Cell and molecular biology underpinning the effects of PEDF on cancers in general and osteosarcoma in particular.
Cancer is becoming an increasingly common disease in which abnormal cells aggressively grow, invade, and metastasize. In this paper, we review the biological functions of PEDF (pigmented epithelium-derived factor) against cancer, with a focus on a particular type of bone cancer called osteosarcoma. PEDF is a 50 kDa glycoprotein and is a potent inhibitor of angiogenesis, via its ability to decrease proliferation and migration of endothelial cells. This paper critically examines the anticancer activities of PEDF via its role in antiangiogenesis, apoptosis-mediated tumor suppression, and increased tumor cell differentiation. Recently, an orthotopic model of osteosarcoma was used to show that treatment with PEDF had the greatest impact on metastases, warranting an evaluation of PEDF efficacy in other types of cancers.


Transient x-ray diffraction with simultaneous imaging under high strain-rate loading.
Real time, in situ, multiframe, diffraction, and imaging measurements on bulk samples under high and ultrahigh strain-rate loading are highly desirable for micro- and mesoscale sciences. We present an experimental demonstration of multiframe transient x-ray diffraction (TXD) along with simultaneous imaging under high strain-rate loading at the Advanced Photon Source beamline 32ID. The feasibility study utilizes high strain-rate Hopkinson bar loading on a Mg alloy. The exposure time in TXD is 2-3 μs, and the frame interval is 26.7-62.5 μs. Various dynamic deformation mechanisms are revealed by TXD, including lattice expansion or compression, crystal plasticity, grain or lattice rotation, and likely grain refinement, as well as considerable anisotropy in deformation. Dynamic strain fields are mapped via x-ray digital image correlation, and are consistent with the diffraction measurements and loading histories.


Suppression methods of radon emanation from phosphorus fertiliser and diatomaceous earth.
The present paper shows methods to suppress radon emanation from artificial porous materials such as phosphorous fertiliser or diatomaceous earth with a small amount of radium. The basic concept of suppression is making the radon emanation mechanism 'null', which comes from the fact that recoil is the main mechanism of radon emanation at room temperature. Nullifying may be done through removal of water in the pore volume by heating and through removal of pores by melting or filling with sulphur. These radon emanation suppression methods were tried for phosphorous fertiliser and diatomaceous earth with a small amount of radium. The melting method was the most effective of all. Sustainability of these methods was also studied. The melting method was the most sustainable. The heating method was also sustainable for diatomaceous earth in spite of a long-term immersion in water.


Limited penetration of perfluorocarbon in porcine pancreas preserved by two-layer method with (19)fluorine magnetic resonance spectroscopy and headspace gas chromatography.
The mechanism of the two-layer method (TLM) of pancreas preservation is unclear. Facilitating oxygen diffusion into preserved pancreas has been suggested, but direct measurements of tissue pO(2) have yielded conflicting results. The degree of penetration of perfluorocarbon (PFC) into the pancreas during TLM storage is unknown. Segments of porcine pancreas (7.5 cm in length) were preserved either in University of Wisconsin solution (UW) alone (n = 6) or in TLM for 24 h (n = 6). Pancreatic samples were analyzed using Varian INOVA 9.4 T MR scanner. External PFC standard was introduced for quantification. Four consecutive transverse images of 4 mm thickness were obtained using a spin-echo sequence. (19)Fluorine magnetic resonance spectroscopy ((19)F MRS) was performed with the same parameters except with more averages. MR data were confirmed by headspace chromatography. PFC standard was readily detected in (19)F MR images. There was no signal from pancreas in (19)F MR images following either UW or TLM storage. (19)F MR spectra typical of PFC were not obtained from either UW- or TLM-preserved pancreas with nonlocalized (19)F MRS. Mean concentration of PFC in TLM pancreas measured by head space chromatography was 0.011 nl/g (SD ± 0.006), not significantly different from background concentration (0.012 nl/g, SD ± 0.006) in UW pancreas (p = 0.42). There was no evidence of penetration of PFC into pancreas tissues investigated either by MR or chromatography in organs preserved at hypothermia by TLM, and mechanisms of TLM remain speculative.


A mutation in GJB3 is associated with recessive erythrokeratodermia variabilis (EKV) and leads to defective trafficking of the connexin 31 protein.
Erythrokeratodermia variabilis (EKV) is a skin disorder characterized by variable (transient) erythemas and fixed keratosis. The disorder maps to chromosome 1p34-35, a location that contains the GJB3 gene encoding the gap junction protein connexin 31. Until now, only heterozygote mutations in the form of dominant inheritance have been described in this gene associated with EKV. We report here a homozygote mutation in the connexin 31 gene, found in a family that shows recessive inheritance of the disorder, thus providing the first molecular support for a recessive variant of EKV. The entire GJB3 coding sequence was scanned for mutations by sequencing. We detected a T-->C transition at position 101 of the coding sequence, which replaces a leucine with a proline at residue 34 of the protein (L34P). Evolutionary analysis shows that this mutation is located at a highly conserved region of connexin in the first putative transmembrane helix (TMH). In transfected keratinocytes, L34P connexin 31 had a cytoplasmic distribution, suggesting that the mutant form of this protein will not form normal gap junctions between adjacent cells. The change of leucine to proline is likely to alter the structure of the first TMH of connexin by inducing a kink, thus influencing connexon structure and function.


Cloning, molecular characterization, and expression of the genes encoding the lytic functions of lactococcal bacteriophage phi LC3: a dual lysis system of modular design.
The genes encoding the lysis proteins of Lactococcus lactis bacteriophage phi LC3 were cloned, sequenced, and expressed in Escherichia coli. The phi LC3 lysis genes, lysA and lysB, encode a membrane-disrupting protein (LysA) of 88 amino acids, and a cell wall degrading protein (LysB) of 429 amino acids, which shares significant sequence similarity with lysins from the Streptococcus pneumoniae phages Cp-1, Cp-7, and Cp-9, and Lactobacillus delbrueckii phage mv1. Both LysA and LysB function in E. coli, as judged by lysis of the E. coli host cells and by lytic activity against lactococcal cells when the cloned lysA and lysB genes are expressed. The LysA protein possesses two putative transmembrane helices and highly charged N- and C-termini, and is structurally similar to phage holins that are known to induce lesions in the inner membrane through which phage endolysin can be released to its cell wall substrate. The C-terminal end of LysB contains two highly homologous sequence repeats of 43 amino acids. The LysB repeats show strong sequence similarity to repeats found in lytic enzymes from other Gram-positive bacteria and from Bacillus subtilis phage phi 29 and PZA, as well as in some functionally unrelated proteins, and they are possibly involved in binding of the enzyme to the cell wall substrate. The organization of the dual phi LC3 lysis system supports earlier suggestions that exchange of modular units is an important principle in protein evolution.


The role of α-synuclein and tau hyperphosphorylation-mediated autophagy and apoptosis in lead-induced learning and memory injury.
Lead (Pb) is a well-known heavy metal in nature. Pb can cause pathophysiological changes in several organ systems including central nervous system. Especially, Pb can affect intelligence development and the ability of learning and memory of children. However, the toxic effects and mechanisms of Pb on learning and memory are still unclear. To clarify the mechanisms of Pb-induced neurotoxicity in hippocampus, and its effect on learning and memory, we chose Sprague-Dawley rats (SD-rats) as experimental subjects. We used Morris water maze to verify the ability of learning and memory after Pb treatment. We used immunohistofluorescence and Western blotting to detect the level of tau phosphorylation, accumulation of α-synuclein, autophagy and related signaling molecules in hippocampus. We demonstrated that Pb can cause abnormally hyperphosphorylation of tau and accumulation of α-synuclein, and these can induce hippocampal injury and the ability of learning and memory damage. To provide the new insight into the underlying mechanisms, we showed that Grp78, ATF4, caspase-3, autophagy-related proteins were induced and highly expressed following Pb-exposure. But mTOR signaling pathway was suppressed in Pb-exposed groups. Our results showed that Pb could cause hyperphosphorylation of tau and accumulation of α-synuclein, which could induce ER stress and suppress mTOR signal pathway. These can enhance type II program death (autophgy) and type I program death (apoptosis) in hippocampus, and impair the ability of learning and memory of rats. This is the first evidence showing the novel role of autophagy in the neurotoxicity of Pb.


[Clinical significance of the doppler evaluation in ductus venosus, hepatic veins and pulmonary veins].
Doppler evaluation of the fetal venous system at present improves assessment of fetal well-being in many conditions. Actually, analysis of ductus venosus waveforms seems to be the most important. It place role in detection of genetic abnormalities (in low pregnancies), prediction of outcomes growth-restricted fetuses, assessment of severity of heart failure due to congestive heart anomalies, fetal infections, hydrops fetalis. Hepatic veins are known rather as an additional parameter (for ductus venosus) in the severely compromised fetus. Doppler evaluation of pulmonary veins may be useful in prediction of fetal lung maturity and in detection some difficult circulatory anomalies.


Non-invasive monitoring of microbial triterpenoid production using nonlinear microscopy techniques.
Introduction: Bioproduction of plant-derived triterpenoids in recombinant microbes is receiving great attention to make these biologically active compounds industrially accessible as nutraceuticals, pharmaceutics, and cosmetic ingredients. So far, there is no direct method for detecting triterpenoids under physiological conditions on a cellular level, information yet highly relevant to rationalizing microbial engineering. Methods: Here, we show in a proof-of-concept study, that triterpenoids can be detected and monitored in living yeast cells by combining coherent anti-Stokes Raman scattering (CARS) and second-harmonic-generation (SHG) microscopy techniques. We applied CARS and SHG microscopy measurements, and for comparison classical Nile Red staining, on immobilized and growing triterpenoid-producing, and non-producing reference Saccharomyces cerevisiae strains. Results and Discussion: We found that the SHG signal in triterpenoid-producing strains is significantly higher than in a non-producing reference strain, correlating with lipophile content as determined by Nile red staining. In growing cultures, both CARS and SHG signals showed changes over time, enabling new insights into the dynamics of triterpenoid production and storage inside cells.


Expression and function of the metabotropic purinergic P2Y receptor family in experimental seizure models and patients with drug-refractory epilepsy.
ATP is released into the extracellular space during pathologic processes including increased neuronal firing. Once released, ATP acts on P2 receptors including ionotropic P2X and metabotropic P2Y receptors, resulting in changes to glial function and neuronal network excitability. Evidence suggests an involvement of P2Y receptors in the pathogenesis of epilepsy, but there has been no systematic effort to characterize the expression and function of the P2Y receptor family during seizures and in experimental and human epilepsy. Status epilepticus was induced using either intra-amygdala kainic acid or pilocarpine to characterize the acute- and long-term changes in hippocampal P2Y expression. P2Y expression was also investigated in brain tissue from patients with temporal lobe epilepsy. Finally, we analyzed the effects of two specific P2Y agonists, ADP and UTP, on seizure severity and seizure-induced cell death. Both intra-amygdala kainic acid and pilocarpine-induced status epilepticus increased the transcription of the uracil-sensitive P2Y receptors P2ry2 , P2ry4 , and P2ry6 and decreased the transcription of the adenine-sensitive P2Y receptors P2ry1 , P2ry12 , P2ry13 . Protein levels of P2Y1 , P2Y2 , P2Y4 , and P2Y6 were increased after status epilepticus, whereas P2Y12 expression was decreased. In the chronic phase, P2ry1 , P2ry2 , and P2ry6 transcription and P2Y1 , P2Y2 , and P2Y12 protein levels were increased with no changes for the other P2Y receptors. In hippocampal samples from patients with temporal lobe epilepsy, P2Y1 and P2Y2 protein expression was increased, whereas P2Y13 levels were lower. Demonstrating a functional contribution of P2Y receptors to seizures, central injection of ADP exacerbated seizure severity, whereas treatment with UTP decreased seizure severity during status epilepticus in mice. The present study is the first to establish the specific hippocampal expression profile and function of the P2Y receptor family after experimental status epilepticus and in human temporal lobe epilepsy and offers potential new targets for seizure control and disease modification.


Isocyano Enones: Addition-Cyclization Cascade to Oxazoles.
Copper iodide catalyzes the conjugate addition of organometallic and heteroatom nucleophiles to isocyano enones to afford oxazoles. A range of enolates, metalated nitriles, amines, and thiols undergo catalyzed conjugate addition to cyclic and acyclic oxoalkene isocyanides. Mechanistic studies suggest that copper complexation facilitates the nucleophilic attack on the isocyano enone to generate an enolate that cyclizes onto the isocyanide leading to a variety of substituted acyclic or ring-fused oxazoles.


Quantitative analysis of immunoglobulin G subclasses in the rat.
Quantitative ELISAs have been developed for the four immunoglobulin G (IgG) subclasses (IgG1, IgG2a, IgG2b and IgG2c) of the rat. These assays were shown to have excellent sensitivity, reproducibility and adequate specificity for studies of natural IgG and antigen-elicited IgG responses. The sensitivity (working range for each isotype assay) was: IgG1, 1.6 to 200 ng/ml; IgG2a, 8 to 200 ng/ml; IgG2b, 1.6 to 200 ng/ml; and IgG2c, 1.6 to 1000 ng/ml. The isotype sum and the direct assay of total plasma IgG agreed closely. The utility of these assays was demonstrated in a study of the development of total IgG and of the specific IgG response following immunization with tetanus toxoid (TT). For total IgG, the predominant isotype was IgG2b (64% of total IgG) followed by IgG2a (29%), IgG1 (4%) and IgG2c (3%). In contrast, the anti-TT response was mainly of the IgG1 subclass (57% of total anti-TT). These quantitative assays should prove useful for investigating the response to experimental vaccines and the influence of cytokines on class switching in vivo.


[Comorbidities in HIV infection and aging with HIV ].
HIV infection has become a chronic condition with a life-long treatment. As AIDS-related mortality is decreasing, persons living with HIV are aging, their life expectancy tending to reach that of the general population. Aging with the virus and on antiretroviral drugs is raising new challenges: "non AIDS-defining" cancers, cardiovascular diseases, osteoporosis, and maybe neurocognitive disorders represent a new set of comorbidities in this setting, and some of them are now becoming significant causes of death. It is now clear that risk factors for these conditions include the classical risk factors known in the general population, but also risk factors specifically related to the history of HIV infection and its treatment. As a consequence, treating persons with HIV infection now follows two main objectives: controlling the virus and taking long-term comorbidities into account (prevention, testing and treatment). Specificitiesare linked to the existence of HIV-specific risk factors and to the problem of drug-drug interactions with antiretrovirals.


Neutralization of human immunodeficiency virus type 1 by complement occurs by viral lysis.
The ability of complement to inactivate human immunodeficiency virus (HIV) in the presence of specific antibody was evaluated. HIV was treated with complement and/or antibody, and then its titer was determined on the CD4+ H9 cell line. While complement alone had no effect on the HIV titer, complement plus subneutralizing levels of antibody resulted in titer reductions. Complement sources deficient in membrane attack component C5 or C8 did not inactivate antibody-treated HIV, suggesting that neutralization occurred via lysis. This possibility was investigated by assessing release of reverse transcriptase (RT) from the virion. Antibody plus complement, but neither reagent alone, released RT from HIV in a dose-dependent manner. Release of RT did not occur with C5- or C8-deficient sera, also indicating a requirement for membrane attack components. These studies show that complement can neutralize HIV via the classical complement pathway and that this neutralization occurs via C5b-9-mediated viral lysis. Thus, complement may play a major role in resistance to disease by lysing HIV and preventing infection of Fc- and complement receptor-positive cells, as well as CD4+ cells.


A novel robot-assisted knee arthroplasty system (ROSA) and 1-year outcome: A single center experience.
Total knee arthroplasty is a successful procedure in the treatment of knee osteoarthritis. Searches in surgical technique have focused surgeons in particular on implant alignment. For this purpose, the use of robot-assisted total knee arthroplasty has become increasingly common in the last 10 years. A total of 46 patients (66 knees) who were operated for knee osteoarthritis with Robotic Surgical Assistant (ROSA, Zimmer-Biomet, Warshaw, Indiana, USA) between 2021 and 2023 were included in the study. Preoperative planning and intraoperative incision time, total surgical time, range of motion and follow-up time recorded. Oxford knee scores and knee society scores (KSS) of the patients were compared before and after surgery. At the last follow-up Forgotten Joint Score and the sagittal and coronal plane alignments were evaluated. Preoperative mean Oxford score of the right knee of the patients was 18.5 ± 3.2, post-surgery mean Oxford score progressed to 43.5 ± 2.2. While the preoperative left knee Oxford score of the patients was 16.9 ± 2.3, the mean left knee Oxford score improved to 43.4 ± 2.2 postoperatively. The mean KSS score of the patients' right knee preoperatively was 49.7 ± 3.5, and progressed to 89.2 ± 4.7 postoperatively. While the preoperative mean left knee KSS score of the patients was 46.5 ± 4.3, the mean KSS score improved to 89.8 ± 3.2 postoperatively. The mean Forgotten Joint Score of the left knee at the last follow-up of the patients was 77.4 ± 3.8, while the mean Forgotten Joint Score of the right knee was 75.4 ± 5.9. The results of ROSA-supported knee arthroplasty found to be functionally successful.


Pneumatosis cystoides intestinalis associated with massive free air mimicking perforated diffuse peritonitis.
While pneumatosis cystoides intestinalis (PCI) is a rare disease entity associated with a wide variety of gastrointestinal and non-gastrointestinal disorders, PCI associated with massive intra- and retroperitoneal free air is extremely uncommon, and is difficult to diagnose differentially from perforated peritonitis. We present two cases of PCI associated with massive peritoneal free air and/or retroperitoneal air that mimicked perforated peritonitis. These cases highlight the clinical importance of PCI that mimics perforated peritonitis, which requires emergency surgery. Preoperative imaging modalities and diagnostic laparoscopy are useful to make an accurate diagnosis.


Effects of Organic Solvents on Streptomyces griseus Protease I with Transfer Action.
The protease I from Streptomyces griseus var. alcalophilus strongly catalyzed the transfer reaction forming hydroxamic acids of various amino acids, especially aromatic and hydrophobic amino acids. Dimethyl sulfoxide (DMSO), 1,4-butane diol, and glycerol protected this enzyme from heat denaturation. Moreover, only DMSO strongly activated the transfer action of protease I and the velocity of reaction was accelerated three times in the presence of 50% DMSO. The yield of transfer product strongly depended on reaction time and the concentrations of enzyme and substrates in the presence of DMSO. The velocity of the transfer reaction was faster than that of the hydrolysis reaction under the conditions of 0.1 M Phe-OEt, 0.75 M NH2OH, and 50% DMSO.


Adverse pregnancy outcomes following syphilis treatment in pregnancy in the UK.
Syphilis infection in pregnancy is known to cause a number of severe adverse pregnancy outcomes, including second-trimester miscarriage, stillbirth, very pre-term delivery and neonatal death, in addition to congenital syphilis. A retrospective review of women with positive syphilis serology and a pregnancy outcome between 2005 and 2012 in Leeds, UK, was performed. In all, 57 cases of positive syphilis serology in pregnancy were identified: 24 with untreated syphilis treated in the current pregnancy (Group 1); seven with reported but unconfirmed prior treatment who were retreated (Group 2); and 26 adequately treated prior to pregnancy (Group 3). The rate of severe adverse pregnancy outcomes in Group 1 at 21% was significantly higher than the 0% outcome of Group 3 (p = 0.02). The severe adverse pregnancy outcomes were two second-trimester miscarriages, two pre-term births at 25 and 28 weeks and one stillbirth at 32 weeks. There were no cases of term congenital syphilis or term neonatal death, but we observed high rates of other adverse pregnancy outcomes despite treatment during pregnancy. Rapid referral for treatment is needed before 18 weeks in order to minimise adverse pregnancy outcomes.


Optimization of Tissue Culturing and Genetic Transformation Protocol for Casuarina equisetifolia.
Casuarina equisetifolia is widely used in agroforestry plantations for soil stabilization, ecosystem rehabilitation, reclamation, and coastal protection. Moreover, C. equisetifolia has remarkable resistance to typhoons, desert, low soil fertility, drought, and salinity, but not cold. Therefore, it is significant to breed high-quality Casuarina varieties to improve the tolerance and adaptability to cold weather by molecular techniques. The establishment of a rapid and efficient callus induction and regeneration system via tissue culture is pre-requisite for the genetic transformation of C. equisetifolia, which is so far lacking. In this study, we reported an efficient and rapid regeneration system using stem segment explants, in which callus induction was found to be optimal in a basal medium supplemented with 0.1 mg⋅L-1 TDZ and 0.1 mg⋅L-1 NAA, and proliferation in a basal medium containing 0.1 mg⋅L-1 TDZ and 0.5 mg⋅L-1 6-BA. For bud regeneration and rooting, the preferred plant growth regulator (PGR) in basal medium was 0.5 mg⋅L-1 6-BA, and a combination of 0.02 mg⋅L-1 IBA and 0.4 mg⋅L-1 IAA, respectively. We also optimized genetic a transformation protocol using Agrobacterium tumefaciens harboring the binary vector pCAMBIA1301 with β-glucuronidase (GUS) as a reporter gene. Consequently, 5 mg L-1 hygromycin, 20 mg L-1 acetosyringone (As), and 2 days of co-cultivation duration were optimized to improve the transformation efficiency. With these optimized parameters, transgenic plants were obtained in about 4 months. Besides that, Agrobacterium rhizogenes-mediated transformation involving adventitious root induction was also optimized. Our findings will not only increase the transformation efficiency but also shorten the time for developing transgenic C. equisetifolia plants. Taken together, this pioneer study on tissue culturing and genetic transformation of C. equisetifolia will pave the way for further genetic manipulation and functional genomics of C. equisetifolia.


Exendin-4 normalized postcibal glycemic excursions in type 1 diabetes.
Exendin-4 is a reptilian peptide that activates the mammalian receptor for truncated glucagon-like peptide 1 (tGLP-1) with relatively prolonged actions. Exendin-4 and tGLP-1 can reduce blood glucose levels by stimulating insulin secretion, inhibiting glucagon secretion, and delaying gastric emptying. We tested a range of doses of exendin-4 on postcibal glycemic excursions in nine volunteers with type 1 diabetes, all with negligible endogenous insulin secretion, in paired comparisons with vehicle in at least six volunteers with each of six doses. We established a side effect-free dose and an appropriate antecibal time for sc administration of exendin-4. Subsequently, exendin-4 was administered 15 min before breakfast, with usual insulin, to eight of the volunteers. Acetaminophen was ingested with the meal as an indicator of gastric emptying. The mean plasma glucose excursion was reduced by 90%, falling into the normal range, after breakfast, whereas plasma pancreatic polypeptide, glucagon, and acetaminophen levels were reduced, and insulin levels were not affected. Thus, normalization of postcibal glycemia was associated with delayed gastric emptying and suppression of glucagon secretion, without increased secretion or blood levels of insulin. We suggest that tGLP-1 agonists have therapeutic potential as congeners with insulin in C-peptide-negative type 1 diabetes.


Sodium intake and cardiac sympatho-vagal balance in young men with high blood pressure.
We have previously reported that a high sodium intake increases sleep-time blood pressure (BP) in young men. However, there are cases in which this relation does not apply. To account for them, we investigated the relation between sodium intake and cardiac sympatho-vagal balance (SVB) in young men with high BP. Sodium intake was estimated from the amount of urinary sodium excretion over 1 week. Twenty-four-hour (24-h) urinary sodium excretion (Salt24), 24-h ambulatory BP and ECG were obtained on the last day of the observation period. As an index of sodium intake, the expression In(Salt24/Cr24) (Cr24, 24-h urinary creatinine excretion) was used. From power-spectral analysis of ECG-RR intervals during sleep, we obtained the LF/HF ratio between the low-frequency component (LF) and the high frequency component (HF) and used it as an index of SVB. The subjects were male medical students divided into a normal BP group (N-group; n=103) and a high BP group (H-group; n=26, 24-h BP>125/75 mmHg). Mean In(Salt24/Cr24) and LF/HF in the H-group were significantly higher than those in the N-group (LF/HF: 1.86+/-0.44 [SD] vs. 1.37+/-0.30, p<0.001). The calculated discriminant function (D) for the H-group and N-group was D=1.6x + 5y - 11, where x is In(Salt24/Cr24) and y is LF/HF. This formula (D) resulted in high discriminant predictive accuracy (82%) between the groups. If D=0 (the value of the cut-off line determining separation of the groups), the relation y=-0.32x + 2.2 (negative relation between y and x) was obtained. These results suggest that excessive sodium intake in combination with accentuated SVB (LF/HF) increases BP in young men.


Feed intake and milk production in dairy cows fed different grass and legume species: a meta-analysis.
The aim of this meta-analysis was to compare feed intake, milk production, milk composition and organic matter (OM) digestibility in dairy cows fed different grass and legume species. Data from the literature was collected and different data sets were made to compare families (grasses v. legumes, Data set 1), different legume species and grass family (Data set 2), and different grass and legume species (Data set 3+4). The first three data sets included diets where single species or family were fed as the sole forage, whereas the approach in the last data set differed by taking the proportion of single species in the forage part into account allowing diets consisting of both grasses and legumes to be included. The grass species included were perennial ryegrass, annual ryegrass, orchardgrass, timothy, meadow fescue, tall fescue and festulolium, and the legume species included were white clover, red clover, lucerne and birdsfoot trefoil. Overall, dry matter intake (DMI) and milk production were 1.3 and 1.6 kg/day higher, respectively, whereas milk protein and milk fat concentration were 0.5 and 1.4 g/kg lower, respectively, for legume-based diets compared with grass-based diets. When comparing individual legume species with grasses, only red clover resulted in a lower milk protein concentration than grasses. Cows fed white clover and birdsfoot trefoil yielded more milk than cows fed red clover and lucerne, probably caused by a higher OM digestibility of white clover and activity of condensed tannins in birdsfoot trefoil. None of the included grass species differed in DMI, milk production, milk composition or OM digestibility, indicating that different grass species have the same value for milk production, if OM digestibility is comparable. However, the comparison of different grass species relied on few observations, indicating that knowledge regarding feed intake and milk production potential of different grass species is scarce in the literature. In conclusion, different species within family similar in OM digestibility resulted in comparable DMI and milk production, but legumes increased both DMI and milk yield compared with grasses.


Postmortem findings in primary familial amyloidosis with polyneuropathy.
The pathology of primary familia amyloidosis with polyneuropathy is described on the basis of post-mortem examination of six cases from Northern Sweden. Clinically the disease is characterized by progressive sensory and motor disturbances with loss of sensation, muscular wasting and flaccid paralysis. Impotence, urinary bladder dysfunction, motility disturbances of the gastro-intestinal tract and postural hypotension indicate affection of the autonomic nervous system as well. Malabsorption, cardiac insufficiency and vitreous opacites also occur. As regards the distribution of amyloid, the following findings seemed to be characteristic. Usually there were no gross lesions indicating the amyloid disease. Histopathologically, amyloid deposits were observed in great extent in the peripheral nervous system and in various parts of the peripheral autonomic nervous system as well. It occurred extensively in the walls of blood vessels of various calibres, in the perivascular collagenous connective tissue and adjacent to the smooth musculature. Amyloid deposition was also found more or less abundantly in various other organs and tissues. No deposits, however, or only insignificant amounts, were found in the central nervous system, either in the parenchyma of the liver, in the islets of Langerhans, or in the bone marrow. Clinical manifestations seemed to be related to the local deposition of the amyloid substance. Our clinical and pathological findings in this particular type of familial amyloidosis conformed mostly to those previously described.


Drug effects on calcium homeostasis in mouse CA1 hippocampal neurons.
Voltage-dependent Ca2+ channels (VDCC) are important in control of neuronal excitability, synaptic transmission, and many other cellular process. Even the slightest alteration in Ca2+ currents can have a considerable impact on the neuronal function. However, it is still unknown whether Ca2+ currents are affected by neurotoxic drugs such as lead, cobalt, zinc, cadmium, thallium, lanthanum, and aluminum. We have characterized the effects of neurotoxic drugs on Ca2+ homeostasis in CA1 hippocampal C57BL mice. Fura 2-AM fluorescence photometry was used to measure intracellular Ca2+ concentration ([Ca2+]i) in the presence and absence of neurotoxic drugs (10 microM) in response to KCl application. The peak [Ca2+]i due to KCl application was reduced in the presence of lead (60%), cobalt (35%), zinc (62%), cadmium (71%), thallium (27%), and lanthanum (66%). By contrast, in the presence of aluminum the peak [Ca2+]i was either increased (46%) or it was not affected. These results indicate that neurotoxic drugs could block the entry of calcium into CA1 neurons via VDCC.


Effect on cerebral vasospasm of coil embolization followed by microcatheter intrathecal urokinase infusion into the cisterna magna: a prospective randomized study.
Vasospasm remains the leading cause of death and permanent neurological disability in patients with aneurysmal subarachnoid hemorrhage (SAH). The objective of our prospective randomized trial of coil embolization followed by intrathecal urokinase infusion into the cisterna magna (ITUKI therapy) was to test its effectiveness in preventing or alleviating the severity of ischemic neurological deficits caused by vasospasm. We enrolled 110 patients with ruptured intracranial aneurysms eligible for coil embolization and randomly assigned them to embolization with (n=57) or without (n=53) ITUKI therapy performed within 24 hours of aneurysmal SAH. The incidence of symptomatic vasospasms and the clinical outcomes, based on the Glasgow Outcome Scale, 6 months after SAH onset were assessed. There were no side effects or adverse reactions attributable to ITUKI therapy. Symptomatic vasospasm occurred in 5 patients (8.8%) with and 16 (30.2%) without ITUKI therapy; the difference was significant (P=0.012). Although the mortality rate did not differ between the groups, patients with ITUKI therapy had significantly better outcomes than those without (P=0.036). Our results demonstrate that ITUKI therapy significantly reduced the occurrence of symptomatic vasospasm. Although it did not completely prevent vasospasms, ITUKI therapy resulted in a lower rate of permanent neurological deficits.


A Novel Method for the Management of Anophthalmic Socket.
An orbital defect causes severe facial asymmetry and disfigurement that result in an immense emotional trauma to the patient and is also associated with economic, esthetic, and psychological problems. A prosthetic replacement is the treatment of choice in helping individual to return to his normal life by producing an acceptable and lifelike appearance. This case report describes the critical areas of fabrication of ocular prosthesis for a patient with missing right eye due to trauma to eye ball in an accident. Patient had given a history of surgical enucleation of the eye 15 days after ocular trauma. A polymethyl methacrylate ocular prosthesis was planned. The technique described in this case report presents the use of both custom-made and stock eye shell in an attempt to include the benefits of both. A novel attempt was made to simulate eye movements and exact color matching to that of contralateral eye to provide a better and functional ocular prosthesis to the patient.


N-methylethanolamine attenuates cardiac fibrosis and improves diastolic function: inhibition of phospholipase D as a possible mechanism.
Ventricular fibrosis is promoted by many effectors that chronically activate phospholipase D (PLD), and induces cardiac dysfunction and heart failure in cardiovascular diseases. Since ethanolamine is a product of PLD, we hypothesised that an administration of an analogue of ethanolamine, N-methylethanolamine (MEA), decreases PLD activity through a negative feedback mechanism, suppresses collagen accumulation, and thus prevents organ dysfunction. In human fibroblasts 1-butanol inhibited collagen synthesis and enhanced collagenase production, but iso-butanol did not. These indicate crucial roles of PLD in collagen synthesis and degradation. In fibroblasts, MEA dose-dependently decreased PLD activity, inhibited collagen synthesis and enhanced collagenase production. In a hypertensive heart failure model using Dahl-Iwai salt-sensitive rats, PLD activity increased with progressive ventricular fibrosis, leading to myocardial stiffening and overt heart failure. Long-term administration of MEA did not significantly decrease blood pressure, however, but decreased PLD activity and collagen content with inhibited gene expression of collagens, leading to the prevention of myocardial stiffening and haemodynamic deterioration. MEA also attenuated ventricular hypertrophy, another detrimental structural alteration. MEA may exert therapeutic effects on cardiac disorders due to ventricular fibrosis through suppression of PLD activity and modulation of the fibrosis pathway even without relief from mechanical stress.


Contractile response and mitral regurgitation after temporary interruption of long-term cardiac resynchronization therapy.
Cardiac resynchronization therapy (CRT) utilizing biventricular pacing (BVP) is a promising treatment modality for symptomatic patients with chronic left ventricular (LV) systolic dysfunction and intraventricular conduction delay. Clinical studies have shown short-term improvement in contractile function and mid-term improvement in clinical status with CRT. The objective of this study was to evaluate the haemodynamic consequences of temporary interruption of CRT after long-term stimulation. Twenty patients (16 men, 4 women) with LV dysfunction and New York Heart Association class III or IV heart failure, despite optimal medical therapy and a QRS interval of at least 120 ms, received a transvenous BVP system at the age of 66 (interquartile range, 61-69). Patients were studied after a median duration of 427 days (interquartile range, 281-563) of continuous CRT and again 72 h after cessation of BVP. Withdrawal of CRT resulted in a significant decline in maximal rate of LV systolic pressure rise from 711 mmHg/s (interquartile range, 640-816) to 442 mmHg/s (interquartile range, 389-582) (P=0.0001) and increases in mitral effective regurgitant orifice area from 4.8 mm(2) (interquartile range, 0.0-7.8) to 9.1 mm(2) (interquartile range, 5.7-13.3) (P=0.0001), mitral regurgitant volume from 7.8 mL (interquartile range, 0.0-11.5) to 16.0 mL (interquartile range, 10.7-20.8) (P=0.0001) and fraction from 13.8% (interquartile range, 0.0-19.2) to 27.7% (interquartile range, 14.6-34.0) (P=0.0002) determined by Doppler echocardiography. Cessation of long-term BVP leads to a decline in LV systolic performance and an increase in functional mitral regurgitation. These results indicate a sustained benefit of long-term CRT and support the notion to maintain CRT indefinitely.


Development and characterization of SV40 immortalized rat parotid acinar cell lines.
Rat parotid salivary gland acinar cells were transfected by CaPO4 precipitation using a plasmid containing a replication-defective simian virus (SV40) genome. Out of 30 clonal cell lines, 2 were shown to have moderate to high levels of cytodifferentiation and salivary gland acinar cell function. Functional studies with the two cell lines indicated that the beta-adrenergic agonist (isoproterenol), vasoactive intestinal peptide prostaglandin E1, and forskolin were effective activators of intracellular cyclic adenosine 3':5'-cyclic monophosphate production. Phenylephrine, carbamylcholine, and UTP were effective in increasing inositol phosphate production and intracellular free calcium levels, whereas substance P was without affect. Utilizing indirect immunofluorescence analysis, both cell lines were shown to express the SV40 large T antigen. Electron microscopic evaluation documented moderate to high levels of cytodifferentiation with the maintenance of tripartite junctional complexes, cellular polarization, and presence of moderate amounts of secretory granules and rough endoplasmic reticulum. The two cell lines had doubling times of 22 and 36 h, respectively.


Ionothermal Synthesis of Germanosilicate Zeolites Constructed with Double-Four-Ring Structure-Building Units in the Presence of Organic Base.
The crystallization chemistry of silica-based zeolites in ionic liquids remains highly puzzling and interesting in the field of zeolite science. Herein, we report the successful ionothermal synthesis of germanosilicate zeolites. The ionothermal templating effect with respect to the structure, alkalinity and concentration of organic additives was comparatively studied. The results showed that a small amount of organic base could effectively aid the dissolution of silica source and facilitate the crystallization of germanosilicate zeolites with ionic liquid as template. Remarkably, STW and IRR structures constructed with double-four-ring (D4R) structure-building units were ionothermally prepared using 1-ethyl/butyl-3-methyl imidazolium and 1-benzyl-3-methyl imidazolium ionic liquids as template, respectively. Ionothermal synthesis tailored with organic base showed suitable chemistry for the formation of germanium-containing siliceous D4R units. This finding will be helpful for the rational exploration of novel extra-large-pore zeolitic structures.


[SOR SAVOIR PATIENT Cancer and fatigue. Information dedicated to cancer patients and relatives].
In response to the evolution of the information-seeking behaviour of patients and concerns from health professionals regarding cancer patient information, the French National Federation of Comprehensive Cancer Centres (FNCLCC) introduced, in 1998, an information and education program dedicated to patients and relatives,the SOR SAVOIR PATIENT program. The methodology of this program adheres to established quality criteria regarding the elaboration of patient information. Cancer patient information, developed in this program, is based on clinical practice guidelines produced by the FNCLCC and the twenty French regional cancer centres, the National League against Cancer, The National Cancer Institute, the French Hospital Federation, the National Oncology Federation of Regional and University Hospitals,the French Oncology Federation of General Hospitals, many learned societies, as well as an active participation of patients, former patients and caregivers. The handbookSOR SAVOIR PATIENT Cancer and Fatigue is an adapted version of different publications regarding fatigue in oncology. It is meant to provide a basis for the explanationof the disease and to facilitate discussions with the healthcare team. It is available from the FNCLCC (101, rue de Tolbiac, 75013 Paris, Tel. (0033) 1, 01 76 64 78 00,www.fnclcc.fr). This document has been validated at the end of 2005 and published in January 2006. SOR SAVOIR PATIENT guides are systematically updated when new research becomes available. This article is extract from the handbook SOR SAVOIR PATIENT Cancer and Fatigue and concerns the causes and effects of fatigue and how to cope with fatigue. This information allow patients to better understand the causes and effects of fatigue, how to cope fatigue...which represent important patient information needs. This article is meant to inform patients and relatives about the disease and its treatments. It also offers health professionals a synthetic evidence-based patient information source which facilitates discussions with the patient.


Dietary -carbamylglutamate and rumen-protected -arginine supplementation ameliorate fetal growth restriction in undernourished ewes.
This study was conducted with an ovine intrauterine growth restriction (IUGR) model to test the hypothesis that dietary -carbamylglutamate (NCG) and rumen-protected -Arg (RP-Arg) supplementation are effective in ameliorating fetal growth restriction in undernourished ewes. Beginning on d 35 of gestation, ewes were fed a diet providing 100% of NRC-recommended nutrient requirements, 50% of NRC recommendations (50% NRC), 50% of NRC recommendations supplemented with 20 g/d RP-Arg (providing 10 g/d of Arg), and 50% of NRC recommendations supplemented with 5 g/d NCG product (providing 2.5 g/d of NCG). On d 110, maternal, fetal, and placental tissues and fluids were collected and weighed. Ewe weights were lower ( < 0.05) in nutrient-restricted ewes compared with adequately fed ewes. Maternal RP-Arg or NCG supplementation did not alter ( = 0.26) maternal BW in nutrient-restricted ewes. Weights of most fetal organs were increased ( < 0.05) in RP-Arg-treated and NCG-treated underfed ewes compared with 50% NRC-fed ewes. Supplementation of RP-Arg or NCG reduced ( < 0.05) concentrations of β-hydroxybutyrate, triglycerides, and ammonia in serum of underfed ewes but had no effect on concentrations of lactate and GH. Maternal RP-Arg or NCG supplementation markedly improved ( < 0.05) concentrations of AA (particularly arginine-family AA and branched-chain AA) and polyamines in maternal and fetal plasma and in fetal allantoic and amniotic fluids within nutrient-restricted ewes. These novel results indicate that dietary NCG and RP-Arg supplementation to underfed ewes ameliorated fetal growth restriction, at least in part, by increasing the availability of AA in the conceptus and provide support for its clinical use to ameliorate IUGR in humans and sheep industry production.


A prospective, randomized, multicenter, controlled study of the safety of Seprafilm adhesion barrier in abdominopelvic surgery of the intestine.
Seprafilm adhesion barrier (Seprafilm) has been proven to prevent adhesion formation after abdominal and pelvic surgery. This article reports safety results, including the postoperative incidence of abdominal and pelvic abscess and pulmonary embolism, from a large, multicenter trial designed to evaluate the safety and effectiveness of Seprafilm for reduction of adhesion-related postoperative bowel obstruction after abdominopelvic surgery. A total of 1791 patients participated in this prospective, randomized, multicenter, multinational, single-blind, controlled study in patients undergoing abdominopelvic surgery, the majority of whom had inflammatory bowel disease. Just before closure of the abdomen, patients were randomized to a Seprafilm or no-treatment control group. Patients received an average of 4.4 and as many as 10 Seprafilm adhesion barriers applied to organs and tissue surfaces that sustained direct surgical trauma and to suspected adhesiogenic surfaces. Complications that occurred within the first month after surgery were evaluated. During the safety evaluation period, the difference between the Seprafilm and control groups for the incidence of abscess (4 vs. 3 percent, respectively) or pulmonary embolism (<1 percent in both groups) was not statistically significant (P > 0.05). Foreign body reaction was not reported in either group. Fistula (2 vs. <1 percent) and peritonitis (2 vs. <1 percent) occurred more frequently (P <or= 0.05) in the Seprafilm group. In a subpopulation of patients in whom Seprafilm was wrapped around a fresh bowel anastomosis, leak-related events, which included anastomotic leak, fistula, peritonitis, abscess, and sepsis, occurred more frequently (P <or= 0.05). There were no other differences in the incidence, severity, or causative relationship of complications between study groups. This study confirmed the safety of Seprafilm adhesion barrier with respect to abdominal abscess, pelvic abscess, and pulmonary embolism when administered to patients undergoing abdominopelvic surgery. Foreign body reaction was not reported for any patient. However, wrapping the suture or staple line of a fresh bowel anastomosis with Seprafilm should be avoided, because the data suggest that this practice may increase the risk of sequelae associated with anastomotic leak.


Exploring the threshold premium for viable community based health insurance schemes in Nigeria.
The national health insurance scheme of Nigeria recently proposed a national premium for community based insurance scheme. This study determined the capacity of households in the rural and urban areas in Nigeria to pay for the premium and different hypothetical health insurance schemes namely national health insurance scheme, national urban health insurance scheme, national rural health insurance scheme and regional health insurance schemes. It determined the likely impact of different premiums on membership across socio-economic status quintiles, and then determined the threshold premium affordable to rural and urban households. The results show that the mean capacity to pay for the households in different regions ranged from US$194 ± 100 to US$986 ± 907. The threshold premiums of the national health insurance scheme, urban national health insurance and rural health insurance schemes were US$66, US$154 and US$53 respectively. Overall, the threshold premium for rural national health insurance scheme and national health insurance schemes were affordable to the lowest socio economic group. Hence, it is recommended that threshold premium for rural national health insurance scheme be adopted as the maximum premium not to be exceeded in the proposed national health insurance scheme.


Cytotoxicity of Exogenous Acetoacetate in Lithium Salt Form Is Mediated by Lithium and Not Acetoacetate.
The ketogenic diet has recently gained interest as potential adjuvant therapy for cancer. Many researchers have endeavored to support this claim in vitro. One common model utilizes treatment with exogenous acetoacetate in lithium salt form (LiAcAc). We aimed to determine whether the effects of treatment with LiAcAc on cell viability, as reported in the literature, accurately reflect the influence of acetoacetate. Breast cancer and normal cell lines were treated with acetoacetate, in lithium and sodium salt forms, and cell viability was assessed. The effect of LiAcAc on cells was mediated by Li ions. Our results showed that the cytotoxic effects of LiAcAc treatment were significantly similar to those caused by LiCl, and also treatment with NaAcAc did not cause any significant cytotoxic effect. Treatment of cells with LiAcAc is not a convincing in vitro model for studying ketogenic diet. These findings are highly important for interpreting previously published results, and for designing new experiments to study the ketogenic diet in vitro.


Historical changes of the Mediterranean Sea ecosystem: modelling the role and impact of primary productivity and fisheries changes over time.
The Mediterranean Sea has been defined "under siege" because of intense pressures from multiple human activities; yet there is still insufficient information on the cumulative impact of these stressors on the ecosystem and its resources. We evaluate how the historical (1950-2011) trends of various ecosystems groups/species have been impacted by changes in primary productivity (PP) combined with fishing pressure. We investigate the whole Mediterranean Sea using a food web modelling approach. Results indicate that both changes in PP and fishing pressure played an important role in driving species dynamics. Yet, PP was the strongest driver upon the Mediterranean Sea ecosystem. This highlights the importance of bottom-up processes in controlling the biological characteristics of the region. We observe a reduction in abundance of important fish species (~34%, including commercial and non-commercial) and top predators (~41%), and increases of the organisms at the bottom of the food web (~23%). Ecological indicators, such as community biomass, trophic levels, catch and diversity indicators, reflect such changes and show overall ecosystem degradation over time. Since climate change and fishing pressure are expected to intensify in the Mediterranean Sea, this study constitutes a baseline reference for stepping forward in assessing the future management of the basin.


c-MYC-miRNA circuitry: a central regulator of aggressive B-cell malignancies.
MYC (c-Myc) deregulation has been frequently associated with aggressive lymphomas and adverse clinical outcome in B-cell malignancies. MYC has been implicated in controlling the expression of miRNAs, and MYC-regulated miRNAs affect virtually all aspects of the hallmarks of MYC-driven lymphomas. Increasing evidence has indicated that there is significant cross-talk between MYC and miRNAs, with MYC regulating expression of a number of miRNAs, resulting in widespread repression of miRNA and, at the same time, MYC being subjected to regulation by miRNAs, leading to sustained MYC activity and the corresponding MYC downstream pathways. Thus, these combined effects of MYC overexpression and downregulation of miRNAs play a central regulatory role in the MYC oncogenic pathways and MYC-driven lymphomagenesis. Here, we provide biological insight on the function of MYC-regulated miRNAs, the mechanisms of MYC-induced miRNA repression, and the complicated feedback circuitry underlying lymphoma progression, as well as potential therapeutic targets in aggressive B-cell lymphomas.


The measurement of lung water content.
It is clear that lung water content or things related to lung water content can be measured. The major question is whether useful information will be obtained to make development worthwhile. In my experimental laboratory we have used, then abandoned, the measurement of lung water content in life by various techniques. We have special needs, of course, for very sensitive methods which will detect minimal injury and very small changes in lung water content. In the clinic, however, this may not be so serious a limitation, although one is always endeavoring to achieve diagnosis of minimal injury and minimal edema. Although static methods for measuring lung water content are available in profusion, none has been proven to be more useful than the chest roentgenogram. Kinetic methods are being developed which have the potential of being sensitive to minimal lung injury, such as leads to edema.


Microchimerism and rejection in clinical transplantation.
Haemopoietic microchimerism has been identified in recipients of solid-organ transplants and is thought by some to be critical for the development and maintenance of immunological tolerance. The aim of this study was to correlate prospectively the persistence of donor cells with clinical outcome in recipients of kidney, kidney and pancreas, and liver transplants. Persistence of donor cells in recipient peripheral blood was assessed at 3 days, and at 1, 3, 6, and 12 months after transplantation by a two-stage nested PCR technique to detect donor MHC HLA DR gene specifically. A pretransplant blood sample was collected from each patient to serve as an individual negative control. Seven liver, six kidney and pancreas, and 17 kidney patients were enrolled. 12 of the 17 kidney patients and all of the kidney and pancreas, and liver recipients were suitable for analysis. Exact matches for donors and recipients at the HLA DR loci (n = 1) or inability to obain primer pair specificity among similar HLA DR types (n = 4), meant that we were unable to analyse five patients. Donor DNA was detected in 20 (80%) of 25, ten (40%) of 25, seven (30%) of 23, five (22%) of 23, and six (32%) of 19 recipients at 3 days, and 1, 3, 6 and 12 months post-transplant, respectively. Within individuals, the detection of donor DNA varied over time; only two patients had detectable donor DNA at all times. Analysis of the whole group of transplant patients showed a similar frequency and severity of rejection episodes in patients with and without microchimerism as defined by detectable donor DR genes. These data suggest that a significant percentage of the recipients had persistent donor class II DNA in the peripheral circulation for at least 1 year after transplantation. We showed that a pretransplant blood sample is critical to avoid a false-positive result, and suggest that detectable chimerism may vary over time in individual patients. Therefore, analysis of microchimerism with a single, post-transplant analysis may not help in making clinical decisions for individual patients.


Evaluation of positron emission tomography imaging to detect lymph node metastases in patients with extramammary Paget's disease.
Patients with extramammary Paget's disease (EMPD) have a relatively good prognosis, when spread of the tumor cells is limited to the epidermis. However, invasive EMPD has a poor prognosis, when the patients have regional lymph node metastasis. Detection of nodal metastasis is thus mandatory to manage EMPD. To evaluate the 18 F-fluorodeoxyglucose positron emission tomography (FDG-PET) imaging to assess lymph node metastasis, 15 patients with histologically proven primary EMPD were enrolled in this study. All patients underwent whole-body PET prior to sentinel lymph node biopsy (SLNB). The maximum standardized uptake value (SUVmax) of more than 2.5 was evaluated as positive PET indicative of malignancy. Among 14 cases with the primary genital lesions, 11 cases underwent bilateral SLNB of the inguinal nodal basin and the remaining three cases unilateral SLNB. One case with a primary axillary lesion underwent unilateral SLNB of the axillary nodal basin. Therefore, a total of 26 regional basins were investigated. In general, nodal basins can be categorized into four groups: (i) histologically negative and PET negative (true negative); (ii) histologically positive and PET negative (false negative); (iii) histologically positive and PET positive (true positive); and (iv) histologically negative and PET positive (false positive) groups. In the 26 nodal basins, there were 19 true negative and seven true positive cases, and neither false negative nor false positive cases were observed. The mean SUVmax was significantly higher in the true positive basins (8.03 ± 3.34) than in the true negative basins (0.26 ± 0.56). The SUVmax value may be useful for detection of nodal metastasis.


Mineralogy, geochemistry, and micromorphology of human kidney stones (urolithiasis) from Mersin, the southern Turkey.
This study describes the primary characteristics of the selected kidney stones surgically removed from the patients at the Mersin University Hospital in the southern Turkey and interprets their formation via petrographic, geochemical, XRD, SEM-EDX, and ICP-MS/OES analyses. The analytical results revealed that the kidney stones are composed of the minerals whewellite, struvite, hydroxyapatite, and uric acid alone or in different combinations. The samples occur in staghorn, bean-shaped composite, and individual rounded particle shapes, which are controlled by the shape of the nucleus and the site of stone formation. The cross-section of the samples shows concentric growth layers due to variations in saturation, characterizing the metastable phase. Kidney stone formation includes two main stages: (i) nucleation and (ii) aggregation and/or growth. Nucleation was either Randall plaque of hydroxyapatite in tissue on the surface of the papilla or a coating of whewellite on the plaque, or crystallization as free particles in the urine. Subsequently, aggregation or growth occurs by precipitation of stone-forming materials around the plaque or coating carried into the urine, or around the nucleus formed in situ in the urine. Urinary supersaturation is the main driving force of crystallization processes; and is controlled by many factors including bacterially induced supersaturation.


Endoscopic photodynamic therapy using talaporfin sodium for recurrent intranasal carcinomas after radiotherapy in three dogs.
Radiation is the treatment of choice for canine nasal tumours but, in almost all cases, there is local recurrence associated with poor prognosis. This report describes the effect of endoscopic photodynamic therapy using talaporfin sodium for canine intranasal carcinoma recurring after radiation therapy. Rhinoscopic photodynamic therapy was administered after radiation therapy in three dogs with recurrent intranasal carcinoma. Two to 24 illuminations of a 665-nm diode laser were performed two hours after intravenous bolus injection of 5·0 mg/kg of talaporfin sodium. Photodynamic therapy induced almost complete remission and prolonged survival time in all cases suggesting that it might be a useful treatment for intranasal carcinomas that recur after radiation.


Stability of small ubiquitin-like modifier (SUMO) proteases OVERLY TOLERANT TO SALT1 and -2 modulates salicylic acid signalling and SUMO1/2 conjugation in Arabidopsis thaliana.
Small ubiquitin-like modifier proteases 1 and 2 (SUMO1/2) have been linked to the regulation of salicylic acid (SA)-mediated defence signalling in Arabidopsis thaliana. In order to define the role of the SUMO proteases OVERLY TOLERANT TO SALT1 and -2 (OTS1/2) in defence and to provide insight into SUMO1/2-mediated regulation of SA signalling, we examined the status of SA-mediated defences in ots1/2 mutants. The ots1 ots2 double mutant displayed enhanced resistance to virulent Pseudomonas syringae and higher levels of SA compared with wild-type (WT) plants. Furthermore, ots1 ots2 mutants exhibited upregulated expression of the SA biosynthesis gene ICS1 in addition to enhanced SA-responsive ICS1 expression beyond that of WT. SA stimulated OTS1/2 degradation and promoted accumulation of SUMO1/2 conjugates. These results indicate that OTS1 and -2 act in a feedback loop in SA signalling and that de novo OTS1/2 synthesis works antagonistically to SA-promoted degradation, adjusting the abundance of OTS1/2 to moderate SA signalling. Accumulation of SUMO1/2 conjugates coincides with SA-promoted OTS degradation and may play a positive role in SA-mediated signalling in addition to its repressive roles reported elsewhere.


[Myocardial perfusion visualized with SPECT: three-dimensional representation].
A recently developed computer program for three-dimensional (3D) reconstruction of SPECT images has been employed to study myocardial perfusion in coronaropathic patients using MIBI-99mTc or 201Tl chloride. By subtracting after-stress from at-rest 3D reconstructed images, even small ischemic lesions could be located in the myocardium, with good morphological definition. The general characteristics of the method and some clinical results are here presented.


Single-Crystal Growth and Room-Temperature Magnetocaloric Effect of X-Type Hexaferrite Sr2Co2Fe28O46.
X-type hexaferrites have been receiving considerable attention due to their promising applications in many magnetic-electronic fields. However, the growth of single-crystal X-type hexaferrite is still a challenge. Herein we reported, for the first time, the preparation of single crystal X-type hexaferrite Sr2Co2Fe28O46 (Sr2Co2X) with high-quality and large size using floating-zone method with laser as the heating source. The crystals show rhombohedral symmetry with space group of R-3m (No. 166, a = 5.8935(1) Å and c = 83.7438(17) Å). Co2+ and Fe3+ oxidation states were confirmed by the X-ray absorption near-edge spectroscopy. The prepared Sr2Co2X exhibits a spin reorientation transition from easy-cone to easy-axis at T2 of 343 K and a ferrimagnetism-paramagnetism transition at Curie temperature (TC) of ∼743 K. The spin reorientation transition was accompanied by magnetocaloric effect (MCE). Both conventional and inverse MCEs were observed near T2 with a magnetic field applied along the c-axis. The maximum value of the magnetic entropy change along the c-axis was evaluated to be 1.1 J/kg·K for a magnetic field change of 5 T.


[Construction of recombinant human smad 7 adenoviral vector and its expression in vitro].
The recombinant human Smad7 adenoviral vector was constructed by direct DNA cloning protocol and then transfected into 293 cells for virus packaging. After amplification and purification, the recombinant adenovirus was used to infect the keloid fibroblasts. The Smad7 mRNA transcription of the infected cells was detected by RT-PCR. The recombinant Adeno-Smad7 was correctly constructed and confirmed by both restriction analysis and PCR analysis. RT-PCR showed the over expression of adenovirus mediated Smad7 mRNA in keloid cells. These results demonstrated that the recombinant Smad7 adenoviral vector can be expressed in cultured cells in vitro, and it may provide a new therapeutic strategy for keloid gene therapy.


Correlation between tumor microenvironment-associated factors and the efficacy and prognosis of neoadjuvant therapy for rectal cancer.
The tumor microenvironment contributes to the survival and development of tumor cells and is therefore a key target for cancer therapy. The tumor microenvironment has unique physical and chemical properties and is associated with inflammation and immunity. To examine the correlation between tumor microenvironment-associated factors and the efficacy and prognosis of neoadjuvant therapy for rectal cancer, and to compare the differences between two treatments [neoadjuvant chemotherapy (NAC) vs. neoadjuvant chemoradiotherapy (NACR)], an immunohistochemical method was used to measure the expression levels of CD4+ tumor-infiltrating lymphocytes (TILs), cluster of differentiation (CD)8+TILs, forkhead box P3 (FOXP3)+TILs, cytotoxic T lymphocyte-associated antigen-4+TILs and programmed death ligand-1 (PD-L1)+TILs in 109 patients with rectal cancer, pre- and post-neoadjuvant therapy. The significance of these protein expression patterns was also analyzed using tissue microarrays, and the prognostic significance of these findings evaluated. The results indicated that high levels of CD4+TILs, CD8+TILs and PD-L1+TILs may be associated with favorable responses to neoadjuvant therapy, whereas high levels of FOXP3+TILs were associated with poor therapeutic responses. Expression levels of CD8+TILs and FOXP3+TILs following neoadjuvant therapy were independent prognostic factors and affected the total survival of patients subjected to neoadjuvant therapy for the treatment of rectal cancer. Moreover, the effects of NAC and NACR on the tumor microenvironment may be different.


Sortase-deficient lactobacilli: effect on immunomodulation and gut retention.
Surface proteins of probiotic microbes, including Lactobacillus acidophilus and Lactobacillus gasseri, are believed to promote retention in the gut and mediate host-bacterial communications. Sortase, an enzyme that covalently couples a subset of extracellular proteins containing an LPXTG motif to the cell surface, is of particular interest in characterizing bacterial adherence and communication with the mucosal immune system. A sortase gene, srtA, was identified in L. acidophilus NCFM (LBA1244) and L. gasseri ATCC 33323 (LGAS_0825). Additionally, eight and six intact sortase-dependent proteins were predicted in L. acidophilus and L. gasseri, respectively. Due to the role of sortase in coupling these proteins to the cell wall, ΔsrtA deletion mutants of L. acidophilus and L. gasseri were created using the upp-based counterselective gene replacement system. Inactivation of sortase did not cause significant alteration in growth or survival in simulated gastrointestinal juices. Meanwhile, both ΔsrtA mutants showed decreased adhesion to porcine mucin in vitro. Murine dendritic cells exposed to the ΔsrtA mutant of L. acidophilus or L. gasseri induced lower levels of pro-inflammatory cytokines TNF-α and IL-12, respectively, compared with the parent strains. In vivo co-colonization of the L. acidophilus ΔsrtA mutant and its parent strain in germ-free 129S6/SvEv mice resulted in a significant one-log reduction of the ΔsrtA mutant population. Additionally, a similar reduction of the ΔsrtA mutant was observed in the caecum. This study shows for the first time that sortase-dependent proteins contribute to gut retention of probiotic microbes in the gastrointestinal tract.


WAIS characteristics of non-pathological obsessive and hysteric styles.
Tested traditional clinical hypotheses about the cognitive functioning of individuals (N = 16) with an obsessive or an hysteric style in a non-pathological population using selected subtests of the WAIS. Individuals identified as having an obsessive style displayed the predicted patterns (Information and Vocabulary greater than Comprehension), while their hysteric counterparts displayed only a trend toward certain predicted patterns (Comprehension greater than Information and Vocabulary). Predicted between-group differences were significant. Higher base rates of obsessive features in a college population may account for the weaker trends within the hysteric group. Generally, the results appear to support the likelihood that nonpathological forms of the two styles display patterns of cognitive functioning similar to those of their more pathological counterparts.


The neonatal intubation causes defects in primary teeth of premature infants.
This study aimed to evaluate the relationship between intubation during the neonatal period and enamel defects in primary teeth of preterm infants. It was an observational, prospective, analytical and sampling of convenience. We selected 157 children who had average birth weight of 1656.3±627.8 g, gestational age of 31.7±2.7 weeks and the examination of chronological age 2.2±0.6 years old. Clinical examination of the oral cavity showed that the frequency of enamel defects was higher (86.3%) among children intubated when compared to non-intubated children (13.7%). The enamel defects was found to be inversely proportional to gestational age. The intubation time was related to the probability of occurrence of DDE (P<0.001), in other words, the greater the number of days intubated, the greater the chance of DDE. In children intubated, hypoplasia mainly affected the upper teeth on the left side of the mouth. Tracheal intubation in the neonatal period is the main cause of enamel defects in primary teeth of children born preterm. The longer the duration of intubation, the greater the chance of developing dental enamel defect. The area of action during movement of the laryngoscope toggle corresponds to the region most affected by tooth enamel hypoplasia in children intubated, upper right central incisor, lateral incisor and upper left.


Phase separation under ultraslow cooling: Onset of nucleation.
We discuss the interplay between a slow continuous drift of temperature, which induces continuous phase separation, and the nonlinear diffusion term in the phi(4)-model for phase separation of a binary mixture. This leads to a bound for the stability of diffusive demixing. It is demonstrated that the same findings apply in other models, except for slight modifications of the bound. In practice stable diffusive demixing can only be achieved when special precautions are taken in experiments on real mixtures. Therefore, the recent observations on complex dynamical behavior in such systems should be considered as a new challenge for understanding generic features of phase-separating systems.


Role of Neutrophils in Psoriasis.
Psoriasis is a common inflammatory disease that can involve the skin, joints, or both. The abnormalities of innate immunity play crucial roles in the pathogenesis of psoriasis. Neutrophils are the most abundant leukocytes in the circulation. Emerging evidences have demonstrated that neutrophils may play a role in autoimmune diseases. The neutrophil-to-lymphocyte ratio (NLR), the activity of neutrophils, and the number of NETotic cells were significantly higher in psoriasis patients compared to healthy controls. The number of low-density granulocytes (LDGs) in the blood of psoriasis patients was significantly higher than those in the control blood. Furthermore, neutrophils may play important roles in the cardiovascular risk in psoriasis. However, the exact role of neutrophils in psoriasis remains unclear. In this review, we highlight the role of neutrophils in the pathogenesis of psoriasis.


Flavonoid profile, antioxidant and antiglycation properties of Retama sphaerocarpa fruits extracts.
Retama sphaerocarpa occurs in the Mediterranean area of North-east Africa and in the Iberian Peninsula, and grows on a variety of soil types and climatic conditions. Used in Algerian folk medicine, it is a valuable species for revegetation and soil restoration. The aim of this study is to evaluate flavonoid composition and antioxidant and antiglycation properties of methanolic and aqueous extracts from R. sphaerocarpa fruits. HPLC-PDA/ESI-MS was used to identify/quantify flavonoid content. Antioxidant activity was evaluated by Folin-Ciocalteu, ORAC, FRAP, TEAC, and DPPH assays, and antiglycation capability by glucose/fructose-BSA assay. Results showed that fruits contain isoflavones (daidzein and genistein derivatives) and flavonols (apigenin, isorhamnetin, kaempferol and quercetin derivatives), and extracts (especially the methanolic one, richer in flavonoids) possess good in vitro antioxidant and antiglycation properties. These findings evidence that R. sphaerocarpa fruits are a source of valuable phytochemicals, with potential applications in the field of phytopharmaceuticals and in food industry.


Simultaneous Robot-assisted Laparoscopic Excision of Pre-pyloric Gastrointestinal Stromal Tumor and Cholecystectomy.
Operating on more than a single procedure in a same surgical intervention saves time, anesthesia duration and can increase the overall quality of life by lowering the duration of hospital stay and minimizing patient anxiety. But such interventions require expertise, high surgical performance, and precision in anatomical manipulation. We present a case of an outstanding performance of a unique minimally invasive simultaneous approach of removing a pre-pyloric gastrointestinal stromal tumor (GIST) along with a cholecystectomy by a robot-assisted laparascopic surgical system. So far, only 33 cases of GIST have been reported in literature that were managed by robot-assistance, and this case is the first of its kind. This is the case of a 60-year-old overweight female who presented for a follow-up for chest discomfort, shortness of breath, chronic gastric reflux and classical features of cholecystitis along with diarrheal and constipation episodes. A gastroduodenoscopy showed a mass in the pre-pyloric area that extended in the luminal cavity. A robot-assisted laparascopic approach was planned, and with precision and surgical expertise the mass was removed along with a cholecystectomy. The surgical specimen were confirmed on histopathology.


Toxicity of L-DOPA coated iron oxide nanoparticles in intraperitoneal delivery setting - preliminary preclinical study.
Iron oxide nanoparticles are promising candidates for theranostics in cancer, that aims to achieve in one-step precise tumor imaging by magnetic resonance, and targeted therapy through surface attached anti-cancer drugs. The aim of this study was to investigate in preclinical setting the biocompatibility of new iron oxide-based nanoparticles that were coated with L-DOPA for improved dispersion in biological media. These nanostructures (NPs) were designed for biomedical applications as contrast agents and/or drug carriers. We investigated the effect exerted in vitro by NPs and L-DOPA on the viability and proliferation of normal mouse L929 fibroblasts. NPs exhibited good biocompatibility against these cells. Moreover, L-DOPA contained in NPs sustained fibroblasts proliferation and/or limited anti-proliferative effects of naked nanoparticles. In the animal study, C57BL/6 mice were injected intraperitoneally with a single dose of NPs (approximately 125 mg/kg body weight). We followed up hematological and histological parameters for one, three and seven days after NPs administration. Results indicated that NPs possibly induced local inflammation and consequent recruitment of peripheral lymphocytes, whilst the decrease of platelet counts may reflect tissue lesions caused by NPs. The histopathological study showed mild to moderate alterations in the hepatocytes, splenic and renal cells, while the brain parenchyma only presented nonspecific congestive changes. Taken altogether, the preclinical study indicated that the new iron oxide nanoparticles coated with L-DOPA were biocompatible against fibroblasts and had a convenient toxicological profile when administered intraperitoneally in a single dose to C57BL/6 mice. Accordingly, the proposed nanostructure is a promising candidate for imaging and treating dispersed peritoneal tumors.


Diabetes (db/db) mutation-induced ovarian involution: progressive hypercytolipidemia.
Ovarian atrophy and reproductive tract incompetence are recognized consequences of the progressive expression of the overt, diabetes-obesity syndrome (DOS) in C57BL/KsJ (db/db) mutant mice. The present studies evaluated the progressive changes in ovarian cytoarchitecture, endocrine expression, and reproductive tract cytolipidemic parameters that promote reproductive failure and ovarian involution during the pre-onset, initial, progressive, and chronic expression stages of the DOS. Paired littermate control (normal: +/?) and diabetic (mutant: db/db) C57BL/KsJ females were selected for analysis of ovarian parameters at 2 weeks (pre-onset expression of DOS), 4 weeks (initial DOS expression), 8 weeks (progressive DOS: hyper-glycemic/lipidemic), and 16 weeks (overt/chronic DOS expression) of age. All 4- to 16-week-old (db/db) groups were obese, hyperglycemic, and hyperinsulinemic as compared with age-matched (+/?) controls. Prior to phenotypic expression of the DOS (2 week groups), ovarian interstitial cytolipidemia characterized the perifollicular and cortical regions of db/db tissue samples relative to +/? indices, while comparable body weight, blood glucose, as well as serum insulin and ovarian steroid hormone concentrations characterized both the +/? and db/db groups. Overt DOS expression in the 4-week-old db/db groups was characterized by body obesity, systemic hyperglycemia-hyperinsulinemia, and extensive hypercytolipidemia of ovarian folliculothecal compartments, as well as enhanced tissue lipase activities. By 8 weeks of age, progressive hypercytolipidemia characterized interstitial, thecal, and follicular granulosa cell layers of db/db tissue samples concurrent with suppressed ovarian steroid hormone production, enhanced lipid sequestration, and exacerbation of systemic hyper-glycemia/insulinemia. By 16 weeks of age, the chronic-DOS was characterized by extensive ovarian follicular involution, cortical perivascular hyperlipidemic infiltration, thecal cell atrophy, and follicular granulosa lipid imbibition. These data indicate that db/db mutation-induced ovarian structural and functional involution is a direct reflection of the cellular metabolic shift towards lipogenesis, indicated by the progressive cytoarchitectural transformation into adipocyte-like entities. The cytological indications of cellular metabolic compromise, which precede the phenotypic expression of the DOS indices, suggests that correction of these abnormal shifts in ovarian endocrine and cellular metabolism may restore, delay, or prevent the further compromise of ovarian function by db/db mutation expression.


An immunogenetic analysis of resistance to herpes simplex virus retinitis in inbred strains of mice.
Specific inbred strains of mice have been shown to vary considerably in their resistance and susceptibility to herpes simplex virus (HSV) infection. We injected 2 X 10(5) plaque forming units (PFU) of the KOS strain of HSV-1 intracamerally into one eye of BALB/c, C57Bl/6, and F1 (BALB/c X C57Bl/6) mice. HSV-1 antigens were localized in frozen sections of enucleated eyes at 10 to 14 days post-inoculation. Injected eyes of BALB/c mice showed an anterior uveitis with HSV-1 antigens in the anterior segment and an intact retina free of HSV antigens. The retina of the contralateral uninjected eye was necrotic and contained HSV-1 antigens. In both C57Bl/6 and F1 mice, HSV antigens were limited to anterior segment structures in the injected eye, whereas, in contrast to BALB/c mice, the contralateral retina appeared histologically normal and contained no viral antigens. The C57Bl/6 and F1 strains remained relatively resistant to retinal infection even if pretreated with up to 800 Rads of irradiation. The retinas of normal or sublethally irradiated C57Bl/6 and F1, but not BALB/c strains, were also resistant to intravitreal injection of HSV. These results suggest that resistance to HSV retinitis is a dominantly inherited trait, which depends only partly upon immunologic factors and may be heavily influenced by the inherent ability of host cells from different murine strains to support a productive viral infection.


Economic evaluation of implementation strategies in health care.
Economic evaluations can inform decisions about the efficiency and allocation of resources to implementation strategies-strategies explicitly designed to inform care providers and patients about the best available research evidence and to enhance its use in their practices. These strategies are increasingly popular in health care, especially in light of growing concerns about quality of care and limits on resources. But such concerns have hardly motivated health authorities and other decision-makers to spend on some form of economic evaluation in their assessments of implementation strategies. This editorial addresses the importance of economic evaluation in the context of implementation science-particularly, how these analyses can be most efficiently incorporated into decision-making processes about implementation strategies.


Proteogenomics of clear cell renal cell carcinoma response to tyrosine kinase inhibitor.
The tyrosine kinase inhibitor (TKI) Sunitinib is one the therapies approved for advanced renal cell carcinoma. Here, we undertake proteogenomic profiling of 115 tumors from patients with clear cell renal cell carcinoma (ccRCC) undergoing Sunitinib treatment and reveal the molecular basis of differential clinical outcomes with TKI therapy. We find that chromosome 7q gain-induced mTOR signaling activation is associated with poor therapeutic outcomes with Sunitinib treatment, whereas the aristolochic acid signature and VHL mutation synergistically caused enhanced glycolysis is correlated with better prognosis. The proteomic and phosphoproteomic analysis further highlights the responsibility of mTOR signaling for non-response to Sunitinib. Immune landscape characterization reveals diverse tumor microenvironment subsets in ccRCC. Finally, we construct a multi-omics classifier that can detect responder and non-responder patients (receiver operating characteristic-area under the curve, 0.98). Our study highlights associations between ccRCC molecular characteristics and the response to TKI, which can facilitate future improvement of therapeutic responses.


Survey of retail milk composition as affected by label claims regarding farm-management practices.
A trend in food labeling is to make claims related to agricultural management, and this is occurring with dairy labels. A survey study was conducted to compare retail milk for quality (antibiotics and bacterial counts), nutritional value (fat, protein, and solids-not-fat), and hormonal composition (somatotropin, insulin-like growth factor-1 [IGF-1], estradiol, and progesterone) as affected by three label claims related to dairy-cow management: conventional, recombinant bovine somatotropin (rbST)-free (processor-certified not from cows supplemented with rbST), or organic (follows US Department of Agriculture organic practices). Retail milk samples (n=334) from 48 states were collected. Based on a statistical analysis that reflected the sampling schema and distributions appropriate to the various response variables, minor differences were observed for conventional, rbST-free, and organic milk labels. Conventionally labeled milk had the lowest (P<0.05) bacterial counts compared to either milk labeled rbST-free or organic; however, these differences were not biologically meaningful. In addition, conventionally labeled milk had significantly less (P<0.05) estradiol and progesterone than organic milk (4.97 vs 6.40 pg/mL and 12.0 vs 13.9 ng/mL, respectively). Milk labeled rbST-free had similar concentrations of progesterone vs conventional milk and similar concentrations of estradiol vs organic milk. Concentrations of IGF-1 in milk were similar between conventional milk and milk labeled rbST-free. Organic milk had less (P<0.05) IGF-1 than either conventional or rbST-free milk (2.73 ng/mL vs 3.12 and 3.04 ng/mL, respectively). The macronutrient profiles of the different milks were similar, except for a slight increase in protein in organic milk (about 0.1% greater for organic compared to other milks). Label claims were not related to any meaningful differences in the milk compositional variables measured. It is important for food and nutrition professionals to know that conventional, rbST-free, and organic milk are compositionally similar so they can serve as a key resource to consumers who are making milk purchase (and consumption) decisions in a marketplace where there are misleading milk label claims.


Growth, development, and nutritional physiology of grasshoppers from subarctic and temperate regions.
Despite the importance of developmental rate, growth rate, and size at maturity in the life history of poikliotherms, the trade-offs among these traits and selection pressures involved in the evolution of these traits are not well understood. This study compared these traits in a grasshopper, Melanoplus sanguinipes F. (Orthoptera: Acrididae), from two contrasting geographical regions, subarctic Alaska and temperate Idaho. The growing season in the interior of Alaska is about 80 d shorter than at low-elevation sites in Idaho. We hypothesized that the Alaskan grasshoppers would show more rapid growth and development than grasshoppers from Idaho, at the cost of greater sensitivity to food quality. On a diet of lettuce and wheat bran, grasshoppers from Alaska developed from egg hatch to adult more rapidly than those from Idaho at each of three different temperature regimes. Averaged over all temperature treatments, the weight of the Alaskan grasshoppers was about 5% less than that of the Idaho grasshoppers at the adult molt. Feeding and digestive efficiencies were determined for the final two instars using two meridic diets: one with a high concentration of nutrients and the other with the same formulation but diluted with cellulose. Alaskan grasshoppers again developed more rapidly, weighed less, and had faster growth rates than those from Idaho. Alaskan grasshoppers supported their more rapid growth by increasing postingestive efficiencies; that is, they had higher conversion rates of digested matter to biomass on the high-quality diet, greater assimilation of food on the low-quality diet, and greater efficiency of nitrogen assimilation or retention on both diets. There was no evidence that performance of Alaskan grasshoppers suffered any more than that of the Idaho grasshoppers on the low-quality diet.


[Therapy of tinnitus. Tympanic cavity infusion of lidocaine and steroid solution].
Tinnitus is an otological symptom which is often encountered and is yet difficult to treat. If tinnitus is of cochlear origin then it seems reasonable to assume that a total depression of the cochlear function will abolish cochlear tinnitus. To achieve this depression, transtympanic injections of a local anesthetic (4% Lidocaine) to anesthetize the inner ear and of Decadoron were conducted in a patient suffering from tinnitus. One hundred and sixty-eight patients (220 ears) who had suffered from relatively long-term tinnitus were included in this study. In almost all of the cases the clinical symptoms and the otological findings (i.e., the audiogram and caloric test) indicated that the probable lesion underlying the tinnitus was located within the end organ. In some cases this injection brought a transient (for few days), slight, neurosensorial deafness in the low-frequency range. This auditory disorder, however, was completely restored without sequelae. Our results are summarized as follows: in 76 ears, tinnitus was abolished completely, in 109 ears, tinnitus was considerably ameliorated, in 35 ears, tinnitus was slightly ameliorated or no effect. One hundred and nine patients (138 ears) who had suffered from tinnitus were included in this study. Decadoron was applied to the middle ear cavity by transtympanic injection. Our results are summarized as follows: in 87 ears, tinnitus was abolished, in 39 ears, tinnitus was considerably ameliorated, in 14 ears, tinnitus was slightly ameliorated or no effect.


Management of sterno-mediastinitis.
With an incidence rate of 1-4%, mediastinitis following cardiac surgery is a rarely occurring complication, but may show a mortality rate of up to 50%. Risk factors for sternal instability are insulin-dependent diabetes mellitus, obesity, immunosuppressed state, chronic obstructive pulmonary disease, osteoporosis, history of radiation, renal failure, body height, smoking and nutritional state. The aim of this paper is to show an overview of this clinical picture, present the risk factors and elucidate the therapy options chronologically. As a result of interdisciplinary cooperation, a therapy concept has developed which is adapted to the patient individually. Therapy begins with the simplest measures and, if deemed necessary, this is then escalated step by step. The aim of the treatment is to bring the infection under control, which requires radical surgical debridement, removal of infected and necrotic tissue, removal of all foreign bodies (including wires and osteosynthesis material) and the removal of all infected, necrotic osseous material if necessary followed by vacuum-assisted closure therapy. The reconstruction of defects of the anterior chest wall is achievable using different muscle flaps. Mostly the muscle pectoralis major is used unilaterally or bilaterally with or without disinsertion of the tendon. Other options are the omental flap, the muscle latissimus dorsi flap or the muscle rectus abdominis flap. A combined approach comprising surgical debridement, short-term vacuum therapy and subsequent myoplastic coverage has proved successful and can be carried out with a high standard of safety.


A Review of a Century of Studies on South American Leaf Blight of the Rubber Tree.
In the past, South American leaf blight (SALB) of the rubber tree has been responsible for very severe damage in rubber plantations in South America. It is still the main obstacle holding back the development of rubber cultivation on the American continent and is a major risk for Asia and Africa, which are still exempt from this scourge. However, knowledge about the disease and about rubber tree resistance factors has progressed over the last decade, suggesting some solutions, notably for varietal improvement. This article is an overview of knowledge on this subject, particularly the most recent achievements.


[Determination of acrylamide residue in cosmetics by isotope dilution-liquid chromatography-tandem mass spectrometry].
Abstract: A comprehensive analytical method based on isotope dilution-liquid chromatography-tandem mass spectrometry (LC-MS/MS) has been developed for the determination of acrylamide residue in cosmetics. Water-soluble cosmetic sample was extracted with water, and the extract was centrifuged, then the upper solution was cleaned up by an Oasis HLB solid phase extraction cartridge. Oil-soluble cosmetic sample was extracted by liquid-liquid partition with n-hexane and water. The qualitative and quantitative analyses were carried out for the analyte in the multiple reaction monitoring (MRM) mode after the chromatographic separation on a Waters Atlantis T3 column (150 mm x 2.1 mm, 3 microm). The quantification was performed with 13C3-acrylamide as internal standard. The limit of quantification (LOQ) for acrylamide was 0.1 mg/kg. The mean recoveries were 87.7%-95.8% at the spiked levels of 0.1-1.0 mg/kg with the intra-day precision less than 10% and the inter-day precision less than 12%. The method is suitable for the determination of acrylamide in cosmetics.


[Construction of digital three-dimensional models of renal stones and virtual surgery simulation].
To construct three-dimensional (3D) models of renal stones and perform percutaneous nephrolithotomy (PCNL) virtual surgery simulation. Methods CT images were obtained from 8 patients with renal stones. Images segmentation and reconstruction were performed using MIMICS 10.0 software to construct the 3D model of the renal stones, which provided the anatomical relationships between the kidney and the adjacent organs. The optimal PCNL virtual surgery simulation for each individual case was performed using FreeForm Modeling System on the basis of the 3D model. Eight 3D models of renal stone were constructed. The 3D model of the renal stones represented the interrelationships of the stones, intrarenal vessel, and the collecting system with the adjacent anatomical structures. Individualized PCNL virtual surgery simulations including percutaneous puncture, dilatation and pneumatic lithotripsy were performed successfully in all the 8 3D models. Digital 3D model of renal stone provides the reliable and comprehensive imaging information for surgical design, and PCNL virtual surgery simulation has important clinical significance to improve the stone clearance rate and reduce the surgical complications.


Effects of nicotine on the translation of stem cell therapy.
Although stem cell therapy has tremendous therapeutic potential, clinical translation of stem cell therapy has yet to be fully realized. Recently, patient comorbidities and lifestyle choices have emerged to be important factors in the efficacy of stem cell therapy. Tobacco usage is an important risk factor for numerous diseases, and nicotine exposure specifically has become increasing more prevalent with the rising use of electronic cigarettes. This review describes the effects of nicotine exposure on the function of various stem cells. We place emphasis on the differential effects of nicotine exposure in vitro and as well as in preclinical models. Further research on the effects of nicotine on stem cells will deepen our understanding of how lifestyle choices can impact the outcome of stem cell therapies.


Impact of trimethoprim-sulfamethoxazole prophylaxis on falciparum malaria infection and disease.
Trimethoprim-sulfamethoxazole (TS) prophylaxis is recommended for persons living with human immunodeficiency virus infection and acquired immunodeficiency syndrome in Africa. TS and the antimalarial combination sulfadoxine-pyrimethamine (SP) share mechanisms of action and resistance patterns, and concerns about the impact of TS resistance on SP efficacy have contributed to reluctance to implement TS prophylaxis in Africa. To determine whether TS prophylaxis impairs SP efficacy for treatment of uncomplicated falciparum malaria, we conducted a randomized, controlled, open-label study of TS prophylaxis. Two hundred and forty children 5-15 years old were randomized in a 2 : 1 fashion to receive either thrice-weekly TS for 12 weeks or no prophylaxis and were treated with SP for subsequent episodes of malaria. The incidence of malaria, SP efficacy, and the prevalence of parasite mutations that confer antifolate drug resistance were measured. TS prophylaxis had a 99.5% protective efficacy against episodes of clinical malaria, with 97% efficacy against infection. Four SP treatment failures occurred in the control group, and none occurred in the TS group. No evidence was seen for selection by TS of antifolate resistance-conferring mutations in parasite dihydrofolate reductase or dihydropteroate synthase during subclinical infections. In this setting of low antifolate resistance, TS was highly effective in preventing falciparum malaria infection and disease and did not appear to select for SP-resistant parasites.


Functional Photoacoustic and Ultrasonic Assessment of Osteoporosis: A Clinical Feasibility Study.
Objective and Impact Statement. To study the feasibility of combined functional photoacoustic (PA) and quantitative ultrasound (US) for diagnosis of osteoporosis in vivo based on the detection of chemical and microarchitecture (BMA) information in calcaneus bone. Introduction. Clinically available X-ray or US technologies for the diagnosis of osteoporosis do not report important parameters such as chemical information and BMA. With unique advantages, including good sensitivity to molecular and metabolic properties, PA bone assessment techniques hold a great potential for clinical translation. Methods. By performing multiwavelength PA measurements, the chemical information in the human calcaneus bone, including mineral, lipid, oxygenated-hemoglobin, and deoxygenated-hemoglobin, were assessed. In parallel, by performing PA spectrum analysis, the BMA as an important bone physical property was quantified. An unpaired t-test and a two-way ANOVA test were conducted to compare the outcomes from the two subject groups. Results. Multiwavelength PA measurement is capable of assessing the relative contents of several chemical components in the trabecular bone in vivo, including both minerals and organic materials such as oxygenated-hemoglobin, deoxygenated-hemoglobin, and lipid, which are relevant to metabolic activities and bone health. In addition, PA measurements of BMA show good correlations (R2 up to 0.65) with DEXA. Both the chemical and microarchitectural measurements from PA techniques can differentiate the two subject groups. Conclusion. The results from this initial clinical study suggest that PA techniques, by providing additional chemical and microarchitecture information relevant to bone health, may lead to accurate and early diagnosis, as well as sensitive monitoring of the treatment of osteoporosis.


Brief Report: European Mitochondrial Haplogroups Impact on Liver Fibrosis Progression Among HCV and HIV/HCV-Coinfected Patients From Northwest Spain.
The impact of mitochondrial DNA haplogroups on the outcome of liver fibrosis was evaluated in 362 hepatitis C virus infection (HCV)-monoinfected and HIV/HCV-coinfected patients (147 and 215, respectively) in clinical follow-up at 2 reference hospitals in the Northwest of Spain. The mitochondrial DNA haplogroup H was the most prevalent (50.3%) in this population. The cluster Others and V were recognized as risk factors for the development of liver fibrosis while haplogroup H and HCV genotype 4 confer a lower risk. This information might be useful for prioritization of HCV treatment, especially for F0-F1 patients for whom there is no urgency for treatment.