Specific tumor markers in diagnostic cytology. Immunoperoxidase studies of carcinoembryonic antigen, lysozyme and other tissue antigens in effusions, washes and aspirates.
The immunoperoxidase technique was used to identify specific tumor markers in exfoliated cells in fine needle aspirates and body fluids. Carcinoembryonic antigen (CEA) and lysozyme staining was evaluated in cytocentrifuge preparations from 42 malignant effusions and aspirates and 16 benign effusions. Reactive mesothelial cells were negative for CEA and lysozyme or showed faint peripheral cytoplasmic staining. Malignant cells from 50% of the adenocarcinomas studied were positive for CEA. All tumors studied were negative for lysozyme. These staining patterns are helpful in the differential diagnosis of reactive mesothelial and adenocarcinoma cells, a frequent diagnostic dilemma. Moreover, demonstration of specific tumor antigens (e.g., prostatic acid phosphatase, calcitonin and immunoglobulin) helped define the origin of metastatic malignancy in selected cases. Estrogen receptor activity was also identified in tumor cells using this technique. Immunoperoxidase was helpful in the evaluation of malignant cytologic specimens from patients with more than one tumor. Interpretation of staining patterns is discussed, with reference to the limitations of the technique. Immunoperoxidase methods maintain cytologic detail, are readily adaptable to diagnostic cytology and increase the specificity of cytologic diagnosis.


Structure-modifying capacity of anti-tumour necrosis factor-alpha therapy in ankylosing spondylitis.
Spondylarthropathies (SpA) present mainly with spondylitis, pauciarticular peripheral arthritis and enthesopathy. Ankylosing spondylitis (AS) is the prototype disease in this concept. Other entities include reactive arthritis, arthritis in patients with inflammatory bowel disease, some forms of psoriatic arthritis and undifferentiated SpA. NSAIDs are the classical cornerstone of medical therapy in patients with SpA. The effect of these drugs on disease progression, more specifically the ankylosis, is uncertain. Sulfasalazine can be combined with NSAIDs, particularly if peripheral arthritis symptoms persist. However, this combination therapy is not effective for the spondylitis symptoms. Indeed, AS is one of the rheumatic diseases for which no real disease-modifying antirheumatic treatment is available. Challenges in chronic autoimmune arthritis have changed dramatically, especially since biotechnological compounds became available. These compounds allow for a specific intervention in the immune cascade underlying the disease. Tumour necrosis factor (TNF)-alpha antagonists (monoclonal antibodies such as infliximab, or soluble receptors such as etanercept) are the first representative drugs in this category. Open-label studies have shown the efficacy of these new targeted drugs, which has been confirmed by controlled studies, at least in the short term. Improvements in several clinical parameters, function, quality of life, biological parameters, histopathological synovial characteristics and magnetic resonance imaging, have all been observed. As a result of these favourable results, anti-TNFalpha therapy has been approved for the treatment of AS and should be considered for patients with severe axial symptoms and elevated serological markers of inflammatory activity who have responded inadequately to conventional nonsteroidal therapy. There is evidence that this new therapeutic approach has a disease- and even structure-modifying effect in SpA. In this context, structure modification should not only be seen as inhibition of bone and cartilage destruction but more broadly as modulation of tissue histology. Some questions remain unanswered, such as the long-term efficacy and safety of anti-TNFalpha therapy, the extent of structural benefit and the cost effectiveness. However, despite these concerns, anti-TNFalpha therapy represents a major therapeutic advancement in the treatment of AS.


Psychological testing on the Internet: new problems, old issues.
The Internet has significantly changed the way people conduct business, communicate, and live. In this article, the authors' focus is on how the Internet influences the practice of psychology as it relates to testing and assessment. The report includes 5 broad sections: background and context, new problems yet old issues, issues for special populations, ethical and professional issues, and recommendations for the future. Special attention is paid to implications for people with disabling conditions and culturally and linguistically diverse persons. The authors conclude that ethical responsibilities of psychologists and current psychometric standards, particularly those regarding test reliability and validity, apply even though the way in which the tests are developed and used may be quite different.


Two-wavelength operation of a double-pass planar dye laser amplifier.
The simultaneous multiple line operation of a double pass dye laser amplifier is reported. Standard schemes have been used to generate two independently tunable lines and to scan one narrow line linearly around a fixed one. A simple, new scheme is illustrated, which allows symmetric splitting of narrow laser lines.


Synthesis and properties of a series of β-cyclodextrin/nitrone spin traps for improved superoxide detection.
Three new DEPMPO-based spin traps have been designed and synthesized for improved superoxide detection, each carrying a cyclodextrin (CD) moiety but with a different alkyl chain on the phosphorus atom or with a long spacer arm. EPR spectroscopy allowed us to estimate the half-life of the superoxide spin adducts which is close to the value previously reported for CD-DEPMPO (t1/2 ≈ 50-55 min under the conditions investigated). The spectra are typical of superoxide adducts (almost no features of the HO˙ adduct that usually forms with time for other nitrone spin traps such as DMPO) and we show that at 250 μM, the new spin trap enables the reliable detection of superoxide by 1 scan at the position opposite to the corresponding spin trap without the CD moiety. The resistance of the spin adducts to a reduction process has been evaluated, and the superoxide spin adducts are sensitive to ascorbate and glutathione (GSH), but not to glutathione peroxidase/GSH, reflecting the exposed nature of the nitroxide moiety to the bulk solvent. To understand these results, 2D-ROESY NMR studies and molecular dynamics pointed to a shallow or surface self-inclusion of the nitrone spin traps and of nitroxide spin adducts presumably due to the high flexibility of the permethyl-β-CD rim.


[Ribosomal dysentery vaccine. II. Biological trials of active protection for guinea pigs and mice].
Ribosomal vaccine from Sh. sonnei injected subcutaneously once or twice in physiological saline or in Freund's complete adjuvant produces a marked protective effect against experimental keratoconjunctivitis in guinea pigs. Inhibition of the protective effect by high doses (above 100 microgram) of ribosomal vaccine is evident after a single, but not repeated injections. Protective effect in mice is achieved by immunization with very low doses of ribosomal vaccine: ED50 is 1.2 ng after challenge with 5.6 LD50. The nature of immunogenic factor responsible for the biological activity of the ribosome vaccine is still obscure. In contrast to Boivin's antigen, ribosomal preparations, even in high doses (1000--2000 microgram), have no toxic effect on mice and guinea pigs.


A rapid shallow breathing index threshold of 85 best predicts extubation success in chronic obstructive pulmonary disease patients with hypercapnic respiratory failure.
The rapid shallow breathing index (RSBI) is used clinically to help predict a patient's likelihood of successful liberation from mechanical ventilation (MV). However, the traditional threshold (<105 breaths/min/L) may underperform in patients with chronic obstructive pulmonary disease (COPD). We sought to determine the optimal RSBI threshold for COPD patients to improve the diagnostic accuracy for predicting successful ventilator liberation. This was a prospective observational multicenter study of COPD patients [according to Global initiative for Chronic Obstructive Lung Disease (GOLD) criteria] admitted to the Medical ICUs of eight academic medical centers. All patients were intubated for hypercapnic respiratory failure and met the American Thoracic Society/European Respiratory Society guidelines to participate in a weaning trial. Ventilator weaning was conducted according to a defined protocol. RSBI was measured through the ventilator after 120 minutes of spontaneous breathing trial (SBT). Ninety patients were included (39 males and 51 females). Forty-three patients (48%) were successfully extubated whereas 47 patients (52%) failed extubation. Significant differences were observed between groups for duration-of-intubation [duration of intubation (DoI); P<0.0001], spontaneous tidal volume (VT) (P=0.03), and the ratio of dynamic-to-static compliance (P=0.005). The RSBI threshold of ≤85 breaths/min/L performed best: area under curve (AUC) receiver operating characteristic (ROC) curves 0.91, sensitivity 95.6%, specificity 90.4%, positive predictive value (PPV) 95.5%, and negative predictive value (NPV) 90.6%., positive likelihood ratio (LR+) 5.48, negative likelihood ratio (LR-) 0.25, and the diagnostic accuracy 91.7%. In post-ROC analyses, DoI and hospital length-of-stay (LOS) did not impact performance. In COPD patients intubated with hypercapnia, RSBI ≤85 breaths/min/L outperformed the widely used threshold <105 breaths/min/L, yielding a 95.5% probability of extubation success, independent of ventilation duration or hospital LOS.


[Growth hormone (BST) in animal production].
This study was conducted with the objective to evaluate and reach to the conclusion wether is growth factor in human for BST hormone which is species specific (bovine). Based in this, the effect of BST hormone on milk production specially in cows was analyzed, with a fundamental application, in meat production in: bovine, swine poultry y egg production. This arise a question related to the inter-reaction with the sexual behavior and maternity of this hormone. For this reason, the mechanism of action this hormone such as: lactogenesis, nitrogin level, ribosomal RNA (rRNA), protoglicans, etc. were analyzed and the necessary precaution and biological effects with the respect to the consumption of the food produced using this hormone were stated.


An integrated delivery systems review: common problems to be addressed.
The most critical element in developing a successful IDS is identifying the needs and goals of the parties within the context of the realities of their local health care market. It is therefore unwise to select the structure of a proposed IDS until this process has been completed. An honest goals assessment might result in the immediate formation of a PHO, MSO, medical foundation or other formal IDS, or might alternatively point in the direction of something much less structured, such as a joint marketing contractual arrangement (sometimes called a "PHA"), which can be relatively inexpensive to implement and can provide a fairly immediate response to quickly changing market conditions. Some organizations might even decide to utilize a number of different IDS vehicles in order to offer physicians a menu of affiliation options. The legal issues that arise when forming an IDS can almost always be dealt with in a reasonable manner. The real key to success is entering into integration discussions with an open mind, rather than a preconceived commitment to a particular integration.


The incidence and pathogenesis of cardiopulmonary deterioration after abrupt withdrawal of inhaled nitric oxide.
We studied the effect of abrupt discontinuation of inhaled nitric oxide (iNO) in patients receiving this drug for treatment of acute hypoxemic respiratory failure (AHRF), in order to determine the need for continued therapy, the incidence and nature of adverse events, and the risk factors predicting these adverse events. Thirty-one patients who showed an initial increase in Pa(O(2)) of > 20 mm Hg in response to iNO underwent a discontinuation trial at 10 to 30 h after beginning iNO. Indwelling arterial and pulmonary artery catheters facilitated monitoring of hemodynamic and gas-exchange parameters. For the group, discontinuation of iNO caused a significant decrease in Pa(O2 ), arterial and mixed venous oxygen saturation, and ratio of Pa(O(2)) to fraction of inspired oxygen (FI(O(2))). Three patterns of response were observed. Eight of 31 (25.8%) patients had minimal changes in oxygenation or hemodynamics, suggesting no need for ongoing therapy. Fifteen of 31 (48%) patients had worsened gas exchange as a predominant response. Eight of 31 patients exhibited hemodynamic collapse, defined as > 20% fall in cardiac output and/or mean arterial blood pressure. In this last subgroup, the pattern of cardiovascular changes suggested that this response arose from an acute increase in right ventricular afterload, and was not a consequence of gas-exchange abnormalities. In all cases, reinstitution of iNO promptly reversed worsened hemodynamics and gas exchange. Independent factors associated with an increased risk of cardiovascular collapse included multisystem organ failure, older age, and initial blood pressure increase in response to iNO; a smaller change in the ratio of Pa(O(2)) to FI(O(2)) with initiation of iNO therapy also tended to correlate with this phenomenon. We conclude that careful and monitored discontinuation of iNO in patients with AHRF will identify substantial fractions of patients who are either receiving no benefit from this therapy or who require iNO to maintain an adequate circulation and are therefore at risk for adverse outcome with transport or inadvertent discontinuation of iNO. Future trials of iNO should recognize this complication of such therapy and include assessments for it.


Immunohistochemical distribution of extracellular matrix components and keratin in experimentally induced otitis media.
The distribution of collagen types I, III, and IV and of laminin, fibronectin, and keratin was studied in otitis media experimentally induced by Streptococcus pneumoniae in the chinchilla. The expression of interstitial collagen types I and III and of fibronectin was increased in the subepithelial space that was thickened by inflammation in the acute period of infection. The expression of collagen type IV in the subepithelial space could be seen in the early period. The epithelial cells in the middle ear changed from flat cuboidal to pseudostratified columnar in pneumococcus-inoculated ears, and the number of keratin-positive epithelial cells in the middle ear increased remarkably after infection. These results indicate that changes in epithelial cell differentiation effected by the extracellular matrix correlate with changes in expression of keratin. It is proposed that the extracellular matrix may contribute to tissue repair in the middle ear after bacterial infection by interfering with cell proliferation of epithelial cells and fibroblasts.


Automatic molecular collection and detection by using fuel-powered microengines.
We design and fabricate a simple self-powered system to collect analyte molecules in fluids for surface-enhanced Raman scattering (SERS) detection. The system is based on catalytic Au/SiO/Ti/Ag-layered microengines by employing rolled-up nanotechnology. Pronounced SERS signals are observed on microengines with more carrier molecules compared with the same structure without automatic motions.


The corepressor N-CoR and its variants RIP13a and RIP13Delta1 directly interact with the basal transcription factors TFIIB, TAFII32 and TAFII70.
Repression of transcription by the classical nuclear receptors (e.g. TR, RAR), the orphan nuclear receptors (e.g. Rev-erbAalpha/beta), Mxi-1 and Mad bHLH-zip proteins and the oncoproteins PLZF and LAZ3/BCL6 is mediated by the corepressors N-CoR and SMRT. The interaction of the corepressors with the components involved in chromatin remodelling, such as the recruiting proteins Sin3A/B and the histone deacteylases HDAc-1 and RPD3, has been analysed in detail. The N-CoR/Sin3/HDAc complexes have a key role in the regulation of cellular proliferation and differentiation. However, the interaction of these corepressors with the basal transcriptional machinery has remained obscure. In this study we demonstrated that the N-terminalrepression domains and the receptor interactiondomains (RID) of N-CoR and its splice variants, RIP13a and RIP13Delta1, directly interact with TAFII32 in vivo and in vitro . We show that interaction domain II within the N-CoR and RIP13a RID is required for the interaction with TAFII32. We also observed that N-CoR directly interacts with each of the basal factors, TFIIB and TAFII70, and can simultaneously interact with all three basal factors in a non-competitive manner. Furthermore, we provide evidence that suggests the RVR/Rev-erbbeta-corepressor complex also interacts with the general transcriptional machinery, and that the physicalassociation of TFIIB with N-CoR also occurs in the presence of Sin3B and HDAc-1. Interestingly, we observed that N-CoR expression ablated the functional interaction between TFIIB and TAFII32 that is critical to the initiation of transcription. In conclusion, this study demonstrates that the N-terminal repressor region and the C-terminal RIDs are part of the corepressor contact interface that mediates the interaction with the general transcription factors, and demonstrates that TAFs can also directly interact with corepressors to mediate signals from repressors to the basal machinery. We also suggest that N-CoR interacts with the central components of the transcriptional initiation process (TFIIB, TAFs) and locks them into a non-functional complex or conformation that is not conducive to transcription.


Tobacco tax as a health protecting policy: a brief review of the New Zealand evidence.
To review the evidence relating to tobacco taxation as a health and equity protecting policy for New Zealand. Searches of Medline, EconLit, ECONbase, Index NZ, and library databases for literature on tobacco taxation. The New Zealand evidence indicates that increases in tobacco prices are associated with decreases in tobacco consumption in the general population over the long term. This finding comes from multiple studies relating to: tobacco supplies released from bond, supermarket tobacco sales, household tobacco expenditure data, trends in smoking prevalence data, and from data on calls to the Quitline service. For the 1988-1998 period, the overall price elasticity of demand for all smoking households was estimated to be such that a 10% price increase would lower demand by 5% to 8%. Two studies are suggestive that increased tobacco affordability is also a risk factor for higher youth smoking rates. There is evidence from two studies that tobacco price increases reduce tobacco consumption in some low-income groups and one other study indicates that tobacco taxation is likely to be providing overall health benefit to low-income New Zealanders. These findings are broadly consistent with the very large body of scientific evidence from other developed countries. There is good evidence that tobacco taxation is associated with reduced tobacco consumption in the New Zealand setting, and some limited evidence for equity benefits from taxation increases. Substantial scope exists for improving tobacco taxation policy in New Zealand to better protect public health and to improve equity.


Encoding fear intensity in human sweat.
Humans, like other animals, have an excellent sense of smell that can serve social communication. Although ample research has shown that body odours can convey transient emotions like fear, these studies have exclusively treated emotions as categorical, neglecting the question whether emotion quantity can be expressed chemically. Using a unique combination of methods and techniques, we explored a dose-response function: Can experienced fear intensity be encoded in fear sweat? Specifically, fear experience was quantified using multivariate pattern classification (combining physiological data and subjective feelings with partial least-squares-discriminant analysis), whereas a photo-ionization detector quantified volatile molecules in sweat. Thirty-six male participants donated sweat while watching scary film clips and control (calming) film clips. Both traditional univariate and novel multivariate analysis (100% classification accuracy; Q2: 0.76; R2: 0.79) underlined effective fear induction. Using their regression-weighted scores, participants were assigned significantly above chance (83% > 33%) to fear intensity categories (low-medium-high). Notably, the high fear group (n = 12) produced higher doses of armpit sweat, and greater doses of fear sweat emitted more volatile molecules (n = 3). This study brings new evidence to show that fear intensity is encoded in sweat (dose-response function), opening a field that examines intensity coding and decoding of other chemically communicable states/traits. This article is part of the Theo Murphy meeting issue 'Olfactory communication in humans'.


Si-based technologies for reduction of the pollutant leaching from landfills and mine tails.
Monosilicic and polysilicic acids were shown to react with different types of the pollutants. The direction of these reactions can be managed by changing the monosilicic and polysilicic acid concentration in soil or water media. The objective of this study was to determine the effect of Si-treated calcium metallurgical slag and battery slag on the As, Se, Cd, Pb, Ni, Cr, and Hg mobility and bioavailability in mine tailings (Xikuangshan mine, Hunan, China). The results of column experiment showed that the Si-activated slags reduced leaching of As, Se, Cd, Pb, Ni, Cr, and Hg by 13-89% and transformed them into plant-unavailable forms. The greenhouse test has demonstrated that the Si-treated slags provided reinforced plant resistance to heavy metal toxicity and reduced pollutants in barley and pea leaves. Si-treated local solid slags could be used for creating the biogeochemical barriers on the pollutant streams from landfills or mine tailings sites.


Dilemmas in management of osteoporosis in patients with complete androgen insensitivity syndrome.
Complete androgen insensitivity syndrome (CAIS)-resulting in 46,XY karyotype, but female phenotype-is a disorder of sex development and primary amenorrhea, but its effect on bone mineral density (BMD) is singular and difficult to manage. Androgens are an important modulator of bone remodeling and health, and the androgen receptor (AR) is pivotal for signaling within the bone cells. CAIS results in a severely disrupted AR throughout the body, causing an elevated risk of early osteoporosis. Timing of gonadectomy and hormone replacement therapy protocols are not established, creating a wide variety of treatment plans and BMD profiles. Our objective is to report a patient with CAIS status post prepubertal orchiectomy that developed early osteoporosis and to describe the lack of optimal strategies and consensus available to improve bone health in this population. Additionally, our case illustrates the fact there are no guidelines advocating the use of newer drugs for osteoporosis in this population.


Pharmacological activity of novel 2-hydroxyacetophenone isatin derivatives on cardiac and vascular smooth muscles in rats.
Isatin (1H-indole-2,3 dione) is an endogenous compound with biological activities. Many of its derivatives have pharmacological effects, including inhibition of cyclic guanosine monophosphate levels in cardiac tissue; sedative-hypnotic profiles; anticonvulsant, analgesic, antithermic, and anti-inflammatory activities; and anxiolytic, antimicrobial, and proapoptotic effects. Carbamates derived from isatin have a vasorelaxant profile. This study investigated the activity of 2 novel 2-hydroxyacetophenone derivatives of isatin (named MB101 and MB130) on the contractility of rat aorta and papillary muscles. Both compounds induced a concentration-dependent relaxation (5-100 μM) in the endothelium-intact aorta that was abolished by N-nitro-L-arginine methyl ester. Atropine, a muscarinic receptor antagonist, significantly prevented vasodilatation of 100 μM MB101. In contrast, atropine caused no significant alteration in MB130-induced vasorelaxation. Naloxone, a nonselective opioid receptor antagonist, completely prevented the relaxing effect of MB101 and MB130 at all concentrations. In papillary muscles, only MB130 induced a significant depression, and this contractile response was not altered by propranolol and atropine. Both the compounds reduced systolic and diastolic pressures in a dose-dependent manner in anesthetized rats. The 2-hydroxyacetophenones produced direct effects on vascular tonus through either muscarinic or opioid pathways. MB130 produced cardiac depression by opioid receptors and bradykinin because pretreatment HOE140 or with naloxone, an antagonist of type-2, bradykinin were able to partially block the decrease in twitch amplitude in papillary muscles induced by MB130. These findings provide information for designing new strategies for the treatment of cardiovascular disorders.


Silencer of death domains controls cell death through tumour necrosis factor-receptor 1 and caspase-10 in acute lymphoblastic leukemia.
Resistance to apoptosis remains a significant problem in drug resistance and treatment failure in malignant disease. NO-aspirin is a novel drug that has efficacy against a number of solid tumours, and can inhibit Wnt signaling, and although we have shown Wnt signaling to be important for acute lymphoblastic leukemia (ALL) cell proliferation and survival inhibition of Wnt signaling does not appear to be involved in the induction of ALL cell death. Treatment of B lineage ALL cell lines and patient ALL cells with NO-aspirin induced rapid apoptotic cell death mediated via the extrinsic death pathway. Apoptosis was dependent on caspase-10 in association with the formation of the death-inducing signaling complex (DISC) incorporating pro-caspase-10 and tumor necrosis factor receptor 1 (TNF-R1). There was no measurable increase in TNF-R1 or TNF-α in response to NO-aspirin, suggesting that the process was ligand-independent. Consistent with this, expression of silencer of death domain (SODD) was reduced following NO-aspirin exposure and lentiviral mediated shRNA knockdown of SODD suppressed expansion of transduced cells confirming the importance of SODD for ALL cell survival. Considering that SODD and caspase-10 are frequently over-expressed in ALL, interfering with these proteins may provide a new strategy for the treatment of this and potentially other cancers.


Expanding health insurance coverage in vulnerable groups: a systematic review of options.
Vulnerable groups are often not covered by health insurance schemes. Strategies to extend coverage in these groups will help to address inequity. We used the existing literature to summarize the options for expanding health insurance coverage, describe which countries have tried these strategies, and identify and describe evaluation studies. We included any report of a policy or strategy to expand health insurance coverage and any evaluation and economic modelling studies. Vulnerable populations were defined as children, the elderly, women, low-income individuals, rural population, racial or ethnic minorities, immigrants, and those with disability or chronic diseases. Forty-five databases were searched for relevant documents. The authors applied inclusion criteria, and extracted data using pre-coded forms, on contents of health insurance schemes or programmes, and used the framework approach to establish categories. Of the 21,528 articles screened, 86 documents were finally included. Descriptions about the USA dominated (72), with only five from Africa, six from Asia and two from South America. We identified six main categories: (1) changing eligibility criteria of health insurance; (2) increasing public awareness; (3) making the premium more affordable; (4) innovative enrollment strategies; (5) improving health care delivery; and (6) improving management and organization of the insurance schemes. All six categories were found in the literature about schemes in the USA, and schemes often included components from each category. Strategies in developing countries were much more limited in their scope. Evaluation studies numbered 25, of which the majority were of time series design. All studies found that the expansion strategies were effective, as assessed by the author(s). In countries expanding coverage, the categories identified from the literature can help policy makers consider their options, implement strategies where it is common sense to do so and establish appropriate implementation monitoring.


[Animal tissue polynucleotide phosphorylase].
Localization, physico-chemical and catalytic properties and possible biological functions of polynucleotide phosphorylase (PNPase) from animal tissues are discussed. In animal tissue cells PNPase has multiple localization; the major amount of the enzyme is localized in the endoplasmic reticulum ribosomes. In the nuclei PNPase, similar to other endo- and exo-RNAses participates in the processing of precursor molecules of mature forms of RNA, whereas in the cytoplasm it is involved in the destruction of polyribosomes in the polyribosomes of rapidly growing tissues the activity of PNPase is extremely decreased. The mechanisms regulating the PNPase activity in rapidly growing tissues are discussed.


Not chewing food among the Thai elderly with complete denture.
The study aims to investigate the use of a complete denture in terms of not chewing food and determining the strength of association between not chewing food and several potential risk factors among the Thai elderly. Under the support of the "Khao Aroi" or "Delicious Rice" or "Dental Implant" Project of Institute of Dentistry, Department of Medical Services, Ministry of Public Health, and in co-operation with the Ministry of Science and Technology during 2007-2011, a cross-sectional survey by multi-stage cluster sampling was conducted in 2008, in 21 provinces, 87 hospitals, with 2,676 Thai elderly. The sample was drawn from a sampling frame of 58,043 target Thai people aged 60 years and over under the Dental Prosthesis Service Campaign (DPSC) project during 2005 and 2007. All Thai elderly, who received a complete denture from the DPSC project at least three months prior were surveyed from May to October 2008 through questionnaires. Data were analyzed by a set of descriptive analyses and binary logistic regression models. Not chewing food among the Thai elderly, after receiving a complete denture, was 12.5%, quite a bit more effective than ordinary work. Nontaluck found 38% for the proportion not wearing dentures in the 30-baht health care program. This finding is confirmed by the work of Dalodom et al that the use of dentures by Thai elderly was 93% in the DPSC project. The important risk factors that influenced not to chew food were satisfaction with dentures, patients satisfaction with the denture fitting and care, while controlling the amount of dentures, respectively. Satisfaction of patients with their dentures, good oral health care in fitting denture work, and good communication between dentists and patients are important keys affecting the use of dentures.


Biotic mortality factors affecting emerald ash borer (Agrilus planipennis) are highly dependent on life stage and host tree crown condition.
Emerald ash borer (EAB), Agrilus planipennis, is a serious invasive forest pest in North America responsible for killing tens to hundreds of millions of ash trees since it was accidentally introduced in the 1990 s. Although host-plant resistance and natural enemies are known to be important sources of mortality for EAB in Asia, less is known about the importance of different sources of mortality at recently colonized sites in the invaded range of EAB, and how these relate to host tree crown condition. To further our understanding of EAB population dynamics, we used a large-scale field experiment and life-table analyses to quantify the fates of EAB larvae and the relative importance of different biotic mortality factors at 12 recently colonized sites in Maryland. We found that the fates of larvae were highly dependent on EAB life stage and host tree crown condition. In relatively healthy trees (i.e., with a low EAB infestation) and for early instars, host tree resistance was the most important mortality factor. Conversely, in more unhealthy trees (i.e., with a moderate to high EAB infestation) and for later instars, parasitism and predation were the major sources of mortality. Life-table analyses also indicated how the lack of sufficient levels of host tree resistance and natural enemies contribute to rapid population growth of EAB at recently colonized sites. Our findings provide further evidence of the mechanisms by which EAB has been able to successfully establish and spread in North America.


[Prevention of infection transmission in dental laboratories].
The professional activity in a dental laboratory is associated with a high risk for infection transmission through the manipulation of impressions and prostheses contaminated with patients' saliva and blood. To assess the compliance of dental technicians in lasi town dental laboratories with the methods used for preventing infection transmission in their practices. This questionnaire-based survey included 61 dental technicians aged 22 to 58 years from 29 dental laboratories. The 17 questions were related to the protection equipment, air ventilation, and disinfection of surfaces, instruments, impressions, and prostheses. SPSS 14 system, Chi-Square test were used for data analysis, and the levels of statistical significance were set at p < 0.05. 90.2% of the subjects claim the need of prosthetic items disinfection upon arrival at the laboratory from the dental office (p < 0.05). The protection equipment is used by 49.1% of the dental technicians included in this survey (full equipment 18.0%, safety glasses 45.9%, mask 37.7%, rubber gloves 19.6%). 59.1% of the laboratories are provided with air ventilation, while surface disinfection is common practice in 85.2%. Of the study subjects 62.1% disinfect the impressions, 26.1% the final prosthesis, and 25.0% disinfect the interocclusal registrations (p < 0.05). Educational programs aimed at increasing dental technicians' awareness of infection control by adopting the most effective prevention measures are essential for reducing the incidence of technicians, dentists, and patients; exposure.


The peripheral nervous system supports blood cell homing and survival in the Drosophila larva.
Interactions of hematopoietic cells with their microenvironment control blood cell colonization, homing and hematopoiesis. Here, we introduce larval hematopoiesis as the first Drosophila model for hematopoietic colonization and the role of the peripheral nervous system (PNS) as a microenvironment in hematopoiesis. The Drosophila larval hematopoietic system is founded by differentiated hemocytes of the embryo, which colonize segmentally repeated epidermal-muscular pockets and proliferate in these locations. Importantly, we show that these resident hemocytes tightly colocalize with peripheral neurons and we demonstrate that larval hemocytes depend on the PNS as an attractive and trophic microenvironment. atonal (ato) mutant or genetically ablated larvae, which are deficient for subsets of peripheral neurons, show a progressive apoptotic decline in hemocytes and an incomplete resident hemocyte pattern, whereas supernumerary peripheral neurons induced by ectopic expression of the proneural gene scute (sc) misdirect hemocytes to these ectopic locations. This PNS-hematopoietic connection in Drosophila parallels the emerging role of the PNS in hematopoiesis and immune functions in vertebrates, and provides the basis for the systematic genetic dissection of the PNS-hematopoietic axis in the future.


Advances and challenges in the surgical treatment of metastatic bone disease.
There are numerous challenges facing the orthopaedic surgeon who treats metastatic bone disease in the twenty-first century. The orthopaedic surgeon must be familiar with the indications for surgical intervention, the available implants for fixation of a given anatomic lesion, the appropriateness of fixation versus resection and replacement, and the viability of newer, less invasive treatment options for a given lesion. Determination of the best surgical candidates still is controversial, especially in the arena of prophylactic treatment. Recent advances have made fixation with intramedullary devices and standard plates simpler and more rigid. The advent and improvement of megaprostheses has made complex joint reconstructions more durable. Advances in interventional radiology such as radiofrequency ablation and percutaneous vertebroplasty and acetabuloplasty with polymethylmethacrylate (PMMA) continue to be promising options for future treatment. Better methods are necessary to evaluate the status of the patients preoperatively and postoperatively, to classify functional improvement after surgical treatment, and to determine the impact of treatment on the quality of life.


Retinoic acid and interferon alpha act synergistically as antiangiogenic and antitumor agents against human head and neck squamous cell carcinoma.
Head and neck squamous cell carcinoma (HNSCC) is an aggressive malignancy in which multiple independent lesions develop over time throughout the mucosa of the upper aerodigestive tract. Therefore, the comprehensive treatment of this neoplasm must include a chemopreventive arm to hold premalignant lesions in check, a role well-suited to antiangiogenic agents. Retinoic acid (RA) and interferon alpha (IFN-alpha), drugs with known biological activity against HNSCC when used individually, are also inhibitors of angiogenesis. Here we show that they are remarkably synergistic antiangiogenic agents able to inhibit both the growth and the neovascularization of HNSCC injected into the floor of the mouth of nude mice. The mechanism of action of these drugs as antiangiogenic agents was 2-fold. They decreased the angiogenic activity of the tumor cells, and they caused the endothelial cells to become refractory to inducers of angiogenesis. When tumor cells were treated in vitro with IFN-alpha A/D, there was a dramatic drop in their secretion of interleukin-8, the major angiogenic factor produced by these tumors. When combined with RA, which causes tumor cells to secrete an inhibitor of angiogenesis, there was a synergistic inhibition of both tumor cell growth and secreted angiogenic activity. The combination of RA and IFN-alpha also acted synergistically on endothelial cells by reducing their responsiveness to both interleukin-8 and tumor conditioned media. Doses of each drug could be reduced by two logs without loss of activity. When animals bearing human HNSCC tumor cells were treated systemically with a combination of RA and IFN-alpha A/D at doses that were ineffective when used alone, dramatic decreases in both tumor growth and tumor angiogenesis were seen. These data suggest that the use of antiangiogenic mixtures may be a particularly effective way to design future chemoprevention protocols against HNSCC.


[The methodological characteristics of determining the basic and trace elements in the serum and peripheral blood cells by the x-ray fluorescence method].
Analytical parameters of instrumental methods of the element analysis of biomedical objects are compared and the place occupied by x-ray fluorescent analysis (RFA) among them is demonstrated. The methods for preparing the specimens of liquid media of the organism and the RFA are simple, rapid, involve no disintegration of the sample, and allow measurements of elements at sigma 1 = 0.02 at concentrations of 12 micrograms/ml. The method is preferable and promising for some basic elements (P, S, Cl, K, Ca), which are difficult to measure by other methods. The levels of S, K, Ca, Fe, Zn, and Cu were measured in erythrocytic mass and blood serum of normal subjects, patients with asthma and aplastic anemia, and recipients of allogenic kidneys.


Overexpression of the fat mass and obesity associated gene (FTO) in breast cancer and its clinical implications.
Incidence of breast cancer is increasing and seems to be associated with fatty foods, metabolism, and so on. The fat mass and obesity associated gene (FTO) has been intensively investigated in diabetes, obesity and the other diseases. Previous studies have reported that FTO SNPs are associated with breast cancer risk. Here, we investigated the expression of FTO in human breast cancer tissues and its relationship with the clinicopathological features. In this retrospective study, tissues from 79 patients with breast cancer were collected, as well as 43 cases of adjacent breast tissues. Immunohistochemistry was used to detect the expression of FTO. Statistical analysis was performed to assess the association between FTO expression and the clinicopathological features of breast cancer. FTO was expressed in both mammary epithelial and breast cancer tissues, but with different degree. The expression level of FTO in breast cancer tissues was significantly higher than that in the adjacent breast tissues (P < 0.001). The percentage of FTO-positive expression in cases with hormone receptor (HR) negative and HER2 amplification was significantly higher than that in those with HR positive and HER2 negative (P = 0.001, P < 0.001). The positivity rate of FTO in breast cancer with P53 positive and histological grade 3 seemed to be higher than that with P53 negative and histological grade 1 or 2, respectively (P = 0.077, P = 0.082). There was no association between FTO expression and age, T stage, LN status, TNM stage, Ki67, and BMI in breast cancer. Besides, FTO expression in HER2-overexpressed subtype was significantly higher than that in Triple-negative and Luminal A/B1 subtypes (P < 0.001). Our study suggests that FTO expression may have a vital role in the carcinogenesis of breast cancer, especially in HER2-overexpressed breast cancer.


Young adult birthday celebrations as windows of risk for alcohol and cannabis use: 21st birthdays compared to other young adult birthdays.
Alcohol use among college students during 21st birthday celebrations constitutes a well-known example of event-specific drinking when alcohol use is both pervasive and heavy. Less is known about how 21st birthday alcohol use compares to other birthday celebrations during young adulthood, whether similar increases occur for cannabis use on 21st birthdays, and whether the "21st birthday effect" is similar for noncollege young adults. Alcohol and cannabis use during 19th to 25th birthday celebrations were explored among college and noncollege students. Participants were 720 young adults of ages 18 to 23 (M = 21.1, SD = 1.7) at enrollment who completed 24 monthly surveys, and 204 reported on a 21st birthday. Participants resided in a state where cannabis was legal and were asked the month following their birthday whether they engaged in alcohol and cannabis use as part of their birthday celebration. Multilevel models found a 21st birthday effect for alcohol use as individuals consumed over twice as many drinks on their 21st birthday than would have been expected given age trends in birthday drinking, and this effect held for college and noncollege students. A 21st birthday effect for cannabis was not found. 21st birthday celebrations represent a high-risk drinking event for young adults in general, and the current findings suggest event-specific prevention programs targeting all young adults turning 21 are warranted. Unlike alcohol where turning 21 is associated with socially and culturally normative use, a similar 21st birthday effect was not found for cannabis. (PsycInfo Database Record (c) 2022 APA, all rights reserved).


Investigating racial differences in coping with chronic osteoarthritis pain.
Osteoarthritis is a prevalent disease in older patients of all racial groups, and it is known to cause significant pain and functional disability. Racial differences in how patients cope with the chronic pain of knee or hip osteoarthritis may have implications for utilization of treatment modalities such as joint replacement. Therefore, we examined the relationships between patient race and pain coping strategies (diverting attention, reinterpreting pain, catastrophizing, ignoring sensations, hoping and praying, coping self-statements, and increasing behavior activities) for hip and knee osteoarthritis. This is a cross-sectional survey of 939 veterans 50 to 79 years old with chronic hip or knee osteoarthritis pain recruited from VA primary care clinics in Philadelphia and Pittsburgh. Patients had to have moderate to severe hip or knee osteoarthritis symptoms as measured by the WOMAC index. Standard, validated instruments were used to obtain information on attitudes and use of prayer, pain coping strategies, and arthritis self-efficacy. Analysis included separate multivariable models adjusting for demographic and clinical characteristics. Attitudes on prayer differed, with African Americans being more likely to perceive prayer as helpful (adjusted OR = 3.38, 95% CI 2.35 to 4.86) and to have tried prayer (adjusted OR = 2.28, 95% 1.66 to 3.13) to manage their osteoarthritis pain. Upon evaluating the coping strategies, we found that, compared to whites, African Americans had greater use of the hoping and praying method (beta = 0.74, 95% CI 0.50 to 0.99). Race was not associated with arthritis pain self-efficacy, arthritis function self-efficacy, or any other coping strategies. This increased use of the hoping and praying coping strategy by African Americans may play a role in the decreased utilization of total joint arthroplasty among African Americans compared to whites. Further investigation of the role this coping strategy has on the decision making process for total joint arthroplasty should be explored.


Comparison of viral and nonviral vectors for gene transfer to human endothelial progenitor cells.
The ability of endothelial progenitor cells (EPCs) to home to sites of neoangiogenesis makes them attractive candidates for use in the field of gene therapy. The efficacy of this approach depends on the efficiency of the vector used for transgene delivery. In this study, we have compared the efficiency of adenovirus, five serotypes of AAV2, VSVG-pseudotyped lentivirus, and nonviral plasmid/liposome DNA vectors to deliver the green fluorescence protein reporter gene to human early EPCs to determine efficacy and vector-related cell toxicity. Adenovirus proved most effective with efficiencies of up to 80% with low levels of cell death. Lower levels of expression were seen with other vectors. Electroporation proved unsuitable at the parameters tested. We have also identified at least two distinct subpopulations that exist in the heterogeneous parent EPC culture, one of which is amenable to transduction with adenovirus and one that is not. In addition, adenoviral transduction did not disrupt the ability of the cells to incorporate into endothelial structures in vitro. We have found adenovirus to be the most efficient of the vector systems tested for gene delivery to EPCs, an effect that is mediated almost entirely by one of two identified subpopulations.


Multiple dentoalveolar traumatic injury: a case report (3 years follow up).
Dental trauma with children and adolescents is a serious dental public health problem. Traumatic injuries on permanent teeth are common, and dramatic episodes can occur during childhood. Cases of dental avulsions and reimplantations, dentoalveolar fractures, several forms (lateral, extrusive and intrusive) of luxations, concussion, subluxation, gingival lacerations and hard, pulpal dental tissue lesions have been extensively reported. This case report presents the therapy for severe trauma caused by multiple traumatic injuries to the dentoalveolar complex of a patient.


Multiplex mRNA profiling for the identification of body fluids.
We report the development of a multiplex reverse transcription-polymerase chain reaction (RT-PCR) method for the definitive identification of the body fluids that are commonly encountered in forensic casework analysis, namely blood, saliva, semen, and vaginal secretions. Using selected genes that we have identified as being expressed in a tissue-specific manner we have developed a multiplex RT-PCR assay which is composed of eight body fluid-specific genes and that is optimized for the detection of blood, saliva, semen, and vaginal secretions as single or mixed stains. The genes include beta-spectrin (SPTB) and porphobilinogen deaminase (PBGD) for blood, statherin (STATH) and histatin 3 (HTN3) for saliva, protamine 1 (PRM1) and protamine 2 (PRM2) for semen, and human beta-defensin 1 (HBD-1) and mucin 4 (MUC4) for vaginal secretions. The known or presumed functions of these genes suggest an extremely restricted pattern of gene expression, which is a basic requirement for incorporation into a tissue-specific assay. The methodology is based upon gene expression profiling analysis in which the body fluid-specific genes are identified by detecting the presence of appropriate mRNA species using capillary electrophoresis/laser induced fluorescence. An mRNA-based approach, such as the multiplex RT-PCR method described in the present work, allows for the facile identification of the tissue components present in a body fluid stain and could supplant the battery of serological and biochemical tests currently employed in the forensic serology laboratory.


Outcome of surgical resection of pulmonary metastasis from urinary tract transitional cell carcinoma.
There is little information on pulmonary metastasectomy of urinary tract transitional cell carcinoma (TCC). In this study, we examined the long-term outcome and the factors associated with long-term survival after pulmonary metastasectomy of urinary tract TCC based on a 20-year single center experience. Between 1984 and 2005, 18 patients (12 men, six women) underwent pulmonary metastasectomy of the urinary tract TCC in our hospital. The clinicopathological and surgical data of these patients obtained from the medical records were analyzed in this retrospective study. The time interval between lung resection and death, or latest follow-up ranged from two to 200 months (median 52). Survival analysis was conducted by the Kaplan-Meier method and log-rank test. The cumulative three- and five-year survival rates were 59.8% and 46.5%, respectively. The number of resected metastatic tumors (solitary vs. multiple) was associated with long-term survival (P<0.05). The five-year survival rate of patients with solitary metastasis was 85.7% while that of patients with multiple metastases was 20.0%. Pulmonary metastasectomy of urinary tract TCC is associated with a favorable outcome, and solitary metastasis is associated with long-term survival. Aggressive management of solitary pulmonary metastasis from a urinary tract TCC is feasible in selected patients.


Usefulness of the Eosinophilic Esophagitis Histologic Scoring System in Distinguishing Active Eosinophilic Esophagitis From Remission and Gastroesophageal Reflux Disease.
Eosinophilic esophagitis (EoE) is defined as esophageal dysfunction in the presence of > 15 intraepithelial eosinophils per high-power field (eos/hpf) in either the mid or distal esophagus. The current focus of EoE pathologic evaluation is the peak eosinophil count (PEC), although histologic features other than eosinophilic inflammation are also commonly observed. In addition, histologic variance between the mid and distal esophagus in EoE has not been rigorously studied. The aim of our study was to utilize a recently developed EoE histologic scoring system (EoEHSS) to compare the mid and the distal esophageal histology in patients with active EoE (EoE-A), EoE in remission (EoE-R), and gastroesophageal reflux disease (GERD). EoEHSS was used to prospectively evaluate the severity and extent of changes in multiple histopathologic features (PEC; basal zone hyperplasia (BZH); eosinophilic abscesses (EA); eosinophil surface layering (ESL); dilated intercellular spaces (DIS); surface epithelial alteration (SEA); dyskeratotic epithelial cells (DEC); lamina propria fibrosis (LPF)) in the mid and distal esophageal biopsies in 85 pediatric patients at a tertiary medical center. These patients were divided into three cohorts: EoE-A (n = 36), EoE-R (n = 12) and GERD (n = 37). Total grade (severity) and stage (extent) scores were significantly higher in EoE-A compared to EoE-R and GERD patients in both the mid and the distal esophagus. The mean total grade scores in the mid esophagus, but not the distal esophagus remained higher in EoE-R as compared to GERD patients. Specific histopathologic features independent of PEC were different in distal and mid esophagus in EoE-A. About one-half of children with active EoE had different EoEHSS scores in their mid and distal esophageal biopsies. EoEHSS yields histologic insights beyond those derived from PEC and helps in more objective, reproducible and accurate diagnosis of EoE and GERD. It also provides a more comprehensive understanding into the pathophysiology of EoE.


In Vitro Activity of Cefiderocol against a Global Collection of Carbapenem-Resistant Acinetobacter baumannii Isolates.
Background: Cefiderocol is a novel siderophore cephalosporin with potent activity against multi-drug-resistant Gram-negative pathogens including carbapenem-resistant Acinetobacter baumannii (CRAB). Methods: The susceptibility of 313 non-duplicate CRAB isolates with defined carbapenem resistance mechanisms from a global collection to cefiderocol, ceftazidime, ceftazidime/avibactam, ceftolozane/tazobactam, ciprofloxacin, colistin, imipenem/relebactam, meropenem, meropenem/vaborbactam, minocycline, and piperacillin/tazobactam was determined using the broth microdilution method. Isolates were obtained from various body sites from patients in 47 countries in five world regions between 2012 and 2016. The identification of carbapenem resistance mechanisms and assignment to A. baumannii international clonal lineages were based on whole genome sequencing. Results: Cefiderocol showed greater activity than comparator antimicrobials of the β-lactam class, including novel β-lactams combined with β-lactamase inhibitors, ciprofloxacin, and minocycline. Cefiderocol MIC50 and MIC90 values were 0.5 mg/L and 4 mg/L, respectively, while colistin had comparable activity with a higher MIC50 at 1 mg/L and a lower MIC90 value of 2 mg/L. Many isolates with elevated cefiderocol MICs ≥ 4 mg/L represented A. baumannii international clone (IC) 1 and harbored a metallo-β-lactamase. Conclusions: While cefiderocol is a useful addition to the limited armamentarium of drugs targeting this problematic pathogen, a considerable part of CRAB isolates had elevated MIC values in a range of 4 -> 32 mg/L, including all isolates with a metallo-β-lactamase.


MicroRNA-21 orchestrates high glucose-induced signals to TOR complex 1, resulting in renal cell pathology in diabetes.
Hyperglycemia induces a wide array of signaling pathways in the kidney that lead to hypertrophy and matrix expansion, eventually culminating in progressive kidney failure. High glucose-induced reduction of the tumor suppressor protein phosphatase and tensin homolog deleted in chromosome 10 (PTEN) contributes to renal cell hypertrophy and matrix expansion. We identified microRNA-21 (miR-21) as the molecular link between high glucose and PTEN suppression. Renal cortices from OVE26 type 1 diabetic mice showed significantly elevated levels of miR-21 associated with reduced PTEN and increased fibronectin content. In renal mesangial cells, high glucose increased the expression of miR-21, which targeted the 3'-UTR of PTEN mRNA to inhibit PTEN protein expression. Overexpression of miR-21 mimicked the action of high glucose, which included a reduction in PTEN expression and a concomitant increase in Akt phosphorylation. In contrast, expression of miR-21 Sponge, to inhibit endogenous miR-21, prevented down-regulation of PTEN and phosphorylation of Akt induced by high glucose. Interestingly, high glucose-stimulated miR-21 inactivated PRAS40, a negative regulator of TORC1. Finally, miR-21 enhanced high glucose-induced TORC1 activity, resulting in renal cell hypertrophy and fibronectin expression. Thus, our results identify a previously unrecognized function of miR-21 that is the reciprocal regulation of PTEN levels and Akt/TORC1 activity that mediate critical pathologic features of diabetic kidney disease.


Huang-Lian-Jie-Du-Decotion induced protective autophagy against the injury of cerebral ischemia/reperfusion via MAPK-mTOR signaling pathway.
Huang-Lian-Jie-Du-Decotion (HLJDD, Hwangryun-Hae-Dok-Decotion in Japan), an ancient antipyretic and detoxifying traditional Chinese medicine formula, was reported to have protective effect on ischemic stroke. To investigate the therapeutic effect of HLJDD on ischemic stroke and explore its mode of action. A model of ischemic stroke in the rat was established after transient middle cerebral artery occlusion (MCAO) followed by reperfusion. Rats were assigned randomly to groups of control, sham, transient ischemia/reperfusion (I/R), and three treatment groups by HLJDD at 2.5, 5.0, 10.0mg/kg. The neurological deficit, the cerebral infarct size, morphology abnormality, biochemical parameters were examined, and the levels of relevant proteins were determined by immunoblotting analysis to evaluate the protective effects of HLJDD on ischemic stroke and explore the underlying mechanism. Compared with I/R group, HLJDD significantly ameliorated neurological deficit and histopathology changes, decreased infarct area, and restored the levels of biochemical indicators including nitric oxide (NO), malondialdehyde (MDA), glutathione (GSH), glutathione disulfide (GSSG), total superoxide dismutase (T-SOD), Cu/Zn-SOD, Mn-SOD and glutathione peroxidase (GSH-PX). HLJDD also notably elevated the levels of microtubule-associated protein 1 light chain 3 (LC3), Beclin-1, and other autophagy related genes (Atgs), promoted the activation of extracellular signal-regulated kinases (ERK), protein kinase B (Akt), 3-phosphoinositide-dependent kinase (PDK1), and inhibited the activation of mammalian target of rapamycin (mTOR), c-Jun N-terminal protein kinases (JNK), p38, phosphatase and tensin homolog (PTEN). HLJDD showed neuroprotective effects on ischemic stroke, at least in part to the induced protective autophagy via the regulation of mitogen-activated protein kinase (MAPK) signals. This Akt-independent protective autophagy is favorable in the treatment of stroke, avoiding unfavorable side-effects associated with the inactivation of Akt. The efficacy of HLJDD on ischemic stroke and its safety warranted by its long-term clinical use in traditional Chinese medicine favored further study to develop HLJDD as an effective therapeutic agent to treat ischemic stroke.


Percutaneous injection of metrizamide into spinal cord cysts for preoperative diagnosis of syringomyelia.
Five cases of syringomyelia are reported in which the spinal cysts were percutaneously punctured and filled with metrizamide for preoperative diagnosis. There were no side effects from the puncture or the contrast medium. In all cases the cyst was larger than had been demonstrated by previous myelography. A communication to the fourth ventricle was seen in two cases. Four patients had surgical treatment; the neurologic deficits improved in two patients, while the condition of the others has remained unchanged.


Naturally rare versus newly rare: demographic inferences on two timescales inform conservation of Galápagos giant tortoises.
Long-term population history can influence the genetic effects of recent bottlenecks. Therefore, for threatened or endangered species, an understanding of the past is relevant when formulating conservation strategies. Levels of variation at neutral markers have been useful for estimating local effective population sizes (N e ) and inferring whether population sizes increased or decreased over time. Furthermore, analyses of genotypic, allelic frequency, and phylogenetic information can potentially be used to separate historical from recent demographic changes. For 15 populations of Galápagos giant tortoises (Chelonoidis sp.), we used 12 microsatellite loci and DNA sequences from the mitochondrial control region and a nuclear intron, to reconstruct demographic history on shallow (past ∽100 generations, ∽2500 years) and deep (pre-Holocene, >10 thousand years ago) timescales. At the deep timescale, three populations showed strong signals of growth, but with different magnitudes and timing, indicating different underlying causes. Furthermore, estimated historical N e of populations across the archipelago showed no correlation with island age or size, underscoring the complexity of predicting demographic history a priori. At the shallow timescale, all populations carried some signature of a genetic bottleneck, and for 12 populations, point estimates of contemporary N e were very small (i.e., < 50). On the basis of the comparison of these genetic estimates with published census size data, N e generally represented ∽0.16 of the census size. However, the variance in this ratio across populations was considerable. Overall, our data suggest that idiosyncratic and geographically localized forces shaped the demographic history of tortoise populations. Furthermore, from a conservation perspective, the separation of demographic events occurring on shallow versus deep timescales permits the identification of naturally rare versus newly rare populations; this distinction should facilitate prioritization of management action.


Occurrence of secondary ischemic events among persons with atherosclerotic vascular disease.
Few data exist for large managed care populations on the occurrence of subsequent acute ischemic events in persons with established atherosclerotic vascular disease. We estimated the occurrence of secondary stroke, acute myocardial infarction (AMI), and vascular deaths among 2 large, managed care samples. With the use of International Classification of Diseases, Ninth Revision, Clinical Modification codes, patients aged > or =40 years and with stroke, AMI, or peripheral arterial disease (PAD) were identified from administrative data of UnitedHealthcare plans during 1995-1998. Stroke, AMI, and PAD cohorts were identified within a commercial insurance sample and a Medicare sample. Cumulative occurrences of subsequent stroke, AMI, or vascular death were estimated by survival analysis. In the stroke commercial cohort (n=1631; mean age, 62.1 years), cumulative occurrence of subsequent events was 4.2%, 6.5%, 9.8%, and 11.8% at 0.5, 1, 2, and 3 years, respectively; cumulative secondary event occurrence in the AMI commercial cohort (n=6458; mean age, 56.0 years) was 3.5%, 4.8%, 7.3%, and 8.5% and in the PAD commercial cohort (n=5813; mean age, 59.2 years) was 1.5%, 2.8%, 4.8%, and 6.5%, respectively. Cumulative secondary event occurrences were even higher in stroke (n=1518; mean age, 79.5 years), AMI (n=2197; mean age, 76.2 years), and PAD (n=5033; mean age, 76.6 years) cohorts of the Medicare sample: 18.1%, 17.0%, and 8.7%, respectively, at 3 years. More than 75% of each stroke cohort's secondary events were strokes; more than 75% of each AMI cohort's secondary events were AMIs. Of the PAD cohorts' secondary events, 27% to 39% were strokes, 48% to 57% were AMIs, and 13% to 16% were vascular deaths. Among these managed care enrollees with existing atherosclerotic vascular disease, subsequent ischemic events represent a significant symptomatic disease burden. Given these findings, it is very important to determine whether secondary prevention strategies are being effectively used to manage patients with diagnosed atherosclerosis.


Clinical, epidemiological, and etiological profile of inpatients with community-acquired pneumonia at a general hospital in the Sumaré microregion of Brazil.
To analyze the clinical, etiological, and epidemiological aspects of community-acquired pneumonia (CAP) in hospitalized individuals. We prospectively studied 66 patients (> 14 years of age) with CAP admitted to the Hospital Estadual Sumaré, located in the Sumaré microregion of Brazil, between October of 2005 and September of 2007. We collected data related to clinical history, physical examination, pneumonia severity index (PSI) scores, and laboratory tests (blood culture; sputum smear microscopy and culture; serology for Chlamydophila pneumoniae, Mycoplasma pneumoniae, and Legionella pneumophila; and detection of Legionella sp. and Streptococcus pneumoniae antigens in urine). The mean age of patients was 53 years. Most had a low level of education, and 55.7% presented with at least one comorbidity at the time of hospitalization. The proportion of elderly people vaccinated against influenza was significantly lower among the inpatients than in the general population of the Sumaré microregion (52.6% vs. > 70%). Fever was less common among the elderly patients (p < 0.05). The clinical evolution was associated with the PSI scores but not with age. The etiology was confirmed in 31 cases (50.8%) and was attributed to S. pneumoniae, principally detected by the urinary antigen test, in 21 (34.4%), followed by C. pneumoniae, in 5 (8.2%). The mortality rate was 4.9%, and 80.3% of the patients were classified as cured at discharge. The knowledge of the etiologic profile of CAP at the regional level favors the appropriate choice of empirical treatment, which is particularly relevant in elderly patients and in those with comorbidities. The lack of influenza vaccination in elderly patients is a risk factor for hospitalization due to CAP.


Clinical pharmacokinetics of AZD3199, an inhaled ultra-long-acting β2-adrenoreceptor agonist (uLABA).
The clinical pharmacokinetics of AZD3199, an ultra-long-acting β2-agonist, were investigated in healthy volunteers and patients with asthma or chronic obstructive pulmonary disease (COPD). Five studies are presented: one single ascending dose study in healthy Caucasian males; two multiple ascending dose studies in healthy males, one in Caucasians and one in Japanese; a Phase IIA asthma study; and a Phase IIB COPD study. Subjects received AZD3199 via a Spira nebulizer (Turbuhaler; equivalent delivered doses 5-3200 μg) or Turbuhaler (single delivered doses of 120-1920 μg or repeated delivered once-daily doses 240-1,680 μg). AZD3199 pharmacokinetics were assessed using total plasma concentration and urinary excretion, and tolerability using adverse events, clinical laboratory tests, and physical examinations. AZD3199 appeared rapidly in the systemic circulation following single and multiple dosing in healthy volunteers and patients (maximum plasma concentration within 30 minutes), with dose-proportional time-independent pharmacokinetics. Plasma exposure to unmetabolized drug was similar in healthy volunteers and patients with asthma, but relatively lower in patients with COPD. Estimated terminal half-life was up to 142 hours in healthy Caucasian males. AZD3199 was well tolerated and showed no or at most mild systemic effects. AZD3199 plasma exposure in healthy volunteers and patients suggested linear pharmacokinetics and a long half-life. Systemic availability was similar in healthy subjects and patients with asthma, but was lower in patients with COPD. These clinical trials suggest that AZD3199 is well-tolerated in healthy male volunteers and patients, with no safety concerns identified to preclude further evaluation.


High immunogenicity of intracellular myelin oligodendrocyte glycoprotein epitopes.
Multiple sclerosis (MS) is an inflammatory and demyelinating disease of the CNS with associated axonal loss. There is strong evidence for an autoimmune pathogenesis driven by myelin-specific T cells. Myelin oligodendrocyte glycoprotein (MOG) induces a type of experimental autoimmune encephalomyelitis in animals which is very MS-like since there are demyelinating CNS lesions and axonal loss. This underscores the potential role of MOG in MS pathogenesis. We performed a T cell reactivity pattern analysis of MS patients at the onset of relapse or progression of neurological deficits and controls that were stratified for the genetic risk factor HLA-DRB1*1501. For the first time, we show that there is an HLA-DR-restricted promiscuous dominant epitope for CD4(+) T cells within the transmembrane/intracellular part of MOG comprising aa 146-154 (FLCLQYRLR). Surprisingly, controls had broader T cell reactivity patterns toward MOG peptides compared with MS patients, and the transmembrane and intracellular parts of MOG were much more immunogenic compared with the extracellular part. Measurements of in vitro binding affinities revealed that HLA-DRB1*1501 molecules bound MOG 146-154 with intermediate and HLA-DRB1*0401 molecules with weak affinities. The binding of MOG 146-154 was comparable or better than myelin basic protein 85-99, which is the dominant myelin basic protein epitope in context with HLA-DRB1*1501 molecules in MS patients. This is the first study in which the data underscore the need to investigate the pathogenic or regulatory role of the transmembrane and intracellular part of MOG for MS in more detail.


Human vitreous transplantation.
This lecture presents the experience in 200 implantations of human eye-bank vitreous through the pars plana of eyes with complicated retinal detachments. Though the success rate was modest, it shows that a large-bore instrument can be passed into the vitreous cavity of the eye with relative impunity and sets the stage for the present popular machine vitrectomy. In addition, the paper presents the author's experience with human vitreous transplantation by the 'open sky' transcorneal technique for otherwise hopeless vitreous opacities.


Efficacy of masks and face coverings in controlling outward aerosol particle emission from expiratory activities.
The COVID-19 pandemic triggered a surge in demand for facemasks to protect against disease transmission. In response to shortages, many public health authorities have recommended homemade masks as acceptable alternatives to surgical masks and N95 respirators. Although mask wearing is intended, in part, to protect others from exhaled, virus-containing particles, few studies have examined particle emission by mask-wearers into the surrounding air. Here, we measured outward emissions of micron-scale aerosol particles by healthy humans performing various expiratory activities while wearing different types of medical-grade or homemade masks. Both surgical masks and unvented KN95 respirators, even without fit-testing, reduce the outward particle emission rates by 90% and 74% on average during speaking and coughing, respectively, compared to wearing no mask, corroborating their effectiveness at reducing outward emission. These masks similarly decreased the outward particle emission of a coughing superemitter, who for unclear reasons emitted up to two orders of magnitude more expiratory particles via coughing than average. In contrast, shedding of non-expiratory micron-scale particulates from friable cellulosic fibers in homemade cotton-fabric masks confounded explicit determination of their efficacy at reducing expiratory particle emission. Audio analysis of the speech and coughing intensity confirmed that people speak more loudly, but do not cough more loudly, when wearing a mask. Further work is needed to establish the efficacy of cloth masks at blocking expiratory particles for speech and coughing at varied intensity and to assess whether virus-contaminated fabrics can generate aerosolized fomites, but the results strongly corroborate the efficacy of medical-grade masks and highlight the importance of regular washing of homemade masks.


Implant-supported overdenture therapy: a 3- to 8-year prospective study.
Inflammatory changes in periimplant soft tissues and loss of alveolar bone can develop as in periodontal diseases. This clinical phenomena has been described as periimplantitis. Microorganisms such as Gram-negative anaerobic rods, spirochetes, and bacteroides that are seen in subgingival flora in periodontitis have also been found in sulcular microflora in periimplantitis. The purpose of this study was to evaluate periimplant tissue changes in totally edentulous patients who had implant-supported overdentures for 3 to 8 years (5-5.5 years) clinically from both a subjective and an objective point of view. The clinical parameters used in this study can be helpful in the evaluation of periimplant tissue health.


The 39-kilodalton subunit of eukaryotic translation initiation factor 3 is essential for the complex's integrity and for cell viability in Saccharomyces cerevisiae.
Eukaryotic translation initiation factor 3 (eIF3) in the yeast Saccharomyces cerevisiae comprises about eight polypeptides and plays a central role in the binding of methionyl-tRNAi and mRNA to the 40S ribosomal subunit. The fourth largest subunit, eIF3-p39, was gel purified, and a 12-amino-acid tryptic peptide was sequenced, enabling the cloning of the TIF34 gene. TIF34 encodes a 38,753-Da protein that corresponds to eIF3-p39 in size and antigenicity. Disruption of TIF34 is lethal, and depletion of eIF3-p39 by glucose repression of TIF34 expressed from a GAL promoter results in cessation of cell growth. As eIF3-p39 levels fall, polysomes become smaller, indicating a role for eIF3-p39 in the initiation phase of protein synthesis. Unexpectedly, depletion results in degradation of all of the subunit proteins of eIF3 at a rate much faster than the normal turnover rates of these proteins. eIF3-p39 has 46% sequence identity with the p36 subunit of human eIF3. Both proteins are members of the WD-repeat family of proteins, possessing five to seven repeat elements. Taken together, the results indicate that eIF3-p39 plays an important, although not necessarily direct, role in the initiation phase of protein synthesis and suggest that it may be required for the assembly and maintenance of the eIF3 complex in eukaryotic cells.


Synthesis, antitubulin, and antiproliferative SAR of C3/C1-substituted tetrahydroisoquinolines.
The syntheses and antiproliferative activities of novel substituted tetrahydroisoquinoline derivatives and their sulfamates are discussed. Biasing of conformational populations through substitution on the tetrahydroisoquinoline core at C1 and C3 has a profound effect on the antiproliferative activity against various cancer cell lines. The C3 methyl-substituted sulfamate (±)-7-methoxy-2-(3-methoxybenzyl)-3-methyl-6-sulfamoyloxy-1,2,3,4-tetrahydroisoquinoline (6 b), for example, was found to be ∼10-fold more potent than the corresponding non-methylated compound 7-methoxy-2-(3-methoxybenzyl)-6-sulfamoyloxy-1,2,3,4-tetrahydroisoquinoline (4 b) against DU-145 prostate cancer cells (GI50 values: 220 nM and 2.1 μM, respectively). Such compounds were also found to be active against a drug-resistant MCF breast cancer cell line. The position and nature of substitution of the N-benzyl group in the C3-substituted series was found to have a significant effect on activity. Whereas C1 methylation has little effect on activity, introduction of C1 phenyl and C3-gem-dimethyl substituents greatly decreases antiproliferative activity. The ability of these compounds to inhibit microtubule polymerisation and to bind tubulin in a competitive manner versus colchicine confirms the mechanism of action. The therapeutic potential of a representative compound was confirmed in an in vivo multiple myeloma xenograft study.


An Iodabenzene Story.
We call iodabenzene a cyclic (CH)5I molecule. A planar iodabenzene would have 8 π electrons, a situation best avoided by an out-of-plane distortion to a bird-like geometry. The electronic structure and charge distribution of this molecule resemble those of Meisenheimer complexes, derivatives of (CH)5CH2-. A similar substitution strategy, of π-acceptors in ortho and para positions, works in both cases to planarize and stabilize such derivatives. Some 40 kcal/mol (73 kcal/mol for the unsubstituted case) below the bird, a classical 5-iodocyclopentadiene structure awaits, reached through a bicyclic transition state. The calculated activation barrier for the highly exothermic reaction to a classical Lewis structure nevertheless make us optimistic about the chances of detecting and even isolating the bird isomer.


Flow-Based CL-SMIA for the Quantification of Protein Biomarkers from Nasal Secretions in Comparison with Sandwich ELISA.
Protein biomarkers in nasal secretions can be used as a measure to differentiate between allergies, airway diseases and infections for non-invasive diagnostics. The point-of-care quantification of biomarker levels using flow-based microarray facilitates precise and rapid diagnosis and displays the potential for targeted and effective treatment. For the first time, we developed a flow-based chemiluminescence sandwich microarray immunoassay (CL-SMIA) for the quantification of nasal interferon-beta (IFN-β) on the Microarray Chip Reader-Research (MCR-R). Polycarbonate foils are used as a cost-effective surface for immobilizing capture antibodies. By using a commercially available set of anti-human IFN-β antibodies, the CL-SMIA can be compared directly to an enzyme-linked immunosorbent assay (ELISA) performed in microtiter plates concerning the bioanalytical performance and economic issues. Pre-incubation of the sample with detection antibodies facilitates the lower consumption of detection antibodies, as this allows for a longer interaction time between the antibody and the biomarker. The direct injection of pre-incubated samples into the microarray chips eliminates the adsorption of proteins in the tubing as well as the contamination of the tubing and valves of the MCR-R with clinical samples. The small flow cell allows for a low sample volume of 50 μL. The limit of detection of 4.53 pg mL-1 was slightly increased compared to a sandwich ELISA performed on microtiter plates which were 1.60 pg mL-1. The possibility to perform the CL-SMIA in a multiplexed mode makes it a promising assay for the rapid and cost-effective non-invasive detection of biomarkers in nasal secretions.


Tyrosine-kinase dependent TGF-beta and extracellular matrix expression by mechanical stretch in vascular smooth muscle cells.
Vascular hypertrophy, which is characterized by proliferation of vascular smooth muscle cells (VSMC) and accumulation of extracellular matrix (ECM), is a major pathological change in blood vessels after chronic exposure to hypertension. Blood pressure is transmitted to the arterial walls and counterbalanced by mechanical stress, leading to stretching of circumferentially oriented VSMC, which may play some role in the pathogenesis of vascular hypertrophy. The present study was designed, therefore, to investigate the effect of mechanical stretch on the expression of ECM components and transforming growth factor-beta (TGF-beta), a potent stimulator for ECM production, and to examine the signal transduction mechanisms of the induction of TGF-beta in cultured rat VSMC. VSMC were subjected to cyclic stretch to provide a maximal elongation of 20% at a rate of 60 cycles per minute for up to 24 h. Mechanical stretch stimulated TGF-beta1 mRNA expression in a time- and elongation-dependent manner. Indeed, the secretion of TGF-beta proteins into the culture media was increased after stretch. Stretch also stimulated mRNA expression of the ECM components, type I and type IV collagen, and fibronectin, which was largely inhibited by addition of neutralizing antibody against TGF-beta. The tyrosine kinase inhibitors genistein and herbimycin A blocked the induction of TGF-beta1 and type I collagen by stretch, while protein kinase C inhibitors, the calcium channel blockers nitrendipine and gadolinium, or Ca removal from the media had no effect. These results suggest that stretch-induced, tyrosine kinase-mediated autocrine/paracrine production of TGF-8 may play a critical role in the progression of vascular remodeling associated with high blood pressure.


Highlights from the International Summit on Intellectual Disability and Dementia Implications for Brazil.
In October of 2016, an interdisciplinary group representing North and South American and European countries met in Glasgow, Scotland, to scrutinize universal issues regarding adults with intellectual disability (ID) affected by dementia and to produce recommendations and guidelines for public policy, practice, and further research. The aim of this paper is to apprise relevant outcomes of the Summit targeting Brazilian researchers, clinicians, and nongovernmental organizations in the field of ageing and dementia that are committed to developing the Brazilian national dementia plan. Three core themes were covered by the Summit: i) human rights and personal resources, ii) personalized services and caregiver support, and iii) advocacy and public impact. The exploration of the themes highlighted variations across countries, and revealed consensual views on matters such as international networks, guidance for practices, and advocacy on behalf of both people with ID affected by dementia, and their families. The authors outline the challenges Brazil must confront regarding ageing and dementia and proffer recommendations to address the needs of adults with ID affected by dementia within this scenario; both of which would help in developing the Brazilian national dementia plan.


Modeling of a spatially resolved ion temperature diagnostic for inertial confinement fusion.
The performance of modern laser-driven inertial confinement fusion (ICF) experiments is degraded by contamination of the deuterium-tritium (DT) fuel with high-Z material during compression. Simulations suggest that this mix can be described by the ion temperature distribution of the implosion, given that such contaminants deviate in temperature from the surrounding DT plasma. However, existing neutron time-of-flight (nTOF) diagnostics only measure the spatially integrated ion temperature. This paper describes the techniques and forward modeling used to develop a novel diagnostic imaging system to measure the spatially resolved ion temperature of an ICF implosion for the first time. The technique combines methods in neutron imaging and nTOF diagnostics to measure the ion temperature along one spatial dimension at yields currently achievable on the OMEGA laser. A detailed forward model of the source and imaging system was developed to guide instrument design. The model leverages neutron imaging reconstruction algorithms, radiation hydrodynamics and Monte Carlo simulations, optical ray tracing, and more. The results of the forward model agree with the data collected on OMEGA using the completed diagnostic. The analysis of the experimental data is still ongoing and will be discussed in a separate publication.


Impaired neurogenesis of the dentate gyrus is associated with pattern separation deficits: A computational study.
The separation of input patterns received from the entorhinal cortex (EC) by the dentate gyrus (DG) is a well-known critical step of information processing in the hippocampus. Although the role of interneurons in separation pattern efficiency of the DG has been theoretically known, the balance of neurogenesis of excitatory neurons and interneurons as well as its potential role in information processing in the DG is not fully understood. In this work, we study separation efficiency of the DG for different rates of neurogenesis of interneurons and excitatory neurons using a novel computational model in which we assume an increase in the synaptic efficacy between excitatory neurons and interneurons and then its decay over time. Information processing in the EC and DG was simulated as information flow in a two layer feed-forward neural network. The neurogenesis rate was modeled as the percentage of new born neurons added to the neuronal population in each time bin. The results show an important role of an optimal neurogenesis rate of interneurons and excitatory neurons in the DG in efficient separation of inputs from the EC in pattern separation tasks. The model predicts that any deviation of the optimal values of neurogenesis rates leads to different decreased levels of the separation deficits of the DG which influences its function to encode memory.


Sexual risk behaviors and sexually transmitted infection prevalence in an outpatient psychiatry clinic.
Nearly 3% of Americans experience severe and persistent mental illness (SPMI) and behaviors that place affected individuals at risk for sexually transmitted infections (STIs) are common. Few data describe the prevalence of risk behaviors or STI among persons with SPMI. We aim to quantitate STI/human immunodeficiency virus risk and determine the STI prevalence amongst outpatient psychiatric clinic attendees. Psychiatric outpatients were approached to participate in an interviewer-administered survey collecting data on their sexual history, psychiatric history, and risk behaviors. Females submitted self-collected vaginal swabs, whereas males submitted urine to be tested for Neisseria gonorrhoeae, Chlamydia trachomatis, and Trichomonas vaginalis (women only). The prevalence of N. gonorrhoeae was 1%, C. trachomatis 3.3% and T. vaginalis 15.7%. Exchanging sex for drugs was the only behavior independently associated with having an STI in this population. Taking a sexual history in persons with SPMI is important. Those engaging in high-risk behavior should be routinely screened for STI/human immunodeficiency virus allowing for detection, treatment, and preventive education.


Content analysis of food advertising in Turkish television.
Television (TV) viewing has been implicated in children's weight gain. We aimed to conduct a comprehensive content analysis of TV food advertising in Turkey. TV advertisements (ads) in the four most popular national free to air Turkish TV channels, were assessed on two weekdays and two weekend days at four time periods of the day; 0800-1200,1200-1600,1600-2000 and 2000-2400 h for each TV channel (64 h assessed for each TV channel), making a total of 256 h. Each ad was analysed for food and drink content, duration and audiovisual properties. There were 8853 TV ads and 2848 of these were related to food (32.1%). A majority of food ads included high-calorie, high-fat, high-sugar food and drink rather than core/healthy foods (81%). Chocolate and chocolate bars were the most frequently advertised food/drink product, followed by cakes, coffee, tea, candies, gum, fast food, chips, juices/carbonated beverages, margarine and ice-cream formed the highest rate of food products advertised in decreasing order. Thirty per cent of all obesogenic/unhealthy ads targeted childhood by using audiovisual techniques. The proportion of total advertisements which were for food or drink, and the proportion of food advertisements that were for unhealthy foods were both much higher at the weekend (33% vs. 30% and 84% vs. 78%, respectively). The time period between 1600 and 2000 h was the most concentrated time slot (33%) for food advertising. This study provides data for the first time on the high levels of obesogenic food advertising on Turkish TV. This should alarm policy-makers to set limits on food advertising targeted towards children especially in countries like Turkey in which childhood obesity is emerging as an important public health issue.


Genome-Wide Discovery of Microsatellite Markers from Diploid Progenitor Species, Arachis duranensis and A. ipaensis, and Their Application in Cultivated Peanut (A. hypogaea).
Despite several efforts in the last decade toward development of simple sequence repeat (SSR) markers in peanut, there is still a need for more markers for conducting different genetic and breeding studies. With the effort of the International Peanut Genome Initiative, the availability of reference genome for both the diploid progenitors of cultivated peanut allowed us to identify 135,529 and 199,957 SSRs from the A (Arachis duranensis) and B genomes (Arachis ipaensis), respectively. Genome sequence analysis showed uneven distribution of the SSR motifs across genomes with variation in parameters such as SSR type, repeat number, and SSR length. Using the flanking sequences of identified SSRs, primers were designed for 51,354 and 60,893 SSRs with densities of 49 and 45 SSRs per Mb in A. duranensis and A. ipaensis, respectively. In silico PCR analysis of these SSR markers showed high transferability between wild and cultivated Arachis species. Two physical maps were developed for the A genome and the B genome using these SSR markers, and two reported disease resistance quantitative trait loci (QTLs), qF2TSWV5 for tomato spotted wilt virus (TSWV) and qF2LS6 for leaf spot (LS), were mapped in the 8.135 Mb region of chromosome A04 of A. duranensis. From this genomic region, 719 novel SSR markers were developed, which provide the possibility for fine mapping of these QTLs. In addition, this region also harbors 652 genes and 49 of these are defense related genes, including two NB-ARC genes, three LRR receptor-like genes and three WRKY transcription factors. These disease resistance related genes could contribute to resistance to viral (such as TSWV) and fungal (such as LS) diseases in peanut. In summary, this study not only provides a large number of molecular markers for potential use in peanut genetic map development and QTL mapping but also for map-based gene cloning and molecular breeding.


[Inhibition of Copper Transporter-1 by Ammonium Tetrathiocarbolybdate in the Treatment of Pancreatic Cancer].
To examine copper transporter 1 (CTR1) expression in pancreatic carcinoma cells, orthotopic xenograft pancreatic tumor model and clinical samples, and verify the effect of copper chelating agent ammonium tetrathiomolybdate (TM) regulate the expression of CTR1 in pancreatic carcinoma cells and the inhibition of pancreatic carcinoma. The expressions of copper transporter CTR1 and antioxidant protein 1 (ATOX1) in 22 clinical pancreatic ductal carcinoma and paracancer tissues 0.5-1 cm away from the tumor were measured by immunohistochemistry (IHC). PANC-1 cells were used to construct 5 orthotopic xenograft pancreatic tumor of nude mice models. Pancreatic cancer tissues and corresponding normal pancreatic tissues were collected, and the expressions of CTR1 and ATOX1 were detected by IHC and compared with clinical tissues. The proliferation of pancreatic carcinoma cells PANC-1 treated with 10, 30, 50, 100 μmol/L TM for 24 h, 48 h, 72 h was measured by CCK8 assay. The migration abilities of PANC-1 cells treated with 50 μmol/L TM for 24 h, 48 h were detected by scratch test. The expressions of CTR1, vascular endothelial growth factor (VEGF) and CyclinD1 proteins in PANC-1 cells treated with 10, 30, 50, 100 μmol/L TM for 48 h were measured by Western blot. Then the subcutaneous tumor-bearing model of nude mice were established with PANC-1 cells, and the growth of tumor was observed after oral administration of 0.3 mg/d and 1.0 mg/d of TM, respectively. The immunohistochemical results indicated that 19 of the 22 clinical pancreatic ductal cancer tissues of carcinoma patients had high expression of CTR1, and the same high expression of CTR1 was found in the orthotopic transplanted tumor tissues of PANC-1 nude mice. The proliferation inhibition of PANC-1 cells increased with the concentration of TM increased and the treatment time prolonged. The expressions of intracellular CTR1, VEGF and CyclinD1 all decreased with the concentration of TM increased. The cell migration ability decreased after the PANC-1 cells treated with TM. The tumor growth of PANC-1 tumor-bearing nude mice was inhibited after different doses of TM were delivered. The reduction in tumor volume and weight was more pronounced in the high-dose TM group (P<0.05). The expression of CTR1 is abnormally elevated in pancreatic carcinoma, and treatment with copper chelating agent for this target may help to inhibit pancreatic carcinoma.


Uptake of hematoporphyrin derivative by normal and malignant cells: effect of serum, pH, temperature, and cell size.
Normal and malignant cells were incubated with hematoporphyrin derivative (HPD) and their uptake and retention of HPD were analyzed by flow cytometry. In standard growth medium the amount of HPD taken up by cells was proportional to the added HPD concentration and reached a plateau level after 5-6 h of incubation. The uptake occurred in two steps; within seconds a large amount of HPD became loosely bound to the cells, presumably the outer membrane. This was followed by a slower uptake of HPD into the cytoplasm. The loosely bound portion could be washed from the cells by medium containing either fetal calf serum or serum albumin. At low temperatures the uptake into the cytoplasm was strongly reduced. A major determinant of HPD uptake was the concentration of serum in the medium. At any particular concentration of HPD below 200 mg/liter, increasing concentrations of fetal calf serum or bovine serum albumin resulted in a reduction in the amount of HPD taken up by cells. A further factor affecting uptake was the pH of the medium. At low pH (pH 6) the rate of HPD incorporation was much higher than at pH 7.4. Under identical conditions of incubation, HPD uptake was proportional to cell size as estimated using the low angle light scatter signal in the flow cytometer. Our data suggest that acidic pH, differences in extracellular serum concentrations of malignant tumor tissue, as well as the increased size of tumor cells may play an important role in the selective uptake of HPD by malignant tumors.


beta-Peptides as inhibitors of protein-protein interactions.
We became interested several years ago in exploring whether 14-helical beta-peptide foldamers could bind protein surfaces and inhibit protein-protein interactions, and if so, whether their affinities and specificities would compare favorably with those of natural or miniature proteins. This exploration was complicated initially by the absence of a suitable beta-peptide scaffold, one that possessed a well-defined 14-helical structure in water and tolerated the diverse sequence variation required to generate high-affinity protein surface ligands. In this perspective, we describe our approach to the design of adaptable beta-peptide scaffolds with high levels of 14-helix structure in water, track the subsequent development of 14-helical beta-peptide protein-protein interaction inhibitors, and examine the potential of this strategy for targeting other therapeutically important proteins.


Changing epidemiology of hepatitis A virus infection--a comparative study in central eastern Poland (1990-1999).
A comparative seroepidemiological study (1990 vs. 1998/99) on HAV infection, was carried out in population from middle-eastern Poland. Anti-HAV was tested in 1450 subjects from 0 to over 50 years of age and the results were compared with those observed in 1990, in 1000 individuals of the same age range and from the same geographical area. Overall anti-HAV prevalence was 58.4% in 1990 vs. 30.6% in 1998/99. This decline of HAV infection in Polish population indicates that the number of non-immune adults is increasing, with higher risk of symptomatic infection in the near future. The surveillance and prevalence data presented here have implications for developing the strategy for use of hepatitis A vaccine.


Long non-coding RNAs as a predictive markers of group 3 medulloblastomas.
ObjectiveThe appropriate treatments for the different molecular subgroups of medulloblastomas are challenging to determine. Hence, this study aimed to examine the expression profiles of long non-coding RNAs (LncRNAs) to determine a marker that may be important for treatment selection in these subgroups.MethodsChanges in the expression of LncRNAs in the tissues of patients with medulloblastoma, which are classified into four subgroups according to their clinical characteristics and gene expression profiles, were examined via reverse transcription polymerase chain reaction. Moreover, there association with patient prognosis was evaluated.ResultsThe expression levels of MALAT1 and SNGH16 were significantly higher in patients with group 3 medulloblastoma than in those with other subtypes. Patients with high expression levels of MALAT1 and SNGH16 had a relatively shorter overall survival than those with low expression levels.ConclusionsPatients with group 3 medulloblastoma have a high MALAT1 level, which is associated with poor prognosis. Therefore, MALAT1 can be a new therapeutic target in medulloblastoma.


Estimation of the elastic modulus of child cortical bone specimens via microindentation.
Purpose: Non-pathological child cortical bone (NPCCB) studies can provide clinicians with vital information and insights. However, assessing the anisotropic elastic properties of NPCCB remains a challenge for the biomechanical engineering community. For the first time, this paper provides elastic moduli values for NPCCB specimens in two perpendicular directions (longitudinal and transverse) and for two different structural components of bone tissue (osteon and interstitial lamellae). Materials and Methods: Microindentation is one of the reference methods used to measure bone stiffness. Here, 8 adult femurs (mean age 82 ± 8.9 years), 3 child femurs (mean age 13.3 ± 2.1 years), and 16 child fibulae (mean age 10.2 ± 3.9 years) were used to assess the elastic moduli of adult and child bones by microindentation. Results: For adult specimens, the mean moduli measured in this study are 18.1 (2.6) GPa for osteons, 21.3 (2.3) GPa for interstitial lamellae, and 13.8 (1.7) GPa in the transverse direction. For child femur specimens, the mean modulus is 14.1 (0.8) GPa for osteons, lower than that for interstitial lamellae: 15.5 (1.5) GPa. The mean modulus is 11.8 (0.7) GPa in the transverse direction. Child fibula specimens show a higher elastic modulus for interstitial lamellae 15.8 (1.5) than for osteons 13.5 (1.6), with 10.2 (1) GPa in the transverse direction. Conclusion: For the first time, NPCCB elastic modulus values are provided in longitudinal and transverse directions at the microscale level.