Clinical, Cytogenetic and Molecular Cytogenetic Outcomes of Cell-Free DNA Testing for Rare Chromosomal Anomalies.
The scope of cell-free DNA (cfDNA) testing was expanded to the genome, which allowed screening for rare chromosome anomalies (RCAs). Since the efficiency of the test for RCAs remains below the common aneuploidies, there is a debate on the usage of expanded tests. This study focuses on the confirmatory and follow-up data of cases with positive cfDNA testing for RCAs and cases with screen-negative results in a series of 912 consecutive cases that underwent invasive testing following cfDNA testing. Chorion villus sampling (CVS), amniocentesis (AS), fetal blood sampling, and term placenta samples were investigated using classical cytogenetic and molecular cytogenetic techniques. Out of 593 screen-positive results, 504 (85%) were for common aneuploidies, 40 (6.7%) for rare autosomal trisomies (RATs), and 49 (8.3%) for structural chromosome anomalies (SAs). Of the screen-positives for RATs, 20 cases were evaluated only in fetal tissue, and confined placental mosaicism (CPM) could not be excluded. Among cases with definitive results (n = 20), the rates of true positives, placental mosaics, and false positives were 35%, 45%, and 10%, respectively. Among screen-positives for SAs, 32.7% were true positives. The confirmation rate was higher for duplications than deletions (58.3% vs. 29.4%). The rate of chromosomal abnormality was 10.9% in the group of 256 screen-negatives with pathological ultrasound findings. This study provides further data to assess the efficiency of expanded cfDNA testing for RATs and SAs. The test efficiency for cfDNA seems to be higher for duplications than for deletions, which is evidence of the role of expert ultrasound in identifying pregnancies at increased risk for chromosome anomalies, even in pregnancies with screen-negatives. Furthermore, we discussed the efficiency of CVS vs. AC in screen-positives for RATs.


Navigation by environmental geometry: the use of zebrafish as a model.
Sensitivity to environmental shape in spatial navigation has been found, at both behavioural and neural levels, in virtually every species tested, starting early in development. Moreover, evidence that genetic deletions can cause selective deficits in such navigation behaviours suggests a genetic basis to navigation by environmental geometry. Nevertheless, the geometric computations underlying navigation have not been specified in any species. The present study teases apart the geometric components within the traditionally used rectangular enclosure and finds that zebrafish selectively represent distance and directional relationships between extended boundary surfaces. Similar behavioural results in geometric navigation tasks with human children provide prima facie evidence for similar underlying cognitive computations and open new doors for probing the genetic foundations that give rise to these computations.


Effect of a dietary supplementation with linseed oil and selenium to growing rabbits on their productive performances, carcass traits and fresh and cooked meat quality.
The present experiment tested a dietary supplementation with linseed oil and selenium to growing rabbits. The basal diet (B) contained 3% sunflower oil, while it was substituted with 3% linseed oil in the experimental feed (S). The selenium (Se) content of the two diets was 0.10 vs. 0.46 mg/kg. Rabbits were fed with B diet from the age of 18 days. One group was fed with the B diet until 11 weeks of age (group B), whereas the experimental groups were fed with S diet for 1, 2, 3 or 4 weeks (groups S1, S2, S3 and S4, respectively), before slaughtering (11 weeks of age). Live performance and carcass traits of rabbits, fatty acid (FA) profile and selenium content of their hind leg (HL) and Longissimus thoracis et lumborum (LTL) meat were considered in this study. In addition, the effect of two different cooking methods on the nutritional value of the enriched HL meat was also assessed. The tested dietary supplementation only minimally affected the live performance and carcass traits of rabbits. The S supplementation significantly reduced the Σ n-6 FA and increased the Σ n-3 FA of the HL meat and LTL meat, compared to the B diet (p < 0.001); thus, n-6/n-3 ratio was improved (p < 0.001). In addition, HL meat and LTL meat of S fed rabbits were significantly enriched in Se reaching a twofold increase in both meat cuts (p < 0.01). Therefore, the S supplementation improved the functional value of the rabbit meat. The heat treatment affected cooking loss, Se and vitamin E contents as well as the oxidative status of the HL meat (p < 0.001), with the different cooking methods providing different results. In addition, even if the beneficial C20:5 n-3 and C22:6 n-3 decreased with cooking, the n-6/n-3 ratio remained unaffected.


High miR-122 expression promotes malignant phenotypes in ccRCC by targeting occludin.
Renal cell carcinoma (RCC) is the most common neoplasm of the adult kidney, and clear cell RCC (ccRCC) represents its most common histological subtype. Although several studies have reported high expression of miR-122 in ccRCC, its physiological role remains unclear. To clarify the role of miR-122 in ccRCC, we compared miR-122 expression levels in non-cancerous tissue and ccRCC. Significant upregulation of miR-122 was observed in ccRCC specimens. Moreover, ccRCC patients with high miR-122 expression showed poor progression-free survival compared to those with low miR-122 expression. Overexpression of miR-122 using an miRNA mimic promoted proliferation, migration, and invasion activities of ccRCC cells. miR-122 directly targets occludin, a known component of tight junctions. Occludin knockdown promoted the cell migration activity but not proliferation or invasion activities of ccRCC cells. In human clinical specimens, miR-122 expression inversely correlated with occludin protein expression. These findings show that miR-122 is an oncomiR in ccRCC.


Identification of Lactic Acid Bacteria in Fruit Pulp Processing Byproducts and Potential Probiotic Properties of Selected Lactobacillus Strains.
This study aimed to identify lactic acid bacteria (LAB) in byproducts of fruit (Malpighia glabra L., Mangifera indica L., Annona muricata L., and Fragaria vesca L.) pulp processing. Fifty strains of LAB were identified using matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS) and 16S rRNA gene sequence (16S rRNA) analysis. Species belonging to Lactobacillus genus were the predominant LAB in all fruit pulp processing byproducts. The average congruency between the MALDI-TOF MS and 16S rRNA in LAB species identification reached 86%. Isolates of L. plantarum, L. brevis, L. pentosus, L. lactis and L. mesenteroides were identified with 100% congruency. MALDI-TOF MS and 16S rRNA analysis presented 86 and 100% efficiency of LAB species identification, respectively. Further, five selected Lactobacillus strains (L. brevis 59, L. pentosus 129, L. paracasei 108, L. plantarum 49, and L. fermentum 111) were evaluated for desirable probiotic-related properties and growth behavior on two different cultivation media. The exposure to pH 2.0 sharply decreased the counts of the different Lactobacillus strains after a 1 or 2 h incubation, while varied decreases were noted after 3 h of exposure to pH 3.0. Overall, the exposure to pH 5.0 and to bile salts (0.15, 0.30, and 1.00%) did not decrease the counts of the Lactobacillus strains. All tested Lactobacillus strains presented inhibitory activity against Staphylococcus aureus, Salmonella Typhimurium, Salmonella Enteritidis, Listeria monocytogenes and Escherichia coli, and presented variable susceptibility to different antibiotics. The selected Lactobacillus strains presented satisfactory and reproducible growth behavior. In conclusion, MALDI-TOF MS and 16S rRNA analysis revealed high efficiency and congruency for LAB species identification, and the selected Lactobacillus strains may be candidates for further investigation of novel probiotic strains.


The biological effect of the nitroimidazole derivative of a polypyridyl ruthenium complex on cancer and endothelial cells.
The ruthenium polypyridyl complexes [Ru(dip)2(bpy/bpy-2-nitroIm)](2+) (dip = 4,7-diphenyl-1,10-phenanthroline, bpy = 2,2'-bipyridine, bpy-2-nitroIm = 4-[3-(2-nitro-1H-imidazol-1-yl)propyl]) were found to be ca. ten times more cytotoxic against breast cancer (4T1) and human lung adenocarcinoma epithelial cells (A549) than a well-known anticancer drug, cisplatin. Even though the Ru complexes were quite cytotoxic towards FVB mouse lung microvascular endothelial cells (MLuMEC FVB) their efflux from these non transformed cells was much more efficient than from cancer ones. Both Ru complexes accumulated in cells. The cellular uptake of both Ru complexes occurs through passive diffusion while the nitroimidazole derivative is also endocytosed. They arrest cell growth in the S-phase and induce apoptosis. Such cell response can result from activation of oxidative stress by Ru complexes. The modulation of the mRNA expression profile for genes which might be involved in metastasis and angiogenesis processes by Ru complexes was analyzed for both cancer (4T1) and endothelial (MLuMEC FVB) cells. Ru complexes appeared to have a distinct impact on cell adhesion and migration as well as they affect endothelial cell vasculature. They are not only cytotoxic but are also potentially invasive and anti-metastatic agents. This work illustrates the putative future development of polypyridyl ruthenium.


Glycosphingolipids of the model fungus Aspergillus nidulans: characterization of GIPCs with oligo-alpha-mannose-type glycans.
Aspergillus nidulans is a well-established nonpathogenic laboratory model for the opportunistic mycopathogen, A. fumigatus. Some recent studies have focused on possible functional roles of glycosphingolipids (GSLs) in these fungi. It has been demonstrated that biosynthesis of glycosylinositol phosphorylceramides (GIPCs) is required for normal cell cycle progression and polarized growth in A. nidulans (Cheng, J., T.-S. Park, A. S. Fischl, and X. S. Ye. 2001. Mol. Cell Biol. 21: 6198-6209); however, the structures of A. nidulans GIPCs were not addressed in that study, nor were the functional significance of individual structural variants and the downstream steps in their biosynthesis. To initiate such studies, acidic GSL components (designated An-2, -3, and -5) were isolated from A. nidulans and subjected to structural characterization by a combination of one-dimensional (1-D) and 2-D NMR spectroscopy, electrospray ionization-mass spectrometry (ESI-MS), ESI-MS/collision-induced decomposition-MS (MS/CID-MS), ESI-pseudo-[CID-MS]2, and gas chromatography-MS methods. All three were determined to be GIPCs, with mannose as the only monosaccharide present in the headgroup glycans; An-2 and An-3 were identified as di- and trimannosyl inositol phosphorylceramides (IPCs) with the structures Man alpha 1-->3Man alpha 1-->2Ins1-P-1Cer and Man alpha 1-->3(Man alpha 1-->6)Man alpha 1-->2Ins1-P-1Cer, respectively (where Ins = myo-inositol, P = phosphodiester, and Cer = ceramide). An-5 was partially characterized, and is proposed to be a pentamannosyl IPC, based on the trimannosyl core structure of An-3.


The afferent pupillary defect as an early manifestation of occult temporal arteritis.
A 76-year-old man had excellent visual acuity and an afferent pupillary defect (Marcus-Gunn pupil) on one side. After several weeks of investigation, a diagnosis of biopsy-proved temporal arteritis was made. I believe that this is the first case of "occult" temporal arteritis with essentially normal vision and with an afferent pupillary defect as the sole original manifestation of the disease.


Medical adventure in Nepal.
In 1977 a request for teaching of otologic surgery from a Nepalese doctor to a Canadian colleague resulted in Doctor David Boon and his wife, Joan, travelling to Nepal in February, 1979, as volunteers. They participated in the "Lions Club of Kathmandu First Free Ear Camp" sponsored jointly by the International Sound Foundation Society and the Lions Club of Kathmandu. Fifteen hundred patients were seen and otosclerosis was one of the commonest ear diseases encountered. Adhesive otitis media with attic cholesteatoma was prevalent and a few cases of childhood serous otitis media were diagnosed. Severe sensorineural hearing loss was also prevalent and related to heredity, post febrile illness, and ototoxic drugs. Seventy surgical procedures were performed consisting of mastoidectomy, stapes reconstruction, tympanoplasty and myringotomy.


The use of computer simulation in the design and analysis of cell proliferation experiments.
The simulation language CELLSIM is used to model a population of cells undergoing proliferation, death and migration. It is shown that standard analytical methods can successfully describe the system in its unperturbed state, but may be considerably in error if the system has recently been subjected to cytotoxic insult. It is suggested that laboratory experiments should be performed on perturbed systems only if simulations have shown that the methods of data analysis will be satisfactorily powerful and accurate.


The Development and Characteristics of Ancient Harbours-Applying the PADM Chart to the Case Studies of Ostia and Portus.
Over the last 20 years, the geoarchaeology of ancient harbours has been a very active area of research around the Mediterranean basin, generating much palaeoenvironmental data from many sites, including estimations of sedimentation rates, the height of the ancient sea-level at different dates and palaeo-geographical reconstructions. Combining this information has proved a major challenge. This article proposes a new chart called the Palaeoenvironmental Age-Depth Model (PADM chart), that allows the researchers to combine all relevant indicators in order to estimate harbour potential of a given ancient port, and to generate comparable data between harbours in terms of degree of closure and water depth available against a synchronised chronology. This new approach, developed in the context of the ERC-funded RoMP Portuslimen project, takes into account estimations of water depths relating to differing Roman ship draughts at different periods. It is tested against the palaeoenvironmental evidence published over 10 years from two Roman harbours located at the mouth of the river Tiber: Ostia and Portus. This reveals that: (1) there has been an underestimate of the real sedimentation rates due to the margins of error of the radiocarbon dates; (2) there was effective control of the water column by dredging; (3) there were different periods of control of the sedimentation. We suggest that the navigability of the Ostia harbour by ships with shallower draughts was maintained until sometime between the 2nd c. BC and 1st c. AD, while at Portus it was retained until the 6th-7th c. AD.


Health-related quality of life impact of bevacizumab when combined with irinotecan, 5-fluorouracil, and leucovorin or 5-fluorouracil and leucovorin for metastatic colorectal cancer.
To compare the time to deterioration in health-related quality of life (HRQoL) in patients with previously untreated metastatic colorectal cancer receiving a 5-fluorouracil (5-FU)-based chemotherapy regimen with or without the addition of bevacizumab (BV) in two randomized, placebo-controlled studies. Prespecified HRQoL endpoints in the phase II (Study 2192) and phase III (Study 2107) studies were time to deterioration in HRQoL, measured by the Functional Assessment of Cancer Therapy-Colorectal (FACT-C) Colorectal Cancer Subscale (CCS), Trial Outcome Index (TOI-C), and FACT-C total score. Time to deterioration in HRQoL was evaluated for patients with baseline and postbaseline assessments, using the stratified log-rank test. In the pivotal phase III trial, HRQoL baseline and postbaseline CCS scores were available for 127 patients receiving irinotecan, 5-FU, and leucovorin (LV) (IFL) and 122 patients receiving IFL plus BV. The time to deterioration in HRQoL did not differ significantly between treatment groups as measured by the CCS, TOI-C, or FACT-C total score. In the phase II study, baseline and postbaseline CCS scores were available for 77 and 89 patients receiving 5-FU and LV and 5-FU and LV plus BV, respectively. In that study, the time to deterioration in HRQoL was similar between groups as measured by the CCS and TOI-C scores, but was significantly longer in the 5-FU and LV plus BV arm than in the 5-FU and LV plus placebo arm for the FACT-C total score. When added to 5-FU chemotherapy, BV significantly prolonged overall survival and progression-free survival without compromising HRQoL.


Fibrinogen alpha and gamma genes and factor VLeiden in children with thromboembolism: results from 2 family-based association studies.
Previous case-control studies showed that genetic variation in the fibrinogen gamma gene (FGG) increased the risk for deep vein thrombosis (VT) in adults. We investigated the association between the fibrinogen alpha (FGA) and FGG haplotypes, the factor V(Leiden)-mutation, and pediatric VT and thromboembolic stroke (TS) in 2 independent study samples. Association analysis revealed that the FGA-H1 and FGG-H2 haplotypes were significantly overtransmitted to VT patients (FGA-H1, P = .05; FGG: H2, P = .032). In contrast, the FGG-H3 haplotype was undertransmitted (P = .022). In an independent study sample, FGA-H1 (P = .008) and FGG-H2 (P = .05) were significantly associated with TS. The association of FGA and FGG haplotypes with VT was more pronounced in FV(Leiden)-negative families (FGA-H1, P = .001; FGG-H2, P = .001), indicating a genetic interaction between both risk factors. The risk-conferring FGG-H2 and the protective FGG-H3 haplotypes correlated with low (FGG-H2) and high (FGG-H3) levels of the gamma' chain variant, respectively. These results provide independent and novel evidence that FGA-H1 and FGG-H2 variants are associated with an increased risk of VT and TS in children. The observed negative correlation of genetic VT risk with the plasma levels of the fibrinogen gamma' variant suggests that FGG-H2 and -H3 haplotypes modify thrombosis risk by controlling the level of this FGG splice isoform.


Health Insurance Type and Control of Hypertension Among US Women Living With and Without HIV Infection in the Women's Interagency HIV Study.
Health care access is an important determinant of health. We assessed the effect of health insurance status and type on blood pressure control among US women living with (WLWH) and without HIV. We used longitudinal cohort data from the Women's Interagency HIV Study (WIHS). WIHS participants were included at their first study visit since 2001 with incident uncontrolled blood pressure (BP) (i.e., BP ≥140/90 and at which BP at the prior visit was controlled (i.e., <135/85). We assessed time to regained BP control using inverse Kaplan-Meier curves and Cox proportional hazard models. Confounding and selection bias were accounted for using inverse probability-of-exposure-and-censoring weights. Most of the 1,130 WLWH and 422 HIV-uninfected WIHS participants who had an elevated systolic or diastolic measurement were insured via Medicaid, were African-American, and had a yearly income ≤$12,000. Among participants living with HIV, comparing the uninsured to those with Medicaid yielded an 18-month BP control risk difference of 0.16 (95% CI: 0.10, 0.23). This translates into a number-needed-to-treat (or insure) of 6; to reduce the caseload of WLWH with uncontrolled BP by one case, five individuals without insurance would need to be insured via Medicaid. Blood pressure control was similar among WLWH with private insurance and Medicaid. There were no differences observed by health insurance status on 18-month risk of BP control among the HIV-uninfected participants. These results underscore the importance of health insurance for hypertension control-especially for people living with HIV.


Phase angle spectroscopy on transparent conducting polymer electrodes for real-time measurement of epithelial barrier integrity.
To facilitate automated real-time monitoring of the formation or disruption of an epithelial monolayer, phase angle spectroscopy was performed in custom-designed cell culture dishes including a transparent conductive polymer-based 2-electrode device. A peak in φ amplitude at 103-105 Hz specifically correlated to increased capacitance by proliferating cells. Dynamic monitoring of cell density, and barrier integrity during monolayer formation and disruption were investigated in combination with live-cell microscopy.


Dysregulation of apoptosis in cancer.
Each day, approximately 50 to 70 billion cells perish in the average adult because of programmed cell death (PCD). Cell death in self-renewing tissues, such as the skin, gut, and bone marrow, is necessary to make room for the billions of new cells produced daily. So massive is the flux of cells through our bodies that, in a typical year, each of us will produce and, in parallel, eradicate a mass of cells equal to almost our entire body weight. The morphologic ritual cells go through when experiencing PCD has been termed apoptosis and is executed by a family of intracellular proteases, called caspases. Unlike accidental cell deaths caused by infarction and trauma, these physiologic deaths culminate in fragmentation of cells into membrane-encased bodies which are cleared through phagocytosis by neighboring cells without inciting inflammatory reactions or tissue scarring. Defects in the processes controlling PCD can extend cell life span, contributing to neoplastic cell expansion independently of cell division. Moreover, failures in normal apoptosis pathways contribute to carcinogenesis by creating a permissive environment for genetic instability and accumulation of gene mutations, promoting resistance to immune-based destruction, allowing disobeyance of cell cycle checkpoints that would normally induce apoptosis, facilitating growth factor/hormone-independent cell survival, supporting anchorage-independent survival during metastasis, reducing dependence on oxygen and nutrients, and conferring resistance to cytotoxic anticancer drugs and radiation. Elucidation of the genes that constitute the core machinery of the cell death pathway has provided new insights into tumor biology, revealing novel strategies for combating cancer.


Effects of pesticides and antibiotics on penaeid shrimp with special emphases on behavioral and biomarker responses.
The purpose of the present study is to provide information on the current state of knowledge regarding the effects of pesticides and antibiotics used in aquaculture on penaeid shrimp, one of the most common aquatic products for human consumption, with a special emphasis on the use of behavioral, physiological, and biochemical response. These include behavior; feeding rate changes; respiration rate, oxygen consumption, and osmoregulation alterations; nucleic acids, protein, and glycogen synthesis; cholinesterase activity inhibition; ATPase activity; and oxidative stress responses. This paper also deals with residues of antibiotics and pesticides in penaeid shrimp. Antibiotics and pesticides used in aquaculture may have adverse effects on treated animals and human consumers health if they are not correctly used. As a complement to the measurement of antibiotic and pesticide residues in tissues, the use of behavioral and biomarker responses can provide more relevant biological information on the potential adverse effects of antibiotics and pesticides on penaeid shrimp health.


Glutathione S-transferase and P-glycoprotein expressions in neuroblastoma.
This study was planned to evaluate the prognostic role of glutathione S-transferase pi (GST-pi) and P-glycoprotein (P-gp) expressions in children with neuroblastoma. Sections from formalin-fixed paraffin-embedded tumor blocks from 52 neuroblastoma cases (17 with localized, 35 with advanced disease) were subjected to immunohistochemistry for P-gp and GST-pi expressions. The overall number of tumors positive for P-gp and GST-pi were 19 (36.5%) and 21 (40.4%), respectively. Twenty-two tumors were negative for both GST-pi and P-gp expressions, whereas 10 expressed both proteins. The distribution of staining status of samples in the groups of both proteins showed no significant difference. No relation between the expressions of both proteins and the clinical characteristics of the patients was demonstrable. The differenes between the survival rates of patients with positive and negative staining for P-gp expression were not statistically significant. Although 2 common mechanisms of multiple drug resistance, P-gp and GST-pi, might be responsible for drug resistance in neuroblastoma, this complex mechanism has no direct significant impact on prognosis. Multiple mechanisms at cellular levels are responsible for the resistance against antineoplastic therapies in neuroblastoma.


Poor presurgical performance on both verbal and visual memory measures is associated with low risk for memory decline following left temporal lobectomy for intractable epilepsy.
Studies have shown a lower risk for verbal memory decline following dominant anterior temporal lobectomy (ATL) among patients with poor, presurgical verbal memory scores. It is unclear however, if the risk of decline is increased in patients who also have reduced visual memory. Objective and subjective memory outcome following left ATL was examined in twelve patients with reduced presurgical visual and verbal memory scores. Only one patient demonstrated a meaningful decline in memory scores, with a decline in visual memory following surgery. Presurgically, this patient demonstrated poor memory bilaterally on Wada testing and small discrepancy in hippocampal volumes. She was also one of two patients who continued to have seizures post-surgery. This preliminary study suggests that patients with unilateral, left TLE and poor verbal and visual memory are unlikely to show meaningful memory declines following left ATL, particularly if they demonstrate expected patterns on Wada testing, hippocampal volume discrepancy (left < right), and postsurgical seizure-freedom.


The pericarp extract of Prunus persica attenuates chemotherapy-induced acute nephrotoxicity and hepatotoxicity in mice.
The fruit of Prunus persica L. (peach) is one of the common fruits. Its seed is well known as a traditional medicine (Persicae Semen) in Japan, China, and other Asian countries. However, the biological activities of P. persica fruit except its seed are poorly understood. This study was aimed at evaluating the protective effect of the pericarp extract of P. persica (PPE) against cisplatin-induced acute toxicity in mice. PPE (500 mg/kg, p.o.) showed a significant protection against the acute nephrotoxicity and hepatotoxicity induced by a single administration of cisplatin (45 mg/kg, i.p.) over a 16-hour period in mice. Its protective effect was evaluated by serum and tissue biochemical parameters. The pretreatment with PPE for 7 days prevented the cisplatin-induced decrease in the kidney and liver weights as a percentage of the total body weight. PPE significantly inhibited both the cisplatin-induced elevation in serum blood urea nitrogen and creatinine levels caused by kidney damage and the cisplatin-induced increase in serum alanine aminotransferase and aspartate aminotransferase levels by the liver damage. In addition, the administration of PPE caused recovery of the cisplatin-mediated changes in levels of serum nitric oxide and tissue lipid peroxidation, and reduced glutathione content returned to control levels. These results suggest that PPE protects against cisplatin-induced nephrotoxicity and hepatotoxicity by reducing cisplatin-induced oxidative stress in mice.


Updated recommendations of the International Dengue Initiative expert group for CYD-TDV vaccine implementation in Latin America.
Dengue disease represents a large and growing global threat to public health, causing a significant burden to health systems of endemic countries. For countries considering vaccination as part of their Integrated Management Strategy for Prevention and Control of Dengue, the World Health Organization currently recommends the first licensed dengue vaccine, CYD-TDV for: individuals aged 9 years or above from populations with high transmission rates, based on either seroprevalence criteria or pre-vaccination screening strategies, and for persons with confirmed prior exposure to infection in moderate to lower transmission settings. This paper describes the main conclusions of the Sixth Meeting of the International Dengue Initiative (IDI) held in June 2018, following release of a new product label by the manufacturer, updated WHO-SAGE recommendations, additional scientific evidence on vaccine performance, and reports of experiences by implementing countries. Considerations were made regarding the need for improving the quality of epidemiological and surveillance data in the region to help define the convenience of either of the two vaccination strategies recommended by WHO-SAGE. Extensive discussion was dedicated to the pros and cons of implementing either of such strategies in Latin America. Although, in general, a seroprevalence-based approach was preferred in high transmission settings, when cost-effectivity is favorable pre-vaccination screening is a convenient alternative. Cost-effectiveness evaluations can assist with the decisions by public health authorities of whether to introduce a vaccine. Where implemented, vaccine introduction should be part of a public health strategy that includes the participation of multiple sectors of society, incorporating input from scientific societies, ministries of heath, and civil society, while ensuring a robust communication program.


Hypothalamo-pituitary portal blood concentrations of beta-endorphin during suckling in the ewe.
Matched hypothalamo-pituitary portal and jugular blood samples were collected over about 6 h from 7 lactating Corriedale ewes penned with their lambs, and a careful record was kept of ewe/lamb behaviour. Hypothalamo-pituitary portal blood concentrations of beta-endorphin were measured by radioimmunoassay and the secretion rates were calculated; these were related to peripheral plasma prolactin and LH concentrations, and the sucking bouts of the lambs. Basal LH concentrations remained less than 1 ng/ml with 0-2 pulses of 1.5-3.5 ng/ml amplitude per 6-h collection period. Prolactin secretion was episodic with individual baselines varying from 24 to 286 ng/ml, and peak concentrations of 50-631 ng/ml. Portal beta-endorphin was secreted in an episodic pattern with individual baseline secretion rates varying from 0.125 to 0.495 ng/min, and peak secretion rates of 0.768 to 3.216 ng/min. A close correlation was seen between sucking bouts and the secretion of portal beta-endorphin and peripheral prolactin; 86% of sucking bouts resulted in a significant release of beta-endorphin, and 46% of sucking bouts resulted in a significant release of prolactin. These results show that hypothalamic beta-endorphin is released in response to the sucking stimulus. This provides support for the hypothesis that, during lactation, beta-endorphin acts within the hypothalamus to reduce GnRH release and hence depress pituitary gonadotrophin secretion.


EFFECT OF DEXAMETHASONE AND NITROGEN MUSTARD ON THE PRODUCTION OF RHEUMATOID FACTOR IN RHEUMATOID ARTHRITIS.
The effect of dexamethasone and nitrogen mustard on the production of rheumatoid factor, as measured by sensitized sheep cell and latex agglutination tests, was studied in 19 patients with classical rheumatoid arthritis. Dexamethasone was given orally in a daily dose of 6-8 mg. which was slowly reduced after a two-week period. Nitrogen mustard was infused in the usual therapeutic dose of 0.3 mg./kg. The level of circulating rheumatoid factor decreased, following administration of each agent, after a latent period of 10 days. The effect was most marked at around 30 days. Dexamethasone was more potent than nitrogen mustard. Both drugs together caused transient disappearance of rheumatoid factor in one patient.It is concluded that dexamethasone and nitrogen mustard have the capacity to suppress the formation of the macroglobulins associated with rheumatoid arthritis.


Linear mitochondrial deoxyribonucleic acid from the yeast Hansenula mrakii.
The mitochondrial deoxyribonucleic acid (mtDNA) from a petite-negative yeast, Hansenula mrakii, was studied. A linear restriction map was constructed with 11 restriction enzymes. The linearity of the genome was confirmed by direct end labeling of the molecule, followed by restriction analysis. The molecular weight of the DNA was found to be 55,000 base pairs. This is the first linear mtDNA found in yeast species. Using specific gene probes obtained from Saccharomyces cerevisiae mtDNA, we have constructed a gene map of H. mrakii mtDNA. The arrangement of genes in this linear genome was very different from the circular mtDNA of other known yeasts.


Ultrasound diagnosis of fetal anomalies: an analysis of perinatal management of 318 consecutive pregnancies in a multidisciplinary setting.
The objectives of this study are to analyse the perinatal management decisions made in a multidisciplinary setting following the prenatal diagnosis of fetal anomalies and to evaluate to what extent, in clinical practice, decisions about obstetric management are attuned to those about neonatal management. Data on perinatal management of 318 consecutive singleton pregnancies presented to a multidisciplinary perinatal team in a tertiary centre were collected retrospectively. The multidisciplinary perinatal team decided upon non-aggressive obstetric management in 20% of the cases and consented to termination of pregnancy in 10% of the cases. The multidisciplinary perinatal team decided upon neonatal management in 112(36%) of all fetuses. In 100(89%) of these fetuses, standard neonatal management, and in 12(11%), no neonatal life-sustaining treatment was decided upon. Implementation of the decisions of the multidisciplinary perinatal team on the various management modalities ranged from 88 to 100%. The multidisciplinary perinatal team worked well in making decisions about obstetric management. In 30% of the cases, this concerned end-of-life decisions. However, for the majority of cases, the perinatal team did not plan neonatal management before birth and thereby did not attune obstetric and neonatal management to each other. This probably reflects the different attitudes towards end-of-life decisions between obstetricians and neonatologists. However, to ensure a consistent perinatal management, a multidisciplinary perinatal team has to make prenatal decisions about both obstetric and neonatal management.


Sodium channel subtypes are differentially localized to pre- and post-synaptic sites in rat hippocampus.
Voltage-gated Na+ channels (Nav ) modulate neuronal excitability, but the roles of the various Nav subtypes in specific neuronal functions such as synaptic transmission are unclear. We investigated expression of the three major brain Nav subtypes (Nav 1.1, Nav 1.2, Nav 1.6) in area CA1 and dentate gyrus of rat hippocampus. Using light and electron microscopy, we found labeling for all three Nav subtypes on dendrites, dendritic spines, and axon terminals, but the proportion of pre- and post-synaptic labeling for each subtype varied within and between subregions of CA1 and dentate gyrus. In the central hilus (CH) of the dentate gyrus, Nav 1.1 immunoreactivity was selectively expressed in presynaptic profiles, while Nav 1.2 and Nav 1.6 were expressed both pre- and post-synaptically. In contrast, in the stratum radiatum (SR) of CA1, Nav 1.1, Nav 1.2, and Nav 1.6 were selectively expressed in postsynaptic profiles. We next compared differences in Nav subtype expression between CH and SR axon terminals and between CH and SR dendrites and spines. Nav 1.1 and Nav 1.2 immunoreactivity was preferentially localized to CH axon terminals compared to SR, and in SR dendrites and spines compared to CH. No differences in Nav 1.6 immunoreactivity were found between axon terminals of CH and SR or between dendrites and spines of CH and SR. All Nav subtypes in both CH and SR were preferentially associated with asymmetric synapses rather than symmetric synapses. These findings indicate selective presynaptic and postsynaptic Nav expression in glutamatergic synapses of CH and SR supporting neurotransmitter release and synaptic plasticity.


Agents of human anaplasmosis and Lyme disease at Camp Ripley, Minnesota.
The transmission dynamics of Anaplasma phagocytophilum (Ap) and Borrelia burgdorferi (Bb) among Ixodes scapularis (Is) and mammalian hosts was investigated at Camp Ripley, an area representative of central Minnesota. Prevalence of white-footed mouse infection with Ap and Bb were 20% and 42%, respectively, with a coinfection level of 14%. Peak levels of infection with both agents occurred in May. The average levels of seropositivity to Ap and Bb were 29.3% and 48%, respectively. Of the mice infected with Ap, 47.5% were able to eliminate the pathogen as compared with 19.4% of mice infected with Bb. Ap was detected in 88.4% of 43 eastern chipmunks examined and isolated from 44.7% of the animals. Bb was present in 72.7% of 11 chipmunks examined, and 100% of the animals were also infected with Ap. The seasonality of tick activity differs from that reported for the New York area. Is infestation of mice began in May with peak nymphal infestation also occurring in May (7.4 per infested mouse) and overlapping with peak larval infestation in June (77.1 per infested mouse). Infestation ranged from 100% in May to 34.5% in October. Is comprised 98.4% of the ticks infesting the mice. The temporal pattern of the developmental stages of Is infesting chipmunks was the same as for mice, except that the tick burdens were greater. The nymphal stage peaked in May (81.3 per animal), and the larval stage peaked in June (164.7 per animal). Infestation was 100% in May-August, and >99% of the ticks were Is. Antibodies to Ap were present in >80% of the white-tailed deer examined, but they were infected with the Ap-1 variant rather than the Ap strain infecting mice and humans. Antibodies to Bb were detected in >80% of the deer, but Bb DNA was only detected in 1.5% of blood specimens.


Comparison of haemoglobin levels and blood-transfusion requirements in patients on haemodialysis and on chronic ambulatory peritoneal dialysis.
Comparison of haemoglobin (Hb) and haematocrit (HCT) levels and blood-transfusion requirements in two groups of patients with end-stage renal disease, one on haemodialysis and the other on continuous ambulatory peritoneal dialysis (CAPD), revealed that patients on CAPD had significantly higher Hb and HCT levels than their counterparts on haemodialysis. Blood-transfusion requirements were significantly lower in the CAPD group. There was no correlation between Hb levels and serum creatinine or albumin levels. Two anephric patients on haemodialysis had relatively high transfusion requirements, and this may have had an influence on the results. An analysis of 10 individual patients who were transferred from haemodialysis to CAPD revealed that half of them experienced a significant increase in Hb and HCT levels after having been on CAPD for 12 months. The Hb/HCT response of individual patients was extremely variable, and did not correlate with the number of blood transfusions. There was no significant change in transfusion requirements during the period on CAPD.


Radially aligned, electrospun nanofibers as dural substitutes for wound closure and tissue regeneration applications.
This paper reports the fabrication of scaffolds consisting of radially aligned poly(ε-caprolactone) nanofibers by utilizing a collector composed of a central point electrode and a peripheral ring electrode. This novel class of scaffolds was able to present nanoscale topographic cues to cultured cells, directing and enhancing their migration from the periphery to the center. We also established that such scaffolds could induce faster cellular migration and population than nonwoven mats consisting of random nanofibers. Dural fibroblast cells cultured on these two types of scaffolds were found to express type I collagen, the main extracellular matrix component in dural mater. The type I collagen exhibited a high degree of organization on the scaffolds of radially aligned fibers and a haphazard distribution on the scaffolds of random fibers. Taken together, the scaffolds based on radially aligned, electrospun nanofibers show great potential as artificial dural substitutes and may be particularly useful as biomedical patches or grafts to induce wound closure and/or tissue regeneration.


Analysis of three variables in sampling solutions used to assay bacteria of hands: type of solution, use of antiseptic neutralizers, and solution temperature.
Tests were performed using the sterile bag technique to determine the effects of type of sampling solution, use of antiseptic neutralizers, and solution temperature on the detection and quantitation of bacteria on hands. Using paired hand cultures, three sampling solutions were compared: quarter-strength Ringer solution, a phosphate buffer containing Triton X-100, and the same buffer containing antiseptic neutralizers. The phosphate buffer containing Triton X-100 was significantly better than quarter-strength Ringer solution in mean bacterial yield; the neutralizer-containing sampling solution was slightly better than Triton X-100-containing solution, although differences were not significant at the P = 0.05 level. Temperature (6 or 23 degrees C) of the sampling solution showed no consistent effect on bacterial yield from hands tested with the fluid containing neutralizers.


Genomewide association study reveals a risk locus for equine metabolic syndrome in the Arabian horse.
Equine obesity can cause life-threatening secondary chronic conditions, similar to those in humans and other animal species. Equine metabolic syndrome (EMS), primarily characterized by hyperinsulinemia, is often present in obese horses and ponies. Due to clinical similarities to conditions such as pituitary pars intermedia dysfunction (formerly equine Cushing's disease), conclusive diagnosis of EMS often proves challenging. Aside from changes in diet and exercise, few targeted treatments are available for EMS, emphasizing the need for early identification of at-risk individuals to enable implementation of preventative measures. A genomewide association study (GWAS) using Arabian horses with a history of severe laminitis secondary to EMS revealed significant genetic markers near a single candidate gene () that may play a role in cholesterol homeostasis. The best marker, BIEC2-263524 (chr14:69276814 T > C), was correlated with elevated insulin values and increased frequency of laminitis ( = 0.0024 and = 9.663 × 10, respectively). In a second population of Arabian horses, the BIEC2-263524 marker maintained its associations with higher modified insulin-to-glucose ratio (MIRG) values ( = 0.0056) and BCS ( = 0.0063). Screening of the predicted coding regions by sequencing identified a polymorphic guanine homopolymer and 5 haplotypes in the 3' untranslated region (UTR). An 11 guanine (11-G) allele at was correlated with elevated insulin values in the GWAS population ( = 0.0008) and, in the second population, elevated MIRG and increased BCS > 6.5 ( = 0.0055 and = 0.0162, respectively). The BIEC2-263524-C and the 3' UTR -11(G) polymorphisms were correlated at a 98% frequency, indicating strong linkage disequilibrium across this 150-kb haplotype. Assays for these markers could diagnose horses with a genetic predisposition to develop obesity. Additionally, discovery of FAM174A function may improve our understanding of the etiology of this troubling illness in the horse and warrants investigation of this locus for a role in metabolic- and obesity-related disorders of other species.


Full shift assessment of back and head postures in overhead crane operators with and without symptoms.
Prolonged sitting with a flexed back and neck is recognized as being associated with an increased risk of neck and back pain disorders among overhead crane operators. The aim of this study was to compare back and head postures over a full shift of work between operators who experience back and neck pain, and healthy operators. In a first phase, the prevalence of musculoskeletal symptoms was assessed using the Nordic questionnaire among 120 crane operators. Based on first phase results, 17 operators with back/neck disorders were matched with 15 healthy operators based on age and selected to participate in the second phase of the study. Postures and movements were continuously measured over an 8 h shift using inclinometers. The highest 12-month prevalence of musculoskeletal disorders was found in the lower back, neck and knees. Case and control groups differed significantly in back and head flexion angles at the 50th percentiles APDF (p < 0.05). There was also a significant difference in the time spent working in an extreme posture of the back and head between groups (p < 0.05). This is the first study to document work postures assumed during a full work shift and to compare postures between symptomatic and healthy overhead crane operators. Physical exposure in case group operators was characterized by more awkward and extreme postures in the back and head. The results of this study demonstrate that effective prevention strategies directed towards musculoskeletal disorders are required that address awkward work postures for overhead crane operators.


[Change in cellular surface structures and volume under the action of colchicine].
Effect of colchicine upon the surface structures and volume of embryonic pig kidney cells and mouse ascite carcinoma Krebs II cells involved an increase of the cells volume. This was confirmed by the scanning electron microscopy data. The surface of colchicine-treated pig cells has less microvilli due, probably, to their enlarged volume. Swelling of mitochondrial matrix as well as some other ultrastructural changes in cytoplasm of the drug-treated cells suggest that the increase in the volume is a result of cell hydration. Disturbance of the osmotic equilibrium following the depolymerization of microtubles in the mitotic spindle and cytoplasm, is discussed.


What matters most? Students' rankings of simulation components that contribute to clinical judgment.
As the pedagogy of health care simulation matures, the level of guidance provided and types of simulation components included increasingly vary. To prepare students for professional practice, one university embedded Tanner's model of clinical judgment within the nursing curricula and integrated simulations. There was interest in seeking students' opinions of "what matters most" in the design and delivery of simulations, which may vary from the academic's viewpoint. Senior undergraduate nursing students (N = 150) from three types of study programs rated 11 simulation components in relation to clinical judgment. The three student groups rated all components above 2.9 on a 5-point Likert scale, with some variation across groups for component rankings. The highest ranking components for applying clinical judgment were facilitated debriefing, postsimulation reflection, and guidance by the academic. The lowest ranked components were patient case notes and briefing and orientation to the simulation area. Age and previous nursing experience did not influence the study variables.


A randomised crossover trial of chest physiotherapy in non-cystic fibrosis bronchiectasis.
Regular chest physiotherapy is advocated in non-cystic fibrosis bronchiectasis despite little evidence supporting its routine use. This study aimed to establish the efficacy of regular chest physiotherapy in non-cystic fibrosis bronchiectasis compared with no regular chest physiotherapy. 20 patients not practising regular chest physiotherapy were enrolled in a randomised crossover trial of 3 months of twice daily chest physiotherapy using an oscillatory positive expiratory pressure device compared with 3 months of no chest physiotherapy. The primary end-point was the Leicester Cough Questionnaire (LCQ). Additional outcomes included 24-h sputum volume, forced expiratory volume in 1 s (FEV(1)), forced vital capacity (FVC), forced expiratory flow at 25-75% of FVC (FEF(25-75%)), maximum inspiratory pressure (MIP), maximum expiratory pressure (MEP), exercise capacity, sputum microbiology and St George's Respiratory Questionnaire (SGRQ). The treatment effect was estimated using the differences of the pairs of observations from each patient. There was a significant improvement in all domains and total LCQ score with regular chest physiotherapy (median (interquartile range) total score improvement 1.3 (-0.17-3.25) units; p = 0.002). 24-h sputum volume increased significantly with regular chest physiotherapy (2 (0-6) mL; p = 0.02), as did exercise capacity (40 (15-80) m; p = 0.001) and SGRQ total score (7.77 (-0.99-14.5) unit improvement; p = 0.004). No significant differences were seen in sputum bacteriology, FEV(1), FVC, FEF(25-75%), MIP or MEP. Regular chest physiotherapy in non-cystic fibrosis bronchiectasis has small, but significant benefits.


Assessment of Quality of Life in Migraine.
Quality of life is the perception of an individual's position in life associated with his objectives, expectations, interests, and standard's of life. Health-related quality of life, on the other hand, includes satisfaction with his health and emotional reaction to his state of health. Primary headaches are encountered commonly in adults during their most productive years like end of puberty and at the beginning of 50's. Migraine alone is responsible for 1.3% of years with disability in the world, all headaches together being responsible for twice of this load. Headaches both worsen quality of life of individuals and place a significant burden on the society. This review will focus on the effects of primary headaches, especially migraine, on quality of life and tools used to evaluate these effects.


Legislative funding of athletic training positions in public secondary schools.
In 1991, approximately 21 000 student athletes were actively participating in organized athletics in Hawaii's 61 (38 public and 23 private) secondary schools. Of the 61 schools, only 5 (all private) employed full-time, NATABOC-certified athletic trainers (ATCs) to facilitate the sports health care of their respective student athletes. In an attempt to convince the state legislature that providing funding to hire ATCs was a primary health and safety issue in the state, a community-based educational platform was established and a twofold needs-assessment study was implemented statewide. The educational platform was aimed at parents, coaches, athletic directors, and school administrators. The needs-assessment studies consisted of a 30-question survey on the current practices of sports health care and a year-long injury surveillance survey within the 38 public secondary schools. There were significant differences between the public and private schools with respect to the practice of sports health care. The public school student athletes demonstrated a normative incidence of injury rate. These findings definitively quantified and qualified the need to hire ATCs in the public secondary schools. In July of 1993, the State of Hawaii funded a 2-year athletic training pilot program for approximately $1.2 million, following an extensive lobbying effort and media campaign.


[Diagnosis and surgical methods of managing patients with chronic abdominal ischaemia].
Presented herein are the findings of examination of sixty-two patients with clinical manifestations of chronic abdominal ischaemia predominantly induced by stenosis of the celiac trunk. The authors carried out a comparative analysis of efficacy of instrumental methods of diagnosis of chronic abdominal ischaemia syndrome, having also investigated the lesions of the visceral branches by the findings of angiography. Also presented herein are the outcomes of various methods of surgical correction: 47 reconstructive and conditionally reconstructive operations, 10 transcutaneous endovascular angioplasties, also considering complications of the immediate postoperative period as well as short- and long-term outcomes of surgical treatment.


Effectiveness of upper limb exercises and breathing exercises in COPD stable patients during COVID-19 pandemic era.
This study was a quasi-experiment conducted from August to November 2020 involving 10 COPD stable patients. In the first meeting at the hospital, patients were taught breathing techniques and upper-limb exercise movements which subsequently had to be done and recorded at home. Patients then sent the videos to the research team via whatsapp to be evaluated. Prior to starting the 4-week with twice-a-week frequency home-based rehabilitation, and again at the end of it, patients' conditions were evaluated based on the following factors: lung functional capacity was measured by 6MWD (6 Minutes Walking Distance), Perceived Exertion Scale by mMRC (modified Medical Research Council) and Borg, the quality of life by SGRQ (St. George's Respiratory Questionnaire) index, the severity of symptoms by CAT (COPD Assessment Test) and changes in muscle mass. Statistical analysis was conducted using the Wilcoxon and paired t-test. After 4 weeks of home training with twice-a-week frequency, the results showed significant improvement, with p-value < 0.05, in the increased 6MWD value (16.4 ± 4.45 to 19.8 ± 3.64), mMRC (1.90 ± 1.10 to 0.90 ± 0.87), Borg (3.05 ± 1.53 to 1.40 ± 1.42), CAT (15.7 ± 6.63 to 11.8 ± 5.24) and muscle mass (28.36 ± 2.89 to 31.86 ± 3.97). The method produced positive outcomes in patients' lung function capacity, severity of symptoms, exertion scale, muscle mass, and general quality of life. Accordingly, the home-based rehabilitation programme was as effective as the programme conducted at health-care centers.


Fossil evidence for the origin of aquatic locomotion in archaeocete whales.
Recent members of the order Cetacea (whales, dolphins, and porpoises) move in the water by vertical tail beats and cannot locomote on land. Their hindlimbs are not visible externally and the bones are reduced to one or a few splints that commonly lack joints. However, cetaceans originated from four-legged land mammals that used their limbs for locomotion and were probably apt runners. Because there are no relatively complete limbs for archaic archaeocete cetaceans, it is not known how the transition in locomotory organs from land to water occurred. Recovery of a skeleton of an early fossil cetacean from the Kuldana Formation, Pakistan, documents transitional modes of locomotion, and allows hypotheses concerning swimming in early cetaceans to be tested. The fossil indicates that archaic whales swam by undulating their vertebral column, thus forcing their feet up and down in a way similar to modern otters. Their movements on land probably resembled those of sea lions to some degree, and involved protraction and retraction of the abducted limbs.


30-MONTH POST-BREAST CANCER TREATMENT LYMPHOEDEMA.
BACKGROUND: Quantification of lymphoedema (LE) has been problematic, and the reported incidence of LE varies greatly among women treated with surgery and radiation for breast cancer. AIMS: This study aims to describe LE occurrence over time among breast cancer survivors using four diagnostic criteria based on three measurement techniques. METHODS: Limb volume and symptom assessment data were followed after surgery every three months for 12 months, then every six months for 30 months. Limb volume changes (LVC) were measured by circumferences and by perometry, and by symptom experience via interview. Standard survival analysis methods identified when the criteria indicating LE were met. RESULTS: Trends in LE occurrence are reported for data from 211 participants. At 30 months post-treatment, LE incidence ranged from 41-91%, with 2cm being the highest estimation method and self-reported signs and symtoms (SS) the lowest. CONCLUSIONS: This 30-month analysis supports the previous 12-month analysis in finding the 2cm criteria as the most liberal definition of LE. Self-reporting of heaviness and swelling, along with 10% LVC, represented the most conservative definitions (41% and 45%, respectively).


Antioxidant response of osteoblasts to doxycycline in an inflammatory model induced by C-reactive protein and interleukin-6.
Investigation of osteoblastic responses to oxidative stress, induced by C-reactive protein (CRP) and IL-6 and ameliorating effects of doxycycline (Dox); using assays for 5-alpha dihydrotestosterone (DHT) as an antioxidant marker of healing. IL-6 and CRP are risk markers of periodontitis and prevalent comorbidities in periodontitis subjects. Confluent monolayer cultures of osteoblasts were incubated with radiolabelled testosterone (14C-T) as substrate, in the presence or absence (Control) of pre-determined optimal concentrations of CRP, IL-6, Dox; alone and in combination (n=8) for 24h in MEM. The eluent was solvent-extracted for steroid metabolites. They were separated using TLC in a benzene/ acetone solvent system 4:1 v/v; and quantified using radioisotope scanning. The identity of formed metabolites was confirmed using the mobility of cold standards added to the samples and disclosed in iodine. Further confirmation of the authenticity of DHT was carried out by combined gas chromatrography-mass spectrometry, after derivatization to pentafluorobenzyloxime trimethyl silyl ether. The yields of DHT from 14C-testosterone showed 2-fold and 1.8-fold- inhibition in response to IL-6 and CRP respectively and 28% stimulation in response to Dox, via the 5-alpha reductase pathway. The combination of IL-6 + CRP showed a 2-fold reduction in the yields of DHT, elevated to control values when combined with Dox (n=8; p<0.001). Yields of 4-androstenedione showed an inverse relationship to those of DHT, in response to the agents tested, in keeping with the 17-beta hydroxysteroid dehydrogenase pathway. Inhibition of DHT synthesis in osteoblasts by IL-6 and CRP was overcome by doxycycline. Oxidative actions of IL-6 and CRP; and antioxidant actions of Dox are reinforced by the metabolic yields of DHT in response to agents tested. Using a novel metabolically active model allows closer extrapolation to in vivo conditions; in the context of adjunctive therapeutic applications for periodontitis and prevalent comorbidities.


Meningiomas in children and adolescents.
To review the diagnosis, treatment, and long-term outcome of children and adolescents with meningiomas diagnosed by a single institution and compare these findings with other published data. A 25-year retrospective analysis of 18 patients with meningioma diagnosed at Children's Hospital Medical Center, Cincinnati, Ohio was performed. A literature review of published reports was undertaken to compare evaluation. treatment, and outcome for similar patients. Patients ranged from ages 19 months to 17 years at diagnosis. The most common symptoms were headache (5) and seizures (5), although most patients had multiple symptoms. The brain was the primary location of tumor in 17 patients, with the remaining tumor located in the spine. Comorbid diagnoses were common, including developmental delay, balanced chromosomal translocation, type I diabetes mellitus, neurofibromatosis, Klinefelter syndrome, and seizures. Eleven patients had gross total resection performed. Four patients had malignant meningiomas. Two patients were treated with radiotherapy only, one had chemotherapy only, and two underwent both. Karyotype abnormalities most commonly involved chromosome 22, but other abnormalities were present. Sixteen patients remain alive and two patients, having had malignant tumors, are dead of disease. Long-term sequelae include seizures, diabetes insipidus, blindness, neuropsychologic abnormalities, and multiple surgical procedures. Only three patients are self-described as being without problems. Based on this study and a literature review, the roles of surgery, radiation, and chemotherapy remain unclear. Long-term outcome for patients with meningiomas, especially as it relates to cognitive function, is rarely reported. This group of patients has a high incidence of morbidity associated not only with treatment but also with preexisting diseases. These data indicate the need for a national cooperative group study to better understand the evaluation, treatment, and outcome for children and adolescents who are treated for meningiomas.


Quantification of mtDNA in single oocytes, polar bodies and subcellular components by real-time rapid cycle fluorescence monitored PCR.
Oocytes, in general, are greatly enriched in mitochondria to support higher rates of macromolecular synthesis and critical physiological processes characteristic of early development. An inability of these organelles to amplify and/or to accumulate ATP has been linked to developmental abnormality or arrest. The number of mitochondrial genomes present in mature mouse and human metaphase II oocytes was estimated by fluorescent rapid cycle DNA amplification, which is a highly sensitive technique ideally suited to quantitative mitochondrial DNA (mtDNA) analysis in individual cells. A considerable degree of variability was observed between individual samples. An overall average of 1.59 x 10(5) and 3.14 x 10(5) mtDNA molecules were detected per mouse and human oocyte, respectively. Furthermore, the mtDNA copy number was examined in polar bodies and contrasted with the concentration in their corresponding oocytes. In addition, the density of mtDNA in a cytoplasmic sample was estimated in an attempt to determine the approximate number of mitochondria transferred during clinical cytoplasmic donation procedures as well as to develop a clinical tool for the assessment and selection of oocytes during in vitro fertilisation procedures. However, no correlation was identified between the mtDNA concentration in either polar bodies or cytoplasmic samples and their corresponding oocyte.


Are Differences in Dysphagia Assessment, Oral Care Provision, or Nasogastric Tube Insertion Associated with Stroke-Associated Pneumonia? A Nationwide Survey Linked to National Stroke Registry Data.
Stroke-associated pneumonia (SAP) is a common complication associated with poor outcomes. Early dysphagia screening and specialist assessment is associated with a reduced risk of SAP. Evidence about oral care and nasogastric tube (NGT) placement is equivocal. This study aimed to expose variations in dysphagia management practices and explore their associations with SAP. Speech pathologists from 166 stroke units in England and Wales were surveyed about dysphagia assessment and management, oral care, and NGT placement. Survey data were then linked to the Sentinel Stroke National Audit Programme (SSNAP), the national register of stroke. Univariable and multivariable linear regression models were fitted to estimate the association between dysphagia management practices and SAP incidence. 113 hospitals completed the survey (68%). Variation was evident in dysphagia screening protocols (DSPs), oral care, and NGT practice while specialist swallow assessment data patterns were more consistent. Multivariable analysis showed no evidence of an association in incidence of SAP when using a water-only hospital DSP compared to a multiconsistency DSP (B -0.688, 95% CI: -2.912 to 1.536), when using written swallow assessment guidelines compared to not using written guidelines (B 0.671, 95% CI: -1.567 to 2.908), when teams inserted NGTs overnight compared to teams which did not (B -0.505, 95% CI: -2.759 to 1.749), and when teams had a written oral care protocol compared to those which did not (B -1.339, 95% CI: -3.551 to 0.873). Variation exists in dysphagia screening and management, but there was no evidence of an association between clinical practice patterns and incidence of SAP. Further research with larger sample sizes is needed to examine association with SAP.


N₂reduction and hydrogenation to ammonia by a molecular iron-potassium complex.
The most common catalyst in the Haber-Bosch process for the hydrogenation of dinitrogen (N(2)) to ammonia (NH(3)) is an iron surface promoted with potassium cations (K(+)), but soluble iron complexes have neither reduced the N-N bond of N(2) to nitride (N(3-)) nor produced large amounts of NH(3) from N(2). We report a molecular iron complex that reacts with N(2) and a potassium reductant to give a complex with two nitrides, which are bound to iron and potassium cations. The product has a Fe(3)N(2) core, implying that three iron atoms cooperate to break the N-N triple bond through a six-electron reduction. The nitride complex reacts with acid and with H(2) to give substantial yields of N(2)-derived ammonia. These reactions, although not yet catalytic, give structural and spectroscopic insight into N(2) cleavage and N-H bond-forming reactions of iron.


Ion exchange in KTiOPO4 crystals irradiated by copper and hydrogen ions.
Cs(+)-K+ ion exchanges were produced on KTiOPO4 crystals which is prior irradiated by Cu+ can H+ ions. The energy and dose of implanted Cu+ ions are 1.5 MeV and 0.5 x 10(14) ions/cm2, and that of H+ are 300 keV and 1 x 10(16) ions/cm2, respectively. The temperature of ions exchange is 430 degrees C, and the time range from 15 minutes to 30 minutes. The prism coupling method is used to measure the dark mode spectra of the samples. Compared with results of ion exchange on the sample without irradiations, both the number of guided mode and its corresponding effective refractive index are decreased. The experimental results indicate that the ion exchange rate closely related with the lattice damage and the damage layers formed in the depth of maximum nuclear energy deposition act as a barrier to block the ions diffuse into the sample and the concentration of defects can modify the speed of ion exchange..


Nitrous oxide sedation in pediatric patients undergoing gastrointestinal endoscopy.
The ideal medication to administer to children before gastrointestinal endoscopy procedures has yet to be found. The efficacy of using inhaled nitrous oxide during endoscopy in children was assessed in a pilot study. Patients aged 5 to 17 years, referred to our hospital for diagnostic upper gastrointestinal endoscopy or rectosigmoidoscopy procedures, were eligible for enrollment in this study. All received 50% nitrous oxide in oxygen (Entonox; AGA, Rueil-Malmaison, France) before endoscopy and some of them again during endoscopy. The pediatric endoscopist and the nurse performing the procedure were separately asked to rate cooperation, emotional state, drowsiness and overall efficacy of sedation. Oxygen saturation and adverse effects were recorded throughout the procedure. After endoscopy, children scored their degree of pain during the procedures on a visual analog scale (0, no pain; 100, agony) and on a body outline (projective method). Any adverse effects were noted. Thirty-seven patients were enrolled in the study. Thirty patients underwent diagnostic upper gastrointestinal endoscopy and seven diagnostic rectosigmoidoscopy. The median time from administration of nitrous oxide until insertion of the endoscope was 5 minutes (range, 3-8 minutes). Good or excellent efficacy of the sedation was noted in 92% of children by the endoscopist and in 89% by the nurses. Good or excellent cooperation was noted in 92% of the children by the endoscopist and in 78% by the nurses. The children's pain score on the visual analog scale ranged from 5 to 100 (median, 20) for upper gastrointestinal endoscopy and from 0 to 30 (median, 0) for rectosigmoidoscopy. The time of discharge after endoscopy, defined as the time elapsed between the end of the endoscopy and discharge from the endoscopy suite, varied from 1 to 7 minutes (median, 1.5 minutes). Entonox provides rapid and effective analgesia without heavy sedation, leads to adequate relaxation and cooperation, and facilitates quick and efficient endoscopy. The effect of Entonox was of short duration, allowing the children to leave the endoscopy unit without need for a long recovery period. The adverse effects of Entonox appeared to be minor, and their duration was always brief. Nitrous oxide-oxygen inhalation may provide a valuable alternative to conventional sedation regimens during gastrointestinal endoscopy in children, but randomized and prospective studies comparing nitrous oxide sedation and conventional sedation regimens are necessary.


Increased Serum Levels of Hepcidin and Ferritin Are Associated with Severity of COVID-19.
BACKGROUND The aim of this study was to assess the diagnostic utility of iron homeostasis determinations for prediction of severity of COVID-19. MATERIAL AND METHODS This was a retrospective study enrolling a total of 50 patients diagnosed with the novel coronavirus disease-19 (COVID-19) from February 27, 2020 to March 30, 2020, including a severe group (12 patients) and a mild group (38 patients). For the control group, 50 healthy people were examined during the same period. We compared clinical laboratory data and iron homeostasis biomarkers among the 3 groups. ROC curve analysis was used to assess diagnoses. RESULTS Patients diagnosed with severe COVID-19 had higher hepcidin and serum ferritin levels than in other groups (p<0.001). A combination test of hepcidin and serum ferritin provided the best specificity and sensitivity in the prognosis of COVID-19 severity. Logistic regression analysis showed hepcidin and serum ferritin independently contributed to the severity of COVID-19. Hepcidin and serum ferritin tandem testing predicted COVID-19 severity with 94.6% specificity, while hepcidin and serum ferritin parallel testing had a sensitivity of 95.7%. CONCLUSIONS Iron homeostasis had a robust association with the occurrence of severe COVID-19. Iron homeostasis determinations were specific and sensitive for the early prediction of disease severity in COVID-19 patients and thus have clinical utility.


Translational opportunities in the prenatal immune environment: Promises and limitations of the maternal immune activation model.
The prenatal environment, and in particular, the maternal-fetal immune environment, has emerged as a targeted area of research for central nervous system (CNS) diseases with neurodevelopmental origins. Converging evidence from both clinical and preclinical research indicates that changes in the maternal gestational immune environment can alter fetal brain development and increase the risk for certain neurodevelopmental disorders. Here we focus on the translational potential of one prenatal animal model - the maternal immune activation (MIA) model. This model stems from the observation that a subset of pregnant women who are exposed to infection during pregnancy have an increased risk of giving birth to a child who will later be diagnosed with a neurodevelopmental disorder, such as autism spectrum disorder (ASD) or schizophrenia (SZ). The preclinical MIA model provides a system in which to explore causal relationships, identify underlying neurobiological mechanisms, and, ultimately, develop novel therapeutic interventions and preventative strategies. In this review, we will highlight converging evidence from clinical and preclinical research that links changes in the maternal-fetal immune environment with lasting changes in offspring brain and behavioral development. We will then explore the promises and limitations of the MIA model as a translational tool to develop novel therapeutic interventions. As the translational potential of the MIA model has been the focus of several excellent review articles, here we will focus on what is perhaps the least well developed area of MIA model research - novel preventative strategies and therapeutic interventions.


Racial analysis of patients with myocardial infarction complicated by heart failure and/or left ventricular dysfunction treated with valsartan, captopril, or both.
African Americans have a high incidence of heart failure (HF). Limited retrospective observational subgroup analyses of patients with left ventricular systolic dysfunction (LVSD) suggest marginal benefit of angiotensin-converting enzyme inhibitors in the prevention of HF hospitalizations or total mortality in African Americans. Very few data exist concerning the effectiveness of angiotensin receptor blockers in this population. Baseline characteristics, treatments, and outcomes of patients from the U.S. (3,390 white and 340 African-American patients) in the VALIANT (VALsartan In Acute myocardial iNfarcTion) trial were compared. This trial included patients with an acute myocardial infarction (MI) after initial stabilization and documented LVSD and/or HF. Patients were randomly assigned to receive treatment with valsartan, captopril, or the combination; follow-up continued for up to 3 years (median 24.7 months). African Americans had more coronary risk factors, more markers of poor outcome after MI, and were less likely to be revascularized when compared with white patients. After adjusting for treatment assignment, baseline characteristics, and post-infarction parameters, no difference was found in the 3-year rate of all-cause mortality, cardiovascular mortality, rehospitalization for HF, recurrent MI, or stroke between the 2 groups. African Americans sustaining an acute MI with LVSD and/or HF had similar clinical outcomes compared with white Americans. Valsartan, captopril, or the combination had comparable effects on cardiovascular morbidity and mortality in African Americans and white Americans.


Endothelial nitric oxide synthase gene variation associated with chronic kidney disease after liver transplant.
To identify single nucleotide polymorphisms (SNPs) associated with risk of developing chronic kidney disease (CKD), a prevalent comorbidity, after liver transplant (LT). This study consists of a cohort of adult (> or =18 years) primary-LT recipients who had normal renal function before LT and who survived 1 year or more after LT at a high-volume US LT program between January 1, 1990, and December 31, 2000. Patients with adequate renal function (estimated glomerular filtration rate, > or =40 mL/min per 1.73 m(2) during follow-up; n=308) and patients with incident CKD (estimated glomerular filtration rate, <40 mL/min per 1.73 m(2) after LT; n=92) were identified. To investigate the association of 6 candidate genes with post-LT CKD, we selected SNPs that have been associated with renal function in the literature. Hazard ratios were estimated using Cox regression, adjusted for potential confounding variables. The variant allele (298Asp) of the Glu298Asp SNP in the endothelial nitric oxide synthase gene (NOS3) was significantly associated with CKD after LT (P=.05; adjusted for multiple comparisons). The 5-year incidence of CKD was 70% among patients homozygous for the NOS3 variant allele (298Asp) compared with 42% among those not homozygous for the NOS3 variant allele. Specifically, homozygosity for the NOS3 variant allele conferred a 2.5-fold increased risk of developing CKD after LT (P=.005, adjusted for confounding variables). Homozygosity for the variant allele of NOS3 (298Asp) is associated with CKD after LT and may be useful for identifying recipients at higher risk of post-LT CKD.


Endoscopic plantar fasciotomy: preliminary study with cadaveric specimens. 1991.
The authors have developed an endoscopic approach to a plantar fasciotomy. This technique would minimize the surgical trauma that is normally induced with a conventional type of heel spur surgery. The authors believe that this new technique will provide an earlier return to normal ambulation, less loss of work, and earlier, overall increased patient comfort.


Nuclear morphometry predicts disease-free interval for clinically localized adenocarcinoma of the prostate treated with definitive radiation therapy.
Men treated for prostate cancer often have unexpected outcomes despite predictive models based on stage, grade and prostate-specific antigen (PSA). Previous results have indicated that nuclear morphometry can predict patient outcome in urologic malignancies. Application of this analytical method in prostate cancer treated with radiation therapy is limited. We have evaluated the predictive ability of nuclear morphometry in such patients. Histologic sections from 23 men with clinically localized adenocarcinoma of the prostate treated with radiation therapy were studied. Nuclear morphometric parameters were assessed using a previously described and validated system. Univariate and multivariate logistic regression analyses and a Cox proportional hazards model were used to assess the ability of nuclear morphometric parameters to predict recurrence and disease-free interval. Ten patients had no recurrence with median follow-up of 47. 5 months, while 13 had recurrence. Gleason grade was not predictive of treatment outcome. Pre-treatment PSA data, available for only 11 patients, were predictive of treatment outcome. Several nuclear morphometric parameters predicted recurrence, including upper quartile of suboptimal circle fit and upper quartile of feret-diameter ratio. A prognostic factor score incorporating these 2 parameters was derived, which predicted disease-free interval (p = 0.0014). Int. J. Cancer (Pred. Oncol.) 84:594-597, 1999.


Enhancer detection and developmental expression of zebrafish sprouty1, a member of the fgf8 synexpression group.
Signaling pathways mediated by receptor tyrosine kinases (RTKs) are under positive and negative regulation, and misregulation of RTK signaling results in developmental defects and malignancy. A major class of antagonists of Fgf and Egf signaling are the Sprouty proteins. Through an enhancer detection approach, we isolated the sprouty1 (spry1) gene, expressed in multiple developing organs during embryogenesis. We analyzed expression of spry1 between tail bud stage and 10 days postfertilization. From the tail bud stage on, transcript and reporter are detected in the craniofacial region and in the mid-hindbrain boundary, where expression persists until adulthood. Further expression domains are the telencephalon, hindbrain, dorsal diencephalon and epiphysis, branchial arches, pituitary, and the tubular gill epithelium. In the trunk spry1 is also prominently expressed in pronephros, the lateral line and tail fin. Sprouty1 acts in Fgf signaling downstream of Fgfr1, as its expression is abrogated through the small molecule inhibitor of this receptor, SU5402.


Ischemic insults derepress the gene silencer REST in neurons destined to die.
A subset of genes implicated in genetic and acquired neurological disorders encode proteins essential to neural patterning and neurogenesis. The gene silencing transcription factor neuronal repressor element-1 silencing transcription factor (REST)/neuron-restrictive silencer factor (NRSF) plays a critical role in elaboration of the neuronal phenotype. In neural progenitor and non-neural cells, REST acts by repression of a subset of neural genes important to synaptic plasticity and synaptic remodeling, including the AMPA receptor (AMPAR) subunit GluR2. Here we show that global ischemia triggers REST mRNA and protein expression. REST suppresses GluR2 promoter activity and gene expression in neurons destined to die. Because the GluR2 subunit governs AMPAR Ca2+ permeability, these changes are expected to have profound effects on neuronal survival. In keeping with this concept, acute knockdown of the REST gene by antisense administration prevents GluR2 suppression and rescues post-ischemic neurons from ischemia-induced cell death in an in vitro model. To our knowledge, our study represents the first example of ischemia-induced induction of a master transcriptional regulator gene and its protein expression critical to neural differentiation and patterning in adult neurons. Derepression of REST is likely to be an important mechanism of insult-induced neuronal death.


Fate of chlorate present in cattle wastes and its impact on Salmonella Typhimurium and Escherichia coli O157:H7.
Chlorate salts are being developed as a feed additive to reduce the numbers of pathogens in feedlot cattle. A series of studies was conducted to determine whether chlorate, at concentrations expected to be excreted in urine of dosed cattle, would also reduce the populations of pathogens in cattle wastes (a mixture of urine and feces) and to determine the fate of chlorate in cattle wastes. Chlorate salts present in a urine-manure-soil mixture at 0, 17, 33, and 67 ppm had no significant effect on the rates of Escherichia coli O157:H7 or Salmonella Typhimurium inactivation from batch cultures. Chlorate was rapidly degraded when incubated at 20 and 30 degrees C with half-lives of 0.1 to 4 days. Chlorate degradation in batch cultures was slowest at 5 degrees C with half-lives of 2.9 to 30 days. The half-life of 100 ppm chlorate in an artificial lagoon system charged with slurry from a feedlot lagoon was 88 h. From an environmental standpoint, chlorate use in feedlot cattle would likely have minimal impacts because any chlorate that escaped degradation on the feedlot floor would be degraded in lagoon systems. Collectively, these results suggest that chlorate administered to cattle and excreted in wastes would have no significant secondary effects on pathogens present in mixed wastes on pen floors. Lack of chlorate efficacy was likely due to low chlorate concentrations in mixed wastes relative to chlorate levels shown to be active in live animals, and the rapid degradation of chlorate to chloride at temperatures of 20 degrees C and above.


The protective role of vitamin E in vascular amyloid beta-mediated damage.
Amyloid beta peptide (Abeta) accumulation produces the senile plaques in the brain parenchyma characteristic of Alzheimer's Disease (AD) and the vascular deposits of Cerebral Amyloid Angiopathy (CAA). Oxidative stress is directly involved in Abeta-mediated cytotoxicity and antioxidants have been reported as cytoprotective in AD and CAA. Vitamin E has antioxidant and hydrophobic properties that render this molecule as the main antioxidant present in biological membranes, preventing lipid peroxidation, carbonyl formation and inducing intracellular modulation of cell signalling pathways. Accordingly, vascular damage produced by Abeta and prooxidant agents can be decreased or prevented by vitamin E. The protective effect of vitamin E against Abeta cytotoxicity in vascular cells in comparison to the neuronal system is reviewed in this chapter.


Inhibition of Mevalonate Pathway Prevents Adipocyte Browning in Mice and Men by Affecting Protein Prenylation.
Recent research focusing on brown adipose tissue (BAT) function emphasizes its importance in systemic metabolic homeostasis. We show here that genetic and pharmacological inhibition of the mevalonate pathway leads to reduced human and mouse brown adipocyte function in vitro and impaired adipose tissue browning in vivo. A retrospective analysis of a large patient cohort suggests an inverse correlation between statin use and active BAT in humans, while we show in a prospective clinical trial that fluvastatin reduces thermogenic gene expression in human BAT. We identify geranylgeranyl pyrophosphate as the key mevalonate pathway intermediate driving adipocyte browning in vitro and in vivo, whose effects are mediated by geranylgeranyltransferases (GGTases), enzymes catalyzing geranylgeranylation of small GTP-binding proteins, thereby regulating YAP1/TAZ signaling through F-actin modulation. Conversely, adipocyte-specific ablation of GGTase I leads to impaired adipocyte browning, reduced energy expenditure, and glucose intolerance under obesogenic conditions, highlighting the importance of this pathway in modulating brown adipocyte functionality and systemic metabolism.


Evaluation of the efficacy of laser peripheral iridoplasty in reversing the darkroom provocative test result in Chinese patients with primary angle closure status post laser iridotomy.
To investigate the efficacy and safety of krypton laser peripheral iridoplasty (LPIP) for Chinese patients with primary angle closure (PAC) or primary angle-closure glaucoma (PACG) status post laser iridotomy in reversing the positive results of the dark room provocative test (DRPT). This study was prospective, noncomparative, interventional case series. Thirty-three patients (thirty-eight eyes) with PAC or PACG status post patent laser iridotomy and maintained normal intraocular pressure (IOP) but with positive DRPT results were enrolled. All the subjects were treated with krypton LPIP. DRPT was repeated after krypton LPIP. Results of DRPT were recorded. The visual acuity, IOP and gonioscopy were analyzed before and after krypton LPIP. A minimum time limit for follow-up was 6mo. Thirty-three patients (thirty-eight eyes) were followed for 17.7±8.37mo (range 7-41mo) after LPIP. Positive results of DRPT decreased from 38 eyes to 9 eyes (23.7%) after LPIP. Peripheral anterior synechiae of angle in 34 of 38 eyes (89.5%) remained unchanged at dynamic gonioscopy throughout the follow-up period after LPIP. LPIP decreased positive rates of the DRPT significantly. The mechanism may be that LPIP minimized contact between the peripheral iris and trabecular meshwork, which is a key factor for developing peripheral anterior synechiae.


Characterization of cold-sensitive secY mutants of Escherichia coli.
Mutations which cause poor growth at a low temperature, which affect aspects of protein secretion, and which map in or around secY (prlA) were characterized. The prlA1012 mutant, previously shown to suppress a secA mutation, proved to have a wild-type secY gene, indicating that this mutation cannot be taken as genetic evidence for the secA-secY interaction. Two cold-sensitive mutants, the secY39 and secY40 mutants, which had been selected by their ability to enhance secA expression, contained single-amino-acid alterations in the same cytoplasmic domain of the SecY protein. Protein export in vivo was partially slowed down by the secY39 mutation at 37 to 39 degrees C, and the retardation was immediately and strikingly enhanced upon exposure to nonpermissive temperatures (15 to 23 degrees C). The rate of posttranslational translocation of the precursor to the OmpA protein (pro-OmpA protein) into wild-type membrane vesicles in vitro was only slightly affected by reaction temperatures ranging from 37 to 15 degrees C, and about 65% of OmpA was eventually sequestered at both temperatures. Membrane vesicles from the secY39 mutant were much less active in supporting pro-OmpA translocation even at 37 degrees C, at which about 20% sequestration was attained. At 15 degrees C, the activity of the mutant membrane decreased further. The rapid temperature response in vivo and the impaired in vitro translocation activity at low temperatures with the secY39 mutant support the notion that SecY, a membrane-embedded secretion factor, participates in protein translocation across the bacterial cytoplasmic membrane.


Nuclear eIF4E Stimulates 3'-End Cleavage of Target RNAs.
The eukaryotic translation initiation factor eIF4E is nuclear and cytoplasmic where it plays roles in export and translation of specific transcripts, respectively. When we were studying its mRNA export activity, we unexpectedly discovered that eIF4E drives the protein expression of elements of the 3'-end core cleavage complex involved in cleavage and polyadenylation (CPA), including CPSF3, the enzyme responsible for cleavage, as well as its co-factors CPSF1, CPSF2, CPSF4, Symplekin, WDR33, and FIP1L1. Using multiple strategies, we demonstrate that eIF4E stimulates 3'-end cleavage of selected RNAs. eIF4E physically interacts with CPSF3, CPSF1, and uncleaved target RNA, suggesting it acts directly and indirectly on the pathway. Through these effects, eIF4E can generate better substrates for its mRNA export and translation activities. Thus, we identified an unanticipated function for eIF4E in 3'-end processing of specific target RNAs, and this function could potentially affect the expression of a broad range of oncoproteins.


Role of lipid, apolipoprotein levels and apolipoprotein E genotype in young Italian patients with myocardial infarction.
Studies of young patients with acute myocardial infarction (AMI) have demonstrated that conventional risk factors are usually responsible for their premature atherosclerosis. No account has yet been published of the risk profile of young Italians surviving an AMI. In this study, the conventional risk factors, lipids and apolipoproteins, and apolipoprotein E (APOE) allele distribution were evaluated in 98 consecutive AMI survivors (94 males, 4 females) aged 40.1 +/- 3.9 for at least three months after their acute event. These survivors were matched for age, sex, body mass index and presence of diabetes mellitus with 98 controls selected from subjects admitted to the same hospital for other reasons. Lipid profiles and APOE polymorphism were determined in both groups. Coronary angiography during hospitalization showed the absence of critical stenosis in 6.6% of the survivors, mono-vessel disease in 57.7%, and multi-vessel disease in 35.5%. The survivors had a higher frequency of smoking, hypertension, family history for coronary artery disease (CAD) and dyslipidemia, and a much greater frequency of 3 or more risk factors than the controls: Odd ratios (OR) 7.4, 95% confidence interval (CI) 2.5-18.6, p = 0.0000. Significant differences were found between the groups for triglycerides (p = 0.000002), total cholesterol (p = 0.003), LDL-cholesterol (p = 0.012), HDL-cholesterol (p = 0.0002), apolipoprotein AI (p = 0.00001), and Apolipoprotein B (p = 0.000001). No differences were observed in APOE allele distribution (APOE*4 0.11 vs 0.08, APOE*3 0.86 vs 0.89, APOE*2 0.03 vs 0.03), nor in lipid profile when both higher risk genotype (E3/4, E4/4, E2/4) and lower risk genotype groups (E2/2, E2/3, E3/3) were analysed. OR were calculated as measures of the association of the E4-positive genotypes with AMI. They indicated a non-significant increase in risk of AMI when the survivors were compared with the controls (OR 1.78, 95% CI 0.84-3.70, p = 0.13). This study provides further evidence that conventional coronary risk factors are usually present in young AMI patients. The APOE*4 allele was associated with a 1.8 non-significant increase in the risk of AMI in our group with premature CAD. Comparison with controls showed that the presence of three or more risk factors sharply increased the probability of premature CAD and that hyper-triglyceridemia is an independent risk factor. The data on APOE polymorphism are less certain and a larger study is needed.


The impact of class I compression stockings on the peripheral microperfusion of the lower limb: A prospective pilot study.
The use of medical compression stockings (MCS) in patients with peripheral arterial disease (PAD) and diabetes is the subject of an ongoing critical debate. While reducing leg edema of various origins by improving venous back flow, there is a concern about additional arterial flow obstruction when compression therapy is applied in pre-existing PAD. The aim of this study is to obtain further information on the use of class I MCS in patients with advanced PAD and to evaluate the framework conditions for a safe application. The total collective (n = 55) of this prospective, clinical cohort study consisted of 24 patients with PAD Fontaine stage IIb and higher studied before revascularization, of whom 16 patients were examined again after revascularization, and 15 healthy participants included for reference. The microperfusion of the lower extremity of all participants was examined in a supine, elevated, and sitting position using the oxygen to see (O2C) method. The results indicate that leg positioning had the strongest influence on microcirculation (SO2 and flow: p = 0.0001), whereas MCS had no significant effect on the perfusion parameters (SO2: p = 0.9936; flow: p = 0.4967) and did not lead to a deterioration of values into critical ranges. Mild medical compression therapy appears to be feasible even in patients with advanced PAD. Larger studies are warranted to observe any long-term effects, in particular for the treatment of reperfusion edema after revascularization.


Novel insights into the aetiology of granulomatosis with polyangiitis-a case-control study using the Clinical Practice Research Datalink.
We aimed to provide insights into the aetiology of granulomatosis with polyangiitis (GPA), by conducting a large case-control study using a general population-based, prospectively collected database of healthcare records. We compared all incident cases of GPA in the Clinical Practice Research Datalink 1990-2014, with up to 10 age-, sex- and general practice-matched controls. We identified potential risk factors, recorded numbers of cases and controls exposed to each, and calculated odds ratios (ORs) using conditional logistic regression. Our main analysis excluded data recorded during 1 year before diagnosis, to prevent early symptoms being mistaken for risk factors. We identified 757 people with GPA and matched 7546 controls. People with GPA were five times more likely to have a previous diagnosis of bronchiectasis (OR = 5.1, 95% CI: 2.7, 9.4; P < 0.0001), and these effects remained stable in diagnoses recorded >5 years prior to diagnosis. People with GPA were two to three times more likely than controls to have previous diagnoses of autoimmune diseases or chronic renal impairment, and these effects also remained stable >5 years prior to diagnosis. People with GPA were more likely to have a diagnosis of pulmonary fibrosis (OR = 5.7, 95% CI: 1.7, 19.5; P = 0.01) and sinus infections (OR = 2.7, 95% CI: 1.8, 4.2; P < 0.0001) recorded in the 3 years before diagnosis, but not before this. We also found former smoking, some medications and higher socio-economic status significantly, but less strongly, associated. We found novel long-term associations between GPA and pre-existing bronchiectasis and autoimmune diseases.


Optimization the Process of Chemically Modified Carbon Nanofiber Coated Monolith via Response Surface Methodology for CO2 Capture.
In the present study, a sequence of experiments was performed to assess the influence of the key process parameters on the formation of a carbon nanofiber-coated monolith (CNFCM), using a four-level factorial design in response surface methodology (RSM). The effect of reaction temperature, hydrocarbon flow rate, catalyst and catalyst promoter were examined using RSM to enhance the formation yield of CNFs on a monolith substrate. To calculate carbon yield, a quadratic polynomial model was modified through multiple regression analysis and the best possible reaction conditions were found as follows: a reaction temperature of 800 °C, furfuryl alcohol flow of 0.08525 mL/min, ferrocene catalyst concentration of 2.21 g. According to the characterization study, the synthesized CNFs showed a high graphitization which were uniformly distributed on a monolith substrate. Besides this, the feasibility of carbon dioxide (CO2) adsorption from the gaseous mixture (N2/CO2) under a range of experimental conditions was investigated at monolithic column. To get the most out of the CO2 capture, an as-prepared sample was post-modified using ammonia. Furthermore, a deactivation model (DM) was introduced for the purpose of studying the breakthrough curves. The CO2 adsorption onto CNFCM was experimentally examined under following operating conditions: a temperature of 30-50 °C, pressure of 1-2 bar, flow rate of 50-90 mL/min, and CO2 feed amount of 10-40 vol.%. A lower adsorption capacity and shorter breakthrough time were detected by escalating the temperature. On the other hand, the capacity for CO2 adsorption increased by raising the CO2 feed amount, feed flow rate, and operating pressure. The comparative evaluation of CO2 uptake over unmodified and modified CNFCM adsorbents confirmed that the introduced modification procedure caused a substantial improvement in CO2 adsorption.


Design and fabrication of a low-cost, multispectral imaging system.
This paper reports the design and construction of a low-cost, multispectral imaging system using a single, large format CCD and an array of 18 individual lenses coupled to individual spectral filters. The system allows the simultaneous acquisition of 18 subimages, each with potentially different optical information. The subimages are combined to create a composite image, highlighting the desired spectral information. Because all the subimages are acquired simultaneously, the composite image shows no motion artifact. Although the present configuration uses 17 narrow bandpass optical filters to obtain multispectral information from a scene, the system is designed to be a general purpose, multiaperture platform, easily reconfigured for other multiaperture imaging modes.


Vitamin E supplementation in streptozotocin-treated rats alters cerebellar and plasma nitric oxide metabolism.
Nitric oxide (NO) free radicals appear to contribute to the pathogenesis of a number of disorders including diabetes mellitus. The aim of this study was to determine the effects of streptozotocin (STZ)-induced diabetes on nitric oxide (NO) metabolites in plasma and cerebellar nitric oxide synthase (NOS) activity. Further, it was of interest to determine whether an antioxidant, vitamin E, could reverse the STZ-induced effects. STZ significantly decreased cerebellar NOS but increased the level of plasma total nitrite + nitrate and the level of plasma nitrate. Supplementation with vitamin E effectively reduced the STZ-induced effects. Data demonstrate that vitamin E may serve as a protective antioxidant in STZ-induced diabetes.