Laboratory and field survival of Spodoptera frugiperda (Lepidoptera: Noctuidae) on Bt and non-Bt maize and its susceptibility to insecticides.
Field-evolved resistance of fall armyworm (FAW), Spodoptera frugiperda (Smith), has been reported to Bt maize technologies in Brazil. The control failures of FAW by Bt maize increased the use of insecticides for their control. However, no information is available on the interaction between resistant FAW and their response to insecticides. Here, we evaluated the survival of FAW strains on Bt and non-Bt maize in laboratory and field conditions, and their susceptibility to insecticides. In the laboratory, resistant FAW larvae reared on Bt and non-Bt maize showed a similar susceptibility to spinetoram (LC50 = 0.16-0.18 µg a.i. cm-2 ) and chlorfenapyr (LC50 = 0.17-0.20 µg a.i. cm-2 ). However, their susceptibility was lower than that of the susceptible strain reared on non-Bt maize: LC50 = 0.05 (spinetoram) and 0.08 (chlorfenapyr) µg a.i. cm-2 . In contrast, heterozygous strains had similar susceptibility to the susceptible strain. In field trials, no differences in FAW survival were detected between strains when the commercial dose of two insecticides was applied in Bt and non-Bt maize. FAW strains surviving on Bt and non-Bt maize, at the same development stage, have similar susceptibility to insecticides. The integrated pest management practices and insect resistance management importance of these results are discussed. © 2019 Society of Chemical Industry.


Luteal-phase ovarian stimulation increases the number of mature oocytes in older women with severe diminished ovarian reserve.
In older women with severe diminished ovarian response (DOR), in vitro fertilization (IVF) treatment is much less successful due to the low number of mature oocytes collected. The objective of this study was to assess whether follicular-phase stimulation (FPS) and luteal-phase stimulation (LPS) in the same menstrual cycle (double ovarian stimulation) in older women with severe DOR will produce a higher number of oocytes compared to FPS alone. Women with DOR (n = 69; mean age = 42.4) who underwent double ovarian stimulation for IVF were included. Women underwent ovarian stimulation in FPS using clomiphene citrate, letrozole, and gonadotropins followed by oocyte retrieval. The next day following oocyte retrieval, women underwent a second ovarian stimulation (LPS) using the same medications followed by a second oocyte retrieval. T-test was performed in order to compare the clinical characteristics and outcome in the same participant between FPS and LPS. Although antral follicle count at the start of FPS tended to be higher than at the start of the LPS cycle, there was no statistically significant difference between the duration of ovarian stimulation, peak estradiol levels, number of small (<14 mm) or large (≥ 14 mm) follicles, the total number of oocytes retrieved, or the total number of mature oocytes. Each woman had double the number of mature oocytes collected following a double ovarian stimulation compared to FPS alone. The addition of LPS to the conventional FPS increases the number of mature oocytes retrieved in the same IVF cycle, thus potentially increasing the chances of pregnancy in older women with severe DOR. AFC: antral follicle count; BMI: body mass index; DOR: diminished ovarian reserve; E2: estradiol; FPS: follicular-phase stimulation; FSH: follicle stimulating hormone; GnRH: gonadotropin-releasing hormone; HCG: human chorionic gonadotropin; IRB: institutional review board; IVF: in vitro fertilization; LH: luteinizing hormone; LPS: luteal-phase stimulation; MII: metaphase II.


Fatty acid composition of milk from Holstein cows fed oleamide or canola oil.
Based on previous in vitro results that showed reduced biohydrogenation of oleamide by ruminal microbes, this study was conducted to determine whether the addition of oleamide to the diets of dairy cows would enhance the C18:1 concentration in milk. Nine first lactation Holstein cows were fed three diets in a 3 x 3 Latin square replicated three times. Each period lasted 3 wk. The total mixed diets consisted of 42% corn silage and 58% concentrate (dry matter basis) with either no added fat (control), 3.5% high oleic canola oil, or 3.5% oleamide. Dry matter intake was reduced when oleamide was added to the diet but not when canola oil was added. Milk yields were the same for cows fed all three diets. Canola oil reduced fat-corrected milk yield and milk fat concentration, but these were not affected by oleamide. Milk protein concentration was lower for cows fed oleamide than for cows fed canola oil. Milk C18:1 averaged 23.16% of total fatty acids for cows fed the control diet and increased to 35.13% when canola oil was fed. Oleamide further increased C18:1 to 48.16% of total fatty acids in milk. All fatty acids with > or = 16 carbon chain length were reduced by oleamide. Oleamide was more effective than was canola oil in this study at increasing the oleic acid content of bovine milk. Oleamide reduced dietary intake when added at 3.5% of the dietary dry matter but still had no effect on milk yield or milk composition.


Role of autophagy in advanced atherosclerosis (Review).
Atherosclerosis (AS) remains the leading cause for global cardiovascular disease morbidity and mortality, and a major cause of cardiopathy, myocardial infarction and peripheral vascular diseases. Macrophages serve a critical role in atherosclerotic plaque stabilization and rupture, and the selective removal of macrophages may be beneficial in improving plaque stability. Autophagy is a process of self‑feeding, during which cytoplasmic proteins or organelles are packaged into vesicles and fused with the lysosome to form an autophagosome. The newly formed autophagosome can degrade internalized proteins, and this process may be used to serve the metabolic and self‑renewal requirements of the cell. Autophagy serves an important role in maintaining cell homeostasis and promoting cell survival, and therefore an imbalance in autophagy is closely associated with multiple diseases.


Dorsal approach to presacral biopsy: technical case report.
Biopsy of the presacral space is often awkward, technically difficult, and unrewarding when the sacrum is intact and the procedure is performed either by open operation or with computed tomographic guidance through the abdomen or perineum. We describe a patient with metastatic adenocarcinoma who presented with leg pain and computed tomographic evidence of a high, small mass anterior to an intact sacrum. By drilling a hole through the sacrum lateral to the canal and between the roots, a biopsy of such a mass may be performed easily, safely, and quickly. A dorsal approach to presacral biopsy may be easily performed with readily available technology.


Laser Desorption Postionization Mass Spectrometry Imaging of Folic Acid Molecules in Tumor Tissue.
Mass spectrometry imaging (MSI) is an innovative and powerful tool in biomedical research. It is well-known that folic acid (FA) has a high affinity for folic acid receptor (FR), which is overexpressing in epithelial cancer. Herein, we propose a novel method to diagnose cancer through direct mapping of the label-free FA spatial distribution in tissue sections by state-of-the-art laser desorption postionization-mass spectrometry imaging (LDPI-MSI). Compared with other tumor imaging methods, such as fluorescence imaging, photoacoustic imaging (PAI), magnetic resonance imaging (MRI), and micro-SPECT/CT, complicated synthesis and labeling processes are not required. The LDPI-MSI was performed on 30 μm thick sections from a murine model of breast cancer (inoculation of 4T1 cells) that were predosed with 20 mg/kg of FA. The image obtained from the characteristic mass spectrometric signature of FA at m/z 265 illustrated that FA was concentrated primarily in tumor tissue and displayed somewhat lower retention in adjacent normal controls. The results suggest that the proposed method could be used potentially in cancer diagnosis.


A comparison and cost-effectiveness analysis of peripheral catheter dressings.
Peripheral catheter dressing use is common but information about cost-effectiveness remains limited. A prospective, descriptive 3-month study was conducted to 1) assess the cost-effectiveness of two dressings used for peripheral venous catheters and 2) identify statistical associations between the effectiveness variables and the patient's gender and age, category of the professional involved in care, and length of time the dressing was in place. The study was conducted among a homogenous sample of 120 adult patients; the majority (71/59.2%) were women, mean age 54.5 (+/- 18.8) years. All catheters were inserted in the surgical unit of the University of São Paulo Hospital: 54 traditional (microporous tape) and 66 transparent film dressings were applied. Clinical effectiveness was defined as dressing adherence and the absence of complications. Cost effectiveness was assessed using incremental analysis and potential statistical associations. The measured outcomes are expressed in terms of the cost per unit/patient of success or effect. Traditional dressings were found to have a lower total cost ($12.53) but were less adherent (P <0.001) compared to film dressings. The rate of complications in each group was similar. Results confirm that traditional dressings may be used for short-term use catheter care (approximately 3 days); whereas, film dressings may be more cost-effective for longer-term use. Larger studies assessing the cost-effectiveness of various dressings to secure longer-term use catheters are needed.


Anticipatory tonal coarticulation in Thai noun compounds after unilateral brain damage.
The time course and extent of anticipatory coarticulation between tones was investigated in normal and brain-damaged Thai-speaking subjects. Subjects were classified into five groups including 11 young normal, 9 old normal, 12 right hemisphere, 9 left hemisphere fluent, and 6 left hemisphere nonfluent. Stimuli consisted of five bisyllabic noun compounds with a falling tone on the initial syllable and each of the five Thai tones (mid, low, falling, high, rising) on the final syllable. Height and slope of F0 was measured at 10% intervals throughout the duration of the initial syllable. Results indicated anticipatory effects on both height and slope of the falling tone. Height effects extended throughout from the beginning. The falling tone was generally higher when occurring before the low/rising tones than when occurring before the mid/falling/high tones. Slope effects were restricted to the terminal portion. The falling tone before low/rising tones exhibited a steeper slope than before falling/high tones. In magnitude of effect, patients with left and right hemisphere lesions were statistically indistinguishable from those of normal subjects. No differences were noted in coarticulatory patterns as a function of aphasia type. All brain-damaged speakers were more variable in F0 production than normals. Findings are interpreted to highlight properties of nonfluent aphasic speech and neurological bases of speech production.


In vitro propagation of threatened terrestrial orchid, Malaxis khasiana Soland ex. Swartz through immature seed culture.
Rapid in vitro propagation of the terrestrial orchid, M. khasiana through immature seed culture was achieved. Immature seeds of 8-9 week after pollination (WAP) cultured on MS medium (2% sucrose) supplemented with 500 mgl(-1) casein-hydrolysate and 1 microM N6-benzyladenine (BA) exhibited germination of 75% seeds after 107 days of culture and subsequently supported the development of PLBs. Subsequent culture on MS medium enriched with 6 microM of indole-3-acetic acid (IAA), 18 microM each of BA and kinetin induced multiple shoots and plantlets. Transfer of PLBs to MS medium with 0.1% activated charcoal (AC) facilitated rapid proliferation of PLBs, while AC at 0.2% favored shoot bud induction and rhizome enlargement. The plantlets, developed on medium with IAA, BA and kinetin, after hardening in vitro for 8-10 weeks were planted in community pots and transferred to poly-house. The plantlets showed 65% survival under field conditions.


Four cDNAs encoding lipoprotein receptors from shrimp (Pandalopsis japonica): structural characterization and expression analysis during maturation.
As in all other oviparous animals, lipoprotein receptors play a critical role in lipid metabolism and reproduction in decapod crustaceans. Four full-length cDNAs encoding lipoprotein receptors (Paj-VgR, Paj-LpR1, Paj-LpR2A, and Paj-LpR2B) were identified from Pandalopsis japonica through a combination of EST screening and PCR-based cloning. Paj-LpR1 appears to be the first crustacean ortholog of insect lipophorin receptors, and its two paralogs, Paj-LpR2A and Paj-LpR2B, exhibited similar structural characteristics. Several transcriptional isoforms were also identified for all three Paj-LpRs. Each expression pattern was unique, suggesting different physiological roles for these proteins. Paj-VgR is an ortholog of vitellogenin (Vg) receptors from other decapod crustaceans. A phylogenetic analysis of lipoproteins and their receptors suggested that the nomenclature of Vgs from decapod crustaceans may need to be changed. A PCR-based transcriptional analysis showed that Paj-VgR and Paj-LpR2B are expressed almost exclusively in the ovary, whereas Paj-LpR1 and Paj-LpR2A are expressed in multiple tissues. The various transcriptional isoforms of the three Paj-LpRs exhibited unique tissue distribution profiles. A transcriptional analysis of each receptor using tissues with different GSI values showed that the change in transcription of Paj-VgRs, Paj-LpR2A and Paj-LpR1 was not as significant as that of Vgs during maturation. However, the transcriptional levels of Paj-LpR2B decreased in ovary at maturation, suggesting that their transcriptional regulation is involved in reproduction.


Faecal calprotectin in patients with suspected colorectal cancer: a diagnostic accuracy study.
NICE guidance exists for the use of faecal calprotectin (FC) when irritable bowel syndrome or inflammatory bowel disease are suspected. Often, however, colorectal cancer is considered within the differential. Should FC have a high diagnostic accuracy for colorectal cancer, it may be applicable as a primary care screening test for all patients with lower gastrointestinal symptoms. To determine the negative and positive predictive value (NPV/PPV) of FC in patients referred from primary care with suspected colorectal cancer. A diagnostic accuracy study conducted at a single secondary care site Consenting patients referred with suspected colorectal cancer within the '2-week wait' pathway provided a stool sample for FC prior to investigation. FC levels were reconciled with end diagnoses: cancer, adenomatous polyps ≥10 mm, and all enteric organic disease. A total of 654 patients completed the evaluation; median age 69 years, female 56%. The NPV for colorectal cancer was 98.6% and 97.2% when including polyps ≥10 mm. The PPV for all organic enteric disease was 32.7%. The diagnostic yield for cancer based on clinical suspicion was 6.3%. By altering the FC cut-off to fix the NPV at 97.0%, the PPV for cancer increased from 8.7% to 13.3%. FC has a high NPV for colorectal cancer and significant polyps in patients with suspected cancer. In total, 27.8% of patients had a normal FC and could safely have been spared a '2-week wait' referral. The addition of FC testing into the current symptom-based assessment has the potential to increase colorectal cancer detection rate yet be clinically and cost effective.


An Incidental Finding of Takotsubo Cardiomyopathy in a Trauma Case.
Takotsubo cardiomyopathy (TC) is a transient condition characterized by left ventricular wall motion abnormalities, ventricular systolic dysfunction, and apical ballooning. When initially presented, the pathology is often erroneously attributed to acute coronary syndrome (ACS) or acute-onset heart failure due to similar symptoms and electrocardiogram (ECG) findings. However, upon further review of imaging, coronary arteries are often void of disease. The highest prevalence of Takotsubo cardiomyopathy is noted in elderly, postmenopausal women who recently experienced an emotionally or physically triggering event. Although the true underlying pathophysiology of Takotsubo cardiomyopathy remains poorly elucidated, a few leading concepts suggest that stress-induced sympathetic responses may lead to catecholamine-induced cardiotoxicity. Other ideologies implicate poor coronary perfusion, neurogenic myocardial stunning, and coronary artery vasospasms. As features of TC are transient, it has an excellent prognosis, and patients see improvement in ventricular function and symptoms within weeks after the initiation of therapy. In this paper, we discuss a case of TC noted incidentally on imaging in a middle-aged female presenting with encephalopathy after a motor vehicle accident.


Serum angiotensin-converting-enzyme in rabbits with and without pulmonary granulomatosis. Granulomatosis induced with complete-Freund's-adjuvant or BCG.
An animal model with pulmonary, non-caseating, granulomatosis was successfully reproduced in rabbits utilizing intravenous injections of complete-Freund's-adjuvant (CFA) or BCG. Granuloma formation from CFA injections was limited to the lungs, but BCG injections caused systemic granulomatosis (lung, liver and spleen) irrespective of whether the BCG was dissolved in saline or in incomplete-Freund's-adjuvant (IFA). Serum angiotensin-converting-enzyme (ACE) levels began to rise approximately 15 days following the intravenous injection of CFA, but similar rises following the injection of IFA without granuloma formation suggest that the ACE rise was not necessarily reflective of granuloma formation in rabbits. BCG in saline caused no rise in serum ACE, but when suspended in IFA the ACE rise was comparable to that resulting from IFA alone. However, the ACE level of broncho-alveolar-lavage cells obtained from rabbits 21 days post-injection of CFA was 7-fold higher than that of lavaged cells obtained 42 days post injection, correlating with an acute alveolitis occurring early during granuloma formation. These studies confirm the usefulness of intravenous injections of CFA or BCG for inducing a granulomatous state, but show that the assay of serum ACE is not useful for reflecting the granulomatous state in rabbits. In addition, serum ACE levels are 2-5 X higher in rabbits than in humans and tend to fluctuate spontaneously following delivery of the animals to the laboratory.


Proinflammation: a common denominator or initiator of different pathophysiological disease processes.
Proinflammation is a widespread phenomenon. It has an association with the stress (patho)physiology and is connected with various diseases. Recently, it has been discussed if proinflammation may represent a common (pre)condition in different disease states. Evidence for a common proinflammatory pattern in a variety of diseases is analyzed. Proinflammatory (pre)conditions and immune response patterns serve as a common modality in a number of clinically separate diseases. Here, nitric oxide pathways often play a significant role as well. On molecular basis, proinflammation potentially illustrates a common denominator and/or an initiator. Like stress, proinflammation seems to be a crucial autoregulatory concept. It normally serves a positive biological goal: Proinflammatory activities, e.g., are initiated to overcome infection or invasion of potentially deleterious biological agents (bacteria, viruses, parasites etc.). While fighting invasion, proinflammation usually shortens biological 'battles' and therefore ameliorates disease-related detrimental or subjectively unpleasing phenomena. However, proinflammation has beneficial and deteriorating capacities and may yet exert detrimental effects. This is especially true, when the fine balance between the different immune response pathways, between anti- and proinflammatory mechanisms, can not be kept. This may occur when a challenge becomes overwhelming or when patterns of a chronic (patho)physiological activity are presented. Thus, proinflammation may represent a relatively unspecific, overlapping/ analogous state, underlying various clinical disease manifestations.


Co-occurrence of Methanosarcina mazei and Geobacteraceae in an iron (III)-reducing enrichment culture.
Methanosaeta harundinacea and Methanosarcina barkeri, known as classic acetoclastic methanogens, are capable of directly accepting electrons from Geobacter metallireducens for the reduction of carbon dioxide to methane, having been revealed as direct interspecies electron transfer (DIET) in the laboratory co-cultures. However, whether their co-occurrences are ubiquitous in the iron (III)-reducing environments and the other species of acetoclastic methanogens such as Methanosarcina mazei are capable of DIET are still unknown. Instead of initiating the co-cultures with pure cultures, two-step cultivation was employed to selectively enrich iron (III)-reducing microorganisms in a coastal gold mining river, Jiehe River, with rich iron content in the sediments. First, iron (III) reducers including Geobacteraceae were successfully enriched by 3-months successive culture on amorphous Fe(III) oxides as electron acceptor and acetate as electron donor. High-throughput Illumina sequencing, terminal restriction fragment length polymorphism (T-RFLP) and clone library analysis based on 16S rRNA genes revealed that the enrichment cultures actively contained the bacteria belong to Geobacteraceae and Bacilli, exclusively dominated by the archaea belong to Methanosarcinaceae. Second, the enrichment cultures including methanogens and Geobacteraceae were transferred with ethanol as alternative electron donor. Remarkably, aggregates were successively formed in the enrichments after three transfers. The results revealed by RNA-based analysis demonstrate that the co-occurrence of Methanosarcina mazei and Geobacteraceae in an iron (III)-reducing enrichment culture. Furthermore, the aggregates, as close physical contact, formed in the enrichment culture, indicate that DIET could be a possible option for interspecies electron transfer in the aggregates.


Expression of TGF-betas and TGF-beta type II receptor in cerebrospinal fluid of patients with idiopathic normal pressure hydrocephalus.
We investigated cerebrospinal fluid (CSF) samples from 21 patients with idiopathic normal pressure hydrocephalus (INPH) and 14 controls without neurological disease. The concentrations of leucine-rich alpha-2-glycoprotein (LRG), transforming growth factor (TGF)-beta1, 2, 3 and TGF-beta type II receptor (TbetaR-II) in CSF were measured using ELISA. TGF-beta1, TbetaR-II and LRG CSF levels of patients with INPH were significantly higher than controls, whereas no significant differences in TGF-beta2 levels were found between INPH patients and controls. The present study suggests that TGF-betas expressions may be modulated differently in patients with INPH. These results also indicate that the CSF level assay of TGF-beta1, TbetaR-II and LRG is useful for the diagnosis of patients with INPH, and TGF-beta1, TbetaR-II and LRG may be involved in the pathogenesis of the disease.


Total synthesis, structure revision, and absolute configuration of (+)-yatakemycin.
The total synthesis of the reported structure 2 for yatakemycin, an exceptionally potent, naturally occurring antitumor agent disclosed in 2003, and its lack of correlation with the natural product are detailed. On the basis of spectroscopic distinctions between 2 and yatakemycin, the natural product structure was reformulated as 3, now bearing a thiomethyl ester versus thioacetate in the left-hand subunit. Total synthesis of 3 provided a compound nearly identical to but still subtly distinct from the natural product. A second reformulation of the yatakemycin structure as 1, incorporating the alternatively substituted right-hand subunit as well as the initial thiomethyl ester reformulation, was confirmed by total synthesis of both (+)- and ent-(-)-1 in studies that also unambiguously established the absolute configuration of the natural product.


Changes in urinary incontinence and quality of life after four years. A population-based study of women aged 22-50 years.
To investigate (a) the incidence and remission rates of female urinary incontinence (UI), (b) changes in type of UI and quality of life (QoL), and (c) whether professional help had been consulted regarding UI. A 4-year follow-up population-based cohort study. Surahammar, Sweden, a community of 10,500 inhabitants. All 118 incontinent and 130 continent women aged between 22 and 50 years. Changes in type of UI were measured using the Detrusor Instability Score (DIS), which was used to distinguish between the stress incontinent and the urge incontinent women. Changes in QoL were measured using the SF-36 Health Survey. The mean annual incidence and remission rates of UI were the same (4%). The majority of women (83%) reported unchanged UI after 4 years and 77% of these women had stress incontinence. At follow-up, the changes in QoL scores were significantly greater in five out of eight dimensions in the persistently incontinent group compared with the persistently continent group. QoL scores did not change significantly from baseline to the 4-year follow-up within the incidence and remission groups. Three of four women with UI had not sought professional help. At 4-year follow-up the type of UI is fairly stable in women below 50 years of age. The QoL decreases in five dimensions, but the clinical relevance of this might be questioned. Most women with UI had not sought professional help.


Multiflat Bands and Strong Correlations in Twisted Bilayer Boron Nitride: Doping-Induced Correlated Insulator and Superconductor.
Two-dimensional materials, obtained by van der Waals stacking of layers, are fascinating objects of contemporary condensed matter research, exhibiting a variety of new physics. Inspired by the breakthroughs of twisted bilayer graphene (TBG), we demonstrate that twisted bilayer boron nitride (TBBN) is an even more exciting novel system that turns out to be an excellent platform to realize new correlated phases and phenomena; exploration of its electronic properties shows that in contrast to TBG in TBBN multiple families of 2,4, and 6-fold degenerate flat bands emerge without the need to fine tune close to a "magic angle", resulting in dramatic and tunable changes in optical properties and exciton physics, and providing an additional platform to study strong correlations. Upon doping, unforeseen new correlated phases of matter (insulating and superconducting) emerge. TBBN could thus provide a promising experimental platform, insensitive to small deviations in the twist angle, to study novel exciton condensate and spatial confinement physics, and correlations in two dimensions.


The amyloid cascade hypothesis: are we poised for success or failure?
The first description of Alzheimer's disease (AD) was made in 1907 by Alois Alzheimer (Allgemeine Zeitschrift fur Psyciatrie und Psychisch-Gerichtliche Medizin 64, 3, 1907), although other contemporary physicians had made similar, and rather more complete, assessments of the neuropathological changes present in the AD brain (Fischer, Monatsschr Psychiat Neurol 22, 17, 1907). Our knowledge of AD has increased dramatically and continues to accelerate. This year is 25 years after the publication of a series of papers that, in various ways, articulated the amyloid cascade hypothesis (ACH) for AD (Beyreuther and Masters, Brain Pathol 1, 241-251, 1991; Hardy and Allsop, Trends Pharmacol Sci 12, 383-388, 1991; Selkoe, Neuron 6, 487-498, 1991; Hardy and Higgins, Science 256, 184-185, 1992). This review will cover some familiar territory, but we shall also place the ACH into a wider context, compare it with other hypotheses for AD, explore the evolution of the hypothesis to encompass new findings, and determine, irrespective of the merits of the hypothesis itself, whether it has been useful for the research field, both in academia and in industry. Finally, we shall review how the ACH has led to a number of therapeutic approaches, all of which have, to date, failed to reach their primary efficacy end-points in clinical trials and reflect upon what the future may hold. We review the amyloid cascade hypothesis (ACH) and compare it with other hypotheses that have been posited to explain the initiation and progression Alzheimer's disease. We document the data that support the ACH, and also reflect upon its deficiencies. We list the recent clinical failures of amyloidocentric drugs and anticipate the results that new therapeutic approaches may deliver. This article is part of the 60th Anniversary special issue.


Hyperplastic and neoplastic alterations in the livers of white perch (Morone americana) from the Chesapeake Bay.
White perch (Morone americana) sampled from 15 estuaries of the Chesapeake Bay contained a variety of hyperplastic and neoplastic alterations in their livers. The lesions were derived from bile ductular epithelium and/or hepatocytes. The biliary lesions consisted of hyperplasias and adenomas. The hepatocellular lesions consisted of focal populations of altered cells and neoplasms, of clear-cell and basophilic morphologic appearance. The hepatocellular lesions were conspicuous in the absence of the decreased amount of copper accumulation. In this respect, the cells comprising these lesions are reminiscent of cells from hepatocellular neoplasia in mice and rats resistant to accumulation of iron.


Multipathogen infections and multifactorial pathogenesis involved in noble pen shell (Pinna nobilis) mass mortality events: Background and current pathologic approaches.
Disease outbreaks in several ecologically or commercially important invertebrate marine species have been reported in recent years all over the world. Mass mortality events (MMEs) have affected the noble pen shell (Pinna nobilis), causing its near extinction. Our knowledge of the dynamics of diseases affecting this species is still unclear. Early studies investigating the causative etiological agent focused on a novel protozoan parasite, Haplosporidium pinnae, although further investigations suggested that concurrent polymicrobial infections could have been pivotal in some MMEs, even in the absence of H. pinnae. Indeed, moribund specimens collected during MMEs in Italy, Greece, and Spain demonstrated the presence of a bacteria from within the Mycobacterium simiae complex and, in some cases, species similar to Vibrio mediterranei. The diagnostic processes used for investigation of MMEs are still not standardized and require the expertise of veterinary and para-veterinary pathologists, who could simultaneously evaluate a variety of factors, from clinical signs to environmental conditions. Here, we review the available literature on mortality events in P. nobilis and discuss approaches to define MMEs in P. nobilis. The proposed consensus approach should form the basis for establishing a foundation for future studies aimed at preserving populations in the wild.


The effect of a brief mindfulness induction on processing of emotional images: an ERP study.
The ability to effectively direct one's attention is an important aspect of regulating emotions and a component of mindfulness. Mindfulness practices have been established as effective interventions for mental and physical illness; however, the underlying neural mechanisms of mindfulness and how they relate to emotional processing have not been explored in depth. The current study used a within-subjects repeated measures design to examine if focused breathing, a brief mindfulness induction, could modulate event-related potentials (ERPs) during emotional image processing relative to a control condition. We related ERP measures of processing positive, negative, and neutral images (the P300 and late positive potential - LPP) to state and trait mindfulness measures. Overall, the brief mindfulness induction condition did not influence ERPs reflecting emotional processing; however, in the brief mindfulness induction condition, those participants who reported feeling more decentered (a subscale of the Toronto Mindfulness Scale) after viewing the images had reduced P300 responses to negative versus neutral images.


In vitro modulation of keratinocyte-derived interleukin-1 alpha (IL-1 alpha) and peripheral blood mononuclear cell-derived IL-1 beta release in response to cutaneous commensal microorganisms.
The ability of a range of skin commensal microorganisms to modulate interleukin-1 (IL-1) release by cultured human keratinocytes and peripheral blood mononuclear cells (PBMCs) was investigated by a combination of enzyme-linked immunosorbent assays and bioassays. Three fractions (formaldehyde-treated whole cells, culture supernatants, and cellular fractions) were prepared from Propionibacterium acnes, Propionibacterium granulosum, Staphylococcus epidermidis, Staphylococcus capitis, Staphylococcus hominis, and Malassezia furfur serovar B. The levels of immunochemical IL-1 alpha released by cultured keratinocytes during coincubations with these microbial fractions ranged from 0 to 136 pg/ml and were maximal after 72 h. No microbial fraction consistently upregulated immunochemical IL-1 alpha release by freshly isolated keratinocytes from two donors and a transformed cell line, all of which produced the cytokine constitutively to various extents. Bioassays revealed that most of the IL-1 released was biologically inactive. In contrast, whole cells of formaldehyde-treated P. granulosum and S. epidermidis significantly stimulated release of IL-1 beta by PBMCs from three donors compared with the negative control (culture medium). Release was maximal at 24 h. Coincubation with intact cells of the yeast M. furfur significantly decreased levels of IL-1 beta below the values for the negative control by PBMCs from all three donors. There was good correlation between bioassay data and immunoassay data for IL-1 beta, and the depressive effect of M. furfur cells on cytokine production by all three cultures of PBMCs was mirrored in the levels of bioactive cytokine. This reduction in IL-1 beta release by PBMCs by M. furfur may provide an explanation why dermatoses thought to be caused by this yeast are essentially noninflammatory or only mildly inflammatory.


[Results of heart transplantation: experience of 233 grafts].
Heart failure is one of the leading causes of hospitalization and death. The aim of this study was to evaluate long term outcomes after cardiac transplantation. A retrospective review of 222 consecutive cardiac allograft recipients who underwent 233 transplantations between 1986 to 2000 was undertaken. Cardiomyopathy (123) and ischemic heart disease (87) were the most common indications. Mean age was 51 years +/- 11, and male gender was predominant (184). 33 patients (14.8%) died in the post operative period, mainly from graft failure (24 pts). During the follow-up period (total 1157 pt/yrs, mean 6.2 +/- 5 yrs, max 16 yrs), 60 late deaths occurred from cancer (21), graft failure (13), infection (13), and miscellaneous (13). Retransplantations were performed in 11 patients. The actuarial survival of the entire cohort was 75%, 66% and 50% at 1, 5, and 10 years respectively. Cardiac transplantation gives satisfactory long term results for patients with end-stage heart failure, providing good exercise tolerance and survival for 10 years or more in a large number of patients. Improvement in immunosuppression therapy is responsible for decrease in acute rejection rate. Reduction in HLA mismatch should allow for better immunomodulation and decreased incidence of cardiac allograft vasculopathy and malignancies.


Cloning, sequencing and restriction fragment length polymorphism analysis of a porcine cDNA for OCT2.
A full-length pig cDNA for the POU-domain protein OCT2 has been isolated and sequenced. The 478 amino acid-long reading frame in pig OCT2 is 97% identical to human OCT2A, indicating strong conservation of function for this immunoglobulin regulatory protein. To investigate the potential use of this cDNA for mapping and identifying linkage of OCT2 to economic traits, restriction fragment length polymorphism (RFLP) analysis was used to identify a TaqI polymorphism. A population of 60 unrelated animals, as well as multigenerational families, were typed for this RFLP and showed variability in several American and Chinese breeds. The TaqI polymorphism was also detected by a non-POU-domain OCT2 probe, demonstrating that this RFLP is located in the OCT2 gene. This result suggests that OCT2 is likely to be a single-copy gene in swine as seen in other mammals.


Cardiovascular Risk in Users of Mirabegron Compared with Users of Antimuscarinic Treatments for Overactive Bladder: Findings from a Non-Interventional, Multinational, Cohort Study.
During clinical trials, mirabegron, a β3-adrenoreceptor agonist, was associated with increased vital signs vs placebo in patients with overactive bladder. The purpose of this study was to compare incidence rates of adverse cardiovascular (CV) outcomes following mirabegron or antimuscarinic use. We conducted an observational post-marketing safety study utilising real-world data. The study population was identified within five sources: Danish and Swedish National Registers, Clinical Practice Research Datalink (UK), Optum (USA) and Humana (USA). Episodes of time when patients were new users of mirabegron or antimuscarinics (October 2012-December 2018) were sourced from prescriptions and matched on propensity scores. Occurrences of major adverse cardiovascular events (MACE), acute myocardial infarction (AMI), stroke, CV mortality and all-cause mortality were identified. Outcome incidence rates and hazard ratios from Cox models were estimated. Overall, 152,026 mirabegron and 152,026 antimuscarinic episodes were matched. The population consisted of 63.1% women and 72.6% were ≥ 65 years old. There were no appreciable differences in the incidence rates of MACE, AMI or stroke between users of mirabegron and antimuscarinics. Incidence rates of CV mortality (hazard ratio 0.83, 95% confidence interval 0.73-0.95) and all-cause mortality (hazard ratio 0.80, 95% confidence interval 0.76-0.84) were no higher with mirabegron vs antimuscarinics. Results restricted to episodes at high risk for CV events or stratified by age (< 65 years, ≥ 65 years) or prior overactive bladder medication use were consistent with overall findings. This large, multinational study found no higher risk of MACE, AMI, stroke, CV mortality or all-cause mortality among users of mirabegron relative to users of antimuscarinics.


Validation of an early childhood caries risk assessment tool in a low-income Hispanic population.
There is a recognized need for valid risk assessment tools for use by both dental and nondental personnel to identify young children at risk for, or with, precavitated stages of early childhood caries (i.e., early stage decalcifications or white spot lesions).The aim of this study is to establish concurrent criterion validity of "MySmileBuddy" (MSB), a novel technology-assisted ECC risk assessment and behavioral intervention tool against four measures of ECC activity: semi-quantitative assays of salivary mutans streptococci levels, visible quantity of dental plaque, visual evidence of enamel decalcifications, and cavitation status (none, ECC, severe ECC). One hundred eight children 2-6 years of age presenting to a pediatric dental clinic were recruited from a predominantly Spanish-speaking, low-income, urban population. All children received a comprehensive oral examination and saliva culture for assessment of ECC indicators. Their caregivers completed the iPad-based MSB assessment in its entirety (15-20 minutes). MSB calculated both diet and comprehensive ECC risk scores. Associations between all variables were determined using ordinal logistic regression. MSB diet risk scores were significantly positively associated with salivary mutans (P < 0.05), and approached significance with visible plaque levels (P < 0.1). MSB comprehensive risk scores were significantly associated with both oral mutans and visible plaque (P < 0.05). Neither was associated with visually evident decalcifications or cavitations. Findings suggest that MSB may have clinical utility as a valid risk assessment tool for identifying children with early precursors of cavitations but does not add value in identifying children with extant lesions.


Functional evaluation of prevascularization in one-stage versus two-stage tissue engineering approach of human bio-artificial muscle.
A common shortcoming of current tissue engineered constructs is the lack of a functional vasculature, limiting their size and functionality. Prevascularization is a possible strategy to introduce vascular networks in these constructs. It includes among others co-culturing target cells with endothelial (precursor) cells that are able to form endothelial networks through vasculogenesis. In this paper, we compared two different prevascularization approaches of bio-artificial skeletal muscle tissue (BAM) in vitro and in vivo. In a one-stage approach, human muscle cells were directly co-cultured with endothelial cells in 3D. In a two-stage approach, a one week old BAM containing differentiated myotubes was coated with a fibrin hydrogel containing endothelial cells. The obtained endothelial networks were longer and better interconnected with the two-stage approach. We evaluated whether prevascularization had a beneficial effect on in vivo perfusion of the BAM and improved myotube survival by implantation on the fascia of the latissimus dorsi muscle of NOD/SCID mice for 5 or 14 d. Also in vivo, the two-stage approach displayed the highest vascular density. At day 14, anastomosis of implanted endothelial networks with the host vasculature was apparent. BAMs without endothelial networks contained longer and thicker myotubes in vitro, but their morphology degraded in vivo. In contrast, maintenance of myotube morphology was well supported in the two-stage prevascularized BAMs. To conclude, a two-stage prevascularization approach for muscle engineering improved the vascular density in the construct and supported myotube maintenance in vivo.


Buccal bone crest dynamics after immediate implant placement and ridge preservation techniques: review of morphometric studies in animals.
To review morphometric studies performed in animals assessing the dynamics of the buccal bone crest after immediate implant placement and ridge preservation techniques. A bibliographic search in PubMed was performed. Studies that analyzed morphometrically in animals the buccal bone crest dynamics after immediate implant placement or ridge preservation techniques were included. Twenty-five studies met the inclusion criteria. Immediate implant placement does not prevent the resorption of the buccal bone crest. To minimize this resorption, 2 mm width of the buccal bone crest, palatal/lingual implant placement, and an adequate implant diameter for the width of the ridge are required. The regeneration of the gap after immediate implant placement limits the resorption of the buccal bone crest. Flap elevation and implant surface showed no relation with this resorption. Ridge preservation techniques associated with mucogingival surgery minimize buccal bone crest resorption. Biomaterials are more effective than autograft. Immediate implant placement does not prevent the resorption of the buccal bone crest after dental extraction. Ridge preservation techniques minimize this resorption.


Trait anger expressiveness and pain-induced beta-endorphin release: support for the opioid dysfunction hypothesis.
The anger management styles of anger-in (inhibition) and anger-out (direct expression) are positively associated with pain responsiveness. Opioid blockade studies suggest that hyperalgesic effects of trait anger-out, but not those of trait anger-in, are mediated in part by opioid analgesic system dysfunction. The current study tested the opioid dysfunction hypothesis of anger-out using an alternative index of opioid function: pain-induced changes in plasma endogenous opioids. Plasma beta-endorphin (BE) was assessed at rest and again following exposure to three laboratory acute pain tasks (finger pressure, ischemic, and thermal) in 14 healthy controls and 13 chronic low back pain (LBP) subjects. As expected, acute pain ratings correlated positively with measures of anger-in (both groups) and anger-out (LBP group; p's<.05). Greater pain-induced increases in BE were associated with significantly lower pain ratings in both groups (p's<.05). Hierarchical multiple regression indicated that greater anger-out significantly predicted smaller pain-induced BE increases (p<.05). Subject type did not moderate this association (p>.10). Anger-in did not display significant main or interaction effects on pain-induced BE changes (p's>.10). The significant association between anger-out and BE release partially mediated the hyperalgesic effects of anger-out on pain unpleasantness, and was not attenuated by statistical control of general negative affect. This suggests unique associations with expressive anger regulation. Elevated trait anger-out therefore appears to be associated with opioid analgesic system dysfunction, whether it is indexed by responses to opioid blockade or by examining circulating endogenous opioid levels. Possible "statextrait" interactions on these anger-related opioid system differences are discussed.


Types of obstructions in double-chambered right ventricle: mid-term results.
The double-chambered right ventricle (DCRV) is increasingly recognized as a distinct obstruction entity. The nature of the obstruction is not well defined. Patients with DCRV were prospectively studied during the last 4 years according to the following criteria: 1) pressure gradient by echo Doppler and cardiac catheterization within the right ventricle; 2) angiographic demonstration, and 3) surgical confirmation. From March 1997 to March 2001, 10 new cases were included. Age ranged from 2 to 14 years (mean 9.5 +/- 4.4 years), weight ranged from 9.9 to 75 kg (mean 23 +/- 13.6 kg), and height from 0.85 to 1.48 m (mean 114 +/- 19 cm). Systolic gradient by echo Doppler ranged from 20 to 135 mmHg (mean 86 +/- 44 mmHg) and by cardiac catheterization, 18 to 130 mmHg (mean 78 +/- 35 mmHg). In terms of angiographic findings, in six patients the right ventriculogram showed an oblique and low obstruction; in four patients the obstruction was high and horizontal. With regard to surgical findings, angiographic findings were confirmed by the surgeon except in one patient, in whom both types of obstruction were present. No mortality was observed. With follow-up 4 to 40 months after surgery (mean 24 +/- 15 months), 8 of 10 patients were evaluated; all corresponded to class I NYHA. Systolic gradient by echo Doppler ranged from 0 to 11 mmHg (mean 4 +/- 6 mmHg). DCRV IS PRODUCED BY THE FOLLOWING THREE TYPES OF MUSCULAR OBSTRUCTIONS: low and oblique obstruction; high and horizontal obstruction, and mixed obstruction. Mid-term surgical results are satisfactory.


Outcomes of a Multicenter, Prospective, Crossover, Randomized Controlled Trial Evaluating Subperception Spinal Cord Stimulation at ≤1.2 kHz in Previously Implanted Subjects.
The WHISPER randomized controlled trial (RCT) evaluates safety and clinical effectiveness of subperception spinal cord stimulation (SCS) at ≤1.2 kHz in subjects previously implanted with an SCS system for treatment of chronic, neuropathic pain. WHISPER is a prospective, multicenter RCT with a crossover design sponsored by Boston Scientific, Marlborough, MA (ClinicalTrials.gov: NCT02314000). Eligible subjects were randomized (N = 140) to receive subperception or supraperception for three months and then crossed over to receive the alternative. Upon completion of crossover period, subjects who preferred subperception were followed up to one year. Overall pain, quality-of-life, and other outcomes were collected in the study. The primary endpoint was the overall pain responder rate (≥50% improvement from baseline) with no increase in medications. Secondary endpoints consisted of pain scores, physical disability, quality of life, and treatment preference. The study met its primary endpoint and demonstrated noninferiority between supraperception and subperception in a prespecified cohort of 70 randomized subjects (Interim Analysis). Thirty-nine percent of subjects with subperception settings and 29% with supraperception settings had a greater than or equal to 50% reduction in their overall pain scores with no increase in average daily medication at three-months post-activation as compared with baseline. Further assessment of all participating study subjects (N = 140) revealed similar results. Subjects were previously implanted 3.8 ± 2 years and had a disability score (Oswestry Disability Index) of 70.2 ± 11.4 at study start. Of the randomized subjects that completed the End of Period 2 Visit, 93 (66%) preferred subperception SCS and their mean overall pain reduced from 7.3 ± 1.1 (N = 89) at baseline to 4.0 ± 2.1 (N = 80) at 12-months post-activation. Post hoc analysis also demonstrated that multiple options provide superior outcomes, as supported by a 74% increase in the responder rate when subjects could choose their most effective option (47%) compared with supraperception alone (27%). Subperception SCS at ≤1.2 kHz is safe and effective in subjects with extreme physical disability and previously implanted for chronic pain. Further, by providing study participants with different waveform options, increased pain relief was achieved.


Prevalence and Risk Factors of Urticaria With a Focus on Chronic Urticaria in Children.
Limited data is available on the prevalence and risk factors of acute and chronic urticaria in children. Our purpose was to determine the prevalence and identify the risk factors of acute and chronic urticaria in Korean children. This population-based study examined 4,076 children (age 4 to 13 years) who were enrolled in the 2015 prospective Seongnam Atopy Project (SAP 2015) in Korea. The parents completed an urticaria questionnaire that included questions regarding the duration, severity, and triggering factors of urticaria. Blood sampling (n=464) was performed to measure vitamin D, total eosinophil count (TEC), and total IgE levels, and skin prick tests (n=503) were done. The prevalences of the life-time, acute, and chronic urticaria were 22.5%, 13.9%, and 1.8% (chronic continuous urticaria, 0.7%; and chronic recurrent urticaria, 1.1%), respectively. Acute urticaria was significantly associated with allergic diseases and parental history of allergy (P<0.001), but chronic urticaria was not associated with these clinical factors. There was no significant difference in the 25-hydroxyvitamin D level between subjects with chronic urticaria and controls (P=0.124). Chronic continuous urticaria was associated with living in a new residence (aOR=2.38, 95% CI=1.02-5.54, P=0.044) and belonging to a family with a high income (aOR=4.24, 95% CI=1.24-14.56, P=0.022). A total of 1.8% of children were found to have chronic urticaria. Living in a new residence and belonging to a family with a high income increased the risk of chronic continuous urticaria.


Clinical Results of Modified Frontalis Suspension Technique Using Preserved Fascia Lata for Congenital Ptosis.
The purpose of this study was to evaluate the clinical results of modified frontalis suspension technique with preserved fascia lata and to analyze the results according to age and preoperative ptosis degree. This study involved a retrospective review of the electronic medical records of congenital ptosis patients who underwent unilateral or bilateral frontalis sling surgery using preserved fascia lata between March 1, 2004 and December 31, 2012. Seventy-seven patients (99 eyes) were included in the study. The mean age of the patients at the time of surgery was 6.2 ± 6.7 years. Mean follow-up time was 5.4 ± 3.2 years. Among 77 patients, 22 patients (28.5%) had a mild degree of ptosis, 39 (50.6%) had moderate, and 16 (20.7%) had a severe degree of ptosis. A satisfactory result (good and fair) was achieved in 65 of the 77 patients (84.4%) and a poor result was recorded in 12 patients (15.5%). Preoperative ptosis degree had no effect on the surgical success rate (19/22 [86.3%] in the mild group versus 34/39 [87.1%] in the moderate group versus 12/16 [75%] in the severe group, P = 0.243). There was no significant difference in surgical success rate between the unilateral and bilateral ptosis groups (45/55 [81.8%] versus 20/22 [90.9%], P = 0.479 respectively), between sexes (41/46 [89.1%] in male versus 24/31 [77.4%] in female, P = 0.271), or age groups (52/60 [86.6%] in younger group versus 13/17 [76.4%] in elder group, P = 0.526). Recurrence of ptosis did not differ according to the preoperative ptosis degree (3/22 [13.6%] in the mild group, 5/39 [12.8%] in the moderate group, and 2/16 [12.5%] in the severe group, P = 0.994). Age also had no influence on the ptosis recurrence. The preoperative marginal reflex distance 1 of 0.41 ± 1.06 mm increased to 1.67 ± 0.80 mm postoperatively (P = 0.000). The authors identified the long-term efficacy of preserved fascia lata in frontalis sling surgery with a modified frontalis suspension method for all age groups of patients. There was a small rate of recurrence (12.9%) over a maximum of 9 years of follow-up, which was corrected with additional surgery.


Studies with prazosin--a new effective hypotensive agent. I. Open clinical study of prazosin in combination with other antihypertensive agents.
The use of prazosin, a new antihypertensive agent, in combination with other conventional antihypertensive agents, in a hospital outpatient clinic setting, was studied in a mixed group of 104 hypertensive patients. Prazosin effectively lowered the lying and standing blood pressure in the majority of patients whose blood pressure was uncontrolled or poorly controlled before the introduction of prazosin. Blood pressure control was adequately maintained in patients who were given prazosin because of the occurrence of side effects of other antihypertensive medication. No significant change in renal function attributable to prazosin was found in patients with normal or impaired renal function.


Evaluation of pelvic and breast examination skills of interns in obstetrics and gynecology and internal medicine.
The purpose of this study was to evaluate the pelvic and breast examination skills of a group of interns who were entering obstetrics and gynecology and internal medicine and to determine whether previous experience predicts performance. This was a prospective study that, with the use of an examination with a standardized format of 26 skills, assessed the performance of 10 interns who were entering internal medicine and 9 interns who were entering obstetrics and gynecology. chi(2) analysis and Fisher exact tests were used. There was no significant difference in overall performance on the pelvic and breast examinations between the two groups. The obstetrics and gynecology interns performed significantly better (P<.05) on the three skills that assessed professional conduct. There was considerable variability within each group. There was no correlation between previous clinical experience and performance on the skills assessment, nor was there a correlation between perceived competence and actual performance. Previous clinical experience does not predict performance in a standardized assessment of pelvic and breast examination skills nor does it account for the great variability in competence levels in interns who are entering obstetrics and gynecology and internal medicine.


Fatal poisoning by alcohol and heroin.
Drug abuse with alcohol consumption have been on the rise in Split-Dalmatian County for a while now. This article reports two separate cases with three deaths due to fatal combinations of heroin and alcohol. The first case of poisoning is related to a young couple, a 30-year-old man and a 28-year-old woman, who were found dead in a car, surrounded by cans of a variety alcoholic drinks. Two needles were found beside the bodies as well. The victims were registered drug abusers who had been in withdrawal programs. The second case was a 29-year-old man who was found dead in a house. Three fresh injection marks were visible on his right arm, and two needles were near his body. He was not known as a drug addict, but he had tried to commit suicide recently. Carboxyhaemoglobin was found in blood samples of both victims from the first case. The concentration was 25% and that could contribute to their death. In both described cases blood alcohol concentration was higher then 1.60 g kg(-1). Toxicology tests were positive for heroin, meconin, acetaminophen, 6-acetylmorphine, codeine, noscapine and papaverine. Ethanol, being a respiratory depressant, combined with morphine drastically increases the risk of rapid death due to respiration failure.


Antiaromaticity in distal bisfluorenyl dications separated by multiple discrete spacer units.
The effect of spacers on the antiaromaticity of bisfluorenyl dications was examined. For systems such as 4a-c in which extensive delocalization of the positive charge through the pi-system is not possible, a relationship based primarily on localized hyperconjugation as well as the distance between the fluorenyl systems and their antiaromaticity was demonstrated. Dications 2a-c and 3a-c also show the relationship, but it is further modulated by delocalization through the pi-system. Calculated assessment of antiaromaticity was supported by experimental shifts for 2a,b and 3a-c.


Statistical model of the natural history of cervical carcinoma. II. Estimates of the transition time from dysplasia to carcinoma in situ.
Estimates are presented of the transition probabilities and transition times from dysplasia to carcinoma in situ of the uterine cervix based on a statistical model of the natural history of this disease. The estimates, obtained from a longitudinal study of 557 women, were contrasted with prevalence rates obtained in a self-selected sample of over 11,000 women from Barbados, West Indies. These two independent sets of estimates, based on two different experimental designs, were shown to be concordant. The formula for the computation of the standard deviation of these estimates was given, together with the results of this computation for the observed sample data. The effects of those covariables that have been associated with the incidence of cervical neoplastic disease on these estimates were examined. The transition times and probabilities were associated with the total number of pregnancies but were not dependent on age at first coitus or age at first pregnancy. The results of this investigation provide an index of the history of cervical neoplastic disease that might be of use in contrasting the experience of different subsets of the population with respect to their transition probabilities and transition times through the several stages of the disease process.


The morphologic features of the bronchi, bronchioles, and alveoli in chronic airway obstruction: a clinicopathologic study.
A 6-year semiquantitative clinicopathologic study revealed that among 196 men and 46 women 40 or more years of age at death, the severity of destructive emphysema was overwhelmingly the most important morphologic correlate of the clinical state of chronic airway obstruction. The pathogenic mechanisms whereby emphysema may lead to airway obstruction are probably multifactorial, but our data are consistent with a growing consensus that loss of small airway support by surrounding lung tissue in emphysema may cause kinking, tortuosity, and collapse of the airways, with subsequent increased airflow resistance and clinical obstruction. Pathologic changes (inflammation, fibrosis, increased goblet cells, and mucous gland enlargement) in large or small airways in the absence of much emphysema were very seldom associated with significant chronic airway obstruction, and correlated rather poorly with chronic airway obstruction, regardless of severity of emphysema. A subjective method of evaluating mucous gland enlargement in the large airways was consistently better than the Reid Index in correlations with clinical and anatomic abnormalities, presumably because it took all glands into consideration. The clinical features of subjects with severe centrilobular versus severe panlobular emphysema were essentially the same. "Blue bloater" and "pink puffer" clinical types of chronic airway obstruction continued to reveal differences in airway pathologic features, but no longer revealed a major difference in the severity of emphysema at the time of death. Presumably this was due, at least partially, to improved treatment, longer survival, and fusion into a similar end-stage. The total exposure to cigarette smoke was quantitatively related to clinical chronic airway obstruction and to both alveolar and airway pathologic features.


[Particular histological features of a case of Sweet's syndrome induced by G-CSF].
Sweet's syndrome may occur during medullar aplasia, especially after treatment with exogenous growth factors such as G-CSF. In this context, Sweet's syndrome presents particular histological features that we detail in this observation. A 50 year-old man was treated for multiple myeloma with a mobilizating chemotherapy prior to autologous stem cell transplantation. Four days after the onset of G-CSF, he presented with a febrile generalized eruption of erythematous infiltrated lesions. Histological examination of a skin biopsy showed a neutrophilic infiltrate associated with atypical xanthomized histiocytes and vascular hyperplasia with marked endothelial turgescence. Treatment with a short cause of oral corticosteroids was efficient. The classical histological features of Sweet's syndrome consist in a dermal neutrophilic infiltrate with edema. In our patient, we noticed the presence of atypical histiocytes among the dermal neutrophilic infiltrate. These histiocytes are described in maculo-papular eruptions induced by G-CSF, and should not be confused with a malignant infiltrate associated with a hemopathy. Vascular hyperplasia may be related to the angiogenic properties of G-CSF. Knowledge of these histological features would enable clinicians and histologists to recognize the appropriate diagnosis.


Epileptic seizures in systemic lupus erythematosus.
To evaluate the frequency and risk factors of epileptic seizures in a large cohort of patients with systemic lupus erythematosus (SLE). Five hundred nineteen consecutive patients with SLE were studied, with follow-up ranging from 4 to 7.8 years. The type and frequency of risk factors associated with acute and recurrent epileptic seizures in SLE were determined. Sixty (11.6%) patients with epileptic seizures were identified. Epileptic seizures occurred at the onset of SLE symptoms in 19 (31.6%) and after the onset of SLE in 41 of 60 (68.3%) patients. Fifty-three of 60 (88.3%) patients had acute symptomatic epileptic seizures, and 7 of 60 (11.7%) had recurrent epileptic seizures. Variables associated with acute epileptic seizures at SLE onset were stroke (p = 0.0004) and antiphospholipid antibodies (p = 0.0013). Epileptic seizures during follow-up were related to nephritis (p = 0.001), antiphospholipid antibodies (p = 0.005), and epileptic seizures at disease onset (p = 0.00001). All seven patients who presented recurrent epileptic seizures had antiphospholipid syndrome and interictal epileptic abnormalities on EEG. Epileptic seizures were observed in 11.2% of systemic lupus erythematosus (SLE) patients. Antiphospholipid antibodies and stroke were related to epileptic seizures at SLE disease onset. Patients with renal flares, epileptic seizures at SLE disease onset, and antiphospholipid antibodies were at greater risk for acute symptomatic seizures during follow-up. Recurrence of epileptic seizures occurred in 1.3% of patients and was associated with antiphospholipid syndrome.


Acidosis and glucocorticoids concomitantly increase ubiquitin and proteasome subunit mRNAs in rat muscle.
In rat muscle metabolic acidosis increases ATP-dependent protein degradation and levels of mRNAs for ubiquitin (Ub) and proteasome subunits. Because adrenalectomy (ADX) abolishes the proteolytic response to acidosis in muscle, we examined whether glucocorticoids (GCs) are necessary for acidosis-induced changes in Ub and proteasome mRNAs in muscles. Total RNA content of the white fiber extensor digitorum longus or mixed fiber gastrocnemius muscles were lowest in muscles of ADX rats given acid plus GCs. In contrast, the abundance of Ub and C2 and C9 proteasome subunits mRNAs were increased in muscles from this group compared with untreated ADX rats or ADX rats given acid or GCs alone. Because total RNA is reduced, the increase in these mRNAs in muscles of ADX rats receiving acid plus GCs provides evidence for a specific activation of the ATP-dependent-Ub-proteasome pathway. Thus, GCs are required but not sufficient to produce the coordinated increase in mRNAs encoding ubiquitin and proteasome subunits occurring in muscles of acidotic rats.


The dialog between health and foreign policy in Brazilian cooperation in human milk banks.
Mother's milk is the primary source of nourishment in early infancy. When this source is unavailable, secondary sources may be used, such as human milk banks. The first milk bank in Brazil was created in 1943, and they have been used ever since. A national model was developed through a number of phases, culminating in the Brazilian Network of Human Milk Banks. This gave rise to a number of international cooperation projects, with the Brazilian model particularly relevant for developing nations. The main objective of this analysis is to understand what drives Brazil to promote milk banks internationally. To do this we tried to understand the relationship between health and foreign policy, expressed here as soft power, as here the two areas dialog with one another. The results include gains in both areas and the affirmation of health as a central goal of the national interest cluster of the case.


Is left lobe adult-to-adult living donor liver transplantation ready for widespread use? The US experience (1998-2010).
Living donor liver transplantation (LDLT) is an accepted treatment for patients with end-stage liver disease. To minimize risk to the donor, left lobe (LL) LDLT may be an ideal option in adult LDLT. This study assessed the outcomes of LL-LDLT compared with right lobe (RL) LDLT in adults (1998-2010) as reported to the United Network for Organ Sharing (UNOS) Organ Procurement and Transplantation Network (OPTN). A total of 2844 recipients of LDLT were identified. Of these, 2690 (94.6%) underwent RL-LDLT and 154 (5.4%) underwent LL-LDLT. A recent increase in the number of LL-LDLTs was noted: average numbers of LL-LDLTs per year were 5.2 during 1998-2003 and 19.4 during 2004-2010. Compared with RL-LDLT recipients, LL-LDLT recipients were younger (mean age: 50.5 years vs. 47.0 years), had a lower body mass index (BMI) (mean BMI: 24.5 kg/m(2) vs. 26.8 kg/m(2)), and were more likely to be female (64.6% vs. 41.9%). Donors in LL-LDLT had a higher BMI (mean BMI: 29.4 kg/m(2) vs. 26.5 kg/m(2)) and were less likely to be female (30.9% vs. 48.1%). Recipients of LL-LDLT had a longer mean length of stay (24.9 days vs. 18.2 days) and higher retransplantation rates (20.3% vs. 10.9%). Allograft survival in LL-LDLT was significantly lower than in RL-LDLT and there was a trend towards inferior patient survival. In Cox regression analysis, LL-LDLT was found to be associated with an increased risk for allograft failure [hazard ratio (HR): 2.39)] and inferior patient survival (HR: 1.86). The number of LL-LDLTs has increased in recent years.


The use of bifunctional NOP/mu and NOP receptor selective compounds for the treatment of pain, drug abuse, and psychiatric disorders.
The NOP receptor, the fourth receptor in the opioid receptor family, is found throughout the brain and is involved in a variety of CNS systems and pathways. The endogenous ligand for NOP receptors, nociceptin/orphanin FQ (now called N/OFQ), was originally thought to increase a painful stimulus since intracerebroventricular (i.c.v.) administration of this heptadecapeptide led to a decrease in tail-flick and hot-plate latency in mice. Further studies suggested that N/OFQ blocks opiate analgesia when administered i.c.v. but potentiates opiate analgesia and has antinociceptive activity when administered intrathecally. I.c.v. administration of N/OFQ has other beneficial actions including inhibition of reward induced by several different abused drugs, as well as anti-anxiety activity. Recent work has demonstrated that individual small molecules that activate both NOP and mu receptors possess mu-mediated antinociceptive activity with reduced reward, as determined by conditioned place preference tests. Furthermore, selective NOP receptor agonists appear to be active in certain chronic pain models and reduce both drug craving and anxiety. NOP receptor antagonists may also have therapeutic benefits since both peptide and small molecule antagonists have anti-depressant activity in two different animal models. Therefore, both selective NOP receptor compounds and non-selective compounds, with both NOP receptor and mu opioid receptor activity, appear to have potential for clinical use for several neurological and psychiatric disorders including acute and chronic pain, drug abuse, anxiety and depression.


Characterization of interactions of enteropathogenic Escherichia coli O127:H6 with mammalian cells in vitro.
Previous studies have identified two bacterial factors involved in enteropathogenic Escherichia coli (EPEC) infection. A plasmid-mediated EPEC adherence factor (EAF) is responsible for initial and localized adherence. A chromosomally encoded E. coli attachment and effacement factor (eae) is involved in effacement of the eukaryotic cell surface and characteristic "pedestal" formation. By using isogenic strains deficient in either EAF, eae, or both, the process of EPEC adherence and entry in vitro was examined. While EAF proved necessary and sufficient for efficient bacterial association with HEp-2 cells, both EAF and eae were required for efficient effacement of and entry into these cells and other cultured cell lines. Invasion mediated by eae was markedly inhibited by cytochalasin D and colchicine. Afimbrial adhesion or type I pili from uropathogenic strains of E. coli substituted for EAF in EAF-Eae+ strains to provide initial adherence to HEp-2 cells and to facilitate actin condensation.


Interdisciplinary Care for a Patient with Amelogenesis Imperfecta: A Clinical Report.
This manuscript describes an interdisciplinary approach over a period of 8 years combining surgical and prosthodontic treatment of a young patient diagnosed with hypocalcified-type amelogenesis imperfecta and anterior open bite. The treatment procedures included transitional restorations, orthodontic treatment, and maxillofacial surgery with a one-piece Le Fort I osteotomy, bilateral mandibular osteotomy, and genioplasty. The definitive prosthetic rehabilitation consisted of 28 zirconia-based ceramic single crowns restoring both esthetics and function. Photographs and radiographs associated with clinical evaluation were used in the maintenance period. Two-year follow-up revealed satisfactory results and no deterioration in the restorations.


IFN-beta 2, B cell differentiation factor 2, or hybridoma growth factor (IL-6) is expressed and released by human epidermal cells and epidermoid carcinoma cell lines.
IL-6, which is also known as IFN-beta 2, hybridoma growth factor, hepatocyte-stimulating factor, and B cell differentiation factor, mediates acute phase responses including fever, has lymphocyte-stimulating capacities, and antiviral activity. IL-6 is produced by monocytes, fibroblasts, certain lymphocytes, and various tumor cells. The present study demonstrates that this multifunctional cytokine is released also by normal human epidermal cells (EC) and human epidermoid carcinoma cell lines (A431, KB). Accordingly, supernatants derived from freshly isolated EC, long term keratinocyte cultures, A431, or KB cells stimulated the proliferation of a hybridoma growth factor/IL-6-dependent plasmacytoma cell line (B9). IL-6 constitutively was produced in the presence of serum proteins. The addition of IL-1 alpha, IL-1 beta, or the tumor promoter PMA significantly enhanced the synthesis and release of EC-derived IL-6 (EC-IL 6). Like monocyte or fibroblast-derived IL-6, EC-IL-6 exhibited Mr microheterogeneity within 21 and 28 kDa. Similarly in Western blotting experiments an antiserum directed against human rIFN-beta 2/IL-6 detected the different Mr forms of EC-IL-6. Moreover, this antiserum was able to block the B9 cell growth-promoting capacity of EC-IL-6 strongly suggesting that this EC-derived mediator is closely related, if not identical with IL-6. This was further confirmed by Northern blot analysis detecting IL-6 specific mRNA both in long term cultured keratinocytes and A431 cells by hybridization with a cDNA fragment encoding for B cell differentiating factor 2/IL-6. Therefore, in addition to the production of other cytokines as previously reported, EC and in particular keratinocytes also synthesize and release IL-6. This further supports the important regulatory role of the epidermis during the pathogenesis of inflammatory, autoimmune, and neoplastic diseases.


Endogenous fat loss and true total tract digestibility of poultry fat in adult dogs.
Fat plays an important role in the carnivore diet. It has high digestibility and high energy content and likely improves digestibility of the diet when present in greater amounts, suggesting that endogenous fat adversely affects the apparent digestibility of fat in low-fat diets. This study aimed to determine the endogenous fat loss (EFL) and true total tract digestibility (TTTD) of fat in dogs by using diets having different fat:carbohydrate ratios. Furthermore, the apparent total tract digestibility (ATTD) of macronutrients and energy, food intake, fecal output, and stool quality were evaluated. Twelve adult Beagle dogs were stratified into three 10-d periods in a 6 × 3 balanced incomplete Latin square design. Dietary treatments included a low-fat basal diet (3.4% fat) supplemented with 6 poultry fat levels (1, 4, 10, 12, 16, or 20%). The dogs were individually housed in metabolic cages and fed to meet the maintenance energy requirements. The ME intake was similar across the diets, despite the clearly low palatability of the 1 and 4% fat diets. Dietary ATTD of DM, OM, fat, and GE were improved after fat inclusion ( < 0.001). The ATTD of CP was not affected by dietary fat increase ( > 0.05). The amount of fecal output decreased with increasing level of fat in the diet, but the fecal score was not affected. The stool quality was close to ideal (2.4-2.8) and no different among diets. The EFL was estimated using 2 regression methods and was expressed as 155 mg∙kg BW∙d or 7.9 g/kg of DMI. The TTTD of poultry fat was the same irrespective of the dietary fat level. Poultry fat was 99.3% digestible for the dogs. The relation between EFL and fat intake was higher for the lower-fat diets, explaining the ATTD of fat increase according to the dietary fat inclusion. In conclusion, dietary fat is well digested by dogs irrespective of the level included, close to 100%. The ATTD of fat in low-fat diets is underestimated because the endogenous content is proportionally greater than that in high-fat diets.


Light induced catalytic intramolecular hydrofunctionalization of allylphenols mediated by porphyrin rhodium(iii) complexes.
Catalytic intramolecular hydrofunctionalization of allylphenols to heterocyclic compounds mediated by rhodium(iii) porphyrin complexes was described. The Wacker-type intermediate β-heterocyclic alkyl rhodium complex was independently synthesized and crystallized.


Localized delivery of proteins in the brain: can transport be customized?
Certain central nervous system (CNS) diseases are characterized by the degeneration of specific cell populations. One strategy for treating neurodegenerative diseases is long-term, controlled delivery of proteins such as epidermal growth factor (EGF) and nerve growth factor (NGF). Since proteins permeate through brain capillaries very slowly, local administration using polymeric implants, continuous infusion pumps, or transplanted, protein-secreting cells may be required to achieve therapeutic concentrations in the tissue. The efficiency of local distribution, and hence effectiveness of local therapy, depends on the rate of protein migration through tissue. The rate of dispersion of molecules in a quiescent, isotropic medium can be characterized by the molecular diffusion coefficient, D, which can be measured by techniques such as quantitative autoradiography, iontophoresis, and fluorescence photobleaching recovery (FPR). These methods are reviewed, with an emphasis on their application to measurement of D for proteins in the brain. Biophysical techniques yield quantitative descriptions of local protein distribution and may enable discrimination of mechanisms of protein transport in the brain. This capability suggests a new paradigm for design of protein therapies, in which proteins and delivery systems are collectively customized to provide sustained protein availability over predetermined volumes of tissue.


Oral garenoxacin in the treatment of acute bacterial maxillary sinusitis: a Phase II, multicenter, noncomparative, open-label study in adult patients undergoing sinus aspiration.
Garenoxacin is a des-F(6)-quinolone with in vitro activity against key respiratory pathogens, including Streptococcus pneumoniae, Hemophilus influenzae, Staphylococcus aureus, and Moraxella catarrhalis. Limited data are available regarding the effect of garenoxacin in the treatment of acute bacterial sinusitis. The aim of this study was to assess the efficacy and tolerability of garenoxacin in adults with acute bacterial maxillary sinusitis undergoing a pre-treatment diagnostic sinus aspirate. This Phase II, multicenter, noncomparative, open-label study was conducted at 30 centers in the United States, Mexico, Argentina, and Europe. Male and female patients aged 18 to 80 years with clinical signs and symptoms lasting >or=5 but <or=28 days and radiologic signs (air-fluid level, opacification, mucosal thickening) of acute maxillary sinusitis were eligible. The entry criteria for the 5-day treatment regimen did not include mucosal thickening of >or=5 mm because it was believed that improvement in mucosal thickening might not be reliably measurable at the 5-day time point. All patients received garenoxacin 400 mg QD for 5 or 10 days. Maxillary sinus needle aspiration for Gram stain, routine culture, and susceptibility testing were performed before treatment, and, if clinically indicated, during and after treatment. Bacteriologic eradication (negative culture on repeat sinus aspiration) and cure rates (complete resolution of all signs and symptoms) were assessed at a test-of-cure visit 5 to 18 days after the end of treatment. The occurrence of adverse events was recorded by the investigators up to 30 days after the last administration of garenoxacin by questioning patients. A total of 546 patients were enrolled and 543 were randomized (5-day cohort: mean age, 40 years; mean weight, 76 kg; 56% women; 10-day cohort: mean age, 41 years; mean weight, 77 kg; 58% women). Clinically evaluable patients included 253 in the 5-day cohort and 266 in the 10-day cohort. Cure rates were 93% (236/253; 95% CI, 89%-96%) and 91% (243/266; 95% CI, 87%-94%) for evaluable patients in the 5- and 10-day cohorts, respectively. Bacteriologic eradication rates in microbiologically evaluable patients were 94% in both cohorts (5 days, 204/217; 10 days, 182/193). Eradication rates in the 5- and 10-day cohorts were as follows: S pneumoniae, 94% (62/66) and 93% (39/42); H influenzae, 100% (30/30) and 93% (26/28); S aureus, 96% (23/24) and 91% (31/34); and M catarrhalis, 89% (8/9) and 86% (12/14). Of the 9 patients with acute bacterial sinusitis due to multidrug-resistant S pneumoniae, 8 achieved clinical cure with garenoxacin treatment. Adverse events (AEs) most frequently reported were diarrhea (<or=2%), nausea (2%-6%), headache (2%-6%), and dizziness (<or=2%). Two percent of patients withdrew because of an AE (allergic reaction, adverse gastrointestinal effects, dyspnea, dizziness, headache, or elevation in liver enzymes). In this population of patients with signs and symptoms of acute maxillary sinusitis, oral garenoxacin 400 mg QD for 5 or 10 days eradicated 94% of bacterial pathogens associated with acute bacterial sinusitis in this population and appeared to be well tolerated in adults.


Influence of vagus nerve stimulation on vestibulo-ocular reflex.
Vagus nerve stimulation (VNS), as used for the treatment of intractable epilepsy, may interfere with signals from viscera and modify the integration of autonomic afferent fibers in the brainstem. In order to detect an influence of VNS on vestibular function, the vestibulo-ocular reflex (VOR) of 5 patients was examined before and during VNS. Nonsignificant alterations of the maximum slow-phase velocity of the VOR were found. A significant clinical alteration of the VOR during VNS was not observed.


Improved safety standards are needed to better protect younger children at playgrounds.
Playground-related traumatic brain injuries (TBIs) in children remain a considerable problem world-wide and current safety standards are being questioned due to historical reasons where the injury thresholds had been perpetuated from automobile industry. Here we investigated head injury mechanisms due to falls on playgrounds using a previously developed and validated age-scalable and positionable whole body child model impacted at front, back and side of the head simulating head-first falls from 1.59 meters (m). The results show that a playground material passing the current testing standards (HIC < 1000 and resultant linear acceleration <200 g) resulted in maximum strain in the brain higher than known injury thresholds, thus not offering sufficient protection especially for younger children. The analysis highlights the age dependence of head injuries in children due to playground falls and the youngest have a higher risk of brain injury and skull fracture. Further, the results provide the first biomechanical evidence guiding age-dependent injury thresholds for playground testing standards. The results also have direct implications for novel designs of playground materials for a better protection of children from TBIs. Only making the playground material thicker and more compliant is not sufficient. This study represents the first initiative of using full body human body models of children as a new tool to improve playground testing standards and to better protect the children at playgrounds.


EVOLUTION OF MYCOBACTERIUM TUBERCULOSIS AND IMPLICATIONS FOR VACCINE DEVELOPMENT.
Tuberculosis (TB) is a growing public health threat, particularly in the face of the global epidemics of multidrug resistance. Given the limited efficacy of the current TB vaccine and the recent clinical failure of the most advanced new TB vaccine candidate, novel concepts for vaccine design should be explored. Most T cell antigens in the human-adapted Mycobacterium tuberculosis complex (MTBC) are evolutionarily conserved and under strong purifying selection, indicating that host immune responses targeting these antigens might not be protective. By contrast, a few highly variable T cell epitopes have recently been discovered, which could serve as alternative vaccine antigens. Moreover, there is increasing evidence that the human-adapted MTBC has been co-evolving with the human host for a long time. Hence, studying the interaction between bacterial and human genetic diversity might help identify additional targets that could be exploited for TB vaccine development.


Holistic view of the seascape dynamics and environment impact on macro-scale genetic connectivity of marine plankton populations.
Plankton seascape genomics studies have revealed different trends from large-scale weak differentiation to microscale structures. Previous studies have underlined the influence of the environment and seascape on species differentiation and adaptation. However, these studies have generally focused on a few single species, sparse molecular markers, or local scales. Here, we investigated the genomic differentiation of plankton at the macro-scale in a holistic approach using Tara Oceans metagenomic data together with a reference-free computational method. We reconstructed the FST-based genomic differentiation of 113 marine planktonic taxa occurring in the North and South Atlantic Oceans, Southern Ocean, and Mediterranean Sea. These taxa belong to various taxonomic clades spanning Metazoa, Chromista, Chlorophyta, Bacteria, and viruses. Globally, population genetic connectivity was significantly higher within oceanic basins and lower in bacteria and unicellular eukaryotes than in zooplankton. Using mixed linear models, we tested six abiotic factors influencing connectivity, including Lagrangian travel time, as proxies of oceanic current effects. We found that oceanic currents were the main population genetic connectivity drivers, together with temperature and salinity. Finally, we classified the 113 taxa into parameter-driven groups and showed that plankton taxa belonging to the same taxonomic rank such as phylum, class or order presented genomic differentiation driven by different environmental factors. Our results validate the isolation-by-current hypothesis for a non-negligible proportion of taxa and highlight the role of other physicochemical parameters in large-scale plankton genetic connectivity. The reference-free approach used in this study offers a new systematic framework to analyse the population genomics of non-model and undocumented marine organisms from a large-scale and holistic point of view.


Extrarenal abnormalities in Tc-99m DTPA renal perfusion studies due to hypervascularized tumors.
In cases of impaired renal perfusion and/or function, Tc-99m DTPA renal flow studies are often used as screening procedures. Besides the demonstration of pathological changes in renal perfusion and/or function, various extrarenal abnormalities may sometimes be detected. Three cases of hypervascular tumors were detected during the course of Tc-99m DTPA renography. These findings stimulated further diagnostic clarification revealing extended extrarenal lesions associated with several different etiologies: angiomyolipoma in tuberous sclerosis, extramedullary manifestations of plasma-cytoma, and metastasis of renal carcinoma. One should be aware of these extrarenal abnormalities in renal flow studies since these three tumor entities frequently exhibit increased vascularity.


Oncogenic function of angiopoietin-2 in vitro and its modulation of tumor progression in colorectal carcinoma.
Angiopoietin-2 (Ang-2) has been investigated in cancer primarily in terms of its angiogenic function, and its role as an oncogene has yet to be elucidated. The current study hypothesized that Ang-2 may be an oncogene and have a function in tumor progression. An investigation of the function of Ang-2 in the LoVo colorectal cancer (CRC) cell line in vitro, which expresses a high level of Ang-2, was performed by knocking down endogenous expression with a targeted short hairpin RNA. The aggressive phenotypic effects of Ang-2 on experimental and control group cells were assessed using cell proliferation, migration and invasion assays. The association between Ang-2 expression levels and clinicopathological factors was evaluated in 415 CRC tissues using immunohistochemistry. Suppressing Ang-2 expression decreased cellular proliferation, invasion and migration in an in vitro study. Ang-2 overexpression was observed in 46% of patients with CRC and was significantly associated with pT (P=0.048), pN (P<0.001), venous invasion (P=0.023), lymphatic invasion (P<0.001) and tumor-node-metastasis stage (P=0.022). Furthermore, Ang-2 overexpression was an independent prognostic factor in pN stages 1 and 2. These results reveal that Ang-2 may be an oncogene in colorectal carcinogenesis and its expression may exert aggressive phenotypic effects during tumor progression. In addition, Ang-2 expression may serve as a prognostic marker and a potential drug target.


[Intra-arterial infusion chemotherapy for recurrent breast cancer via an implantable system--the second report].
Intra-arterial infusion chemotherapy via an implantable port catheter has been applied in 16 patients with locally recurrent breast cancer. The regimen consisted of induction and subsequent maintenance: intra-arterial infusion of epirubicin (EPI). Non-responders were entered into the second-line regimen consisting of Methotrexate and 5-FU (MF). The results were as follows: 1) The response rate (CR+PR) of EPI to locoregional lesions was 50%, and the median duration of response was 5.7 months. 2) The response rate and the duration of response of MF were 25% and 3 months, respectively. 3) Patients with ER-rith, no previous therapy and a long disease-free interval tended to have a high rate of response to intra-arterial infusion therapy. 4) Improvements of QOL, such as intractable pain, infection and severe lymphedema were recognized in 68.6% of the cases. In more than half of the cases, these treatments were carried out in an outpatient clinic. 5) Leucopenia and catheter or portal problems were encountered in 68.6% and 25.0%, respectively. We conclude that intra-arterial infusion chemotherapy via implantable system is a promising modality with regard to therapeutic effect and improvement of quality of life.


Two-color scattering for the measurement of neutrals at the edge of fusion devices.
Laser two-color scattering (TCS) is proposed to detect the neutral species in the edge of fusion devices, namely, tokamaks. TCS uses two wavelengths to probe both the laser Rayleigh scattering and Thomson scattering of the neutral-electron bath, with emphasis on neutral density measurements such as that of hydrogen and deuterium. Modeling of the Rayleigh scattering of tokamak neutral species under various plasma conditions (electron density and temperature) shows that, with an appropriate filtering of the Thomson signal and by going to ultraviolet-region wavelengths, identification of the Rayleigh signal can be achieved. Photon count and signal fractions are calculated in two test cases, one in the midplane region of the National Spherical Torus Experiment and one in the divertor region of DIII-D. An uncertainty analysis and discussion of the feasibility of the TCS diagnostic is also presented.


Temperature Dependence of Electrophoretic Mobility and Hydrodynamic Radius of Microgels of Poly(N-isopropylacrylamide).
Electrostatic interactions in charged microgels, which are dominated by the microgel net charge, play a crucial role in colloidal stabilization and loading of small, charged molecules. In this study, the temperature dependences of electrophoretic mobility μ and hydrodynamic radius Rh were measured for a slightly ionized poly(N-isopropylacrylamide) (PNIPA) microgel in a dilute suspension. A decrease in Rh was observed in the temperature range between 30 °C and 35 °C, corresponding to the lower critical solution temperature of PNIPA, and an increase in |μ| was observed in a higher temperature range between 34 °C and 37 °C. The analysis based on electrophoresis theory for spherical polyelectrolytes indicated that the net charge of the microgel decreased as the microgel was deswollen.


Is there a role of lipid-lowering therapies in the management of fatty liver disease?
Atherogenic dyslipidemia is characterized by increased triglyceride-rich lipoproteins and low high-density lipoprotein cholesterol concentrations. It is highly prevalent in non-alcoholic fatty liver disease (NAFLD) and contributes to the increased cardiovascular risk associated with this condition. Alongside insulin resistance it plays an important pathogenetic role in NAFLD/non-alcoholic steatohepatitis (NASH) development and progression. It has been shown that cholesterol-lowering reduces cardiovascular risk more in NAFLD vs non-NAFLD high-risk individuals. This evidence highlights the importance of effective lipid modulation in NAFLD. In this narrative review the effects of the most commonly used lipid-lowering therapies on liver outcomes alongside their therapeutic implications in NAFLD/NASH are critically discussed. Preclinical and clinical evidence suggests that statins reduce hepatic steatosis, inflammation and fibrosis in patients with NAFLD/NASH. Most data are derived from observational and small prospective clinical studies using changes in liver enzyme activities, steatosis/fibrosis scores, and imaging evidence of steatosis as surrogates. Also, relevant histologic benefits were noted in small biopsy studies. Atorvastatin and rosuvastatin showed greater benefits, whereas data for other statins are scarce and sometimes conflicting. Similar studies to those of statins showed efficacy of ezetimibe against hepatic steatosis. However, no significant anti-inflammatory and anti-fibrotic actions of ezetimibe have been shown. Preclinical studies showed that fibrates through peroxisome proliferator-activated receptor (PPAR)α activation may have a role in NAFLD prevention and management. Nevertheless, no relevant benefits have been noted in human studies. Species-related differences in PPARα expression and its activation responsiveness may help explain this discrepancy. Omega-3 fatty acids reduced hepatic steatosis in numerous heterogeneous studies, but their benefits on hepatic inflammation and fibrosis have not been established. Promising preliminary data for the highly purified eicosapentaenoic acid require further confirmation. Observational studies suggest that proprotein convertase subtilisin/kexin9 inhibitors may also have a role in the management of NAFLD, though this needs to be established by future prospective studies.


Quantum computing with incoherent resources and quantum jumps.
Spontaneous emission and the inelastic scattering of photons are two natural processes usually associated with decoherence and the reduction in the capacity to process quantum information. Here we show that, when suitably detected, these photons are sufficient to build all the fundamental blocks needed to perform quantum computation in the emitting qubits while protecting them from deleterious dissipative effects. We exemplify this by showing how to efficiently prepare graph states for the implementation of measurement-based quantum computation.


Anterior Segment Findings in Patients With Osteogenesis Imperfecta: A Case-Control Study.
To evaluate the anterior segment parameters in patients with osteogenesis imperfecta (OI) compared with healthy control subjects. Seventeen patients with OI and 19 age-matched healthy controls were included into this cross-sectional case-control study. Corneal topographic, topometric and Belin-Ambrósio Enhanced Ectasia Display III analysis, corneal densitometry (12-mm corneal diameter), and lens densitometry measurements were obtained by using the Pentacam HR-Scheimpflug imaging system (Oculus, Wetzlar, Germany). The corneal endothelial cell properties were determined by specular microscopy. In comparison to the control group, patients with OI had significantly higher front astigmatism (0.8 ± 0.4 vs. 1.4 ± 1.1 mm, P = 0.026), thinner thinnest corneal thickness (556.4 ± 32.7 μm vs. 482.5 ± 66.9 μm, P = 0.002), smaller corneal volume (62.4 ± 3.5 mm vs. 53.7 ± 6.4 mm, P < 0.001), lower anterior chamber depth (3.2 ± 0.3 mm vs. 3.0 ± 0.2 mm, P = 0.009), higher index of vertical asymmetry (0.1 ± 0.04 vs. 0.2 ± 0.11, P < 0.001), higher posterior elevation (6.0 ± 2.7 μm vs. 11.9 ± 7.8 μm, P = 0.002), lower maximum Ambrósio relational thickness indice (456.6 ± 67.5 vs. 365.6 ± 115.7, P = 0.009), and higher final "D" value (0.7 ± 0.4 vs. 2.0 ± 1.6, P = 0.002). The corneal and lens densitometry values were similar in all concentric zones and layers in both groups except that 6 to 10 mm in the center. Corneal densitometry was higher in eyes with OI than that in the control group (9.8 ± 1.7 and 8.8 ± 1.0, P = 0.010). There was no difference in endothelial cell morphology between the groups (P > 0.05). The morphologic parameters determined on the corneal analysis are in general agreement with the known pathophysiology of OI. Corneal analysis may prove useful in monitoring patients with OI in clinical practice.


[Effects of serum anti-sperm antibodies positive on the Fas/Fas-L apoptosis pathway in the testis tissue and testicular germ cells of pubertal male rats].
To establish a rat model of anti-sperm antibody (AsAb)-mediated immune infertility, and investigate the effects of serum AsAb positive on the Fas/Fas-L apoptosis pathway in testis tissue and testicular germ cells of pubertal male rats. Thirty 5-week-old Wistar male rats were included in this study, 10 killed for preparation of sperm suspension, 10 as normal controls, and the other 10 made models of AsAb-positive immune infertility (experimental group). Four weeks after modeling, the testes of the rats were harvested for observation of the changes in the testis tissue under the light microscope and detection of the expressions of Fas, Fas-L and Caspase-3 proteins by immunohistochemistry. Compared with the control group, the experimental group showed obvious apoptotic changes in the testis tissue and remarkably increased expressions (OD value) of Fas (161.87 +/- 5.37 vs 176.97 +/- 4.58), Fas-L (150.27 +/- 8.65 vs 187.52 +/- 7.76) and Caspase-3 (120.37 +/- 6.76 vs 157.65 +/- 7.38) (P < 0.01). Serum AsAb affected the infertility of pubertal male rats, and its mechanisms might be associated with up-regulated expression of Fas, Fas-L and Caspase-3 proteins in the Fas/Fas-L apoptotic pathway.