Audit and the birth of the abdomino-perineal excision for carcinoma of the rectum.
Sir Ernest Miles first performed his radical abdomino-perineal excision for carcinoma of the rectum in 1907. This event was the culmination of almost a decade of audit in which he carefully studied the outcomes of patients with rectal carcinoma. Miles's interpretation of his audit led, in a stepwise manner, to gradual changes in his operative technique and the eventual development of the radical abdomino-perineal operation; the operation that bears his name. The Miles operation and the principles upon which it is based, would lead to an improved outcome for patients with rectal carcinoma.


The influence of anisotropic Rashba spin-orbit coupling on current-induced spin polarization in graphene.
We consider a disordered graphene layer with anisotropic Rashba spin-orbit coupling subjected to a longitudinal electric field. Using the linear response theory we calculate current-induced spin polarization including in-plane normal and parallel components with respect to the electric field direction. Unlike the case of isotropic Rashba spin-orbit where the normal component of spin polarization is linear in terms of Fermi energy around the Dirac point, anisotropic Rashba spin-orbit can result in non-linear dependence of this component at such energies within the Lifshitz points. Furthermore, we show that anisotropic Rashba interaction allows for tuning the direction of spin polarization from perpendicular direction to the parallel one such that for certain values of Rashba parameters the magnitudes of both components can also be quenched. The effect of carriers scattering on randomly distributed non-magnetic disorders is also taken into account by calculating vertex correction. This results in modification of spin polarization components depending on the relative strength of Rashba parameters.


Does a histidine-rich protein from Plasmodium lophurae have a function in merozoite penetration?
Autoradiography was used to localize the distribution of L-[3H]histidine incorporated in vitro by developing segmenters of Plasmodium lophurae. Under conditions used for the visualization of high specific activity loci, radioactivity appeared associated mainly with the histidine-rich protein of cytoplasmic granules as well as with rhoptries and micronemes of merozoites. The isolated histidine-rich protein caused agglutination of erythrocytes and increased their osmotic fragility. Based on the observed evidence suggesting the presence of this histidine-rich protein in the polar organelles of merozoites and its reactivity with erythrocyte membranes, the hypothesis that such a protein may have a function in the penetration of merozoites is proposed.


18F-FDG PET/CT in monoclonal plasma cell disorders.
Plasma cell disorders are a heterogeneous group caused by the monoclonal proliferation of lymphoplasmacytic cells in the bone marrow. Multiple Myeloma (MM) is the most serious and prevalent plasma cell dyscrasia, with a median age of onset of 60 years.MM displays significant genetic, biological and clinical heterogeneity with subsequent imaging heterogeneity, evident in contemporary imaging modalities (PET/CT and MRI). Evidence suggests that MM is always preceded by precursor stages of monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma.


Opioid Agonist Treatment and Improved Outcomes at Each Stage of the HIV Treatment Cascade in People Who Inject Drugs in Ukraine.
The HIV treatment cascade is a crucial tool to guide HIV prevention and treatment strategies. The extent to which opioid agonist treatments (OATs) such as methadone and buprenorphine influence this cascade was examined in a nationwide study of people who inject drugs (PWID) in Ukraine. Cross-sectional stratified survey of PWID followed by HIV and hepatitis C virus testing in 5 Ukrainian cities. Opioid-dependent PWID (N = 1613) were sampled from January 2014 to March 2015. Analysis was confined to 520 participants with HIV, with 184 (35.4%) prescribed OAT. Weighted logistic regression models were used to assess independent factors associated with the 5 steps in the HIV treatment cascade. Compared with PWID not on OAT (N = 336), participants who prescribed OAT (N = 184) were significantly more likely to be diagnosed (91% vs. 71%), linked (81% vs. 52%), and retained (69% vs. 35%) in HIV care, and prescribed (56% vs. 31%) and optimally (>95% of doses) adherent to antiretroviral therapy (41% vs. 22%). Receiving OAT contributed most as an independent factor with every step of the cascade. Other steps in the HIV treatment cascade were influenced by age, depression, and geographical variability. OAT remains an essential and effective strategy to not only treat patients with opioid use disorder, but also a crucial strategy to engage PWID in care to meet UNAIDS 90-90-90 targets. Geographical differences suggest local structural impediments. With low OAT coverage prescribed for 2.9% of the estimated 347,000 PWID in Ukraine, OAT expansion requires strategic interventions that target the individual, clinical care settings, policies, and funding.


Liquid chromatographic separation and UV determination of certain antihypertensive agents.
Three antihypertensive agents were extracted and isolated from commercial formulations. These were purified and characterized by melting point, lambdamax and IR. The percentage recovery by extraction process was in the range 81-91%. Active ingredients from binary formulations were separated by RP-HPLC using methanol-water (50:50 v/v) and by TLC using CHCl3-CH3OH (6:1) as mobile phase. Detection was by UV at 210 nm in HPLC, and by iodine vapors in TLC. The solvent conditions from TLC were transferred to open column chromatographic separation. Quantitative determination was carried out using TLC and column chromatography supplemented with UV spectrophotometry. Recovery was in the range 82-93%. Two combination of drugs, viz. amlodipine+ramipril and amlodipine+enalapril, were separated by the three modes of liquid chromatography. The percentage recovery was in the range 80-92% by open column.


Identification of cholecystokinin from frog and turtle. Divergence of cholecystokinin and gastrin occurred before the evolution of amphibia.
Cholecystokinins from brain and small intestine of the bullfrog (Rana catesbeiana) and red-eared slider turtle (Pseudomys scripta) were isolated. The purifications were monitored by an antiserum specific for the common C-terminus of mammalian cholecystokinin and gastrin. The peptide structures were identified by sequence analysis of the intact peptides and proteolytic fragments, mass spectrometry, and amino acid analysis. Brain and small intestine of both species contained cholecystokinin-8 and substantial amounts of cholecystokinin-7. Furthermore, the small intestine of both frog and turtle contained a major fraction of the immunoreactive material as large peptides consisting of 69 residues and 70 residues, respectively. The structure for frog cholecystokinin-69 is ASSSAQLKPFQRIDGTSDQKAVIGAMLAKYLQTRKAGSSTGRYAVLPNRPVIDPTHRINDRDYMGWMDF .NH2 and the structure for turtle cholecystokinin-70 is VPSSAGQLKPIQRLDGNVDQKANIGALLAKYLQQARKGPTGRISMMGNRVQNIDPTHRINDRDYMGWMD F.NH2. All the isolated peptides were tyrosine sulfated at the seventh last residue. The peptides are highly similar to each other and to mammalian cholecystokinins (70% mutual identity and more than 50% identity with human cholecystokinin). Thus, they are clearly related to the known mammalian cholecystokinins. Both peptides include the monobasic and dibasic cleavage sites giving rise to cholecystokinins-33, -39, and -58 in mammals. However, only a small amount of turtle cholecystokinin-40 (corresponding to mammalian cholecystokinin-39) was isolated. This confirms that post-translational processing is highly species dependent. Recently, we isolated peptides from frog and turtle antrum. Following their origin they were named gastrins in spite of their C-terminal cholecystokinin-like structure. Thus, two different cholecystokinin/gastrin peptides exist in frog and turtle justifying the choice of two names. This finding of two members of the cholecystokinin/gastrin family in frog shows that the divergence of cholecystokinin and gastrin occurred simultaneously with or earlier than the appearance of amphibia during phylogenesis. Frog cholecystokinin and gastrin show sufficient similarity along the whole sequence to support the notion of a gene duplication of a common ancestor.


Lipid abnormalities of xanthomatous nerves.
The lipid composition of nerves, with and without xanthomatous alteration, and other tissues, was investigated post-mortem in a 36-year-old man with cholestatic hepatitis of unknown cause and insulin-dependent diabetes mellitus (IDDM). Cholesteryl esters were found to be markedly increased in both endoneurium and epi- and perineurium of hepatic nerves (showing xanthomatous change), but not in sciatic nerve (without this change). Cholesteryl ester concentrations were also increased, but to a lesser degree, in kidney tissue. The fatty acid composition of stored cholesteryl esters in hepatic nerve endoneurium revealed that oleic acid was the most favoured substrate for esterification. A widespread depletion of triacylglycerol was also demonstrated in hepatic and sciatic nerves and liver and skin tissues obtained from this patient. This abnormality did not appear to be due to an alcoholic or biliary cirrhosis, or to inanition. Whether the depletion of triacylglycerol is drug-related or represents an endogenous metabolic error remains unclear.


The Association of Therapy Adherence and Thyroid Function in Adult Patients with Phenylketonuria.
The standard, lifelong therapy of phenylketonuria (PKU) is a natural protein-restricted diet complemented with phenylalanine (Phe)-free L-amino acid mixtures that provide the daily necessary micronutrients. To assess thyroid function and structure and the iodine status of early-treated adult PKU (ETPKU) patients in Hungary. Sixty-nine PKU patients (aged 18-41 years) and 50 healthy controls were enrolled in the study. Thyroid hormones, serum thyroglobulin, thyroid antibodies, urinary iodine, and selenium concentrations were measured, and thyroid ultrasound was performed. The incidence of thyroid dysfunction was infrequent (n = 2). Blood Phe was negatively correlated with thyroid-stimulating hormone (TSH), and PKU patients had higher free thyroxine and lower TSH levels than healthy controls. Although optimal iodine status was found in the entire PKU population, by dividing the patients according to their therapy compliance, we observed that lower therapy adherence was associated with mild iodine deficiency and lower urinary selenium levels. The results of this study suggest that iodine status is strongly influenced by the adherence to therapy in ETPKU patients. No or not enough medical food consumption combined with a low-Phe diet can lead to subclinical iodine deficiency.


A case of epiglottic entrapment in a cat.
The objective of this study was to describe a case of epiglottic entrapment in a cat. A 5-month-old male neutered Russian Blue cat was evaluated for progressive stertorous upper airway sounds, acute onset vestibulopathy and abnormal laryngeal anatomy. Endotracheal intubation was only able to be achieved using videoscopic guidance and identified concern for severe nasopharyngeal stenosis. A computerized tomography scan revealed otitis interna, narrowed nasopharynx and no definitive cause for the stertorous breathing. The cat recovered very slowly from anaesthesia due to concern for airway obstruction following extubation. It was discharged the following day and then passed away at home 2 weeks later. Necropsy revealed that the epiglottis was obscured by 2 cm of redundant mucosal tissue extending from the base of the tongue to the larynx resulting in epiglottic entrapment. Also noted was chronic, severe otitis interna and externa. Upper airway obstruction is suspected to be the cause of sudden death. To the authors' knowledge, this is the first report of these oropharyngeal anatomic abnormalities in a cat.


Recommendations for the derivation and use of biota-sediment bioaccumulation models for carcinogenic polycyclic aromatic hydrocarbons.
Carcinogenic polycyclic aromatic hydrocarbons (cPAHs) are important sediment contaminants that can pose health risks to people who eat shellfish from contaminated sites. Biota-sediment accumulation factors (BSAFs) are quotients of colocated lipid-normalized tissue concentrations and organic carbon (OC)-normalized sediment concentrations, whereas biota-sediment accumulation regressions (BSARs) are models describing the relationships between these tissue and sediment concentrations. BSAR/Fs (BSARs and/or BSAFs) are commonly used to back-calculate sediment preliminary remediation goals (PRGs) from target tissue concentrations; the PRGs are then used to set target action levels (i.e., sediment concentrations above which remedial actions will be prescribed). The cPAH BSAR/Fs reported across sites and species are highly variable due to both site- and species-specific differences and inconsistent BSAR/F calculation methods and assumptions. We reviewed past studies, identified best practices for developing BSAR/Fs, and compiled publicly available colocated tissue and sediment data for 7 cPAHs from 13 sites across the United States. Of the 249 unique cPAH data sets compiled for various species, only 17 yielded acceptable BSAR/Fs, 16 of which were for clams. The influence of BSAR/Fs on sediment remedial action decisions and costs can be disproportionate to the quality of the statistical models from which they are derived. Therefore, it is important to establish and follow best practices for deriving BSAR/Fs and for deciding whether and how BSAR/Fs should be used. Based on our review and analysis, we highlight the advantages of relying on BSARs and propose a consistent method for deriving and judging the reliability of these relationships. We also offer guidance for evaluating the ramifications of BSAR uncertainty on remedial decision making at contaminated sediment sites, and we discuss alternative ways to make risk management decisions in the absence of a reliable site-specific BSAR. Integr Environ Assess Manag 2017;13:1060-1071. © 2017 SETAC.


[Changes in hepatobiliary enzymes and its isoenzymes in intrahepatic cholestasis in pregnancy].
Serum alkaline phosphatase (AKP), gamma-glutamyl transpeptidase (gamma-GT), 5'-nucleotidase (5'-NT), leucine aminopeptidase (LAP), AKP gamma-GT isoenzymes, and lipoprotein-X (LP-X) were measured in 97 normal pregnant women and 40 patients with intrahepatic cholestasis of pregnancy (ICP). It was found that in ICP the changing patterns in the four hepatobiliary enzymes were different in different gestational weeks of 3 rd trimester. The changes of gamma-GT and 5'NT were more significant, especially the latter. Six bands were found both in serum AKP and gamma-GT isoenzymes. In ICP the rate of occurrence of AKP1 and AKP2 isoenzymes were elevated. Thus, gamma-GT, 5'-NT, AKP and gamma-GT isoenzymes might be more sensitive parameters for monitoring intrahepatic cholestasis of pregnancy.


Users' understanding of medical knowledge in general practice.
Much emphasis is now being placed on the quality of medical care, and various ways are being developed to assess the medical knowledge of general practitioners. It is increasingly recognised that the users perspective on health care is important, and that the views of health care professionals do not and cannot represent patients' views. In order to explore whether or not a large-scale survey, which asked people to rate their doctors' medical knowledge, yielded meaningful results, this paper draws on findings from a study involving in-depth interviews with 26 lay people who had already completed the General Practice Assessment Survey questionnaire. When completing the questionnaires, patients had been asked to consider the 'technical care' provided by their general practitioners and to make a judgement about their doctors' medical knowledge. When interviewed at a later date, some people explained that they defined medical knowledge as knowledge of 'disease and treatments', while others defined it as knowledge of the 'whole person', and some defined a knowledgeable doctor as one who would acknowledge uncertainty. Patients appeared to have made judgements about their general practitioners' medical knowledge based on many factors, such as their experience of illness, perceptions of professional training, contact with other health care professionals in both primary and secondary care, and exposure to the media. The paper discusses the nature of medical knowledge, and concludes that although patient surveys are useful for the evaluation of interpersonal care and access to care, asking patients about their general practitioners' medical knowledge may yield invalid results. This is partly because patients defined medical knowledge in different ways, and partly because it appears that relatively few patients had enough knowledge about their own particular illnesses, or about possible alternative treatments, to make informed judgements about their general practitioners' medical knowledge.


The outcomes of 31 cases of trisomy 13 diagnosed in utero with various management options.
There are few reports on the prognosis of prenatally diagnosed trisomy 13 in relation to postnatal management. The aim of this study was to report on the prenatal and postnatal outcomes and postnatal management of trisomy 13 fetuses that were prenatally diagnosed at our center between 2003 and 2015. The data were retrospectively reviewed from medical records. Of the 31 cases of trisomy 13, 12 patients were diagnosed before 22 weeks of gestation, and 19 were diagnosed at or after 22 weeks of gestation. Nine families opted for termination of the pregnancy, 14 fetuses died, and 8 were born alive. Aggressive treatment was requested in two of the live births, with one patient achieving long-term survival (7 years). The other died during infancy (Day 61). One out of four who received palliative treatment is alive at two years of age with only nutrition supplementation. These three patients who achieved neonatal survival had few structural anomalies. Fetal death and early neonatal death are common in trisomy 13; however, fetuses that receive medical treatment for cases without major ultrasound abnormalities may achieve neonatal survival. Therefore, it is useful to provide comprehensive information, including precise ultrasound findings and treatment options, to parents with trisomy 13 fetuses during genetic counseling.


Synthesis of Organic-Inorganic Hybrid Perovskite/MOF Composites from Pb-MOF Using a Mechanochemical Method.
The specific structure and diverse properties of hybrid organic-inorganic perovskite materials make them suitable for use in photovoltaic and sensing fields. In this study, environmentally stable organic-inorganic hybrid perovskite luminescent materials using Pb-MOF as a particular lead source were prepared using a mechanochemical method. Based on the fluorescence intensity of the MAPbBr3/MOF composite, the mechanized chemical preparation conditions of Pb-MOF were optimized using response surface methodology. Then, the morphological characteristics of the MAPbBr3/MOF composite at different stages were analyzed using electron microscopy to explore its transformation and growth process. Furthermore, the composite form of MAPbBr3 with Pb-MOF was studied using XRD and XPS, and the approximate content of MAPbBr3 in the composite material was calculated. Benefiting from the increase in reaction sites generated from the crush of Pb-MOF during mechanical grinding, more MAPbBr3 was generated with a particle size of approximately 5.2 nm, although the morphology of the composite was significantly different from the initial Pb-MOF. Optimal performance of MAPbBr3/MOF was obtained from Pb-MOF prepared under solvent-free conditions, with a milling time of 30 min, milling frequency of 30 Hz and ball-material of 35:1. It was also confirmed that the mechanochemical method had a good universality in preparing organic-inorganic hybrid perovskite/MOF composites.


Application of Differential Entropy in Characterizing the Deformation Inhomogeneity and Life Prediction of Low-Cycle Fatigue of Metals.
The relation between deformation inhomogeneity and low-cycle-fatigue failure of T2 pure copper and the nickel-based superalloy GH4169 under symmetric tension-compression cyclic strain loading is investigated by using a polycrystal representative volume element (RVE) as the material model. The anisotropic behavior of grains and the strain fields are calculated by crystal plasticity, taking the Bauschinger effect into account to track the process of strain cycles of metals, and the Shannon's differential entropies of both distributions of the strain in the loading direction and the first principal strain are employed at the tension peak of the cycles as measuring parameters of strain inhomogeneity. Both parameters are found to increase in value with increments in the number of cycles and they have critical values for predicting the material's fatigue failure. Compared to the fatigue test data, it is verified that both parameters measured by Shannon's differential entropies can be used as fatigue indicating parameters (FIPs) to predict the low cycle fatigue life of metal.


Investigation of the reduced high-potential iron-sulfur protein from chromatium vinosum and relevant model compounds: a unified picture of the electronic structure of [Fe(4)S(4)](2+) systems through magnetic and optical studies.
Magnetization measurements and variable temperature optical spectroscopy have been used to investigate, within the 4-300 K temperature range, the electronic structure of the reduced high-potential iron protein (HiPIP) from Chromatium vinosum and the model compounds (Cat)(2)[Fe(4)S(4)(SR)(4)], where RS(-) = 2,4,6-triisopropylphenylthiolate (1), 2,6-diphenylphenylthiolate (2), diphenylmethylthiolate (3), 2,4,6-triisopropylbenzylthiolate (4, 4'), 2,4,6-triphenylbenzylthiolate (5, 5'), 2,4,6-tri-tert-butylbenzylthiolate (6), and Cat(+) = (+)NEt(4) (1, 2, 3, 4', 5', 6), (+)PPh(4) (4, 5). The newly synthesized 2(2)(-), 3(2)(-), 5(2)(-), and 6(2)(-) complexes are, as 1(2)(-) and 4(2)(-), excellent models of the reduced HiPIPs: they exhibit the [Fe(4)S(4)](3+/2+) redox couple, because of the presence of bulky ligands which stabilize the [Fe(4)S(4)](3+) oxidized core. Moreover, the presence of SCH(2) groups in 4(2)(-), 5(2)(-), and 6(2)(-), as in the [Fe(4)S(4)] protein cores, makes them good biomimetic models of the HiPIPs. The X-ray structure of 2 is reported: it crystallizes in the orthorhombic space group Pcca with no imposed symmetry and a D(2)(d)()-distorted geometry of the [Fe(4)S(4)](2+) core. Fit of the magnetization data of the reduced HiPIP and of the 1, 2, 3, 4, 5, and 6 compounds within the exchange and double exchange theoretical framework leads to exchange coupling parameters J = 261-397 cm(-)(1). A firm determination of the double exchange parameters B or, equivalently, the transfer integrals beta = 5B could not be achieved that way. The obtained |B| values remain however high, attesting thus to the strength of the spin-dependent electronic delocalization which is responsible for lowest lying electronic states being characterized by delocalized mixed-valence pairs of maximum spin (9)/(2). Electronic properties of these systems are then accounted for by the population of a diamagnetic ground level and excited paramagnetic triplet and quintet levels, which are respectively J and 3J above the ground level. Optical studies of 1, 2, 4', 5', and 6 but also of (NEt(4))(2)[Fe(4)S(4)(SCH(2)C(6)H(5))(4)] and the isomorph (NEt(4))(2)[Fe(4)S(4)(S-t-Bu)(4)] and (NEt(4))(2)[Fe(4)Se(4)(S-t-Bu)(4)] compounds reveal two absorption bands in the near infrared region, at 705-760 nm and 1270-1430 nm, which appear to be characteristic of valence-delocalized and ferromagnetically coupled [Fe(2)X(2)](+) (X = S, Se) units. The |B| and |beta| values can be directly determined from the location at 10|B| of the low-energy band, and are respectively of 699-787 and 3497-3937 cm(-)(1). Both absorption bands are also present in the 77 K spectrum of the reduced HiPIP, at 700 and 1040 nm (Cerdonio, M.; Wang, R.-H.; Rawlings, J.; Gray, H. B. J. Am. Chem. Soc. 1974, 96, 6534-6535). The blue shift of the low-energy band is attributed to the inequivalent environments of the Fe sites in the protein, rather than to an increase of |beta| when going from the models to the HiPIP. The small differences observed in known geometries of [Fe(4)S(4)](2+) clusters, especially in the Fe-Fe distances, cannot probably lead to drastic changes in the direct Fe-Fe interactions (parameter beta) responsible for the delocalization phenomenon. These differences are however magnetostructurally significant as shown by the 261-397 cm(-)(1) range spanned by J. The cluster's geometry, hence the efficiency of the Femicro(3)-S-Fe superexchange pathways, is proposed to be controlled by the more or less tight fit of the cluster within the cavity provided by its environment.


Dynamic assessment of paranasal sinus ventilation using xenon-enhanced computed tomography.
Disease of the paranasal sinuses is a common and costly condition. Evaluation of the efficacy of either medical or surgical methods of treatment is limited by the lack of quantitative methods to characterize sinus ventilation, which may be an important determinant of the baseline physiological state of the sinuses. Xenon-enhanced computed tomography (Xe-CT) measurement of sinus ventilation provides a noninvasive method of quantifying maxillary sinus ventilation using the nonradioactive, radiodense gas Xe as a tracer. Study subjects breathed a mixture of Xe gas and oxygen through a close-fitting nasal mask during serial CT imaging of a single radiographic plane through the maxillary sinuses--a generally well-tolerated protocol. Analysis of the sinus density-time curves allowed calculation of first-order exponential time constants from which specific ventilation rates could be determined for individual sinuses. Previously developed data analysis techniques were used to assess the statistical significance of the data and determine confidence intervals, allowing examination of the effects of noise in the data, and to demonstrate areas for further study protocol refinement. We conclude that Xe-CT measurement of sinus ventilation is a potentially valuable noninvasive technique for the diagnostic imaging of the human maxillary sinus.


Ecological aspects of water impoundment in the tropics.
Recognition of the potentially harmful effects of water development in the tropics had led to increasing efforts to assess the environmental impact of such projects prior to construction. Decisions regarding the development or non-development of water resources must be based on sound investigation of both the long-and short-term effects of reservoir construction and operation. The environmental effects of water impoundment vary greatly with the characteristics of the region as well as the type of reservoir to be constructed (area and depth of reservoir, ratio of water inflow to storage). Of major concern are the reduction of reservoir capacity as sediments accumulate behind the dam and the loss of these sediments to downstream agriculture and fisheries. The potential impact of altered flow regimes, siltation, reduction in beach formation and nutrient enrichment at the mouths of rivers, and the possibility of saltwater encroachment should receive careful stdy. A thorough description of the plants and animals to be affected by inundation should be made to determine the possible loss of rare or key organisms as well as the potential development of "nuisance species". Included in this survey should be a detailed study of existing fish and the potential for commercial fishery development in the proposed reservoir. Consideration should be given to vegetation removal in the reservoir basin prior to inundation, since decaying vegetation can result in deoxygenation, formation of hydrogen sulfide, possible development of suitable habitats for undesirable species and snagging of fish nets. Sanitation and land use practices as well as erosion in the watershed surrounding the reservoir must be controlled to prevent accelerated eutrophication caused by increased nutrient loading. Inundation in tropical areas can have serious sociological and human health implications including the increase of diseases, e.g., malaria, schistosomiasis, onchocerciasis, and dysentery, and the probable resettlement and alteration of land use practices. Census information and surveys concerning land use, housing and health standards and the social and economic structure of the community to be affected must be evaluated in order to anticipate and avoid potential problems. The archaeologic, historic, scenic and recreational value of the site to be inundated must also be considered. Studies of the EL Cajón site on the Sula River in Honduras and the Purari River Project in Papua, New Guinea, are utilized as examples in this report.


State of the art - how I manage immune thrombocytopenia.
The management of patients with immune thrombocytopenia (ITP) is rapidly evolving. Over the last 15 years, a number of novel treatments have improved practice, with many steroid-sparing agents and a reduction in the progression to splenectomy. Although this has improved clinical care, many therapeutic challenges remain. There is no diagnostic test, no biomarkers to direct treatment and few comparative studies to help management decisions. Development of up to date guidelines is difficult with little high-grade evidence. First line treatment continues to be steroids and intravenous immunoglobulins (IVIG) although both are often poorly tolerated and not curative. Common second line treatments include rituximab, immunosuppressive agents, such as azathioprine and mycophenolate mofetil, and the thrombopoietin receptor agonists romiplostim and eltrombopag. There are no comparative studies to decide between these agents and treatment is generally individualized, depending on comorbidity. Use of splenectomy has declined and is generally reserved for patients with chronic disease, although the exact position of splenectomy is subject to debate. Further understanding of the cause of disease in individual patients may help guide treatment. Randomized controlled studies of common treatments and novel treatments for refractory patients are urgently needed.


Xanthoma tendinosum in a normolipemic ectodermal dysplasia patient.
A female patient with congenital ectodermal dysplasia is described, who developed xanthoma tendinosum in her hands simulating rheumatoid arthritis. The serum lipids of this patient were normal. Both ectodermal dysplasia and xanthoma tendinosum in a normolipemic patient are rather uncommon and to our knowledge have not been previously reported in one and the same patient.


Congruency of color-sound crossmodal correspondence interacts with color and sound discrimination depending on color category.
People occasionally associate color (e.g., hue) with sound (e.g., pitch). Previous studies have reported color-sound associations, which are examples of crossmodal correspondences. However, the association between both semantic and perceptual factors with color/sound discrimination in crossmodal correspondence remains unclear. To clarify this, three psychological experiments were conducted, where Stroop tasks were used to assess automatic process on the association. We focused on the crossmodal correspondence between color (Experiment 1)/color word (Experiment 2) and sound. Participants discriminated the color/word or the sound presented simultaneously. The results showed the color-sound bidirectional enhancement/interference of the response by certain associations of the crossmodal correspondence (blue-drop and yellow-shiny) in both experiments. These results suggest that these Stroop effects were caused by the semantic factor (color category) and the perceptual factor (color appearance) was not necessary for the current results. In Experiment 3, response modulation by color labeling was investigated to clarify the influence of subjective labeling. Participants labeled a presented ambiguous color, which was a hue specification between two specific colors, by listening to the sound. The results revealed that the Stroop effect was caused only when the presented color was classified as the color related to the presented sound. This showed that subjective labeling played a role in the regulation of the effect of crossmodal correspondences. These findings should contribute to the explanation of crossmodal correspondences through semantic mediation.


Effect of a sintering process on the electrical properties of SnO2 gas sensors.
SnO2 is a widely used sensor material that exhibits high sensitivity. It is known for its complex sensing characteristics, and its microstructure is an important parameter related to electrical properties and mechanical rigidity. Understanding of its microstructural effects is therefore essential to examine sensing mechanisms that may apply to industrial devices. In this work, the effect of a sintering process on the electrical properties is investigated. The sintering temperature and the relative density were chosen as process variables. The grain size of the specimen increased as the sintering temperature increased, whereas the relative density did not change. The apparent activation energy for conduction varied as the compacting pressure and the sintering conditions changed. Samples with a high density and large particle size showed low activation energy for conduction and low sensitivity at 375 degrees C. In an attempt to improve the properties, the powder was heat-treated at 1000 degrees C for 10 hours before compacting and sintering. The samples with heat-treated powder showed a slight decrease in the activation energy depending on the density and comparable sensitivity compared to non-treated powder at a high density. Pre-treatment of powder can be a simple means of thermal stability under high operating temperatures.


Biliary Tract Disease in Girls and Young Women With Rett Syndrome.
We reviewed medical records and conducted a nationwide survey to characterize the clinical features and determine the prevalence of biliary tract disease in girls and women with Rett syndrome (RTT). Sixty-two individuals with RTT and biliary tract disease were identified from the membership of Rett Syndrome Organization and patient files of the principal investigator. Medical records of 46 individuals were reviewed for presenting features, diagnostic tests, and treatment outcomes of biliary tract disease. We designed a questionnaire that probed the frequency of risk factors and treatment outcomes of biliary tract disease in RTT. The questionnaire was completed by 271 parents whose daughters met the clinical criteria for RTT and/or had MECP2 mutations and participated in the Natural History of Rett Syndrome Study. Presenting symptoms identified by record review included abdominal pain (94%), irritability (88%), weight loss (64%), and vomiting (52%). Biliary dyskinesia, cholecystitis, and cholelithiasis were identified in 90%, 77%, and 70%, respectively, by cholescintigraphy, surgical pathology, and abdominal ultrasound. The prevalence of biliary tract disease was 4.4% (n = 12) in the RTT cohort. Risk factors included older age (P < 0.001) and a positive family history (P < 0.01). Diagnoses included cholecystitis (n = 5), biliary dyskinesia (n = 6), and cholelithiasis (n = 7). Ten individuals underwent surgery; 7 had resolution of symptoms after surgical intervention. Biliary tract disease is not unique to RTT, but may be under-recognized because of the cognitive impairment of affected individuals. Early diagnostic evaluation and intervention may improve the health and quality of life of individuals affected with RTT and biliary tract disease.


The Parenting Experiences of Hispanic Adolescent Fathers: A Life Course Theory Perspective.
Using a life course theory perspective, this qualitative descriptive study explored how Hispanic adolescent fathers view fatherhood, and how their perception of parenthood is shaped by critical life events. Hispanics are one of the largest ethnic groups, as well as one of the populations that is overrepresented in adolescent births in the United States. Despite this, Hispanic adolescent fathers are understudied and underrepresented in research. Participants were recruited from a community-based fatherhood program. Semi-structured interviews were conducted with Hispanic fathers, ages 16 years to 23 years. Participants conveyed their grief over fragmented family relationships and limited interactions with their own father. Some lived in hostile environments where they frequently experienced racism, discrimination, and neighborhood violence. The cumulative impact of these events resulted in substance use and emotional distress. Becoming a father was a sentinel event that helped resolve negative perceptions about fatherhood. Fatherhood also motivated participants towards a more productive, meaningful life.


Navigating time and uncertainty in health technology appraisal: would a map help?
Healthcare systems are increasingly under pressure to provide funding for innovative technologies. These technologies tend to be characterized by their potential to make valued contributions to patient health in areas of relative unmet need, and have high acquisition costs and uncertainty within the evidence base on their actual impact on health. Decision makers are increasingly interested in linking reimbursement strategies to the degree of uncertainty in the evidence base and, as a result, reimbursement for innovative technologies is frequently linked to some form of patient access or risk-sharing scheme. As the dominant methods of economic evaluation report final outcomes only at the time horizon of the analysis, they present only aggregated information. This omits much of the information available on how net benefit is distributed within the time horizon. In this article, we introduce the Net Benefit Probability Map (NBPM), which maps net health benefit versus time to identify how certain decision makers can be about the benefit of technologies at multiple time points. Using an illustrative example, we show how the NBPM can inform decision makers about how long it will take for innovative technologies to 'pay off', how methodological choices on discount rates affect results and how alternative payment mechanisms can reduce the risk for decision makers facing innovative technologies.


Effect of sodium hexanitrocobaltate (III) decomposition on its staining of intracellular potassium ions.
The effect was examined of the chemical decomposition of the potassium stain sodium hexanitrocobaltate (III) (SHC), on its ability to produce stain granules of consistent size that could be used to estimate the K+ contents of stomatal guard cells. Stomata in detached epidermis from leaves of Vicia faba (fava bean) were stimulated to accumulate K+ by treating them with fusicoccin. Stomatal apertures and the fraction of guard cell area covered by K+ precipitate granules (K+ score) were measured by digitizing photographic enlargements, and K+ scores were correlated with the age of stain that had been stored either in open or closed containers. The ability of stain aged in open containers to produce consistent fractional cell coverage was compared to 1) the ability of identically treated stain to precipitate K+ from solutions of KCI, and to 2) the kinetics of decomposition of SHC. It was found that the fractional coverage of guard cells of stomata opened to the same apertures decreased with a first order rate constant of 2.3 x 10(-5)/sec. The mass of precipitate formed by treatment of KCl solutions was unchanged for 2 hr after initial preparation of the SHC, and decreased thereafter with a first order rate constant of 1.0 x 10(-5)/sec. When stored in tightly sealed containers, nearly 100 hr were required for an occasionally opened bottle of SHC to decay to the same efficacy as a solution left open to the air for 8 hr.


Simulation to aid in interpreting biological relevance and setting of population-level protection goals for risk assessment of pesticides.
Specific protection goals (SPGs) comprise an explicit expression of the environmental components that need protection and the maximum impacts that can be tolerated. SPGs are set by risk managers and are typically based on protecting populations or functions. However, the measurable endpoints available to risk managers, at least for vertebrates, are typically laboratory tests. We demonstrate, using the example of eggshell thinning in skylarks, how simulation can be used to place laboratory endpoints in context of population-level effects as an aid to setting the SPGs. We develop explanatory scenarios investigating the impact of different assumptions of eggshell thinning on skylark population size, density and distribution in 10 Danish landscapes, chosen to represent the range of typical Danish agricultural conditions. Landscape and timing of application of the pesticide were found to be the most critical factors to consider in the impact assessment. Consequently, a regulatory scenario of monoculture spring barley with an early spray treatment eliciting the eggshell thinning effect was applied using concentrations eliciting effects of zero to 100% in steps of 5%. Setting the SPGs requires balancing scientific, social and political realities. However, the provision of clear and detailed options such as those from comprehensive simulation results can inform the decision process by improving transparency and by putting the more abstract testing data into the context of real-world impacts.


Novelties in the pathophysiology and management of portal hypertension: new treatments on the horizon.
Portal hypertension (PH) is responsible for the most severe complications of cirrhosis and leading cause of death and liver transplantation. The standard pharmacological treatment available for PH currently consists of the use of a non-selective beta-blocker. However, a significant proportion of patients do not respond to pharmacological treatment. This has led to the development of identifiable targets for the discovery of new horizons in PH treatment. Recently, there has been significant progress in understanding the mechanism behind PH, which is a product of increased hepatic vascular resistance including structural changes and functional change due to endothelial dysfunction. Moreover, increased portal inflow is the outcome of dilation of splanchnic vessels and hyperdynamic circulation. Here, challenges in formulating potential pharmacological treatment as well as current potential targets for PH will be reviewed. During the past decades, there have been many efforts to explore new techniques to stimulate liver regeneration in addition to pharmacological treatment. The bone marrow (BM) stem cells which differentiate into mature hepatocytes are thought to contribute to liver regeneration and have been found to demonstrate great potential as regenerative medicine in different therapeutic applications. Based on these insights, we explore the current and potential novel therapeutic uses of BM stem cell therapy in PH.


Characterization of type-II spontaneous parametric down-conversion in domain-engineered PPLN.
We characterize spontaneous parametric downconversion in a domain-engineered, type-II periodically poled lithium niobate (PPLN) crystal using seeded emission and single-photon techniques. Using continuous-wave (CW) pumping at 775 nm wavelength, the signal and idler are at 1532.5 nm and 1567.5 nm, respectively. The domain-engineered crystal simultaneously phasematches signal and idler pairs: [H(1532.5 nm), V(1567.5 nm)] and [V(1532.5 nm), H(1567.5 nm)]. We observe the tuning curves of these processes through difference-frequency generation and through CW fiber-assisted, single-photon spectroscopy. These measurements indicate good matching in amplitude and bandwidth of the two processes and that the crystal can in principle be used effectively to generate polarization-entangled photon pairs.


A New Polyoxometalate (POM)-Based Composite: Fabrication through POM-Assisted Polymerization of Dopamine and Properties as Anode Materials for High-Performance Lithium-Ion Batteries.
Organic substrates are indispensable in the fabrication of multifunctional polyoxometalate (POM)-based composites for various applications. A new molybdovanadophosphoric heteropolyacid (PMo10 V2 )-based polydopamine (PDA) composite (PMo10 V2 /PDA) is first synthesized through a facile, in situ polymerization method under hydrothermal conditions, without the addition of extra buffer solution. The obtained PMo10 V2 /PDA composite shows homogeneous microsphere morphology. Through utilization of the adhesive ability of PDA, the composite can be used as an anode material without additional binder for rechargeable lithium-ion batteries. Excellent electrochemical performances are obtained, with a high, stable specific capacity of 915.3 mA h g-1 at a current density of 100 mA g-1 , remarkable rate capability, and good cycling stability (≈93 % capacity retention after 300 cycles at a high current density of 1000 mA g-1 ).


Effects of the aromatic substitution pattern in cation-π sandwich complexes.
A computational study investigating the effects of the aromatic substitution pattern on the structure and binding energies of cation-π sandwich complexes is reported. The correlation between the binding energies (Ebind) and Hammett substituent constants is approximately the same as what is observed for cation-π half-sandwich complexes. For cation-π sandwich complexes where both aromatics contain substituents the issue of relative conformation is a possible factor in the strength of the binding; however, the work presented here shows the Ebind values are approximately the same regardless of the relative conformation of the two substituted aromatics. Finally, recent computational work has shown conflicting results on whether cation-π sandwich Ebind values (Ebind,S) are approximately equal to twice the respective half-sandwich Ebind values (Ebind,HS), or if cation-π sandwich Ebind,S values are less than double the respective half-sandwich Ebind,HS values. The work presented here shows that for cation-π sandwich complexes involving substituted aromatics the Ebind,S values are less than twice the respective half-sandwich Ebind,HS values, and this is termed nonadditive. The extent to which the cation-π sandwich complexes investigated here are nonadditive is greater for B3LYP calculated values than for MP2 calculated values and for sandwich complexes with electron-donating substituents than those with electron-withdrawing groups.


Application of ethanol improves the resin-dentin bond strength of a two-bottle, self-etching primer-adhesive.
To investigate whether the application of ethanol to a two-step self-etching adhesive can improve its resin-dentin bond performance. Four different ethanol concentrations were added to the adhesive of Clearfil SE Bond to create four ethanol primers (40, 60, 80 or 100% ethanol). 24 extracted third molars were divided into four groups. Each group corresponded to one of the four hydrophobic ethanol primer concentrations. The teeth in the control group were bonded with Clearfil SE Bond according to the manufacturer's instructions. The primed teeth in the experimental groups were treated with the ethanol primer prior to application of the solvent-free adhesive. Microtensile bond strengths (mTBS) were tested 24 hours after specimen preparation. Another 14 teeth were bonded using the same methods to evaluate mTBS after 1 year. Nanoleakage was evaluated under field-emission scanning electron microscopy before and after aging. In the 24-hour group, the mTBS in the 60% ethanol/40% adhesive primer group increased significantly (21.6%, P < 0.05) over the no ethanol control. After 12-month water storage, the bond strength of that experimental group was still higher than that of the control group (19.5%, P < 0.05). Before aging, the nanoleakage was clearly seen in the control group but hardly any was seen in the experimental group. After aging, the nanoleakage increase in the experimental group was much less than that in the control group.


New insights on the taxonomy and phylogenetic relationships of the Neotropical genus Phoebis (Pieridae: Coliadinae) revealed by molecular and morphological data.
Phoebis Hübner (1819) is a genus of the Neotropical subfamily Coliadinae (Lepidoptera: Pieridae). The highest diversity is found in the Greater Antilles islands in the Caribbean region. Although from the taxonomic point of view, Phoebis seems to be a stable genus, there is no phylogenetic hypothesis corroborating the monophyly of the genus. In this study, we used both morphological characters and a genetic dataset consisting of one mitochondrial (COI) and three nuclear markers (RpS5, MDH, Wingless). The matrix was concatenated and analysed with parsimony under implied weights (IW). Also, the concatenated data set was analysed using maximum likelihood and Bayesian inference evolutionary methods, and ancestral states reconstruction with characters traditionally used for classification of Phoebis was carried out. The same topology was recovered by Parsimony, ML and BI analysis, and suggest that Phoebis is not a monophyletic genus, with Aphrissa and Rhabdodryas nested within it. Our findings allow us to consider the genera Rhabdodryas syn.rev. and Aphrissa syn.rev. to be synonyms of Phoebis. These results have implications for the systematics of Phoebis and the genera that should be accepted in Coliadinae.


Optimum transport in systems with time-dependent drive and short-ranged interactions.
We consider a one-dimensional lattice gas model of hardcore particles with nearest-neighbor interaction in presence of a time-periodic external potential. We investigate how attractive or repulsive interaction affects particle transport and determine the conditions for optimum transport, i.e., the conditions for which the maximum dc particle current is achieved in the system. We find that the attractive interaction in fact hinders the transport, while the repulsive interaction generally enhances it. The net dc current is a result of the competition between the current induced by the periodic external drive and the diffusive current present in the system. When the diffusive current is negligible, particle transport in the limit of low particle density is optimized for the strongest possible repulsion. But when the particle density is large, very strong repulsion makes particle movement difficult in an overcrowded environment and, in that case, the optimal transport is obtained for somewhat weaker repulsive interaction. Our numerical simulations show reasonable agreement with our mean-field calculations. When the diffusive current is significantly large, the particle transport is still facilitated by repulsive interaction, but the conditions for optimality change. Our numerical simulations show that the optimal transport occurs at the strongest repulsive interaction for large particle density and at a weaker repulsion for small particle density.


High glucose contributes to the proliferation and migration of non-small cell lung cancer cells via GAS5-TRIB3 axis.
Despite the growing number of studies exhibited an association of diabetes mellitus (DM) and lung cancer progression, the concrete mechanism of DM aggravating lung cancer has not been elucidated. This study was to investigate whether and how high glucose (HG) contribute to the proliferation and migration of non-small cell lung cancer (NSCLC) cells in vitro. In the present study, we confirmed that HG promoted the proliferation and migration of NSCLC cells, and also induced an anti-apoptosis effect on NSCLC cells. Moreover, HG inhibited the expression of GAS5 in NSCLC cells but elevated the protein level of TRIB3. GAS5 overexpression promoted the degradation of TRIB3 protein by ubiquitination and inhibited the HG induced-proliferation, anti-apoptosis and migration of NSCLC cells. Importantly, TRIB3 overexpression reversed the effects of GAS5 on the HG-treated NSCLC cells. Taken together, down-regulated GAS5 by HG significantly enhanced the proliferation, anti-apoptosis and migration in NSCLC cells through TRIB3, thus promoting the carcinogenesis of NSCLC.


Intrinsic curvature in the VP1 gene of SV40: comparison of solution and gel results.
DNA restriction fragments that are stably curved are usually identified by polyacrylamide gel electrophoresis because curved fragments migrate more slowly than normal fragments containing the same number of basepairs. In free solution, curved DNA molecules can be identified by transient electric birefringence (TEB) because they exhibit rotational relaxation times that are faster than those of normal fragments of the same size. In this article, the results observed in free solution and in polyacrylamide gels are compared for a highly curved 199-basepair (bp) restriction fragment taken from the VP1 gene in Simian Virus 40 (SV40) and various sequence mutants and insertion derivatives. The TEB method of overlapping fragments was used to show that the 199-bp fragment has an apparent bend angle of 46 +/- 2 degrees centered at sequence position 1922 +/- 2 bp. Four unphased A- and T-tracts and a mixed A3T4-tract occur within a span of approximately 60 bp surrounding the apparent bend center; for brevity, this 60-bp sequence element is called a curvature module. Modifying any of the A- or T-tracts in the curvature module by site-directed mutagenesis decreases the curvature of the fragment; replacing all five A- and T-tracts by random-sequence DNA causes the 199-bp mutant to adopt a normal conformation, with normal electrophoretic mobilities and birefringence relaxation times. Hence, stable curvature in this region of the VP1 gene is due to the five unphased A- and T- tracts surrounding the apparent bend center. Discordant solution and gel results are observed when long inverted repeats are inserted within the curvature module. These insertion derivatives migrate anomalously slowly in polyacrylamide gels but have normal, highly flexible conformations in free solution. Discordant solution and gel results are not observed if the insert does not contain a long inverted repeat or if the long inverted repeat is added to the 199-bp fragment outside the curvature module. The results suggest that long inverted repeats can form hairpins or cruciforms when they are located within a region of the helix backbone that is intrinsically curved, leading to large mobility anomalies in polyacrylamide gels. Hairpin/cruciform formation is not observed in free solution, presumably because of rapid conformational exchange. Hence, DNA restriction fragments that migrate anomalously slowly in polyacrylamide gels are not necessarily stably curved in free solution.


Association of Current and Lifetime DSM-IV Drug use Disorder Diagnoses to 6-Month Changes in Smoking Behavior in Risky Drinking Smokers: A Pilot Study.
Alcohol and other drug use disorders co-occur with cigarette smoking and negatively impact cessation outcomes. This study examined the differential effects of current and lifetime DSM-IV drug diagnoses on the 6-month smoking outcomes of 84 untreated heavy drinking smokers who were motivated to quit smoking in the next 6-months. Generalized estimating equations (GEE) assessed changes in nicotine dependence, readiness to quit smoking, and prevalence of heavy smoking from baseline to 6-months as a function of time, baseline drinking severity, and drug diagnosis. GEE models showed that nicotine dependence and prevalence of heavy smoking decreased over 6-months, irrespective of drug diagnosis and baseline alcohol consumption. Several 3-way interactions were found, showing differences in the rate of change over time in readiness to quit smoking and prevalence of heavy smoking as a function of current versus lifetime drug diagnosis and higher versus lower of baseline alcohol consumption. Conclusions/Importance: Drug diagnoses are common in risky drinking smokers, and significantly impede changes in smoking behavior and motivation to quit. Treatment planning for smoking cessation should include a thorough assessment of current and past drug use behavior to determine the impact on readiness to quit and quit success. Mechanisms of change in smokers with multiple substance use diagnoses should be examined.


Making family-centered care a reality.
Family-centered care means, in the broadest sense, welcoming the family as partners in the care of the child. Family-centered care challenges us to create a new vision of a hospital environment that works in a very different way and that can actually improve clinical outcomes. This report describes one hospital's journey into family-centered care--its accomplishments and its challenges. It should be noted that, although this report describes family-centered care in a children's hospital, the philosophy beautifully adapts to an adult facility.


Nobiletin, a Polymethoxy Flavonoid, Protects Against Cardiac Hypertrophy Induced by Pressure-Overload via Inhibition of NAPDH Oxidases and Endoplasmic Reticulum Stress.
An increase in oxidative stress has been implicated in the pathophysiology of pressure-overload induced cardiac hypertrophy. Nobiletin (NOB), extracted from the fruit peel of citrus, possesses anti-oxidative property. Our study aimed to investigate the protective role of NOB in the progression of cardiac hypertrophy in vivo and in vitro. Mice received aortic banding (AB) operation to induce cardiac hypertrophy. Experimental groups were as follows: sham+vehicle (VEH/SH), sham+NOB (NOB/SH), AB+vehicle (VEH/AB), and AB+ NOB (NOB/AB). Animals (n = 15 per group) were treated with vehicle or NOB (50 mg/kg) for 4 weeks after disease onset. NOB prevented cardiac hypertrophy induced by aortic banding (AB), as assessed by the cross-sectional area of cardiomyocytes, heart weight-to-body weight ratio, gene expression of hypertrophic markers and cardiac function. In addition, NOB supplementation blunted the increased expression of NAPDH oxidase (NOX) 2 and NOX4 and mitigated endoplasmic reticulum (ER) stress and myocyte apoptosis in cardiac hypertrophy. Furthermore, NOB treatment attenuated the neonatal rat cardiomyocyte (NRCM) hypertrophic response stimulated by phenylephrine (PE) and alleviated ER stress. However, our data showed that NOB dramatically inhibited NOX2 expression but not NOX4 in vitro. Finally, we found that knockdown of NOX2 attenuated ER stress in NRCMs stimulated by PE. Inhibition of oxidative and ER stress by NOB in the myocardium may represent a potential therapy for cardiac hypertrophy. Moreover, there is a direct role of NOX2 in regulating ER stress stimulated by PE.


Erythropoietin administration increases splenic erythroferrone protein content and liver TMPRSS6 protein content in rats.
Erythroferrone (ERFE) and TMPRSS6 are important proteins in the regulation of iron metabolism. The objective of the study was to examine splenic ERFE and liver TMPRSS6 synthesis in rats treated with a combination of iron and erythropoietin (EPO). EPO was administered to female Wistar rats at 600U/day for four days, iron-pretreated rats received 150mg of iron before EPO treatment. Content of ERFE and TMPRSS6 proteins was determined by commercial antibodies. Iron pretreatment prevented the EPO-induced decrease in hepcidin expression. Content of phosphorylated SMAD 1,5,8 proteins was decreased in the liver by both EPO and iron plus EPO treatment. Fam132b expression in the spleen was increased both by EPO and iron plus EPO treatments; these treatments also significantly induced splenic Fam132a expression. ERFE protein content in the spleen was increased both by EPO and iron plus EPO to a similar extent. EPO administration increased TMPRSS6 content in the plasma membrane-enriched fraction of liver homogenate; in iron-pretreated rats, this increase was abolished. The results confirm that iron pretreatment prevents the EPO-induced decrease in liver Hamp expression. This effect probably occurs despite high circulating ERFE levels, since EPO-induced ERFE protein synthesis is not influenced by iron pretreatment.


RING E3 ligases: key regulatory elements are involved in abiotic stress responses in plants.
Plants are constantly exposed to a variety of abiotic stresses, such as drought, heat, cold, flood, and salinity. To survive under such unfavorable conditions, plants have evolutionarily developed their own resistant-mechanisms. For several decades, many studies have clarified specific stress response pathways of plants through various molecular and genetic studies. In particular, it was recently discovered that ubiquitin proteasome system (UPS), a regulatory mechanism for protein turn over, is greatly involved in the stress responsive pathways. In the UPS, many E3 ligases play key roles in recognizing and tethering poly-ubiquitins on target proteins for subsequent degradation by the 26S proteasome. Here we discuss the roles of RING ligases that have been defined in related to abiotic stress responses in plants. [BMB Reports 2017; 50(8): 393-400].


Regulation of the timing of oligodendrocyte differentiation: mechanisms and perspectives.
Axonal myelination is an essential process for normal functioning of the vertebrate central nervous system. Proper formation of myelin sheaths around axons depends on the timely differentiation of oligodendrocytes. This differentiation occurs on a predictable schedule both in culture and during development. However, the timing mechanisms for oligodendrocyte differentiation during normal development have not been fully uncovered. Recent studies have identified a large number of regulatory factors, including cell-intrinsic factors and extracellular signals, that could control the timing of oligodendrocyte differentiation. Here we provide a mechanistic and critical review of the timing control of oligodendrocyte differentiation.


Recent and current advances in PET/CT imaging in the field of predicting epidermal growth factor receptor mutations in non-small cell lung cancer.
Tyrosine kinase inhibitors (TKIs) are a significant treatment strategy for the management of non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutation status. Currently, EGFR mutation status is established based on tumor tissue acquired by biopsy or resection, so there is a compelling need to develop non-invasive, rapid, and accurate gene mutation detection methods. Non-invasive molecular imaging, such as positron emission tomography/computed tomography (PET/CT), has been widely applied to obtain the tumor molecular and genomic features for NSCLC treatment. Recent studies have shown that PET/CT can precisely quantify EGFR mutation status in NSCLC patients for precision therapy. This review article discusses PET/CT advances in predicting EGFR mutation status in NSCLC and their clinical usefulness.


Restoration of fertility by gonadotropin replacement in a man with hypogonadotropic azoospermia and testicular adrenal rest tumors due to untreated simple virilizing congenital adrenal hyperplasia.
Classical congenital adrenal hyperplasia (CAH), a genetic disorder characterized by 21-hydroxylase deficiency, impairs male fertility, if insufficiently treated. A 30-year-old male was referred to our clinic for endocrine and fertility assessment after undergoing unilateral orchiectomy for a suspected testicular tumor. Histopathological evaluation of the removed testis revealed atrophy and testicular adrenal rest tumors (TARTs) and raised the suspicion of underlying CAH. The remaining testis was also atrophic (5 ml) with minor TARTs. Serum 17-hydroxyprogesterone levels were elevated, cortisol levels were at the lower limit of normal range, and gonadotropins at prepubertal levels, but serum testosterone levels were within the normal adult range. Semen analysis revealed azoospermia. CAH was confirmed by a homozygous mutation g.655A/C>G (IVS2-13A/C>G) in CYP21A2. Hydrocortisone (24 mg/m(2)) administered to suppress ACTH and adrenal androgen overproduction unmasked deficient testicular testosterone production. As azoospermia persisted due to sustained hypogonadotropic hypogonadism, a combined s.c. gonadotropin replacement with human chorionic gonadotropin (hCG) (1500 IU twice weekly) and FSH (human menopausal gondadotropin (hMG) 150 IU three times weekly) was initiated. Normalization of testosterone levels and a stable low sperm concentration (0.5 mill/ml) with good sperm motility (85% A+B progressive) were achieved within 21 months of treatment. Despite persisting TARTs, while receiving treatment, the patient successfully impregnated his wife twice, the latter impregnation leading to the birth of a healthy girl. TARTs in unrecognized (simple virilizing) CAH may lead to unnecessary orchiectomy. In hypogonadotropic, azoospermic CAH, a combined treatment with oral corticosteroids and subcutaneously administered hCG and FSH can successfully restore testicular testosterone production and fertility, even if only one hypoplastic and atrophic testis with adrenal rest tumors is present.


A simple real-time assay for in vitro translation.
A high-throughput assay for real-time measurement of translation rates in cell-free protein synthesis (SNAP assay) is described. The SNAP assay enables quantitative, real-time measurement of overall translation rates in vitro via the synthesis of O(6)-alkylguanine DNA O(6)-alkyltransferase (SNAP). SNAP production is continuously detected by fluorescence produced by the reaction of SNAP with a range of quenched fluorogenic substrates. The capabilities of the assay are exemplified by measurements of the activities of Escherichia coli MRE600 ribosomes and fluorescently labeled E. coli mutant ribosomes in the PURExpress translation system and by determination of the 50% inhibitory concentrations (IC50) of three common macrolide antibiotics.


Two-Dimensional Frank-Kasper Z Phase with One Unit-Cell Thickness.
Z phase is one of the three basic units by which the Frank-Kasper (F-K) phases are generally assembled. Compared to the other two basic units, that is, A15 and C15 structures, the Z structure is rarely experimentally observed because of a relatively large volume ratio among the constituents to inhibit its formation. Moreover, the discovered Z structures are generally the three-dimensional ordered Gibbs bulk phases to conform to their thermodynamic stability. Here, we confirmed the existence of a metastable two-dimensional F-K Z phase that has only one unit-cell height in the crystallography in a model Mg-Sm-Zn system, using atomic-scale scanning transmission electron microscopy combined with the first-principles calculations. Self-adapted atomic shuffling can convert the simple hexagonal close-packed structure to the topologically close-packed F-K Z phase. This finding provides new insight into understanding the formation mechanism and clustering behavior of the F-K phases and even quasicrystals in general condensed matters.


Differential tumor cell targeting of anti-HER2 (Herceptin) and anti-CD20 (Mabthera) coupled nanoparticles.
Two types of antibody-labeled nanoparticles (mAb-NPs) were prepared with the aim to achieve specific tumor targeting. Anti-HER2 and anti-CD20 monoclonal antibodies (mAb) were used as model ligands. Small poly(dl-lactic acid) nanoparticles (PLA NPs) with a mean size of about 170 nm were prepared by the salting out method. Thereafter, the coating of PLA NPs with mAbs was performed in two steps. First, thiol groups (-SH) were introduced on the surface of PLA-NPs by a two-step carbodiimide reaction. The number of -SH groups on the surface of NPs increased from 150 to 400 mmol-SH/mol PLA when cystamine concentrations of 25-1518 mol cystamine/mol PLA were used during the thiolation reaction. In the second step, covalent coupling of antibodies to thiolated NPs (NPs-SH) was obtained via a bifunctional cross-linker, m-maleimidobenzoyl-N-hydroxy-sulfosuccinimide ester (sulfo-MBS). For both mAbs anti-HER2 and anti-CD20, respectively, the number of -SH functions on the NPs had no influence on the amount of mAb coupled to the NPs. Approximately, 295 anti-HER2 and 557 anti-CD20 molecules, respectively, were covalently coupled per nanoparticle. The NPs size after the coupling reactions was about 250 nm. The specific interaction between tumor cells and mAb-NPs was determined by confocal microscopy using two cell lines: SKOV-3 human ovarian cancer cells (overexpressing HER2) and Daudi lymphoma cells (overexpressing CD20). The results showed the selective targeting of mAb-NPs to tumor cells overexpressing the specific antigen. While anti-CD20 labeled NPs (anti-CD20 NPs) bound to and remained at the cellular surface, anti-HER2 labeled NPs (anti-HER2 NPs) were efficiently internalized. The mAb-NPs represent a promising approach to improve the efficacy of NPs in active targeting for cancer therapy while the choice of the antibody-target system defines the fate of the mAb-NPs after their binding to the cells.


Pharmacy Interns' Perception of Their Professional Role.
Objective. To determine pharmacy interns' perceptions of the roles of the pharmacist and pharmacy prior to and during the pharmacy internship and to compare their perceptions with those of their supervisors and the pharmacy customers. Methods. Questionnaires were completed and submitted by 395 interns prior to and during their internships. Interns interviewed their supervisors and two to four local customers. Results. Ninety-six supervisors and 285 customers were interviewed. Interns' perceptions were aligned with those of their supervisors in that both groups indicated that a pharmacist's most important role is that of a clinical leader. Furthermore, interns' perception of customers' expectations regarding the pharmacy were well aligned with customers' actual expectations with regard to service. Conclusion. The study illustrates that interns became more aligned in their perceptions due to the pharmacy internship. The study findings imply that the pharmacy internship influences interns' perception of the pharmacy and pharmacist's roles in society through complex individual and social learning processes.


Role of uridine triphosphate in the phosphorylation of 1-beta-D-arabinofuranosylcytosine by Ehrlich ascites tumor cells.
Pyrimidine nucleotide pools were investigated as determinants of the rate of phosphorylation of 1-beta-D-arabinofuranosylcytosine (ara-C) by Ehrlich ascites cells and cell extracts. Cells were preincubated for 2 h with 10 microM pyrazofurin, 10 mM glucosamine, 50 microM 3-deazauridine, or 1 mM uridine in order to alter the concentrations of pyrimidine nucleotides. Samples of the cell suspensions were taken for assay of adenosine 5'-triphosphate (ATP), uridine 5'-triphosphate (UTP), cytidine 5'-triphosphate, guanosine 5'-triphosphate, deoxycytidine 5'-triphosphate (dCTP), and deoxythymidine 5'-triphosphate; then 1 microM [3H]ara-C was added and its rate of intracellular uptake was measured for 30 min. 3-Deazauridine lowered dCTP and stimulated ara-C uptake; however, pyrazofurin and glucosamine were potent inhibitors of ara-C uptake although they also decreased dCTP levels. Uridine stimulated ara-C uptake despite an increase in dCTP. A crude cytoplasmic extract was prepared by a procedure which permitted results of ara-C kinase assays to be expressed as pmol per min per 10(6) cells as in the cellular uptake studies. When assayed in the presence of mixtures of ribo- and deoxyribonucleoside triphosphates at concentrations close to their cellular levels, ara-C kinase activity closely approximated the cellular uptake rate for the five incubation conditions. Deletion of cytidine 5'-, guanosine 5'-, or deoxythymidine 5'-triphosphate from the assay mixture had little effect, while deletion of dCTP increased kinase activity 9-fold. Elimination of ATP also did not alter kinase activity in the presence of the remaining five ribo- and deoxyribonucleoside triphosphates; however, deletion of UTP reduced activity to 22% of the rate with the control mixture. When ara-C kinase was assayed with only 3 mM ATP, dCTP was a very potent inhibitor (50% inhibition concentration = 0.4 microM). Inhibition was complete at 10 microM dCTP, a concentration below the intracellular dCTP level in control cells (25 microM). With 0.9 mM UTP, enzyme activity was 2-fold greater in the absence of dCTP and the dCTP was 15-fold less potent as an inhibitor (50% inhibition concentration = 6 microM). We conclude that the actual phosphate donor for the phosphorylation of 1 microM ara-C in Ehrlich cells is UTP and not ATP. These observations suggest that successful combination protocols aimed at stimulating ara-C uptake by means of a decrease in dCTP levels must simultaneously preserve or increase UTP pools.


Prevalence of Low Vitamin D in Patients with Breast Cancer in a Predominantly Hispanic Population at the American-Mexican Border.
Low level of vitamin D (VD) has been linked with a higher risk of cancers. The aim of this study was to assess the prevalence of low VD in patients with breast cancer in a predominantly Mexican Hispanic/Latino patient population, a fast growing and relatively understudied population. We sought to evaluate the serum VD levels in breast cancer patients diagnosed at the Texas Tech University Breast Cancer Center in El Paso, TX, between May 2013 and May2014 via a retrospective chart review of the Electronic Medical Records. We identified a total of 83 consecutive breast cancer patients with available VD levels. Mean age 57 yr, 94% were Hispanics. VD was insufficient (<30 ng/ml) in 86% of patients (95% CI: 0.76-0.92) and it was deficient (<20 ng/ml) in 39% (95% CI: 0.28-0.50). VD deficiency is widely prevalent in Hispanic/Latino patients with breast cancer. This is quite alarming in view of possible increased risk of cancer with low VD and potentially worse cancer outcomes. This calls for increased efforts to screen for, diagnose, and treat VD deficiency in this patient population. Further pharmacogenomics studies are warranted to explore the underlying etiology of VD deficiency in this paradoxically sunny region.


Glucose Sensing Using Capacitive Biosensor Based on Polyvinylidene Fluoride Thin Film.
A polyvinylidene fluoride (PVDF) film-based capacitive biosensor was developed for glucose sensing. This device consists of a PVDF film sandwiched between two electrodes. A capacitive biosensor measures the dielectric properties of the dielectric layers at the interface between the electrolyte and the electrode. A glucose oxidase (GOx) enzyme was immobilized onto the electrode to oxidize glucose. In practice, the biochemical reaction of glucose with the GOx enzyme generates free electron carriers. Consequently, the potential difference between the electrodes is increased, resulting in a measurable voltage output of the biosensor. The device was tested for various glucose concentrations in the range of 0.013 to 5.85 M, and various GOx enzyme concentrations between 4882.8 and 2.5 million units/L. We found that the sensor output increased with increasing glucose concentration up to 5.85 M. These results indicate that the PVDF film-based capacitive biosensors can be properly applied to glucose sensing and provide opportunities for the low-cost fabrication of glucose-based biosensors based on PVDF materials.


Female sexual offenders in the educational system: a brief overview.
Female sexual offenders comprise the minority of sexual offenders in the criminal justice system. However, empirical research reveals that sexual offenses against adolescents by females are a bigger problem than previously thought, particularly in the educational system. The authors review some of the data in the criminal justice system as well as in empirical research studies about female sexual offenders, with a specific focus on females who commit sexual crimes against students who are minors.


Low Density Lipoprotein Peptide-Conjugated Gold Nanorods for Combating Gastric Cancer.
As a potential drug carrier, the toxicity of gold nanorods (AuNRs) has been extensively studied to ensure their safety. Some of these studies reported that AuNRs caused a series of toxic cell responses and inspired the hypothesis that AuNRs may act as anti-cancer agents. In the present study, we synthesized AuNRs (72× 17 nm) and low density lipoprotein (LDL) peptide-RLT modified AuNRs to test this hypothesis. A tumor cell inhibition assay was conducted in five cell lines, and RLT-AuNRs demonstrated the most efficient inhibition of SGC-7901 cells. RLT-AuNRs inhibited SGC-7901 cells and increased SGC-7901 cell apoptosis more effectively than did AuNRs and DOX in vitro. Treatment with RLT-AuNRs reduced the tumor volume, decreased the tumor weight, and enhanced the tumor inhibition rates. RLT-AuNRs showed comparable anti-tumor efficacy with DOX but possessed higher in vivo safety than did DOX. Nude mice treated with RLT-AuNRs showed good health and gained weight during the ten-day anti-tumor therapy. Histological results showed no tissue toxicity of RLT-AuNRs. Therefore, RLT-AuNRs may be a viable anti-tumor agent for gastric cancer.


Treatment of functional constipation with the Yun-chang capsule: a double-blind, randomized, placebo-controlled, dose-escalation trial.
Functional constipation is a common functional bowel disorder for which there is no reliable medical treatment. This study was designed to determine the therapeutic efficacy and safety of the Yun-chang capsule, a Chinese herbal formula, in the treatment of patients with functional constipation. In our multi-center, prospective, double-blind, randomized, placebo-controlled, dose-escalation trial, patients with functional constipation received 70 mg of Yun-chang capsule plus 35 mg placebo (group A), 105 mg of Yun-chang capsule (group B), or 105 mg placebo (group C), three times daily for 2 weeks. The primary end-points were the changes in main symptom score and cumulative symptom score 2 weeks after the treatment. The secondary end-points were adverse events. A total of 140 patients were recruited and 132 met the inclusion criteria; 44 patients constituted each of the three treatment groups. Compared with patients in group C, patients in groups A and B had significant improvement in the main symptom score, cumulative symptom score, the change from baseline of the main symptom score, and the change from baseline of the cumulative symptom score at week 1 and week 2. The scores showed slight superiority of group B over group A at week 1 and week 2, although these differences were not statistically significant. There were no differences in adverse events. The Yun-chang capsule is efficacious and safe for the treatment of patients with functional constipation. Larger and longer-term trials are required to fully assess the benefits and safety of this treatment for functional constipation.


Note: measurement of the runaway electrons in the J-TEXT tokamak.
The runaway electrons have been measured by hard x-ray detectors and soft x-ray array in the J-TEXT tokamak. The hard x-ray radiations in the energy ranges of 0.5-5 MeV are measured by two NaI detectors. The flux of lost runaway electrons can be obtained routinely. The soft x-ray array diagnostics are used to monitor the runaway beam generated in disruptions since the soft x-ray is dominated by the interaction between runaway electrons and metallic impurities inside the plasma. With the aid of soft x-ray array, runaway electron beam has been detected directly during the formation of runaway current plateau following the disruptions.


Clinical significance of massive proteinuria in primary IgA nephropathy with and without nephrotic syndrome: a single center cohort study.
Both primary IgA nephropathy (IgAN) with and without nephrotic syndrome (NS) can present massive proteinuria (24-h urinary protein ≥3.5 g/d). The clinical significance of massive proteinuria may be different in the two entities and needs further research. Data of 1870 patients with biopsy-proven IgAN in our hospital from January 2011 to December 2022 was retrospectively reviewed. A total of 242 IgAN patients with massive proteinuria were enrolled. Patients who presented with nephrotic syndrome at renal biopsy were included in the IgAN with NS cohort (IgAN-NS). The IgAN with nephrotic-range proteinuria cohort (IgAN-NR) consisted of 1:1 matched cases from the remaining according to age, gender, estimated glomerular filtration rate (eGFR) at baseline, and follow-up time. The clinical and pathological characteristics between the two cohorts were analyzed. The IgAN-NS had a significantly higher proteinuria level than the IgAN-NR (p < .001). Cluster analysis revealed that proteinuria was associated with lipids in IgAN-NS, while it was associated with inflammatory indicators in IgAN-NR. When the complete remission of proteinuria (CR) was not achieved, the Kaplan-Meier analysis showed the prognosis of IgAN-NS was significantly worse than that of IgAN-NR (p = .04). Then, our GLMM model and line chart showed that the serum albumin level of the IgAN-NR was always evidently higher than that of the IgAN-NS while the significant difference in urinary albumin/creatinine ratio between the two cohorts gradually disappeared during the short-term follow-up (1 year). Moreover, the Cox regression analysis showed that the increased serum albumin was an independent protective factor for the poor outcomes (eGFR decreased from the baseline ≥ 30% continuously or reached end-stage renal disease [ESRD]). The IgAN-NS had poorer clinicopathologic manifestation than IgAN-NR, including severer massive proteinuria. When the CR was not achieved, the prognosis of IgAN-NS was inferior to that of the IgAN-NR.


Complicated infective endocarditis necessitating ICU admission: clinical course and prognosis.
To study incidence, clinical course and prognostic factors in patients admitted to medical intensive care units (ICUs) because of a complicated course of infective endocarditis. This was a retrospective multicenter observational study of 4106 patients admitted to four medical ICUs in one tertiary hospital and one university hospital between 1994 and 1999. Infective endocarditis was identified in 33 (0.8%) patients. Of these, 26 were male, mean age was 59 +/- 12 and APACHE-III score was 75 +/- 31. Reasons for transfer to the ICU were congestive heart failure in 64%, septic shock in 21%, neurological deterioration in 15% and cardiopulmonary resuscitation in 9%. Inotropes or vasoconstrictors were required in 73% and multiorgan failure developed in 64% of the patients. Prosthetic valve endocarditis was present in 21%. Gram-positive cocci were found in 96% of all positive cultures; cultures were negative in 27% of the patients. Transthoracic echocardiograms were diagnostic in only 33% and transesophageal studies were required in 91% to confirm diagnosis or fully to delineate the extent of disease. Surgical intervention was performed in 60% of the patients, and the remaining 40% were only treated medically. The APACHE-III score on admission did not differ statistically between the two groups (69 +/- 30 versus 84 +/- 34, P = 0.17). In-patient mortality was 84% in patients treated medically, and 35% in surgically treated patients. Using multivariate analysis, acute renal failure on admission was identified as the independent single predictor for in-patient death (OR 5, 95% CI 1.04-24.03, P = 0.04). The prognosis for patients with infective endocarditis requiring admission to a medical ICU is serious. Nevertheless, the data suggest that surgical intervention may be successfully performed in a substantial number of patients despite the presence of severe shock and occurrence of multiorgan failure.


The Pselaphinae (Coleoptera: Staphylinidae) of Madagascar. III. Additional description of Andasibe sahondrae Hlaváč & Baňař, 2012 based on males.
An additional description of Andasibe sahondrae Hlaváč & Baňař, 2012 is given due to the discovery of male, male terminalia and sexual dimorphism are described. Distribution of the species is illustrated.


Correlative Microscopy of Lamellar Hole-Associated Epiretinal Proliferation.
Purpose. To describe morphology of lamellar hole-associated epiretinal proliferation (LHEP) removed from eyes with lamellar macular holes (LMH). Methods. Based on optical coherence tomography data, 10 specimens of LHEP were removed from 10 eyes with LMH during standard vitrectomy. Specimens were prepared for correlative light and electron microscopy (CLEM) using an immunonanogold particle of 1.4 nm diameter that was combined with a fluorescein moiety, both having been attached to a single antibody fragment. As primary antibodies, we used antiglial fibrillary acidic protein (GFAP), anti-CD45, anti-CD64, anti-α-smooth muscle actin (α-SMA), and anticollagen type I and type II. Results. In LHEP, GFAP-positive cells possess ultrastructural characteristics of fibroblasts and hyalocytes. They represent the major cell types and were densely packed in cell agglomerations on vitreous collagen strands. Epiretinal cells of LHEP rarely demonstrated contractive properties as α-SMA-positive myofibroblasts were an infrequent finding. Conclusion. CLEM indicates that epiretinal cells in LHEP might originate from the vitreous and that remodelling processes of vitreous collagen may play an important role in pathogenesis of eyes with LMH.


Visualization and targeting of LGR5+ human colon cancer stem cells.
The cancer stem cell (CSC) theory highlights a self-renewing subpopulation of cancer cells that fuels tumour growth. The existence of human CSCs is mainly supported by xenotransplantation of prospectively isolated cells, but their clonal dynamics and plasticity remain unclear. Here, we show that human LGR5+ colorectal cancer cells serve as CSCs in growing cancer tissues. Lineage-tracing experiments with a tamoxifen-inducible Cre knock-in allele of LGR5 reveal the self-renewal and differentiation capacity of LGR5+ tumour cells. Selective ablation of LGR5+ CSCs in LGR5-iCaspase9 knock-in organoids leads to tumour regression, followed by tumour regrowth driven by re-emerging LGR5+ CSCs. KRT20 knock-in reporter marks differentiated cancer cells that constantly diminish in tumour tissues, while reverting to LGR5+ CSCs and contributing to tumour regrowth after LGR5+ CSC ablation. We also show that combined chemotherapy potentiates targeting of LGR5+ CSCs. These data provide insights into the plasticity of CSCs and their potential as a therapeutic target in human colorectal cancer.


Clinical Therapeutic Effects of the Application of Doxycycline in the Treatment of Periodontal Disease.
To compare the therapeutic effects of the application of doxycycline-full dose (100 mg) and sub-dose (20 mg) in the treatment of periodontal disease. A total of 60 patients with periodontal disease were examined. Patients are divided into two groups: A) treated with antimicrobial dose of 100 mg doxycycline once daily for 30 days, and B) treated with 2 x 20 mg/day. doxycycline, during 75 days. Among all patients a conservative treatment was carried out and ordinated the proper dose doxycycline in total dose during treatment from 3 gr. Index of dental plaque by Löe-Sillness, index of gingival inflammation and gingival bleeding by Cowell were followed. Values of dental plaque in relation first examination, 10th, 20th day, 1 month and 2.5 months, showed that after 2.5 months, average value (x = 0.83) of dental plaque in second group is slightly less than the value (x = 0.93) of dental plaque in the first group. The average value (x = 0.17) of gingival inflammation in second group is significantly less than the value (x = 0.50) of gingival inflammation in the first group. The average value (x = 0.97) of gingival bleeding in patients from the first group was significantly higher than value(x = 0.37) of gingival bleeding in the second group. Patients whose therapy was helped by a sub-dose doxycycline demonstrated positive therapeutic effects on gingival inflammation and bleeding.


Reducing night shift exposure: a pilot study of rota, night shift and age effects on sleepiness and fatigue.
The reduction of exposure to longer runs of successive night duties is often one of the aims of 'best practice' intervention. The objective of this pilot study was to examine the effects of a change in rota upon sleepiness and fatigue, and potential age-related issues in relation to the change. Participants were 102 police officers, mean age 33.60 (sd 6.11), mean shiftwork experience = 10.56 years (sd 6.84). Testing occurred at least one month before the change from the existing 'Ottawa' system to a new rota that split a run of 7 consecutive night shifts into blocks of 3 and 4 within the rota cycle, and 6 months after the change. Measures of critical flicker fusion, subjective fatigue and sleepiness, and stimulant intake were taken in relation to selected night shifts on both rotas. Older officers tended to report higher fatigue and sleepiness, and higher caffeine intake than the younger shiftworkers irrespective of rota or shift. The findings tend to suggest that the change of rota had little effect but that age may play a substantial role in responses to night work.


Transcriptomic analysis of dorsal and ventral subiculum after induction of acute seizures by electric stimulation of the perforant pathway in rats.
Preconditioning is a mechanism in which injuries induced by non-lethal hypoxia or seizures trigger cellular resistance to subsequent events. Norwood et al., in a 2010 study, showed that an 8-h-long period of electrical stimulation of the perforant pathway in rats is required for the induction of hippocampal sclerosis. However, in order to avoid generalized seizures, status epilepticus (SE), and death, a state of resistance to seizures must be induced in the hippocampus by a preconditioning paradigm consisting of two daily 30-min stimulation periods. Due to the importance of the subiculum in the hippocampal formation, this study aims to investigate differential gene expression patterns in the dorsal and ventral subiculum using RNA-sequencing, after induction of a preconditioning protocol by electrical stimulation of the perforant pathway. The dorsal (dSub) and ventral (vSub) subiculum regions were collected by laser-microdissection 24 h after preconditioning protocol induction in rats. RNA sequencing was performed in a Hiseq 4000 platform, reads were aligned using the STAR and DESEq2 statistics package was used to estimate gene expression. We identified 1176 differentially expressed genes comparing control to preconditioned subiculum regions, 204 genes were differentially expressed in dSub and 972 in vSub. The gene ontology enrichment analysis showed that the most significant common enrichment pathway considering up-regulated genes in dSub and vSub was steroid metabolism. In contrast, the most significant enrichment pathway considering down-regulated genes in vSub was axon guidance. Our results indicate that preconditioning induces changes in the expression of genes related to synaptic reorganization, increased cholesterol metabolism, and astrogliosis in both dSub and vSub. Both regions also presented a decrease in the expression of genes related to glutamatergic transmission and an increase in expression of genes related to complement system activation and GABAergic transmission. The down-regulation of proapoptotic and axon guidance genes in the ventral subiculum suggests that preconditioning may induce a neuroprotective environment in this region.


Influencing factors of urban innovation and development: a grounded theory analysis.
Urban innovation and development are a core driver for promoting the industrial, economic, and social development of cities. However, the factors that affect the innovation and development of cities lack systematic analysis as well as interaction analysis. Based on a multidimensional perspective, this study suggests that natural, economic, and social factors are three major factors conditioning urban innovation and development. A grounded theoretical qualitative method is further adopted to code relevant research literatures, news reports and interview materials, resulting in an onion factors model. We find that natural factors-including environmental quality, geographic location, and city scale-are prerequisite for conditioning urban innovation and development. Economic factors are also key, including economic level, industrial structure, industrial agglomeration, and technological innovation. Social factors are guarantee factors, including administrative hierarchy, cultural environment, population structure, and government management and services, i.e., they are essential for cities to become adaptable in the current dynamic situation. The study provides theoretical support and practical directions for the formulation of policies for urban innovation development.


Acute undifferentiated leukemia limited to neck lymph nodes and a large mediastinal mass.
In the 2016 update of the World Health Organization (WHO) classification of myeloid neoplasms, acute undifferentiated leukemia (AUL) was defined by a lack of lineage-specific markers. AUL has very poor prognosis and no established therapies due to its rarity. We report a case of a 31-year-old man with AUL who showed complete molecular response to an acute lymphoblastic leukemia (ALL)-based regimen and received allogeneic hematopoietic stem cell transplantation. The patient's blast cells were CD7-positive and localized to lymph nodes in the neck and to a large mediastinal mass; there was also rearrangement of the T-cell receptor delta locus. Although the tumor showed characteristics of T-cell lymphoblastic lymphoma, it was categorized as AUL based on WHO classification. This case suggests that a high-intensity conditioning regimen could be effective for rare cases of AUL that present only in the extramedullary mass, and chemotherapy for AUL should be selected based on the characteristics of the blasts.


Identification and preliminary characterization of saliva-interacting surface antigens of Streptococcus mutans by immunoblotting, ligand blotting, and immunoprecipitation.
The ability of surface protein antigens of Streptococcus mutans to interact with salivary components was examined by Western blot and immunoprecipitation methods. Immunoblotting of S. mutans OMZ175 wall-associated antigens revealed 10 major antigens, designated according to their estimated molecular weights. Four of them, with molecular weights of 135,000, 125,000, 120,000, and 115,000 in their denaturated form, bound salivary components. This property was further investigated by immunoprecipitation experiments: the reactivity with saliva was confirmed for antigens with molecular weights of 135,000, 125,000, and 120,000 in their native form, and their locations on the bacterial cell surface were established. These three antigens were characterized as glycoproteins; they directly bound concanavalin A, and pronase abolished their antigenicity, which was partly retained after treatment with NaIO4. Because of their distribution in several other stains of S. mutans, it will be of interest to study their possible implication in the mechanism of attachment of streptococcal strains to saliva-coated tooth surfaces.


Dendritic structural plasticity and neuropsychiatric disease.
The structure of neuronal circuits that subserve cognitive functions in the brain is shaped and refined throughout development and into adulthood. Evidence from human and animal studies suggests that the cellular and synaptic substrates of these circuits are atypical in neuropsychiatric disorders, indicating that altered structural plasticity may be an important part of the disease biology. Advances in genetics have redefined our understanding of neuropsychiatric disorders and have revealed a spectrum of risk factors that impact pathways known to influence structural plasticity. In this Review, we discuss the importance of recent genetic findings on the different mechanisms of structural plasticity and propose that these converge on shared pathways that can be targeted with novel therapeutics.


Clinical experience with autologous M2 macrophages in children with severe cerebral palsy.
Stem cell-based therapy is considered to be a new approach for the treatment of cerebral palsy (CP). Given the potent anti-inflammatory activity and high regenerative potential of M2 macrophages, these cells may be an alternative source for cell transplantation. To evaluate the safety and efficacy of autologous M2 macrophages, we conducted a pilot clinical trial in 21 children with severe CP. The primary outcome measure was safety, which included assessment of mortality of any cause, immediate adverse reactions, and serious adverse effects and comorbidities during 5-year follow-up. The secondary outcome measure was functional improvement in Gross Motor Function Measure (66-item GMFM) test, Peabody Developmental Motor Scale-Fine Motor (PDMS-FM) test, Ashworth scale, MRC scale, and an easy-to-understand questionnaire for evaluation of cognitive functions in our modification. Intradural injection of M2 cells (in mean dose of 0.8 × 10(6)/kg) into the lumbar spinal area did not induce any serious adverse events. No cases of mortality, psychomotor worsening, exacerbation of seizures, and long-term comorbidities, including tumors, were observed during a 5-year follow-up. After 3 months, GMFM score increased from 13.7 ± 7.8 to 58.6 ± 14.6, PDMS-FM score improved from 0.76 ± 0.42 to 5.05 ± 0.97, and the Ashworth score decreased from 3.8 ± 0.21 to 3.3 ± 0.24. Along with gross and fine motor function enhancement, an improvement of cognitive activity (from 1.62 ± 0.41 to 4.05 ± 0.64, according to questionnaire assessment) and reduction of seizure syndrome were registered as well. The neurological improvements did not diminish during the 5-year follow-up period. The data obtained suggest that cell therapy based on M2 macrophages is safe, does not induce early adverse effects and long-term comorbidities, and is accompanied with a significant improvement of motor and cognitive activities in severe CP patients. This manuscript is published as part of the International Association of Neurorestoratology (IANR) special issue of Cell Transplantation.