[The prognostic value of uveal melanoma cell type].
To determine the prognostic value of a uveal melanoma (UM) cell type for the development of metastases (MTS). The investigation enrolled 96 patients (96 eyes) with UM after enucleation. Forty-one patients without signs of MTS were included in this group, who were followed up for more than 36 months (mean, 70.5 months (36 to 105 months)), 55 patients with MTS who were followed up for an average of 21 months (2 to 44 months). The MTS and non-MTS groups were statistically homogeneous in age, gender, tumor size, location, and ciliary body involvement in the process, as well as in extrabulbar growth. There were spindle cell, mixed cell, and epithelioid cell UMs in 44, 35, and 21% of patents, respectively. The tumors in patients without MTS were noted to be significantly more likely to have spindle cell-type UM (p<0.0001). Mixed cell and epithelioid cell UMs were more frequently detected in patients with MTS (p<0.0001), which was believed to be due to the presence of epithelioid cells in both cell types. A survival analysis showed that the 3- and 5-year survival rates for patients with spindle cell UM were significantly higher than that for those with epithelioid cell or mixed cell UM (p<0.001); the 3-and 5-year survival rates for spindle cell UM were 78 and 70%, respectively; those for mixed cell UM were 37 and 24%; and those for epithelioid cell UM were 50 and 31%. The similar survival rates for patients with mixed cell or epithelioid cell type UM could conclude that it is advisable to use the binary principle - the presence or absence of epithelioid cells in the tumor, when assessing a UM cell type as a prognostic factor.


Concentrations of putrescine, spermidine, and spermine in duodenum and pancreas as affected by the ratio of arginine to lysine and source of methionine in broilers under heat stress.
An experiment was designed to investigate the effect of Arg, Lys, Met, and environmental temperature on broiler performance and associated changes in duodenal and pancreatic polyamines. Two groups of 26-d-old Ross male broilers raised under thermoneutral (TN) conditions were reallocated to 4 rooms kept at heat stress (HS) or TN. Birds were fed equimolar amounts of 2-hydroxy-4-(methylthio) butanoic acid (HMB) or DL-Met (DLM) at requirement levels with Arg:Lys at 0.95 or 1.40. Twelve replicates of 4 birds were offered each diet ad libitum. Body weight gain, efficiency of dietary CP accretion (CPE), feed intake, and feed conversion ratio were ascertained from 26 to 33 d and from 34 to 47 d of age. One bird per cage was killed at 33 and 47 d, and samples of duodenum and pancreas were assayed for putrescine, spermidine, and spermine (Spm), together with estimates of duodenal villus height. From 26 to 33 d, birds fed HMB performed better than those fed DLM, but only at TN conditions. From 34 to 47 d, feeding HMB tended to optimize CPE when added to diets high in Arg. However, lower CPE was obtained when HMB was added to low-Arg diets, whereas birds fed DLM were unaffected by these treatments (P < 0.10). Methionine source, Arg:Lys, or both affected the concentrations of duodenal and pancreatic polyamines, with some changes correlating with performance variables during HS (P > 0.05). It was found that HS caused lower tissue spermidine (P < 0.001) and higher pancreatic Spm (P = 0.08) from 34 to 47 d. Putrescine concentrations were affected by diet and HS, depending on tissue and experimental period. Pancreatic Spm correlated negatively with changes in CPE influenced by Arg:Lys by Met source interaction in chronically heat-stressed birds. The possible association between polyamine metabolism and some of the effects of the Arg:Lys by Met source interaction observed in chronically stressed birds deserves further investigation.


Total Syntheses of Nannocystins A and A0, Two Elongation Factor 1 Inhibitors.
Asymmetric total syntheses of nannocystins A and A0 were achieved in a convergent route starting from simple materials. Nannocystin family natural products bear potent anticancer activity as elongation factor 1 inhibitors. In this synthesis, the challenging tertiary amide bond was constructed by peptide coupling between an acyl chloride and a secondary amine. A late-stage ring-closing metathesis reaction successfully rendered the macrocycle. This efficient synthetic strategy should be applicable to other nannocystins and analogues and therefore should benefit future structure-activity relationship studies.


Biogenesis: number mysticism in protein thinking.
Historically, great minds have been tantalized by the idea that integers contain hidden, subtle meanings that could give us deep insights into natural (and supernatural) phenomena. Numerological analysis has been used in religion, mythology, and the sciences. In the field of proteins, integers played a stimulating role during early struggles to unravel structure, but they ultimately proved constrictive and misleading. In contrast, the introduction of imaginary (or complex) numbers into the algebra and numerical analysis of ligand-protein affinities can open new perspectives into such interactions.


Internal optical urethrotomy is the treatment of choice in stenosis of the bladder neck after open prostate adenectomy.
Open adenomectomy of the prostate, although performed less frequently, is still indicated in patients with prostate adenoma > 100 ml. This study assessed the frequency of isolated bladder neck stenosis after surgery and the effectiveness of internal optical urethrotomy as monotherapy and in combination with transurethral resection in the treatment of this complication. One thousand five hundred thirty-eight Millin's operations and 381 trans-vesical adenomectomies were performed in patients with prostate adenoma. In 50 patients, the circular hemostatic suture was applied using the de la Peña technique because of bleeding after surgery. The retrospective analysis compared the incidence of isolated bladder neck stenosis depending on the type of surgery. Isolated bladder neck stenosis or narrowing of the neck combined with partial stenosis of the site after adenomectomy occurred in 0.52% (8/1539) of patients after Millin's operation and in 1.05% of patients (4/381) after trans-vesical adenomectomy. All strictures of the bladder after trans-vesical surgery occurred within 12 month after the procedure, and 25% of stenoses after Millin's operation occurred many years after the surgery. Internal optical urethrotomy as monotherapy or in combination with scar resection resulted in recovery after one treatment in 16 out of 17 patients. Internal optical urethrotomy as monotherapy or in combination with scar resection was effective in nearly all patients with bladder neck stenosis.


Effect of vitamins A, E and C on liver enzyme activity in rats exposed to organophosphate pesticide diazinon.
Diazinon, a commonly used organophosphorus pesticide, has been widely used throughout the world in agriculture and horticulture to control insects that feed on crops, ornamentals, lawns, fruits, vegetables and other food products. The toxicity of the DZN causes adverse effects on many organs. The purpose of this study was to examine the protective effect of vitamins A, E and C on liver enzymes alanine transaminase (ALT), Aspartate aminotransferase (AST) and Lactate Dehydrogenase (LDH) in rats exposed to diazinon. In this study, male wistar rats were randomly divided into 10 different groups. The groups were administered normal saline, soybean oil (as the solvent for diazinon and fat-soluble vitamins), diazinon, (30 mg kg(-1), vitamins E, C and A (100, 500 mg kg(-1) and 400 IU kg(-1), respectively) and a combination of diazinon with the same dose of each vitamin intraperitoneally i.p.daily for 14 days. Seven days after the final injection, the animals were anesthetized and blood samples were taken. The photometric method was used to measure the activity of the enzymes. The activities of ALT and AST in the diazinon group were significantly higher than that observed in the control group; however, the diazinon/vitamin E, A, C group displayed significant reduction in ALT and AST activities compared to the diazinon group. The lowest level of LDH enzyme activity was observed in the dazinon/vitamin C group and this was statistically lower than the diazinon group. The results of this study revealed that vitamin E, A and C have a potent protective effect against diazinon-induced hepatotoxicity in rats, which may be due to the scavenging of free radicals and increased antioxidant status.


Transgenic swine: expression of human CD39 protects against myocardial injury.
CD39 (ectonucleoside triphosphate diphosphohydrolase-1; ENTPD-1) rapidly hydrolyzes ATP and ADP to AMP; AMP is hydrolyzed by ecto-5'-nucleotidase (CD73) to adenosine, an anti-thrombotic and cardiovascular protective mediator. While expression of human CD39 in a murine model of myocardial ischemia/reperfusion (I/R) injury confers cardiac protection, the translational therapeutic potential of these findings requires further testing in a large animal model. To determine if transgenic expression of CD39 reduces infarct size in a swine model of myocardial ischemia/reperfusion injury, transgenic pigs expressing human CD39 (hCD39) were generated via somatic cell nuclear transfer and characterized. Expression of hC39 in cardiac tissue was confirmed by immunoblot and immunohistochemistry. Myocardial I/R injury was induced by intracoronary balloon inflation in the left anterior descending (LAD) artery for 60 min followed by 3 hours of reperfusion. The ischemic area was delineated by perfusion with 5% phthalo blue and the myocardial infarct size was determined by triphenyl tetrazolium chloride (TTC) staining. During ischemia, the rate-pressure product was significantly lower in control versus hCD39-Tg swine. Following reperfusion, compared to littermate control swine, hCD39-Tg animals displayed a significant reduction in infarct size (hCD39-Tg: 17.2 ± 4.3% vs. 44.7 ± 5.2%, P=0.0025). Our findings demonstrate for the first time that the findings in transgenic mouse models translate to large animal transgenic models and validate the potential to translate CD39 into the clinical arena to attenuate human myocardial ischemia/reperfusion injury.


Modulation of redox homeostasis under suboptimal conditions by Arabidopsis nudix hydrolase 7.
Nudix hydrolases play a key role in maintaining cellular homeostasis by hydrolyzing various nuceloside diphosphate derivatives and capped mRNAs. Several independent studies have demonstrated that Arabidopsis nudix hydrolase 7 (AtNUDT7) hydrolyzes NADH and ADP-ribose. Loss of function Atnudt7-1 mutant plants (SALK_046441) exhibit stunted growth, higher levels of reactive oxygen species, enhanced resistance to pathogens. However, using the same T-DNA line, two other groups reported that mutant plants do not exhibit any visible phenotypes. In this study we analyze plausible factors that account for differences in the observed phenotypes in Atnudt7. Secondly, we evaluate the biochemical and molecular consequences of increased NADH levels due to loss of function of AtNUDT7 in Arabidopsis. We identified a novel conditional phenotype of Atnudt7-1 knockout plants that was contingent upon nutrient composition of potting mix. In nutrient-rich Metro-Mix, there were no phenotypic differences between mutant and wild-type (WT) plants. In the nutrient-poor mix (12 parts vermiculite: 3 parts Redi-earth and 1 part sand), mutant plants showed the characteristic stunted phenotype. Compared with WT plants, levels of glutathione, NAD+, NADH, and in turn NADH:NAD+ ratio were higher in Atnudt7-1 plants growing in 12:3:1 potting mix. Infiltrating NADH and ADP-ribose into WT leaves was sufficient to induce AtNUDT7 protein. Constitutive over-expression of AtNudt7 did not alter NADH levels or resistance to pathogens. Transcriptome analysis identified nearly 700 genes differentially expressed in the Atnudt7-1 mutant compared to WT plants grown in 12:3:1 potting mix. In the Atnudt7-1 mutant, genes associated with defense response, proteolytic activities, and systemic acquired resistance were upregulated, while gene ontologies for transcription and phytohormone signaling were downregulated. Based on these observations, we conclude that the differences observed in growth phenotypes of the Atnudt7-1 knockout mutants can be due to differences in the nutrient composition of potting mix. Our data suggests AtNUDT7 plays an important role in maintaining redox homeostasis, particularly for maintaining NADH:NAD+ balance for normal growth and development. During stress conditions, rapid induction of AtNUDT7 is important for regulating the activation of stress/defense signaling and cell death pathways.


The highly rearranged mitochondrial genomes of three economically important scale insects and the mitochondrial phylogeny of Coccoidea (Hemiptera: Sternorrhyncha).
The mitochondrial genomes (mitogenomes) of scale insects are less known in comparison to other insects, which hinders the phylogenetic and evolutionary studies of Coccoidea and higher taxa. Herein, the complete mitogenomes of Unaspis yanonensis, Planococcus citri and Ceroplastes rubens were sequenced for Coccoidea. The 15,220-bp long mitogenome of U. yanonensis contained the typical set of 37 genes including 13 PCGs, 22 tRNA genes and two rRNA genes; the 15,549-bp long mitogenome of P. citri lacked the tRNA gene trnV; the 15,387-bp long mitogenome of C. rubens exhibited several shortened PCGs and lacked five tRNA genes. The mitochondrial gene arrangement of the three mitogenomes was different from other scale insects and Drosophila yakuba. Most PCGs used standard ATN (ATA, ATT, ATC and ATG) start codons and complete TAN (TAA or TAG) termination codons. The ND4L had the highest evolutionary rate but COX1 and CYTB were the lowest. Most tRNA genes had cloverleaf secondary structures, whereas the reduction of dihydrouridine (DHU) arms and TψC arms were detected. Tandem repeats, stem-loop (SL) structures and poly-[TA]n stretch were found in the control regions (CRs) of the three mitogenomes. The phylogenetic analyses using Bayesian inference (BI) and maximum likelihood methods (ML) showed identical results, both supporting the inner relationship of Coccoidea as Coccidae + (Pseudococcidae + Diaspididae).


A general assay for antibody catalysis using acridone as a fluorescent tag.
A simple and highly sensitive catalysis assay is demonstrated based on analyzing reactions with acridonetagged compounds by thin-layer chromatography. As little as 1 pmol of product is readily visualized by its blue fluorescence under UV illumination and identified by its retention factor (Rf). Each assay requires only 10 microliters of solution. The method is reliable, inexpensive, versatile, and immediately applicable in repetitive format for screening catalytic antibody libraries. Three examples are presented: (i) the epoxidation of acridone labeled (S)-citronellol. The pair of stereoisomeric epoxides formed is resolved on the plate, which provides a direct selection method for enantioselective epoxidation catalysts. (ii) Oxidation of acridone-labeled 1-hexanol to 1-hexanal. The activity of horse liver alcohol dehydrogenase is detected. (iii) Indirect product labeling of released aldehyde groups by hydrazone formation with an acridone-labeled hydrazide. Activity of catalytic antibodies for hydrolysis of enol ethers is detected.


Biochemical and haematological response to alcohol intake.
In a clinical survey of 7735 middle-aged men, alcohol consumption has been related to 25 biochemical and haematological measurements obtained from a single blood sample. Most measurements showed some association with alcohol consumption, gamma-glutamyl transferase (GGT) being the most strongly associated. Lead, mean corpuscular haemoglobin (MCH), mean corpuscular volume, high-density lipoprotein-cholesterol (HDL-C), urate and aspartate transaminase also showed substantial associations with alcohol intake. Using a discriminant analysis technique, a simple score based on five variables (GGT, HDL-C, urate, MCH and lead) provided the best discrimination between heavy drinkers (e.g. more than three pints of beer daily) and occasional drinkers, but still failed to identify more than half of the heavy drinkers. This combined score may prove a useful measure of an individual's biochemical/haematological response to alcohol consumption for use in epidemiological and clinical studies of alcohol related disorders. The use of such indices should complement but not replace measures of alcohol intake derived from questionnaires.


Effects of inhaled salbutamol in primary pulmonary hypertension.
Although lung function is grossly normal in patients with primary pulmonary hypertension (PPH), mild-to-moderate peripheral airflow obstruction can be found in the majority of patients with this disease. Therefore, beta2-agonists may affect pulmonary function, blood gases and haemodynamics in patients with PPH. Pulmonary function testing, blood gas measurements and right heart catheterisation was performed in 22 patients with PPH and the acute effects of inhaled salbutamol (0.2 mg) were measured. Salbutamol caused an increase in the forced expiratory volume in one second (FEV1) from 2446+/-704 to 2550+/-776 mL. The mean expiratory flow at 50% of the vital capacity (MEF50) rose from 58+/-17 to 66+/-21% pred. The pulmonary artery pressures remained unchanged after inhalation of salbutamol, but the cardiac output increased significantly from 3.9+/-1.4 to 4.2+/-1.4 L x min(-1) accompanied by significant increases in stroke volume and mixed venous oxygen saturation as well as a significant decrease in pulmonary vascular resistance. The arterial oxygen tension rose from 9+/-2.4 kPa (68+/-18 mmHg) at baseline to 9.7+/-2.8 kPa (73+/-21 mmHg) after inhalation of salbutamol, the alveolo-arterial oxygen gradient values improved from 6+/-2.5 kPa (45+/-19 mmHg) to 5.1+/-2.9 kPa (38+/-22 mmHg), respectively. Inhaled salbutamol has beneficial acute effects on pulmonary function, blood gases and haemodynamics in patients with primary pulmonary hypertension.


Genome-wide profiling of mouse RNA secondary structures reveals key features of the mammalian transcriptome.
The understanding of RNA structure is a key feature toward the comprehension of RNA functions and mechanisms of action. In particular, non-coding RNAs are thought to exert their functions by specific secondary structures, but an efficient annotation on a large scale of these structures is still missing. By using a novel high-throughput method, named chemical inference of RNA structures, CIRS-seq, that uses dimethyl sulfate, and N-cyclohexyl- N'-(2-morpholinoethyl) carbodiimide metho-p-toluenesulfonate to modify RNA residues in single-stranded conformation within native deproteinized RNA secondary structures, we investigate the structural features of mouse embryonic stem cell transcripts. Our analysis reveals an unexpected higher structuring of the 5′ and 3′ untranslated regions compared to the coding regions, a reduced structuring at the Kozak sequence and stop codon, and a three-nucleotide periodicity across the coding region of messenger RNAs. We also observe that ncRNAs exhibit a higher degree of structuring with respect to protein coding transcripts. Moreover, we find that the Lin28a binding protein binds selectively to RNA motifs with a strong preference toward a single stranded conformation. This work defines for the first time the complete RNA structurome of mouse embryonic stem cells,revealing an extremely distinct RNA structural landscape. These results demonstrate that CIRS-seq constitutes an important tool for the identification of native deproteinized RNA structures.


Report writing and testimony.
Guidelines for providing competent and fair medicolegal reports and testimony are provided. Among them are (1) remaining within one's area of clinical competence when performing medicolegal work, (2) obtaining board certification from a legitimate specialty board, (3) considering the patients' claims and diagnoses from the opposing medicolegal viewpoint, and (4) Performing differential diagnosis in each case. Experts are asked to strive for honesty, fairness, thoroughness, and accuracy while avoiding the attempts at persuasion which sometimes are made by legal referral sources.


Preferential secretion of R-type alpha-amylase molecules in rice seed scutellum at high temperatures.
Exposure of fresh scutella excised from 4-day-old rice seedlings to higher temperatures, (40-42 degrees C), drastically reduced the biosynthesis of alpha-amylase as determined by the incorporation of [(35)S]methionine into the immunoprecipitable product. However, the intracellular transport and extracellular secretion of the enzyme molecules were enhanced at high temperatures, indicating that the biosynthesis and secretion of alpha-amylase are distinguishable in their temperature dependency. At the higher temperature regime (>==40 degrees C), the complex-type alpha-amylase isoform, resistant to hydrolytic digestion by endo-beta-N-acetylglucosaminidase H (Endo-beta-H) was predominantly secreted, whereas at lower temperatures (<==15 degrees C), the isoform susceptible to Endo-beta-H attack was the major molecular form secreted.


Home-based advance care programme is effective in reducing hospitalisations of advanced heart failure patients: a clinical and healthcare cost study.
In end-stage heart failure (HF) that is not eligible for mechanical assist device or heart transplant, palliative care serves to maximise symptom control and quality of life. We sought to evaluate the impact of home-based advance care programme (ACP) on healthcare utilisation in end-stage HF patients. Prospectively collected registry data on all end-stage HF recruited into ACP between July 2008 and July 2010 were analysed. Chart reviews were conducted on HF database and hospital electronic records. Phone interview and home visit details by ACP team were extracted to complete data entry. HF and all-cause hospitalisations 1 year before, and any time after ACP inception were defined as events. For the latter analysis, follow-up duration adjustment to event episodes was performed to account for death less than a year. Forty-four patients (mean age 79 years, 39% men) were followed up for 15±8 months. Fifty-seven percent had diabetes, 80% ischaemic heart disease, and 60% chronic kidney disease. All reported functional class III/IV at enrolment. Mean serum sodium was 136±6 mmol/L, and creatinine 186±126 mmol/L. Thirty (68%) died within the programme. Mean time to death was 5.5 months. Mean all-cause and HF hospitalisations were 3.6 and 2.0 per patient before enrolment, but improved to 1.0 and 0.6 respectively after ACP. Thirty-six (71%) patients had fewer HF hospitalisations. When only those who survived more than a year were considered (n = 14), 10 (71%) and 9 (64%) experienced reduced HF (mean: 1.4 episodes per patient) and all-cause hospitalisations (mean: 2.2 episodes per patient) respectively. Home-based advance care programme is potentially effective in reducing healthcare utilisation of end-stage HF patients, primarily by reducing HF rehospitalisations, and in probably saving costs as well.


Efficient electron transfer in functional assemblies of pyridine-modified NQDs on SWNTs.
Nanocrystal quantum dot (NQD)/single-walled carbon nanotube (SWNT) hybrid nanomaterials were synthesized, assembled into field effect transistors (FETs) via dielectrophoresis (DEP), and characterized optically and electronically. The pyridine moiety functioned as a short, noncovalent linker between the NQDs and SWNTs and allowed more efficient carrier transfer through the assemblies without deleteriously altering electronic structures. Photoluminescence studies of the resulting assemblies support an efficient carrier transfer process in CdSe-py-SWNTs unlike that of CdSe/ZnS-py-SWNTs. The use of DEP as a means of controlling the assembly process allowed the creation of a SWNT array containing densely packed CdSe NQDs across a 2 mum gap between electrodes. Observations and characterization of the photocurrent, resistivity, gate dependence, and optical properties of these systems suggest efficient electron transfer from photoexcited NQDs to SWNTs.


Arterial stiffness in prehypertension: a possible vicious cycle.
The pathophysiological abnormalities associated with increased arterial stiffness and/or abnormal pressure wave reflection may play crucial roles in increasing the risk of development of cardiovascular events. On the other hand, prehypertension, defined as a systolic blood pressure of 120-139 and/or a diastolic blood pressure of 80-89 mmHg, is a "danger zone" for the later development of hypertension and is also associated with an increased incidence of cardiovascular diseases and cardiovascular mortality. We discuss the association among arterial stiffness/pressure wave reflection, prehypertension, and the later development of hypertension. Several prospective studies have demonstrated that increased arterial stiffness/abnormal pressure wave reflection are risk factors for the later development of hypertension in subjects with prehypertension. On the contrary, persistence of prehypertention accelerates the age-related increase of the arterial stiffness. Thus, arterial stiffness and prehypertension may be elements of a vicious cycle, and other cardiovascular risk factors, such as aging and abnormal glucose metabolism, may aggravate this cycle. In the future, development of a simple technique to assess large/small arterial stiffness and an effective strategy to reduce arterial stiffness in subjects with prehypertension is warranted.


Variation in Growth, Colonization of Maize, and Metabolic Parameters of GFP- and DsRed-Labeled Fusarium verticillioides Strains.
Autofluorescent proteins are frequently applied as visual markers in the labeling of filamentous fungi. Genes gfp and DsRed were transformed into the genome of Fusarium verticillioides via the Agrobacterium tumefaciens-mediated transformation method. The selected transformants displayed a bright green or red fluorescence in all the organelles of the growing fungal mycelia and spores (except for the vacuoles) both in cultures and in the maize (Zea mays) roots they colonized. The results of gene-specific polymerase chain reaction (PCR) analysis and the thermal asymmetrical interlaced (TAIL)-PCR analysis demonstrated that gfp and DsRed were integrated on different chromosomes of the fungus. Reductions in the colony growth on the plates at pH 4.0 and 5.5 was observed for the green fluorescent protein (GFP)-transformant G3 and the DsRed-transformant R4, but transformants G4 and R1 grew as well as the wild-type strain at pH 4.0. The speed of growth of all the transformants was similar to the wild-type strain at pH ≥ 7. The insertion of gfp and DsRed did not alter the production of extracellular enzymes and fumonisin B by F. verticillioides. The transformants expressing GFP and DsRed proteins were able to colonize maize roots. However, the four transformants examined produced fewer CFU in the root samples than the wild-type strain during a sampling period of 7 to 28 days after inoculation.


Human Papillomavirus Infection as a Possible Cause of Spontaneous Abortion and Spontaneous Preterm Delivery.
Based on the current literature, we aimed to provide an overview on Human Papillomavirus prevalence in normal pregnancies and pregnancies with adverse outcome. We conducted a systematic literature search in PubMed and Embase. Data extracted from the articles and used for analysis included HPV prevalence, pregnancy outcome, geographical location, investigated tissue types, and HPV detection methods. The overall HPV prevalence in normal full-term pregnancies was found to be 17.5% (95% CI; 17.3-17.7) for cervix, 8.3% (95% CI; 7.6-9.1) for placental tissue, 5.7% (95% CI; 5.1-6.3) for amniotic fluid, and 10.9% (95% CI; 10.1-11.7) for umbilical cord blood. Summary estimates for HPV prevalence of spontaneous abortions and spontaneous preterm deliveries, in cervix (spontaneous abortions: 24.5%, and preterm deliveries: 47%, resp.) and placenta (spontaneous abortions: 24.9%, and preterm deliveries: 50%, resp.), were identified to be higher compared to normal full-term pregnancies (P < 0.05 and P < 0.0001). Great variation in HPV prevalence was observed between study populations of different geographical locations. This review demonstrates an association between spontaneous abortion, spontaneous preterm delivery, and the presence of HPV in both the cervix and the placenta. However, a reliable conclusion is difficult to draw due to the limited number of studies conducted on material from pregnancies with adverse outcome and the risk of residual confounding.


Identification of putative neurotransmitters in the lizard parietal eye.
The retina of the parietal eye of lizards is a simple vertebrate retina that may be useful in studies of basic principles of information processing in visual systems. The chemical substances which mediate the cell-to-cell communication of this eye are not known. As a step in attempting to understand the cellular basis for visual information processing the authors have studied the ability of the parietal eye to synthesize conventional neurotransmitter substances. The eyes were incubated in radiolabeled precursors, then an extract of the tissue was subjected to high-voltage paper electrophoresis. The results of this study indicate that gamma-amino butyric acid (GABA) was synthesized from glutamic acid, acetylcholine (ACh) was synthesized from choline and serotonin (5-HT) was synthesized from tryptophan. Endogenous 5-HT was localized at sites outside the sensory epithelium by immunohistochemical means. Autoradiography following an incubation with 3H-GABA revealed uptake by lens cells and probably both glia and neurons. The authors conclude that GABA and ACh may be involved in the processing of visual information within the parietal eye but that 5-HT probably is not.


Intensity dependence of cation kinetic energies from 2,5-dihydroxybenzoic acid near the infrared matrix-assisted laser desorption/ionization threshold.
The mechanisms responsible for matrix-assisted laser desorption/ionization (MALDI) are far from being well understood, particularly where infrared laser irradiation is used to initiate the process. We measured the emission yields and kinetic energy distributions of positive ions emitted from 2,5-dihydroxybenzoic acid loaded with angiotensin II in a standard MALDI preparation during irradiation with an infrared free-electron laser tuned to 2.94 microm. As the laser intensity is scanned through the MALDI threshold, we see a marked change in the energy distributions of the matrix ion. Above threshold, the energy distributions of both analyte and matrix cations are constant over a broad range of laser intensities. This behavior does not appear to be consistent with any extant model of the MALDI mechanism.


Three-dimensional structure of protein C inhibitor predicted from structure of alpha 1-antitrypsin with computer graphics.
The three-dimensional structure of a proteolytically modified protein C inhibitor, a member of the serine protease inhibitor superfamily, was constructed with computer graphics based on its amino acid sequence homology with that of the modified alpha 1-antitrypsin whose structure had been elucidated by X-ray crystallography. The intact form of protein C inhibitor was predicted with an alpha-carbon model based on its hydrophilicity and hydrogen bond pattern. Furthermore, a model of its interaction with activated protein C was constructed based on the structure of the complex between trypsin and its inhibitor, which had been determined by X-ray crystallography.


A naïve Gaussian Bayes classifier for detection of mental activity in gait signature.
A probabilistic modelling is presented to detect mental activity from gait signature recorded from healthy subjects. The proposed scheme is based on principal component analysis with reduced feature dimension followed by a naïve Gaussian Bayes classifier. The leave-one-out cross-validation shows the detection accuracy of 94% with specificity and sensitivity of 96% and 98.3%, respectively. The research has a potential application in the prevention of elderly risk falls, lie detection and rehabilitation among Parkinson's patients.


Rapid assembly of matrix metalloprotease inhibitors using click chemistry.
[reaction: see text] A panel of 96 metalloprotease inhibitors was assembled using "click chemistry" by reacting eight zinc-binding hydroxamate warheads with 12 azide building blocks. Screens of the bidentate compounds against representative metalloproteases provided discerning inhibition fingerprints, revealing compounds with low micromolar potency against MMP-7. The relative ease and convenience of the strategy in constructing focused chemical libraries for rapid in situ screening of MMPs is thereby demonstrated.


Induction of delta-Aminolevulinic Acid Synthase Activity and Inhibition of Heme Synthesis in Euglena gracilis by N-Methyl Mesoporphyrin IX.
N-Methyl mesoporphyrin IX, an inhibitor of heme synthesis, increases extractable delta-aminolevulinic acid (ALA) synthase activity when administered to growing cultures of Euglena gracilis Klebs strain Z Pringsheim in micromolar concentrations. Wild-type light-grown green cells and white aplastidic cells exhibited 2.8-fold and 1.8-fold increases, respectively, in ALA synthase activity within five to six hours after incubation with 4 x 10(-6) molar N-methyl mesoporphyrin IX. Protoheme levels were decreased and (59)Fe incorporation into heme was inhibited by N-methyl mesoporphyrin IX, indicating that, as in animal cells, N-methyl mesoporphyrin IX acts specifically to block iron insertion into protoporphyrin IX. Chlorophyll synthesis in wild-type cells was not affected within the first 6 hours after administration of N-methyl mesoporphyrin IX.


Molecular based modeling of associating fluids via calculation of Wertheim cluster integrals.
We examine a virial-like treatment for the equation of state of associating fluids defined in terms of a detailed molecular model. The approach implements Wertheim's formulation of statistical thermodynamics of a classical fluid of molecules having strong directionally dependent association interactions. We employ the theory in its fundamental form, which expresses the pressure as an expansion in two or more aggregation densities, which themselves are related to each other by other series expansions. We employ Mayer-sampling Monte Carlo simulations to evaluate the cluster integrals defining the coefficients appearing in these series, yielding a multidensity virial-like equation of state, appropriate for the molecular system for which the cluster integrals were computed. We demonstrate this approach with a well-studied Lennard-Jones + association model, considering cases of atoms having one and two binding sites, respectively, and including all clusters involving up to four atoms. It is shown for this application that the Wertheim treatment is vastly superior to the standard (single-density) virial formulation, which fails in its description of the associating-fluid equation of state at very low densities. The Wertheim formulation for associating fluids is seen to be effective up to densities where the standard virial treatment to the same order begins to fail when applied to nonassociating fluids.


Leg cramps: differential diagnosis and management.
Leg cramps are a common problem, especially in the elderly. The differential diagnosis is extensive and includes the following conditions: true cramps, such as those related to heat, hemodialysis and electrolyte disturbances, as well as idiopathic cramps (the most common type); contractures occurring in conditions such as metabolic myopathies and thyroid disease; tetany, which is usually related to electrolyte disturbances, and dystonias, such as occupational cramps and those related to antipsychotic medications. Other leg problems that are not cramps, such as restless legs syndrome and periodic leg movements, also must be distinguished. The etiology of idiopathic leg cramps is not clear. Treatments for leg cramps include stretching exercises, quinine sulfate and vitamin E, but no treatment is conclusively effective. Nonetheless, in many patients relief of symptoms is achieved with one or more of these treatments.


[Brain evoked potential in schizophrenic patients].
The authors reviewed the literature on evoked potentials in mentally ill patients, with particular emphasis on schizphreniacs. The commonly observed abnormalities were as follows: 1) higher SEPs amplitudes with less waveshape variability during first 100 ms in non-depressed chronic, paranoid or undifferentiated patients with florid psychotic symptoms; normal SEPs amplitudes in acute or latent schizophrenics and in chronic depressed schizophrenics but without florid psychotic symptoms; 2) reduced SEPs and VEPs amplitude recovery and faster latency recovery; 3) reduced AEPs amplitude and latency; 4) greater VEPs waveshape variability and tendency to be "reducers" in hallucinating patients; reduced amplitude and latency recovery; prolonged latencies in patients with positive family history (schizophrenia or affective disorders in close relatives); prolonged N2 latency in motor responses to "easy" and "difficult" stimuli; reduced activity of "late potentials"; 5) greater waveshape variability in all modalities in chronic schizophrenics, abnormal P300 (reduced amplitude, lack of P300 or negative "effect of uncertainty") and abnormal CNV (less "readiness" potential, prolonged negativity with motor responses).


Why might poor sleep quality lead to depression? A role for emotion regulation.
Disordered sleep is strongly linked to future depression, but the reasons for this link are not well understood. This study tested one possibility - that poorer sleep impairs emotion regulation (ER), which over time leads to increased depressive symptoms. Our sample contained individuals with a wide range of depression symptoms (current depression, N = 54, remitted depression, N = 36, and healthy control, N = 53), who were followed clinically over six months and reassessed for changes in depressive symptom levels. As predicted, maladaptive ER mediated both cross-sectional and prospective relationships between poor sleep quality and depression symptoms. In contrast, an alternative mediator, physical activity levels, did not mediate the link between sleep quality and depression symptoms. Maladaptive ER may help explain why sleep difficulties contribute to depression symptoms; implications for interventions are discussed.


Spatial-division multiplexed hybrid Raman and Brillouin optical time-domain reflectometry based on multi-core fiber.
Spatial-division multiplexed (SDM) hybrid Raman- and Brillouin- optical time-domain reflectometry (RODTR and BODTR) utilizing the multi-core fiber has been proposed and experimentally demonstrated. The solution is proposed in order to overcome the incompatible input pump power required for hybrid ROTDR and BOTDR in single mode fiber (SMF), while ensuring the capability of discriminative measurement between temperature and strain. What's more, the central core has been intentionally chosen to implement BOTDR so as to avoid bending-induced cross-sensitivity on Brillouin frequency shift (BFS) measurement. The proposed system utilizes a single laser source, shared pump generation devices, but separate interrogation fiber channels, thus enabling efficient input power management for the two reflectometry, allowing for simultaneous measurement of spontaneous Raman scattering and Brillouin scattering. The worst temperature and strain resolutions are estimated to be about 2.2 °C and 40 με respectively in 6 km sensing range with 3 m spatial resolution.


Antitumoral Effect of Hibiscus sabdariffa on Human Squamous Cell Carcinoma and Multiple Myeloma Cells.
Cancer is a leading cause of death worldwide. Despite therapeutic improvements, some cancers are still untreatable. Recently there has been an increasing interest in the use of natural substances for cancer prevention and treatment. Hibiscus sabdariffa (HS) is a plant, belonging to Malvaceae family, widespread in South Asia and Central Africa. HS extract (HSE) used in folk medicine, gained researchers' interest thanks to its antioxidant, anti-inflammatory, and chemopreventive properties. In the present study, we initially assessed HSE effect on a panel of human tumor cell lines. Then we focused our study on the following that are most sensitive to HSE action cell lines: Multiple Myeloma (MM) cells (RPMI 8226) and Oral Squamous Cell Carcinoma (OSCC) cells (SCC-25). In both RPMI 8226 and SCC-25 cells, HSE impaired cell growth, exerted a reversible cytostatic effect, and reduced cell motility and invasiveness. We evaluated the involvement of MAPKs ERK1/2 and p38 in HSE effects by using specific inhibitors, U0126 and SB203580, respectively. For both SCC-25 and RPMI 8226, HSE cytostatic effect depends on p38 activation, whereas ERK1/2 modulation is crucial for cell motility and invasiveness. Our results suggest that HSE may be a potential therapeutic agent against MM and OSCC.


A longitudinal study of the prevalence of Nipah virus in Pteropus lylei bats in Thailand: evidence for seasonal preference in disease transmission.
After 12 serial Nipah virus outbreaks in humans since 1998, it has been noted that all except the initial event in Malaysia occurred during the first 5 months of the year. Increasingly higher morbidity and mortality have been observed in subsequent outbreaks in India and Bangladesh. This may have been related to different virus strains and transmission capability from bat to human without the need for an amplifying host and direct human-to-human transmission. A survey of virus strains in Pteropus lylei and seasonal preference for spillover of these viruses was completed in seven provinces of Central Thailand between May 2005 and June 2007. Nipah virus RNA sequences, which belonged to those of the Malaysian and Bangladesh strains, were detected in the urine of these bats, with the Bangladesh strain being dominant. Highest recovery of Nipah virus RNA was observed in May. Of two provincial sites where monthly surveys were done, the Bangladesh strain was almost exclusively detected during April to June. The Malaysian strain was found dispersed during December to June. Although direct contact during breeding (in December to April) was believed to be an important transmission factor, our results may not entirely support the role of breeding activities in spillage of virus. Greater virus shedding over extended periods in the case of the Malaysian strain and the highest peak of virus detection in May in the case of the Bangladesh strain when offspring started to separate may suggest that there may be responsible mechanisms other than direct contact during breeding in the same roost. Knowledge of seasonal preferences of Nipah virus shedding in P. lylei will help us to better understand the dynamics of Nipah virus transmission and have implications for disease management.


Comparison of the flexural strength of two dual cure adhesive resin cements under oral simulated conditions: an in-vitro study.
The purpose of this in vitro study was to evaluate the flexural strength of the newly developed self-adhesive dual cure resin cement and compare it with conventional resin cement under oral simulated conditions. A conventional resin cement (Calibra) and self adhesive resin cement (RelyX U100) were selected and 40 specimens of each cement were fabricated for the study. Half of these specimens were polymerized directly whereas the other half were polymerized through 2 mm of porcelain disc. Specimens were tested after 24hrs and after 30 days immersion in artificial saliva. A three point bending test was performed using universal testing machine at a crosshead speed of 1mm/min. Overall RelyX U100 showed higher mean flexural strength compared to Calibra (141.55 MPa, 119.46MPa, respectively). When the specimens of both the cements were light cured through 2 mm porcelain disc, their flexural strength decreased significantly. The mean flexural strength of both self adhesive and conventional dual cure adhesive resin cements was increased significantly after storage in artificial saliva for 30 days at 37 degreeC. Among the two dual cure resin cements, the self adhesive dual cure cement (RelyX U100) showed increased overall mean flexural strength as compared to conventional resin cement (Calibra) under all the curing and storage protocols.


[Effect of short-term manganese chloride intoxicatuion on anxiety and fear of young rats].
Manganese is an essential trace element for all living organisms. Though some neurological dysfunction take place during intoxication caused by excessive exposure of this metal. The goal of this research was to elucidate the emotional state, in particular anxiety and fear in three groups of young male rats. Two groups of 30 day old rat pups were given drinking water with MnCl(2)·4H(2)O dissolved in, the doses were 1mg/ml (I group) and 10 mg/ml (II group), and the third group was control animals. Before starting and a day after of termination manganese consumption the animals were tested in the "open field" and "elevated-plus maze". In two month old rat pups compared to one month ones the elevation of anxiety was observed that led to increase of fear. 30 day intoxication of one month old rat pups with both doses of manganese (1 and 10 mg/ml) induces: strengthening of motor and orienting-explorative activity, decrease in the level of anxiety and fear. During the intoxication of animals with above mentioned doses of manganese chloride the dose-dependant effect is not observed.


Dihydromyricetin ameliorates oxygen‑glucose deprivation and re‑oxygenation‑induced injury in HT22 cells by activating the Wnt/β‑catenin signaling pathway.
Dihydromyricetin (DMY) is a natural flavonoid that possesses a wide range of pharmacological properties. The aim of the present study was to determine whether DMY could protect against nerve cell injury following ischemic stroke through antioxidant and neuroprotective effects. The effects of DMY on the viability, oxidative stress and apoptosis of HT22 cells following oxygen‑glucose deprivation and re‑oxygenation (OGD/R) were examined using MTT, lactate dehydrogenase (LDH), superoxide (SOD), malondialdehyde (MDA), western blot and TUNEL assays. Furthermore, Wnt/β‑catenin signaling proteins in OGD/R‑stimulated HT22 cells were detected in the presence or absence of DMY. In a separate experiment, the effect of DMY on OGD/R‑induced HT22 cell injury was also observed in the presence of the Wnt/β‑catenin inhibitor, XAV939. The results demonstrated that DMY had no impact on the survival of untreated HT22 cells, although DMY treatment significantly increased cell viability and inhibited cytotoxicity, oxidative stress and apoptosis following OGD/R. In addition, DMY upregulated the expression of Wnt/β‑catenin in OGD/R‑stimulated HT22 cells. In conclusion, DMY protected HT22 cells from OGD/R‑induced oxidative stress and apoptosis, and its effects may be mediated by the activation of the Wnt/β‑catenin signaling pathway.


Passive sampler used for simultaneous measurement of breathing zone size distribution, inhalable dust concentration and other size fractions involving large particles.
The particle size-dependent sampling velocity of the passive dust sampler developed by Vinzents (1996) is investigated under field conditions. Microscopical determination of the projected area equivalent diameter is used to quantify particles deposited on the sampler foils. Parameters for a semi-empirical model for particle deposition velocities on upward and forward facing foils are fitted to the data and it is shown that deposition mechanisms other than gravitational settling on the upward facing foil can be neglected. For calculation of airborne mass concentration no information on particle density is needed and only the ratio between the dynamic and volume shape factors needs to be known. Given the sampling velocity, the airborne mass per diameter interval is calculated from samples obtained in the wood industry, from which inhalable dust concentrations are calculated. The results are in line with parallel samples obtained with an inhalable dust sampler. A 'total' dust sampling characteristic can be fitted which reproduces measured 'total' dust with a closed face monitor. The results of this study demonstrate the validity of the passive dust sampling principle in environments involving even large (>100 microm) particles and the potential to predict the concentration of several size fractions.


Sulfated malto-oligosaccharides bind to basic FGF, inhibit endothelial cell proliferation, and disrupt endothelial cell tube formation.
The interaction of basic FGF (bFGF) with heparin, heparan sulfate and related sugars can potentiate or antagonize bFGF activity, depending on the size of the saccharide used. Oligosaccharides based on heparin structures, as small as six sugar residues, have been demonstrated to bind to bFGF and block its activity, while larger structures (> 10 sugar residues) tend to potentiate bFGF. In this study we have synthesized a series of compounds designed to test the requirements of size and sulfation for binding of oligosaccharides to bFGF. These oligosaccharides are not derived from heparin, but rather, are linear chains of glucose linked alpha 1-4 (malto-oligosaccharides) that have been chemically sulfated. In addition to bFGF binding, these compounds were tested for their ability to block basic functions of endothelial cells that are known to be mediated, at least in part, by bFGF. We report that the ability of sulfated malto-oligosaccharides to block binding of bFGF to heparan sulfate was dependent on the size (at least a tetrasaccharide is required), and the degree of sulfation. The activity profile in the bFGF ELISA closely correlated with the ability of these compounds to block REEC or HMVEC tube formation on Matrigel. There was a similar relationship of size and sulfation to the ability of the sulfated malto-oligosaccharides to inhibit endothelial cell growth for most human and rat EC types tested. The single exception was REEC cell growth. One isolate of these cells was stimulated by sulfated malto-oligosaccharides rather than inhibited by them, while a second isolate was neither stimulated nor inhibited. This stimulation showed no correlation with inhibition of bFGF binding in the ELISA assay, suggesting that growth of this cell type was probably not dependent on bFGF. Compounds derived from this series of sulfated, malto-oligosaccharides have the potential to function as bFGF antagonists, are relatively easy to produce, and possess relatively low anticoagulant properties.


Buccal dental-microwear and dietary ecology in a free-ranging population of mandrills (Mandrillus sphinx) from southern Gabon.
Analyses of dental micro- and macro-wear offer valuable information about dietary adaptations. The buccal surface of the teeth does not undergo attrition, indicating that dental microwear may directly inform about food properties. Only a few studies have, however, investigated the environmental and individual factors involved in the formation of such microwear in wild animals. Here, we examine variation of buccal microwear patterns of mandibular molars in a large free-ranging population of mandrills (Mandrillus sphinx). We first explore the influence of seasonality and individual's sex, age and tooth macrowear-expressed as the percent of dentine exposure (PDE)-on six microwear variables. Second, we analyze the interplay between individual's diet and PDE. In a last analysis, we revisit our results on mandrills in the light of other primate's microwear studies. We show that the average buccal scratch length and the frequency of vertical buccal scratches are both higher during the long dry season compared to the long rainy season, while we observe the inverse relationship for disto-mesial scratches. In addition, females present more disto-mesial scratches than males and older individuals present higher scratch density, a greater proportion of horizontal scratches but a lower proportion of vertical scratches than young animals. PDE yields similar results than individual's age confirming earlier results in this population on the relationship between age and tooth macrowear. Because seasonality and individual characteristics are both known to impact mandrills' diet in the study population, our results suggest that buccal microwear patterns may inform about individual feeding strategies. Furthermore, PDE increases with the consumption of potentially abrasive monocotyledonous plants, independently of the individuals' age, although it is not affected by food mechanical properties. Finally, buccal scratch densities by orientation appear as relevant proxies for discriminating between different primate taxa.


Bacterial Replication Rate Modulation in Combination with Antimicrobial Therapy: Turning the Microbe against Itself.
A major clinical challenge for treating infectious diseases is the duration of antimicrobial therapy required to eradicate the pathogen. We hypothesized that modulation of the bacterial replication rate in the context of an antimicrobial exposure is coupled with the rate and extent of bactericidal effects. Herein we describe results from in vitro infection model (one compartment, 24-h model; hollow fiber, 10-day model) studies designed to probe the relationship between the bacterial replication rate and the rate and extent of bactericidal effects in the context of an effective antibiotic exposure. The bacterial replication rate was modulated by adjusting the sodium chloride concentration (0 to 8%) in the growth media (Mueller-Hinton II broth). The study drug selected was levofloxacin, and the challenge isolate was Staphylococcus aureus ATCC 29213 (levofloxacin MIC, 0.125 mg/liter). Within each in vitro infection model, human levofloxacin concentration-time profiles (half-life, 7 h) were simulated and the challenge isolate was subjected to an effective exposure (free-drug area under the concentration-time curve over 24 h divided by the MIC [AUC/MIC ratio], 65; administered as a single dose or daily for 10 days). Over the course of each study, samples were taken from each model for bacterial density determinations and drug concentration assay using liquid chromatography-tandem mass spectrometry (LC-MS/MS). In the 24-h one-compartment in vitro infection model studies, as the bacterial replication rate increased, so too did the rate (slope, 0 to 4 h) and extent (24-h CFU count per milliliter) of bacterial killing. In the 10-day hollow-fiber infection model studies, the times until a reduction of bacterial density to 1 × 102 CFU/ml occurred were 10 days in the media in which the challenge isolate grew slowly and approximately 2 days in the media in which the challenge isolate grew rapidly. Together, these data provide a proof of concept for new adjunctive therapeutic options with respect to the use of antimicrobial agents alone that reduce treatment durations. Such adjunctive therapies hold promise for marked reductions in the tonnage of antimicrobial agents administered to patient populations and selection pressure toward antimicrobial resistance.


Ring opening of a sterically crowded 1,2-oxaphosphetane complex.
The first example of a ring opening reaction of a 1,2-oxaphosphetane complex is reported, i.e., water in the presence of [Li(12-crown-4)]Cl furnished a C-OH functional phosphinito complex. Employment of the latter in ring forming reactions with Me2ECL2 (E = Si, Ge) using different nitrogen bases is also described.


[Radiation sterilization of units of a Mars descent module--a miniature meteorological station].
Subject of the test was a procedure of electron sterilization of Mars descent module units. As a result, data on distribution of absorbed dose field across the surface and by the entire volume of the mockup of a miniature meteorological station (MMS) were obtained In addition, electron sterilization technology was developed and the range of absorbed dose from electron radiation that will sterilize reliably packaged MMS hardware were defined in the interval from 30 to 40 kGy.


A one-pot synthesis of 7-phenylindolo[3,2-a]carbazoles from indoles and β-nitrostyrenes, via an unprecedented reaction sequence.
A six-step one-pot reaction was designed for synthesizing homodimeric 7-phenylindolo[3,2-a]carbazoles from 1H-indoles and β-nitrostyrenes, in the presence of SnCl(2)·2H(2)O. The reactions proceeded under very mild conditions and the desired heterocycles were obtained in moderate to good yields. An unprecedented mechanism involving sequential indole dimerization, regioselective nucleophilic conjugate addition of the resulting 2,3'-biindole to β-nitrostyrene and formal intramolecular [4 + 2]-cycloaddition is proposed.


Comprehensive analysis of normal adjacent to tumor transcriptomes.
Histologically normal tissue adjacent to the tumor (NAT) is commonly used as a control in cancer studies. However, little is known about the transcriptomic profile of NAT, how it is influenced by the tumor, and how the profile compares with non-tumor-bearing tissues. Here, we integrate data from the Genotype-Tissue Expression project and The Cancer Genome Atlas to comprehensively analyze the transcriptomes of healthy, NAT, and tumor tissues in 6506 samples across eight tissues and corresponding tumor types. Our analysis shows that NAT presents a unique intermediate state between healthy and tumor. Differential gene expression and protein-protein interaction analyses reveal altered pathways shared among NATs across tissue types. We characterize a set of 18 genes that are specifically activated in NATs. By applying pathway and tissue composition analyses, we suggest a pan-cancer mechanism of pro-inflammatory signals from the tumor stimulates an inflammatory response in the adjacent endothelium.


Evolutionary genetics and infertility.
Mapping the human genome and advances in human evolution indicate a critical role for genetics in the study of reproduction. Literature in human evolution, genetics and reproduction. This paper will focus on three points: (1) the course of primate evolution, (2) implications of this course for reproduction in humans, and (3) evolutionary mechanisms. Reproduction is the driving force of evolution, and sex selection is the important factor in determining reproductive activity. The hypothesis will be presented that the reproductive inefficiency of Homo sapiens (one of four pregnancies succeeds) is the consequence of the development of genetic isolation from other species of Homo that was necessary to drive the evolution of Homo sapiens. This hypothesis is based on the evidence that Homo sapiens and Homo neanderthalensis are separate species and that intermating would not yield fertile offspring (Haldane's Rule). This mating barrier involves zoological and linguistic differences and genetic mechanisms preventing fertile interspecies mating (chromosomal incompatibilities, disruption of genomic imprinting and recessive lethal defects). The medical and philosophical implications of modern reproductive technologies that may circumvent mating barriers must be addressed prospectively: propagation of genetic defects that would be eliminated by natural selection; the specter of 'genetic enhancement'; human cloning; and attempts to control the future direction of the evolution of Homo sapiens.


Inverse design of two-dimensional structure by self-assembly of patchy particles.
We propose an optimization method for the inverse structural design of self-assembly of anisotropic patchy particles. The anisotropic interaction can be expressed by the spherical harmonics of the surface pattern on a patchy particle, and thus, arbitrary symmetries of the patch can be treated. The pairwise interaction potential includes several to-be-optimized parameters, which are the coefficients of each term in the spherical harmonics. We use the optimization method based on the relative entropy approach and generate structures by Brownian dynamics simulations. Our method successfully estimates the parameters in the potential for the target structures, such as square lattice, kagome lattice, and dodecagonal quasicrystal.


[Molecular Mechanisms of Interactions between Mitochondria and the Endoplasmic Reticulum: A New Look at How Important Cell Functions are Supported].
Interactions between the endoplasmic reticulum (ER) and mitochondria have received insufficient attention until recently. However, distorted contacts between the ER and mitochondria were identified as an important factor in the etiopathogenesis of neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. In view of these new data, the mechanisms of ER-mitochondrial interactions are necessary to study in detail in order to develop new diagnostic and therapeutic approaches to neurodegenerative diseases and to extend basic knowledge of the physiology of the eukaryotic cell. The review focuses on the functions of mitochondria-associated ER membranes (MAMs). Structural elements of the MAM system, their contributions to the vital cell functions (calcium and lipid homeostasis, autophagy, fusion and division of mitochondria, and the regulation of their number), and the role of MAM dysfunctions in the pathogenesis of various neurodegenerative diseases are considered.


Self-Supported FeCo2S4 Nanotube Arrays as Binder-Free Cathodes for Lithium-Sulfur Batteries.
Inhibiting the shuttle effect, buffering the volume expansion, and improving the utilization of sulfur have been the three strategic points for developing a high-performance lithium-sulfur (Li-S) battery. Driven by this background, a flexible sulfur host material composed of FeCo2S4 nanotube arrays grown on the surface of carbon cloth is designed for a binder-free cathode of the Li-S battery through two-step hydrothermal method. Among the rest, the interconnected carbon fiber skeleton of the composite electrode ensures the basic electrical conductivity, whereas the FeCo2S4 nanotube arrays not only boost the electron and electrolyte transfer but also inhibit the dissolution of polysulfides because of their strong chemical adsorption. Meanwhile, the hollow structures of these arrays can provide a large inner space to accommodate the volume expansion of sulfur. More significantly, the developed composite electrode also reveals a catalytic action for accelerating the reaction kinetic of the Li-S battery. As a result, the FeCo2S4/CC@S electrode delivers a high discharge capacity of 1384 mA h g-1 at the current density of 0.1 C and simultaneously exhibits a stable Coulombic efficiency of about 98%.


Genetic diversity analysis of common beans based on molecular markers.
A core collection of the common bean (Phaseolus vulgaris L.), representing genetic diversity in the entire Mexican holding, is kept at the INIFAP (Instituto Nacional de Investigaciones Forestales, Agricolas y Pecuarias, Mexico) Germplasm Bank. After evaluation, the genetic structure of this collection (200 accessions) was compared with that of landraces from the states of Oaxaca, Chiapas and Veracruz (10 genotypes from each), as well as a further 10 cultivars, by means of four amplified fragment length polymorphisms (AFLP) +3/+3 primer combinations and seven simple sequence repeats (SSR) loci, in order to define genetic diversity, variability and mutual relationships. Data underwent cluster (UPGMA) and molecular variance (AMOVA) analyses. AFLP analysis produced 530 bands (88.5% polymorphic) while SSR primers amplified 174 alleles, all polymorphic (8.2 alleles per locus). AFLP indicated that the highest genetic diversity was to be found in ten commercial-seed classes from two major groups of accessions from Central Mexico and Chiapas, which seems to be an important center of diversity in the south. A third group included genotypes from Nueva Granada, Mesoamerica, Jalisco and Durango races. Here, SSR analysis indicated a reduced number of shared haplotypes among accessions, whereas the highest genetic components of AMOVA variation were found within accessions. Genetic diversity observed in the common-bean core collection represents an important sample of the total Phaseolus genetic variability at the main Germplasm Bank of INIFAP. Molecular marker strategies could contribute to a better understanding of the genetic structure of the core collection as well as to its improvement and validation.


Progression to hypervascular hepatocellular carcinoma: correlation with intranodular blood supply evaluated with CT during intraarterial injection of contrast material.
To analyze the correlation between intranodular blood supply of borderline lesions (ie, dysplastic nodules or hypovascular well-differentiated hepatocellular carcinoma [HCC] nodules) and their progression to hypervascular classic HCC in cirrhotic livers. One hundred seventy-six borderline lesions seen at computed tomography (CT) during arterial portography (CTAP) and CT during hepatic arteriography (CTHA) were evaluated in 49 patients with cirrhosis who underwent repeated CTAP and/or CTHA but no therapy. On the basis of CTAP findings, nodules were categorized as group A (showing almost the same portal venous supply as the surrounding liver), group B (showing decreased portal venous supply) or group C (showing partially absent portal venous supply); on the basis of CTHA findings, nodules were categorized as group I (showing almost the same arterial supply as the liver), group II (showing decreased arterial supply), or group III (showing partially increased arterial supply). Progression to classic HCC was observed in 29.4% of group A nodules, 53.9% of group B nodules, and 87.9% of group C nodules within 1,000 days; in 58.6% of group I nodules, 12.9% of group II nodules, and 92.2% of group III nodules within 730 days; and in 0% of nodules in group A and I, 28% of nodules in group B and/or II, and 88.7% of nodules in group C and/or III within 730 days. Evaluation of intranodular blood supply was valuable in predicting the prognosis in borderline lesions, except when only arterial blood supply was evaluated.


[Randomized controlled trials in Japan--lung cancer].
Randomized controlled trials conducted in Japan were reviewed. Using PubMed, 12 papers published after 1990 were selected. Six papers presented at the annual meeting of the American Society of Clinical Oncology from 1999 to 2002 were also added for use in this review. According to the results of those trials, cisplatin plus either irinotecan or docetaxel for advanced non-small cell lung cancer, cisplatin plus irinotecan for small cell lung cancer and concurrent chemoradiotherapy for a localized disease of both small and non-small cell lung cancers have been established as standard treatments. No adjuvant treatment method for resected patients has been proved to be sufficiently effective.


Characterization of biofilm formation by Exiguobacterium strains in response to arsenic exposure.
In this work, we characterized the composition, structure, and functional potential for biofilm formation of Exiguobacterium strains isolated from the Salar de Huasco in Chile in the presence of arsenic, an abundant metalloid in the Salar that exists in different oxidation states. Our results showed that the Exiguobacterium strains tested exhibit a significant capacity to form biofilms when exposed to arsenic, which would contribute to their resistance to the metalloid. The results highlight the importance of biofilm formation and the presence of specific resistance mechanisms in the ability of microorganisms to survive and thrive under adverse conditions.


[Clinical case of the month. A case of acute rhabdomyolysis].
A 83 years old patient was admitted with a complex clinical picture including cutaneous rash, muscular pain, rhabdomyolysis and renal failure. The clinical picture suggests a dermatopolymyositis. Despite of high dose corticotherapy, the patient died on day 22. The anatomical examination shows a cholangiocarcinoma disseminated locally as well as in the lungs and bones.


Voice restoration after laryngectomy.
Speech therapists have traditionally played a major part in voice restoration after laryngectomy. Nurses have a potentially complementary role to play, which is explored in this article. The three main methods of voice restoration are outlined and the nurse's role in the management of laryngectomy patients is discussed.


Acute Gastrointestinal Bleed from a Gastrointestinal Stromal Tumour Impersonating an Arteriovenous Malformation of the Jejunum.
Gastrointestinal stromal tumours (GIST) are neoplasms which originate from the mesenchymal tissue of the gastrointestinal tract. We report on a GIST presenting with acute gastrointestinal bleeding that mimicked an arteriovenous malformation (AVM) on imaging and at surgery. A 61-year-old female presented with a short history of melaena and severe anaemia. After resuscitation, upper gastrointestinal endoscopy showed a profusely bleeding varix in the proximal jejunum which was treated with glue injection. Contrast-enhanced CT showed a heterogeneous lesion in the proximal jejunum with strong arterial phase enhancement, supplied by a branch of the superior mesenteric artery and drained by a prominent tributary of the superior mesenteric vein, suggestive of an AVM. The mass was resected, and histology revealed a GIST with no evidence of an AVM or angiodysplasia. A GIST may be considered, though imaging suggests a diagnosis of an AVM in patients presenting with acute gastrointestinal bleeds. In such circumstances, surgical resection and pathological assessment will be confirmatory.


Cleavable Amide Bond: Mechanistic Insight into Cleavable 4-Aminopyrazolyloxy Acetamide at Low pH.
The cleavage of amide bonds under mild acidic conditions is a rare chemical event. N-Acetamide bond of peptides is extremely stable even under the strongest organic acid trifluoromethanesulfonic acid. This report mechanistically describes a new cleavable amide bond in 4-aminopyrazolyloxy acetamide peptide analogues under mild acidic conditions such as trifluoroacetic acid (10-20%) or HCl (0.1-4.0 N) at room temperature, and the formation of unusual lactam from 4-aminopyrazolyloxy acetic acid after evaporation of solvent. This is a rare chemical event in peptide bond, which could be explored as acid-sensitive protecting group of free amines.


Biomechanical Analysis of Subclinical Keratoconus With Normal Topographic, Topometric, and Tomographic Findings.
To investigate the corneal biomechanical responses of subclinical keratoconus with normal topographic, topometric, and tomographic findings. In this prospective observational study, the study group was selected from patients with clinically evident keratoconus in one eye and subclinical keratoconus with normal topographic, topometric, and tomographic findings in the fellow eye. The control group was selected from candidates for contact lens use. The biomechanical analyses were performed using the Corvis ST (Oculus Optikgeräte, Wetzlar, Germany). The following parameters were analyzed: A1 velocity, A2 velocity, A1 length, A2 length, deformation amplitude ratio, stiffness parameter at the first applanation, Corvis Biomechanical Index, and Tomographic and Biomechanical Index (TBI). The study group consisted of 21 patients (10 men and 11 women; mean age: 27.7 ± 6.9 years), and the control group consisted of 35 patients (17 men and 18 women; mean age: 26.1 ± 5.8 years). No significant differences were found between the eyes with subclinical keratoconus and normal eyes in corrected distance visual acuity and the topographic, topometric, and tomographic parameters (P > .05). Significant differences were found in the values of A2 length, A1 velocity, A2 velocity, and TBI between the subclinical keratoconus group and the control group (P < .05). In distinguishing eyes with subclinical keratoconus from normal eyes, the TBI showed the highest area under the curve (0.790; cut-off: 0.29; sensitivity: 67%; specificity: 86%) in the receiver operating characteristic analysis. Biomechanical analysis with the Corvis ST may be used as a complementary diagnostic method in detecting subclinical keratoconus. [J Refract Surg. 2019;35(4):247-252.].


[Evaluation of radiotherapy for state I ovarian carcinoma].
To investigate the role of radiotherapy for stage I epithelial ovarian carcinoma, the results in 91 patients treated from 1970-1989 were retrospectively analysed. There were 60 patients treated by operation combined with chemotherapy, 31 patients by operation combined with chemotherapy and radiotherapy. Patients in both groups were comparable with regard to age, clinical stage, histology grade, type of operation and chemotherapeutic regimen. The 5-year actuarial survival rate was 78.3% for those receiving additional radiotherapy and 72.4% for those without additional radiotherapy. The recurrence rate was 32.2% with a median recurrence time of 34 months in the former group while 60.6% and 18.6% months for the latter. Radiotherapy did not confer survival advantage in the treatment of stage I ovarian cancer, but it could decrease recurrence rate and delay onset of recurrence.


Public health surveillance in the U.S. Department of Veterans Affairs: evaluation of the Praedico surveillance system.
Early threat detection and situational awareness are vital to achieving a comprehensive and accurate view of health-related events for federal, state, and local health agencies. Key to this are public health and syndromic surveillance systems that can analyze large data sets to discover patterns, trends, and correlations of public health significance. In 2020, Department of Veterans Affairs (VA) evaluated its public health surveillance system and identified areas for improvement. Using the Centers for Disease Control and Prevention (CDC) Guidelines for Evaluating Public Health Surveillance Systems, we assessed the ability of the Praedico Surveillance System to perform public health surveillance for a variety of health issues and evaluated its performance compared to an enterprise data solution (VA Corporate Data Warehouse), legacy surveillance system (VA ESSENCE) and a national, collaborative syndromic surveillance platform (CDC NSSP BioSense). Review of system attributes found that the system was simple, flexible, and stable. Representativeness, timeliness, sensitivity, and Predictive Value Positive were acceptable but could be further improved. Data quality issues and acceptability present challenges that potentially affect the overall usefulness of the system. Praedico is a customizable surveillance and data analytics platform built on big data technologies. Functionality is straightforward, with rapid query generation and runtimes. Data can be graphed, mapped, analyzed, and shared with key decision makers and stakeholders. Evaluation findings suggest that future development and system enhancements should focus on addressing Praedico data quality issues and improving user acceptability. Because Praedico is designed to handle big data queries and work with data from a variety of sources, it could be enlisted as a tool for interdepartmental and interagency collaboration and public health data sharing. We suggest that future system evaluations include measurements of value and effectiveness along with additional organizations and functional assessments.


Carbene and Acid Cooperative Catalytic Reactions of Aldehydes and o-Hydroxybenzhydryl Amines for Highly Enantioselective Access to Dihydrocoumarins.
A highly enantioselective method for quick access to dihydrocoumarins is reported. The reaction involves a cooperative catalytic process with carbene and in situ generated Brønsted acid as the catalysts. α-Chloro aldehyde and readily available and stable o-hydroxybenzhydryl amine substrates were used to generate reactive azolium ester enolate and ortho-quinone methide (o-QM) intermediates, respectively, to form dihydrocoumarins with exceptionally high diastereo- and enantioselectivities. The catalytic reaction products can be easily transformed to valuable pharmaceuticals and bioactive molecules.


X11L2, a new member of the X11 protein family, interacts with Alzheimer's beta-amyloid precursor protein.
We screened proteins for interaction with Alzheimer's beta-amyloid precursor protein (APP) and cloned a new member of the X11 protein family, X11L2. The PID/PTB element of X11L2 protein interacted with the intracellular domain of APP by GST binding assay, and in vivo interaction was confirmed by coimmunoprecipitation from cell extracts overexpressing APP and HA-tagged X11L2. This gene encoded 575 amino acids and the deduced amino acid sequence was highly homologous to rat Mint3. Three protein-protein interaction domains, a PID/PTB and two PDZ elements, were conserved among the X11 protein family, and the N-terminal region of X11L2 protein had several putative SH3 binding motifs, PXXP. Unlike other members of the X11 protein family, X11L2 mRNA was expressed in various tissues.


The relationship between the structure and functionality of essential PUFA delivery systems based on sodium caseinate with phosphatidylcholine liposomes without and with a plant antioxidant: an in vitro and in vivo study.
The aim of this work was to establish the main relationship between the structure and functionality of supramolecular complexes formed by sodium caseinate (SC) with phosphatidylcholine (PC) liposomes filled with fish oil (FO) to an equal mass ratio of n-3 to n-6 polyunsaturated fatty acids (PUFA) in the absence and presence of one of the most effective plant antioxidants, namely the essential oil of clove buds (EOC). The functionality of the supramolecular complexes (SC-PC-FO and SC-PC-FO-EOC) was considered from the point of view of the possibility of their use as effective delivery systems for long-chain n-3 PUFAs (eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids from FO). The laser light scattering method was used in the static, dynamic and electrophoretic modes to characterize the structure and thermodynamic parameters of the supramolecular complexes in an aqueous medium. It was found that the SC-PC-FO and SC-PC-FO-EOC complex particles had the following similar properties: nanosize; a spherical shape; 100% solubility in an aqueous medium (pH 7.0, ionic strength = 0.001 M); a high encapsulating ability of SC (up to 70%) in relation to the studied liposomes; and a high protective ability relative to lipid autooxidation (up to 96% on the 20th day of storage at room temperature in light). In addition, a sequential transformation of both the structural and thermodynamic parameters has been observed for the complex particles under in vitro simulated gastrointestinal (GI) conditions in accordance with the INFOGEST protocol. A greater release of the encapsulated lipids from the enzymatically hydrolyzed complex particles was observed at the small intestine stage compared to their release at the gastric stage. These data were in good agreement with those on the assessment of the bioavailability of the target PUFAs in in vivo experiments based on the chronic intake of aqueous solutions of the complexes (both SC-PC-FO and SC-PC-FO-EOC) by experimental mice for 92 days. Liver lipid profiles of the mice, obtained by gas-liquid chromatography, showed the following: (i) an almost twofold increase in the DHA content as compared with that of the control; (ii) an almost threefold decrease in the mass ratio of arachidonic acid (AA) (C20:4 n-6) to DHA (C22:6 n-3) compared to that of the control due to both a significant decrease in the AA content and a simultaneous pronounced increase in the DHA content; and (iii) an almost twofold decrease in the mass ratio of the total amounts of n-6 to n-3 PUFAs compared to that of the control.


Next generation syndromic surveillance: molecular epidemiology, electronic health records and the pandemic Influenza A (H1N1) virus.
In the early phase of the 2009 A (H1N1) pandemic a marked increase in severity and a shift in the age distribution toward younger persons was found, with higher severity reported in patients with pre-existing medical conditions and pregnant women. Consistent with previous pandemics, the age and clinical history of the patients play a critical role in the morbidity and mortality associated with the pandemic virus. This is the first influenza pandemic in the information era, where enormous amounts of information will be available from the pathogen and the patient. Recent advances in molecular techniques have provided an enormous amount of information about pathogens in near real time and at relatively low cost. Electronic Health Records (EHRs) provide another enormously rich set of information about patients, which include patient preconditions, previous exposures, immunization history, presenting complaints, duration and severity of illness, treatment history, and geographic location. An infectious disease is a complex interplay between host and pathogen. The morbidity and mortality of a virus depend on the virus, the patient, and the environment. To evaluate and understand the severity of the pandemic virus and to identify the populations at risk of mild or severe, life-threatening illness, it is compulsory to integrate viral and patient information in a fast and accurate way. Both advances in biomedical informatics with the creation of EHRs and molecular techniques provide the framework to achieve these aims.


A fusion protein with the receptor-binding domain of vascular endothelial growth factor-A (VEGF-A) is an antagonist of angiogenesis in cancer treatment: Simultaneous blocking of VEGF receptor-1 and 2.
Vascular endothelial growth factor (VEGF) is an angiogenic factor that signals through VEGFR-1 and VEGFR-2, which are expressed preferentially in proliferating endothelial cells. Thus, simultaneous blockage of both VEGF receptors may provide a more efficient therapeutic response in cancer treatment. We created a recombinant fusion protein (RBDV-IgG1 Fc), which is composed of the receptor binding domain of human VEGF-A (residues 8-109) and the Fc region of human IgG1 immunoglobulin. The recombinant protein can bind to both mouse VEGFR-1 and VEGFR-2 to decrease VEGF-induced proliferation and tube formation of endothelial cells in vitro. In this study, the RBDV-IgG1 Fc fusion protein reduced the effects of proliferation, migration and tube formation induced by VEGF in murine endothelial cells in vitro. In vivo tumor therapy with RBDV-IgG1 Fc resulted in tumor inhibition by reducing angiogenesis. Pathological evidence also shows that RBDV-IgG1 Fc can seriously damage vessels, causing the death of tumor cells. These findings suggest that this chimeric protein has potential as an angiogenesis antagonist in tumor therapy.


Crohn's ileitis complicated by amyloidosis: observations and therapeutic considerations.
We present a patient with clinically asymptomatic amyloidosis associated with Crohn's ileitis. A distinction should be made between immunocytic dyscrasia associated with amyloidosis (formerly primary or myeloma-associated amyloidosis) and acquired systemic amyloidosis (formerly secondary amyloidosis). We compare the natural course of amyloidosis complicating Crohn's disease with these complicating familial Mediterranean fever (FMF), and discuss the role of resection and the rationale behind colchicine therapy. Our patient is the first reported case in which colchicine therapy alone has been successful in the prophylactic treatment of amyloidosis complicating Crohn's ileitis.


Reciprocal Regulation of Hippo and WBP2 Signalling-Implications in Cancer Therapy.
Cancer is a global health problem. The delineation of molecular mechanisms pertinent to cancer initiation and development has spurred cancer therapy in the form of precision medicine. The Hippo signalling pathway is a tumour suppressor pathway implicated in a multitude of cancers. Elucidation of the Hippo pathway has revealed an increasing number of regulators that are implicated, some being potential therapeutic targets for cancer interventions. WW domain-binding protein 2 (WBP2) is an oncogenic transcriptional co-factor that interacts, amongst others, with two other transcriptional co-activators, YAP and TAZ, in the Hippo pathway. WBP2 was recently discovered to modulate the upstream Hippo signalling components by associating with LATS2 and WWC3. Exacerbating the complexity of the WBP2/Hippo network, WBP2 itself is reciprocally regulated by Hippo-mediated microRNA biogenesis, contributing to a positive feedback loop that further drives carcinogenesis. Here, we summarise the biological mechanisms of WBP2/Hippo reciprocal regulation and propose therapeutic strategies to overcome Hippo defects in cancers through targeting WBP2.


Single-site beta-diiminate zinc catalysts for the ring-opening polymerization of beta-butyrolactone and beta-valerolactone to poly(3-hydroxyalkanoates).
Polymerization of beta-butyrolactone (BBL) and beta-valerolactone (BVL) using the zinc alkoxide initiator (BDI-1)ZnO(i)()Pr [(BDI-1) = 2-((2,6-diisopropylphenyl)amido)-4-((2,6-diisopropylphenyl)imino)-2-pentene] proceeds very rapidly under mild conditions to produce poly(3-hydroxybutyrate) (PHB) and poly(3-hydroxyvalerate) (PHV), respectively. For the monomer-to-initiator ratio 200:1, PHB number-average molecular weights (M(n)) are proportional to conversion throughout the reaction and polydispersity indices (PDIs) are narrow, consistent with a living polymerization. Higher monomer-to-initiator ratios can be used to achieve high molecular weight PHB (M(n) > 100 000). End-group analysis verifies that the polymerization of BBL follows a coordination-insertion mechanism, where complexes of the form (BDI-1)ZnOCH(Me)CH(2)CO(2)R are the active species. Variable temperature NMR experiments show that (BDI-1)ZnO(i)()Pr is monomeric in benzene-d(6) solution. In contrast, (BDI-2)ZnO(i)()Pr [(BDI-2) = 2-((2,6-diethylphenyl)amido)-4-((2,6-diethylphenyl)imino)-2-pentene] is a poor initiator at room temperature because it prefers to form a bis-mu-isopropoxide dimer in solution. According to kinetic studies, propagation by (BDI-1)ZnO(i)()Pr is first order in both monomer as well as (BDI-1)ZnO(i)()Pr concentration. These results lead us to propose a monometallic active species. Several results suggest that elimination side reactions are slowly catalyzed by zinc alkoxides, leading to degradation of the polymer.


Fibro-osseous Lesions of the Jaw: A Report of Two Cases.
Fibro-osseous lesions of the maxillofacial bones comprise a diverse group of pathologic conditions that include developmental lesions, reactive or dysplastic diseases, and neoplasms. The concept of fibro-osseous lesions has evolved over the last several decades and now includes two major entities: fibrous dysplasia and ossifying fibroma. The less common lesions include florid osseous dysplasia, periapical dysplasia, focal sclerosing osteomyelitis, proliferative periostitis of Garre, and osteitis deformans. We report two cases, the first, a craniofacial polyostotic fibrous dysplasia, and the second, a juvenile ossifying fibroma of maxilla.


Diabetes-related events in adolescents and young adults: opportunities for psychosocial interventions.
This study was conducted to evaluate predictive factors of diabetes-related emergency room (ER) visits and hospitalizations among adolescents and young adults (AYA) with type 1 diabetes (T1D). Baseline demographic, medical, and psychosocial variables were collected for 177 AYA with T1D. Medical records were reviewed to identify ER visits and hospitalizations related to diabetes. Those with diabetes-related events had significantly higher hemoglobin A1c (A1c) values at baseline (p = 0.0001) and during an average 3.36 years of follow-up (p < 0.0001). Participants with events were more likely to have Medicaid or no insurance vs. private insurance (p = 0.0006) and were more likely to be on multiple daily injections vs. insulin pumps (p = 0.0159). Participants with events reported greater diabetes impact on their lives and their parents reported less autonomy in AYA with events (p = 0.0435). These results suggest that when participants were transferring from pediatric to adult care services, factors such as A1c, insurance status and diabetes treatment are associated with diabetes-related events. Further research is needed to elucidate a causative relationship and develop focused interventions to reduce diabetes-related events during this high-risk time. Autonomy should be further explored to determine its role in diabetes-related events during this transition period.


Cell Type-Specific Expression of Corticotropin-Releasing Hormone-Binding Protein in GABAergic Interneurons in the Prefrontal Cortex.
Corticotropin-releasing hormone-binding protein (CRH-BP) is a secreted glycoprotein that binds CRH with very high affinity to modulate CRH receptor activity. CRH-BP is widely expressed throughout the brain, with particularly high expression in regions such as the amygdala, hippocampus, ventral tegmental area and prefrontal cortex (PFC). Recent studies suggest a role for CRH-BP in stress-related psychiatric disorders and addiction, with the PFC being a potential site of interest. However, the molecular phenotype of CRH-BP-expressing cells in this region has not been well-characterized. In the current study, we sought to determine the cell type-specific expression of CRH-BP in the PFC to begin to define the neural circuits in which this key regulator is acting. To characterize the expression of CRH-BP in excitatory and/or inhibitory neurons, we utilized dual in situ hybridization to examine the cellular colocalization of CRH-BP mRNA with vesicular glutamate transporter (VGLUT) or glutamic acid decarboxylase (GAD) mRNA in different subregions of the PFC. We show that CRH-BP is expressed predominantly in GABAergic interneurons of the PFC, as revealed by the high degree of colocalization (>85%) between CRH-BP and GAD. To further characterize the expression of CRH-BP in this heterogenous group of inhibitory neurons, we examined the colocalization of CRH-BP with various molecular markers of GABAergic interneurons, including parvalbumin (PV), somatostatin (SST), vasoactive intestinal peptide (VIP) and cholecystokinin (CCK). We demonstrate that CRH-BP is colocalized predominantly with SST in the PFC, with lower levels of colocalization in PV- and CCK-expressing neurons. Our results provide a more comprehensive characterization of the cell type-specific expression of CRH-BP and begin to define its potential role within circuits of the PFC. These results will serve as the basis for future in vivo studies to manipulate CRH-BP in a cell type-specific manner to better understand its role in stress-related psychiatric disorders, including anxiety, depression and addiction.


Nonlinear optical waveguides generated in lithium niobate by swift-ion irradiation at ultralow fluences.
A novel method to produce optical waveguides is demonstrated for lithium niobate (LiNbO(3)). It is based on electronic excitation damage by swift ions, i.e., with energies at approximately 1 MeV/amu or above. The new technique uses high-energy medium-mass ions, such as Cl, with electronic stopping powers above the threshold value for amorphization (5-6 keV/nm), reaching the maximum value a few micrometers inside the crystal. At the ultralow fluence regime (10(12)-10(13) cm(-2)) an effective nanostructured medium is obtained that behaves as an optical waveguide where light propagates transversally to the amorphous nanotracks created by every single impact. The method implies a reduction of 4 orders of magnitude with respect to He implantation. The optical waveguides present reasonable losses (~10 dB/cm) and significant second-harmonic generation (SHG) and electro-optic (EO) responses (>50% bulk) for the lowest fluences.


HIV Infection and Long-Term Residual Cardiovascular Risk After Acute Coronary Syndrome.
Background It is unclear whether HIV infection affects the long-term prognosis after an acute coronary syndrome (ACS). The objective of the current study was to compare rates of major adverse cardiac and cerebrovascular events after a first ACS between people living with HIV (PLHIV) and HIV-uninfected (HIV-) patients, and to identify determinants of cardiovascular prognosis. Methods and Results Consecutive PLHIV and matched HIV- patients with a first episode of ACS were enrolled in 23 coronary intensive care units in France. Patients were matched for age, sex, and ACS type. The primary end point was major adverse cardiac and cerebrovascular events (cardiac death, recurrent ACS, recurrent coronary revascularization, and stroke) at 36-month follow-up. A total of 103 PLHIV and 195 HIV- patients (mean age, 49 years [SD, 9 years]; 94.0% men) were included. After a mean of 36.6 months (SD, 6.1 months) of follow-up, the risk of major adverse cardiac and cerebrovascular events was not statistically significant between PLHIV and HIV- patients (17.8% and 15.1%, P=0.22; multivariable hazard ratio [HR], 1.60; 95% CI, 0.67-3.82 [P=0.29]). Recurrence of ACS was more frequent among PLHIV (multivariable HR, 6.31; 95% CI, 1.32-30.21 [P=0.02]). Stratified multivariable Cox models showed that HIV infection was the only independent predictor for ACS recurrence. PLHIV were less likely to stop smoking (47% versus 75%; P=0.01) and had smaller total cholesterol decreases (-22.3 versus -35.0 mg/dL; P=0.04). Conclusions Although the overall risk of major adverse cardiac and cerebrovascular events was not statistically significant between PLHIV and HIV- individuals, PLHIV had a higher rate of recurrent ACS. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT00139958.


Proteomic analysis of mashua (Tropaeolum tuberosum) tubers subjected to postharvest treatments.
Mashua (Tropaeolum tuberosum) is an important food in certain areas of the Andean region, where it is popularly believed to possess medicinal properties. Several studies have previously shown the potential of this tuber as a source of bioactive compounds. Traditionally, the tuber is exposed to the sun before consumption, in order to reduce its bitterness. The present work aims to study, at the proteome level, the differential abundance of proteins in tubers subjected to different postharvest treatments: sun-exposure (SUN), shade (SHA), refrigeration (COLD) and shade combined with sun-exposure (SHA-SUN) compared to recently harvested tubers (INIT). Results showed that sun exposure for prolonged times (9 days) resulted in increased abundance of proteins classified as heat shock proteins, intracellular traffic, disease/defense and protein degradation. Our results reflect that the sun treatment activates defense systems and osmoprotection adjustment against water loss and reactive oxygen species.


Use of textile dyeing technology to create an infection-resistant functionalized polyester biomaterial.
Infection is a major complication when utilizing implantable devices. The purpose of this study was to create a functionalized polyethylene terephthalate (polyester) biomaterial with sustained antimicrobial properties using textile-dyeing technology. Polyester was hydrolyzed via exposure to sodium hydroxide (NaOH) to provide two functional sites within the polymeric backbone. A modified textile dyeing technique known as thermofixation or pad-heating (pad-heat) in conjunction with autoclaving was employed to directly incorporate the fluoroquinolone antibiotic Ciprofloxacin (Cipro) into polyester fibers. Woven polyester segments were placed into various concentrations of boiling NaOH solutions to create carboxylic acid and hydroxyl groups (HYD). The segments were then sprayed (padded) with a 5 mg mL(-1) Cipro solution and dried overnight, followed by exposure to intense heat and autoclaving. Untreated HYD, Cipro-dipped, and pad-heat-treated HYD segments were then washed under stringent conditions. The antimicrobial activity of the each material was determined via zone of inhibition. Untreated HYD controls had no antimicrobial activity at any of the time periods examined. Cipro-dipped HYD segments had no antimicrobial activity after 1 h. In contrast, antimicrobial activity for autoclaved, pad-heat-treated HYD segments persisted for 80 days (length of study). Autoclave usage prior to plating affected antimicrobial activity substantially. Additionally, varying hydrolysis concentrations did not significantly affect overall Cipro release. Thus, Cipro application to HYD polyester via thermofixation resulted in controlled, sustained antibiotic release over an extended period of time. The long-term infection resistance provided by this technique may address major problems of infection from which implantable devices suffer.


Assessment of subtalar joint neutral position: a cadaveric study.
Subtalar joint (STJ) neutral position is the position typically used by clinicians to obtain a cast representation of a patient's foot before fabrication of biomechanical functional orthosis. But no method for measuring STJ neutral position has been proven accurate and reproducible by different testers. This study was conducted to investigate the STJ neutral position in normal feet in cadavers. Twelve fresh-frozen specimens of amputated lower legs were used. Pressure-sensitive films were inserted into the anterior and posterior articulation of STJ. The contact areas for various foot positions and under axial loads of 600 N were determined based on the gray level of the digitized film. The STJ neutral positions were determined as the ankle-foot position where the maximum contact area was achieved, because the neutral position of a joint was defined as the position where the concave and convex surfaces were completely congruous. In ankle-foot neutral position, the contact area of STJ was (2.79 +/- 0.24) cm(2). In the range of motion of adduction-abduction (ADD-ABD), the maximum contact area was (3.00 +/- 0.26) cm(2) when the foot was positioned 10 degrees of ABD (F = 221.361, P < 0.05). In the range of motion of dorsiflexion-plantarflexion (DF-PF), the maximum contact area was (3.61 +/- 0.25) cm(2) when the foot was positioned 20 degrees of DF (F = 121.067, P < 0.05). In the range of motion of inversion-eversion (INV-EV), the maximum contact area was (3.14 +/- 0.26) cm(2) when the foot was positioned 10 degrees of EV (F = 256.252, P < 0.05). Joints, such as STJ, therefore, are not necessarily in neutral position when the ankle-foot is placed in the traditional concept of neutral position. The results demonstrate that the most approximate STJ neutral position was in the foot position of 10 degrees of abduction, 20 degrees of dorsiflexion and 10 degrees of eversion.