Cardiac catheterization is underutilized after in-hospital cardiac arrest.
Indications for immediate cardiac catheterization in cardiac arrest survivors without ST elevation myocardial infarction (STEMI) are uncertain as electrocardiographic and clinical criteria may be challenging to interpret in this population. We sought to evaluate rates of early catheterization after in-hospital ventricular fibrillation (VF) arrest and the association with survival. Using a billing database we retrospectively identified cases with an ICD-9 code of cardiac arrest (427.5) or VF (427.41). Discharge summaries were reviewed to identify in-hospital VF arrests. Rates of catheterization on the day of arrest were determined by identifying billing charges. Unadjusted analyses were performed using Chi-square, and adjusted analyses were performed using logistic regression. One hundred and ten in-hospital VF arrest survivors were included in the analysis. Cardiac catheterization was performed immediately or within 1 day of arrest in 27% (30/110) of patients and of these patients, 57% (17/30) successfully received percutaneous coronary intervention. Of those who received cardiac catheterization the indication for the procedure was STEMI or new left bundle branch block (LBBB) in 43% (13/30). Therefore, in the absence of standard ECG data suggesting acute myocardial infarction, 57% (17/30) received angiography. Patients receiving cardiac catheterization were more likely to survive than those who did not receive catheterization (80% vs. 54%, p<.05). In patients receiving cardiac catheterization, more than half received this procedure for indications other than STEMI or new LBBB. Cardiac catheterization was associated with improved survival. Future recommendations need to be established to guide clinicians on which arrest survivors might benefit from immediate catheterization.


Bcl-XL: A multifunctional anti-apoptotic protein.
B-cell lymphoma-extra large (Bcl-XL) is one of the anti-apoptotic proteins of the Bcl-2 family that is localized in the mitochondria. Bcl-XL is one of the key regulators of apoptosis that can also regulate other important cellular functions. Bcl-XL is overexpressed in many cancers, and its inhibitors have shown good therapeutic effects. Bcl-XL interacts with Beclin 1, a key factor regulating autophagy. Bcl-XL is essential for the survival of neurons and plays protective roles in neuronal injuries. It can promote the growth of neurons and the correct formation of neural networks, enhance synaptic plasticity, and control neurotoxicity. Bcl-XL can also promote the transport of Ca2+ to mitochondria, increase the production of ATP, and improve metabolic efficiency. In addition, targeting Bcl-XL has shown potential value in autoimmune diseases and aging. In this review, we summarize the functions of Bcl-XL in cancer, autophagy, Ca2+ signaling, neuroprotection, neuronal growth and synaptic plasticity, energy metabolism, immunity, and senescence as revealed by investigations conducted in the past 10 years. Moreover, we list some inhibitors that have been developed based on the functions of Bcl-XL.


Microemboli are not a prerequisite in retinal artery occlusive diseases.
Retinal artery occlusion (RAO) is caused by arterio-arterial or cardiovascular emboli in about 50% of all cases, but the role of non-embolic causes remains unclear. We studied 27 patients with amaurosis fugax (AFX), branch retinal artery occlusion (BRAO), central retinal artery occlusion (CRAO) and anterior ischaemic optic neuropathy (AION). Patients underwent an evaluation of cerebrovascular and cardiovascular risk factors, measurement of haemorheological parameters, and Doppler/duplex sonography including ultrasound detection of cerebral microembolic signals and echocardiography. Forty-one per cent of the patients had internal carotid atherosclerosis but only one patient had microembolic signals, probably due to a cardiac thrombus. Vascular risk factors, especially hypertension, were present in 82% of the patients correlating with abnormal haemorheological parameters such as increased thrombocyte reactivity. Our results indicate that altered haemorheological parameters, especially increased thrombocyte reactivity and vascular risk factors such as arterial hypertension, are non-embolic causes of vascular disease in a significant number of patients with RAO. This should guide diagnostic and therapeutic considerations concerning RAO in cases without proven embolic sources.


Transnasal pancreaticobiliary drains. Indications and insertion technique.
The insertion of pancreaticobiliary drains at the time of endoscopic retrograde cholangiopancreatography can provide access to the bile or pancreatic duct, decompress an obstructed biliary tree, and allow infusion of solubilizing agents to effect gallstone dissolution. Twenty-six patients underwent 32 attempts at drain placement with 90 percent success and 6 percent minor complication rates. The use of pancreaticobiliary drains should supplement traditional diagnostic and therapeutic modalities in patients with surgical lesions of the pancreas or biliary tree.


Metal-Enhanced Fluorescence by Bifunctional Au Nanoparticles for Highly Sensitive and Simple Detection of Proteolytic Enzyme.
Although fluorescence-based analytical methods have been used in intracellular analyses, their sensitivity is low for the precise analysis of intracellular proteolytic enzymes to observe cell apoptosis related to cancer and neurodegenerative diseases. In this study, a metal-enhanced-fluorescence (MEF)-based highly sensitive biosensor for the detection of proteolytic enzymes is proposed for the first time by using a bifunctional Au nanoparticle (AuNP), which is connected to the fluorophore by both single-stranded DNA (ssDNA) and a peptide. Once caspase-3, a proteolytic enzyme, cuts the peptide specifically, the fluorescence signal is drastically increased because the ssDNA maintains an optimal distance for the MEF. The proposed sensing method shows the highly sensitive detection of caspase-3 based on just a simple enzymatic cleavage reaction within 1 h, and caspase-3-related preapoptotic cell detection was successfully carried out with high sensitivity. The proposed sensing method is a rapid, simple, and one-step technique for the real-time monitoring of intracellular proteolytic enzymes and can be applied to the early diagnosis of cancer and neurodegenerative diseases.


Catalytic mechanism of 5-chlorohydroxyhydroquinone dehydrochlorinase from the YCII superfamily of largely unknown function.
TftG, 5-chloro-2-hydroxyhydroquinone (5-CHQ) dehydrochlorinase, is involved in the biodegradation of 2,4,5-trichlorophenoxyacetate by Burkholderia phenoliruptrix AC1100. It belongs to the YCII superfamily, a group of proteins with largely unknown function. In this work, we utilized structural and functional studies, including the apo-form and 2,5-dihydroxybenzoquinone binary complex crystal structures, computational analysis, and site-directed mutagenesis, to determine the dehydrochlorination mechanism. The His-Asp dyad, which initiates catalysis, is strongly conserved in YCII-like proteins. In addition, other catalytically important residues such as Pro-76, which orients the His-Asp catalytic dyad; Arg-17 and Ser-56, which form an oxyanion hole; and Asp-9, which stabilizes the oxyanion hole, are among the most highly conserved residues across the YCII superfamily members. The comprehensive characterization of TftG helps not only for identifying effective mechanisms for chloroaromatic dechlorination but also for understanding the functions of YCII superfamily members, which we propose to be lyases.


FANCM and FAAP24 maintain genome stability via cooperative as well as unique functions.
The DNA remodeling enzyme FANCM and its DNA-binding partner, FAAP24, constitute a complex involved in the activation of Fanconi anemia (FA) DNA damage response mechanism, but neither gene has distinct patient mutants. In this study, we created isogenic models for both FANCM and FAAP24 and investigated their integrated functions in DNA damage response. We found that FANCM and FAAP24 coordinately facilitate FA pathway activation and suppress sister chromatid exchange. Importantly, we show that FANCM and FAAP24 possess nonoverlapping functions such that FAAP24 promotes ATR-mediated checkpoint activation particularly in response to DNA crosslinking agents, whereas FANCM participates in recombination-independent interstrand crosslink repair by facilitating recruitment of lesion incision activities, which requires its translocase activity. Our data suggest that FANCM and FAAP24 play multiple, while not fully epistatic, roles in maintaining genomic integrity.


Myocardial ischemia during stroke: scintigraphic demonstration.
In a 74-year old female, admitted to the Acute Stroke Unit for a cerebral reversible ischemic attack, we investigated the occurrence of ischemic alterations on ECG, recorded during an acute relapse, using 99mTc (MIBI) myocardial scintigraphy. Scintigrams showed a transient anteroseptal and inferior hypoperfusion. This is the first direct demonstration of myocardial ischemia occurring during stroke.


Purification of betaine-aldehyde dehydrogenase from spinach leaves and preparation of its antibody.
Betaine-aldehyde dehydrogenase was purified from spinach leaves and characterized. The molecular weight of the enzyme was estimated to be 120 kDa by a gel filtration chromatography. The enzyme was judged to consist of two identical pieces of the monomeric subunit with molecular weight of 60 kDa. A specific polyclonal antibody was raised against the enzyme subunit.


The calcium-release channel from cardiac sarcoplasmic reticulum: function in the failing and acutely ischaemic heart.
Junctional SR membrane vesicles have been isolated from chronically failing human hearts explanted at transplant operations. Vesicles have been incorporated into artificial planar phospholipid bilayers and the activity of single calcium-release channels investigated under voltage-clamp conditions. The properties of these channels are similar to those previously reported from normal animal tissue and do not provide evidence that the function of individual calcium-release channels is altered in the failing heart. Using radio-labelled ryanodine binding as a specific marker for the calcium-release channel, we demonstrate that, in the sheep heart, ischaemia results in the degradation of the calcium-release channel. The activation of proteases and oxidant stress in the ischaemic and re-perfused post-ischaemic myocardium are likely mediators of cell injury. Using the protease trypsin and the photosensitisation of rose bengal to generate the reactive oxygen species (ROS) singlet oxygen and superoxide radicals we demonstrate a direct effect on the calcium-release channel in vitro. Exposure of junctional SR vesicles to trypsin or oxidant stress resulted in the progressive loss of specific ryanodine binding and the degradation of high molecular weight proteins identified by polyacrylamide gel electrophoresis. The activity of single channels was also modified during exposure to proteolysis or oxidant stress; an initial increase in channel opening was observed followed by irreversible loss of channel function. Degradation of specific proteins, such as the calcium-release channel, may contribute to contractile dysfunction in the ischaemic and reperfused post-ischaemic myocardium.


GC-MS approach revealing hidden nitrite reactions in hemolysate using 18O-labelled nitrite and cysteine-based thiols.
In erythrocytes, nitric oxide (NO) and its autoxidation product nitrite undergo multiple reactions with hemoglobin species to form nitrate, Fe-nitrosyl hemoglobin (HbFe(II)NO), S-nitrosohemoglobin (HbCysβ93SNO), and other intermediates including nitrito-methemoblobin HbFe(III)ONO, nitro-methemoblobin HbFe(III)NO2 and nitrous anhydride (N2O3). Here, we report a stable-isotope dilution GC-MS assay that allows studying reactions of nitrite in hemolysate. The method is based on the use of 18O-labelled nitrite in combination with l-cysteine or N-acetyl-l-cysteine ethyl ester and GC-MS measurement of unlabelled and labelled nitrite and nitrate species. This approach reveals reactions that are hidden at physiological nitrite concentrations.


Impact of folic acid on regulatory B lymphocytes from patients with systemic lupus erythematosus in vitro.
Epigenetic modifications of genomes are of particular interest as numerous studies indicate the correlation between DNA methylation and the development of systemic lupus. As a major methyl group donor, folic acid is an important participant in this process. The aim of this study is to determine the effect of low or high dose folate co-culturing with peripheral blood mononuclear cells (PBMCs) on the secretion of interleukin (IL)10 from regulatory cells from lupus patients or from healthy volunteers. PBMCs from lupus patients and healthy volunteers were isolated and separated CD19+ B cell populations were cultured in the presence of 4 μg/mL or of 16 μg/mL of folic acid and the DNA methylation level as well as the percentages of B lymphocytes were measured. In another experiment, PBMCs were stimulated in vitro for IL10 production with 1 μg/mL recombinant human CD40L and with 2.5 μg/mL unmethylated CpG dinucleotides and cultured in the presence of 4 μg/mL or of 16 μg/mL of folic acid. Although co-culturing with low or high folic acid concentrations had no effect on the methylation level of B lymphocytes, particular patients showed an increase in the population of CD19+ IL10+ as well as of CD19- IL10+ cells. The observed increase may be a consequence of additional indirect or direct methylation of DNA in specific loci of the targeted cells. However, further analysis would clarify the exact mechanism of action of folate and would reveal its immunomodulating potential in this autoimmune disease.


Dying with cancer, living well with advanced cancer.
There are 1.7 million deaths from cancer in Europe each year and by 2020 the World Health Organisation (WHO) estimates that, globally, more than 15 million people will experience cancer and 10 million will die from it each year. Furthermore, as new therapies are developed, people are living longer with cancer than in the past, and the population with cancer will be older. We used epidemiologically based needs assessment approaches to estimate the number of people in Europe with symptoms and problems, published data and reviews to appraise treatment options, issues of communication, family care, bereavement and socio-demographic factors affecting care, and a European survey to consider the types of services. In addition, we used systematic literature review data to appraise the effectiveness of services and factors affecting place of death. The quality of life of virtually all cancer patients with advanced disease is impaired by one or more symptoms, emotional, social, spiritual and communication concerns. Patients have a median of 11 symptoms. In Europe there are up to 1.6 million patients with pain each year, and in around one third of these it will be severe, requiring complex treatment. Almost an equal number are affected by fatigue, and more than 1 in 2 are affected by anxiety and/or depression, breathlessness, insomnia, nausea, constipation and/or anorexia. There is a complex interaction of factors affecting place of death--related to illness, the individual and environment--and although most people want to die at home, in most countries the majority of cancer patients die in hospital. In response to patient and family needs, systematic review shows the effectiveness of palliative care services. However, the distribution of services across Europe is inequitable. Palliative care is becoming increasingly recognised as a vital component of cancer care, but requires investment in research, education and services, incorporating appropriate needs assessment and outcome measurements.


Macroparasite life histories.
Parasites and parasitism is common. Worm macroparasites have evolved life-history traits that allow them to successfully transmit between spatially and temporally separated patches of host resource and to survive within these environments. Macroparasites have common life-history strategies to achieve this, but these general themes are modified in a myriad of ways related to the specific biology of their hosts. Parasite life histories are also dynamic, responding to conditions inside and outside of hosts, and they continue to evolve, especially in response to our attempts to control them and the harm that they cause.


Temperature and pH growth profile prediction of newly isolated bacterial strains from alkaline soils.
Soil microorganisms can form complex and varied communities which interact with each other in many different ways depending on environmental conditions. These microbial diversities are accompanied by different metabolic paths and adaptability reflected even in extreme environments. In recent decades, the biodiversity of microbes in extreme environments has been in scientific focus because such specifically adapted bacteria can improve bioremediation processes in industrial and agricultural applications. Instead of the time-consuming process of identification of new bacterial strains from habitats rich in microbiota, artificial neural networks have been proposed as a mapping model for resolving the problem of prediction of microbial behaviour. The occurrence and diversity of alkaliphilic sporogenic bacteria in alkaline soils were investigated. For this purpose, soil samples were collected from various locations: leached soil from the Danube river, cement factory wastewater accumulation, deposit of limestone near the Bešenovo lake and the Beli Majdan cave in the Fruška gora mountain. According to the obtained results, two empirical models were developed that gave a good fit to experimental data and were able to predict successfully the pH and temperature growth profiles of the natural isolates. The artificial neural network models showed a reasonably good predictive capability (overall R2 for temperature growth profile was 0.727, while the overall R2 for pH growth profile was 0.906). The developed mathematical models provided adequate precision for practical study in the microbiology laboratory and scale-up processes for a wide range of laboratory and industrial applications, where specifically adapted microbial communities are needed. © 2019 Society of Chemical Industry.


Potential relationship between normalization of endometrial epidermal growth factor profile and restoration of fertility in repeat breeder cows.
The present study characterized alterations of the endometrial epidermal growth factor (EGF) and examined potential relationships between normalization of the EGF and restoration of fertility in repeat breeder cows. In Experiment 1, endometrial tissues were obtained by biopsy on Days 3, 7 and 14 of the estrous cycle from 99 fertile dairy cows and normal ranges of uterine tissue EGF concentrations were determined. Then, eight fertile cows were examined for endometrial EGF concentrations on Days 3, 7 and 14 during the three consecutive estrous cycles. All eight cows had a normal EGF profile (EGF concentrations were within the normal ranges of all 3 days) in all three estrous cycles and endometrial EGF concentrations were similar among the three estrous cycles. In Experiment 2, 61 repeat breeder cows were examined EGF profile and 43 (70.5%) cows had altered EGF profiles compared with control profiles. A typical alteration was characterized by decreased concentrations on Days 3 and 14 and accounted for 86.0% of all alterations. When repeat breeder cows with altered EGF profiles (n=17) were left untreated, abnormality persisted in 14 (82.4%) cows at the second examination and only 3 animals became pregnant within the next two estrous cycles. Among 15 cows showing a typical alteration at the first examination, 11 (73.3%) cows had the same alteration until the third examination performed after two infertile inseminations following the second examination. When repeat breeder cows with altered EGF profiles (n=26) were given one of four therapeutic treatments, cows in which the EGF profile normalized after treatment had a greater pregnancy rate than those with altered profiles (11/14 animals versus 3/12 animals pregnant; P<0.05). In conclusion, suppressed endometrial EGF concentrations on Days 3 and 14 may be common alterations and persist between estrous cycles in repeat breeder cows. Potential relationship between normalization of the endometrial EGF profile and restoration of fertility was observed. Additional study to confirm results of the treatment is, however, necessary because the present study used a limited number of animals. Nevertheless, current data suggest that normalization of the EGF profile is one of the prerequisite factors to restore fertility.


Increasing the hydrophyte removal rate of dissolved inorganic phosphorus using a novel Fe-Mg-loaded activated carbon hydroponic substrate with adsorption-release dual functions.
At present, the plant floating bed is mostly used to remediate aquaculture tail water since its obvious advantage of eco-friendly. However, there is still the problem of low phosphorus removal efficiency due to the balance between the floating bed coverage area and the aquaculture area, as well as the phosphorus content fluctuation in water. To solve this problem, a phosphorus-controlling hydroponic substrate prepared from granular activated carbon loaded with nanoiron-magnesium hydroxide (AC-Fe-Mg) was prepared, and the phosphorus adsorption and slow-release performance of AC-Fe-Mg were evaluated. Moreover, the effect of the combination of AC-Fe-Mg and I. pseudacorus L. on phosphorus purification was studied. AC-Fe-Mg exhibited superior adsorption and release ability for phosphorus without substantial interference from coexisting substances such as Cl-, NO3-, HCO3- and humic acid (HA) within the pH range of 5-9. Finally, the phosphorus removal rate reached 98.66% under the combined effect of I. pseudacorus L. and AC-Fe-Mg at the initial P concentration of 20 mg L-1. At a high P-level, phosphorus was sequestered by AC-Fe-Mg and consumed as a growth nutrient by I. pseudacorus L. At a low P-level, phosphorus was released from AC-Fe-Mg and provided to I. pseudacorus L. The regulatory ability of AC-Fe-Mg can provide plants with continuous and stable phosphorus, and maintain the nitrogen-phosphorus ratio for plant demand. Thus, the dissolved inorganic phosphorus was controlled and efficiently removed. Accordingly, the novel AC-Fe-Mg with adsorption and slow-release dual functions can be used as a hydroponic substrate of emergent plants to improve water purification.


WITHDRAWN: Generation of F0F1-ATPase nanoarray by Dip-Pen Nanolithography and its application as biosensor.
This article has been withdrawn consistent with Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). The Publisher apologizes for any inconvenience this may cause.


Current dysphonia trends in patients over the age of 65: is vocal atrophy becoming more prevalent?
The current trends in geriatric voice referrals including the number of patients over the age of 65 years seen per year, the common diagnostic patterns, and specifically the number of patients with vocal atrophy were assessed. Retrospective cohort study. A retrospective chart review of all patients seen at the Emory Voice Center for otolaryngologic complaints between the years of 2004 and 2009 was performed. Of the 6,360 patients seen over a 6-year period, 21% were over the age of 65 years. Fifty-eight percent of patients over the age of 65 years had vocal complaints, with the most common diagnoses being vocal atrophy (25%), neurologic vocal dysfunction (23%), and vocal fold immobility (19.2%). Of those patients diagnosed with vocal atrophy, the majority opted for voice therapy (57%), followed by reassurance (39%), and injection laryngoplasty (6%). There was a statistically significant improvement in mean pretherapy and post-therapy voice-related quality of life (VRQOL) score. As the number of people in the over 65-year-old age bracket increases, so do the number of geriatric referrals. Although diagnostic trends remain the same, vocal atrophy is becoming more prevalent, with a large number of patients seeking intervention. This will likely result in an increased need for health resources in the future.


SOS1 regulates HCC cell epithelial-mesenchymal transition via the PI3K/AKT/mTOR pathway.
The influence of son of sevenless homolog 1 (SOS1) on invasion and metastasis of hepatocellular carcinoma (HCC) cells was investigated. HCC cells were transfected with siRNA and lentivirus to achieve SOS1 knock down/overexpression and changes in RNA and protein levels analyzed by q-PCR and Western blotting (WB). Transwell assay was utilized to assess variations in cell invasion and migration in vitro and by a lung metastasis model of liver cancer in vivo. High expression of SOS1 was observed in most human liver cancers, which indicated a worse prognosis. SOS1 knockout in HepG2 cells significantly decreased cell invasion and migration. SOS1 knockout also reduced the number of metastatic foci in a lung metastasis model of HCC established in nude mice. SOS1 knockout inhibited the epithelial-mesenchymal transition (EMT) in HepG2 cells as well as the PI3K/AKT/mTOR pathway. Overexpression of SOS1 in Huh7 cells had the opposite effect. To conclude, SOS1 may induce the EMT by the activation of the PI3K/AKT/mTOR pathway, thereby enhancing invasion, migration and metastasis of HCC cells. These findings may expose SOS1 as a new HCC therapeutic target.


Rheumatoid pseudocyst (geode) of the femoral neck without apparent joint involvement.
Typically, rheumatoid cysts are associated with obvious joint involvement and are located in the subchondral portion of the adjacent joint. Giant pseudocysts (geodes) are uncommon and are characteristically associated with extensive joint destruction. The patient described in this report had a giant pseudocyst of the femoral neck but no joint involvement. To the best of my knowledge, this is the first report of such a manifestation of a giant pseudocyst. As such, it posed a somewhat difficult diagnostic problem.


Analysis of radiolucent gallstones by computed tomography for in vivo estimation of stone components.
Successful oral litholytic and other nonoperative therapies of gallstones require exact determination of the stone components. Since computed tomography (CT) provides highly sensitive measurement of density, we performed a study to evaluate whether CT measurement of stone density allows a prediction of the composition of radiolucent gallstones. Twenty-eight patients presenting with 29 radiolucent gallbladder (n = 17) or common bile duct stones (n = 12) were included. Prior to operative or endoscopic therapy the attenuation values (Hounsfield Units, HU) were assessed in vivo by CT under standardized conditions (Somatom II, 125 KV, 130 mAs). After surgical or endoscopic stone removal the concrements were dehydrated, homogenized and then analysed by infra-red spectroscopy. The previously measured Hounsfield units were not known to the investigator. Eighteen cholesterol and 11 pigment stones could be identified. The attenuation values (Hounsfield units) of cholesterol stones amounting to 28-98 HU (48.7 +/- 4.4 HU) differed significantly (P less than 0.001) from pigment stones (90-120 HU/105.5 +/- 2.8 HU). We conclude that computed tomography provides exact discrimination between cholesterol and non-cholesterol stones in vivo. Since only cholesterol stones can be dissolved by cheno- and ursodeoxycholic acid we recommend measurement of the radiodensity of gallstones by CT prior to any litholytic therapy. Furthermore the prediction of the stone composition facilitates the decision on extracorporeal shock wave lithotripsy and the selection of specific solvents for contact lysis via a nasobiliary probe.


Paternal effects on offspring traits in Scaphiopus couchi (Anura: Pelobatidae).
Maternal half-siblings sired by large male Scaphiopus couchi had higher probabilities of surviving than maternal half-sibs sired by smaller males. Half-sibs sired by large and small males did not differ in tadpole body weight, duration of larval period, number of toadlets produced, or toadlet body weight. These results suggest that which male a female mates with may influence important components of her offspring's fitness.


On the mechanical, electronic, and optical properties of the boron nitride analog for the recently synthesized biphenylene network: a DFT study.
Recently, a new 2D carbon allotrope named biphenylene network (BPN) was experimentally realized. Here, we use density functional theory (DFT) calculations to study its boron nitride analogue sheet's structural, electronic, and optical properties (BN-BPN). Results suggest that BN-BPN has good structural and dynamic stabilities. It also has a direct bandgap of 4.5 eV and significant optical activity in the ultraviolet range. BN-BPN Young's modulus varies between 234.4[Formula: see text]273.2 GPa depending on the strain direction. Density functional theory (DFT) simulations for the electronic and optical properties of BN-BPN were performed using the CASTEP package within the Biovia Materials Studio software. The exchange and correlation functions are treated within the generalized gradient approximation (GGA) as parameterized by Perdew-Burke-Ernzerhof (PBE) and the hybrid functional Heyd-Scuseria-Ernzerhof (HSE06). For convenience, the mechanical properties were carried out using the DFT approach implemented in the SIESTA code, also within the scope of the GGA/PBE method. We used the double-zeta plus polarization (DZP) for the basis set in these cases. Moreover, the norm-conserving Troullier-Martins pseudopotential was employed to describe the core electrons.


Climatological trends in satellite-derived aerosol optical depth over North India and its relationship with crop residue burning: Rural-urban contrast.
Columnar Aerosol Optical Depths (AOD) over an urban area (Chandigarh) and a rural area (Khera, Fatehgarh Sahib district) situated in the Indo-Gangetic Plains (IGP) of India were analysed to study their temporal heterogeneity in terms of interannual, seasonal and monthly variations. Over the last few decades, IGP has become one of the global hotspots of air pollution due to the increased anthropogenic activities such as traffic, industries, agricultural waste burning etc. Level-2 AODs (550 nm) were retrieved from the Moderate Resolution Imaging Spectroradiometer (MODIS) sensors onboard NASA's Terra and Aqua satellites, for a period of 14 years (2005-2018). The climatological mean Terra-MODIS (Aqua-MODIS) AOD over the urban location was ~0.497 ± 0.238 (0.474 ± 0.228), whereas over the rural location it was 0.542 ± 0.269 (0.534 ± 0.282). Linear trend analysis estimated an increase in annual mean Terra-MODIS (Aqua-MODIS) AOD at a rate of ~0.009 (0.013) per year over the urban site; whereas over the rural location the rate of increase was ~0.003 (0.004) per year. Results show that the observed increase is ~1.49% (2.41%) of climatological mean AOD over the urban location for Terra-MODIS (Aqua-MODIS), whereas, over the rural location, it was ~0.50% (0.67%). Using the HYSPLIT trajectory model, it was concluded that, during post-monsoon, the observed high AODs can be related to massive crop residue burning in the IGP region. These AOD trends can also be used to track the regional anthropogenic air-pollution changes. An empirical relation between AOD and PM10 was established, which can be used to estimate PM10 over the urban and rural areas of IGP (using MODIS AODs), complementing the sparse ground-based monitoring. Further, satellite-based air pollution data can be used for baseline assessment and understanding the impact of control policies such as National Clean Air Programme and to support formulate evidence-based pollution control strategies.


Immunogenicity of a Two Dose Regimen of Moderna mRNA Beta/Omicron BA.1 Bivalent Variant Vaccine Boost in a Randomized Clinical Trial.
We compared the serologic responses of one versus two doses of a variant vaccine (Moderna mRNA-1273 Beta/Omicron BA.1 bivalent vaccine) in adults. A two-dose boosting regimen with a variant vaccine did not increase the magnitude or the durability of the serological responses compared to a single variant vaccine boost.


Selective cleavage of human IgG by the matrix metalloproteinases, matrilysin and stromelysin.
We have shown that two of the matrix metalloproteinases (MMPs), matrilysin and stromelysin-1, are capable of cleaving all of the human IgG subclasses. The cleavage occurs at a conserved site in the CH(2) domain of the heavy chain of IgG, releasing a single chain Fc-like fragment. We have not been able to demonstrate cleavage of IgA, IgD, IgM or IgE classes, which lack the cleavage site, nor could we show cleavage of IgG by collagenase, gelatinase, macrophage metalloelastase or membrane-type (MT)-MMP. This cleavage of IgG, by separating the antigen-binding (Fabprime prime or minute)(2) from the Fc portion, will remove much of the immunoglobulins' functionality, e.g. complement fixation, Fc receptor binding. In the context of a tumour producing matrilysin or stromelysin, this may represent a way in which the tumour protects itself from ADCC. In inflamed or damaged tissues where plasma protein leakage occurs, degradation by MMPs may be a mechanism for clearance of IgG.


Bypass of pyrimidine dimers in DNA of bacteriophage T4 via induction of primer RNA.
Bacteriophage T4 has a third pathway for repair of damaged DNA besides excision repair and recombination repair. This pathway is a mechanism for the toleration of lesions rather than the repair of lesions. The substrate for this process is gapped DNA copied from a damaged template. Evidence indicates that these gaps are filled, giving rise to daughter strands that are sensitive to heat and to treatments with RNAase. These daughter strands subsequently serve as templates for DNA that is resistant to RNAase. This third pathway is dependent upon gene 41 (RNA-priming protein), gene uvsZ (function unknown) and gene 30 (polynucleotide ligase) and is presumed to consist of 4 steps: (1) induction of primer RNA opposite the lesion in the template; (2) elongation of primers by DNA polymerase; (3) ligation of daughter-strand fragments, without removal of primer RNA; (4) replication of DNA carrying RNA sequences, giving homogeneous DNA strands. We have called this process 'Re-initiation repair'.


Sustained Effect of Delayed-Release Dimethyl Fumarate in Newly Diagnosed Patients with Relapsing-Remitting Multiple Sclerosis: 6-Year Interim Results From an Extension of the DEFINE and CONFIRM Studies.
Delayed-release dimethyl fumarate (DMF; also known as gastro-resistant DMF) demonstrated clinical and neuroradiologic efficacy and safety in the Phase 3 DEFINE and CONFIRM trials, and in the extension study (ENDORSE), in patients with relapsing-remitting multiple sclerosis (RRMS). This post hoc analysis assessed DMF efficacy in newly diagnosed patients with RRMS with 6-year minimum follow-up. Patients randomized in DEFINE/CONFIRM to DMF 240 mg twice (BID) or thrice daily (TID) continued on same dosage in ENDORSE. Patients randomized to placebo (PBO) or glatiramer acetate (CONFIRM only) were re-randomized to DMF BID or TID. Results for DMF BID (approved dosage) are reported. Newly diagnosed patients were diagnosed within 1 year prior to DEFINE/CONFIRM entry and either treatment-naive or previously treated with corticosteroids alone. The newly diagnosed population included 144 patients continuously treated with DMF BID in DEFINE/CONFIRM and ENDORSE (DMF/DMF) and 85 treated with PBO for 2 years in DEFINE/CONFIRM followed by 4 years of DMF BID in ENDORSE (PBO/DMF). At 6 years (ENDORSE Year 4), the annualized relapse rates [ARR; 95% confidence interval (CI)] were 0.137 (0.101, 0.186) and 0.168 (0.113, 0.252) for DMF/DMF and PBO/DMF, respectively; representing 19% risk reduction (P = 0.3988). PBO/DMF patients demonstrated improvements in ARR after switching to DMF in ENDORSE: 0.260 (0.182, 0.372) for Years 0-2 (DEFINE/CONFIRM) and 0.102 (0.064, 0.163) for Years 3-6 (ENDORSE), representing 61% risk reduction for Years 3-6 versus Years 1-2 (P < 0.0001). The proportion of patients with 24-week confirmed disability progression (95% CI) at 6 years was 15.7% (10.3%, 23.7%) in DMF/DMF and 24.3% (15.9%, 36.2%) in PBO/DMF, representing 49% risk reduction versus PBO/DMF (P = 0.0397). Long-term DMF treatment demonstrated strong and sustained efficacy in newly diagnosed patients. Results suggest greater clinical benefits with earlier initiation of treatment in this patient population. Biogen. ClinicalTrials.gov identifiers, NCT00835770 (ENDORSE); NCT00420212 (DEFINE); NCT00451451 (CONFIRM).


Differences in Spatiotemporal Patterns of Vehicle Collisions with Wildlife and Livestock.
Road ecology research has tended to focus on wildlife-vehicle collisions (WVCs) while omitting or failing to differentiate domestic (i.e., livestock) animal-vehicle collisions (DAVCs). This has limited our understanding of where, when, and how frequently DAVCs occur, and whether these patterns differ from those for WVCs. We used a 10-year collision data set for the U.S. state of Montana to compare temporal and spatial patterns of DAVCs versus WVCs at multiple scales. WVCs exhibited two diel peaks (dawn and dusk) versus only one prominent peak (late evening/early night) for DAVCs. Seasonal patterns of WVCs and DAVCs were broadly similar, but DAVCs exhibited a more pronounced late-fall peak. At the county scale, DAVCs were overrepresented relative to WVCs in most of eastern Montana and underrepresented in most of western Montana. WVC and DAVC hotpots did not show strong overlap at the 1-mile road segment scale. Our results suggest that DAVCs warrant greater attention, and they may represent a high priority for management and mitigation measures in some areas because (1) they can be locally common even when regionally rare, (2) they are more dangerous to motorists on a per-collision basis than WVCs, and (3) they can present a legal liability for livestock owners. Mitigation measures for DAVCs may differ from those for WVCs and require further development and testing. Future data collection efforts should include information not only on the location and timing of animal-vehicle collisions, but also on the species of animals killed.


Sensory receptors associated with the stylets and cibarium of the rice brown planthopper, Nilapavarta lugens.
The stylets of Nilapavarta lugens consist of two maxillae that interlock to form separate food and salivary ducts partially surrounded by two mandibles. The ultrastructure of the sensory innervation of the stylets is described. Each maxilla possesses five neurones which extend to the tip of the stylet. The mandibles also contain five neurones, four of which are paired. The paired neurones comprise a shorter dendrite extending part of the way along the stylet and a longer one extending to the tip. The possible functions of these neurones are discussed. Gustatory receptors are located in the small passageway leading from the food duct to the cibarium. The receptors are in two distinct groups on the epipharyngeal side and one group on the hypopharyngeal side of the food canal. Two to five neurones innervate each receptor which connects to the food canal via a small pore.


Bacterial contamination on household toys and association with water, sanitation and hygiene conditions in Honduras.
There is growing evidence that household water treatment interventions improve microbiological water quality and reduce diarrheal disease risk. Few studies have examined, however, the impact of water treatment interventions on household-level hygiene and sanitation. This study examined the association of four water and sanitation conditions (access to latrines, improved sanitation, improved water and the plastic biosand filter) on the levels of total coliforms and E. coli on existing and introduced toys during an on-going randomized controlled trial of the plastic biosand filter (plastic BSF). The following conditions were associated with decreased bacterial contamination on children's toys: access to a latrine, access to improved sanitation and access to the plastic BSF. Overall, compared to existing toys, introduced toys had significantly lower levels of both E. coli and total coliforms. Results suggest that levels of fecal indicator bacteria contamination on children's toys may be associated with access to improved water and sanitation conditions in the home. In addition, the fecal indicator bacteria levels on toys probably vary with duration in the household. Additional information on how these toys become contaminated is needed to determine the usefulness of toys as indicators or sentinels of water, sanitation and hygiene conditions, behaviors and risks.


Response of chickens carrying germline insert ALVA11 to challenge with a field strain of subgroup A avian leukosis virus.
The ALVA11 germline insert in chickens is a defective subgroup A avian leukosis virus (ALV) proviral insert that expresses a low-to-moderate level of subgroup A ALV envelope glycoprotein. Chicks carrying or lacking ALVA11 were evaluated for response to challenge by RPL-42, a pathogenic field strain of subgroup A ALV, by either exposure to chicks shedding RPL-42 or direct injection with various doses of RPL-42. Chicks carrying ALVA11 were significantly more resistant, as measured by infectious virus and viral antibody status, to horizontal infection and direct injection of RPL-42 than chicks lacking ALVA11.


Lesions in suprachiasmatic nuclei simulate effects of pinealectomy on prolactin release in ovariectomized and sulpiride-treated female rats.
Previous studies indicate that the pineal gland alters prolactin secretion, and it was suggested that at least part of the effect of the pineal hormone melatonin on prolactin release may be mediated by the hypothalamic structures. In this study, pinealectomy and lesions of the suprachiasmatic nuclei were found to alter serum levels of prolactin in the same direction, an effect that was counteracted by daily afternoon melatonin administration. Melatonin, but not other pineal indoles, also prevented sulpiride-induced prolactin secretion in pinealectomized or suprachiasmatic nuclei-lesioned and ovariectomized rats, which suggested that the pineal gland can modulate prolactin secretion by acting through a dopamine mechanism independent of hypothalamic suprachiasmatic structures.


Interstitial Pneumonia with Autoimmune Features: What the Rheumatologist Needs to Know.
This narrative review will focus on the role of the rheumatologist in evaluating patients with interstitial lung disease (ILD) without a defined rheumatic disease and will outline the current classification criteria for interstitial pneumonia with autoimmune features (IPAF) and describe what is known regarding IPAF pathobiology, natural history, prognosis, and treatment. Lastly, knowledge gaps and opportunities for future research will be discussed. IPAF is a recently defined classification of ILD patients who have features suggesting an autoimmune-mediated process, but do not fulfill current rheumatic disease criteria. The goal of the IPAF criteria is to provide a uniform case definition for the study of autoimmune ILD patients who do not currently fit within standard ILD diagnostic categories, ultimately improving diagnosis and therapy. Many of these patients are referred for rheumatologic evaluation to aid the diagnostic process. The care of the IPAF patient is complex and is multidisciplinary with pulmonology, rheumatology, pathology, radiology, physical therapy, primary care, pulmonary transplant providers all serving vital roles. The rheumatologist has several roles which include classification, disease monitoring, and management.


A case of lymphocytic interstitial pneumonia presenting with a ground glass nodule as an initial finding.
A 65-year-old woman had a ground glass nodule, which was suspicious for lung cancer, in her right lung S6 by chest computed tomography. For diagnosis, video-assisted thoracoscopic surgery was performed, and the specimen showed a pathological pattern of lymphocytic interstitial pneumonia (LIP). Four years after surgery, new localized ground glass shadows gradually increased on the base of the lung. However, because she had no respiratory symptoms and had normal respiratory function, she was observed with no medication. Subsequently, no other underlying diseases associated with LIP developed. The ground glass nodule was the initial lesion of LIP.


Poland syndrome with extracorporeal intercostal liver herniation and thoracic myelomeningocele.
Poland syndrome is characterized by hypoplastic unilateral chest wall structures. These chest wall deformities may be associated with upper extremity anomalies. The association of Poland syndrome with either intercostal liver herniation or a spinocerebral deformity has been described, but there is no report of both findings encountered simultaneously. This is the first report of a newborn child with Poland syndrome associated with an intercostal liver segment herniation and thoracic myelomeningocele with features of an Arnold-Chiari II cerebral malformation.


Characterization of the maize prolamin box-binding factor-1 (PBF-1) and its role in the developmental regulation of the zein multigene family.
A maize prolamin box (P-box)-binding factor (PBF-1) has been purified and characterized from immature endosperm tissue. PBF-1 has a molecular weight of 38kDa. It is detected only in endosperm, but not in root or leaf tissues, consistent with its tissue-specific function. Site-directed mutagenesis experiments reveal that both the P-box and its flanking sequences are important for PBF-1 DNA binding. Developmental studies show that PBF-1 accumulates in the endosperm from 8 to at least 30days after pollination (DAP). From 16 to 24DAP, however, multiple shifted bands of protein(s)-DNA complexes can be observed, which correlate with an increase in zein gene expression. PBF-1 can also bind to the P-box from '22-kDa' and '19-kDa' zein promoters, but at a lower affinity than to the '27-kDa' zein promoter. The effects of protein dephosphorylation and zinc ion chelators on PBF-1 DNA binding activity are also shown. A model is proposed where PBF-1 serves as a 'recruiter' of class-specific transcription factors like Opaque2 (O2).


Pure endoscopic ultrasonic removal of choroid plexus papillomas of the third ventricle: technical report of two cases.
Tumors of the choroid plexus of the third ventricle are uncommon. Surgical excision is technically challenging because of the rich vascularisation, central location, and high incidence in young children. Open microsurgical resection is considered the standard treatment. However, attempts at purely endoscopic removal of choroid plexus tumors of the third ventricle have also been made in the past, with encouraging results. We report our experience with endoscopic ultrasonic removal of two cases of tumors of the third ventricular choroid plexus. The first case was a large atypical choroid plexus papilloma (WHO grade 2) in the anterior third ventricle associated with hydrocephalus; the second case was a smaller choroid plexus papilloma (WHO grade 1) in the middle/posterior third ventricle without overt hydrocephalus requiring a more anterior neuronavigation guided approach. Choroid plexus papillomas of the third ventricle can be safely treated by a purely endoscopic approach because they are usually smaller than their counterparts in the lateral ventricle and often have a recognizable vascular pedicle. Early detection and control of the vascular pedicle at the choroidal border is key to success. The use of ultrasonic aspirator facilitates and expedites endoscopic access. By alternating surface coagulation with fragmentation and aspiration with the ultrasonic aspirator, the tumor can be removed without difficult dissection maneuvers.


Influence of protic ionic liquids on the structure and stability of succinylated Con A.
We report the synthesis of a series of ionic liquids (ILs) from various ions having different kosmotropicity including dihydrogen phosphate (H(2)PO(4)(-)), hydrogen sulfate (HSO(4)(-)) and acetate (CH(3)COO(-)) as anions and chaotropic cation such as trialkylammonium cation. To characterize the biomolecular interactions of ILs with protein, we have explored the stability of succinylated Con A (S Con A) in the presence of these aqueous ILs, which are varied combinations of kosmotropic anion with chaotropic cation such as triethylammonium dihydrogen phosphate [(CH(3)CH(2))(3)NH][H(2)PO(4)] (TEAP), trimethylammonium acetate [(CH(3))(3)NH][CH(3)COO] (TMAA), trimethylammonium dihydrogen phosphate [(CH(3))(3)NH][H(2)PO(4)] (TMAP) and trimethylammonium hydrogen sulfate [(CH(3))(3)NH][HSO(4)] (TMAS). Circular dichroism (CD) and fluorescence experiments have been used to characterize the stability of S Con A by ILs. Our data distinctly demonstrate that the long alkyl chain IL TEAP is a strong stabilizer for S Con A. Further, our experimental results reveal that TEAP is an effective refolding enhancer for S Con A from a thermally denatured protein structure.


Factors affecting cognitive dysfunction screening for Latinx adults with type 2 diabetes.
To examine influences on screening of Latinx adults with type 2 diabetes for cognitive problems by identifying patient-, clinician-, and clinic-level factors. This was a mixed methods study consisting of semi-structured interviews with Latinx adults with type 2 diabetes (n = 30; mean age = 68; 57% Mexican American) and surveys and interviews with health care providers (n = 15) in Central Texas. Data were examined with thematic analysis (interviews) and descriptive statistics (surveys and inventories). For the interviewed patients, screening was important, but inability to work related to a possible diagnosis of dementia was a concern. Both providers and patients agreed that other health issues (e.g., hyperglycemia) took precedence over cognitive screening. Providers (96.7%) were expected to screen patients but lacked clinic support and time; they relied on patients for initial prompts. Only one clinic required staff education on cognitive screening, with an emphasis on potential cultural differences in test results and adequate resources related to dementia for Latinx adults. Clinics serving Latinx adults have a responsibility to deliver appropriate care. Leadership should consider innovative practices such as the creation, with patients, of educational materials for screening-a need highlighted by most participants.


Jurisdictional trends in opioid overdose deaths, 1988-96.
This report analysed data on opioid overdose mortality between 1988 and 1996 to: examine differences between jurisdictions in the rate of fatal opioid overdose and the rate of increase in overdose; and estimate the proportion of all deaths which were attributed to opioid overdose. Australian Bureau of Statistics (ABS) data were obtained on the number of deaths attributed to opioid dependence (ICD 9 codes 304.0, 304.7) and accidental opioid poisoning (ICD 9 codes E850.0, E850.1). The highest rate of fatal overdose occurred in NSW, followed by Victoria. The standardised mortality rate among other jurisdictions fluctuated quite markedly. While the rate of opioid overdose has increased throughout Australia, the rate of increase has been greater in some of the less-populous states and territories than it has in NSW or Victoria. In 1996, approximately 6.5% of all deaths among people aged 15-24 years and approximately 10% of all deaths among those aged 25-34 were due to opioid overdose. During the interval from 1988 to 1996, the proportion of deaths attributed to opioid overdose increased. From 1988 to 1996, the proportion of deaths attributed to opioid overdose among individuals aged 25-34 years was approximately one-third that attributed to suicide, but this proportion had increased to approximately one-half by 1996. The rate of increase in the proportion of deaths attributed to opioid overdose was higher than the rate of increase in the proportion of deaths attributed to suicide.


Diagnosis and management of primary cicatricial alopecia: part II.
The second part of this 2-part article reviews clinical features, histology, management, and treatment of neutrophilic primary cicatricial alopecias (folliculitis decalvans and dissecting folliculitis) and mixed primary cicatricial alopecias (acne keloidalis, acne necrotica, and erosive pustular dermatosis).


Examining parents' behaviors and supervision of their children in the presence of an unfamiliar dog: does The Blue Dog intervention improve parent practices?
Young children are at particular risk for dog bite injuries. This study examined parents' supervision of and reactions to their children in the vicinity of an unfamiliar dog. A pre/post intervention/control group randomized design assessed whether exposure to The Blue Dog, a dog bite prevention and education program, positively impacted parent behaviors. No group differences in pre or post-intervention measures emerged, indicating that The Blue Dog did not evoke improvements in parents' behaviors. Generally, parents showed risky reactions and encouraged children to interact with the dog, even though they knew very little about the dog's safety or disposition. Supervision measures (proximity, watching) remained unchanged (watching) or more lax (proximity) across sessions. The results highlight the importance of targeting parent behavior, not just child behavior, in programs that aim to reduce risk of childhood dog bites. The Blue Dog did not effectively change parent behavior.


Butterfly-shaped mark: a variant form of nevus flammeus simplex.
A red-violet, rhomboid-shaped mark on the sacrum of 25 children is described. It is recognized, for the first time, as a part of the nevus flammeus simplex distribution; it is less common than the erythema nuchae or the facial salmon patch. It has the tendency to disappear more slowly than other forms of nevus flammeus simplex. No further investigations seem indicated.


Distribution of biotypes of Haemophilus influenzae and H parainfluenzae in patients with cystic fibrosis.
One hundred and eighty eight isolates of Haemophilus influenzae and 187 isolates of H parainfluenzae from patients with cystic fibrosis, patients with respiratory infections but without cystic fibrosis, and patients with neither cystic fibrosis nor respiratory infections were biotyped. Biotype I of H influenzae were found significantly more often in patients with cystic fibrosis compared with those with normal respiratory tracts. On the other hand, biotype II strains of H influenzae were found less often in the cystic fibrosis group. Half of the biotype V strains produced beta-lactamase.


Different approaches to test orientation of self in space: comparison of a 2D pen-and-paper test and a 3D real-world pointing task.
Spatial orientation is based on a complex cortical network with input from multiple sensory systems. It is affected by training, sex and age as well as cultural and psychological factors, resulting in different individual skill levels in healthy subjects. Various neurological disorders can lead to different patterns or specific deficits of spatial orientation and navigation. Accordingly, numerous tests have been proposed to assess these abilities. Here, we compare the results of (1) a validated questionnaire-based self-estimate of orientation/navigation ability (Santa Barbara Sense of Direction Scale, SBSODS) and (2) a validated pen-and-paper two-dimensional perspective test (Perspective Taking Spatial Orientation Test, SOT) with (3) a newly developed test of finger-arm pointing performance in a 3D real-world (3D-RWPT) paradigm using a recently established pointing device. A heterogeneous group of 121 participants (mean age 56.5 ± 17.7 years, 52 females), including 16 healthy volunteers and 105 patients with different vestibular, ocular motor and degenerative brain disorders, was included in this study. A high correlation was found between 2D perspective task and 3D pointing along the horizontal (azimuth) but not along the vertical (polar) plane. Self-estimated navigation ability (SBSODS) could not reliably predict actual performance in either 2D- or 3D-tests. Clinical assessment of spatial orientation and memory should therefore include measurements of actual performance, based on a 2D pen-and-paper test or a 3D pointing task, rather than memory-based questionnaires, since solely relying on the patient's history of self-estimated navigation ability results in misjudgments. The 3D finger-arm pointing test (3D-RWPT) reveals additional information on vertical (polar) spatial performance which goes undetected in conventional 2D pen-and-paper tests. Diseases or age-specific changes of spatial orientation in the vertical plane should not be clinically neglected. The major aim of this pilot study was to compare the practicability and capability of the three tests but not yet to prove their use for differential diagnosis. The next step will be to establish a suitable clinical bedside test for spatial memory and orientation.


Epidemiology, tumour biology and histopathological classification of neuroendocrine tumours of the gastrointestinal tract.
The diffuse neuroendocrine cell gives rise to a heterogeneous population of tumours which differ in their morphological and functional features. The term 'carcinoid', although well established in medical terminology, is therefore no longer adequate to cover the entire spectrum of neuroendocrine neoplasms. Here we use the term neuroendocrine tumours (NET), which was suggested in the WHO classification of 2000, and review the most important NET entities that are currently recognised in the gastrointestinal tract, highlighting their distinguishing features.


Image quality of virtual monochromatic images obtained using 320-detector row CT: A phantom study evaluating the effects of iterative reconstruction and body size.
To compare the image quality between virtual monochromatic spectral (VMS) images obtained using 320-row detector CT and polychromatic 120-kVp images reconstructed with or without iterative reconstruction using various phantom sizes. Torso phantoms simulating three patient sizes and containing four syringes filled with water or different contrast media (5, 10, 15mgI/mL15mgI/ml) were used. The phantoms were scanned using dual-energy (80/135-kVp) and single-energy (120-kVp) protocols at different settings (20mGy, 12mGy, and 6mGy). VMS images were generated at 1-keV intervals (range, 35-135keV). Both the VMS images and the single-energy 120-kVp images were reconstructed using filtered back projection (FBP) and adaptive iterative dose reduction 3D (AIDR-3D). The signal-to-noise ratio (SNR), and the contrast-to-noise ratio (CNR) were assessed. Using FBP reconstruction, the SNR and CNR of the VMS images were lower than or similar to those of the 120-kVp images for most dose settings. Using AIDR-3D reconstruction, however, the 70-keV VMS images had higher SNRs and CNRs than the 120-kVp images at most settings. The image quality of VMS images with FBP reconstruction tended to be lower than that of the 120-kVp images. With the use of AIDR-3D, however, approximately 70-keV VMS images had a higher image quality than the 120-kVp images.


Premature pubarche, ovarian hyperandrogenism, hyperinsulinism and the polycystic ovary syndrome: from a complex constellation to a simple sequence of prenatal onset.
Adolescent girls with a history of premature pubarche have an increased incidence of functional ovarian hyperandrogenism [a form of polycystic ovary syndrome (PCOS)] at adolescence, which is usually associated with hyperinsulinemia and dyslipemia. The hyperinsulinemia and lipid disturbances can often be detected in the prepubertal period and throughout puberty, and are associated with an exaggerated ovarian androgen synthesis. Birthweight SD scores are lower in premature pubarche girls than in control girls, and particularly so in those girls who show hyperinsulinemia and subsequently develop ovarian hyperandrogenism. Therefore, although the mechanisms interlinking the triad of premature pubarche, hyperinsulinism and ovarian hyperandrogenism remain enigmatic, these data indicate that the triad may result, at least in part, from a common early origin, rather than from a direct interrelationship later in life.


Equivalent hearing threshold levels for the Etymotic Research ER-10C otoacoustic emission probe.
To determine the equivalent threshold sound pressure levels (ETSPL) for a commercially available distortion product otoacoustic emission (DPOAE) probe, and to study the impact of probe fitting and eartip size on the calibration. Twenty-eight otologically normal test subjects participated in the ETSPL determination for the Etymotic Research ER-10C probe. ETSPLs were determined up to 16 kHz and were compared to the reference hearing thresholds associated with the ER-3A insert earphone. Both 'regular' and 'baby' foam eartips were used. At most frequencies, no significant threshold differences were observed between the insert earphone and the DPOAE probe. However, at 1 kHz and 4 kHz, the mean thresholds for the insert earphone were generally lower than those for the DPOAE probe, suggesting systematic differences at those frequencies. Repeated calibration runs resulted in deviations of about 0.6 dB. Similar deviations were noticed when using foam eartips of different sizes up to 10 kHz. Knowing the reference thresholds for DPOAE probes enables measurements of (subjective) hearing thresholds and (objective) otoacoustic emissions using the same probe. Probe fitting and eartip size had negligible effect on the determination of ETSPLs. The obtained data may be proposed for inclusion in future audiometry standards.


Changes in aerobic microflora of skin and gills of Mediterranean sardines (Sardina pilchardus) during storage in ice.
Sardines from the Adriatic Sea were examined fresh and after 4 and 8 days of storage in ice. A total of 1500 strains isolated were identified from the gills and the surface of the fish. Pseudomonadaceae, Neisseriaceae, Flavobacterium/Cytophaga, Enterobacteriaceae, coryneform bacteria and Micrococcaceae were the most common bacteria in fresh fish. During storage the pseudomonads (mainly the non-fluorescent strains) increased and became the dominating microflora; the Neisseriaceae (Moraxella, Psychrobacter and Acinetobacter) showed a distinct increase during the first 4 days in ice; the percentage of the other bacterial groups clearly decreased. On the gills the quantitative changes in the microflora were less pronounced than on the surface.


[Not a pneumothorax again! Birt-Hogg-Dubé syndrome: a case report].
Case discussion of a 40-year-old male patient with a history of recurrent pneumothoraces due to Birt-Hogg-Dubé syndrome. In addition to conservative treatment of a pneumothorax on the left side, a subtotal parietal pleurectomy on the right side was performed after recurrence of a pneumothorax 6 years later. CT of the thorax showed high-grade structural remodelling of the lung parenchyma with cystic lung lesions on both sides with a diameter of up to 7.5 cm. After exclusion of alpha-1 antitrypsin deficiency, underlying immunological disease, unremarkable family and occupational history, Birt-Hogg-Dubé syndrome was suspected based on the morphological distribution pattern of the cystic lung lesions. Genetic examination helped detect a heterozygous pathogenic variant in the FLCN gene, namely c.1294_1298del;p.(Ser432Argfs*22). Birt-Hogg-Dubé syndrome is a rare genetic disorder clinically characterized by pulmonary cysts, fibrofolliculomas of the skin and occurrence of clustered renal tumors. In particular, the increased risk of renal malignancies and the risk of spontaneous pneumothoraces underlines the importance of early diagnosis and screening of affected patients and their families.


Risk of second primary cancer in patients with head and neck squamous cell carcinoma: a systemic review and meta-analysis.
Second primary cancer is a common event in patients with head and neck squamous cell carcinoma. However, the incidence and relevant factors vary by studies. We conducted a systematic review and meta-analysis of observational studies to estimate the incidence and relevant risk factors. PubMed and Web of Science were searched for studies published between January 2000 and December 2020 that reported the incidence of SPC in HNSCC patients. Per 1000-person-year incidence and odds ratios were used to estimate the incidence and potential risk factors. Due to the high heterogeneity, random-effects models were used to estimate the incidence and 95% confidence interval. Seven thousand seven hundred thirteen articles were identified from the databases, in which 60 studies were included in this meta-analysis. The pooled incidence of the total, synchronous, and metachronous SPC in patients with HNSCC were 29.116 per 1000-person-year, 6.960 per 1000-person-year, and 26.025 per 1000-person-year, respectively. The head and neck region was the most common area where SPC occurred, followed by the lung (7.472 per 1000-person-year) and upper digestive tract (2.696 per 1000-person-year). Smoking, alcohol consumption, betel quid chewing, primary cancer of T1-2, and N0 were risk factors, while HPV infection (OR 0.47, 95% CI 0.30-0.72) was the protective factor. SPC is frequently observed in HNSCC patients and had great impact on the prognosis. The findings could promote a more individualized follow-up strategy for SPC in HNSCC patients. This systemic review and meta-analysis provide sufficient evidence for the establishment of the follow-up strategy for head and neck squamous cancer patients.


tRNA-halves are prognostic biomarkers for patients with prostate cancer.
Noncoding RNAs play an important role in carcinogenesis; a number of tRNA-halves are expressed in response to androgen stimulation and are involved in prostate cancer (CaP) initiation and progression. In this study, we evaluated the expression profile of androgen-dependent tRNA-halves in CaP. Total RNA was isolated from formalin-fixed paraffin-embedded 58 CaP, and 25 benign prostate hyperplasia tissues. We also studied the expression in serum from 49 localized and 21 metastatic castration-resistant CaP samples. The ligation of a RNA adaptor molecule to the tRNA-halves allowed the specific amplification of 3'/5'-tRNA-halves using quantitative TaqMan reverse transcription polymerase chain reaction. The expression levels were correlated with clinicopathological parameters as well as prostate-specific antigen recurrence free survival. 5'-tRNA-Asp-GUC-half and 3'-tRNA-Asp-GUC-half were up-regulated in CaP tissues compared with benign prostate hyperplasia tissues. An increased expression level of all the 5 candidate tRNA-halves was associated with adverse clinicopathological parameters (pT-stage, pN-stage, prostate-specific antigen, International Society of Urological Pathology /ISUP grade) and a shorter time to biochemical relapse. In serum, 5'-tRNA-Glu-CUC-half was circulating at a higher level in metastatic castration-resistant CaP patients compared to patients with localized CaP. The androgen-dependent tRNA-halves can potentially act as biomarkers to monitor and predict the progression of CaP.


The spectrum of motor disorders in Huntington's disease.
EMG of involuntary muscle contractions and their correlation with clinical pictures in Huntington's disease disclosed a series of motor disorder from chorea to parkinsonism. Irregular brief contractions appearing reciprocally in flexor or extensor muscles were observed in typical chorea with hypotonia. Tonic nonreciprocal contractions appeared in the rigid form. In athetoid movement or dystonic postures, more slowly nonreciprocal fluctuating contractions appeared. In some cases phasic contractions changed from a reciprocal to nonreciprocal pattern by psychic stress. In contrast to the activation of motoneurons in choreatic movements, involuntary brief suppression of voluntary contraction appears in typical chorea. Difference in involuntary movements and muscle tone may result from quantitative differences in involvement of striatal neurons which are the origin of parallel pathways proposed by DeLong and colleagues.


Long-Term Survival of Women with Breast Cancer. Overview Supportive Care Needs Assessment Instruments.
Worldwide, breast cancer is the fifth leading cause of cancer death (after lung, stomach, liver and colon cancer), while among women it is first on the list. The incidence of breast cancer has made a dramatic increase since 1970 which is partly interpreted by the modern western life standards. The expected risk of breast cancer throughout a lifespan of an average is 1 in 11 women. The five-year survival rates for breast cancer are at 80% if it has not spread, and only at 40% for the metastatic type of cancer.The concept of survival comes from the US, where there is an active promotion of self-help difficulties coping strategies. Surviving from cancer may be a mixed experience. Survivors of cancer often say they are still running a full and meaningful life after experiencing a threatening disease. Others may find it difficult to handle the feeling that they have no right to be alive, which is probably related to the guilt of survival after the war. Although the survival potential for some is a satisfactory fee, others may be looking for improvement, change, or to adapt their life and struggle with the late effects of cancer after stopping the treatment.In recent years it has been observed that survival of women with breast cancer has increased significantly because of current antineoplastic therapeutic interventions. The definition of support needs derives from the one of supportive care considering that there is no theoretical framework or specific definition at the moment. "Supportive care is defined as the care which helps the individual and his/her family to deal with the experience of cancer and cover their bodily, emotional, psychological, social, mental and practical needs, as well as their need of information. It includes the period before the final diagnosis, during the diagnosis and the treatments or during the ongoing disease with recurrences and the survivors of the disease." The purpose of this review is to describe the tools used in research to measure and evaluate supportive care needs during long-term survival of women with breast cancer. An electronic search of articles was held in the PubMed database for the period from 2005 up to 2015. The terms used in the search were "breast cancer", "quality of life", "long-term survivorship" and "supportive care needs". The entry criteria of the articles were to be breast cancer diagnosis, written in English, quantitative methodology and include patients with at least a five-year survival. The sorting of articles were based on the inclusion and exclusion criteria according to the MOOSE Checklist systematic review. With the criteria set out, the articles incurred are a total of 249 from which 47 were excluded according to their title, 28 as they were articles of other types of cancer, 61 had direct objective the description of drugs, treatments and their cost, 5 did not study supportive care needs, 49 did not have direct research questions, 4 did not relate to the period of 10 years, and 6 were not associated with a five-year survival. From a total of 249 articles 43 met the inclusion criteria and 23 were finally included. These 23 articles were studied thoroughly by two independent researchers in order to record the analytical tools used by individual researchers to measure the supportive care needs. There were several different methodological approaches identified, particularly in the way of recruiting and determining the patient research sample and complete questionnaires. Altogether 82 different tools were used to measure the support needs. Supportive care needs are divided into organic, psychological, socio-economic and spirituality. The commonly studied supportive care needs are related to mobility/functionality (39.8%), psychological well-being (37.3%), mainly depression, sexuality (14.5%), fatigue (7.2%) and spirituality (4.8%) of the surviving women. Some tools were discovered that studied bodily needs (47.6%), psychological needs (36.6%), a combination of the two (3.7%), socioeconomic needs (8.5%) and mental needs (1.2%). Tools such as Center for Epidemiologic Studies-Depression Scale (17.4%), Physical Component Scale (13%) and Beck Depression Inventory (13%) are included in the most commonly used ones. The supportive care needs of breast cancer women during long-term survivorship are slightly explored, comparing to antineoplasmatic treatment period supportive care needs. This is probably due to the subjective nature of the concept examined. Approximately every scientific team worked on the study of supportive care needs on two or three different dimensions. More frequently examined are Physical and Psychological Care Needs. Gap is observed in exploring the social/economical and spiritual supportive care needs of women with breast cancer survivors as well as practical needs.


Modeling emergency department nursing workload in real time: An exploratory study.
Study of emergency department (ED) nursing workload has been largely subsumed under the related but separate phenomenon of ED crowding. Nursing workload is difficult to quantify directly. This observational study explored modeling ED nursing workload indirectly, in real time, from quantitative data available from the patient tracking computer system (PTCS). Data on 2793 patient visits plus departmental statistics were collected during 167 60-minute survey periods (SP) in a 25-bed hospital ED in the United States. The charge nurse assessed a perceived workload score (WLS) according to pre-determined criteria following each SP as a validation measure. Correlations were calculated between the data and WLS, and strongly correlating variables were incorporated into linear regression models that sought to approximate WLS. A measure of aggregate patient acuity derived from the Emergency Severity Index (ESI) was the strongest predictor of WLS (r = 0.7991). The best-performing model agreed with WLS in 64% of SPs. Good agreement between model output and WLS suggests that ED nursing workload can be estimated indirectly in real time using data from a PTCS. Strong correlation between the ESI derivative and WLS further validates ESI and suggests a new application for the ESI score.


Neurenteric cyst in the cerebellopontine angle with xanthogranulomatous changes: serial MR findings with pathologic correlation.
We report serial MR findings in a middle-aged woman with a neurenteric cyst involving the cerebellopontine angle cistern with xanthogranulomatous changes. On the initial gadolinium-enhanced T1-weighted MR images, the solid portion of the lesion had homogeneously strong enhancement. Follow-up MR images obtained 6 months later showed that the mass had increased in size; however, the solid portion decreased in size. The enhancing solid portion corresponded to the xanthogranulomatous changes on pathologic correlation.


Aged murine killer T-cell clones acquire specific cytotoxicity for P815 mastocytoma cells.
T-cell clones that grow continuously in tissue culture have become a major tool for studying the properties of T lymphocytes. It is therefore important to know to what extent such clones resemble their normal counterparts. Several reports have appeared recently which demonstrate that long-term T-cell lines may lose the specificity for which they were initially selected and acquire cytotoxic activity to a variety of targets, typical of the activity displayed by natural killer cells. We now report a number of instances in which murine cytotoxic T-cell clones have lost their original specific cytotoxic activity but have acquired strong specific cytotoxic activity for P815 mastocytoma target cells. Loss of the original specificity was usually observed after continuous in vitro cultivation for more than 6 months. We propose that this novel type of cytotoxicity should be called aged killer activity.


Assessment of stability of a Himalayan road cut slope with varying degrees of weathering: A finite-element-model-based approach.
Slope stability assessment is essential for safe and sustainable development widely applied in mining, civil, and environmental engineering projects around the world. This study aimed to conduct a stability analysis of a selected Himalayan road cut slope from two different sections, named sections (A) and (B). The strength reduction factor (SRF) based on the finite element method was used to simulate the slope sections using Phase2 software. A mesh pattern of six node triangle elements was used during the numerical simulation. The Mohr-Coulomb parameters and other inputs used in the numerical modelling of the investigated slope were estimated by different geotechnical tests, namely, the direct shear test, density analysis test, rock hardness test, and Brazilian test. The results indicated that the critical SRF of the completely weathered slope profile section (A), with a relatively low overall angle, was found to be 1.25, which is approximately 50% lower than the value obtained in the moderately to highly weathered profile section (B), equal to 2.53. These results are in agreement with other published studies, which revealed that the geometry of a slope influences the weathering grade, which in turn destabilizes the slope. The results of this study will help in engineering slope design considering the influence of weathering.


A thermodynamic study of 5-[3H]hydroxytryptamine binding to human cortex membranes.
Kinetic and equilibrium measurements of [3H]-serotonin (5-hydroxytryptamine) binding to human frontal cortex membranes have been made between 4 and 30 degrees C. The effects of spiperone and ascorbate on binding have also been determined. Under the conditions used, binding was saturable and reversible. Affinity constants derived from kinetic and equilibrium data were comparable. Serotonin binding to several sites had substantial enthalpic as well as entropic components.


[Value of electroencephalographic studies for the evaluation of the neurotoxic effect of metallic mercury].
The results of 373 EEG investigations were analysed. They were obtained in a period of 4 years in 222 workers with occupational exposure to metallic mercury in the synthesis of acetaldehyde and salt electrolysis. Abnormal or borderline abnormal results were found in 13% of them. Results were compared in groups differing in age, duration of occupation, working post and Hg excretion with urine. Significantly greater frequency of increased Hg absorption was found in the group with abnormal records. The authors stressed the following morphological features of EEG in those exposed to Hg: tendency for seizure activity, loss of ability of following of rhythmic flashes, unchanged frequency of background activity despite increasing degree of other abnormalities, absence of low-voltage tracings, persistence of abnormalities in the records after loss of contact with mercury.


Giant ovarian serous cyst and postmenopausal adnexal torsion: An unusual case report and literature review.
Adnexal torsion is an uncommon but urgent surgical situation more frequently observed during the reproductive years and rarely in postmenopausal women. This case report describes a postmenopausal woman with a large left ovarian cyst measuring 18 × 20 × 22 cm who experienced adnexal torsion, which is a rare occurrence in this age group. To avoid the potential requirement for additional surgical procedures in case of cyst recurrence in the remaining ovary or the development of uterine diseases a total abdominal hysterectomy and bilateral salpingo-oophorectomy with cystectomy were performed. Histopathological analysis of the cyst confirmed that it was a benign serous cystadenoma of the ovary. Adnexal torsion can happen at any age but is less likely to occur after menopause. Moreover, giant ovarian cysts (>10 cm) are uncommon, making adnexal torsion on these cysts a rare event. While laparotomy remains the gold standard surgical intervention, laparoscopy is beginning to play a role in management of giant cyst. This report documenting a rare case of adnexal torsion in a postmenopausal woman following a serous giant cystadenoma emphasizes that this surgical emergency can occur at any age. In addition, the report highlights that the presence of an ovarian mass or cyst increases the risk of adnexal torsion, regardless of age.


Phagocytosis of apoptotic and necrotic thymocytes is inhibited by PAF-receptor antagonists and affects LPS-induced COX-2 expression in murine macrophages.
There is evidence that apoptotic cells and oxidized low density lipoprotein (oxLDL) particles have common ligands on their surface consisting of oxidized phospholipids which bind to scavenger receptors in macrophages leading to phagocytosis. Some effects of oxLDL binding to its receptor(s) were shown to be inhibited by Platelet Activating Factor (PAF)-receptor antagonists. Thus, we investigated the effect of PAF-receptor antagonists on the phagocytosis of apoptotic, necrotic and viable thymocytes by murine peritoneal macrophages. It was found that phagocytosis of altered cells is significantly increased compared to viable cells, a phenomenon reversed by pre-treatment of macrophages with PAF-receptor antagonists (WEB2170 and CV3988), PAF or oxLDL. Phagocytosis of altered cells induced negligible expression of cyclooxygenase-2 (COX-2) but strongly potentiated the LPS-induced expression of this enzyme. This phenomenon was restricted to altered cells and was reversed by pre-treatment of macrophages with PAF-receptor antagonists. These findings indicate that apoptotic and necrotic cells share common ligands with PAF and oxLDL and suggest the involvement of PAF-like receptors in the enhanced clearance of these cells.


Standardizing nursing degree curriculum structure in Spain: A mixed-methods study.
Legislation regulating Spanish and European academic curricula prescribes a certain level of knowledge and skills any student must master. Spanish universities freely decide the number of credits assigned to each subject and in which year the subject will be taught. We hypothesize that this flexibility may give way to excessively heterogeneous training across universities in nursing degrees. Such curricula heterogeneity hinders inter-university transfers and weakens educational excellence. 1) To review the existing differences in nursing degrees in Spanish universities; 2) to compare our results against current legislation; 3) to propose changes in the legislation, if necessary. Mixed-methods approach. Spain. We reviewed nursing degree curricula of all 60 Spanish universities. Inter-university differences were analyzed and checked against current legislation. A focus group proposed legislative changes accordingly. Several differences between public and private universities were statistically significant. During the first cycle, public universities´ course loads include more theoretical teachings, more credits in core subjects during the first year, and more compulsory subjects in second year. Private universities are more likely to offer external internships during the first cycle whereas the public ones are more likely to offer them during the second cycle. Public universities offer more credits under the following curricular blocks than private ones: "Nutrition/Dietetics," "Psychiatry," "Public and Community Health," and "Geriatrics." In turn, private universities offer more credits in the areas of "Theory/Methodology," "Ethics/Legislation," "English," and "Theology." Academic curricula meet most of the criteria established by the Spanish and European legislation. The proposed legislative changes aim at standardizing curricula by associating specific credits and their timeline to the teaching blocks. Nursing degree curricula among Spanish universities are highly heterogeneous. Legislative changes to homogenize teaching blocks would facilitate credit validations and student mobility across universities, in addition to increasing nursing degrees´ standardization and excellence.


Impacts of admission serum albumin levels on short-term and long-term mortality in hospitalized patients.
The aim of this study is to assess the association between admission serum albumin and short- and long-term mortality in all hospitalized patients. A single-center cohort study. A retrospective cohort of all adult hospitalized patients at a tertiary referral hospital between January 2009 and December 2013 were analysed. Admission serum albumin was stratified into six groups: ≤2.4, 2.5-2.9, 3.0-3.4, 3.5-3.9, 4.0-4.4 and ≥4.5 g/dl. The outcomes of interest were in-hospital mortality, length of hospital stay and 1-year mortality. Serum albumin of 4-4.4 g/dl was selected as a reference group for outcome comparison. A total of 14 075 patients were studied. Admission serum albumin of ≥4.5 g/dl had the lowest in-hospital and 1-year mortality with progressively increased in-hospital mortality observed with decreased admission serum albumin. In adjusted analysis, compared with serum albumin of 4.0-4.4 g/dl, serum albumin of ≤2.4, 2.5-2.9, 3.0-3.4 and 3.5-3.9 were significantly associated with increased in-hospital and 1-year mortality. In contrast, serum albumin of ≥4.5 g/dl was significantly associated with lower 1-year mortality but not in-hospital mortality. Admission serum albumin <4.0 g/dl was significantly associated with a prolonged hospital stay, while admission serum albumin of ≥4.5 g/dl was significantly associated with shorter hospital stay, compared with serum albumin of 4.0-4.4 g/dl. Low albumin level at admission was progressively associated with increased short- and long-term mortality in all hospitalized patients even when albumin level was considered in normal range.


Semitransparent Organic Solar Cells with Homogeneous Transmission and Colorful Reflection Enabled by an ITO-Free Microcavity Architecture.
Semitransparent organic photovoltaics (ST-OPVs), owing to the merits of high power generation, thermal insulation, and aesthetic features, have become a promising candidate for intellectual building- integrated photovoltaic windows. However, the traditional optical evaluation only focuses on the transmission properties and ignores the reflection behaviors. And the lack of quantitative descriptions for array appearance hinders implementation of ST-OPV based large-area modules. To tackle with these issues, an indium tin oxide (ITO)-free optical microcavity architecture into ST-OPVs for achieving high homogeneity in transmittance with controllable reflective appearances through tunning the thickness of individual component layers is introduced. A set of parameters based on optical characteristics of sub-units to provide a quantitative description for the transmittance brightness, transmissive and reflective color purity, and versatility of optical arrays, is further proposed. The optical simulations reveal that reflection modulation from blue to red colors can be realized for devices based on various bulk-heterojunction material systems through regulating the thickness of active layers and antireflection coatings. This work offers a viable design strategy for ST-OPVs toward applications in next-generation smart photovoltaic windows.


Phase II trial of dacarbazine, mitomycin, doxorubicin, and cisplatin with sargramostim in uterine leiomyosarcoma: a Gynecologic Oncology Group study.
Following a reported 23% response rate (RR) for mitomycin (M), doxorubicin (A), and cisplatin (P) and preliminary data suggesting a superior RR for dacarbazine (D) + MAP + sargramostim, the Gynecologic Oncology Group (GOG) conducted a phase II trial of DMAP + sargramostim in patients with advanced uterine leiomyosarcoma. Eligibility required measurable disease, a GOG performance score of 0-2, and recovery from surgery/radiotherapy. Treatment consisted of sargramostim 250 microg/m2 SC q 12 h days -6 through -3, followed by D 750 mg/m2 IV over 2 h, M 6 mg/m2 IV, A 40 mg/m2 IV and P 60 mg/m2 IV over 2 h on day 1, followed by sargramostim 250 microg/m2 SC days 2-15. Cycles were repeated q 28 days (if ANC > or = 1500/microl and platelets > or = 100,000/microl) until disease progression or toxicity prevented further therapy. Doses were to be reduced by 20% for grade 4 neutropenia >7 days or any grade 4 thrombocytopenia and by 10% for a 1- to 2-week treatment delay for myelosuppression. One of 19 patients who entered the study was ineligible. Eighteen patients received a median of 3.5 cycles (range: 1-6 cycles) of therapy. The overall RR was 27.8% (5.6% complete and 22.2% partial responses). Percent of patients with grade 3 or 4 toxicities included 78% neutropenia, 94% thrombocytopenia, 61% anemia, 44% GI, 28% infection, and 17% azotemia. DMAP + sargramostim produced a 27.8% RR, but its complexity and toxicity precluded further investigation, and the study was closed after the first stage of accrual.


How does patient-centered hospital culture affect clinical physicians' medical professional attitudes and behaviours in chinese public hospitals: a cross-sectional study?
An increasing number of studies on physicians' professionalism have been done since the 2002 publication of Medical Professionalism in the New Millennium: A Physician Charter. The Charter proposed three fundamental principles and ten responsibilities. However, most studies were done in developed countries, and few have been done in China. Additionally, few studies have examined the effect of patient-centered hospital culture (PCHC) on physicians' professionalism. We aimed to investigate physicians' medical professionalism in public hospitals in China, and to assess mediating effect of professional attitudes in the relationship of PCHC with professional behaviours. Self-administered questionnaires including professional attitudes (20 items) and behaviours (10 items) survey and PCHC scale (22 items) were given to clinical physicians in five public hospitals, China. The mediating effect of professional attitudes in the relationship of PCHC with professional behaviours was tested. 232 valid questionnaires were collected. More than 90% (208) respondents agreed with 15 of 20 specific statements on medical professionalism. As for the responsibility of improving quality of care, 54 (23%) respondents disagreed with reporting of incompetent colleagues and as for the responsibility of maintaining professional competence, 49 (21%) disagreed with recertification. More than 185 (83%) respondents reported that they sometimes, usually, or always showed the four positive behaviours on the questionnaire, and 173 (77%) reported that they never showed the six negative behaviours. Mediating effect analysis revealed that two dimensions of PCHC (i.e. value/institution culture and behaviour/material culture) had a significant positive impact on physicians' professional behaviour, and professional attitude played a complete mediation role between them, but another dimension of PCHC (i.e. negative evaluation of hospital) directly affected professional behaviour without influencing professional attitude. Chinese physicians showed positive professional attitudes and behaviours. Different dimensions of PCHC affected physicians' attitudes and behaviours in different ways.


Shedding light on a mysterious link between Toxoplasma gondii and cancer: A review.
The ongoing conflict regarding the affiliation of Toxoplasma gondii to cancer; whether an inducer or a suppressor needs to be resolved. Human epidemiological studies oscillate without attaining a firm ground. Some studies confirmed the detection of high seroprevalence of anti-Toxoplasma antibodies in different cancer patients without further justification whether being causation, co-incidences, or part of opportunistic infections. Others reported a state of resistance to cancer accompanying low titer of anti-Toxoplasma antibody. Worthwhile, preclinical experimental work confirmed the antineoplastic potency of Toxoplasma. Thus, further investigational research is essential to validate the potential application of Toxoplasma as a promising cancer immunotherapeutic vaccine candidate. In this paper, we present a review of this issue by examining epidemiological and preclinical experimental studies that explored the linkage between Toxoplasma gondii and cancer. We consider this review an important step towards shedding a light on this mysterious link and a stepping-stone for potential research work addressing Toxoplasma as a cancer suppressor rather than a cancer inducer.


Correction: Cryptic chytridiomycosis linked to climate and genetic variation in amphibian populations of the southeastern United States.
[This corrects the article DOI: 10.1371/journal.pone.0175843.].


Temporally Robust Eye Movements through Task Priming and Self-referential Stimuli.
Studies have demonstrated connections between eye movements and attention shifts. However, little is known about the general factors that contribute to the self-consistency of idiosyncratic scanpaths as a function of attention shifts over time. The present work repeatedly measured human eye movements at various time intervals that ranged from less than one hour to one year between recording sessions. With and without task context, subjects observed multiple images with multiple areas of interest, including their own sporadically interspersed facial images. As reactions to visual stimuli, the eye movements of individuals were compared within and between subjects. We compared scanpaths with dynamic time warping and identified subjects based on the comparisons. The results indicate that within-subject eye movement comparisons remain more similar than between-subject eye movement comparisons over time and that task context and self-referential stimuli contribute to the consistency of idiosyncrasies in attention shift patterns.


Relationship between the carbohydrate content of apoproteins of VLDL, IDL, and LDL and the plasma level of these lipoproteins in man. Short dietary effect.
A 1,500 Cal test meal was used to study in man the apoprotein B-carbohydrate content and composition of VLDL, IDL and LDL in relation to the variation of plasma lipids and lipoproteins and the VLDL-apoprotein composition. Three essential facts emerge from the study: (1) the mirror image (inverse significant correlation) between VLDL-apo B plasma concentration and N-acetylglucosamine content of apo B; (2) a reduction in total carbohydate concentration of VLDL- and LDL-apo B, 2--4 h after the test meal and a trend to a reduction in the mannose content; (3) a significant correlation between sialic acid and apoprotein B concentration in plasma LDL during fasting. The effect of diet and subsequent fasting on carbohydrates of lipoproteins and the consequence of such changes on lipoprotein uptake are briefly discussed.


[Development of the editable software for dentition defect and dentures].
Discussed how to develop a software for prosthodontics teaching with the models and element libraries of the dentition and dentures. Selected the typical Kennedy's types and prostheses, used the kinds of model and libraries, by the way of the image manipulation, we established an applied software. We established an useful software for the prosthodontics teaching. The software we developed is effective and editable.


Neostigmine in postoperative intestinal paralysis. A double-blind, clinical, controlled trial.
The effect of neostigmine on postoperative intestinal paralysis in 90 patients was investigated in a controlled study. Neostigmine, 0.5 mg, was administered intramuscularly every third hour on the third day after laparotomy, either until passage of flatus or stools was observed, or until a total of three injections were given. No difference between treated and untreated patients was found, and it is suggested that neostigmine is of little or no value in postoperative intestinal paralysis.


Effects of hyperoxia on biochemical indexes of pig aortic endothelial function.
To determine what biochemical indexes might be useful in measuring the endothelial response to hyperoxia in vitro we exposed endothelial cell monolayers (ECM) from pig aortas to either hyperoxic (95% O2:5% CO2, 1 atm) or control conditions (95% air:5% CO2) and made the following measurements: (a) DNA and protein contents remaining in the ECM; (b) lactate dehydrogenase (LDH) activity in the medium; (c) the net uptake of rubidium (Rb+), adenine, and adenosine; and (d) cellular ATP and medium lactate. Twelve hours of hyperoxic exposure did not cause significant changes. After 24 or 48 h of hyperoxia, DNA and protein contents were decreased; LDH activity and the protein-to-DNA ratio were increased; adenosine uptake was decreased per ECM but was unchanged when corrected for culture DNA and protein contents. Adenine uptake was unaltered as were cellular ATP content and medium lactate concentration. The net Rb+ uptake-to-DNA ratio was increased after 24 h but not after 48 h of hyperoxia. The extent of the DNA and LDH changes indicated that the cellular disturbance caused by hyperoxia was progressive from 12 to 48 h. Presence of superoxide dismutase (250 U/ml) prevented both the increase of LDH activity and the decrease of protein after 48 h but did not affect the decrease of DNA. These results suggest that the cells remaining in the ECM after hyperoxia have normal biochemical function and may represent a subpopulation of cells more resistant to oxygen toxicity than the damaged cells.