Buffering effect of fiber coating and its influence on the proof test load in optical fibers.
The tensile force experienced by a coated glass fiber during proof testing is applied to the coating and, therefore, may be reduced because of the buffering effect of the coating. In this study such an effect is evaluated on the basis of an analytical stress model. It is shown that for any finite, even very great, coating compliance, one can always choose a sufficiently long specimen in which the glass fiber is loaded to practically the same level as in an infinitely long composite. The numerical example carried out for a dual-coated fiber, considered for future undersea systems, indicated that if ~10 cm long specimens are employed, 98% of the fiber length will be subjected to a tensile force >99% of the value for the case of an infinitely long fiber. The results obtained can be used for the analysis of the mechanical performance of coated fibers of finite length. They can be utilized, in particular, for selecting appropriate specimen lengths during proof testing.


Cardamonin inhibits the proliferation and metastasis of non-small-cell lung cancer cells by suppressing the PI3K/Akt/mTOR pathway.
Cardamonin, a natural chalcone compound, has been reported to exert anticancer effects in several cancers. However, the specific pharmacological actions of cardamonin on human non-small-cell lung cancer (NSCLC) and the potential mechanisms still remain obscure. Here, we investigated the antineoplastic role of cardamonin in NSCLC both in vitro and in vivo. The proliferation of five NSCLC cell lines was inhibited in a dose-dependent and time-dependent manner with cardamonin treatment. In A549 and H460 cells, cardamonin induced apoptosis by activating caspase-3, upregulating Bax, and downregulating Bcl-2. In addition, cardamonin arrested cells in the G2/M phase and inhibited the expression levels of cyclin D1/CDK4. Moreover, cell migration and invasion were suppressed by reversing epithelial-mesenchymal transition with cardamonin treatment. Further study showed that cardamonin reduced the phosphorylation levels of the downstream effectors of phosphoinositide 3-kinase (PI3K), including protein kinase-B (Akt/PKB) and mammalian target of rapamycin (mTOR). Moreover, in the H460 xenograft model, cardamonin significantly retarded tumor growth. Also, in tumor tissues, we found that cardamonin treatment decreased the expression rates of Ki-67, p-Akt, and p-mTOR. These data suggest that cardamonin suppressed NSCLC cell proliferation and inhibited metastasis partly by restraining the PI3K/Akt/mTOR pathway and it might be an effective therapeutic compound for NSCLC in the future.


Temporary mechanical circulatory support: a review of the options, indications, and outcomes.
Cardiogenic shock remains a challenging disease entity and is associated with significant morbidity and mortality. Temporary mechanical circulatory support (MCS) can be implemented in an acute setting to stabilize acutely ill patients with cardiomyopathy in a variety of clinical situations. Currently, several options exist for temporary MCS. We review the indications, contraindications, clinical applications, and evidences for a variety of temporary circulatory support options, including the intra-aortic balloon pump (IABP), extracorporeal membrane oxygenation (ECMO), CentriMag blood pump, and percutaneous ventricular assist devices (pVADs), specifically the TandemHeart and Impella.


High-utility conserved avian microsatellite markers enable parentage and population studies across a wide range of species.
Microsatellites are widely used for many genetic studies. In contrast to single nucleotide polymorphism (SNP) and genotyping-by-sequencing methods, they are readily typed in samples of low DNA quality/concentration (e.g. museum/non-invasive samples), and enable the quick, cheap identification of species, hybrids, clones and ploidy. Microsatellites also have the highest cross-species utility of all types of markers used for genotyping, but, despite this, when isolated from a single species, only a relatively small proportion will be of utility. Marker development of any type requires skill and time. The availability of sufficient "off-the-shelf" markers that are suitable for genotyping a wide range of species would not only save resources but also uniquely enable new comparisons of diversity among taxa at the same set of loci. No other marker types are capable of enabling this. We therefore developed a set of avian microsatellite markers with enhanced cross-species utility. We selected highly-conserved sequences with a high number of repeat units in both of two genetically distant species. Twenty-four primer sets were designed from homologous sequences that possessed at least eight repeat units in both the zebra finch (Taeniopygia guttata) and chicken (Gallus gallus). Each primer sequence was a complete match to zebra finch and, after accounting for degenerate bases, at least 86% similar to chicken. We assessed primer-set utility by genotyping individuals belonging to eight passerine and four non-passerine species. The majority of the new Conserved Avian Microsatellite (CAM) markers amplified in all 12 species tested (on average, 94% in passerines and 95% in non-passerines). This new marker set is of especially high utility in passerines, with a mean 68% of loci polymorphic per species, compared with 42% in non-passerine species. When combined with previously described conserved loci, this new set of conserved markers will not only reduce the necessity and expense of microsatellite isolation for a wide range of genetic studies, including avian parentage and population analyses, but will also now enable comparisons of genetic diversity among different species (and populations) at the same set of loci, with no or reduced bias. Finally, the approach used here can be applied to other taxa in which appropriate genome sequences are available.


A comparison of the Synemed Glaucoma and the Humphrey 30-2 threshold perimetry tests.
Automated perimeters (in general) are similar; however, caution may be exercised when visual field results from two different instruments are compared. The purpose of this study was to compare threshold measurements in the central field between the Synemed (Optifield 1) Glaucoma Test and the Humphrey 30-2 test in a young patient population. One hundred twenty subjects were tested. The subjects were selected according to specific criteria considering ocular and systemic disease and refractive error. The ages ranged from 15 to 35 years, with a mean age of 25.9 years. The central 30 glaucoma test was used with the Synemed instrument, and the 30-2 test was used with the Humphrey instrument. Mean threshold values for the entire field, hemifields, quadrants, and sectors were compared between instruments. The difference in the mean value for the collective threshold values for each pattern for each instrument were calculated and compared. The difference between the instruments for the mean dB threshold value for each pattern was less than the expected short-term fluctuation and therefore are equivalent for clinical purposes. For the patterns examined here, the Synemed Optifield 1 and Humphrey Field Analyzer provided comparable results in this population.


Disclosures of Cystic Fibrosis-Related Information to Romantic Partners.
In this article, we offer insights into how individuals with cystic fibrosis (CF) share information about their disease with a romantic partner. Using communication privacy management as a sensitizing theoretical construct, four themes emerged following 13 qualitative interviews with persons with CF. Themes about sharing CF-related information with a romantic partner include weighing the risks and benefits of sharing information, the role of health-related triggered rules, the motivations for disclosures, and the reactions from outsiders. Implications of the research suggest a need for more nuanced understandings of how privacy rules are communicated in relationships, how the mismanagement of co-owned information influences future disclosures, how the public-private nature of rare genetic illnesses is managed, and how people with genetic illnesses make disclosure decisions.


Assembly of enveloped viruses in Madin-Darby canine kidney cells: polarized budding from single attached cells and from clusters of cells in suspension.
In confluent monolayers of the dog kidney epithelial cell line Madin-Darby canine kidney (MDCK) assembly of RNA enveloped viruses reflects the functional polarization of the cells. Thus, influenza, Sendai, and Simian virus 5 bud from the apical (free) surface, while vesicular stomatitis virions (VSV) are assembled at basolateral plasma membrane domains (Rodriguez-Boulan, E., and D.D. Sabatini, 1978, Proc. Natl. Acad. Sci. U.S.A., 75:5071-5075). MDCK cells derived from confluent monolayers by dissociation with trypsin-EDTA and maintained as single cells in spinner medium for 12-20 h before infection, lose their characteristic structural polarity. Furthermore, when these cells were infected with influenza or VSV, virions assembled in a nonpolarized fashion over most of the cell surface. However, when dissociated MDCK cells infected in suspension were sparsely plated on collagen gels to prevent intercellular contact and the formation of junctions, the characteristic polarity of viral budding observed in confluent monolayers was again manifested; i.e., VSV budded preferentially from adherent surfaces and influenza almost exclusively from free surface regions. Similar polarization was observed in cells which became aggregated during incubation in spinner medium: influenza budded from the free surface, while VSV was produced at regions of cell-cell contact. It therefore appears that in isolated epithelial cells attachment to a substrate or to another cell is sufficient to trigger the expression of plasma membrane polarity which is manifested in the asymmetric budding of viruses.


Inhibition of human immunodeficiency virus (HIV) infection in vitro by anticarbohydrate monoclonal antibodies: peripheral glycosylation of HIV envelope glycoprotein gp120 may be a target for virus neutralization.
Carbohydrate structures are often involved in the initial adhesion of pathogens to target cells. In the present study, a panel of anticarbohydrate monoclonal antibodies (MAbs) was tested for their ability to inhibit in vitro human immunodeficiency virus infectivity. MAbs against three different N- and O-linked carbohydrate epitopes (LeY, A1, and sialyl-Tn) were able to block infection by cell-free virus as well as inhibit syncytium formation. Inhibition of virus infectivity was independent of virus strain (HTLVIIIB or patient isolate SSI-002), the cell line used for virus propagation (H9 or MT4), and the cell type used as the infection target (MT4, PMC, or selected T4 lymphocytes). Inhibition was observed when viruses were preincubated with MAbs but not when cells were preincubated with MAbs before inoculation, and the MAbs were shown to precipitate 125I-labeled gp120. The MAbs therefore define carbohydrate structures expressed by the viral envelope glycoprotein gp120, indicating that glycans of the viral envelope are possible targets for immunotherapy or vaccine development or both.


CCL2 mediates early renal leukocyte infiltration during salt-sensitive hypertension.
Studies examining mechanisms of Dahl salt-sensitive (SS) hypertension have implicated the infiltration of leukocytes in the kidneys, which contribute to renal disease and elevated blood pressure. However, the signaling pathways by which leukocytes traffic to the kidneys remain poorly understood. The present study nominated a signaling pathway by analyzing a kidney RNA sequencing data set from SS rats fed either a low-salt (0.4% NaCl) diet or a high-salt (4.0% NaCl) diet. From this analysis, chemokine (C-C motif) ligand 2 (CCL2) and chemokine (C-C motif) receptor 2 (CCR2) were nominated as a potential pathway modifying renal leukocyte infiltration and contributing to SS hypertension. The functional role of the CCL2/CCR2 pathway was tested by daily administration of CCR2 antagonist (RS-102895 at 5 mg·kg-1·day-1 in DMSO) or DMSO vehicle for 3 or 21 days by intraperitoneal injections during the high salt challenge. Blood pressure, renal leukocyte infiltration, and renal damage were evaluated. The results demonstrated that RS-102895 treatment ameliorated renal damage (urinary albumin excretion; 43.4 ± 5.1 vs. 114.7 ± 15.2 mg/day in vehicle, P < 0.001) and hypertension (144.3 ± 2.2 vs. 158.9 ± 4.8 mmHg in vehicle, P < 0.001) after 21 days of high-salt diet. It was determined that renal leukocyte infiltration was blunted by day 3 of the high-salt diet (1.4 ± 0.1 vs. 1.9 ± 0.2 in vehicle × 106 CD45+ cells/kidney, P = 0.034). An in vitro chemotaxis assay validated the effect of RS-102895 on leukocyte chemotaxis toward CCL2. The results suggest that increased CCL2 in SS kidneys is important in the early recruitment of leukocytes, and blockade of this recruitment by administering RS-102895 subsequently blunted the renal damage and hypertension.


Review of Trials Currently Testing Stem Cells for Treatment of Respiratory Diseases: Facts Known to Date and Possible Applications to COVID-19.
Therapeutic clinical and preclinical studies using cultured cells are on the rise, especially now that the World Health Organization (WHO) declared coronavirus disease 2019 (COVID-19) a "public health emergency of international concern", in January, 2020. Thus, this study aims to review the outcomes of ongoing clinical studies on stem cells in Severe Acute Respiratory Syndrome (SARS), Acute Respiratory Distress Syndrome (ARDS), and Middle East Respiratory Syndrome (MERS). The results will be associated with possible applications to COVID-19. Only three clinical trials related to stem cells are considered complete, whereby two are in Phase 1 and one is in Phase 2. Basically, the ongoing studies on coronavirus are using mesenchymal stem cells (MSCs) derived from bone marrow or the umbilical cord to demonstrate their feasibility, safety, and tolerability. The studies not related to coronavirus are all in ARDS conditions; four of them are in Phase 1 and three in Phase 2. With the COVID-19 boom, many clinical trials are being carried out using different sources with an emphasis on MSC-based therapy used to inhibit inflammation. One of the biggest challenges in the current treatment of COVID-19 is the cytokine storm, however MSCs can prevent or mitigate this cytokine storm through their immunomodulatory capacity. We look forward to the results of the ongoing clinical trials to find a treatment for the disease. Researchers around the world are joining forces to help fight COVID-19. Stem cells used in the current clinical studies are a new therapeutic promise for COVID-19 where pharmacological treatments seem insufficient.Graphical Abstract.


Acetyl-11-Keto-β-Boswellic Acid Exerts the Anti-Cancer Effects via Cell Cycle Arrest, Apoptosis Induction and Autophagy Suppression in Non-Small Cell Lung Cancer Cells.
Acetyl-11-keto-β-boswellic acid (AKBA) is a triterpenoid, which is the main component of boswellic acid from Boswellia Serrata, a medicinal plant that has shown immense potential in anti-cancer therapy. This study aims to explore the roles and molecular mechanisms of AKBA on cell behavior in non-small cell lung cancer (NSCLC) cells. The effects of AKBA on the cell viability in A549, H460, H1299, and BEAS-2B cells were determined by the CCK-8 assay. The colony formation assay was used to identify the effects of AKBA on cell proliferation. Potential roles of AKBA in regulating the cell cycle, apoptosis, and autophagy in A549 were evaluated by flow cytometry, Western blotting, reverse transcription-polymerase chain reaction (PCR) and immunofluorescence (IF). AKBA reduced cell viability in A549, H460, H1299, and BEAS-2B. In A549 cells, AKBA suppressed the clone formation, arrested the cell cycle at the G0/G1 phase, induced cellular apoptosis. We found that AKBA suppressed the formation of autolysosome, and decreased the expression levels of Beclin-1, LC3A/B-I, and LC3A/B-II proteins. Furthermore, AKBA also inhibited the expression levels of PI3K/Akt signaling pathway proteins. AKBA exerts the anti-cancer effects via cell cycle arrest, apoptosis induction, and autophagy suppression in NSCLC cells. This body of evidence supports the potential of AKBA as a promising drug in the treatment of NSCLC.


Prescribing Safety Assessment 2016: Delivery of a national prescribing assessment to 7343 UK final-year medical students.
Newly graduated doctors write a large proportion of prescriptions in UK hospitals but recent studies have shown that they frequently make prescribing errors. The prescribing safety assessment (PSA) has been developed as an assessment of competence in relation to prescribing and supervising the use of medicines. This report describes the delivery of the PSA to all UK final-year medical students in 2016 (PSA2016). The PSA is a 2-hour online assessment comprising eight sections which cover various aspects of prescribing defined within the outcomes of undergraduate education identified by the UK General Medical Council. Students sat one of four PSA 'papers', which had been standard-set using a modified Angoff process. A total of 7343 final-year medical students in all 31 UK medical schools sat the PSA. The overall pass rate was 95% with the pass rates for the individual papers ranging from 93 to 97%. The PSA was re-sat by 261 students who had failed and 80% of those candidates passed. The internal consistency (Cronbach's alpha) of the four papers ranged from 0.74 to 0.77 (standard error of measurement 4.13-4.24%). There was a statistically significant variation in performance between medical school cohorts (F = 32.6, P < 0.001) and a strongly positive correlation in performance for individual schools between PSA2015 and PSA2016 (r = 0.79, 95% CI 0.61-0.90; P < 0.01). PSA2016 demonstrated the feasibility of delivering a standardized national prescribing assessment online. The vast majority of UK final-year medical students were able to meet a prespecified standard of prescribing competence.


Nutritional, functional, and allergenic properties of silkworm pupae.
Edible insects are a food source that has high nutritional value. Domestic silkworm pupae are an important by-product of sericulture and have a long history as food and feed ingredients in East Asia. Silkworm pupae are a good source of protein, lipids, minerals, and vitamins and are considered a good source of nutrients for humans. Silkworm pupae are a valuable insect source of substances used in healthcare products, medicines, food additives, and animal feed. Because silkworm pupae are being increasingly used in the human diet, potential allergic reactions to the substances they contain must be elucidated. Here, we present an overview of the benefits of silkworm pupae. First, we describe their nutritional value. Second, we report their functional properties and applications, focusing on their potential use in the food and pharmaceutical industries. Finally, we consider the current state of research regarding silkworm pupae-induced allergies.


Accurate timing but increased impulsivity following excitotoxic lesions of the subthalamic nucleus.
Several lines of evidence have implicated the subthalamic nucleus (STN) in behaviors that require precise temporal control. In order to investigate this possibility further, we trained rats to perform a peak-interval (PI) timing task [S. Roberts, Isolation of an internal clock, J. Exp. Psychol. Anim. B 7 (1981) 242-268] with two durations (10 s and 40 s), and then lesioned the STN by microinjection of ibotenic acid. Lesioned animals were able to maintain precise temporal control, yet were unable to inhibit operant responses late in the trial, at times that were unlikely to yield reinforcement. These results indicate the involvement of the STN in impulsive or perseverative response inhibition, but not in temporal processing.


Regulation of cell shape in Euglena gracilis. III. Involvement of stable microtubules.
The role of cytoplasmic microtubules in a recently reported biological clock-controlled rhythm in cell shape of the alga Euglena gracilis (strain Z) was examined using indirect immunofluorescence microscopy. The resulting fluorescent patterns indicated that, unlike many other cell systems, Euglena cells apparently change from round to long to round cell shape without associated cytoplasmic microtubule assembly and disassembly. Instead, the different cell shapes were correlated with microtubule patterns, which suggested that movement of stable microtubules to accomplish cell shape changes. In live intact cells, these microtubules were demonstrated by immunofluorescence to be stable to lowered temperature and elevated intracellular Ca2+ levels, treatments that are commonly used to depolymerize microtubules. In cells extracted in detergent at low temperature or in the presence of elevated Ca2+ levels, the fluorescent image of the microtubules was disrupted. Transmission electron microscopy confirmed the loss of one subset of pellicle microtubules. The difference in microtubule stability to these agents between live intact cells and cells extracted in detergent suggested the presence of a microtubule-stabilizing factor in live cells, which is released from the cell by extraction with detergent, thereby permitting microtubule depolymerization by Ca2+ or lowered temperature. The calmodulin antagonist trifluoperazine prevented the Ca2+-induced disruption of the fluorescent microtubule pattern in cells extracted in detergent. These results implied the involvement of calmodulin in the sensitivity to Ca2+ of the microtubules of cells extracted in detergent.


Ligand modulation of sidechain dynamics in a wild-type human GPCR.
GPCRs regulate all aspects of human physiology, and biophysical studies have deepened our understanding of GPCR conformational regulation by different ligands. Yet there is no experimental evidence for how sidechain dynamics control allosteric transitions between GPCR conformations. To address this deficit, we generated samples of a wild-type GPCR (A2AR) that are deuterated apart from 1H/13C NMR probes at isoleucine δ1 methyl groups, which facilitated 1H/13C methyl TROSY NMR measurements with opposing ligands. Our data indicate that low [Na+] is required to allow large agonist-induced structural changes in A2AR, and that patterns of sidechain dynamics substantially differ between agonist (NECA) and inverse agonist (ZM241385) bound receptors, with the inverse agonist suppressing fast ps-ns timescale motions at the G protein binding site. Our approach to GPCR NMR creates a framework for exploring how different regions of a receptor respond to different ligands or signaling proteins through modulation of fast ps-ns sidechain dynamics.


Lung ultrasound: routine practice for the next generation of internists.
The lung is at the crossroads of ventilation and circulation and can provide a wealth of diagnostic information. In the past, lung ultrasound (LUS) was considered impossible. However, the interplay between air, fluid and pleurae creates distinctive artefacts. Combinations of these artefacts can help differentiate between various pathological processes, including pulmonary oedema, pneumonia, pulmonary embolism, obstructive airway disease and pneumothorax. LUS, when used by experienced physicians, is superior to chest X-ray and comparable to computed tomography for establishing a diagnosis in acutely dyspnoeic patients. LUS allows for rapid, non-invasive and bedside patient assessment. It is therefore unfortunate that unlike many other medical specialists in the Netherlands, internists have not yet incorporated LUS into their daily practice. This review aims to be the starting point for internists wanting to acquire competence in LUS. REVIEW CONTENT: This narrative review describes the principles of ultrasound equipment, LUS artefacts, gives practical guidance to perform LUS and provides a road map towards LUS competence. Furthermore, it presents a decision tree to differentiate between causes of acute dyspnoea. LUS is a promising diagnostic technique that can be of great help for the internist. It can be applied directly at the bedside and can also be used to follow up on disease progression and therapy. It is our belief that it will replace the stethoscope and that it will be the most used imaging technique in the near future, especially in dyspnoeic patients.


Depth profiling of Pu, 241Am and 137Cs in soils from southern Belarus measured by ICP-MS and alpha and gamma spectrometry.
The depth distribution of plutonium, americium, and 137Cs originating from the 1986 accident at the Chernobyl Nuclear Power Plant (NPP) was investigated in several soil profiles in the vicinity from Belarus. The vertical migration of transuranic elements in soils typical of the 30 km relocation area around Chernobyl NPP was studied using inductively coupled plasma mass spectrometry (ICP-MS), alpha spectrometry, and gamma spectrometry. Transuranic concentrations in upper soil layers ranged from 6 x 10(-12) g g(-1) to 6 x 10(-10) g g(-1) for plutonium and from 1.8 x 10(-13) g g(-1) to 1.6 x 10(-11) g g(-1) for americium. These concentrations correspond to specific activities of (239+240)Pu of 24-2400 Bq kg(-1) and specific activity of 241Am of 23-2000 Bq kg(-1), respectively. Transuranics in turf-podzol soil migrate slowly to the deeper soil layers, thus, 80-95%, of radionuclide inventories were present in the 0-3 cm intervals of turf-podzol soils collected in 1994. In peat-marsh soil migration processes occur more rapidly than in turf-podzol and the maximum concentrations are found beneath the soil surface (down to 3-6 cm). The depth distributions of Pu and Am are essentially identical for a given soil profile. (239+240)Pu/137Cs and 241Am/137Cs activity ratios vary by up to a factor of 5 at some sites while smaller variations in these ratios were observed at a site close to Chernobyl, suggesting that 137Cs is dominantly particle associated close to Chernobyl but volatile species of 137Cs are of relatively greater importance at the distant sites.


[Comparison of population coronary heart disease risk estimated by the Framingham original and REGICOR calibrated functions].
The therapeutic consequences of using the Framingham function calibrated by the REGICOR and Framingham investigators (Framingham-REGICOR) in the Spanish population are unknown. The objective of this study was to determine the differences in the classification of the population coronary risk when using the classical Framingham function (Framingham-Wilson) and that calibrated, and its consequences on the theoretical indication of lipid-lowering treatment. The classification into the < 2%, 2-4,9%, 5-9,9%, 10-19,9%, 20-39,9%, and >= 40% risk categories observed by the two functions was compared in 3.270 individuals aged 35 to 74 years with no history of ischaemic heart disease or lipid-lowering drug treatment, recruited in two population samples representative of Girona between 1994 and 2001. The number of lipid-lowering treatment candidates was estimated applying the most recent guidelines for clinical practice, according to the risk level obtained with both functions. The proportion of patients excluded owing to the fact that they already were on lipid-lowering treatment was 6.2%. The Framingham-REGICOR assigned 54.2% of women and 67.9% of men to a lower level of risk as compared to the Framingham-Wilson function. In 0.2% of women and 21.2% of men the decrease was two categories of risk. The figures in diabetic participants were 75.7 and 18.5%, respectively. When the European recommendations published in 2003 were applied, lipid-lowering treatment would have been indicated in 14.5% and in 4.4% of non-diabetic participants by the Framingham-Wilson and the Framingham-REGICOR, respectively. The calibrated Framingham-REGICOR function assigns a lower coronary risk category in more than 50% of women and almost 90% of men than the uncalibrated Framingham function. The calibrated function is more suitable for risk estimation in primary prevention than the original function in Spain.


Alemtuzumab induced ST-segment elevation and acute myocardial dysfunction.
Cardiac toxicity as a side effect of chemotherapeutic agents has been well reported in the literature. Cardiac toxicity secondary to alemtuzumab has been reported, presenting as congestive heart failure and arrhythmias. Here we report a case of acute myocardial dysfunction after administration of a test dose of alemtuzumab. Our patient was a 66-year-old man with a history of small lymphocytic lymphoma/chronic lymphocytic lymphoma who received a test dose of alemtuzumab. Twenty minutes post administration, the patient developed nausea, vomiting, rigors, and tachycardia. Electrocardiography (ECG) showed acute ST-segment elevations in contiguous leads V2-V6, I, and AVL with no associated chest pain. Bedside echocardiogram showed akinesis of the anterior septum, apex, distal anterior wall, and decreased left ventricular ejection fraction. Cardiac catheterization showed non-critical occlusive disease and no intervention was undertaken. Post-catheterization ECG revealed resolution of ST segment elevations, TWI in V4-V6, and prolongation of corrected QT. Repeat echocardiogram 10 days after the event demonstrated no improvement in wall motion or ejection fraction. We discuss the possible mechanisms causing ST-elevations and acute myocardial dysfunction after treatment with alemtuzumab. <Learning objective: Alemtuzumab can cause acute myocardial dysfunction after administration of a test dose. Considering that this is a serious adverse effect, detailed cardiac evaluation and a high level of caution are recommended before administration of alemtuzumab. While no clear etiology could be identified for this side effect, excessive and acute cytokine release triggered by alemtuzumab administration is a possible explanation. This could be potentially attenuated by using anti-interleukin-6 or tumor necrosis factor inhibitors.>.


['Acute respiratory distress syndrome' (ARDS) as a serious complication of influenza].
'Acute respiratory distress syndrome' (ARDS) developed as a serious complication of an infection with the influenza virus A (H1N1) ('swine flu') in 3 children: a 15-year-old girl, a 6-year-old boy and a 14-year-old girl. The latter two patients also suffered from septic shock. Intensive ICU treatment, including mechanical ventilation, did not lead to recovery. The first two patients eventually recovered following treatment with extracorporeal membrane oxygenation (ECMO), but the third patient's condition was too unstable for transfer to an ECMO centre. This patient died.


A functional CFTR-NBF1 is required for ROMK2-CFTR interaction.
In a previous study on inside-out patches of Xenopus oocytes, we demonstrated that the cystic fibrosis transmembrane conductance regulator (CFTR) enhances the glibenclamide sensitivity of a coexpressed inwardly rectifying K+ channel, ROMK2 (C. M. McNicholas, W. B. Guggino, E. M. Schwiebert, S. C. Hebert, G. Giebisch, and M. E. Egan. Proc. Natl. Acad. Sci. USA 93: 8083-8088, 1996). In the present study, we used the two-microelectrode voltage-clamp technique to measure whole cell K+ currents in Xenopus oocytes, and we further characterized the enhanced sensitivity of ROMK2 to glibenclamide by CFTR. Glibenclamide inhibited K+ currents by 56% in oocytes expressing both ROMK2 and CFTR but only 11% in oocytes expressing ROMK2 alone. To examine the role of the first nucleotide binding fold (NBF1) of CFTR in the ROMK2-CFTR interaction, we studied the glibenclamide sensitivity of ROMK2 when coexpressed with CFTR constructs containing mutations in or around the NBF1 domain. In oocytes coinjected with ROMK2 and a truncated construct of CFTR with an intact NBF1 (CFTR-K593X), glibenclamide inhibited K+ currents by 46%. However, in oocytes coinjected with ROMK2 and a CFTR mutant truncated immediately before NBF1 (CFTR-K370X), glibenclamide inhibited K+ currents by 12%. Also, oocytes expressing both ROMK2 and CFTR mutants with naturally occurring NBF1 point mutations, CFTR-G551D or CFTR-A455E, display glibenclamide-inhibitable K+ currents of only 14 and 25%, respectively. Because CFTR mutations that alter the NBF1 domain reduce the glibenclamide sensitivity of the coexpressed ROMK2 channel, we conclude that the NBF1 motif is necessary for the CFTR-ROMK2 interaction that confers sulfonylurea sensitivity.


Affective pictures processing is reflected by an increased long-distance EEG connectivity.
Analysis of affective picture processing by means of EEG has invaded the literature. The methodology of event-related EEG coherence is one of the essential methods used to analyze functional connectivity. The aims of the present study are to find out the long range EEG connectivity changes in perception of different affective pictures and analyze gender differences in these long range connected networks. EEGs of 28 healthy subjects (14 female) were recorded at 32 locations. The participants passively viewed emotional pictures (IAPS, unpleasant, pleasant, neutral). The long-distance intra-hemispheric event-related coherence was analyzed for delta (1-3.5 Hz), theta (4-7.5 Hz), and alpha (8-13 Hz) frequency ranges for F3-T7, F4-T8, F3-TP7, F4-TP8, F3-P3, F4-P4, F3-O1, F4-O2, C3-O1, C4-O2 electrode pairs. Unpleasant pictures elicited significantly higher delta coherence values than neutral pictures (p < 0.05), over fronto-parietal, fronto-occipital, and centro-occipital electrode pairs. Furthermore, unpleasant pictures elicited higher theta coherence values than pleasant (p < 0.05) and neutral pictures (p < 0.05). The present study showed that female subjects had higher delta (p < 0.05) and theta (p < 0.05) coherence values than male subjects. This difference was observed more for emotional pictures than for neutral pictures. This study showed that the brain connectivity was higher during emotional pictures than neutral pictures. Females had higher connectivity between different parts of the brain than males during emotional processes. According to these results, we may comment that increased valence and arousal caused increased brain activity. It seems that not just single sources but functional networks were also activated during perception of emotional pictures.


Psychomotor objectives in occupational therapy education.
This article describes the role of educational objective taxonomies in facilitating the specification of intended learning outcomes and the apparent neglect of objectives directed toward psychomotor learning. A review of the literature indicates extensive material is available on motor learning and on the classification of psychomotor levels of behavior according to a systematic framework. Although many of the categories are functional for special areas, no one system has universal applicability. It is suggested that each discipline may need to draw on the literature to formulate its own taxonomic system, and a model taxonomy is offered for occupational therapy education in which levels of psychomotor performance are differentiated by the degree of individuation, the unique quality of performance introduced by the learner. Examples are given at each level and illustrative objectives combine expected behaviors with selected curriculum areas.


Dolichols, ubiquinones, geranylgeraniol and farnesol as the major metabolites of mevalonate in Phytophthora cactorum.
Farnesol, geranylgeraniol, dolichols and ubiquinones were the main radioactive components of the unsaponifiable lipid recovered from Phytophthora cactorum grown in aerated cultures containing [2-(14)C]mevalonate. The (14)C recovered in each of these components was in the approximate proportion 2:4:3:5. When the culture was not aerated no radioactive ubiquinone was recovered. Most of the (14)C recovered in the dolichols was found in dolichol-15 (37%), with decreasing amounts in dolichol-14 (30%) and -13 (14%) and only a little (5%) in dolichol-16, whereas the major components, by weight, of the mixture (13mug/g of damp-dry tissue) were dolichol-14, -15 and -16 in the approximate proportion of 1:3:1. Radioautography of appropriate chromatograms indicated the presence also of traces of radioactivity in dolichol-9, -10, -11, -12 and -17. Most (80%) of the (14)C recovered in the ubiquinones was associated with ubiquinone-9, the rest being in ubiquinone-8. Most (80%) of the weight of ubiquinones (19mug/g of damp-dry tissue) was also ubiquinone-9. The identification of these compounds was by chromatographic methods and, for the ubiquinones and dolichols, was confirmed by mass spectrometry. In addition, the incorporation of 4R- and/or 4S-(3)H from [4-(3)H]-mevalonates showed the expected stereochemistry of biosynthesis, namely that farnesol, geranylgeraniol and ubiquinones were biogenetically all trans and the dolichols each contained three biogenetically trans isoprene residues, the remaining residues being biogenetically cis. The distribution of (14)C in the components of the whole lipid of the fungus was consistent with 97% of both the farnesol and geranylgeraniol being present as the fatty acid ester. The corresponding value for dolichols was 37%. The observation by other workers, that this fungus does not form either squalene or sterol, was confirmed.


Murine prenatal expression of cholecystokinin in neural crest, enteric neurons, and enteroendocrine cells.
Cholecystokinin (CCK) is a regulatory peptide that is primarily expressed in two adult cell types: endocrine cells of the intestine and neurons of the central nervous system. To determine the ontogeny of CCK expression during intestinal organogenesis, we created a mouse strain in which the CCK gene was replaced by a lacZ reporter cassette using homologous recombination in embryonic stem cells. Initially, CCK expression in the developing intestine was limited to the myenteric plexus of the enteric nervous system. This expression pattern was widespread, extending from the proximal stomach into the colon, yet transient, being detected soon after gut tube closure [embryonic day 10.5 (E10.5)] through E15.5. Since enteric neurons are derived from the neural crest, we examined earlier (E8.5-9.5) embryos and concluded that lacZ was expressed in subpopulations of neural tube and neural crest cells. Endocrine cell expression in the intestinal epithelium occurred later, beginning at E15.5 as enteric neuronal expression was dwindling. This expression persisted to yield the adult pattern of scattered single endocrine cells in the upper small intestine. The data show that CCK is a very early marker of both neuronal and endocrine cell lineages in the developing gastrointestinal tract. Furthermore, reverse transcriptase polymerase chain reaction (RT-PCR) analysis showed that CCK receptor transcripts were detected in embryos as early as E10.5, suggesting that CCK signaling is established early in mouse development. Dev Dyn 1999;216:190-200.


Exploring the post-stimulus undershoot with spin-echo fMRI: implications for models of neurovascular response.
As a consequence of neural stimulation the blood oxygenation-level dependent (BOLD) contrast in gradient-echo echo-planar imaging (GE-EPI) based functional MRI (fMRI) leads to an increased MR signal in activated brain regions. Following this, a BOLD signal undershoot below baseline is generally observed with GE-EPI. The origin of this undershoot has been the focus of many investigations using fMRI and optical modalities, but the underlying mechanisms remain disputed. Here, we investigate the BOLD undershoot following visual stimulation by using a purely T₂-weighted fMRI sequence at 1.5 and 3 T. By taking advantage of the field strength dependency of the T₂ BOLD contrast and complete absence of static dephasing effects due to the pure spin echoes, one can draw conclusions about the origin of the BOLD undershoot and test the hypotheses in the literature. We observe a significant undershoot at both field strengths, with constant undershoot-to-main response ratio. This provides strong evidence that the undershoot is caused by BOLD changes due to elevated post-stimulus deoxyhaemoglobin concentration in the small vessels. 'Delayed vascular compliance' as suggested by the well-known Balloon and Windkessel models does not appear capable of explaining the undershoot. Our results also suggest that blood volume changes in arterioles and capillaries, for which there is consistent evidence from optical imaging studies, cannot alone cause the undershoot. This has important implications for models of neurovascular response and provides further support for the decoupling of changes in the rate of oxygen metabolism and blood flow. In addition, we found that an 'arteriolar balloon' (delayed arterial compliance) may provide a plausible explanation for the temporal characteristics of the BOLD undershoot.


Impact of community health centers and Medicaid on the use of health services.
The impact of improved access to health care through the Federal community health center (CHC) and Medicaid programs was examined in five urban low-income areas. Data on access to care and physician, hospital, and dental services utilization were collected by baseline and followup health surveys in the CHCs' services areas. There was a shift in use from hospital clinics to CHCs. Followup surveys indicated that 23 percent of the population reported CHCs as usual source of care. Travel time to source of care was reduced for users of CHCs. Medicaid coverage of the population in the survey areas increased from 16 to 37 percent between the baseline and followup surveys, an interval of 4 to 7 years. Increases occurred in the use of physicians and dental care between the baseline and followup surveys, but the rates scarcely kept pace with the national rates. Respondents who reported CHCs as their usual source of care, however, had a higher rate of physician visits and a lower rate of hospitalization compared with those using private physicians or hospital clinics as the usual source of care. Respondents with Medicaid coverage usually had higher physician and hospital use, irrespective of usual source of care. Both CHC and Medicaid programs contributed to increased use of dental care by providing financial and dental care resources. Although these two programs greatly facilitated the use of health services, disparity in physician and dental utilization remains between the five low-income areas and the averages for the nation.


[Psoriasis in persons suffering from chronic alcoholism].
Clinical and biochemical examinations of 4 groups of patients (n = 118) have revealed specific features in the clinical picture and course of psoriasis in the subjects with concomitant somatic diseases or chronic alcoholism. These features should be borne in mind during the patients' rehabilitation.


Increase in apparent compressibility of cytochrome c upon oxidation.
The apparent molal adiabatic compressibilities of ferri- and ferrocytochrome c have been determined from measurements of density and sound velocity. The values found were +2.99 X 10(-8) and -2.40 X 10(-8) cm5 mol-1 dyne-1 for the ferri and ferro forms, respectively. Experiments were performed on identical solutions containing either the oxidized or reduced form of protein. Solutions of ferricytochrome c were found to have significantly greater adiabatic compressibility than equivalent solutions of ferrocytochrome c at 25 degrees C and pH 7.15. The remarkable similarity of the three-dimensional structures of the ferri and ferro proteins [Takano, T. & Dickerson, R.E. (1980) Proc. Natl. Acad. Sci. USA 77, 6371-6375] strongly suggests that this difference in compressibility is due to an increase in volume fluctuations within ferricytochrome c relative to the ferro form rather than a change in equilibrium structure or hydration. Such a difference in the dynamic properties of the structures is consistent with both the crystallographic thermal B factors and the observed increase in amide hydrogen exchange kinetics when ferrocytochrome c is oxidized. The relative magnitude of the root mean square volume fluctuations is approximated from an ideal solution treatment of the compressibility data and yields a ratio of delta Vrms (ferri cyt c)/ delta Vrms (ferro cyt c) = 1.3.


Kidney transplantation for treatment of end-stage kidney disease after haematopoietic stem cell transplantation: case series and literature review.
The safety of kidney transplantation (KT) for end-stage kidney disease (ESKD) after haematopoietic stem cell transplantation (HSCT) for haematological disease has not been investigated thoroughly. In this retrospective multicentre study, we investigated the clinical courses of six ESKD patients that received KT after HSCT for various haematological diseases. Data for six such patients were obtained from three institutions in our consortium. Two patients with chronic myeloid leukaemia, one with refractory aplastic anaemia and another one with acute lymphocytic leukaemia received bone marrow transplantation. One patients with acute lymphocytic leukaemia received umbilical cord blood transplantation, and one with mantle cell lymphoma received peripheral blood stem cell transplantation. The patients developed ESKD at a median of 133 months after HSCT. Two patients who received KT and HSCT from the same donor were temporarily treated with immunosuppressive drugs. The other patients received KT and HSCT from different donors and were treated with antibody induction using our standard regimens. For one patient with ABO-incompatible transplantation, we added rituximab, splenectomy, and plasmapheresis. In the observational period at a median of 51 months after KT, only one patient experienced acute T-cell-mediated rejection. Four patients underwent hospitalization because of infection and fully recovered. No patient experienced recurrence of their original haematological disease. All patients survived throughout the observational periods, and graft functions were preserved. Despite the high infection frequency, survival rates and graft functions were extremely good in patients compared with previous studies. Therefore, current management contributed to favourable outcomes of these patients.


The effects of cosmic particle radiation on pocket mice aboard Apollo XVII: XI. Results of eye examination.
Five pocket mice (Perognathus longimembris) were flown on Apollo XVII, and four survived. All the eyes, except one eye from the dead flight mouse, were examined histologically. In the four surviving mice, a total of five cosmic ray particles which had registered in the subscalp particle detectors had trajectories that intersected the eyes. Four of them (Z equal to 6-9 for three of the particles and Z larger than or equal to 10 for the fourth) most likely went through the head before reaching the particle detector, while the thindown direction of the fifth (Z larger than or equal to 10) was not determinable. The retinas of the flight animals were found free from histological alterations such as might have been expected from encounters with cosmic ray particles.


Prevalence of vitamin D insufficiency in African American children with forearm fractures: a preliminary study.
Forearm fractures account for a significant proportion of childhood injuries and seem to be increasing in incidence. Poor vitamin D status increases overall fracture risk in infants with rickets and adults with osteoporosis. Children with vitamin D insufficiency (serum 25-hydroxy vitamin D level <20 ng/mL) have decreased bone mineral density (BMD) compared with children having normal vitamin D status. The relationship between vitamin D status and childhood forearm fracture has not been investigated. This prospective study enrolled African American children, aged 5 to 9 years, with a forearm fracture. Bone health evaluation included measurement of serum 25-hydroxy vitamin D level and BMD by dual energy x-ray absorptiometry scan. Univariable analyses were used to test the associations between fracture status and the independent variables, serum vitamin D level and BMD. Vitamin D levels were available for 17 cases. The mean (+/-SD) 25-hydroxy vitamin D level was 20.1 (+/-7.3) ng/mL with a range of 10 to 38 ng/mL. The mean of this group was at the cut point for vitamin D insufficiency. Ten cases (59%) were vitamin D insufficient. Dual energy x-ray absorptiometry scan results for these patients were consistent with normal bony mineralization for age. A significant proportion of African American children with fractures in our study have vitamin D insufficiency. Analysis of serum 25-hydroxy vitamin D levels and BMD in additional cases and controls will determine the significance of these findings. Vitamin D insufficiency may play a previously unrecognized role in childhood fractures. Strong consideration should be given to routine vitamin D testing in African American children with forearm fractures.


A 20-year Follow-up of the International Early Lung Cancer Action Program (I-ELCAP).
Background The low-dose CT (≤3 mGy) screening report of 1000 Early Lung Cancer Action Program (ELCAP) participants in 1999 led to the International ELCAP (I-ELCAP) collaboration, which enrolled 31 567 participants in annual low-dose CT screening between 1992 and 2005. In 2006, I-ELCAP investigators reported the 10-year lung cancer-specific survival of 80% for 484 participants diagnosed with a first primary lung cancer through annual screening, with a high frequency of clinical stage I lung cancer (85%). Purpose To update the cure rate by determining the 20-year lung cancer-specific survival of participants diagnosed with first primary lung cancer through annual low-dose CT screening in the expanded I-ELCAP cohort. Materials and Methods For participants enrolled in the HIPAA-compliant prospective I-ELCAP cohort between 1992 and 2022 and observed until December 30, 2022, Kaplan-Meier survival analysis was used to determine the 10- and 20-year lung cancer-specific survival of participants diagnosed with first primary lung cancer through annual low-dose CT screening. Eligible participants were aged at least 40 years and had current or former cigarette use or had never smoked but had been exposed to secondhand tobacco smoke. Results Among 89 404 I-ELCAP participants, 1257 (1.4%) were diagnosed with a first primary lung cancer (684 male, 573 female; median age, 66 years; IQR, 61-72), with a median smoking history of 43.0 pack-years (IQR, 29.0-60.0). Median follow-up duration was 105 months (IQR, 41-182). The frequency of clinical stage I at pretreatment CT was 81% (1017 of 1257). The 10-year lung cancer-specific survival of 1257 participants was 81% (95% CI: 79, 84) and the 20-year lung cancer-specific survival was 81% (95% CI: 78, 83), and it was 95% (95% CI: 91, 98) for 181 participants with pathologic T1aN0M0 lung cancer. Conclusion The 10-year lung cancer-specific survival of 80% reported in 2006 for I-ELCAP participants enrolled in annual low-dose CT screening and diagnosed with a first primary lung cancer has persisted, as shown by the updated 20-year lung cancer-specific survival for the expanded I-ELCAP cohort. © RSNA, 2023 See also the editorials by Grenier and by Sequist and Olazagasti in this issue.


Afipia clevelandensis antibodies and cross-reactivity with Brucella spp. and Yersinia enterocolitica O:9.
Afipia clevelandensis is a recently described gram-negative bacterium whose potential pathogenic role in human disease is under investigation. Only one strain, from the pretibial lesion of a patient hospitalized with necrotizing pancreatitis for 5 months, has been isolated. Using an indirect immunofluorescence assay to detect anti-A. clevelandensis antibodies, we found a seroprevalence of 1.5% among 30,194 sera routinely submitted for laboratory diagnosis of rickettsial diseases. However, among the 52 patients who were clinically evaluable and who exhibited detectable antibodies against A. clevelandensis, 42% were eventually diagnosed as certainly or probably having brucellosis and 15% were eventually diagnosed as certainly or probably having Yersinia enterocolitica O:9 infection, which is the serotype most often encountered in Europe. Western immunoblotting and cross-adsorption tests showed that an 11.5-kDa proteinase K-labile band and a 21-kDa proteinase-stable band, presumably lipopolysaccharide, were responsible for cross-reactivity among A. clevelandensis, Brucella abortus, and Y. enterocolitica O:9. Other diagnoses included nosocomial infections and various community-acquired diseases for which the role of A. clevelandensis remains undefined. Physicians and clinical microbiologists should be aware of this cross-reactivity in future assessments of the role of A. clevelandensis in human pathology.


Evaluation of drift gas selection in complex sample analyses using a high performance drift tube ion mobility-QTOF mass spectrometer.
A recently developed uniform-field high resolution ion mobility (IM) quadrupole time of flight (Q-TOF) mass spectrometer is used for evaluating the utility of alternate drift gases for complex sample analyses. This study provides collision cross section comparison for 275 total pesticides including structural isomers in nitrogen, helium, carbon dioxide, nitrous oxide and sulfur hexafluoride drift gases. Furthermore, a set of small molecules and Agilent tune mix compounds were used to study the trends in experimentally derived collision cross section values in argon and the alternate drift gases. Two isomeric trisaccharides, melezitose and raffinose, were used to evaluate the effect of the drift gasses for mobility separation. The hybrid ion mobility Q-TOF mass analyzer used in this study consists of a low pressure uniform field drift tube apparatus coupled to a high resolution Q-TOF mass spectrometer. Conventionally, low pressure ion mobility instruments are operated using helium drift gas to obtain optimal structural information and collision cross-section (CCS) values that compare to theoretical CCS values. The instrument employed in this study uses nitrogen as the standard drift gas but also allows the utility of alternate drift gases for improved structural analysis and selectivity under certain conditions. The use of alternate drift gases with a wide range of polarizabilities allows the evaluation of mobility separation power in terms of induced dipole interactions between the drift gas and the analyte ions.


Integrin βν-mediated phagocytosis of apoptotic cells in Drosophila embryos.
To identify molecules that play roles in the clearance of apoptotic cells by Drosophila phagocytes, we examined a series of monoclonal antibodies raised against larval hemocytes for effects on phagocytosis in vitro. One antibody that inhibited phagocytosis recognized terribly reduced optic lobes (Trol), a core protein of the perlecan-type proteoglycan, and the level of phagocytosis in embryos of a Trol-lacking fly line was lower than in a control line. The treatment of a hemocyte cell line with a recombinant Trol protein containing the amino acid sequence RGD augmented the phosphorylation of focal adhesion kinase, a hallmark of integrin activation. A loss of integrin βν, one of the two β subunits of Drosophila integrin, brought about a reduction in the level of apoptotic cell clearance in embryos. The presence of integrin βν at the surface of embryonic hemocytes was confirmed, and forced expression of integrin βν in hemocytes of an integrin βν-lacking fly line recovered the defective phenotype of phagocytosis. Finally, the level of phagocytosis in a fly line that lacks both integrin βν and Draper, another receptor required for the phagocytosis of apoptotic cells, was lower than that in a fly line lacking either protein. We suggest that integrin βν serves as a phagocytosis receptor responsible for the clearance of apoptotic cells in Drosophila, independent of Draper.


Heterodimerization is required for the formation of a functional GABA(B) receptor.
GABA (gamma-aminobutyric acid) is the main inhibitory neurotransmitter in the mammalian central nervous system, where it exerts its effects through ionotropic (GABA(A/C)) receptors to produce fast synaptic inhibition and metabotropic (GABA(B)) receptors to produce slow, prolonged inhibitory signals. The gene encoding a GABA(B) receptor (GABA(B)R1) has been cloned; however, when expressed in mammalian cells this receptor is retained as an immature glycoprotein on intracellular membranes and exhibits low affinity for agonists compared with the endogenous receptor on brain membranes. Here we report the cloning of a complementary DNA encoding a new subtype of the GABAB receptor (GABA(B)R2), which we identified by mining expressed-sequence-tag databases. Yeast two-hybrid screening showed that this new GABA(B)R2-receptor subtype forms heterodimers with GABA(B)R1 through an interaction at their intracellular carboxy-terminal tails. Upon expression with GABA(B)R2 in HEK293T cells, GABA(B)R1 is terminally glycosylated and expressed at the cell surface. Co-expression of the two receptors produces a fully functional GABA(B) receptor at the cell surface; this receptor binds GABA with a high affinity equivalent to that of the endogenous brain receptor. These results indicate that, in vivo, functional brain GABA(B) receptors may be heterodimers composed of GABA(B)R1 and GABA(B)R2.


Reverberation, storage, and postsynaptic propagation of memories during sleep.
In mammals and birds, long episodes of nondreaming sleep ("slow-wave" sleep, SW) are followed by short episodes of dreaming sleep ("rapid-eye-movement" sleep, REM). Both SW and REM sleep have been shown to be important for the consolidation of newly acquired memories, but the underlying mechanisms remain elusive. Here we review electrophysiological and molecular data suggesting that SW and REM sleep play distinct and complementary roles on memory consolidation: While postacquisition neuronal reverberation depends mainly on SW sleep episodes, transcriptional events able to promote long-lasting memory storage are only triggered during ensuing REM sleep. We also discuss evidence that the wake-sleep cycle promotes a postsynaptic propagation of memory traces away from the neural sites responsible for initial encoding. Taken together, our results suggest that basic molecular and cellular mechanisms underlie the reverberation, storage, and propagation of memory traces during sleep. We propose that these three processes alone may account for several important properties of memory consolidation over time, such as deeper memory encoding within the cerebral cortex, incremental learning several nights after memory acquisition, and progressive hippocampal disengagement.


An outbreak of waterborne cryptosporidiosis in Swindon and Oxfordshire.
An outbreak of cryptosporidiosis resulted in 516 cases in Wiltshire and Oxfordshire. The outbreak caused widespread interest and led to an official inquiry. The majority of cases were in children; 8% of cases were admitted to hospital and the median duration of illness was 3 weeks. The geographical distribution of cases matched the distribution of water supplies from three treatment works and cryptosporidium oocysts were found at these works and in the treated water. Attack rates in electoral wards supplied by the three treatment works were significantly higher than in other wards. The cause of the outbreak appeared to be the failure of normal treatment to remove oocysts. Measures at the treatment works reduced the number of oocysts detected in treated water, after which the outbreak came to an end. The conclusion of the investigations was that cryptosporidiosis is a risk of conventionally treated public water supplies.


Reliability of bounce drop jump parameters within elite male rugby players.
The aims of the study were to investigate the number of familiarization sessions required to establish reliability of the bounce drop jump (BDJ) and subsequent reliability once familiarization is achieved. Seventeen trained male athletes completed 4 BDJs in 4 separate testing sessions. Force-time data from a 20 cm BDJ was obtained using two force plates (ensuring ground contact <250 ms). Subjects were instructed to "jump for maximal height and minimal contact time" while the best and average of four jumps were compared. A series of performance variables were assessed in both eccentric and concentric phases including jump height, contact time, flight time, Reactive Strength Index (RSI), peak power, rate of force development (RFD) and actual dropping height (ADH). Reliability was assessed using the intraclass correlation coefficient (ICC) and coefficient of variation (CV) while familiarization was assessed using a repeated-measures analysis of variance (ANOVA). The majority of DJ parameters exhibited excellent reliability with no systematic bias evident, while the average of 4 trials provided greater reliability. With the exception of vertical stiffness (CV: 12.0%) and RFD (CV: 16.2%), all variables demonstrated low within subject variation (CV range: 3.1-8.9%). Relative reliability was very poor for ADH, with heights ranging from 14.87-29.85 cm. High levels of reliability can be obtained from the BDJ with the exception of vertical stiffness and RFD, however, extreme caution must be taken when comparing DJ results between individuals and squads due to large discrepancies between actual drop height and platform height.


Monoclonal antibody solution hybridization assay for detection of mouse hepatitis virus infection.
A monoclonal antibody solution hybridization (MASH) assay was developed to detect fecal excretion of mouse hepatitis virus (MHV). The assay used a biotinylated cDNA probe to detect viral RNA target sequences by hybridization in solution, capture of hybrids on the solid phase with antibiotin antibody, and immunoassay with an enzyme-labelled monoclonal antibody specific for DNA-RNA hybrids. The MASH assay was used to monitor the time course of enterotropic MHV excretion after oronasal inoculation. Infectivity of the inoculated mice was simultaneously monitored with sentinel animals. The MASH assay detected MHV excretion in all inoculated mice, with the highest mean excretion levels occurring from day 3 through day 9 postinoculation. Mean excretion then decreased gradually to below detection limits by day 21 postinoculation. Sentinels became infected on exposure to inoculated mice up to but not after day 21 postinoculation. Infected sentinel mice showed a time course of virus excretion similar to that of inoculated mice. These results indicate that the MASH assay is useful for rapid, sensitive, and specific detection of MHV in clinical specimens from laboratory mice.


Joint analysis of longitudinal data and recurrent episodes data with application to medical cost analysis.
This paper discusses regression analysis of longitudinal data in which the observation process may be related to the longitudinal process of interest. Such data have recently attracted a great deal of attention and some methods have been developed. However, most of those methods treat the observation process as a recurrent event process, which assumes that one observation can immediately follow another. Sometimes, this is not the case, as there may be some delay or observation duration. Such a process is often referred to as a recurrent episode process. One example is the medical cost related to hospitalization, where each hospitalization serves as a single observation. For the problem, we present a joint analysis approach for regression analysis of both longitudinal and observation processes and a simulation study is conducted that assesses the finite sample performance of the approach. The asymptotic properties of the proposed estimates are also given and the method is applied to the medical cost data that motivated this study.


Parameter estimation using meta-heuristics in systems biology: a comprehensive review.
This paper gives a comprehensive review of the application of meta-heuristics to optimization problems in systems biology, mainly focussing on the parameter estimation problem (also called the inverse problem or model calibration). It is intended for either the system biologist who wishes to learn more about the various optimization techniques available and/or the meta-heuristic optimizer who is interested in applying such techniques to problems in systems biology. First, the parameter estimation problems emerging from different areas of systems biology are described from the point of view of machine learning. Brief descriptions of various meta-heuristics developed for these problems follow, along with outlines of their advantages and disadvantages. Several important issues in applying meta-heuristics to the systems biology modelling problem are addressed, including the reliability and identifiability of model parameters, optimal design of experiments, and so on. Finally, we highlight some possible future research directions in this field.


Succession of the Gut Microbiome in the Tibetan Population of Minjiang River Basin.
Tibetans are one of the oldest ethnic groups in China and South Asia. Based on the analysis of 1,059 Tibetans in the Minjiang River basin at an altitude of 500-4,001 m, we found that the dominant phyla of the Tibetan population were Bacteroidota and Firmicutes, and the main genera were Prevotella and Bacteroides, which were mostly in consistent with other nationalities. We further evaluated in total 115 parameters of seven categories, and results showed that altitude was the most important factor affecting the variation in the microbial community. In the process of emigration from high altitudes to the plain, the gut microbial composition of late emigrants was similar to that of plateau aborigines. In addition, regarding immigration from low altitude to high altitude, the microbial community became more similar to that of high altitude population with the increase of immigration time. Changes in these microbes are related to the metabolism, disease incidence and cell functions of the Tibetan population. The results of other two cohorts (AGP and Z208) also showed the impact of altitude on the microbial community. Our study demonstrated that altitude of habitation is an important factor affecting the enterotype of the microflora in the Tibetan population and the study also provided a basis to explore the interaction of impact parameters with gut microbiome for host health and diseases.


Allogeneic hematopoietic stem-cell transplantation for myeloid sarcoma: a retrospective study from the SFGM-TC.
This retrospective multicenter study assessed the outcome of 51 patients with myeloid sarcoma (MS) who underwent allogeneic hematopoietic stem-cell transplantation (alloHSCT). Most patients had MS presenting in conjunction with acute myeloid leukemia (AML) or after AML. Six patients had isolated MS. The median time between diagnosis and alloHSCT was 8 months (range, 2.8 to 67). Forty patients were in complete remission (CR) at time of alloHSCT. With a median follow-up of 33 (range, 1 to 182) months, the Kaplan-Meier estimates of overall survival (OS) and disease-free survival were 47% (95% CI, 33% to 61%) and 36% (95% CI, 24% to 50%) at 5 years. Twenty patients (39%) relapsed at a median of 204 (range, 35 to 1151) days after alloHSCT, with relapse being the major cause of death. In a Cox multivariate analysis, age > or = 15 years and remission status at time of alloHSCT (CR v other) were associated with improved OS (hazard ratio [HR], 0.27; 95% CI, 0.12 to 0.65; P = .003; and HR, 0.22; 95% CI, 0.08 to 0.57; P = .002, respectively). We conclude that first-line alloHSCT performed early in the course of MS is a valid therapeutic option.


[Clinical and laboratory evaluation of efficiency of pectin supplements in patients with chronic renal failure].
The influence of the pectin biologically active supplements (BAS) on some clinical and laboratory parameters was studied in 66 patients with chronic renal failure. The results of the investigations have evidenced that the studied BAS promotes a regress of clinical signs and elimination of uremic toxicants.


Quantifying the Electrostatics of Polycation-Lipid Bilayer Interactions.
Mechanistic insight into how polycations disrupt and cross cell membranes is needed for understanding and controlling polycation-membrane interactions, yet such information is surprisingly difficult to obtain at the molecular level. We use second harmonic and vibrational sum frequency generation spectroscopies along with quartz crystal microbalance with dissipation monitoring and computer simulations to quantify the interaction of poly(allylamine) hydrochloride (PAH) and its monomeric precursor allylamine hydrochloride (AH) with lipid bilayers. We find PAH adsorption to be reversible and nondisruptive to the bilayer under the conditions of our experiments. With an observed free adsorption energy of -52.7 ± 0.6 kJ/mol, PAH adsorption was found to be surprisingly less favorable relative to AH (-14.6 ± 0.4 kJ/mol) when considering a simple additive model. By experimentally quantifying the number of adsorbates and the average amount of charge carried by each adsorbate, we find that the PAH is associated with only 70% of the positive charges it could hold while the AH remains mostly charged while attached to the membrane. Simulations indicate that PAH pulls in condensed counterions from solution to avoid charge-repulsion along its backbone and with other PAH molecules to attach to, and completely cover, the bilayer surface. In addition, computations indicate that the amine groups shift their pKa values due to the confined environment upon adsorption to the surface. Our results provide experimental constraints for theoretical calculations, which yield atomistic views of the structures that are formed when polycations interact with lipid membranes that will be important for predicting polycation-membrane interactions.


Apodization of terahertz Bragg gratings in subwavelength polymer fiber.
We report on an apodization scheme for terahertz fiber Bragg gratings. The grating consists of only 90 ablated notches on two opposite sides of a subwavelength polymer fiber. The grating strength can be effectively tuned by controlling the longitudinal shift between the two-sided notches, and apodization can be achieved by applying an envelope profile. Side lobe suppression of 14 dB was experimentally observed when compared with an unapodized grating.


Natural killer T cells and autoimmune disease.
Natural killer T (NKT) cells are an unusual subset of innate immune cells that express a surface receptor generated by somatic DNA rearrangement, a hallmark of cells of the adaptive immune system. NKT cells express a highly restricted repertoire of T cell receptors that recognize glycolipid antigens bound with the antigen-presenting molecule CD1d. A hallmark of NKT cells is their capacity to produce copious amounts of immunomodulatory cytokines upon antigenic stimulation, which endows these cells with potent immunoregulatory properties. Consequently, NKT cells have been implicated in regulating a wide variety of immune responses, including immune responses against autoantigens. In patients and mice with a variety of autoimmune diseases, numbers and functions of NKT cells are disturbed, but the relevance of these findings to the etiology of autoimmunity remains to be fully established. Nevertheless, in some mouse models of autoimmunity, NKT cell-deficiency exacerbates disease, suggesting that NKT cells play a role in suppressing autoimmunity. Conversely, specific activation of NKT cells with glycolipid antigens generally protects mice against the development of autoimmunity. Most of these studies have employed the potent sponge-derived NKT cell antigen alpha-galactosylceramide (alpha-GalCer). However, alpha-GalCer treatment in mice was associated with detrimental side effects and treatment efficacy was influenced by a variety of parameters, resulting sometimes in disease exacerbation rather than protection. Recent efforts have focused on developing NKT cell agonists with superior treatment efficacy than alpha-GalCer. Collectively, these studies have identified NKT cells as attractive targets for treatment of human autoimmune diseases.


Five-year safety and efficacy of belatacept in renal transplantation.
Belatacept is a first-in-class co-stimulation blocker in development for primary maintenance immunosuppression. A Phase II study comparing belatacept with cyclosporine (CsA) for prevention of acute rejection and protection of renal function in kidney transplant recipients demonstrated similar efficacy and significantly higher measured GFR at 1 year for belatacept, but the incidence of posttransplantation lymphoproliferative disorder was higher. Here, we present the results for the extension of this trial, which aimed to assess long-term safety and efficacy of belatacept. Seventy-eight of 102 patients who were receiving belatacept and the 16 of 26 who were receiving CsA completed the long-term extension period. GFR remained stable in patients who were receiving belatacept for 5 years, and the incidences of death/graft loss or acute rejection were low. The frequencies of serious infections were 16% for belatacept and 27% for CsA, and neoplasms occurred in 12% of each group. No patients who were treated with belatacept and one patient who was treated with CsA developed posttransplantation lymphoproliferative disorder during the follow-up period. Serious gastrointestinal disorders occurred more frequently with belatacept (12% belatacept versus 8% CsA), and serious cardiac disorders occurred more frequently with CsA (2% belatacept versus 12% CsA). Pharmacokinetic analyses showed consistent exposure to belatacept over time. CD86 receptor saturation was higher in patients who were receiving belatacept every 4 weeks (74%) compared with every 8 weeks (56%). In conclusion, this study demonstrated high patient persistence with intravenous belatacept, stable renal function, predictable pharmacokinetics, and good safety with belatacept over 5 years.


Rice bran attenuated obesity via alleviating dyslipidemia, browning of white adipocytes and modulating gut microbiota in high-fat diet-induced obese mice.
Obesity has become an international public health problem. In this study, an obese mice diet was supplemented with raw rice bran (RRB) or infrared radiation-stabilized rice bran (IRRB) to investigate the attenuation of obesity induced by a high-fat diet. Mice were fed a normal diet or a high-fat diet with and without rice bran supplementation (300 mg per kg body weight per day) by oral gavage for 39 days to investigate the obesity preventive effect. The results indicate that different rice bran supplements reduced body weight, relative adipose tissue weight, inflammation, and serum parameters, and relieve liver steatosis to varying degrees. The data of real-time qPCR and western blots (WB) showed that rice bran activated brown adipose tissue (BAT) and increased white adipose tissue (WAT) browning. Rice bran also reduced the ratio of Firmicutes/Bacteroidetes and enhanced the relative abundance of Akkermansia. In summary, our findings suggest that rice bran intervention played a significant role in reducing dyslipidemia, alleviating inflammation, enhancing thermogenesis and modulating gut microbiota for the prevention and control of obesity.


Control of progesterone receptor transcriptional synergy by SUMOylation and deSUMOylation.
Covalent modification of nuclear receptors by the Small Ubiquitin-like Modifier (SUMO) is dynamically regulated by competing conjugation/deconjugation steps that modulate their overall transcriptional activity. SUMO conjugation of progesterone receptors (PRs) at the N-terminal lysine (K) 388 residue of PR-B is hormone-dependent and suppresses PR-dependent transcription. Mutation of the SUMOylation motif promotes transcriptional synergy. The present studies address mechanisms underlying this transcriptional synergy by using SUMOylation deficient PR mutants and PR specifically deSUMOylated by Sentrin-specific proteases (SENPs). We show that deSUMOylation of a small pool of receptors by catalytically competent SENPs globally modulates the cooperativity-driven transcriptional synergy between PR observed on exogenous promoters containing at least two progesterone-response elements (PRE2). This occurs in part by raising PR sensitivity to ligands. The C-terminal ligand binding domain of PR is required for the transcriptional stimulatory effects of N-terminal deSUMOylation, but neither a functional PR dimerization interface, nor a DNA binding domain exhibiting PR specificity, are required. We conclude that direct and reversible SUMOylation of a minor PR protein subpopulation tightly controls the overall transcriptional activity of the receptors at complex synthetic promoters. Transcriptional synergism controlled by SENP-dependent PR deSUMOylation is dissociable from MAPK-catalyzed receptor phosphorylation, from SRC-1 coactivation and from recruitment of histone deacetylases to promoters. This will provide more information for targeting PR as a part of hormonal therapy of breast cancer. Taken together, these data demonstrate that the SUMOylation/deSUMOylation pathway is an interesting target for therapeutic treatment of breast cancer.


Mechanistic considerations in the molecular epidemiology of head and neck cancer.
Head and neck cancer occurs through a complex multistage process that is likely to involve a combination of carcinogen exposure and genetic susceptibility. The primary cause of head and neck cancer are alcohol consumption and cigarette smoking, although the carcinogenic mechanism for these agents is unclear. Molecular epidemiological studies of head and neck cancer can help to clarify the carcinogenic process in several ways, including identification of metabolizing genes which increase the risk of head and neck cancer, identification of DNA adducts in target cells and analysis of specific gene mutations and their relationship with exposure. This review summarizes current knowledge on the molecular epidemiology of head and neck cancer and attempts to identify those areas where future studies may prove fruitful.


Infectious burden as a determinant of atopy-- a comparison between adults in Finnish and Russian Karelia.
Evidence of the influence of pathogen exposure on the development of atopy and atopic disease is not unequivocal. We investigated the association between markers of infections and occurrence of atopy among adults in eastern Finland and western Russia, two adjacent areas with profound differences in living conditions and lifestyles. Randomly selected adults aged 25-54 years from Finland (n = 790) and from Russia (n = 387) participated in the study. Skin prick tests were performed to 11 common airborne allergens, and at least one positive prick reaction was considered to indicate atopy. Antibodies to different pathogens including hepatitis A virus (HAV), Helicobacter pylori, Toxoplasma gondii, herpes simplex virus (HSV), Chlamydia pneumoniae and the periodontal pathogens Porphyromonas gingivalis and Actinobacillus actinomycetemcomitans were measured. In Finland 34.3% and in Russia 23.3% of the study population was atopic (p < 0.001). Seroprevalences to all these pathogens were significantly higher among the Russians. In multivariate logistic regression analysis, only H. pylori was inversely associated with atopy in Russia. A further stepwise analysis revealed that H. pylori alone can explain 32% of the difference in atopy between the countries, and T. gondii, A. actinomycetemcomitans, HSV and C. pneumoniae had a slightly additive effect, whereas, unexpectedly, seropositivity to HAV and, to a lesser extent, P. gingivalis had an opposite effect. The net result of the stepwise analysis showed that 44% of the difference in atopy between the countries could be explained by seropositivity to these seven pathogens. Seropositivity to select pathogens, particularly to H. pylori, could explain a substantial part of the difference in atopy prevalence between Finland and Russia. Exposure to HAV was not associated with protection against atopy in this adult population.


Curcumin ameliorates asthmatic airway inflammation by activating nuclear factor-E2-related factor 2/haem oxygenase (HO)-1 signalling pathway.
Previous studies have shown that curcumin alleviates asthma in vivo. However, the relationship between curcumin and the nuclear factor-E2-related factor 2 (Nrf2)/haem oxygenase (HO)-1 pathway in asthma treatment remains unknown. The aim of the present study was to investigate the mechanisms of curcumin involved in the amelioration of airway inflammation in a mouse asthma model. Curcumin was administrated to asthmatic mice, and bronchoalveolar lavage fluid was collected. Inflammatory cell infiltration was measured by Giemsa staining. Immunoglobulin E production in bronchoalveolar lavage fluid was measured by enzyme-linked immunosorbent assay. Histological analyses were evaluated with haematoxylin-eosin and periodic acid-Schiff staining. Airway hyperresponsiveness was examined by whole-body plethysmography. Nuclear factor-E2-related factor 2, HO-1, nuclear factor-κB and inhibitory κB/p-inhibitory κB levels in lung tissues were detected by western blot, and Nrf2 activity was measured by electrophoretic mobility shift assay. Tumour necrosis factor-α, interleukin (IL)-1β, and IL-6 levels in the small interfering RNA-transfected cells were detected by enzyme-linked immunosorbent assay. Curcumin treatment significantly reduced immunoglobulin E production, attenuated inflammatory cell accumulation and goblet cell hyperplasia, and ameliorated mucus secretion and airway hyperresponsiveness. Nuclear factor-E2-related factor 2 and HO-1 levels in lung tissues were significantly increased. Meanwhile, Nrf2 activity was enhanced. Nuclear factor-κB and p-inhibitory κB levels were elevated in the lung tissue of ovalbumin-challenged mice. Both were restored to normal levels after curcumin treatment. Haem oxygenase-1 and nuclear Nrf2 levels were enhanced in dose- and time-dependent manners in curcumin-treated RAW264.7 cells. Curcumin blocked lipopolysaccharide-upregulated expression of tumour necrosis factor-α, IL-1β, and IL-6. After the cells were transfected with HO-1 or Nrf2 small interfering RNA, lipopolysaccharide-induced pro-inflammation cytokine expression was significantly restored. In summary, curcumin might alleviate airway inflammation in asthma through the Nrf2/HO-1 pathway, potentially making it an effective drug in asthma treatment.


Pre- and intraoperative tractographic evaluation of corticospinal tract shift.
Magnetic resonance with diffusion tensor image (DTI) may be able to estimate trajectories compatible with subcortical tracts close to brain lesions. A limit of DTI is brain shifting (movement of the brain after dural opening and tumor resection). To calculate the brain shift of trajectories compatible with the corticospinal tract (CST) in patients undergoing glioma resection and predict the shift directions of CST. DTI was acquired in 20 patients and carried out through 12 noncollinear directions. Dedicated software "merged" all sequences acquired with tractographic processing and the whole dataset was sent to the neuronavigation system. Preoperative, after dural opening (in 11) and tumor resection (in all) DTI acquisitions were performed to evaluate CST shifting. The extent of shifting was considered as the maximum distance between the preoperative and intraoperative contours of the trajectories. An outward shift of CST was observed in 8 patients and an inward shift in 10 patients during surgery. In the remaining 2 patients, no intraoperative displacement was detected. Only peritumoral edema showed a statistically significant correlation with the amount of shift. In those patients in which DTI was acquired after dural opening as well (11 patients), an outward shifting of CST was evident in that phase. The use of intraoperative DTI demonstrated brain shifting of the CST. DTI evaluation of white matter tracts can be used during surgical procedures only if updated with intraoperative acquisitions.


Systemic complications of commonly used dermatologic drugs.
Systemic complications of drugs commonly prescribed by dermatologists fortunately are uncommon. Nevertheless, it is extremely important that the dermatologist be aware of medical contraindications to the use of these agents, as well as their potential systemic side effects. These considerations for methotrexate, sulfones, tetracyclines, and corticosteroids are reviewed.


Discussing the undiscussable with the powerful: why and how faculty must learn to counteract organizational silence.
Dialogue is essential for transforming institutions into learning organizations, yet many well-known characteristics of academic health centers (AHCs) interfere with open discussion. Rigid hierarchies, intense competition for resources, and the power of peer review in advancement processes all hamper difficult conversations, thereby contributing to organizational silence, and at great cost to the institution. Information necessary for critical decisions is not shared, individuals and the organization do not learn from mistakes, and diverse perspectives from those with less power are not entertained, or worse, are suppressed. When leaders become more skilled at inviting multiple perspectives and faculty more adept at broaching difficult conversations with those in power, differences are more effectively addressed and conflicts resolved. In this article, the authors frame why this skill is an essential competency for faculty and leaders alike and provide the following recommendations to institutions for increasing capacity in this area: (1) develop leaders to counteract organizational silence, (2) develop faculty members' skills in raising difficult issues with those in positions of power, and (3) train mentors to coach others in raising difficult conversations. The vitality of AHCs requires that faculty and institutional leaders develop relational communication skills and partner in learning through challenging conversations.


Browse or browsing: Investigating goat preferences for feeding posture, feeding height and feed type.
Goats naturally browse different forages in various postures; this differs from typical farm practice, thus there are opportunities to improve goat welfare by understanding what and how they like to eat. We investigated if feeding preference was related to posture, feeder height relative to the ground, and type of feed. Sixteen adult, Saanen cross females participated in two experiments comparing a floor-level feeder (grazing posture; farm standard), with an elevated feeder (browsing posture; Exp1) and a platform-level feeder (raised, grazing posture; Exp2), when two forages (leaves, grass) were offered. Measurements included feed intake (g of DM/feeder), feeder switching frequency, first feeder visited, latency to visit first feeder and exploration and non-feeding activity time. Effects of posture (Exp1), height (Exp2) and feed type were analyzed. Type of feed affected preference for feeding posture and height. All goats consumed leaves over grass (Exp1: POP: 188 ± 6.52 g, GRA: 20.3 ± 7.19 g; Exp2: POP: 191 ± 6.15 g, GRA: 0.231 ± 6.91 g; P < 0.001), and the feeder containing leaves was often visited first (Exp 1: GRA/POP: 94% of visits, P < 0.001, POP/GRA: 53%, P = 0.724; Exp 2: GRA/POP: 91%, P < 0.001; POP/GRA: 69%, P = 0.041). When goats received only leaves, they consumed more from the floor-level (162 ± 22.2 g) vs. elevated level (102 ± 21.9 g) feeder (P = 0.039). When goats received only grass, there was no posture or height preference; however, they changed feeders more frequently (at least 4x (Exp1) and 2x (Exp2) more than other combinations; P > 0.01). Feed intake was negatively affected by exploring time (Exp1 only: r = -0.541; P < 0.001) and performing non-feeding activities (Exp1: r = -0.698; P < 0.001; Exp2: r = -0.673; P < 0.001). We did not identify a preference for elevated feeding posture; however, we suggest that our short test (compared to previous work) encouraged goats to make choices based on line-of-sight and also that the elevated feeder design (replicated from previous work) made leaf access harder. Nonetheless, we highlight that some goats actively used the elevated feeder; this coupled with the clear preference for leaves over grass, suggests that offering feed type and presentation diversity would allow individuals to express their natural feeding behavior more fully.


Heat shock proteins and antigens of Mycobacterium tuberculosis.
The heat shock response of Mycobacterium tuberculosis has been characterized in detail by one- and two-dimensional polyacrylamide gel electrophoresis after metabolic labeling with [35S]methionine and 14C-amino acids. A temperature increase from 37 to 42 degrees C induced elevated synthesis of three major proteins corresponding to the DnaK, GroEL, and GroES proteins of M. tuberculosis previously identified as prominent antigens. At higher temperatures (45 to 48 degrees C), synthesis of GroEL decreased and novel heat shock proteins with molecular masses of 90, 28, 20, and 15 kDa were observed. These new proteins did not comigrate with known antigens during two-dimensional gel electrophoresis. The heat shock response is discussed with regard to the possible importance of transcriptional regulation of mycobacterial genes in vivo.


Attribution of Tropospheric Ozone to NO x and VOC Emissions: Considering Ozone Formation in the Transition Regime.
An improved three-regime (3R) O3 attribution technique for O3 source apportionment in regional chemical transport models is developed to divide the entire range of VOC-NO x-O3 formation sensitivity to VOC-limited, transition, and NO x-limited regimes based on the value of a regime indicator R. The threshold R values to mark the start ( Rts) and end ( Rte) of the transition regime are defined at the point where O3-NO x sensitivity turns from negative to positive and where O3-NO x sensitivity is ten times higher than O3-VOC sensitivity, respectively. Rts and Rte are determined using NO x and VOC sensitivity simulations in a box model with a modified SAPRC-11 mechanism. For the widely used indicator ration R = ( PH2O2 + PROOH)/ PHNO3, which is based on the production rates of H2O2, HNO3 and organic hydroperoxides (ROOH), the recommended Rts and Rte values are 0.047 and 5.142, respectively. Parameterized attribution functions, depending only on the values of R, are developed to apportion modeled in situ O3 formation in the transition regime to NO x and VOCs. The new 3R and the traditional two-regime (2R) schemes are incorporated into the Community Multiscale Air Quality (CMAQ) model to quantify NO x and VOC contributions to regional O3 concentrations in China in August 2013. The 3R approach predicts approximately 5-10 ppb and up to 15 ppb higher NO x contributions to 8 h O3 in in the North China Plain, the Yangtze River Delta and the Pearl River Delta than the 2R approach. The big differences in O3 attribution between 2R and 3R can have significant policy implications for air pollution emission controls.


Intracapsular plastic lens loop fixation in the rabbit.
The fixation of two-loop intraocular plastic lenses has been studied in the laboratory. Twenty rabbit eyes underwent extracapsular lens extraction and placement of plastic lens loops within the capsular remnants. Placement was successful in 25 of 40 (62.5%) attempts. The placement of intracapsular lens loops was studied histologically, and the structural alterations were seen to be minimal. There was virtually no cellular response to the implantation of the plastic lenses, even in the areas of tissue contact.


Franchise medicine: how I avoid being a commodity in a global market.
As facial plastic surgery becomes more global, pressures for practices to become commoditized will increase. Commoditized practices are those in which price drives the quality of the product. Franchised surgical practices have also recently increased within the United States and abroad. These are always commoditized by their corporate philosophies. There are better ways to create value than to lower price to compete with a neighboring practice. By establishing a Transcendent Relationship of growth, both the surgeon and the patient are more satisfied with their facial plastic surgical experiences. Key tools helpful in predicting future directions for a practice, the Four Compass Points and the Average Best Patient, will be introduced.


Sphingosine kinase 1 promotes tumor progression and confers malignancy phenotypes of colon cancer by regulating the focal adhesion kinase pathway and adhesion molecules.
Studies suggest a tumor-promoting function of sphingosine kinase 1 (SphK1) in some types of human tumors, however, its effect on colon cancer is still unclear. The aims of this study were to investigate the roles of SphK1 in the progression and tumor cell phenotypic changes in colon cancer. Moreover, the focal adhesion kinase (FAK) pathway and the expression of intercellular adhesion molecule‑1 (ICAM‑1) and vascular cell adhesion molecule‑1 (VCAM‑1) were detected to explore the mechanisms of SphK1 action. In this study, the expression of SphK1, FAK and phospho-FAK (p-FAK) was analyzed in 66 surgical specimens of primary colon cancer and matched adjacent normal tissues by immunohistochemistry and western blotting. In addition, N,N-dimethylsphingosine (DMS), SphK1 DNA and shRNA transfection were used to regulate the expression and activity of SphK1 in the LOVO colon cancer cell line. Tumor cell phenotypic changes were analyzed by cell viability, invasion and apoptosis assays. Results showed that the expression of SphK1, FAK and p-FAK in colon cancer tissues were significantly stronger compared to those in matched normal tissues. There was a close correlation between the expression of SphK1 and FAK or p-FAK and the co-expression of SphK1, FAK and p-FAK significantly associated with histological grade, Dukes' stage, lymph node metastasis and distant metastasis. Overexpression of SphK1 after DNA transfection enhanced tumor cell viability and invasiveness, but suppressed cell apoptosis. In contrast, suppression of SphK1 by DMS and shRNA reduced tumor cell viability and invasiveness, but promoted cell apoptosis. The expression of FAK, p-FAK, ICAM-1 and VCAM-1 in LOVO cells were increased with the overexpression of SphK1 but decreased with the suppression of SphK1. These findings indicate that SphK1 regulates tumor cell proliferation, apoptosis and invasion, which ultimately contributes to tumor progression and malignancy phenotype in colon cancer. FAK pathway, ICAM-1 and VCAM-1 may play critical roles in this SphK1‑mediated effect.


Regulation of poliovirus 3C protease by the 2C polypeptide.
Poliovirus-encoded nonstructural polypeptide 2C is a multifunctional protein that plays an important role in viral RNA replication. 2C interacts with both intracellular membranes and virus-specific RNAs and has ATPase and GTPase activities. Extensive computer analysis of the 2C sequence revealed that in addition to the known ATPase-, GTPase-, membrane-, and RNA-binding domains it also contains several "serpin" (serine protease inhibitor) motifs. We provide experimental evidence suggesting that 2C is indeed capable of regulating virus-encoded proteases. The purified 2C protein inhibits 3C(pro)-catalyzed cleavage of cellular transcription factors at Q-G sites in vitro. It also inhibits cleavage of a viral precursor by the other viral protease, 2A(pro). However, at least three cellular proteases appear not to be inhibited by 2C in vitro. The 2C-associated protease inhibitory activity can be depleted by anti-2C antibody. A physical interaction between 2C and His-tagged 3C(pro) can be demonstrated in vitro by coimmunoprecipitation of 2C with anti-His antibody. Deletion analysis suggests that the 2C central and C-terminal domains that include several serpin motifs are important for 3C(pro)-inhibitory activity. To examine the 2C protease inhibitory activity in vivo, stable HeLa cell lines were made that express 2C in an inducible fashion. Infection of 2C-expressing cells with poliovirus led to incomplete (or inefficient) processing of viral precursor polypeptides compared to control cell lines containing the vector alone. These results suggest that 2C can negatively regulate the viral protease 3C(pro). The possible role of the 2C protease inhibitory activity in viral RNA replication is discussed.


Complete myelography with metrizamide.
Thorough myelography of the entire spinal cord including the foramen magnum region can be accomplished consistently and promptly after metrizamide injection via lumbar or lateral cervical puncture. When lumbar puncture is used the patient's torso is oblique, but the neck is prone and straight and the table is tilted 20 degrees head-down to allow direct cervical filling with contrast material. Each region is filmed in several projections, the patient being turned gently from the prone cervical to the supine thoracic position. Of 100 cases without block studied in this way, all had adequate cervical and foramen magnum films. In only five was the contrast material too dilute to show the edges of the spinal cord well and the subarachnoid sac adequately in the thoracic region. In 29 patients, there were mild side effects not requiring medication, while 20 had side effects of a more moderate to severe nature. No seizures were encountered. Metrizamide proved a convenient, efficient, and acceptable contrast medium for myelography when a study of the entire spinal cord is indicated.


Adult onset Still's disease in the elderly: a report of two cases.
Two patients with the first symptoms of adult onset Still's disease in their 7th decade are reported. In both cases their advanced age was a main reason for a prolonged delay in diagnosis. Besides the characteristic fever pattern, rash and arthritis, our patients showed other typical features of Still's disease such as splenomegaly, pleuritis, pneumonitis, carpal ankylosis and leukocytosis. In addition both showed marked hepatic abnormalities which seemed to be due to the disease itself in one case and at least in part related to exposure to phenylbutazone and diclofenac in the other.