Fast inferential adaptive optimization of a continuous yeast culture based on carbon dioxide evolution rate.
A fast inferential, multivariable adaptive optimization algorithm based on a fast responding off-gas data, the carbon dioxide evolution rate (CER), has been developed and applied to a continuous baker's yeast culture to maximize the cellular productivity in simulation and experimental studies. In the simulation study the process was optimized based on CER measurements using readily available steady-state data on the ratio between the cellular productivity and the CER. It was shown that the algorithm is two to three times faster than the algorithm based on cell mass concentration measurements. In the experimental study the CER was maximized without any information on the relationship between the cellular productivity and the CER. It took about 40 h for the process to converge, while about 80 h was required when the optimization was based on cell mass measurements. The attained steady state was found to be different but fairly close to that obtained with cell measurements. Briefly discussed is a switching to the cell-mass-based algorithm at the final stage of the optimization to overcome a potential inaccuracy.


Popliteal artery aneurysm. Prompt intervention prevents tragic consequences.
Popliteal artery aneurysm is an important, if uncommon, cause of lower extremity ischemia. About half of cases are asymptomatic. Untreated aneurysms may lead to embolization, rupture, thrombosis, and amputation. Diagnosis involves careful physical examination and use of ultrasound and arteriography. Prompt surgical intervention is essential.


Knockout of ATG5 leads to malignant cell transformation and resistance to Src family kinase inhibitor PP2.
Autophagy can either promote or inhibit cell death in different cellular contexts. In this study, we investigated the role of autophagy in ATG5 knockout (KO) cell line established using CRISPR/Cas9 system. In ATG5 KO cells, RT-PCR and immunoblot of LC3 confirmed the functional gene knockout. We found that knockout of ATG5 significantly increased proliferation of NIH 3T3 cells. In particular, autophagy deficiency enhanced susceptibility to cellular transformation as determined by an in vitro clonogenic survival assay and a soft agar colony formation assay. We also found that ATG5 KO cells had a greater migration ability as compared to wild-type (WT) cells. Moreover, ATG5 KO cells were more resistant to treatment with a Src family tyrosine kinase inhibitor (PP2) than WT cells were. Cyto-ID Green autophagy assay revealed that PP2 failed to induce autophagy in ATG5 KO cells. PP2 treatment decreased the percentage of cells in the S and G2 /M phases among WT cells but had no effect on cell cycle distribution of ATG5 KO cells, which showed a high percentage of cells in the S and G2 /M phases. Additionally, the proportion of apoptotic cells significantly decreased after treatment of ATG5 KO cells with PP2 in comparison with WT cells. We found that expression levels of p53 were much higher in ATG5 KO cells. The ATG5 KO seems to lead to compensatory upregulation of the p53 protein because of a decreased apoptosis rate. Taken together, our results suggest that autophagy deficiency can lead to malignant cell transformation and resistance to PP2.


[Inhibitory action amlexanox on interleukin-3-induced enhancement of histamine releasability of human leukocytes].
Amlexanox, an anti-allergic drug, showed a concentration-dependent inhibition against hrIL-3-induced enhancement of in vitro histamine release from human leukocytes by anti-IgE. The significant inhibitory action of amlexanox was observed in one out of nine and six out of nine allergic subjects at concentrations of 10(-5) M and 10(-4) M, respectively. This means that the inhibitory effect of amlexanox varied from patient to patient. Post-treatment as well as simultaneous treatment with amlexanox produced an inhibitory action on the enhancing effect of hrIL-3, suggesting that hrIL-3-induced enhancement of releasability is a reversible reaction. AA-861, OKY-046, superoxide dismutase and prostaglandin E2 showed no effects on the hrIL-3-induced enhancement of histamine releasability. The inhibitory action of amlexamox to the hrIL-3-induced enhancement of histamine releasability may be a new anti-allergic mechanism, details of which remains unclear.


Damping factor for monitoring the bone interface at dental implants.
The aim of this study is to investigate whether the damping of osseointegrated implants, as measured quantitatively with the Osstell equipment, is related to the fractal dimension of peri-implant bone. Fifty-five maxillary implants in function for 3 years before the present study were investigated. Two Osstell measurements were obtained for each implant with the transducer oriented first palatally and then distally. Using the half-power bandwidth method, the damping was calculated from the frequency/amplitude plot obtained from the Osstell. Damping data were then related to the fractal dimension of peri-implant bone. Fractal dimensions were calculated using a box-counting algorithm on digitally processed intra-oral radiographs of the implants. A Spearman's test was used to verify the correlation between damping and fractal dimension values. All the implants were clinically stable and free from symptoms. The mean ISQ was 63 for the palatal orientation and 71 for the distal orientation. The mean fractal dimension was 1.47; the mean damping value for palatal orientation was 12.3%, while that for the distal orientation was 8.2%. No significant correlation was found. Damping values, measured at peri-implant bone, were found not to be related to a radiographic parameter of trabecular bone pattern like the fractal dimension. The clinical implication would be that Osstell graphs displaying distinct or more rounded peaks might both indicate a stable implant as long as the associated implant stability quotients are in the range of satisfactory values proposed in the literature.


Decision Support Tool for Water Reclamation Beyond Technical Considerations-Egyptian, Moroccan, and Tunisian Case Studies.
While the Middle East and North African (MENA) region is facing challenges to sustain water security, water reclamation has received increasing consideration as a favorable mitigating solution. Despite the availability of adequate technologies, economic, political, legal, social, and environmental constraints often hamper stakeholders, and especially decision makers, from exploiting the existing potential into solution implementation. In the present paper, a comprehensive assessment for water reclamation and reuse was developed. This assessment consisted of 4 objectives: 1) apply a decision-support tool (DST) for water reclamation potential for municipal wastewater, 2) apply a DST for simulating and estimating the lifecycle costs of project-related technologies for water reclamation (municipal and industrial wastewater, as well as drainage canal water), 3) assess the national-level conditions for water reuse with a multicriteria decision analysis (MCA), and 4) establish exemplary strategies, barriers, and measures for water reuse. The present MCA considered 6 thematic subjects: policy and institution, economy, society, water management, legislation, and environment. The assessment was applied to food and nonfood crop irrigation in Egyptian, Moroccan, and Tunisian case studies. For all defined case studies, adapted treatment trains that could treat wastewater to the desired quality at reasonable costs were identified and are presented in the present paper. Results showed that technological options are available for water reuse, but the concept is not widely implemented in Egypt, Morocco, and Tunisia. The present paper identifies key barriers and drivers for the implementation of water reclamation for irrigation. In particular, the considered countries showed different characteristics regarding efficient water management, water pricing, subsidies and wastewater tariffs, implementation of monitoring and reporting systems, or legal aspects regarding the use of reclaimed water for food crop irrigation. Further exploration of case studies on high potential water reuse and financially affordable wastewater reclamation, particularly case studies that explore the impacts of policies and practices across countries, would be useful for helping the MENA region improve their water security situation. Integr Environ Assess Manag 2020;16:885-897. © 2020 SETAC.


TNM Staging Matched-pair Comparison of Surgery After Neoadjuvant Chemoradiotherapy, Surgery Alone and Definitive Chemoradiotherapy for Thoracic Esophageal Squamous Cell Carcinoma.
Introduction: We used the TNM staging matched-pair approach to compare the efficacies of surgery after neoadjuvant chemoradiotherapy (NCT), surgery alone and definitive chemoradiotherapy (CCRT) in patients with localized advanced thoracic esophageal squamous cell carcinoma (ESCC). Methods: A total of 642 patients with ESCC from previous studies were studied. Patients whose treatment involved NCT + surgery and surgery alone were compared with patients receiving CCRT. Prospensity score matched-pair comparison based on pre-treatment TNM staging was developed to assess the efficacies of these treatment options. Results: Prospensity score matched-pair comparison to control for bias generated a cohort of 274 patients who were eligible for comparison. The 3-year OS rate was 70.0% in the NCT + surgery group, compared to 51.7% in the surgery group (p=0.000) and 61.9% in the CCRT group (p=0.082). With the TNM staging matched-pair approach, the CCRT group had more upper thoracic ESCC patients (43/92, 46.7%), while the surgery group had more lower thoracic ESCC patients (37/92, 40.2%). The 3-year OS rates were comparable between the surgery alone group and CCRT group (p=0.109). Conclusions: NCT plus surgery was superior in OS to surgery alone or CCRT. The 3-year OS rates were comparable between the surgery alone group and CCRT group with TNM staging matched-pair approach. Further investigation is warranted to confirm these findings.


Failure and success in the treatment of breast carcinoma in men: a case report.
Male breast cancer (MBC) represents a rare cause of vertebral body compression fractures along with severe pain restricting the patient's daily functioning. Limited number of cases, lack of awareness among patients and physicians leading to delayed management, further increase the average age and disease progression at presentation, resulting in a poor prognosis. Additionally, studies on MBC treatment protocols and the use of female algorithms are unavailable. The implementation of vertebroplasty or kyphoplasty often results in unsatisfactory outcome due to recurrent pain and loss of vertebral height. Stentoplasty could become an alternative procedure, as described in the following case study. 54-yr-old male patient with history of breast carcinoma presented with pain in the vertebral column. Baseline X-ray and CT scan revealed multiple osteosclerotic and osteolytic metastatic lesions in the thoracic vertebrae along with a compression fracture at T9. Stentoplasty was performed to limit fracture progression. Intraoperative scan revealed restoration of the vertebral body shape. Following surgery, direct reduction in pain was obtained. Postoperative 1-year follow-up did not show any loss in height of the operated vertebra. Results of adjuvant chemotherapy administration and a new method of treatment of compression fractures caused by metastatic lesions were compared with previously published studies. Stentoplasty with Vertebral Body Stenting-System is an innovative method that can be applied in kyphoplasty for compression fractures caused by metastatic lesions. Nevertheless, further research on the systemic treatment of MBC is needed.


Use of bacteriological investigations by general practitioners.
The numbers of vaginal swabs, faecal specimens, throat swabs, and urine specimens submitted by 104 city general practitioners to the bacteriology laboratory at Aberdeen differed widely. The doctors who made most use of the laboratory service rarely did so equally for all four investigations but usually for only one or two. Similarly, those who used the service least often made frequent use of one particular investigation. Further studies are needed to identify and evaluate the reasons for the apparently substantial disagreement among general practitioners concerning the value of these diffferent bacteriological investigations in general practice.


The Role of the COP9 Signalosome and Neddylation in DNA Damage Signaling and Repair.
The maintenance of genomic integrity is an important process in organisms as failure to sense and repair damaged DNA can result in a variety of diseases. Eukaryotic cells have developed complex DNA repair response (DDR) mechanisms to accurately sense and repair damaged DNA. Post-translational modifications by ubiquitin and ubiquitin-like proteins, such as SUMO and NEDD8, have roles in coordinating the progression of DDR. Proteins in the neddylation pathway have also been linked to regulating DDR. Of interest is the COP9 signalosome (CSN), a multi-subunit metalloprotease present in eukaryotes that removes NEDD8 from cullins and regulates the activity of cullin-RING ubiquitin ligases (CRLs). This in turn regulates the stability and turnover of a host of CRL-targeted proteins, some of which have established roles in DDR. This review will summarize the current knowledge on the role of the CSN and neddylation in DNA repair.


A newly designed ignition method for miniature radio frequency ion thruster.
The ignition methods used by micro-radio frequency (RF) ion thrusters have a disadvantage, that is, the starting voltage and flow rate are obviously higher than the rated value, which will easily damage the grid after long-term use. To decrease the starting voltage and flow and reduce the damage to the grid, a new ignition system is proposed in this paper. This system uses an intake pipe as the ground electrode, has an inductance coil and a pre-ionization chamber, and enables the miniature RF ion thruster (Harbin Institute of Technology's RF Ion Thruster 4, HRIT-4) to ignite at the rated voltage and flow by means of strong electric field breakdown and electromagnetic coupling. The experimental results show that when the flow rate is 1.0 SCCM, the ignition voltage is lower than 1900 V, and when the flow rate is 1.5 SCCM, the ignition voltage is lower than 1400 V.


Auto-segmentation of head and neck organs at risk in radiotherapy and its dependence on anatomic similarity.
The aim is to study the dependence of deformable based auto-segmentation of head and neck organs-at-risks (OAR) on anatomy matching for a single atlas based system and generate an acceptable set of contours. A sample of ten patients in neutral neck position and three atlas sets consisting of ten patients each in different head and neck positions were utilized to generate three scenarios representing poor, average and perfect anatomy matching respectively and auto-segmentation was carried out for each scenario. Brainstem, larynx, mandible, cervical oesophagus, oral cavity, pharyngeal muscles, parotids, spinal cord, and trachea were the structures selected for the study. Automatic and oncologist reference contours were compared using the dice similarity index (DSI), Hausdroff distance and variation in the centre of mass (COM). The mean DSI scores for brainstem was good irrespective of the anatomy matching scenarios. The scores for mandible, oral cavity, larynx, parotids, spinal cord, and trachea were unacceptable with poor matching but improved with enhanced bony matching whereas cervical oesophagus and pharyngeal muscles had less than acceptable scores for even perfect matching scenario. HD value and variation in COM decreased with better matching for all the structures. Improved anatomy matching resulted in better segmentation. At least a similar setup can help generate an acceptable set of automatic contours in systems employing single atlas method. Automatic contours from average matching scenario were acceptable for most structures. Importance should be given to head and neck position during atlas generation for a single atlas based system.


Breakpoints in Philadelphia chromosome (Ph1)-positive leukemias.
We studied chromosome 22 breakpoints in 24 Philadelphia (Ph1)-positive leukemias. Nineteen of 21 patients with chronic myelogenous leukemia (CML) possessed a chromosomal break within the 5.8 kilobase (kb) breakpoint cluster region (bcr). Furthermore, in one of three cases of acute lymphocytic leukemia (ALL), we found a chromosomal rearrangement in the bcr locus. No chromosomal rearrangements were found in two cases of CML and two cases of ALL using several restriction enzymes. The bcr rearrangement is highly specific for CML. Further analyses will be necessary to determine whether some cases without bcr rearrangement have another specific locus of rearrangement. Two of three cases of CML with blastic crisis had rearrangement of the immunoglobulin gene and T-cell receptor gene. One CML patient with blastic crisis, who achieved complete remission but relapsed thereafter, was found to have the same immunoglobulin gene rearrangement in the blastic crisis and relapse phases, suggesting that the same clone was involved in both crisis and relapse.


[Experimental study on repairing rabbit femoral condyles defect by small intestinal submucosa and HA-TCP compositions at different ratios].
To study an optimal ratio of small intestinal submucosa (SIS) and (hydroxyapatite-tricalcium phosphate, HA-TCP, SIS/HA-TCP) compositions according to the effect of SIS/HA-TCP compositions with different ratios on repairing rabbit femoral condyle defect. Thirty-six rabbits were made into bone defect models of 6 mm in diameter and 10 mm in depth in both sides of femoral condyles. Three different ratios of SIS/HA-TCP compositions (w/w: 1, 0. 5, 0. 25) were implanted into rabbit femoral condyle defect. After 2, 4, 8 and 12 weeks of operation, the repair effect was observed grossly. The histological evaluations were performed by histological scoring system and computer imaging analysis system. The amount of new bone formation in SIS/HA-TCP(0. 5) group was more than that in SIS/HA-TCP(1) and SIS/HA-TCP(0. 25) groups. Histological observation: In SIS/HA-TCP (1) group, few new bone formation was seen and bone defect was repaired in the 12th week. In SIS/HA-TCP (0.5) group, immature woven bone was found in the defect in the 2nd week; more immature woven bone appeared and formed trabeculae in the 4th week; the regenerated bone was vigorously growing into the interspaces of the implanted materials in the 8th week; the implanted materials was basically replaced by bony structure and the lamellar bone appeared in the 12th week. The results of SIS/HA-TCP (0. 25) group were similar to that of SIS/HA-TCP(0. 5) group. The histological scoring was higher in SIS/HA-TCP (0.5) and SIS/HA-TCP (0.25) groups than that in SIS/HA-TCP (1) group (P<0.05) in the 2nd, 4th, 8th, and 12th weeks. The scoring was higher in SIS/HA-TCP (0.5) group than that in SIS/HA-TCP (0.25) group in the 2nd and 12th weeks (P< 0.05). In new bone formation and the degradation of HA-TCP, SIS/HA-TCP (0.5) and SIS/HA-TCPC (0.25) groups were superior to SIS/HA-TCP (1) group (P<0.05), SIS/HA-TCP (0.5) group was superior to SIS/HA-TCP (0.25) group (P<0.05). SIS/ HA-TCP (0.5) has better effects of repairing bone defect and it can be used as a reference ratio in constructing bone scaffolds.


Chain conformation and biological activities of hyperbranched fucoidan derived from brown algae and its desulfated derivative.
A fucoidan derived from marine brown algae has great potential in biomedical filed. Herein, the fucoidan was successfully isolated and purified by using chitosan microspheres, resulting in the sulfate fucoidan (CF) with degree of sulfation (DS) of 0.94. CF was identified to be highly branched, consisting of fucose (77.4%) and galactose (13.9%), etc., supported by the results of GCMS and light scattering with the structure-sensitive parameter of 0.98 in 0.15 M aqueous NaNO3. The individual CF and its desulfated derivative chains adopted sphere-like conformation in water, observed by atomic force microscopy. CF exhibited higher antiangiogenesis than the desulfated one and strong antileukemia activities through inhibiting cell proliferation and inducing cell apoptosis via cell cycle arrest at G1 phase in vitro. This work provided important information that ester sulfate groups of polysaccharide played an important role in the enhancing of bioactivities of fucoidan, and put forward to a potential drug to treat acute myelocytic leukemia (AML) and tumors.


Branched-Chain Amino Acids as Predictors for Individual Differences of Cisplatin Nephrotoxicity in Rats: A Pharmacometabonomics Study.
Nephrotoxicity is the dose-limiting adverse effect of cisplatin with large individual differences. Up to now, little has been done on how to recognize and predict the individual differences in either preclinical or clinical research. In the present study, important postdose indicators were screened out first and integrated into a grouping factor, according to which rats were recognized as lowly or highly sensitive individuals. Then, mass-spectrometry-based untargeted metabolomics approach was performed to dissect the metabolic differences in predose serum of the two groups. Eventually, branched-chain amino acids (BCAAs) were found to be most significant with the lowest p value of Mann-Whitney U test and the highest area under receiving operating characteristic curve (AUC-ROC). The findings were further confirmed by absolute quantitation of BCAAs using liquid chromatography-tandem mass spectrometry. Binary logistic regression showed that in the discovery set absolute BCAA contents in rat predose serum could predict cisplatin nephrotoxicity with accuracy of 85%. This result was validated by another two independent external validation sets with accuracy of 81.8 and 78.8%, respectively. This study could provide new insight into cisplatin nephrotoxicity and may help expedite personalized medicine of cisplatin or other antitumor drugs in future clinical studies.


[Esophageal motility characteristics of refractory heartburn: a study based on high resolution manometry and 24 hour pH-impedance monitoring].
To analyze the esophageal motility characteristics of refractory heartburn with different reflux patterns and preliminarily clarify the roles of esophageal disorder in refractory heartburn. A total of 176 refractory heartburn patients were enrolled from 2009 to 2013. After gastroscopy and 24 hour pH-impedance monitoring, they were divided into 4 groups of reflux esophagitis (RE, n = 29), non-erosive reflux disease with acid reflux (NERD-acid, n = 51), NERD with weakly acidic reflux (NERD-weakly acid, n = 51) and non-reflux associated heartburn (n = 45). All subjects undertake high resolution manometry test and their esophageal motility functions were analyzed by the Chicago classification criteria 2012. Among them, 60.23% (106/176) patients presented esophageal motility disorders. And 42.61% (75/176) fulfilled the criteria of weak peristalsis, 7.39% (13/176) distal esophageal spasm, 4.55% (8/176) rapid contraction, 3.98% (7/176) EGJ outflow obstruction, 1.14% (2/176) hiatus hernia and 1 Jackhammer esophagus. The detection rates of esophageal motility disorder were similar among 4 groups and weak peristalsis was the most common disorder in all groups (41.38% in RE, 37.25% in NERD-acid patients, 54.90% in NERD-weakly acid and 35.56% in non-reflux associated heartburn patients). However, hypertensive motility disorders in non-reflux associated heartburn group (31.11%, 14/45) were more than GERD subgroups (11.45%, 15/131) (P < 0.05) . The relax ratio of low esophagus sphincter (LES) in GERD subgroups were higher than that in non-reflux associated heartburn patients. And the relax ratio of NERD-weakly acid was significantly higher than that in non-reflux associated heartburn patients (65% (50%-80%) vs 58% (42%-67%) , P < 0.05). The integrated relaxation pressure in GERD subgroups were lower than that of non-reflux associated heartburn patients without significant differences (P > 0.05). Esophageal weak peristalsis is one of the most common motility disorders in refractory heartburn patients, and esophageal hypertensive motility disorders are common in non-reflux associated heartburn patients. Esophageal manometry is necessary for the diagnosis and treatment of refractory heartburn.


Surgical resection of left atrial myxoma presenting with acute multiple hemorrhagic cerebral infarctions: a case report.
Brain ischemia resulting from left atrial myxoma embolization has been well documented. In contrast, the link between the development of intracerebral hemorrhage and myxoma in these patients has little coverage in the literature. The main theory describing this relationship stems from the fact that cardiac myxoma cells metastasize to the brain's vessels, causing destruction of the arterial wall with subsequent formation of fusiform aneurysm and further intracranial bleeding. It is assumed that when a diagnosis of left atrial myxoma with neurologic manifestations is made, surgical resection should be performed without delay to prevent repeated tumor embolization; however, systemic anticoagulation treatment during cardiac surgery with cardiopulmonary bypass is not recommended immediately after intracerebral hemorrhage occurs because of the possibility of extending the infarct's size. We describe a patient with acute hemorrhagic brain infarction and an echocardiographically demonstrated left atrial myxoma that was surgically resected successfully in the acute phase after the onset of the neurologic symptoms.


Evolutionary stasis: the stable chromosomes of birds.
Evolution at the molecular level is manifested in a variety of types of change in DNA sequences, including changes in the structure and organisation of chromosomes. However, in birds chromosomal evolution occurs at an unusually slow rate and recent whole-genome comparisons have shown that many chromosomes have remained more or less intact during avian evolution. Here I discuss progress in the development of genetic maps of natural bird populations, which has revealed that the evolutionary stasis of chromosomes often extends to conservation of gene order. The evolutionary stability of bird chromosomes, which might relate to a low frequency of transposable elements, will facilitate the transfer of genomic information from model to non-model organisms and might have a connection to the rarity of postzygotic incompatibilities observed in birds.


X-ray structure of the mature ectodomain of phogrin.
Phogrin/IA-2β and ICA512/IA-2 are two paralogs receptor-type protein-tyrosine phosphatases (RPTP) that localize in secretory granules of various neuroendocrine cells. In pancreatic islet β-cells, they participate in the regulation of insulin secretion, ensuring proper granulogenesis, and β-cell proliferation. The role of their cytoplasmic tail has been partially unveiled, while that of their luminal region remains unclear. To advance the understanding of its structure-function relationship, the X-ray structure of the mature ectodomain of phogrin (ME phogrin) at pH 7.4 and 4.6 has been solved at 1.95- and 2.01-Å resolution, respectively. Similarly to the ME of ICA512, ME phogrin adopts a ferredoxin-like fold: a sheet of four antiparallel β-strands packed against two α-helices. Sequence conservation among vertebrates, plants and insects suggests that the structural similarity extends to all the receptor family. Crystallized ME phogrin is monomeric, in agreement with solution studies but in striking contrast with the behavior of homodimeric ME ICA512. The structural details that may cause the quaternary structure differences are analyzed. The results provide a basis for building models of the overall orientation and oligomerization state of the receptor in biological membranes.


The pathophysiologic basis for the angiographic signs of vascular ectasias of the colon.
Three reliable diagnostic signs were identified on angiograms from 25 patients with ectasias of the right colon: (a) a slowly emptying dilated, tortuous, intramural vein; (b) a vascular tuft; and (c) an early filling vein. The frequency of these signs and the order of their occurrence reflect the different stages in the evolution of ectasias. The earliest and most frequent sign, the slowly emptying vein, reflects ectatic changes in a submocosal vein resulting from chronic intermittent partial obstruction. The vascular tuft represents more advanced lesions and corresponds to extension of the degenerative process to the venules in the mucosa. An early filling vein reflects an arteriovenous communication through a dilated arteriolar-capillary-venular unit-a mucosal ectasia.


Timing of wound coverage in extremity war injuries.
Although several studies have been done on the timing of débridement of open fracture, none has specifically examined the effect of timing of soft-tissue coverage on outcome in the types of lower extremity injury being encountered in Iraq and Afghanistan, namely, injuries associated with the detonation of improvised explosive devices. Complex limb salvage requiring free tissue transfer or rotational flap coverage for soft-tissue defects has been commonly performed during the recent military conflicts in Iraq and Afghanistan. Current treatment protocols favor the inclusion of timely and stable axial limb fixation, radical débridement of all compromised soft tissues and osseous structures, and early wound closure with healthy, well-vascularized autologous tissue. In an attempt to minimize overall morbidity, a comprehensive plan must be made to sequentially reconstruct the involved extremity in order to achieve the highest level of function possible, with a durable construct, in the shortest period of time. Prospective studies are necessary to evaluate the effect of timing of coverage on outcome and on limb salvage.


[Effects of high glucose induced primary cardiomyocytes injury on necroptosis and the related mechanism].
To observe whether necroptosis was happened in high glucose (HG) - induced primary cardiomyocytes injury and to investigate the likely mechanism. The primary cultured cardiomyocytes were divided into 4 groups (n=9): control group (the cardiomyocytes were incubated with 5.5 mmol/L glucose for 48 h), HG group (the cardiomyocytes were incubated with 30 mmol/L glucose for 48 h), HG + necrostatin-1 (Nec-1) group (the cardiomyocytes was co-incubated with necroptosis inhibitor Nec-1 at 100 μmol/L and HG for 48 h) and hypertonic pressure group (HPG, the cardiomyocytes was co-incubated with 5.5 mmol/L glucose and 24.5 mmol/L mannitol for 48 h). Cell viability was measured by MTT method, reactive oxygen species (ROS) generation was measured by DHE staining. The levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β) were tested by ELISA method. The mRNA and protein expressions of necroptosis related genes receptor interacting serine/threonine protein kinase 1 (RIP1), RIP3, mixed lineage kinase domain-like protein (MLKL) were tested by quantitative real-time PCR and Western blot. The results showed HG intervention decreased cardiomyocytes viability, increased ROS generation, up-regulated the levels of TNF-α, IL-6 and IL-1β, increased RIP1, RIP3, MLKL expressions at mRNA and protein levels. Nec-1 treatment attenuated HG-induced increased cardiomyocytes viability, reduced ROS generation, down-regulated the levels of TNF-α, IL-6 and IL-1β, decreased RIP1, RIP3, MLKL expressions at mRNA and protein levels. Necroptosis was happened in high glucose-induced primary cardiomyocytes injury. Inhibition of necroptosis can reduce high glucose-induced cardiomyocytes damage, may be related to inhibition of oxidative stress and depression of inflammative factors releasing.


Mode-coupling study on the dynamics of hydrophobic hydration.
The molecular motion of water in water-hydrophobic solute mixtures was investigated by the mode-coupling theory for molecular liquids based on the interaction-site description. When the model Lennard-Jones solute was mixed with water, both the translational and reorientational motions of solvent water become slower, in harmony with various experiments and molecular dynamics simulations. We compared the mechanism of the slowing down with that of the pressure dependence of the molecular motion of neat water [T. Yamaguchi, S.-H. Chong, and F. Hirata, J. Chem. Phys. 119, 1021 (2003)]. We found that the decrease in the solvent mobility caused by the solute can essentially be elucidated by the same mechanism: That is, the fluctuation of the number density of solvent due to the cavity formation by the solute strengthens the friction on the collective polarization through the dielectric friction mechanism: We also employed the solute molecule that is the same as solvent water except for the amount of partial charges, in order to alter the strength of the solute-solvent interaction continuously. The mobility of the solvent water was reduced both by the hydrophobic and strongly hydrophilic solutes, but it was enhanced in the intermediate case. Such a behavior was discussed in connection with the concept of positive and negative hydrations.


Lipid composition of the rat kidney.
The lipid fractions free fatty acids, triglycerides, cholesterol, cholesterol esters and phospholipids of rat kidney cortex, outer and inner medulla were analyzed by thin-layer chromatography. The concentrations of 23 individual fatty acids in the lipid fractions of each zone were determined by gas chromatography; 14 of them were evaluated by an analysis of variance. For most of the lipid fractions a corticomedullary concentration gradient was found, the highest concentrations occurring in the cortex. The lipid classes primarily determined the pattern of individual fatty acid concentrations. A significant concentration difference between the three zones only existed for 4 of 14 fatty acids. Long chain fatty acids were found in a higher concentration in the phospholipids of cortex and outer medulla (about 95%) in comparison to the inner medulla (65%).


Chronicle of an announced death (thoughts on mid-adulthood).
Middle age can be considered not as the onset of decline, but as a stage of expansion. There has been very little written in the literature on the developmental stages man can expect to experience during his adult life. The criteria and parameters for identifying the level of maturity have relied on terms extracted from developmental theories of childhood. This article deals with the crucial issues and developmental tasks of middle adulthood and the need to define developmental lines based on clinical and epidemiological investigation. The psychotherapeutic problems involved in treating adults in middle age will be presented, including the counter-transference dilemma. It is the author's belief that middle adulthood is a period of transition which opens up options of change and growth once one has worked through the limitations of age and the awareness of one's own death.


Could Carmelite Spirituality Promote Good Mental Health? A brief Tribute to Saint Teresa of Avila in the 500th anniversary of her birth.
Often it is overlooked that Christian Spirituality involves a personal relationship of a human being with God. It is of interest that both the Protestant Reformers and the exponents of the Catholic Counter Reformation agreed upon this. Two of the greatest exponents of the Counter-Reformation, both of whom were made Doctors of the Church because of their teaching on Prayer were Saint Teresa of Avila and Saint John of the Cross. This year is the 500th anniversary of the birth of Saint Teresa of Avila. Here, as a Catholic Psychiatrist, I argue that the teaching of both saints about the prayer life, properly understood, tends to improve self worth, and therefore must tend to help persons with mental health problems.


The effect of raw milk microbial flora on the sensory characteristics of Salers-type cheeses.
The sensory characteristics of Salers Protected Denomination of Origin raw-milk cheeses are linked to the biochemical composition of the raw material (milk) and to the resultant microbial community. To evaluate the influence of the microbial community on sensory characteristics, Salers-type cheeses were manufactured with the same pasteurized milk, reinoculated with 3 different microbial communities from 3 different filtrates from microfiltered milks. Each cheese was subjected to microbial counts (on selective media), biochemical tests, and volatile and sensory component analyses at different times of ripening. Adding different microbial communities to specimens of the same (biochemically identical) pasteurized milk lead to different sensory characteristics of the cheeses. Cheeses with fresh cream, hazelnut, and caramel attributes were opposed to those with fermented cream, chemical, and garlic flavors. The aromatic compounds identified (esters, acids, alcohols, and aldehydes) in these cheeses were quite similar. Nevertheless, one milk was distinguished by a higher content of acetoin, and lower 2-butanone and 3-methylpentanone concentrations. Over the production period of 1 mo, the different cheeses were characterized by the same balance of the microbial population assessed by microbial counts on different media. This was associated with the stability of some sensory attributes describing these cheeses. Nevertheless, there was no linear correlation between microbial flora data and sensory characteristics as measured in this study.


Natural rubber blends for floating theophylline beads.
Natural rubber (NR)'s value has become increasingly important for human applications. This study prepared NR beads as floating drug delivery system by dripping NR latex into hardening solution to obtain spherical beads. Theophylline was loaded as a model drug. NR latex formed into harden beads suddenly after dripping droplets in acidic medium. These NR beads floated instantly and buoyant in HCl buffer for over 8 h with prolonged theophylline release. Their morphologies, crystallinity and thermal properties were observed using microscope, X-ray diffractometer, and thermogravimetry, respectively. Addition of 100 phr sodium bicarbonate increased drug release owing to liberation of carbon dioxide promoting porous NR matrix. Composite of 50 and 200 phr shellac in NR beads floated in HCl buffer for over 12 h. Moreover, 200 phr shellac efficiently retarded release of theophylline from NR composite beads (lower than 10 % in 8 h), whereby promoting theophylline release in phosphate buffer (pH 6.8) (approximately 80 % in 8 h). NR-shellac beads had greater water sorption (2.5 times) and erosion (4.9 times) in phosphate buffer than in HCl buffer. Thus, NR beads exhibited desirable attributes as floating drug delivery system. Both sodium bicarbonate and shellac modified matrix properties and drug release of NR beads.


Recruitment and retention initiatives: nursing students' satisfaction with clinical experience in the mental health field.
The difficulty in attracting graduates of undergraduate nursing programs into mental health remains a challenge for the field. Positive clinical experience has been identified as a potential strategy in encouraging students to regard mental health nursing positively. This paper reports the findings of a survey administered to Undergraduate Nursing Students and Trainee Enrolled Nurses within the mental health area. The purpose of the survey was to measure satisfaction with clinical placements within an Area Mental Health Service. The information provided from the survey is directing the on-going development of clinical placements, clinical supports, education programs and recruitment and retention initiatives for nurses within the Central Sydney Area Mental Health Service. The findings indicate a generally high level of satisfaction with the clinical placement undertaken, however a number of strategies to improve satisfaction with placements were identified.


Decisions in motion: passive body acceleration modulates hand choice.
In everyday life, we frequently have to decide which hand to use for a certain action. It has been suggested that for this decision the brain calculates expected costs based on action values, such as expected biomechanical costs, expected success rate, handedness, and skillfulness. Although these conclusions were based on experiments in stationary subjects, we often act while the body is in motion. We investigated how hand choice is affected by passive body motion, which directly affects the biomechanical costs of the arm movement due to its inertia. With the use of a linear motion platform, 12 right-handed subjects were sinusoidally translated (0.625 and 0.5 Hz). At 8 possible motion phases, they had to reach, using either their left or right hand, to a target presented at 1 of 11 possible locations. We predicted hand choice by calculating the expected biomechanical costs under different assumptions about the future acceleration involved in these computations, being the forthcoming acceleration during the reach, the instantaneous acceleration at target onset, or zero acceleration as if the body were stationary. Although hand choice was generally biased to use of the dominant hand, it also modulated sinusoidally with the motion, with the amplitude of the bias depending on the motion's peak acceleration. The phase of hand choice modulation was consistent with the cost model that took the instantaneous acceleration signal at target onset. This suggests that the brain relies on the bottom-up acceleration signals, and not on predictions about future accelerations, when deciding on hand choice during passive whole body motion.NEW & NOTEWORTHY Decisions of hand choice are a fundamental aspect of human behavior. Whereas these decisions are typically studied in stationary subjects, this study examines hand choice while subjects are in motion. We show that accelerations of the body, which differentially modulate the biomechanical costs of left and right hand movements, are also taken into account when deciding which hand to use for a reach, possibly based on bottom-up processing of the otolith signal.


Immunochemical isolation and characterization of vitellogenin mRNA from liver of estradiol-treated chicks.
Vitellogenin mRNA was purified through three steps. A heavy polysome fraction was obtained by discontinuous sucrose density gradient centrifugation, vitellogenin polysomes were immunoprecipitated with affinity-chromatography-purified anti-lipovitellin IgG and goat anti-rabbit IgG, the enriched mRNA was isolated on a poly(U)-Sepharose column. As judged by its specific activity in a reticulocyte lysate system, vitellogenin mRNA has been enriched a 1000-fold with a recovery of 30%. On 99% formamide 3.4% polyacrylamide gels vitellogenin mRNA has an Mr of 2.4-2.5 X 10(6) and codes for a peptide of Mr 240000, which under our incubation conditions is partially degraded to smaller peptides.


Effect of three interventional bronchoscopic methods on tracheal stenosis and the formation of granulation tissues in dogs.
Therapeutic approaches for tracheal stenosis caused by the formation of exuberant granulation tissues usually include electrocautery, mechanical dilation, laser therapy, argon plasma coagulation (APC), cryotherapy and stent placement. However, restenosis after stent insertion remains a significant limitation. We examined the efficacy of three different approaches, including induction of mechanical lesions, APC performed with different powers or durations and cryotherapy, to identify the method that limited the formation of granulation tissue. Twelve specially bred research mongrel dogs were divided into three groups. In group 1 (four dogs) mild (procedure 1; two dogs) or moderate (procedure 2; two dogs) damage was induced mechanically. Group 2 (six dogs) received APC at different powers or durations (procedure 3: 30 W, 1 cm/s; procedure 4: 30 W, 2 cm/s; procedure 5: 25 W, 3 cm/s). Group 3 (two dogs) received cryotherapy (procedure 6: two freeze-thaw cycles of 30 seconds). Uncovered self-expandable metallic stents were inserted in all dogs to maintain a continuous stimulus to the trachea mucosa. Dogs were monitored for 4 weeks and the relationship between granulation tissue proliferation and method used was analyzed. In group 1, granulation tissue growth increased with more severe mechanical damage. The growth of granulation tissue in group 2 was more pronounced than in group 1, and both dogs in procedure 3 died because of severe stenosis. In this group, the formation of granulation tissue decreased with decreasing power and duration. In group 3, no obvious granulation tissue was found at week 4. Lesions and stimuli from a foreign body (the stent) are two important factors that lead to overgrowth of granulation tissue. Thermal lesions, such as APC, seem to induce greater granulation tissue growth and cartilage damage compared with mechanical and cryotherapy lesions. Cryotherapy in combination with mechanical dilation may be a safe and effective treatment method for managing tracheal stenosis caused by the formation of granulation tissue.


Quaternary Phosphonium Salts as Active Brønsted Acid Catalysts for Friedel-Crafts Reactions.
A readily available quaternary phosphonium salt containing a trifluoroacetonyl group and a tetrakis[3,5-bis(trifluoromethyl)phenyl]borate (BArF4-) counterion was demonstrated to be a highly active Brønsted acid catalyst for Friedel-Crafts-type reactions of an array of electron-rich heteroarenes and aniline derivatives with isatin-derived ketimines, even at 0.1 mol % catalyst loadings.


[Plasma oxysterols and vitamin E concentrations and lipid profile in morbidly obese women].
Morbid obesity (BMI > or = 40 kg/m2) is accompanied by lipid disturbances which may be involved in the increased incidence of atherosclerosis, arterial hypertension and non-insulin-dependent diabetes mellitus. The aim of the study was to assess concentrations of total cholesterol (TC), HDL-cholesterol, LDL-cholesterol, triglycerides (TG), products of cholesterol peroxidation--oxysterols, and the major lipophilic antioxidant--vitamin E, in morbidly obese women without coexisting diseases. The study was performed in 11 morbidly obese women (BMI 42.21 +/- 2.21 kg/m2) and 11 healthy volunteers (BMI 23.0 +/- 2.31 kg/m2). Obese women demonstrated higher concentrations of TG (2.03 +/- 0.78 vs. 0.99 +/- 0.37 mmol/l; p < 0.05), 7-ketocholesterol (7-K) (89.85 +/- 63.03 vs. 41.90 +/- 17.33 ng/ml; p < 0.05) and 7-hydroxycholesterol (7-OH) (456.04 +/- 199.22 vs. 132.37 +/- 53.96 ng/ml; p < 0.05), and lower HDL-cholesterol level (0.74 +/- 0.10 vs. 1.30 +/- +/- 0.17 mmol/l; p < 0.05) compared to the control group, while there were no significant differences between the two groups in concentrations of TC, LDL-cholesterol and vitamin E. Plasma vitamin E/(TC + TG) ratio was lower in obese women (6.42 +/- 2.61 vs. 10.76 +/- 4.57 mumol/mmol; p < 0.05). Tocoferols concentration correlated positively with TG (r = 0.45; p < 0.05) and negatively with 7-OH (r = -0.44; p < 0.05) levels. Moreover, concentration of 7-K correlated positively with the level of HDL (r = 0.54; p < 0.05). In conclusion, despite normal TC and LDL-cholesterol concentrations, there are disturbances in cholesterol peroxidation processes, with the rise in oxysterol levels and the decrease in vitamin E concentration in lipoproteins, which may be involved in the increased incidence of cardiovascular diseases in morbidly obese women.


A nucleolar skeleton of protein filaments demonstrated in amplified nucleoli of Xenopus laevis.
The amplified, extrachromosomal nucleoli of Xenopus oocytes contain a meshwork of approximately 4-nm-thick filaments, which are densely coiled into higher-order fibrils of diameter 30-40 nm and are resistant to treatment with high- and low-salt concentrations, nucleases (DNase I, pancreatic RNase, micrococcal nuclease), sulfhydryl agents, and various nonionic detergents. This filamentous "skeleton" has been prepared from manually isolated nuclear contents and nucleoli as well as from nucleoli isolated by fluorescence-activated particle sorting. The nucleolar skeletons are observed in light and electron microscopy and are characterized by ravels of filaments that are especially densely packed in the nucleolar cortex. DNA as well as RNA are not constituents of this structure, and precursors to ribosomal RNAs are completely removed from the extraction-resistant filaments by treatment with high-salt buffer or RNase. Fractions of isolated nucleolar skeletons show specific enrichment of an acidic major protein of 145,000 mol wt and an apparent pI value of approximately 6.15, accompanied in some preparations by various amounts of minor proteins. The demonstration of this skeletal structure in "free" extrachromosomal nucleoli excludes the problem of contaminations by nonnucleolar material such as perinucleolar heterochromatin normally encountered in studies of nucleoli from somatic cells. It is suggested that this insoluble protein filament complex forms a skeleton specific to the nucleolus proper that is different from other extraction-resistant components of the nucleus such as matrix and lamina and is involved in the spatial organization of the nucleolar chromatin and its transcriptional products.


Rapid aerosol transmission of Salmonella among turkeys in a simulated holding-shed environment.
Once turkeys arrive at Midwest processing plants, they are usually held in large open-sided sheds for 1 to 4 h, waiting to be unloaded. In hot, humid weather, large fans are used to cool the birds. The resultant air currents distribute a significant amount of dust to the turkeys. The dust created in this environment could be a factor in the number of Salmonella-contaminated turkeys entering slaughter plants. The objective of this study was to determine if rapid transmission of Salmonella in turkeys could occur from exposure to Salmonella-contaminated dust similar to what may be experienced in holding sheds or in other high-dust environments prior to slaughter. In the first experiment, trials of 3 different concentrations of Salmonella (1.2 x 10(9), 2.6 x 10(7), and 2.6 x 10(5) cfu/g) were conducted to determine if transmission of Salmonella enterica serovar Typhimurium var. typhimurium(chi)4232 to turkeys 2 to 4 h after aerosol exposure to contaminated feces is possible. Results showed that turkeys became infected after 2 h of exposure to airborne-contaminated feces with a concentration level of 2.6 x 10(5) cfu of Salmonella Typhimurium/g. In the second experiment, consisting of 3 trials, 1 bank (5 cages wide and 3 cages high) of turkeys (n = 15 birds per trial) was exposed to another bank of cages of S. Typhimurium-inoculated (n = 15) birds for 2 to 4 h using a fan similar to the type in processing-plant cooling sheds. Results from this experiment demonstrated that birds could be contaminated with S. Typhimurium after 2 h of exposure. Results of both studies implicate contaminated dust as a route of rapid airborne transmission of Salmonella in turkeys. Processes that generate significant dust prior to slaughter should be regarded as critical control points for Salmonella.


A conventional compression bandage lacks effect on subcutaneous blood flow when walking and during passive dependence in chronic venous insufficiency.
Blood flow in subcutaneous tissue of the lower leg decreased by 45% on changing from recumbency to the sitting position in patients suffering from chronic venous insufficiency. When walking, blood flow increased significantly to values near those measured during resting recumbency. A conventional elastic compression bandage (Weromedium) had no effect on these parameters, indicating that therapeutic gain through compression is not mediated by an improvement in subcutaneous blood flow.


Multiorgan involvement in a pediatric patient with hydatid disease.
Human Echinococcus infection still remains an important health problem in endemic regions. Herein, we report a 5-year-old boy with hydatid disease who has spleen, lung, kidney and liver involvement simultaneously. To our knowledge, there is no pediatric case with hydatid disease in the literature reporting simultaneous involvement of spleen, kidney, liver and lungs as in our case.


Non-specific skin purpura.
Essential thrombocythemia is one of the myeloproliferative neoplasms. Palpable purpura is a rare manifestation that may delay diagnosis and treatment. We report a case of essential thrombocythemia in a 50-year-old man, who presented with recurrent thigh pain for the past one year with nonspecific localized purpura. His full blood count revealed isolated thrombocytosis of 880,000/µL with an impression of myeloproliferative disorder from peripheral blood film. He was referred urgently to the hematology team, which proceeded with a venesection. His condition improved with hydroxyurea. This was a rare case of chronic presentation of myeloproliferative neoplasm detected at a primary care clinic.


Difficult airway management with bonfils fiberscope in case of emergency: acute abdomen with ileus.
This clinical report describes an emergency case of a 49-year-old man, ASA E III status, with clinical symptoms of acute abdomen and ileus, who was scheduled for urgent surgery. Predictors of difficult intubation (Mallampati test Class III, short thyro-mental (< 6 cm) and sterno-mental distance (<10 cm) with limited mouth opening (inter-incisor gap < 3 cm) were associated with significant comorbidity (rheumatoid arthritis, heart disease, obesity (body mass index 32.6 kg m-2), cervical spine mobility and generalized vascular disease). A specialist experienced in airway management decided on one attempt of Bonfils fiberoptic intubation as primary intervention and urgent tracheotomy, if needed, as secondary intervention. Immediately after assuming supine position on the operating table, the patient lost consciousness and cardiac arrest developed. Successful intubation with oxygenation was followed by cardiopulmonary resuscitation. Upon stabilization of the patient's vital functions, urgent surgery was performed. In the emergency case presented, we succeeded quickly to secure the airway with Bonfils fiberoptic intubation, which allowed for appropriate oxygenation and starting resuscitation. The high risk of the possible aspiration was avoided by timely provision of airway in the experienced anesthetist's hands.


Modified Separator Using Thin Carbon Layer Obtained from Its Cathode for Advanced Lithium Sulfur Batteries.
The realization of a practical lithium sulfur battery system, despite its high theoretical specific capacity, is severely limited by fast capacity decay, which is mainly attributed to polysulfide dissolution and shuttle effect. To address this issue, we designed a thin cathode inactive material interlayer modified separator to block polysulfides. There are two advantages for this strategy. First, the coating material totally comes from the cathode, thus avoids the additional weights involved. Second, the cathode inactive material modified separator improve the reversible capacity and cycle performance by combining gelatin to chemically bond polysulfides and the carbon layer to physically block polysulfides. The research results confirm that with the cathode inactive material modified separator, the batteries retain a reversible capacity of 644 mAh g(-1) after 150 cycles, showing a low capacity decay of about 0.11% per circle at the rate of 0.5C.


The uneasy coexistence of predators and pathogens.
Disease and predation are both highly important in ecology, and pathogens with multiple host species have turned out to be common. Nonetheless, the interplay between multi-host epidemics and predation has received relatively little attention. Here, we analyse a model of a predator-prey system with disease in both prey and predator populations and determine reasonable parameter values using allometric mass scaling relations. Our analysis focuses on the possibility of extinction events rather than the linear stability of the model equations, and we derive approximate relations for the parameter values at which we expect these events to occur. We find that if the predator is a specialist, epidemics frequently drive the predator species to extinction. If the predator has an additional, immune prey species, predators will usually survive. Coexistence of predator and disease is impossible in the single-prey model. We conclude that for the prey species, carrying a pathogen can be an effective weapon against predators, and that being a generalist is a major advantage for a predator in the event of an epidemic affecting the prey or both species.


Age-related modulation of angiogenesis-regulating factors in the swine meniscus.
An in-depth knowledge of the native meniscus morphology and biomechanics in its different areas is essential to develop an engineered tissue. Meniscus is characterized by a great regional variation in extracellular matrix components and in vascularization. Then, the aim of this work was to characterize the expression of factors involved in angiogenesis in different areas during meniscus maturation in pigs. The menisci were removed from the knee joints of neonatal, young and adult pigs, and they were divided into the inner, intermediate and outer areas. Vascular characterization and meniscal maturation were evaluated by immunohistochemistry and Western blot analysis. In particular, expression of the angiogenic factor Vascular Endothelial Growth Factor (VEGF) and the anti-angiogenic marker Endostatin (ENDO) was analysed, as well as the vascular endothelial cadherin (Ve-CAD). In addition, expression of Collagen II (COLL II) and SOX9 was examined, as markers of the fibro-cartilaginous differentiation. Expression of VEGF and Ve-CAD had a similar pattern in all animals, with a significant increase from the inner to the outer part of the meniscus. Pooling the zones, expression of both proteins was significantly higher in the neonatal meniscus than in young and adult menisci. Conversely, the young meniscus revealed a significantly higher expression of ENDO compared to the neonatal and adult ones. Analysis of tissue maturation markers showed an increase in COLL II and a decrease in SOX9 expression with age. These preliminary data highlight some of the changes that occur in the swine meniscus during growth, in particular the ensemble of regulatory factors involved in angiogenesis.


[A DNA vaccine encoding the extracellular domain of porcine endoglin induces antitumor immunity in a mouse colon carcinoma model].
Endoglin is a marker of tumor angiogenesis. Increasing evidences proved that passive immunotherapy with anti-endoglin monoclonal antibody can effectively inhibit tumor growth, and xenogeneic homologous DNA vaccine can inhibit cross antitumor immunity. This study was to explore the inhibitory effect of a DNA vaccine encoding the extracellular domain of porcine endoglin (ppEDG) on tumor growth in a mouse colon carcinoma model. ppEDG was used as a DNA vaccine to actively immunize the colon carcinoma-bearing mice. Tumor volume and survival rate of the mice were observed in 3-day intervals. Microvessel density (MVD) was detected by immunohistochemistry; antibodies against self-endoglin were detected by Western blot and ELISA; the B cells that secrete auto-antibodies against self-endoglin were detected by ELISPOT assay. Eighteen days after tumor cell inoculation, the tumor volume was significantly smaller in ppEDG-immunized group than in empty plasmid (e-p) group and normal saline (NS) group (P<0.05), and the survival time was significantly longer in ppEDG-immunized group than in the control groups (P<0.001). MVD was significantly lower in ppEDG-immunized group than in e-p group and NS group (19.2+/-4.5 vs. 76.9+/-14.4 and 81.4+/-16.9, P<0.001). The antibodies against self-endoglin were identified in ppEDG-immunized group; the major subtypes were IgG(1) and IgG(2b). The auto-antibody-producing B cells were much more in ppEDG-immunized group than in e-p group and NS group (82.5+/-14.1 vs. 3.6+/-1.3 and 4.7+/-2.0, P<0.001). ppEDG DNA vaccine could induce the production of auto-antibodies against self-endoglin, which further inhibit angiogenesis and growth of colon carcinoma.


The impact of a free nicotine patch starter kit on quit rates in a state quit line.
All states offer telephone quit lines but they are under-used in part because of the costs associated with promotion. Offering nicotine replacement therapy (NRT) as well as behavioral counseling can increase treatment participation and abstinence rates, but is expensive. Offering less than a full NRT 8-week course can also generate calls to the quit line but less is known about its impact on program outcomes. In October 2004, Oregon--a state with over 3 million people, 500,000 smokers, and a state-funded quit line--introduced the Free Patch Initiative: a free 2-week introductory supply of NRT with phone counseling offered to all callers. We examined the impact of this intervention among insured callers. Most (97.2%) requested free patches, 86.2% used them, and 47.2% obtained additional patches on their own. Six-month outcome data were obtained from insured quit line participants before (n = 268) and after (n = 614) the Initiative launched. Compared with pre-Initiative controls, Free Patch participants were more satisfied with the quit line (84.8% vs. 89.8%; p = .04) and had higher 7-day quit rates using the assumption that eligible nonrespondents are smokers (9.3% vs. 17.0%, OR = 2.0; 95% CI 1.4-2.8) and using respondent only analysis (19% vs. 33.6%, OR = 2.15; 95% CI 1.52-3.04). Offering a free direct mail starter pack of NRT along with telephone counseling is an effective, cost-sharing method for promoting quit line use, enhancing participant satisfaction, and increasing the reach and effectiveness of quit lines among quit line callers with health insurance.


Effects of ethanol and/or caffeine on fetal development and placental amino acid uptake in rats.
The effects of ethanol alone or in combination with caffeine on fetal viability, growth and placental amino acid uptake function in the rat were examined. Compared to pair-fed control values, chronic ethanol exposure reduced fetal survival by 24%, fetal weight by 17%, along with weight decreases of fetal brain (16%), heart (31%), and kidney (48%) as compared to pair-fed control values. Placental weight was significantly increased by 17%. Concomitant caffeine intake generally exacerbated these effects with a further reduction in fetal survival, fetal body and visceral weights. Caffeine intake alone had no consistent effect on these parameters. Acute in vitro (3 mg/ml) and chronic in vivo ethanol exposure reduced placental net uptake of alpha-aminoisobutyric acid (AIB) by 32 and 45%, respectively. Neither acute in vitro (10 micrograms/ml) nor prior chronic caffeine exposure altered villous AIB uptake. Concomitant ethanol and caffeine treatment increased AIB uptake as compared to ethanol alone. However, AIB uptake continued to be reduced (by 22%) as compared to pair-fed control values.


[Smarter Medicine: From the Diagnosis to the Intervention in General and Visceral Surgery].
Smarter Medicine: From the Diagnosis to the Intervention in General and Visceral Surgery Abstract. More is not always a plus. With this slogan, in smarter medicine it is a principle to make a decision together. In general surgery diagnostic or therapeutic interventions have the potential to harm the patient. The admission to the emergency room of a young patient with abdominal pain does not necessarily require a computed tomography. A potential acute appendicitis without typical clinical and laboratory findings could potentially be unmasked by watchful waiting, or even a nonessential operation could be avoided. Possibly, acute cholecystitis or some forms of hollow organ perforation could be treated solely with antibiotics. Is it feasible to treat an acute severe diverticulitis with antibiotics only? In addition, if a colon resection is necessary, could a direct anastomosis be made, and a second operation be avoided? Are there thyroid nodules that do not need removal? The management of diseases in the surgical domain are evaluated with evidence-based medicine in the focus of smarter medicine and newly reconsidered.


The frequency of tetracycline resistance genes in Escherichia coli strains isolated from healthy and diarrheic pet birds.
Pet birds have close contact to human and resistant bacteria can transfer from birds to intestinal flora of human. This study was carried out to determine the tetracycline resistance genes in Escherichia coli strains associated with enteric problem in pet birds. Totally, 295 cloacal swabs were collected from 195 healthy and 100 diarrheic pet birds in Isfahan province, Iran. The presence of E. coli was identified by conventional bacteriological, biochemical, and molecular examinations. The presence of tetracycline resistance genes (tetA, tetB, tetC, tetD, tetE, tetG, tetK, tetL, tetM, tetO, and tetS genes) were examined using three multiplex PCR. The results showed that 18.9% and 43% of cloacal samples of healthy and diarrheic pet birds contained E. coli, respectively. The mean percentage of E. coli isolated from cloacal samples of diarrheic birds was significantly higher than the healthy birds (46.6 vs 23.1%). In healthy birds, out of 37 E. coli isolates, 10 isolates were resistant to tetracycline, harboring tetA and tetB genes (3 tetA vs 7 tetB), but in the diarrheic birds, of 26 resistance E. coli, 11, 12, and 3 strains contained tetA (42.3%), tetB (46.15), and tetA+tetB (11.53%) genes. The percentage of tet genes were significantly higher in diarrheic birds than healthy birds (58.9 vs 24.0%). Both resistant genes of tetA and tetB were detected in E. coli isolates that are related with efflux pump activity. These genes can be transferred between Gram-negative bacteria and they have the potential ability to be transferred to the environment and human flora.


Effects of pergolide on blood pressure and tissue injury in DOCA-salt hypertension.
The present study was designed to evaluate the possible antioxidant effect of pergolide, a DA-2 receptor agonist, in deoxycorticosterone acetate (DOCA)-salt hypertension and its role in endogenous endothelin-1 (ET- 1) production and organ hypertrophy. Male Sprague-Dawley rats were uninephrectomized (UNx) or uninephrectomized, and received subcutaneous implants of DOCA and drank 1% sodium chloride (DOCA). DOCA rats were treated daily for 3 weeks with pergolide (1 mg/kg, i.p.) or vitamin C (1 mg/rat, orally). DOCA-salt treatment increased systolic blood pressure (SBP) in UNx rats by 45 +/- 2 mmHg from 117 +/- 5 to 162 +/- 10 mmHg (p < 0.05), an effect blunted by pergolide and vitamin C. Superoxide generation was not increased in DOCA rats; however, both pergolide and vitamin C significantly reduced superoxide generation by 49 +/- 7% and 52 +/- 13%, respectively (p < 0.05). Plasma ET-1 levels increased twofold in UNx rats but was reduced to 42 +/- 7% (p < 0.05) in DOCA compared to UNx rats. Pergolide and vitamin C reduced plasma ET-1 levels further by 43 +/-10% (p < 0.05) and 46 +/- 8% (p < 0.05), respectively. Pergolide increased urinary Na+ excretion but did not alter urinary protein excretion or the left ventricular and aortic hypertrophy in DOCA rats. These data suggest that the reduction of SBP by pergolide in DOCA-salt hypertension may be attributed to its natriuretic ability, not its ability to reduce superoxide generation or ET- 1 production.


Renal Denervation Influences Angiotensin II Types 1 and 2 Receptors.
The sympathetic and renin-angiotensin systems (RAS) are two critical regulatory systems in the kidney which affect renal hemodynamics and function. These two systems interact with each other so that angiotensin II (Ang II) has the presynaptic effect on the norepinephrine secretion. Another aspect of this interaction is that the sympathetic nervous system affects the function and expression of local RAS receptors, mainly Ang II receptors. Therefore, in many pathological conditions associated with an increased renal sympathetic tone, these receptors' expression changes and renal denervation can normalize these changes and improve the diseases. It seems that the renal sympathectomy can alter Ang II receptors expression and the distribution of RAS receptors in the kidneys, which influence renal functions.


A Novel 5-Methylcytosine- and Immune-Related Prognostic Signature Is a Potential Marker of Idiopathic Pulmonary Fibrosis.
Idiopathic pulmonary fibrosis (IPF) is the most common and highly lethal pulmonary interstitial lung disease. The current study is aimed at investigating reliable markers suitable for the treatment and identification of IPF. This study constructed the first 5-methylcytosine- (m5C-) and immune-related prognostic signature (m5CPS) based on coexpressed genes of m5C regulatory genes and immune-related genes. The m5CPS was established using the training cohort (n = 68) and verified using the test (n = 44) and validation (n = 64) cohorts. The area under the curve (AUC) values were utilized to evaluate the accuracy of m5CPS in predicting the survival of IPF patients. The Kaplan-Meier curves and Cox regression analyses were used to assess the prognostic effect of m5CPS. The AUC was utilized to evaluate the reliability of m5CPS in distinguishing IPF patients from healthy individuals. In terms of the results, m5CPS could predict the one-, three-, and five-year survival rates of IPF patients with high accuracy (AUC = .803-.973). In fact, m5CPS is not only an independent indicator of the poor prognosis of IPF patients (hazard ratio > 1; p < .05) but can also distinguish IPF patients from healthy individuals (AUC = .862). Also, m5CPS may affect the immune response and inflammatory response, and it was positively associated with the infiltration levels of active mast cells (p < .05). In sum, the current study establishes a novel m5CPS for IPF and reveals the role of m5CPS as a reliable marker for predicting the prognosis and disease status of IPF patients.


Growth depth effects of bacteria in ground turkey meat patties subjected to high carbon dioxide or high oxygen atmospheres.
Modified atmosphere packaging (MAP) is used to extend the shelf life of ground meats by altering the gas atmosphere surrounding the meat. This study evaluated how deep MAP bactericidal effects penetrate into a ground meat patty. Patties made from freshly ground turkey breasts were subjected to 2 MAP treatments of high CO(2) (97%) or high O(2) (80% O(2), 20% CO(2)). Total plate and lactic acid bacterial counts were determined for 3 patty depths (top, middle, bottom). Meat surface color and the package gas headspace composition were also measured. All analyses were performed on 0, 3, 6, 9, and 12 d. Changes in gas headspace and meat surface color were also measured at 0, 3, 6, 9, and 12 d. High CO(2) atmosphere maintained a better meat surface color than high O(2) atmosphere over the whole storage period. Overall counts were lower (P < or = 0.05) in a high-CO(2) atmosphere compared with a high-O(2) modified atmosphere. Patties stored under a high-CO(2) atmosphere displayed slower bacterial growth in the top layer compared with the middle and bottom layers. Total plate count did not differ (P > or = 0.05) in layers for patties pack-aged in a high-O(2) atmosphere Lactic acid bacterial counts increased in the high-O(2) modified atmosphere by d 9 and 12 of storage; no increase was observed in CO(2)-packaged patties. Thus, high-CO(2) MAP slowed the growth of total bacteria as well as lactic acid bacteria. Also, there was slower growth in the top meat layer exposed to CO(2) compared with interior layers.


Effect of Probiotics and Herbal Products on Intestinal Histomorphological and Immunological Development in Piglets.
The aim of the study was to evaluate the effect of probiotics and herbal products on the intestinal histomorphological and immunological development in piglets. Accordingly, 2-week-old piglets were allocated in 4 groups: C (basal diet), Pro (basal diet + probiotics), Pro+B (basal diet + probiotics + buckwheat bran), and H (powder of herbs). After 6 weeks of the experiment, 4 piglets from each experimental group were randomly selected and slaughtered at a slaughterhouse. Samples of tissue and digestive content from the jejunum and colon were collected for bacteriological, histological, and immunohistochemical examination. The results showed that probiotics increased the number of Lactobacillus spp. in the small (p < 0.05) and large intestines. The intestinal histomorphology was improved (p < 0.05) in all experimental groups by an increased villus height, VH : CD ration, colon crypt depth, and number of Ki-67+ epithelial cells. A higher number (p < 0.05) of goblet cells and their acidification were observed in group Pro, while the density of goblet cells was decreased by the herbs. Probiotics increased (p < 0.05) the number of intraepithelial lymphocytes (IELs), density of CD3+ cells in Peyer's patches (PPs), and lamina propria (LP). In group H, a dual effect on the CD3+ cell distribution was observed. The herbs reduced (p < 0.05) the number of IELs and CD3+ in LP but increased the distribution of CD3+ cells in PPs. In the colon, herbs increased CD3+ cells in LP as well. It suggests that probiotics and herbs had influence on the intestinal histomorphology and the ability to modulate the mucosal immune system; however, the combination of probiotics and buckwheat bran was not so convincing, probably due to the inhibitory effect of the buckwheat bran on the probiotics used.


Personalized local SAR prediction for parallel transmit neuroimaging at 7T from a single T1-weighted dataset.
Parallel RF transmission (PTx) is one of the key technologies enabling high quality imaging at ultra-high fields (≥7T). Compliance with regulatory limits on the local specific absorption rate (SAR) typically involves over-conservative safety margins to account for intersubject variability, which negatively affect the utilization of ultra-high field MR. In this work, we present a method to generate a subject-specific body model from a single T1-weighted dataset for personalized local SAR prediction in PTx neuroimaging at 7T. Multi-contrast data were acquired at 7T (N = 10) to establish ground truth segmentations in eight tissue types. A 2.5D convolutional neural network was trained using the T1-weighted data as input in a leave-one-out cross-validation study. The segmentation accuracy was evaluated through local SAR simulations in a quadrature birdcage as well as a PTx coil model. The network-generated segmentations reached Dice coefficients of 86.7% ± 6.7% (mean ± SD) and showed to successfully address the severe intensity bias and contrast variations typical to 7T. Errors in peak local SAR obtained were below 3.0% in the quadrature birdcage. Results obtained in the PTx configuration indicated that a safety margin of 6.3% ensures conservative local SAR estimates in 95% of the random RF shims, compared to an average overestimation of 34% in the generic "one-size-fits-all" approach. A subject-specific body model can be automatically generated from a single T1-weighted dataset by means of deep learning, providing the necessary inputs for accurate and personalized local SAR predictions in PTx neuroimaging at 7T.


Genesis of episodic growth hormone secretion.
The secretion of growth hormone (GH) is governed by the remarkably complex interaction of neural and feedback regulatory components. The net result is a striking pulsatile pattern of GH release evident in every mammalian species studied so far. Extensive experimental evidence indicates that the episodic pattern of GH release from the pituitary gland is generated by a delicate interplay between at least two hypothalamic hormones--a stimulatory GH-releasing factor (GRF) and an inhibitory hormone, somatostatin (SRIF). This paper will focus on the interrelation of GRF and SRIF, and on the modulatory influence of GH and insulin-like growth factor (IGF) feedback, in the genesis of episodic GH secretion.


Chemical Fate of a Metamorphic Inducer in Larvae-like Buds of the Cnidarian Cassiopea andromeda.
Larvae-like vegetative buds of the scyphozoan Cassiopea andromeda metamorphose into polyps in the presence of oligopeptides that have a well-defined primary structure. Buds were incubated with the hexapeptide 14C-dansyl-GPGGPA, a representative inducer. Autoradiography of longitudinal sections of these buds revealed rapid internalization of peptide by the buds. Silver grain density was highest in the pre-pedal disc region (or aboral knob) of metamorphosing buds. Larvae and buds sporadically explore their habitat with this aboral knob, searching for a suitable solid substrate to which irreversible attachment will be made. Buds were incubated for 3, 8, or 16 h with 14C-dansyl-GPGGPA, then homogenized and the supernatants analyzed to determine the chemical fate of the inducer. The signal molecule was shown to be partly degraded to 14C-dansyl-GP, partly to 14C-dansyl-G, and in part still present in its original structure. These cleavage products were also found in the surrounding medium after an incubation time of 8 h with 14C-dansyl-GPGGPA, but did not induce metamorphosis. This study suggests that exposure of metamorphosis-inducing peptides to buds of Cassiopea andromeda results in signal termination.


Cross-Species Evaluation of Bioaccumulation Thresholds for Air-Breathing Animals.
In air-breathing organisms, an organic chemical's susceptibility to elimination via urinary excretion and respiratory exhalation can be judged on the basis of the octanol-water partition ratio (KOW) and the octanol-air partition ratio (KOA), respectively. Current regulations specify that chemicals with KOW values of <102 and KOA values of <105 may be screened as non-bioaccumulative in air breathers. Here we used a model-based approach to evaluate whether these thresholds are consistent with a biomagnification factor of 1 for 141 different mammals, birds, and reptiles. Animals with lower rates of respiration (e.g., manatees and sloths) and those ingesting high-lipid diets (e.g., polar bears and carnivorous birds) were predicted to be able to biomagnify persistent chemicals with KOA values of <105. This was also observed for several temperate reptiles due to their lower respiration rates and internal temperatures. Protective KOA thresholds were determined to be <104.85 for mammals, <104.60 for birds, <104.60 for reptiles at >25 °C, and <103.95 for reptiles at ≤25 °C. For all animals, urination alone was not efficient to prevent the biomagnification of any organic chemical. For chemicals with KOW values of <101, we found that biomagnification of persistent chemicals was constrained by the water-air partition ratio (KWA) rather than KOA. Differences in physiology may need to be considered in bioaccumulation assessments of air-breathing species.


Internal diversification of non-Sub-Saharan haplogroups in Sahelian populations and the spread of pastoralism beyond the Sahara.
Today, African pastoralists are found mainly in the Sahel/Savannah belt spanning 6,000 km from west to east, flanked by the Sahara to the north and tropical rainforests to the south. The most significant group among them are the Fulani who not only keep cattle breeds of possible West Eurasian ancestry, but form themselves a gene pool containing some paternally and maternally-transmitted West Eurasian haplogroups. We generated complete sequences for 33 mitogenomes belonging to haplogroups H1 and U5 (23 and 10, respectively), and genotyped 16 STRs in 65 Y chromosomes belonging to haplogroup R1b-V88. We show that age estimates of the maternal lineage H1cb1, occurring almost exclusively in the Fulani, point to the time when the first cattle herders settled the Sahel/Savannah belt. Similar age estimates were obtained for paternal lineage R1b-V88, which occurs today in the Fulani but also in other, mostly pastoral populations. Maternal clade U5b1b1b, reported earlier in the Berbers, shows a shallower age, suggesting another possibly independent input into the Sahelian pastoralist gene pool. Despite the fact that animal domestication originated in the Near East ∼ 10 ka, and that it was from there that animals such as sheep, goats as well as cattle were introduced into Northeast Africa soon thereafter, contemporary cattle keepers in the Sahel/Savannah belt show uniparental genetic affinities that suggest the possibility of an ancient contact with an additional ancestral population of western Mediterranean ancestry.


Prevalence and correlates of eating disorders among Asian Americans: results from the National Latino and Asian American Study.
Our study examines lifetime and 12-month prevalence estimates of eating disorders in Asian American men and women. We also report on the association between social factors and eating disorders, BMI categories, treatment, and impairment. We use data from the National Latino and Asian American Study, a nationally representative survey of the U.S. household population of Latino and Asian Americans. Our present study is based on data from the sample of Asian Americans (N = 2,095). Overall, Asian Americans present with low prevalence for eating disorders. Only lifetime prevalence for binge eating disorder (BED) is significantly higher for Asian women compared to Asian men. Our results show that age is strongly associated with BED and any binge eating. High current BMI of 30-39.9 and >or=40 is strongly associated with BED and any binge eating. Treatment utilization is low, and respondents reported some role impairment. Our findings show that despite low prevalence estimates, eating disorders are present among Asian American men and women. Our data suggest that researchers consider more flexibility in defining and classifying eating disorders, to better detect and measure the prevalence of eating disorders among Asian Americans.


Russian sturgeon cultured in a subtropical climate shows weaken innate defences and a chronic stress response.
Russian sturgeon (Acipenser gueldenstaedtii) has been successfully farmed in Uruguay for the past ten years. However, during the Uruguayan summer fish endure high water temperatures and increased bacterial infections that threaten aquaculture. Our understanding of sturgeon's immune system and its interplay with environmental factors like temperature is almost unknown. This study analysed the way in which seasonal variations affect enzymatic blood components of Russian sturgeon's innate defences, including the serum alternative complement pathway (ACP), ceruloplasmin (Cp) and lysozyme activities. Results showed that summertime conditions in the farm altered these defences in different ways, inducing a significant decrease in ACP and Cp, and an increase in lysozyme. In addition, serum levels of total protein and cortisol decreased in summer, suggesting a chronic stress response was induced in parallel. Subsequently, we analysed whether the increase in water river temperature during summer could account for the observed results. To that end, we acclimated juvenile sturgeons to mild (18 °C) or warm (24 °C) temperatures for 37 days. Like in summer, sturgeons exposed to 24 °C showed lower levels of serum ACP, Cp and total proteins, together with a progressive decrease in body weight and increased fish mortality. Administration of an immunostimulant containing Se and Zn slightly reverted the temperature-induced effects on sturgeon's defences. Altogether, our study provides novel data on various physiological parameters of the Russian sturgeon and highlights the impact warm temperature has on stress and innate immunity in this chondrostean fish.


Hyperkalemia in the elderly.
Hyperkalemia is a common and potentially dangerous condition in elderly patients. These subjects are more likely to have a disease or be taking medications that may induce this disorder. We describe three such cases where the increased concentration of potassium in plasma resulted from decreased renal excretion of this ion, and suggest a simple approach to the etiological diagnosis of hyperkalemia.


Prevention of coalescence during annealing of FePt nanoparticles assembled by convective coating.
FePt nanoparticle suspension was synthesized by reduction of platinum acetylacetonate and decomposition of iron pentacarbonyl in the presence of oleic acid and oleyl amine. The composition of the synthesized nanoparticles was Fe40Pt60. To prevent the coalescence during annealing of FePt nanoparticles we tried two steps of convective coating, where first coating was for silica particle assembly on a silicon substrate and second one was for FePt nanoparticles on the silica layers. It was observed by scanning electron microscopy that FePt nanoparticles were dispersed on the silica surface. After being annealed at 700 degrees C for 30 minutes under nitrogen atmosphere, the particle size of FePt nanoparticles increased slightly from 4 nm to 6 nm but dispersity of the nanoparticles was maintained. Magnetic hysteresis of Fe40Pt60 nanoparticles coating on silica layer after annealing showed typical characteristics of hard magnetic materials, and no incorporation of soft magnetic materials. It was suggested that convective self-assembly with the parallel use of pre-coating that offers solvent flux weakening capillary force between FePt nanoparticles was an effective method to prevent coalescence of nano-sized particles under high temperature annealing.


The prolactin gene is expressed in the hypothalamic-neurohypophyseal system and the protein is processed into a 14-kDa fragment with activity like 16-kDa prolactin.
The 23-kDa form of prolactin (PRL) has been proposed to function as both a mature hormone and a prohormone precursor for different uniquely bioactive forms of the molecule. We have shown that the 16-kDa N-terminal fragment of PRL (16K PRL) inhibits angiogenesis via a specific receptor. In addition, 16K PRL stimulates natriuresis and diuresis in the rat, and kidney membranes contain high-affinity specific binding sites for this PRL fragment. 16K PRL can be derived from an enzymatically cleaved form of PRL (cleaved PRL). With the use of a specific 16K PRL antiserum, we have localized a 14-kDa immunoreactive protein in the paraventricular and supraoptic nuclei of the hypothalamus and in the neurohypophysis. Reverse transcription-polymerase chain reaction of RNA from isolated paraventricular nuclei showed the expression of the full-length PRL mRNA. The neurohypophysis was found to contain the enzymes that produce cleaved PRL, small amounts of PRL, and cleaved PRL. Medium conditioned by neurohypophyseal cultures, enriched with the 14-kDa immunoreactive protein, has antiangiogenic effects that are blocked by the 16K PRL antiserum. These results are consistent with the expression of PRL in the hypothalamic-neurohypophyseal system, and the preferential processing of the protein into a 14-kDa fragment with biological and immunological properties of 16K PRL.


Serotonergic activation during courtship and aggression in the brown anole, Anolis sagrei.
The role of serotonin (5-hydroxytryptamine, 5-HT) in social behavior regulation is not fully understood. While 5-HT release in nuclei of the social behavior network has generally been associated with inhibition of aggressive behavior across multiple classes of vertebrates, less is known about its effects on sexual, especially non-copulatory courtship display behaviors. Furthermore, most research has examined effects at 5-HT release sites, while studies examining the behavioral relevance of source cell populations have generated contradictory findings. This study utilized immunohistochemistry to examine the colocalization of 5-HT with Fos, an immediate early gene product and marker of neural activity, in the raphe and superior reticular nuclei of male brown anoles (Anolis sagrei) exposed to either aggression, courtship, or control social interactions. Supporting previous research, copulation was associated with a decrease in 5-HT activity, while a novel link between 5-HT activity and latency to non-copulatory courtship was also found. Within the aggression group, intensity and frequency of behavior were both associated with decreased 5-HT activity. An effect of social context was also seen, with anoles exposed to either courtship or aggression encounters showing decreased 5-HT activity in certain raphe and superior reticular nuclei populations compared to controls. Interestingly, context effects and behavioral effects were seen at separate brain nuclei, suggesting the presence of separate systems with distinct functional roles.


Outcome trajectory estimation for optimal dynamic treatment regimes with repeated measures.
In recent sequential multiple assignment randomized trials, outcomes were assessed multiple times to evaluate longer-term impacts of the dynamic treatment regimes (DTRs). Q-learning requires a scalar response to identify the optimal DTR. Inverse probability weighting may be used to estimate the optimal outcome trajectory, but it is inefficient, susceptible to model mis-specification, and unable to characterize how treatment effects manifest over time. We propose modified Q-learning with generalized estimating equations to address these limitations and apply it to the M-bridge trial, which evaluates adaptive interventions to prevent problematic drinking among college freshmen. Simulation studies demonstrate our proposed method improves efficiency and robustness.


Long-term results of intravitreal bevacizumab for choroidal neovascularisation in pathological myopia.
To evaluate the long-term results and prognostic factors of intravitreal bevacizumab (IVB) for myopic choroidal neovascularisation (mCNV). Thirty-two eyes of 30 patients with mCNV were included in a prospective case series. Treatment consisted of three monthly 1.25 mg IVB injections. Best corrected visual acuity (BCVA) and CNV area were compared before and after treatment. Prognostic factors included in the regression analyses were age, axial length, baseline BCVA, pretreatment CNV area, CNV location and peripapillary atrophy area. Results were evaluated at 2 years for 32 eyes and at 3 years for 27 eyes. Mean (± SD) baseline BCVA had improved significantly from 30.1 (± 15.6) letters to 45.4 (± 13.0) letters at 3 years (p<0.0001), with a better outcome in eyes with juxtafoveal CNV (40.4 ± 13.5 vs. 54.0 ± 5.8, p=0.001). Baseline BCVA correlated positively with final BCVA (β= 0.560, p=0.001), while age showed a negative correlation (β= -0.399, p=0.01). CNV area decreased from 0.63 (± 0.71) mm(2) at baseline to 0.40 (± 0.57) mm(2) at 3 years (p<0.0001). Peripapillary atrophy area was the only significant contributing determinant for re-treatment (OR 1.20, 95% CI 1.01 to 1.42, p=0.04). A regimen of three monthly IVB injections yielded effective and sustained results in the treatment of mCNV at 3 years of follow-up. Initial BCVA and age were the factors that correlated independently with BCVA outcome.


[Panfilo Castaldi (1430? - 1487): a physician-typographer].
The issue about whether it was Johann Gutenberg in Mainz or Panfilo Castaldi in Feltre (in the Italian region of Veneto) to first invent movable metal type for printing around 1450 still raises a controversy, even though Gutenberg is generally perceived as the one. What is beyond doubt, however, is that Castaldi pioneered the new revolutionary printing method with the historical texts written by great physicians such as Hippocrates, Galen, and Avicenna. His early publishing success raised bitter competition all around him, which eventually drove him out of this flourishing business, and he returned to his long-neglected medical profession. Castaldi's new "art" was received coldly by his apprehensive fellow citizens. As soon as he was buried, they invaded the printing office and, believing that the printing machines were the "devil's instruments", tore it apart.


Structural and thermodynamic characterization of Pal, a phage natural chimeric lysin active against pneumococci.
Pal amidase, encoded by pneumococcal bacteriophage Dp-1, represents one step beyond in the modular evolution of pneumococcal murein hydrolases. It exhibits the choline-binding module attaching pneumococcal lysins to the cell wall, but the catalytic module is different from those present in the amidases coded by the host or other pneumococcal phages. Pal is also an effective antimicrobial agent against Streptococcus pneumoniae that may constitute an alternative to antibiotic prophylaxis. The structural implications of Pal singular structure and their effect on the choline-amidase interactions have been examined by means of several techniques. Pal stability is maximum around pH 8.0 (Tm approximately 50.2 degrees C; DeltaHt = 183 +/- 4 kcal mol(-1)), and its constituting modules fold as two tight interacting cooperative units whose denaturation merges into a single process in the free amidase but may proceed as two well resolved events in the choline-bound state. Choline titration curves reflect low energy ligand-protein interactions and are compatible with two sets of sites. Choline binding strongly stabilizes the cell wall binding module, and the conformational stabilization is transmitted to the catalytic region. Moreover, the high proportion of aggregates formed by the unbound amidase together with choline preferential interaction with Pal dimers suggest the existence of marginally stable regions that would become stabilized through choline-protein interactions without significantly modifying Pal secondary structure. This structural rearrangement may underlie in vitro "conversion" of Pal from the low to the full activity form triggered by choline. The Pal catalytic module secondary structure could denote folding conservation within pneumococcal lytic amidases, but the number of functional choline binding sites is reduced (2-3 sites per monomer) when compared with pneumococcal LytA amidase (4-5 sites per monomer) and displays different intermodular interactions.


Immunological abnormalities associated with liver disease: cause or effect?
Immunological abnormalities are demonstrable in patients with various types of liver damage. These may be (a) non-specific and unrelated to pathogenesis, e.g. auto-antibodies such as anti-nuclear factor; (b) specifically directed against liver antigens but not pathogenetic, e.g. cell mediated immune (CMI) reactions to liver antigen as seen in experimental carbon tetrachloride poisoning; (c) of such a nature as to modify the pathology produced by hepatotoxic agents, e.g. hepatitis B virus or alcohol; (d) primarily responsible for hepatic pathology, e.g. in idiopathic chronic active hepatitis. The latter two possibilities remain unproven although there is growing evidence that immune responses do play some role in the pathogenesis of acute and chronic hepatitis B and possibly also in the pathogenesis of alcoholic liver disease. It seems much less likely that primary abnormalities of the immune systems are responsible for any type of liver disease. In summary, therefore, the available evidence suggests that immune reactions could develop as a consequence of liver damage and only in certain circumstances do these reactions play a role in the development and continuation of hepatic pathology.


The mucus barrier. Its role in gastroduodenal mucosal protection.
A layer of water-insoluble mucus gel has been shown to form a continuous cover over the gastroduodenal mucosal surfaces, of median thickness of 180 micron in stomach in humans. This adherent mucus is the first line in mucosal defence against the natural aggressors, acid and pepsin, in the lumen. Mucus gel provides a stable unstirred layer that supports surface neutralisation of acid by mucosal bicarbonate. Mucus gel is a diffusion barrier to pepsin in the lumen, preventing proteolysis of the underlying epithelial cells. There is, however, a dynamic balance between digestion by pepsin of the mucus layer at its luminal aspect and secretion of new mucus by the epithelium. There is evidence that, in peptic ulcer disease, the rate of peptic degradation of the mucus barrier is increased. Exogenous damaging agents such as ethanol and aspirin permeate the gel matrix of the mucus barrier, rapidly damaging the underlying epithelium. The subsequent reepithelialisation process is protected by a gelatinous coat over ten times thicker than the original adherent mucus layer. This gelatinous coat is primarily a fibrin-based gel with necrotic cells and mucus.


Leukotrienes, fish-oil, and asthma.
Studies suggest that leukotrienes which have been metabolized from arachidonic acid released from membranes phospholipids during cell activation may play a significant role in a variety of inflammatory disorders including the pathophysiology of chronic allergic asthma. Two major types of polyunsaturated fatty acids prominent in marine fish oils are eicosapentaenoic acid (EPA) and docosahexaenoic acid (DCHA). These fish oils limit leukotriene synthesis and biological activities by substituting substrate fatty acids as alternatives to arachidonic acid. Both EPA and DCHA inhibit the conversion of arachidonic acid by the cyclooxygenase pathway to prostanoid metabolites and reduce the production of platelet-activating factor (PAF).