTs conductive network. The SnO2/CNT NNs composites are applied in LIBs, it can be found that the nanonest-like CNT conductive structure provides adequate room for the volume expansion and also helps to transfer the electrons. Electrochemical measurements suggests that the SnO2/CNT NNscomposites achieve high capacity, and still have high electrochemical stability and coulombic efficiency under high current density, which proves the reliability of the synthesis method. This method is expected to be industrialized and also provides new ideas for the preparation of other nanocomposites.


Identification and spatial arrangement of high molecular weight proteins (Mr 300 000-330 000) co-assembling with microtubules from a cultured cell line (rat glioma C6).
The distribution of three high molecular weight proteins, MAP-1 (Mr 330 000), MAP-2 (Mr 300 000) and plectin (Mr 300 000) in various fractions obtained in cycles of temperature-dependent polymerization/depolymerization of microtubules from rat glioma C6 cells was studied. Using gel electrophoresis and immunoautoradiography/immunoblotting all three proteins were found to codistribute only partially with tubulin because considerable parts remained in the cold-insoluble fractions. Moreover, the proteins, particularly MAPs, were proteolytically degraded during cycling. By contrast, when microtubules were polymerized with taxol after isotonic cell lysis a considerable enrichment of MAP-1 and MAP-2 was achieved; again, plectin co-distributed only partially. In this procedure too, MAPs, especially MAP-2, were found to be highly subject to proteolysis, unless free Ca2+-ions were rigorously avoided. Proteolytic fragments generated from MAP-2 were of similar size independent of whether temperature- or taxol-dependent polymerization procedures were used, suggesting the occurrence of a MAP-2-specific protease. When the spatial arrangement of the high Mr proteins on taxol-polymerized C6 cell microtubules was directly visualized using gold-immunoelectron microscopy, a periodical, apparently helical, decoration of microtubules was found for MAP-1 and MAP-2; plectin was irregularly arrayed. A predominantly helical arrangement of both MAPs was demonstrated also for microtubules reconstituted from mammalian brain.


Older people's experiences of dream coaching.
Recalling and talking about dreams could initiate dream work among older people and provide an opportunity for self-confrontation and personal growth, which could in turn promote gerotranscendental development. The present article describes older people's opinions about participating in a dream-coaching group; it also briefly describes the theoretical foundation of dream coaching. The study aim was to investigate older people's experience of participating in a dream-coaching group based on Jungian psychology. A descriptive design was used. Retrospective interviews were explored using qualitative content analysis. The participants were satisfied with the arrangement of the dream-coaching groups. All participants believed that they had recalled their dreams and thought much more about their dreams during the period in which the dream-coaching group met. Three diverse appraisals of participating in a dream-coaching group, which had different effects on the participants, were identified: "An activity like any other activity," "An activity that led to deeper thoughts about the meaning of dreams," and "An activity that led to deeper thoughts both about the meaning of dreams and about how dreams can improve one's understanding of the life situation." It is possible to arrange dream-coaching groups for older people and could be a way to promote personal development using this type of intervention. The study provides some guidance as to how such a group could be organized, thus facilitating use of dream-coaching groups in gerontological care.


Interrupted coarsening in the zero-temperature kinetic Ising chain driven by a periodic external field.
If quenched to zero temperature, the one-dimensional Ising spin chain undergoes coarsening, whereby the density of domain walls decays algebraically in time. We show that this coarsening process can be interrupted by exerting a rapidly oscillating periodic field with enough strength to compete with the spin-spin interaction. By analyzing correlation functions and the distribution of domain lengths both analytically and numerically, we observe nontrivial correlation with more than one length scale at the threshold field strength.


CXCL12/CXCR4 Axis Upregulates Twist to Induce EMT in Human Glioblastoma.
In recent decades, the chemokine receptor CXCR4 and its ligand CXCL12 have been extensively reported to be associated with tumorigenesis. In addition, Twist signaling induces the epithelial-mesenchymal transition (EMT) process in glioblastoma development. In the present study, in vitro assays were used to investigate the role of CXCR4 and Twist in human glioblastoma. We explored the impact of CXCR4 and Twist on human glioblastoma using in vitro protein and gene assays. We found the administration of CXCL12 upregulated the expression of p-ERK, p-AKT, Twist, N-cadherin, and MMP9 in U87 cells, whereas the increase of E-cadherin protein was affected. Subsequently, Twist activity and EMT signaling were directly influenced by PD98059 and LY294002. Most importantly, the genetic silencing of Twist inhibited CXCL12-induced EMT occurrence, including proliferation, migration, and tumor formation of U87 cells. In conclusion, CXCL12/CXCR4 pathway activates ERK and PI3K/AKT signaling to upregulate Twist pathway, leading to the progression of EMT in human glioblastoma. Our study creates a new stage for molecule-targeted therapy of human glioblastoma.


Synthesis and discovery of high affinity folate receptor-specific glycinamide ribonucleotide formyltransferase inhibitors with antitumor activity.
6-Substituted classical pyrrolo[2,3-d]pyrimidine antifolates with a three- to six-carbon bridge between the heterocycle and the benzoyl-L-glutamate (compounds 2-5, respectively) were synthesized starting from methyl 4-formylbenzoate and a Wittig reaction with the appropriate triphenylphosphonium bromide, followed by reduction and conversion to the alpha-bromomethylketones. Cyclocondensation of 2,4-diamino-4-oxopyrimidine with the alpha-bromoketones, coupling with diethyl-L-glutamate, and saponification afforded 2-5. Compounds 2-5 had negligible substrate activity for RFC but showed variably potent (nanomolar) and selective inhibitory activities toward Chinese hamster ovary cells that expressed FRalpha or FRbeta and toward FRalpha-expressing KB and IGROV1 human tumor cells. Inhibition of KB cell colony formation was also observed. Glycinamide ribonucleotide formyl transferase (GARFTase) was identified as the primary intracellular target of the pyrrolo[2,3-d]pyrimidines. The combined properties of selective FR targeting, lack of RFC transport, and GARFTase inhibition resulting in potent antitumor activity are unprecedented and warrant development of these analogues as antitumor agents.


One piece ultracompact totally implantable electromechanical total artificial heart for permanent use.
An ultracompact, one piece, totally implantable electromechanical total artificial heart (TAH) has been developed as a permanent replacement for failing hearts. It consists of left and right pusher plate blood pumps (stroke volume 55 ml) made of titanium alloy (Ti-6Al-7Nb) sandwiching a miniaturized electromechanical actuator between them. The diameter of the TAH is 90 mm, with a thickness of 70 mm, yielding an overall volume of 400 ml. It weighs 450 g. Although it is miniaturized, it provided a maximum pump output of 8 L/min against a left afterload of 100 mm Hg. It required approximately 12 watts to provide a pump output of 6.5 L/min with maximum efficiency of 13.5%. To balance left and right flow, the right stroke length was made 10% shorter than the left, and an auxiliary compliance chamber was used to compensate for additional flow differences between them. Motor commutation pulses and a Hall effect pusher plate sensor signal were used in the controller to implement the left master alternate variable rate mode. The calf fitting study revealed excellent anatomic compatibility, and the first successful survivor was obtained in December 2001. Studies of system endurance and biocompatibility are required to ensure long-term reliability. This TAH is promising for permanent replacement of the failing heart as well as for bridge to heart transplantation for the smaller size group of end-stage cardiac patients.


Proteolytic specificity of Lactobacillus delbrueckli subsp. bulgaricus influences functional properties of mozzarella cheese.
Low-moisture part-skim Mozzarella cheeses were manufactured from 2% fat milk and aged for 21 d. Treatments included cheeses made with one of three different strains of Lactobacillus delbrueckii ssp. bulgaricus in combination with a single strain of Streptococcus thermophilus. A fourth, control treatment consisted of cheeses made with only S. thermophilus. Although total proteolytic ability of these strains, as indicated by the o-phthaldialdehyde analysis, was similar in each of the three strains of L. bulgaricus, these strains exhibited different proteolytic specificities toward the peptide, alpha(s1)-CN (f 1-23). On the basis of their alpha(s1)-CN (f 1-23) cleavage patterns and a previously described classification, these strains were assigned to the groups I, III, and V. The objective of this study was to investigate the influence of lactobacilli proteolytic systems, based on specificity toward alpha(s1)-CN (f 1-23), on functionality of part-skim Mozzarella cheese. Moisture, fat, protein, salt-in-moisture, and moisture in nonfat substances content of cheeses made with groups I, III, and V strain were similar. Control cheese had a lower moisture content than did other treatments. Significant differences were observed in functional properties between cheeses manufactured using groups III and V strains. Cheeses made with groups I and III strains were similar in their meltability, hardness, cohesiveness, melt strength, and stretch quality. Meltability and cohesiveness increased with age, while melt strength and stretch quality decreased with age for all cheeses. Additionally, HPLC showed that total peak areas of water-soluble peptides derived from cleavage of alpha(s1)-CN (f 1-23) by different strains of lactobacilli could be highly correlated to meltability and stretch characteristics of cheeses made with those strains.


Babesiosis caused by a large Babesia species in 7 immunocompromised dogs.
A large unnamed Babesia species was detected in a dog with lymphoma. It was unknown if this was an underrecognized pathogen. Report the historical and clinicopathologic findings in 7 dogs with babesiosis caused by a large unnamed Babesia species characterize the 18S ribosomal ribonucleic acid (rRNA) genes. Seven immunocompromised dogs from which the Babesia was isolated. Retrospective case review. Cases were identified by a diagnostic laboratory, the attending clinicians were contacted and the medical records were reviewed. The Babesia sp. 18S rRNA genes were amplified and sequenced. Six of 7 dogs had been splenectomized; the remaining dog was receiving oncolytic drugs. Lethargy, anorexia, fever, and pigmenturia were reported in 6/7, 6/7, 4/7, and 3/7 dogs. Laboratory findings included mild anemia (7/7) and severe thrombocytopenia (6/7). Polymerase chain reaction (PCR) assays used to detect Babesia sensu stricto species were all positive, but specific PCR assays for Babesia canis and Babesia gibsoni were negative in all dogs. The 18S rRNA gene sequences were determined to be identical to a large unnamed Babesia sp. previously isolated. Cross-reactive antibodies against other Babesia spp. were not always detectable. Five dogs were treated with imidocarb dipropionate and 1 dog with atovaquone/azithromycin; some favorable responses were noted. The remaining dog was untreated and remained a clinically stable carrier. Dogs with pigmenturia, anemia, and thrombocytopenia should be tested for Babesia sp. by PCR. Serology is not sufficient for diagnosis of this Babesia sp. Asplenia, chemotherapy, or both might represent risk factors for persistent infection, illness, or both.


Structure of DNA-cationic surfactant complexes at hydrophobically modified and hydrophilic silica surfaces as revealed by neutron reflectometry.
In this article, we discuss the structure and composition of mixed DNA-cationic surfactant adsorption layers on both hydrophobic and hydrophilic solid surfaces. We have focused on the effects of the bulk concentrations, the surfactant chain length, and the type of solid surface on the interfacial layer structure (the location, coverage, and conformation of the DNA and surfactant molecules). Neutron reflectometry is the technique of choice for revealing the surface layer structure by means of selective deuteration. We start by studying the interfacial complexation of DNA with dodecyltrimethylammonium bromide (DTAB) and hexadecyltrimethylammonium bromide (CTAB) on hydrophobic surfaces, where we show that DNA molecules are located on top of a self-assembled surfactant monolayer, with the thickness of the DNA layer and the surfactant-DNA ratio determined by the surface coverage of the underlying cationic layer. The surface coverages of surfactant and DNA are determined by the bulk concentration of the surfactant relative to its critical micelle concentration (cmc). The structure of the interfacial layer is not affected by the choice of cationic surfactant studied. However, to obtain similar interfacial structures, a higher concentration in relation to its cmc is required for the more soluble DTAB surfactant with a shorter alkyl chain than for CTAB. Our results suggest that the DNA molecules will spontaneously form a relatively dense, thin layer on top of a surfactant monolayer (hydrophobic surface) or a layer of admicelles (hydrophilic surface) as long as the surface concentration of surfactant is great enough to ensure a high interfacial charge density. These findings have implications for bioanalytical and nanotechnology applications, which require the deposition of DNA layers with well-controlled structure and composition.


Integrating visual and tactile information in the perirhinal cortex.
By virtue of its widespread afferent projections, perirhinal cortex is thought to bind polymodal information into abstract object-level representations. Consistent with this proposal, deficits in cross-modal integration have been reported after perirhinal lesions in nonhuman primates. It is therefore surprising that imaging studies of humans have not observed perirhinal activation during visual-tactile object matching. Critically, however, these studies did not differentiate between congruent and incongruent trials. This is important because successful integration can only occur when polymodal information indicates a single object (congruent) rather than different objects (incongruent). We scanned neurologically intact individuals using functional magnetic resonance imaging (fMRI) while they matched shapes. We found higher perirhinal activation bilaterally for cross-modal (visual-tactile) than unimodal (visual-visual or tactile-tactile) matching, but only when visual and tactile attributes were congruent. Our results demonstrate that the human perirhinal cortex is involved in cross-modal, visual-tactile, integration and, thus, indicate a functional homology between human and monkey perirhinal cortices.


Intramucosal adenocarcinoma of the ileum originated 40 years after ileosigmoidostomy.
Small bowel adenocarcinomas (SBAs) are rare carcinomas. They are asymptomatic and usually neither endoscopy nor contrast studies are performed for screening A 72-year-old Japanese male had a positive fecal occult blood test at a regular check-up in 2006. He suffered appendicitis and received an ileosigmoidostomy in 1966. A colonoscopy revealed an irregular mucosal lesion with an unclear margin at the ileum side of the anastomosis. A mucosal biopsy specimen showed adenocarcinoma histopathologically. Excision of the anastomosis was performed for this patient. The resected specimen showed a flat mucosal lesion with a slight depression at the ileum adjacent to the anastomosis. Histological examination revealed a well differentiated intramucosal adenocarcinoma (adenocarcinoma in situ). Immunohistological staining demonstrated the overexpression of p53 protein in the adenocarcinoma. Adenocarcinoma of the ileum at such an early stage is a very rare event. In this case, there is a possibility that the ileosigmoidostomy resulted in a back flow of colonic stool to the ileum that caused the carcinogenesis of the small intestine.


Childhood acute lymphoblastic leukemia: Integrating genomics into therapy.
Acute lymphoblastic leukemia (ALL), the most common malignancy of childhood, is a genetically complex entity that remains a major cause of childhood cancer-related mortality. Major advances in genomic and epigenomic profiling during the past decade have appreciably enhanced knowledge of the biology of de novo and relapsed ALL and have facilitated more precise risk stratification of patients. These achievements have also provided critical insights regarding potentially targetable lesions for the development of new therapeutic approaches in the era of precision medicine. In this review, the authors delineate the current genetic landscape of childhood ALL, emphasizing patient outcomes with contemporary treatment regimens as well as therapeutic implications of newly identified genomic alterations in specific subsets of ALL.