Differential high-altitude adaptation and restricted gene flow across a mid-elevation hybrid zone in Andean tit-tyrant flycatchers.
The tropical Andes are a global hotspot of avian diversity that is characterized by dramatic elevational shifts in community composition and a preponderance of recently evolved species. Bird habitats in the Andes span a nearly twofold range of atmospheric pressure that poses challenges for respiration, thermoregulation, water balance and powered flight, but the extent to which physiological constraints limit species' elevational distributions is poorly understood. We report a previously unknown hybrid zone between recently diverged flycatchers (Aves, Tyrannidae) with partially overlapping elevational ranges. The southern Anairetes reguloides has a broad elevational range (0-4200 m), while the northern Anairetes nigrocristatus is restricted to high elevations (>2200 m). We found hybrids in central Peru at elevations between ~3100 and 3800 m, with A. nigrocristatus above this elevation and A. reguloides below. We analysed variation in haematology, heart mass, morphometrics, plumage and one mitochondrial and three nuclear loci across an elevational transect that encompasses the hybrid zone. Phenotypic traits and genetic markers all showed steep clines across the hybrid zone. Haemoglobin concentration, haematocrit, mean cellular haemoglobin concentration and relative heart mass each increased at altitude more strongly in A. reguloides than in A. nigrocristatus. These findings suggest that A. nigrocristatus is more resistant than A. reguloides to high-altitude hypoxic respiratory stress. Considering that the ancestor of the genus is suggested to have been restricted to high elevations, A. reguloides may be secondarily adapted to low altitude. We conclude that differential respiratory specialization on atmospheric pressure combined with competitive exclusion maintains replacement along an elevational contour, despite interbreeding.


Metabolism of 16, 16-dimethyl-trans-delta 2-prostaglandin E1 methyl ester (ONO-802) following intravenous and vaginal administration to pregnant women.
Following iv and vaginal administration of (5,6-3H2)-ONO-802 (5,6-3H2-16, 16-dimethyl-trans-delta 2-prostaglandin E1 methyl ester) the appearance of radiolabeled compounds in plasma and urine were studied in early pregnant patients. Following iv administration, ONO-802 was rapidly hydrolyzed to the free acid which disappeared from plasma with an approximate half-life of 10-15 min. About 50% of the injected amount of compound was excreted in urine during the first 24 hr after injection. The structures of 16 urinary metabolites were determined. These data demonstrated that, following hydrolysis of ONO-802 to the free acid, the latter can undergo beta- and omega-oxidation like other prostaglandin analogs where enzymatic attack of the 15-hydroxyl group has been blocked. Some of the metabolites were excreted as conjugates (sulfates, glucuronides?) and, in two, the oxo group at C-9 had been reduced to a hydroxyl. Following vaginal administration of ONO-802 (1 mg, 60 microCi) in suppository form, radioactivity corresponding to 100-200 pg/ml of ONO-802 equivalents was found in plasma. The profile of metabolites in urine was qualitatively very similar to that after iv injection of (5,6-3H2)-ONO-802. Based on the data on excretion of metabolites in urine it was calculated that 12-28% of the dose administered vaginally was resorbed into the circulation.


Nuclear location of all three influenza polymerase proteins and a nuclear signal in polymerase PB2.
In order to re-examine the sub-cellular location of the three influenza A/NT/60/68 polymerase proteins PB1, PB2 and PA in infected cells, specific antisera for each polymerase component have been prepared by immunizing rabbits with polymerase-beta-galactosidase fusion proteins synthesized in Escherichia coli. We show that polymerase PB1, PB2, and PA are predominantly associated with the nucleus of influenza-infected MDCK cells by immunocytochemical techniques. In the case of polymerase PB2 we investigate the possibility that nuclear accumulation is an intrinsic property of the PB2 protein. Using a vaccinia-PB2 recombinant virus, we show that PB2 accumulates intra-nuclearly in monkey CV-1 cells in the absence of any other influenza protein, suggesting it contains an intrinsic nuclear signal.


Dosimetry parameters calculation of two commercial iodine brachytherapy sources using SMARTEPANTS with EPDL97 library.
Simulating Many Accumulative Rutherford Trajectories Electron Photon and Neutral Transport Solver (SMARTEPANTS) is a discrete ordinates S N Boltzmann/Spencer-Lewis solver that was developed during 1988-1993 by William Filippone and his students. The code calculates particle fluxes, leakage currents as well as energy and charge deposition for coupled electron/photon in x-y-z geometries both in forward and in adjoin modes. Originally, SMARTEPANTS was designed to utilize CEPXS cross-section library for shielding calculation in satellite electronics. The aim of this study was to adapt SMARTEPANTS to use a new photon cross-section library from Evaluated Photon Data Library, 1997 version (EPDL97) for intravascular brachytherapy (125)Isimulations. A MATLAB (MathworkNatick, Massachusetts) program was written to generate an updated multigroup-Legendre cross-section from EPDL97. The new library was confirmed by simulating intravascular brachytherapy Best® Model 2301 and Intersource (125)I dosimetry parameters using SMARTEPANTS with different energy groups (g), Legendre moments (L) and discrete ordinate orders (S). The dosimetry parameters for these sources were tabulated and compared with the data given by AAPM TG-43 and other reports. The computation time for producing TG-43 parameters was about 29.4 min in case of g = 20, L = 7 and S = 16. The good agreement between the results of this study and previous reports and high computational speed suggest that SMARTEPANTS could be extended to a real-time treatment planning system for (125)I brachytherapy treatments.


Interfacial antiwear and physicochemical properties of alkylborate-dithiophosphates.
Boron compounds have become of interest in tribology because of their unique tribochemical and tribological properties. At the same time, dialkyldithiophosphates (DTPs) of transition metals have been extensively used as multifunctional additives in lubricants to control friction and reduce wear in mechanical systems. Because of the environmental pollution and health hazards of these compounds, ashless compounds with reduced amounts of sulfur and phosphorus are desirable. This work reports on the synthesis, characterization, and tribological properties of a new class of compounds, alkylborate-dithiophosphates. This class combines two high-iron-affinity surface active groups, borate and dialkyldithiophosphate, into a single molecule. The final products, viscous liquids, were characterized by FT-IR, multinuclear (1)H, (13)C, (31)P, and (11)B NMR spectroscopy and thermal analyses. Residues of one representative compound from this class, DPB-EDTP, after thermal analyses were additionally characterized by multinuclear (13)C, (31)P and (11)B MAS and (31)P CP/MAS NMR spectroscopy. Solid-state NMR data suggest that a dominant part of the solid residue of DPB-EDTP consists of borophosphates. Antiwear and friction properties of a mineral oil with these novel additives were evaluated in a four-ball tribometer in comparison with O,O'-di-n-butyl-dithiophosphato-zinc(II), Zn-BuDTP, as a reference lubricant additive. The surface morphology and the elemental composition of the tribofilms were characterized using scanning electron microscopy with energy-dispersive X-rays spectroscopy (SEM/EDS). The results show that alkylborate-dithiophosphates, with substantially reduced amounts of sulfur and phosphorus compared with Zn-BuDTP, have considerably better antiwear and friction performance.


eHealth Delivery of Educational Content Using Selected Visual Methods to Improve Health Literacy on Lifestyle-Related Diseases: Literature Review.
Lifestyle-related diseases, such as stroke, heart disease, and diabetes, are examples of noncommunicable diseases. Noncommunicable diseases are now the leading cause of death in the world, and their major causes are lifestyle related. The number of eHealth interventions is increasing, which is expected to improve individuals' health literacy on lifestyle-related diseases. This literature review aims to identify existing literature published in the past decade on eHealth interventions aimed at improving health literacy on lifestyle-related diseases among the general population using selected visual methods, such as educational videos, films, and movies. A systematic literature search of the PubMed database was conducted in April 2019 for papers written in English and published from April 2, 2009, through April 2, 2019. A total of 538 papers were identified and screened in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) flow diagram. Finally, 23 papers were included in this review. The 23 papers were characterized according to study characteristics (author and year of publication, study design and region where the study was conducted, study objective, service platform, target disease and participant age, research period, outcomes, and research method); the playback time of the educational videos, films, and movies; and the evaluation of the study's impacts on health literacy. A total of 7 studies compared results using statistical methods. Of these, 5 studies reported significant positive effects of the intervention on health literacy and health-related measures (eg, physical activity, body weight). Although most of the studies included educational content aimed at improving health literacy, only 7 studies measured health literacy. In addition, only 5 studies assessed literacy using health literacy measurement tools. This review found that the provision of educational content was satisfactory in most eHealth studies using selected visual methods, such as videos, films, and movies. These findings suggest that eHealth interventions influence people's health behaviors and that the need for this intervention is expected to increase. Despite the need to develop eHealth interventions, standardized measurement tools to evaluate health literacy are lacking. Further research is required to clarify acceptable health literacy measurements.


Pretransplant malignancy in candidates and posttransplant malignancy in recipients of cardiac transplantation.
Malignancy is generally considered a contraindication for cardiac transplantation, whereas secondary malignancy has been described under chronic immunosuppression. We report here the frequency of malignancy encountered among the 495 patients evaluated at our cardiac transplant centre as well as the incidence and the course of post-transplant malignancy among 129 consecutive patients who underwent cardiac-transplantation, with a subsequent minimum follow-up of 6 months. A total of 10 out of 495 patients (2%) evaluated for heart transplantation presented with a history of previous malignancy: 3 of them underwent transplantation (2 survive, 1 died) whereas in the remaining 7 patients neoplasia was considered a contraindication for cardiac transplantation, and all 7 died (4 cardiac, 3 tumor-related deaths). Post-transplant malignancy was diagnosed in 10 of 129 patients (9%) 35 +/- 15 months after transplantation (6 skin cancers, 1 lymphoproliferative disease, 3 solid tumors). No significant association was found between post-transplant malignancy and primary prophylaxis with antithymocyte globulin (ATG) or murine antihuman T-cell monoclonal antibodies (OKT3). These results confirm that pre-transplant malignancy is not an absolute contraindication for cardiac transplantation and that post-transplant follow-up must include careful monitoring of post-transplant malignancy.


Capnometry and anaesthesia.
In the last decade, capnography has developed from a research instrument into a monitoring device considered to be essential during anaesthesia to ensure patient safety. Hence, a comprehensive understanding of capnography has become mandatory for the anaesthetist in charge of patients in the operating room and in the intensive care unit. This review of capnography includes the methods available to determine carbon dioxide in expired air, and an analysis of the physiology of capnograms, which are followed by a description of the applications of capnography in clinical practice. The theoretical backgrounds of the effect of barometric pressure, water vapour, nitrous oxide and other factors introducing errors in the accuracy of CO2 determination by the infra-red technique, currently the most popular method in use, are detailed. Physiological factors leading to changes in end-tidal carbon dioxide are discussed together with the clinical uses of this measurement to assess pulmonary blood flow indirectly, carbon dioxide production and adequacy of alveolar ventilation. The importance of understanding the shape of the capnogram as well as end-tidal carbon dioxide measurements is emphasized and its use in the early diagnosis of adverse events such as circuit disconnections, oesophageal intubation, defective breathing systems and hypoventilation is highlighted. Finally, the precautions required in the use and interpretation of capnography are presented with the caveat that although no instrument will replace the continuous presence of the attentive physician, end-tidal carbon dioxide monitoring can be effective in the early detection of anaesthesia-related intraoperative accidents.


Enhancement of waste activated sludge anaerobic digestion by a novel chemical free acid/alkaline pretreatment using electrolysis.
Anaerobic digestion of waste activated sludge (WAS) is relatively poor due to hydrolysis limitations. Acid and alkaline pretreatments are effective in enhancing hydrolysis leading to higher methane yields. However, chemical costs often prohibit full-scale application. In this study, 12 V two-chamber electrolysis using an anion exchange membrane alters sludge pH without chemical dosing. pH dropped from 6.9 to 2.5 in the anode chamber and increased to 10.1 in the cathode chamber within 15 h. The volatile suspended solids solubilisation of WAS was 31.1% in the anode chamber and 34.0% in the cathode chamber. As a result, dissolved chemical oxygen demand increased from 164 to 1,787 mg/L and 1,256 mg/L in the anode and cathode chambers, respectively. Remixing of sludge from the two chambers brought the pH back to 6.5, hence no chemical neutralisation was required prior to anaerobic digestion. Methane yield during anaerobic digestion at 20 d retention time was 31% higher than that of untreated sludge. An energy balance assessment indicated that the non-optimised process could approximately recover the energy (electricity) expended in the electrolysis process. With suitable optimisation of treatment time and voltages, significant energy savings would be expected in addition to the benefit of decreased sludge volume.


Effects of 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (DOM) and quipazine on heroin self-administration in rhesus monkeys.
The serotonin (5-HT) system is involved in pain modulation, and 5-HT receptor agonists can enhance antinociceptive effects of mu opioid receptor agonists. Less is known about the actions of 5-HT receptor agonists on other effects of opioids. This study examined the effects of non-contingent and contingent administration of the 5-HT(2A) receptor agonists DOM and quipazine on i.v. heroin self-administration in rhesus monkeys. Heroin (0.0001-0.1 mg/kg/infusion) generated an inverted U-shaped dose-response function. Non-contingent administration of DOM (0.1-0.32 mg/kg) flattened the dose-response function in three monkeys and eliminated heroin self-administration in a fourth monkey. Contingent DOM (0.0032-0.032 mg/kg/infusion) alone did not maintain responding above that maintained by saline, and, when added to self-administered heroin, monkeys responded less than for the same unit doses of heroin alone. Non-contingent (0.32-3.2 mg/kg) and contingent (0.0032-0.56 mg/kg/infusion) administration of quipazine flattened the dose-response function in two monkeys, increasing responding maintained by small unit doses of heroin and saline, but failed to enhance responding for heroin in two other monkeys. This study shows that DOM does not enhance, and might attenuate, the positive reinforcing effects of the mu opioid receptor agonist heroin. Quipazine increased responding for saline and small doses of heroin; those effects were modest and observed in only two subjects. Taken together, these data suggest that 5-HT(2A) receptor agonists do not significantly enhance the reinforcing effectiveness of mu opioid receptor agonists and support the view that administering 5-HT drugs in combination with opioids to treat pain might not enhance abuse liability.


Time-domain quanification of amplitude, chemical shift, apparent relaxation time T2, and phase by wavelet-transform analysis. Application to biomedical magnetic resonance spectroscopy.
The wavelet-transform method is used to quantify the magnetic resonance spectroscopy (MRS) parameters: chemical shift, apparent relaxation time T2, resonance amplitude, and phase. Wavelet transformation is a time-frequency representation which separates each component from the FID, then successively quantifies it and subtracts it from the raw signal. Two iterative procedures have been developed. They have been combined with a nonlinear regression analysis method and tested on both simulated and real sets of biomedical MRS data selected with respect to the main problems usually encountered in quantifying biomedical MRS, specifically "chemical noise," resulting from overlapping resonances, and baseline distortion. The results indicate that the wavelet-transform method can provide efficient and accurate quantification of MRS data.


Pharmaceutical terms with onomastic component: quantitative, structural and lexico-semantic analysis.
Introduction: The present paper examines the prevalence and role of eponymic terms in the Latin and English pharmaceutical terminologies. The aim: The authors aim to conduct the quantitative, structural and lexico-semantic analysis of the names of medications with the proprial component. Materials and methods: The research material in the amount of 147 units was obtained by the continuous sampling from the dictionaries, guidebooks and manuals on prescription-writing using the narrative and component analysis methods, by means of which the arrangement, systematization, classification and interpretation of the structural, semantic and functional features of the units under consideration have been conducted. Review and conclusions: The research has resulted in the delineation of the following groups of eponymic terms in the pharmaceutical terminologies of Latin and English: (1) semisolid dosage forms (formae medicamentorum molles): 81 title (55.1%); (2) liquid dosage forms (formae medicamentorum fluidae): 60 lexical units (40.8%); (3) solid dosage forms (formae medicamentorum solidae): 6 cases (4.1%). The analysis of 147 units showed that the most extensive group of pharmaceutical terminology units with the eponymic component are the names that specify the dosage form of medication. The prospects for research are in the further in-depth study to examine the tendencies of eponymization in both synchronic and diachronic aspects.


Indirect stimulation of recombination in Escherichia coli K-12: dependence on recJ, uvrA, and uvrD.
Direct and indirect UV-stimulated homologous genetic recombination was investigated in Escherichia coli strains blocked in several host-encoded functions. Genetic recombination was assayed by measuring beta-galactosidase produced after recombination between two noncomplementing lacZ ochre alleles. Both types of stimulation (direct and indirect) were found to be primarily RecF pathway-mediated. In a rec+ background, both direct and indirect stimulation were found to be dependent on uvrD (coding for helicase II). In a recB21 sbcB15 background, direct and indirect stimulation were uvrD dependent only when the strain was additionally deficient in the UvrABC excision repair pathway. Indirect but not direct stimulation was also dependent on recJ (coding for a 5'-to-3' exonuclease specific for single-stranded DNA) regardless of sbcA or sbcB configuration. The methyl-directed mismatch repair system (mutSLH) also appeared to play an important role in stimulation. On the basis of these findings, we suggest that excision of UV-induced DNA damage is a prelude to UV-mediated stimulation of genetic recombination.


Capturing 3D atomic defects and phonon localization at the 2D heterostructure interface.
The three-dimensional (3D) local atomic structures and crystal defects at the interfaces of heterostructures control their electronic, magnetic, optical, catalytic, and topological quantum properties but have thus far eluded any direct experimental determination. Here, we use atomic electron tomography to determine the 3D local atomic positions at the interface of a MoS2-WSe2 heterojunction with picometer precision and correlate 3D atomic defects with localized vibrational properties at the epitaxial interface. We observe point defects, bond distortion, and atomic-scale ripples and measure the full 3D strain tensor at the heterointerface. By using the experimental 3D atomic coordinates as direct input to first-principles calculations, we reveal new phonon modes localized at the interface, which are corroborated by spatially resolved electron energy-loss spectroscopy. We expect that this work will pave the way for correlating structure-property relationships of a wide range of heterostructure interfaces at the single-atom level.


Geophysicists celebrate two satellites, mourn a third.
Searching for a common theme in a gathering as diverse as the spring meeting of the American Geophysical Union (AGU) in Baltimore last month might seem futile. But satellites, both natural and artificial, provided some of the meeting's high points. Researchers reported on the first science results from the Clementine spacecraft's 2-month sojourn orbiting the moon, the revealing color of the small moon that accompanies the asteroid lda, and the planned termination of the Magellan spacecraft orbiting Venus.


Long-term effects of hydroxyurea in psoriases.
Hydroxyurea is an effective treatment for psoriasis but consistently produces macrocytosis in peripheral blood with a fall in haemoglobin levels and white cell counts. In this long-term study of 16 patients anaemia and leukopenia have proved frequent and troublesome side effects requiring discontinuance of treatment in many cases. In view of these findings hydroxyurea cannot be recommended as the drug of first choice even for treating severe and intractable psoriasis, and it is our opinion that methotrexate is safer and at least as effective in these circumstances. The clearest indications for the use of hydroxyurea appear to be in life-ruining psoriasis when methotrexate treatment has either failed or is contraindicated because of liver damage. A great deal more investigative work is required before these indications can be generally extended.


CT Differentiation of Female Peritoneal Tuberculosis and Peritoneal Carcinomatosis From Normal-Sized Ovarian Cancer.
The purpose of this study was to analyze the computed tomography (CT) features of female peritoneal tuberculosis and peritoneal carcinomatosis from normal-sized ovarian cancer for their differentiation. We analyzed the CT features of 18 female peritoneal tuberculosis and 17 peritoneal carcinomatosis with proven normal-sized ovarian carcinomas. Omental change, mesenteric change, parietal peritoneal thickening, lymph node enlargement, ascites, ovarian CT attenuation, and ovarian capsular change were analyzed. Heterogeneous parenchymal hyperattenuation and capsular change of the ovary were more frequently seen in cases of peritoneal carcinomatosis than in cases of female peritoneal tuberculosis (P = 0.002, P < 0.001, respectively). There were no statistically significant differences in the other CT features. The differentiation of female peritoneal tuberculosis and peritoneal carcinomatosis with normal-sized ovarian cancer by CT may be a diagnostic challenge. Ovarian hyperattenuation and any prominent ovarian capsular change may facilitate the differentiation between these groups.


A comparison of questionnaire and physiological data in predicting future chronic disease risk factor status in an employee population.
The ideal screening tool for worksite health screening programs has not yet been identified, and the effectiveness of screening programs in predicting future chronic disease risk factors status is not well understood. This study compared two commonly used screening tools, health-related questionnaires and measurement of physiological parameters, in terms of their ability to predict future chronic disease risk factor status in an employee population. Data were collected over a 10-year period from Liberty Corporation employees (N = 723). Baseline evaluation included the administration of questionnaires and measurement of physiological data. Follow-up evaluation measured physiological data only. Regression analyses identified the statistically significant predictors of future risk factor status using 1) baseline questionnaire data; 2) baseline physiological data; and 3) both questionnaire and physiological data as predictor variables. Although both screening methods were able to predict future risk factor status, R 2 values were higher in models including baseline physiological measures than models including questionnaire data only. Adding questionnaire data to physiological data provided little or no additional predictive ability. These results suggest that physiological data, particularly baseline measures of a risk factor, are more predictive of future risk factor status than questionnaire data.


The role of gesture as simulated action in reinterpretation of mental imagery.
In two experiments, we examined the role of gesture in reinterpreting a mental image. In Experiment 1, we found that participants gestured more about a figure they had learned through manual exploration than about a figure they had learned through vision. This supports claims that gestures emerge from the activation of perception-relevant actions during mental imagery. In Experiment 2, we investigated whether such gestures have a causal role in affecting the quality of mental imagery. Participants were randomly assigned to gesture, not gesture, or engage in a manual interference task as they attempted to reinterpret a figure they had learned through manual exploration. We found that manual interference significantly impaired participants' success on the task. Taken together, these results suggest that gestures reflect mental imaginings of interactions with a mental image and that these imaginings are critically important for mental manipulation and reinterpretation of that image. However, our results suggest that enacting the imagined movements in gesture is not critically important on this particular task.


Nonhuman primate studies of fear, anxiety, and temperament and the role of benzodiazepine receptors and GABA systems.
Studies of nonhuman primate models have been useful in defining anxious temperament as an individual's stable set of physiologic and behavioral responses and in providing insights regarding human anxiety. Anxious temperament in rhesus monkeys (Macaca mulatta) is marked by excessive anxiety, exaggerated defensive behavioral responses, extreme asymmetric right frontal brain electrical activity, and elevated cerebrospinal fluid levels of corticotropin-releasing hormone and plasma cortisol. In the human brain, extreme asymmetric right frontal activation is likewise associated with negative affect and anxious disposition. Our studies of infant rhesus monkeys using the human intruder paradigm allow us to investigate individual differences in fear-related defensive behavioral responses and suggest that responses to threatening stimuli are mediated by gamma-aminobutyric acid and benzodiazepine receptors. Ongoing studies with nonhuman primates in our laboratory are further examining the neurochemistry underlying individual differences in anxious temperament. We believe that these studies will provide insights into the adaptive and maladaptive responses of humans as they relate to psychopathology as associated with anxiety.


Prognostic factors and seizure outcome in posterior reversible encephalopathy syndrome (PRES) in children with hematological malignancies and bone marrow failure: A retrospective monocentric study.
The aim of this study was to evaluate seizure outcome in children with hematological malignancies and PRES and to identify prognostic factors that could help manage the syndrome. We retrospectively reviewed the report data of 21 patients diagnosed with hematological malignancy or aplastic anemia and PRES between 2008 and 2018. Basic demographic data, oncology treatment, presymptomatic hypertension before PRES manifestation, neurological status, seizure type, and EEG and MRI findings at PRES onset and at the one-year follow-up visit were studied. Patients who developed remote symptomatic seizures or epilepsy were identified. We included 21 children (11 females and 10 males) in the study. Sixteen patients (76.2%) were diagnosed with ALL and the rest individually with AML, CML, T-lymphoma, Burkitt lymphoma, and severe aplastic anemia. Presymptomatic hypertension (PSH) was evaluated in 19 patients and was present in 18 (94.7%). The duration was 9 h and more in 16 patients (88.8%); the severity was grade II in 12 patients (66.7%). Seizures as the initial symptom of PRES were present in 17 patients (80.9%). Four patients (19.0%) were assessed with remote symptomatic seizures. Two of them (9.5%) had ongoing seizures at the one-year follow-up visit and were diagnosed with epilepsy. The presence of gliosis on follow-up MRI indicated worse outcome with development of epilepsy (without statistical significance). PRES syndrome has an overall good prognosis and the evolution to epilepsy is rare. The severity and duration of PSH or seizure severity and EEG findings at PRES onsetwere not associated with worse neurological outcomes in this study.


Characterization of the Canine Anthracycline-Metabolizing Enzyme Carbonyl Reductase 1 (cbr1) and the Functional Isoform cbr1 V218.
The anthracyclines doxorubicin and daunorubicin are used in the treatment of various human and canine cancers, but anthracycline-related cardiotoxicity limits their clinical utility. The formation of anthracycline C-13 alcohol metabolites (e.g., doxorubicinol and daunorubicinol) contributes to the development of anthracycline-related cardiotoxicity. The enzymes responsible for the synthesis of anthracycline C-13 alcohol metabolites in canines remain to be elucidated. We hypothesized that canine carbonyl reductase 1 (cbr1), the homolog of the prominent anthracycline reductase human CBR1, would have anthracycline reductase activity. Recombinant canine cbr1 (molecular weight: 32.8 kDa) was purified from Escherichia coli. The enzyme kinetics of "wild-type" canine cbr1 (cbr1 D218) and a variant isoform (cbr1 V218) were characterized with the substrates daunorubicin and menadione, as well as the flavonoid inhibitor rutin. Canine cbr1 catalyzes the reduction of daunorubicin to daunorubicinol, with cbr1 D218 and cbr1 V218 displaying different kinetic parameters (cbr1 D218 Km: 188 ± 144 μM versus cbr1 V218 Km: 527 ± 136 μM, P < 0.05, and cbr1 D218 Vmax: 6446 ± 3615 nmol/min per milligram versus cbr1 V218 Vmax: 15539 ± 2623 nmol/min per milligram, P < 0.01). Canine cbr1 also metabolized menadione (cbr1 D218 Km: 104 ± 50 μM, Vmax: 2034 ± 307 nmol/min per milligram). Rutin acted as a competitive inhibitor for the reduction of daunorubicin (cbr1 D218 Ki: 1.84 ± 1.02 μM, cbr1 V218 Ki: 1.38 ± 0.47 μM). These studies show that canine cbr1 metabolizes daunorubicin and provide the necessary foundation to characterize the role of cbr1 in the variable pharmacodynamics of anthracyclines in canine cancer patients.


Ridge Width Correlations between Inked Prints and Powdered Latent Fingerprints.
A methodology to estimate the time of latent fingerprint deposition would be of great value to law enforcement and courts. It has been observed that ridge topography changes as latent prints age, including the widths of ridges that could be measured as a function of time. Crime suspects are commonly identified using fingerprint databases that contain reference inked tenprints (flat and rolled impressions). These can be of interest in aging studies as they provide baseline information relating to the original (nonaged) ridges' widths. In practice, the age of latent fingerprints could be estimated following a comparison process between the evidentiary aged print and the corresponding reference inked print. The present article explores possible correlations between inked and fresh latent fingerprints deposited on different substrates and visualized with TiO2 . The results indicate that the ridge width of flat inked prints is most similar to fresh latent fingerprints, and these should be used as the comparison standard for future aging studies.


Variation in cestode assemblages of Mastomys and Arvicanthis species (rodents: Muridae) from Lake Retba in Western Senegal.
We studied patterns of variation in cestode communities of 3 abundant rodent species that live in sympatry in the Niayes of the Retba Lake, Western Senegal. We evaluated whether the host species have the same parasites and, within host species, whether the variability in parasite community is related to intrinsic (sex, age of the host individual) or extrinsic (habitat, season) factors. Arvicanthis niloticus was parasitized by 2 cestode species, namely Inermicapsifer madagascariensis and the highly dominant Raillietina trapezoïdes . Raillietina baeri was the only cestode species found in Mastomys erythroleucus , and there was no cestode in M. huberti . Prevalence and abundance levels of cestodes were very high in A. niloticus , especially in adults. Seasonal and habitat effects were found in both cestode communities of M. erythroleucus and A. niloticus . Local host specificity and abundance/prevalence levels suggested variations in the interaction between rodents and cestode intermediate host species among habitats and seasons.


Neuroprotective Effect of Zataria Multiflora Essential Oil on Rats With Alzheimer Disease: A Mechanistic Study.
Finding herbs with promising effects to prevent or postpone Alzheimer Disease (AD) is highly demanded. The present study aimed at clarifying plausible effects and related mechanism(s) of Zataria Multiflora Essential Oil (ZMEO) against memory impairment in a rat model of the AD. Forty male adult rats were categorized into four groups and treated as follows: 1. The Negative Control (NC): no treatment; 2. Sham control (sham): distilled water by Intracerebroventricular (ICV) injection; 3. The AD control (AD): Aβ 1-42 by ICV injection; and 4. The ZMEO group: Aβ 1-42 by ICV injection and ZMEO at 100 μL/kg/d orally for 20 days. After Congo red staining of the hippocampus, a relative decrease in amyloid deposits was observed in the ZMEO group. Moreover, rats showed better outcomes in Morris Water Maze (MWM) test, reduced hippocampal acetylcholinesterase (AchE) activity, and higher Brain-Derived Neurotrophic Factor (BDNF) content as compared with the AD group (P<0.05). However, no significant changes in antioxidant status was observed (P>0.05). ZMEO has a protective effect against memory impairment in rats with AD at least partly via reducing hippocampal AchE activity and enhancement of BDNF levels without a change in antioxidant status. These findings can pave the way for future studies on the usefulness of this herb in AD prevention.


Symmetry and dynamics of FHF- anion in vacuum, in CD2Cl2 and in CCl4. Ab initio MD study of fluctuating solvent-solute hydrogen and halogen bonds.
FHF- anion is a classic example of a central-symmetric strongly hydrogen bonded system that has been intensively investigated both experimentally and theoretically. In this paper we focus on solvent effects on symmetry, structure and dynamics of the anion. The FHF- anion is studied in vacuum, dissolved in CH2Cl2 and dissolved in CCl4 by ab initio molecular dynamics simulations. We show that CH2Cl2 molecules form CHF hydrogen bonds with lone pairs of fluorine atoms, while CCl4 molecules form halogen bonds. These specific non-covalent solvent-solute interactions are cooperatively coupled to the FHF- hydrogen bonds. The fluctuation of solvent molecules' positions is the driving force changing the FHF- hydrogen bond geometry. Most of the time, the anion is solvated asymmetrically, which leads to the asymmetric bridging particle position, though the time-averaged D∞h symmetry is retained. Interestingly, this transient asymmetrization of FHF- is more pronounced in CCl4, than in CH2Cl2. We show that the 1H and 19F NMR chemicals shifts react sensitively to the changes of anion's geometry and the limiting chemical shifts of free solvated FH and F- are strongly solvent-dependent.


HMGB1+ microparticles present in urine are hallmarks of nephritis in patients with systemic lupus erythematosus.
Non-classical monocytes infiltrate the kidney parenchyma and participate in tissue damage in patients with lupus nephritis (LN). Circulating microparticles (MPs) seem to play critical roles in the activation of monocytes in systemic lupus erythematosus (SLE) patients. This study aims to characterize the phenotypes of MPs and monocyte subsets in LN patients and to determine their potential to discriminate between SLE patients with and without LN. Blood and urine samples from SLE patients were collected. In monocyte subsets from whole blood samples several phenotypic markers were evaluated. MPs were isolated from platelet-poor plasma and urine by centrifugation. This phenotypic marker characterization was performed using multiparametric flow cytometry. We observed that patients with active LN have lower counts of non-classical monocytes than do those without renal involvement. All monocyte subsets exhibited lower expression of CX3CR1 and ICAM-1 in LN than in patients without LN. High frequencies of MP-HMGB1+ and MP-HLA-DR+ were detected in circulation and urine of LN patients. Although MP-HMGB1+ , MP-HLA-DR+ , and MP-CX3CR1+ from urine were able to discriminate between patients with and without LN, only urinary MP-HMGB1+ were different between patients with active and inactive LN. Therefore, these vesicles may be useful as biomarkers of LN.


Psychometric evaluation of the inventory of dimensions of emerging adulthood (IDEA) in China.
Emerging adulthood (EA, age range between 18 to 29 years) is an important developmental stage that is characterized by marked social and psychological changes. Currently, its developmental features are quantified by the Inventory of the Dimensions of Emerging Adulthood (IDEA) but a validated Chinese version of this questionnaire (IDEA-C) is lacking. Thus, this research, which consists of two consecutive studies, aimed to investigate the psychometric properties of the translated IDEA in a Chinese sample of emerging adults. Firstly, a forward-backward translation of the IDEA-C scale was conducted. Item analysis and exploratory factor analysis were performed in Sample 1a (n = 2438), followed by structural validity test in Sample 1b (n = 2461). Concurrent validity and internal consistency were evaluated in Sample 1(n = 4899). Finally, test-retest reliability was tested in Sample 2 (n = 185). Then, the second study aimed to test the factor structure proposed by study 1 in the non-student sample (n = 2200) by confirmatory factor analysis. In addition, the second study also investigated whether the attainment of college education influenced the EA experience of non-student emerging adults in China. And the association was examined between the socioeconomic status of emerging adults and the subscales of IDEA. In the college sample, the IDEA-C scale presented a four-factor structure different from the original five-factor structure (χ2(190)=1116.84, p < 0.001; CFI = 0.97; TLI = 0.96; SRMR = 0.039; RMSEA = 0.050 [90%CI=0.047-0.052]). In addition, IDEA-C exhibited good internal consistency reliability (Cronbach's alpha >0.77), test-retest reliability (r>0.49, p < 0.01) and concurrent validity. And the CFA in non-student sample also showed an adequate fit indices (χ2(158) =710.10, p < 0.001, TLI=0.93, CFI=0.94, SRMR=0.038, RMSEA=0.04 [90%CI=0.037-0.040]) and an adequate internal consistency (Cronbach's alpha >0.64) and test-retest reliability (r>0.43, p < 0.01). The results of the present study confirmed that the Chinese version of the IDEA is found to be valid for measuring psychological characteristics of EA in Chinese-speaking samples of emerging adults.


Rabies in a Dog Imported from Egypt - Connecticut, 2017.
In 2007, the United States successfully eliminated canine rabies virus variant. Globally, however, dogs remain the principal source of human rabies infections. Since 2007, three cases of canine rabies virus variant were reported in dogs imported into the United States, one each from India (2007), Iraq (2008), and Egypt (2015) (1-3). On December 20, 2017, a dog imported into the United States from Egypt was identified with rabies, representing the second case from Egypt in 3 years. An Egyptian-based animal rescue organization delivered four dogs from Cairo, Egypt, to a flight parent (a person solicited through social media, often not affiliated with the rescue organization, and usually compensated with an airline ticket), who transported the dogs to the United States. The flight parent arrived at John F. Kennedy International Airport (JFK) in New York City and, via transporters (persons who shuttle dogs from one state to another), transferred the dogs to foster families; the dogs ultimately were adopted in three states. The Connecticut Department of Public Health Laboratory (CDPHL) confirmed the presence of a canine rabies virus variant in one of the dogs, a male aged 6 months that was adopted by a Connecticut family. An investigation revealed the possibility of falsified rabies vaccination documentation presented on entry at JFK, allowing the unvaccinated dog entry to the United States. This report highlights the continuing risk posed by the importation of dogs inadequately vaccinated against rabies from high-risk countries and the difficulties in verifying any imported dog's health status and rabies vaccination history.


Association of smoking cessation with financial stress and material well-being: results from a prospective study of a population-based national survey.
We used 4 waves of prospective data to examine the association of smoking cessation with financial stress and material well-being. Data (n = 5699 at baseline) came from 4 consecutive waves (2001-2005) of the Household Income and Labour Dynamics in Australia survey. We used mixed models to examine the participant-specific association of smoking cessation with financial stress and material well-being. On average, a smoker who quits is expected to have a 25% reduction (P<.001; odds ratio [OR]=0.75; 95% confidence interval [CI]=0.69, 0.81) in the odds of financial stress. Similarly, the data provided strong evidence (P<.001) that a smoker who quits is likely to experience an enhanced level of material well-being. Our findings indicate that interventions to encourage smoking cessation are likely to improve standards of living and reduce deprivation. The findings provide grounds for encouraging the social services sector to incorporate smoking cessation efforts into their programs to enhance the material or financial conditions of disadvantaged groups. The findings also provide additional incentives for smokers to stop smoking and as such can be used in antismoking campaigns and by smoking cessation services.


Inhibition of invasion and angiogenesis by zinc-chelating agent disulfiram.
Cell invasion and angiogenesis are crucial processes in cancer metastasis that require extracellular matrix (ECM) degradation. Proteolytic degradation of the ECM components is a central event of invasion and angiogenesis processes. During these processes, matrix metalloproteinases (MMPs) seem to be primarily responsible for much of the ECM degradation. Disulfiram is frequently used in the treatment of alcoholism and has been reported to possess antiretroviral activity and can eject intrinsic zinc out of human immunodeficiency virus (HIV) nucleocapsid protein. In this report, we show that disulfiram inhibited invasion and angiogenesis in both tumor and endothelial cells at nontoxic concentrations. The 3H-labeled type IV collagen degradation assay suggested that disulfiram has type IV collagenase inhibitory activity, and this inhibition was responsible for blocking invasion and angiogenesis through cell-mediated and non-cell-mediated pathways. However, the mechanisms underlying cell-mediated signal pathways are not fully characterized. Our data demonstrate that the non-cell-mediated pathway is dominant. Thus, disulfiram could directly interact with MMP-2 and MMP-9 and inhibit their proteolytic activity through a zincchelating mechanism. Addition of zinc could reverse the inhibition of invasiveness and collagenase inhibition through disulfiram treatment. This finding implies that MMP-2 and MMP-9 may be the inhibitory targets for a potential disulfiram treatment. These observations raise the possibility clinical therapeutic applications for disulfiram used as a potential inhibitor of metastatic cell invasion and angiogenesis.


Clinical observation on combined use of herbal medicine and acupuncture for treatment of 50 cases of biliary ascariasis complicated by infection.
50 cases of biliary ascariasis complicated by infection were treated by An Hui Zhi Tong Decoction combined with acupuncture. The cure rate was 72%, with a total effective rate of 96%, the therapeutic effect being better than that of the control group of 42 cases treated by western medicine. This therapy exerts good antipyretic effect, improves the symptoms quickly, and has no adverse side effects, thus its therapeutic effect is certain for treatment of biliary ascariasis complicated by infection.


Taenia saginata taeniosis: copro-antigen time-course in a voluntary self-infection.
Human taeniosis due to Taenia saginata is cosmopolitan where beef is consumed; however, there is little or no information on the symptomatology over the early time-course of human infection. Copro-antigen detection is very useful in community screening for human taeniosis, particularly for T. solium, but there are no data on copro-antigen detection in pre-patent infection. In order to provide insight into this, a voluntary self-infection with T. saginata was undertaken and monitored over a 6-month period using a copro-antigen enzyme-linked immunosorbent assay (ELISA) that we developed using anti-T. saginata antibody based reagents. Tapeworm patency, defined as first proglottid appearance, occurred on day 86 post-infection (pi) and was followed by almost daily release of proglottids (range 1-8) until termination using praziquantel on day 180 pi. The first 10 weeks post-infection (wpi) were essentially asymptomatic, followed by main symptoms of involuntary proglottid discharge throughout the infection period, and abdominal discomfort peaking around 15-19 wpi. Copro-antigens could not be reliably detected until 2 weeks before proglottid patency but then remained highly elevated over the next 15 weeks until treatment. Copro-antigen levels reverted to negative 4 days post-treatment. This time-course study suggests that although copro-antigen ELISA is an excellent diagnostic tool for established patent infections of T. saginata, it may not be reliable for faecal antigen detection in the early infection phase prior to proglottid release for T. saginata and other human taenioses.


Oxygen regulation of airway branching in Drosophila is mediated by branchless FGF.
The Drosophila tracheal (respiratory) system is a tubular epithelial network that delivers oxygen to internal tissues. Sprouting of the major tracheal branches is stereotyped and controlled by hard-wired developmental cues. Here we show that ramification of the fine terminal branches is variable and regulated by oxygen, and that this process is controlled by a local signal or signals produced by oxygen-starved cells. We provide evidence that the critical signal is Branchless (Bnl) FGF, the same growth factor that patterns the major branches during embryogenesis. During larval life, oxygen deprivation stimulates expression of Bnl, and the secreted growth factor functions as a chemoattractant that guides new terminal branches to the expressing cells. Thus, a single growth factor is reiteratively used to pattern each level of airway branching, and the change in branch patterning results from a switch from developmental to physiological control of its expression.


Downregulation of TAF9B by miR-7-5p Inhibits the Progression of Osteosarcoma.
Osteosarcoma (OS) is a malignant bone tumor with high metastatic potential. As a regulatory factor of apoptosis, TATA-box binding protein (TBP) associated factor 9B (TAF9B) is rarely studied in tumors. We investigated the role and mechanism of TAF9B in OS cells by overexpression and knockdown. CCK8, colony formation, transwell, and flow cytometry analysis were performed to detect proliferation, migration, invasion, and apoptosis. TAF9B overexpression promotes the proliferation, migration, and invasion of OS cells, while TAF9B knockdown gives the opposite result. TAF9B inhibits apoptosis by upregulating Bcl-2 and downregulating Bax and Cleaved-caspase-3. Through starBase analysis, it was found that miR-7-5p can bind to the 3'UTR region of TAF9B, which is further confirmed by the dual luciferase reporter system assay. MiR-7-5p downregulates the expression of TAF9B in MG63 and U2OS cells. The proliferation and invasion of OS cells are inhibited after miR-7-5p mimics transfection and are promoted after miR-7-5p inhibitor transfection. TAF9B rescues the inhibitory effect of miR-7-5p on OS cells. TAF9B also activates the AKT/mTOR signaling pathway. According to our results, miR-7-5p inhibits the translation of TAF9B and then suppresses growth and metastasis through the AKT/mTOR signaling pathway in OS cells, thereby indicating the potential value of miR-7-5p and TAF9B as therapeutic targets for human OS.


Degradation, cytotoxicity, and biocompatibility of NIPAAm-based thermosensitive, injectable, and bioresorbable polymer hydrogels.
A thermosensitive, injectable, and bioresorbable polymer hydrogel, poly(N-isopropylacrylamide-co-dimethyl-γ-butyrolactone acrylate-co-acrylic acid) [poly(NDBA)], was synthesized by radical copolymerization with 7.00 mol % dimethyl-γ-butyrolactone acrylate in tetrahydrofuran. The chemical composition was determined by acid titration in conjunction with (1) H NMR quantification. The molecular weight and polydispersity were determined by gel permeation chromatography in conjunction with static light scattering. The degradation properties of the polymer hydrogel were characterized using differential scanning calorimetry, percentage mass loss, cloud point test, and swelling ratio over time. It was found that the initial lower critical solution temperature (LCST) of the polymer is between room temperature and body temperature and that it takes about 2 weeks for the LCST to surpass body temperature under physiological conditions. An indirect cytotoxicity test indicated that this copolymer has relatively low cytotoxicity as seen with 3T3 fibroblast cells. The in vivo-gelation and degradation study showed good agreement with in vitro-degradation findings, and no detrimental effects to adjacent tissues were observed after the complete dissolution of the polymer. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part A:, 2011.


Shapes and Patterns of Heme-Binding Motifs in Mammalian Heme-Binding Proteins.
Heme is a double-edged sword. On the one hand, it has a pivotal role as a prosthetic group of hemoproteins in many biological processes ranging from oxygen transport and storage to miRNA processing. On the other hand, heme can transiently associate with proteins, thereby regulating biochemical pathways. During hemolysis, excess heme, which is released into the plasma, can bind to proteins and regulate their activity and function. The role of heme in these processes is under-investigated, with one problem being the lack of knowledge concerning recognition mechanisms for the initial association of heme with the target protein and the formation of the resulting complex. A specific heme-binding sequence motif is a prerequisite for such complex formation. Although numerous short signature sequences indicating a particular protein function are known, a comprehensive analysis of the heme-binding motifs (HBMs) which have been identified in proteins, concerning specific patterns and structural peculiarities, is missing. In this report, we focus on the evaluation of known mammalian heme-regulated proteins concerning specific recognition and structural patterns in their HBMs. The Cys-Pro dipeptide motifs are particularly emphasized because of their more frequent occurrence. This analysis presents a comparative insight into the sequence and structural anomalies observed during transient heme binding, and consequently, in the regulation of the relevant protein.


[Tobacco and alcohol consumption according to workday in Spain].
To examine the association between smoking and alcohol consumption and the type of working day in the Spanish population Cross-sectional study among employees residing in Spain aged >18 years (N=8,736). We took data from the National Health Survey (2011-2012). Information was collected on the type of working day (morning, afternoon, evening, part-time, reduced hours, and shift-work) and smoking and drinking habits. Demographic characteristics and health- and work-related factors were also taken into account. Adjusted odds ratios (aOR) and 95% confidence intervals (95%CI) were calculated through log-binomial regressions. Among respondents, 32.1% smoked regularly, especially those working the night shift (43.5%). Moderate alcohol consumption was found in 54.8% of workers and excessive consumption in 1.5%. Most of the moderate and heavy drinkers worked part-time, with 57.6% and 1.8% respectively. The aOR of being a smoker was higher among night workers (OR=1.58; 95% CI: 1.01-2.46). None of the work shifts were significantly associated with alcohol consumption. Night shift work was associated with regular smoking. This collective of workers should be monitored closely by occupational health services and regularly undergo programs to control tobacco consumption and smoking-related diseases. Additional research to elucidate the reasons for this association could help to achieve preventive and therapeutic success.


Microtubule-mediated transport of organelles and localization of beta-catenin to the future dorsal side of Xenopus eggs.
The dorsal-ventral axis in frog embryos is specified during the first cell cycle, when the cortex rotates relative to the cytoplasmic core along parallel microtubules associated with the core. Cytoplasmic transfer experiments suggest that dorsal determinants are transported 90 degrees from the vegetal pole to the dorsal equator, even though the cortex rotates only 30 degrees. Here we show that, during rotation, small endogenous organelles are rapidly propelled along the subcortical microtubules toward the future dorsal side and that fluorescent carboxylated beads injected into the vegetal pole are transported at least 60 degrees toward the equator. We also show that deuterium oxide, which broadens the zone of dorsalization even though it reduces the extent of rotation and is known to randomize the microtubules, also randomizes the direction of organelle transport. Moreover, beta-catenin, a component of the Wnt signaling pathway that possesses dorsalizing activity in Xenopus, colocalizes with subcortical microtubules at the dorsal side of the egg at the end of rotation. We propose that cortical rotation functions to align subcortical microtubules, which then mediate the transport of dorsal determinants toward their plus ends on one side of the egg.


Relative contribution of physical activity, sedentary behaviors, and dietary habits to the prevalence of obesity among Kuwaiti adolescents.
The increasing rate of obesity among Kuwaiti adolescents is associated with immediate and long term-risks to their health and well-being. To update data on the prevalence of overweight and obesity among Kuwaiti adolescents and to examine the relative contribution of selected lifestyle factors to overweight and obesity in this population. The present study is part of the Arab Teens Lifestyle Study (ATLS). A total of 906 adolescents (463 boys and 443 girls) aged between 14 and 19 years were selected from Kuwaiti schools by a multistage stratified randomization process. A validated questionnaire was used to collect data on physical activity, sedentary lifestyle, and eating habits. The International Obesity Task Force (IOTF) cutoff values for adolescents under 18 years of age were used to define overweight and obesity. Total energy expenditure was calculated using metabolic equivalent-minutes per week. A general linear model was used to establish the proportion of the variance (expressed in partial eta squared) in excess weight attributable to differences in eating habits and physical activity. The prevalence of overweight and obesity was 50.5% in boys and 46.5% in girls. Among boys, moderate and vigorous activities were found to be significantly negatively associated with overweight and obesity (p < .05), whereas in girls, only those with not less than moderate activities were negatively associated with overweight and obesity (p < .05). Sedentary behaviors, time spent watching television, and time spent working on the computer were not significantly associated with obesity in either sex. Consumption of breakfast, vegetables, and fast foods (boys and girls) and potatoes, cakes and doughnuts, and sweets (girls only) was significantly associated with overweight and obesity (p < .05). In general, the partial eta square explained by physical activity was less than 3.6% in boys compared with less than 1.0% in girls, and eating habits explained less than 1.8% in boys compared with 2.5% in girls. Physical activity explains a greater proportion of variation in body mass index than do eating habits, particularly in boys. Eating habits explain a greater proportion of variation in body mass index than does physical activity in girls. Prospective studies are needed to clarify the relative effects of sedentary behaviors on overweight in adolescents.


Electrical stimulation for wound healing: a review of evidence from in vitro studies, animal experiments, and clinical trials.
This article reviews theories linked to endogenous bioelectric currents and the role they may play in wound repair with further appraisal of in vitro and in vivo research related to the effects of clinically applicable electrical currents on protein synthesis, cell migration, and antibacterial outcomes. In addition, studies on the effects of electrical stimulation (ES) on skin grafts, donor sites, and musculocutaneous flaps in animals are evaluated, as well as assessments of numerous clinical reports that examined the effects of ES on angiogenesis, perfusion, PtcO2, and epithelialization. Finally, a plethora of clinical trials related to the responses of chronic lower extremity wounds to ES therapy are reviewed, with emphasis on wounds caused by venous insufficiency, diabetic neuropathy, and ischemia in patients with and without diabetes mellitus. A glossary that addresses ES terminology is also included.


Cardiovascular radiology. The fibrillatory propensities of contrast agents.
Ventricular fibrillation threshold (VFT), the electrical stimulus strength required to fibrillate the heart during the vulnerable period of the cardiac cycle, has been used to evaluate the properties of many arrhythmogenic and antiarrhythmic drugs, and is easily adaptable to determining ventricular vulnerability following coronary arteriography. Using this method, the authors find that there is a large decrease in VFT within seconds following intracoronary arteriography with 1 ml of sodium meglumine diatrizoate. During the first minute, the threshold decreases by an additional 10%, then returns rapidly and completely to control levels. The change in threshold persists much longer than artery-to-sinus transit time, longer than changes in contractility, and somewhat longer than repolarization changes in the surface electrocardiogram. There is a strong dose relation. Injections through impacted catheters or slow injections cause disproportionate decreases in VFT. Ionic solutions of CaCl2 progressively lower VFT, but, when added to sodium meglumine iothalamate solutions, minimize the fibrillatory potential of ionic contrast agents in a complex way. A modified model of myocardial ischemia produced by intracoronary mercury injection is described. With myocardial ischemia, the fibrillation threshold falls, and during coronary arteriography still lower thresholds are seen. The use of VFT measurements is recommended for further evaluation of the fibrillatory potential of contrast media in clinically relevant situations.


Aspirin inhibits platelet 12-hydroxy-eicosatetraenoic acid formation.
The effects of aspirin on platelet 12-hydroxyeicosatetraenoic acid (12-HETE) formation were studied after administration to humans in platelet-rich plasma (PRP) and in vitro in human PRP and in washed platelets (WPs). Healthy volunteers were given orally either single or repeated (1 week) daily doses (20 and 500 mg) of aspirin. Two hours after a single 20 mg aspirin dose, 12-HETE formation by PRP was significantly inhibited. With the highest aspirin dose used (500 mg), the inhibition of 12-HETE formation was more pronounced and long lasting. Thromboxane B2 (TXB2) synthesis was significantly inhibited at 2 hours with the lowest dose. At the 500 mg dose, platelet aggregation was significantly reduced, and TXB2 formation was almost completely suppressed for at least 24 hours. The degree of inhibition of 12-HETE formation at 2 hours after 1 week of daily treatment (20 and 500 mg) was similar to that achieved at 2 hours after the single dose. As far as TXB2 and platelet aggregation are concerned, the effect of 20 mg aspirin was cumulative. In vitro studies show that aspirin (0.25 to 3 mmol/L concentration) significantly inhibits 12-HETE formation in PRP, but not in WPs, suggesting that plasma is required for the aspirin effect on lipoxygenase products. These results indicate that aspirin, even at low doses, not only affects the platelet cyclooxygenase activity but also exerts reversible inhibition of 12-HETE formation, both in vitro and ex vivo. These data may help to further elucidate the role of hydroxyacids in the anti-inflammatory and antipyretic action of aspirin.


Disease-Modification in Huntington's Disease: Moving Away from a Single-Target Approach.
To date, no candidate intervention has demonstrated a disease-modifying effect in Huntington's disease, despite promising results in preclinical studies. In this commentary we discuss disease-modifying therapies that have been trialled in Huntington's disease and speculate that these failures may be attributed, in part, to the assumption that a single drug selectively targeting one aspect of disease pathology will be universally effective, regardless of disease stage or "subtype". We therefore propose an alternative approach for effective disease-modification that uses 1) a combination approach rather than monotherapy, and 2) targets the disease process early on - before it is clinically manifest. Finally, we will consider whether this change in approach that we propose will be relevant in the future given the recent shift to targeting more proximal disease processes-e.g., huntingtin gene expression; a timely question given Roche's recent decision to take on the clinical development of a promising new drug candidate in Huntington's disease, IONIS-HTTRx.


NAD kinase from Bacillus licheniformis: inhibition by NADP and other properties.
NAD kinase was purified 180-fold from Bacillus licheniformis to determine the role it plays in NADP turnover in this organism. The enzyme was found to have a pH optimum of 6.8 and an apparent Km for NAD of 2.7 mM. The ATP saturation curve was not hyperbolic; 5.5 mM ATP was required to reach half maximal activity. Both Mn2+ and Ca2+ could be substituted for Mg2+. Several compounds including nicotinic acid, nicotinamide, nicotinamide mononucleotide, quinolinic acid, NADPH, ADP, AMP and cyclic AMP did not affect NAD kinase activity. In contrast, the enzyme was inhibited by NADP at concentrations typically found in logarithmic cells of B. licheniformis. This inhibition was competitive with NAD and had a Ki of 0.13 mM. It is suggested that in vivo NAD kinase activity is highly dependent on the concentrations of NAD and ATP and the proportion of oxidized and reduced NADP.


[The nature of interactions between total histones and membranes of isolated lysosomes].
Total fraction of histones increased the permeability of isolated lysosomes as showed the elevation in nonsedimented and free enzymatic activity of the matrix. S-like shape of curves, observed in dose-dependent effect of the histones increased concentrations on the enzymatic activity, indicated the structure transformations of membranes occurring by the cooperative type. Membranotropic effect of histones exceeded the action on non-ionic detergent Triton X-100. Hydrophobic interactions of histones with lysosomal membranes appear to be responsible for the effects observed.


Action and valence modulate choice and choice-induced preference change.
Choices are not only communicated via explicit actions but also passively through inaction. In this study we investigated how active or passive choice impacts upon the choice process itself as well as a preference change induced by choice. Subjects were tasked to select a preference for unfamiliar photographs by action or inaction, before and after they gave valuation ratings for all photographs. We replicate a finding that valuation increases for chosen items and decreases for unchosen items compared to a control condition in which the choice was made post re-evaluation. Whether choice was expressed actively or passively affected the dynamics of revaluation differently for positive and negatively valenced items. Additionally, the choice itself was biased towards action such that subjects tended to choose a photograph obtained by action more often than a photographed obtained through inaction. These results highlight intrinsic biases consistent with a tight coupling of action and reward and add to an emerging understanding of how the mode of action itself, and not just an associated outcome, modulates the decision making process.


Influence of Different Calcium Phosphates on an Experimental Adhesive Resin.
To formulate adhesive resins with 2 wt% of hydroxyapatite (HAp), α-tricalcium phosphate (α-TCP), or octacalcium phosphate (OCP) and to compare these groups with an unfilled adhesive regarding the degree of conversion, polymerization rate, microshear bond strength and mineral deposition. The experimental adhesive resin was formulated mixing 66.6 wt% bisphenol A glycol dimethacrylate (bis-GMA), 33.3 wt% 2-hydroxyethyl methacrylate (HEMA), and a photoinitiator system. OCP, α-TCP, or HAp were added in concentrations of 2 wt% to the adhesive, and a group without additional filler was used as the control. Calcium-phosphate particle sizes were determined using a laser-diffraction particle-size analyzer. The degree of conversion (DC) of the adhesives was determined with FTIR-ATR. The polymerization rate (Rp) was determined using differential scanning calorimetry equipped with a photocalorimetric accessory. Adhesive bonding was evaluated using the microshear bond strength test in sound bovine mandibular incisors. Mineral deposition in human third molars affected by caries was evaluated using micro-Raman spectroscopy after selective removal of carious dentin. Data were analyzed by one-way ANOVA and Tukey's test (α = 0.05). HAp presented the highest mean particle size (26.7 nm), while that of α-TCP was 6.03 nm and OCP was 4.94 nm. The DC of all groups was above 50%. The OCP group showed the fastest Rp, with no difference from the control group (p > 0.05). The α-TCP group presented the highest microshear bond strength (p = 0.005) and mineral deposition at the interface. Incorporation of α-TCP nanofiller into adhesive resins can improve bond strengths and may be a promising strategy to achieve therapeutic remineralization at the composite-dentin interface.


Effect of nanocrystalline hydroxyapatite socket preservation on orthodontically induced inflammatory root resorption.
Orthodontically induced inflammatory root resorption (OIIRR) is considered to be an important sequel associated with orthodontic tooth movement (OTM). OTM after Socket preservation enhances the periodontal condition before orthodontic space closure. The purpose of this study is to investigate the histologic effects of NanoBone®, a new highly nonsintered porous nano-crystalline hydroxyapatite bone on root resorption following OTM. This experimental study was conducted on four male dogs. In each dog, four defects were created at the mesial aspects of the maxillary and mandibular first premolars. The defects were filled with NanoBone®. We used the NiTi closed coil for mesial movement of the first premolar tooth. When the experimental teeth moved approximately halfway into the defects, after two months, the animals were sacrificed and we harvested the area of interest. The first premolar root and adjacent tissues were histologically evaluated. The three-way ANOVA statistical test was used for comparison. The mean root resorption in the synthetic bone substitute group was 22.87 ± 11.25×10(-4)mm(2) in the maxilla and 21.41 ± 11.25×10(-4)mm(2) in the mandible. Statistically, there was no significant difference compared to the control group (p>0.05). The use of a substitution graft in the nano particle has some positive effects in accessing healthy periodontal tissue following orthodontic procedures without significant influence on root resorption (RR). Histological evaluation in the present study showed osteoblastic activity and remodeling environment of nanoparticles in NanoBone®.


Suboptimal pharmacotherapeutic management of chronic stable angina in the primary care setting.
To assess the adequacy of symptomatic treatment for chronic stable angina among primary care patients who receive care from the Department of Veterans Affairs (VA). We conducted a cross-sectional analysis involving 7038 veterans with self-reported coronary heart disease who completed the Seattle Angina Questionnaire and who had made a primary care visit to one of seven VA general internal medicine clinics between May 1997 and January 2000. The main outcome measures included the anginal frequency scale of the questionnaire and receipt of prescriptions for antianginal medication in three classes (beta-blockers, calcium antagonists, and long-acting nitrates). Seventy percent of the patients experienced angina or took sublingual nitroglycerin preparations two or fewer times per week. Of the 30% of patients with more frequent symptoms, 22% were receiving no antianginal medications and 33% were receiving only one class of antianginal medication. Of the patients with frequent angina who were prescribed medications, 18% were taking no medications at the recommended therapeutic dose and 50% were receiving only one class of antianginal medication at the recommended therapeutic dose. A substantial proportion of patients with frequent episodes of chronic stable angina appeared to be receiving an inadequate antianginal regimen in terms of number of agents and dosages. While numerous studies have described inadequate treatment of asymptomatic conditions and risk factors, our results suggest similar deficiencies in addressing a serious and eminently treatable symptomatic problem.


[Technique of endarterectomy from pulmonary artery in chronic thromboembolic pulmonary hypertension].
The article gives detailed description of a technique of pulmonary endarterectomy in chronic thromboembolic pulmonary hypertension. The method is based on the experience of the world leader in surgical treatment of this disease--the clinic of California, San Diego headed by Stuart Jamieson, cardiothoracal clinic Papworth Hospital in the only center in Great Britain, where PE is performed and on the experience obtained by the collective of the Department of hospital surgery of the medical department of the St. Petersburg state University and the City multi-field hospital.


Cystic fibrosis year in review 2019: Section 1 CFTR modulators.
During the year 2019, research and case reports/series in the field of cystic fibrosis (CF) were in abundance. To adequately address the large body of CF research published during 2019, the CF year in review will be divided into three sections. This report is the first section, focusing specifically on new research related to cystic fibrosis transmembrane conductance regulator modulator therapy. Additional sections will concentrate on pulmonary and infections research and the multisystem effects of CF. It is an exciting time to be providing care for patients and their families with CF with all the exciting new discoveries that will be shared in these reviews.


[Structure of alpha-spiral hairpins with short connections in globular proteins].
The analysis of conformations of more than 100 alpha-alpha-hairpins with closely packed helical segments and connections up to four amino acid residues in length was carried out. Five types of the connections were revealed and their phi and psi values on the Ramachandran map were found. Each type of alpha-alpha-hairpins was shown to have a unique sequence pattern for hydrophobic and hydrophilic residues.


Topotecan versus cyclophosphamide, doxorubicin, and vincristine for the treatment of recurrent small-cell lung cancer.
Topotecan and cyclophosphamide, doxorubicin, and vincristine (CAV) were evaluated in a randomized, multicenter study of patients with small-cell lung cancer (SCLC) who had relapsed at least 60 days after completion of first-line therapy. Patients received either topotecan (1.5 mg/m2) as a 30-minute infusion daily for 5 days every 21 days (n = 107) or CAV (cyclophosphamide 1,000 mg/m2, doxorubicin 45 mg/m2, and vincristine 2 mg) infused on day 1 every 21 days (n = 104). Eligibility included the following: bidimensionally measurable disease, Eastern Cooperative Oncology Group performance status of less than or equal to 2, and adequate marrow, liver, and renal function. Response was confirmed by blinded independent radiologic review. Response rate was 26 of 107 patients (24.3%) treated with topotecan and 19 of 104 patients (18.3%) treated with CAV (P = .285). Median times to progression were 13.3 weeks (topotecan) and 12.3 weeks (CAV) (P = .552). Median survival was 25.0 weeks for topotecan and 24.7 weeks for CAV (P = .795). The proportion of patients who experienced symptom improvement was greater in the topotecan group than in the CAV group for four of eight symptoms evaluated, including dyspnea, anorexia, hoarseness, and fatigue, as well as interference with daily activity (P< or =.043). Grade 4 neutropenia occurred in 37.8% of topotecan courses versus 51.4% of CAV courses (P<.001). Grade 4 thrombocytopenia and grade 3/4 anemia occurred more frequently with topotecan, occurring in 9.8% and 17.7% of topotecan courses versus 1.4% and 7.2% of CAV courses, respectively (P<.001 for both). Nonhematologic toxicities were generally grade 1 to 2 for both regimens. Topotecan was at least as effective as CAV in the treatment of patients with recurrent SCLC and resulted in improved control of several symptoms.


Cardiac perfusion changes in patients treated for breast cancer with radiation therapy and doxorubicin: preliminary results.
To determine the incidence and dose dependence of regional cardiac perfusion abnormalities in patients with left-sided breast cancer treated with radiation therapy (RT) with and without doxorubicin (Dox). Twenty patients with left-sided breast cancer underwent cardiac perfusion imaging using single photon emission computed tomography (SPECT) prechemotherapy, pre-RT, and 6 months post-RT. SPECT perfusion images were registered onto 3-dimensional (3D) RT dose distributions. The volume of heart in the RT field was quantified, and the regional RT dose was calculated. A decrease in regional cardiac perfusion was assessed subjectively by visual inspection and objectively using image fusion software. Ten patients received Dox-based chemotherapy (total dose 120-300 mg/m(2)), and 10 patients had no chemotherapy. RT was delivered by tangent beams in all patients to a total dose of 46-50 Gy. Overall, 60% of the patients had new visible perfusion defects 6 months post-RT. A dose-dependent perfusion defect was seen at 6 months with minimal defect appreciated at 0-10 Gy, and a 20% decrease in regional perfusion at 41-50 Gy. One of 20 patients had a decrease in left ventricle ejection fraction (LVEF) of greater than 10% at 6 months; 2/20 patients had developed transient pericarditis. No instances of myocardial infarction or congestive heart failure (CHF) have occurred. RT causes cardiac perfusion defects 6 months post-RT in most patients. Long-term follow-up is needed to assess whether these perfusion changes are transient or permanent and to determine if these findings are associated with changes in overall cardiac function and clinical outcome.


Endohelminth parasites from salmonids in intensive culture from southern Chile.
A total of 228 salmonids (90 Oncorhynchus mykiss, 48 Oncorhynchus kisutch, and 90 Salmo salar) from 8 intensive aquaculture centers in the south of Chile were examined for endohelminths parasites between December 2008 and May 2009. The body cavities of 2 O. mykiss were infected by Diphyllobothrium sp. plerocercoids (prevalence: 6.7%, mean intensity: 1.0, mean abundance: 0.07) from the Lake Tarahuin hatchery on the south of Chiloé Island. Also, tetraphyllidean plerocercoids (prevalence: 3.3%, mean intensity: 1, mean abundance: 0.03) and fourth-stage larvae of Hysterothylacium aduncum (prevalence: 6.7%, mean intensity: 1, mean abundance 0.07) were observed in O. kisutch from a marine hatchery in Chiloé. The occurrences of Diphyllobothrium sp. in a lake and a tetraphyllidean plerocercoid from marine cultured salmonid in Chiloé are reported for first time. No muscular infection by helminths was recorded in the fish examined.


Comparison of the effectiveness of arthrocentesis in acute and chronic closed lock: analysis of clinical and arthroscopic findings.
The objective of this study was to investigate the effectiveness of temporomandibular joint arthrocentesis in acute and chronic closed lock patients. Eighteen patients with closed lock of the temporomandibular joint (TMJ) were treated with fine needle fiber arthroscopic observation following arthrocentesis. Maximal mouth opening (MMO) and intensity of pain (VAS) were evaluated at pretreatment and each posttreatment appointment (one week, one month, three months following treatment). The clinical and arthroscopic findings were analyzed categorizing two groups into: good (A) and poor (B) groups. At pretreatment there was no significance relative to age or the mean MMO and VAS between the groups, but the mean of duration of the symptoms in group B was significantly longer than in group A (P < 0.03). Group B showed more severe synovitis, adhesions, and chondromalacia than group A (P < 0.01). Results suggest that arthrocentesis is more effective in closed lock of short duration where there is less severe synovitis, adhesions, and chondromalacia.


Update on appropriate use criteria for amyloid PET imaging: dementia experts, mild cognitive impairment, and education. Amyloid Imaging Task Force of the Alzheimer's Association and Society for Nuclear Medicine and Molecular Imaging.
Amyloid PET imaging is a novel diagnostic test that can detect in living humans one of the two defining pathologic lesions of Alzheimer disease, amyloid-β deposition in the brain. The Amyloid Imaging Task Force of the Alzheimer's Association and Society for Nuclear Medicine and Molecular Imaging previously published appropriate use criteria for amyloid PET as an important tool for increasing the certainty of a diagnosis of Alzheimer disease in specific patient populations. Here, the task force further clarifies and expands 3 topics discussed in the original paper: first, defining dementia experts and their use of proper documentation to demonstrate the medical necessity of an amyloid PET scan; second, identifying a specific subset of individuals with mild cognitive impairment for whom an amyloid PET scan is appropriate; and finally, developing educational programs to increase awareness of the amyloid PET appropriate use criteria and providing instructions on how this test should be used in the clinical decision-making process.


Mucogingival conditions in the natural dentition: Narrative review, case definitions, and diagnostic considerations.
Mucogingival deformities, and gingival recession in particular, are a group of conditions that affect a large number of patients. Since life expectancy is rising and people are retaining more teeth both gingival recession and the related damages to the root surface are likely to become more frequent. It is therefore important to define anatomic/morphologic characteristics of mucogingival lesions and other predisposing conditions or treatments that are likely to be associated with occurrence of gingival recession. Mucogingival defects including gingival recession occur frequently in adults, have a tendency to increase with age, and occur in populations with both high and low standards of oral hygiene. The root surface exposure is frequently associated with impaired esthetics, dentinal hypersensitivity and carious and non-carious cervical lesions. The objectives of this review are as follows (1) to propose a clinically oriented classification of the main mucogingival conditions, recession in particular; (2) to define the impact of these conditions in the areas of esthetics, dentin hypersensitivity and root surface alterations at the cervical area; and (3) to discuss the impact of the clinical signs and symptoms associated with the development of gingival recessions on future periodontal health status. An extensive literature search revealed the following findings: 1) periodontal health can be maintained in most patients with optimal home care; 2) thin periodontal biotypes are at greater risk for developing gingival recession; 3) inadequate oral hygiene, orthodontic treatment, and cervical restorations might increase the risk for the development of gingival recession; 4) in the absence of pathosis, monitoring specific sites seems to be the proper approach; 5) surgical intervention, either to change the biotype and/or to cover roots, might be indicated when the risk for the development or progression of pathosis and associated root damages is increased and to satisfy the esthetic requirements of the patients. The clinical impact and the prevalence of conditions like root surface lesions, hypersensitivity, and patient esthetic concern associated with gingival recessions indicate the need to modify the 1999 classification. The new classification includes additional information, such as recession severity, dimension of the gingiva (gingival biotype), presence/absence of caries and non-carious cervical lesions, esthetic concern of the patient, and presence/absence of dentin hypersensitivity.


Personality Affects Zebrafish Response to Sertraline.
Sertraline is widely prescribed to treat anxiety and depression. Sertraline acts by blocking serotonin, norepinephrine, and dopamine transporters systems and has been detected in surface waters globally, where it may impact fish behavior. We classified zebrafish personality on three behavioral axes, boldness, anxiety, and sociability, assigning fish as either high or low in each category. The fish were exposed to nominal concentrations of 0, 5, 50, 500, or 5000 ng/L sertraline (measured concentrations: <10, 21.3, 370, and 2200 ng/L, respectively) to assess changes in boldness, anxiety, and sociability after 7 and 28 days. We also measured shoaling behavior and response to an alarm cue, and determined the gut microbiome of a subset of fish. After 7 days there was no overall effect of sertraline on boldness, but there was an interaction between initial personality and sex, with a stronger impact on females classified as low-boldness personality. Sertraline reduced sociability in all treatments compared with the control, but there was again an interaction between sertraline and initial personality. Fish that were classified as low-sociability responded more strongly to sertraline. After 7 days, fish exposed to a nominal concentration of 5000 ng/L (2200 ng/L measured) showed higher anxiety than controls, with the overall pattern of initial behavior retained. After 28 days, similar patterns were observed, but with higher variation. There was only a weak association between the gut microbiome and personality. Overall, the study highlights the importance of considering initial behavior, which can affect response to pollutants. Our results may also be applicable to human studies and provide a mechanism to explain why different individuals respond differently to the drug. Environ Toxicol Chem 2023;00:1-15. © 2023 SETAC.


Potentially amyloidogenic, carboxyl-terminal derivatives of the amyloid protein precursor.
The 39- to 43-amino acid amyloid beta protein (beta AP), which is deposited as amyloid in Alzheimer's disease, is encoded as an internal peptide that begins 99 residues from the carboxyl terminus of a 695- to 770-amino acid glycoprotein referred to as the amyloid beta protein precursor (beta APP). To clarify the processing that produces amyloid, carboxyl-terminal derivatives of the beta APP were analyzed. This analysis showed that the beta APP is normally processed into a complex set of 8- to 12-kilodalton carboxyl-terminal derivatives. The two largest derivatives in human brain have the entire beta AP at or near their amino terminus and are likely to be intermediates in the pathway leading to amyloid deposition.


The bacterial LexA transcriptional repressor.
Bacteria respond to DNA damage by mounting a coordinated cellular response, governed by the RecA and LexA proteins. In Escherichia coli, RecA stimulates cleavage of the LexA repressor, inducing more than 40 genes that comprise the SOS global regulatory network. The SOS response is widespread among bacteria and exhibits considerable variation in its composition and regulation. In some well-characterised pathogens, induction of the SOS response modulates the evolution and dissemination of drug resistance, as well as synthesis, secretion and dissemination of the virulence. In this review, we discuss the structure of LexA protein, particularly with respect to distinct conformations that enable repression of SOS genes via specific DNA binding or repressor cleavage during the response to DNA damage. These may provide new starting points in the battle against the emergence of bacterial pathogens and the spread of drug resistance among them.


Intranasally Administered Exosomes from Umbilical Cord Stem Cells Have Preventive Neuroprotective Effects and Contribute to Functional Recovery after Perinatal Brain Injury.
Perinatal brain injury (PBI) in preterm birth is associated with substantial injury and dysmaturation of white and gray matter, and can lead to severe neurodevelopmental deficits. Mesenchymal stromal cells (MSC) have been suggested to have neuroprotective effects in perinatal brain injury, in part through the release of extracellular vesicles like exosomes. We aimed to evaluate the neuroprotective effects of intranasally administered MSC-derived exosomes and their potential to improve neurodevelopmental outcome after PBI. Exosomes were isolated from human Wharton's jelly MSC supernatant using ultracentrifugation. Two days old Wistar rat pups were subjected to PBI by a combination of inflammation and hypoxia-ischemia. Exosomes were intranasally administered after the induction of inflammation and prior to ischemia, which was followed by hypoxia. Infrared-labeled exosomes were intranasally administered to track their distribution with a LI-COR scanner. Acute oligodendrocyte- and neuron-specific cell death was analyzed 24 h after injury in animals with or without MSC exosome application using terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay and immunohistochemical counterstaining. Myelination, mature oligodendroglial and neuronal cell counts were assessed on postnatal day 11 using immunohistochemistry, Western blot or RT-PCR. Morris water maze assay was used to evaluate the effect of MSC exosomes on long-term neurodevelopmental outcome 4 weeks after injury. We found that intranasally administered exosomes reached the frontal part of the brain within 30 min after administration and distributed throughout the whole brain after 3 h. While PBI was not associated with oligodendrocyte-specific cell death, it induced significant neuron-specific cell death which was substantially reduced upon MSC exosome application prior to ischemia. MSC exosomes rescued normal myelination, mature oligodendroglial and neuronal cell counts which were impaired after PBI. Finally, the application of MSC exosomes significantly improved learning ability in animals with PBI. In conclusion, MSC exosomes represent a novel prevention strategy with substantial clinical potential as they can be administered intranasally, prevent gray and white matter alterations and improve long-term neurodevelopmental outcome after PBI.


Behavioral vs drug treatment for urge urinary incontinence in older women: a randomized controlled trial.
Urinary incontinence is a common condition caused by many factors with several treatment options. To compare the effectiveness of biofeedback-assisted behavioral treatment with drug treatment and a placebo control condition for the treatment of urge and mixed urinary incontinence in older community-dwelling women. Randomized placebo-controlled trial conducted from 1989 to 1995. University-based outpatient geriatric medicine clinic. A volunteer sample of 197 women aged 55 to 92 years with urge urinary incontinence or mixed incontinence with urge as the predominant pattern. Subjects had to have urodynamic evidence of bladder dysfunction, be ambulatory, and not have dementia. Subjects were randomized to 4 sessions (8 weeks) of biofeedback-assisted behavioral treatment, drug treatment (with oxybutynin chloride, possible range of doses, 2.5 mg daily to 5.0 mg 3 times daily), or a placebo control condition. Reduction in the frequency of incontinent episodes as determined by bladder diaries, and patients' perceptions of improvement and their comfort and satisfaction with treatment. For all 3 treatment groups, reduction of incontinence was most pronounced early in treatment and progressed more gradually thereafter. Behavioral treatment, which yielded a mean 80.7% reduction of incontinence episodes, was significantly more effective than drug treatment (mean 68.5% reduction; P=.04) and both were more effective than the placebo control condition (mean 39.4% reduction; P<.001 and P=.009, respectively). Patient-perceived improvement was greatest for behavioral treatment (74.1% "much better" vs 50.9% and 26.9% for drug treatment and placebo, respectively). Only 14.0% of patients receiving behavioral treatment wanted to change to another treatment vs 75.5% in each of the other groups. Behavioral treatment is a safe and effective conservative intervention that should be made more readily available to patients as a first-line treatment for urge and mixed incontinence.


Energy balance at a crossroads: translating the science into action.
One of the major challenges facing the United States is the high number of overweight and obese adults and the growing number of overweight and unfit children and youth. To improve the nation's health, young people must move into adulthood without the burden of obesity and its associated chronic diseases. To address these issues, the American College of Sports Medicine, the Academy of Nutrition and Dietetics, and the US Department of Agriculture/Agriculture Research Service convened an expert panel meeting in October 2012 titled "Energy Balance at a Crossroads: Translating the Science into Action." Experts in the fields of nutrition and exercise science came together to identify the biological, lifestyle, and environmental changes that will most successfully help children and families attain and manage energy balance and tip the scale toward healthier weights. Two goals were addressed: 1) professional training and 2) consumer/community education. The training goal focused on developing a comprehensive strategy to facilitate the integration of nutrition and physical activity (PA) using a dynamic energy balance approach for regulating weight into the training of undergraduate and graduate students in dietetics/nutrition science, exercise science/PA, and pre-K-12 teacher preparation programs and in training existing cooperative extension faculty. The education goal focused on developing strategies for integrating dynamic energy balance into nutrition and PA educational programs for the public, especially programs funded by federal/state agencies. The meeting expert presenters and participants addressed three key areas: 1) biological and lifestyle factors that affect energy balance, 2) undergraduate/graduate educational and training issues, and 3) best practices associated with educating the public about dynamic energy balance. Specific consensus recommendations were developed for each goal.


A reversed phase high performance liquid chromatographic method for determination of rapamycin.
Easily degradating and various isomeric forms of rapamycin (Sirolimus) face the determination of this compound to many challenges. In this study, we developed and validated the isocratic reversed phase high performance liquid chromatographic (RP-HPLC) method for rapamycin. Separation was performed on a C8 column (MZ, 15 × 4.6 mm, 5 μm particle size) using methanol:water (80:20 v/v) as the mobile phase with the flow rate of 1 mL/min. The column temperature was set at 57°C and the detection was carried out at the wavelength of 277 nm. The method was linear over a concentration range of 0.025-2 μg/mL. The coefficient of variation of intra- and inter-day, assessed at three concentration levels of 0.075, 0.3 and 0.900 μg/mL, was less than 2%. Limit of quantification (LOQ) was found 25 ng/mL. The method with high percent recovery and short retention time of rapamycin, was found to be simple, rapid and reproducible.


Analysis of the H19ICR insulator.
Transcriptional insulators are specialized cis-acting elements that protect promoters from inappropriate activation by distal enhancers. The H19 imprinting control region (ICR) functions as a CTCF-dependent, methylation-sensitive transcriptional insulator. We analyzed several insertional mutations and demonstrate that the ICR can function as a methylation-regulated maternal chromosome-specific insulator in novel chromosomal contexts. We used chromosome conformation capture and chromatin immunoprecipitation assays to investigate the configuration of cis-acting elements at these several insertion sites. By comparing maternal and paternal organizations on wild-type and mutant chromosomes, we hoped to identify mechanisms for ICR insulator function. We found that promoter and enhancer elements invariably associate to form DNA loop domains at transcriptionally active loci. Conversely, active insulators always prevent these promoter-enhancer interactions. Instead, the ICR insulator forms novel loop domains by associating with the blocked promoters and enhancers. We propose that these associations are fundamental to insulator function.


Potential application of Metolose in a thermoresponsive transdermal therapeutic system.
The purpose of the present study was to formulate a novel thermoresponsive membrane controlled therapeutic system from Metolose for possible transdermal application. Metolose gel shows thermal gelation property, which can be characterized by two (T(1), T(2)) temperatures. A sharp decrease of viscosity can be measured at T(1), but gelation can be observed at T(2). Different types of Metolose polymers were compared considering their thermoresponsive behaviour. Only thermal gelation was observed in the case of Metolose SM, while Metolose SH showed a sudden decrease of viscosity at T(1). Since this temperature is above the body temperature, so it should be shifted to the skin temperature in case of possible transdermal application. Modulation of thermoresponsibility was followed by rheological method, and the thermoresponsive drug release from Metolose gel was studied by static liberation test. Our results demonstrated that the effect of different salts (NaCl, NaHCO(3), KCl) of various concentrations in Metolose SH gel reduced T(1) to the skin temperature, which enabled enhanced drug release.