Therapeutic recommendations in polycythemia vera based on Polycythemia Vera Study Group protocols.
The PVSG was organized in 1967 to establish effective diagnostic criteria for polycythemia vera, to study the natural history of the disease and to define the optimal treatment. Although polycythemia vera and the other myeloproliferative diseases are relatively uncommon, the PVSG was able to accumulate well over 1,000 patients with these various disorders and to study them according to a total of 15 different protocols. PVSG-01, a long-term randomized controlled study of phlebotomy alone compared with the myelosuppressive agents, 32P or chlorambucil supplemented by phlebotomy, continues to receive follow-up data on 93% of surviving patients 18 years after initiation of the study. During its lifetime, PVSG has developed a widely accepted and highly effective set of criteria for the specific diagnosis of polycythemia vera as well as useful criteria for the diagnosis of essential thrombocythemia. It has gathered an enormous volume of data on the natural history of the myeloproliferative diseases and in particular on the nature of the prevalent complications, such as thrombotic events and hematologic and nonhematologic malignancies. With respect to the final question, the optimal treatment for polycythemia vera, it is apparent that the expectation of a single optimal therapy that would apply to all patients at all ages and stages of the disease was naive. Nevertheless considerable progress has been made. Moreover, the group has defined more precisely than ever before the nature of the complications of the disease and the association of the risks of specific complications with specific forms of therapy. It thus has made it possible to pose the next series of therapeutic questions that must be addressed in this disorder with a greater degree of sophistication than was previously possible.


An exploration of undergraduate nursing and physiotherapy students' views regarding education for patient handling.
To ascertain the views of undergraduate student nurses and physiotherapists regarding their education in patient handling. Musculo-skeletal injuries are an important cause of staff sickness absence and attrition from the nursing profession and are a recognised problem within the physiotherapy profession. Nurses and physiotherapists are at risk of musculo-skeletal injuries as a result of their role in assisting patients with movement. A questionnaire survey was undertaken of undergraduate nursing and physiotherapy students (n = 371) at one university. Most students agreed that university teaching about moving and handling prepared them for clinical practice (64%). Over a third reported that they had never undertaken a written moving and handling risk assessment in clinical practice (38%). Almost half of the sample (40%) admitted undertaking unsafe moving and handling activities. Half (50%) also stated that they would rather 'fit' into the team than challenge unsafe practice. Almost a third (29%) stated that they had begun to experience pain since becoming a student. There were significant differences between nursing and physiotherapy students. Physiotherapy students were more likely to report being supervised when moving and handling and reported being more assertive about adhering to safe practice. The well-being of both nursing and physiotherapy undergraduate students is threatened when students undertake work placements in clinical settings. University-based education in safe patient handling, though important, can be undermined by workplace settings where unsafe practices occur. Collaboration is needed between university educators, managers and practice-based mentors to support students to maintain safe approaches to moving and handling patients. A third of students reported developing pain since becoming a healthcare student. Students entering their professions already injured may leave the workforce owing to poor physical well-being. It is vital that the clinical workplace supports safe systems of working.


Use of the Vertical Profunda Artery Perforator Flap to Capture the Dominant Perforator: A Cadaver Dissection and Imaging Study.
While the originally described transverse profunda artery perforator (tPAP) flap is designed to capture the first profunda perforator, our group hypothesized the dominant perforator may not always be captured in this configuration. This study maps the location of dominant profunda perforators using imaging and cadaveric dissections to determine the probability of capturing dominant perforators with the transverse flap design versus the vertical PAP (vPAP) variant. Fifty preoperative magnetic resonance angiogram or computed tomographic angiogram scans (100 total extremities) were examined from autologous breast reconstruction patients between 2015 and 2019. Profunda perforator characteristics that were examined included the distance from the pubic tubercle to the infragluteal fold (IGF), the distance of the perforators from the IGF, distance posterior to the gracilis, the diameter of the perforator at fascial exit, and total number of perforators present. Profunda perforator dissection was performed in 18 cadaveric extremities. Analysis included mean distance from pubic tubercle, distance posterior to the gracilis, diameter at fascial exit, and total number of perforators. In imaging analysis, the mean distance from the IGF to the fascial exit of all dominant perforators was 7.04 cm. The mean diameter of the dominant perforator at the fascial exit was 2.61 mm. Twenty-six thighs (26%) demonstrated dominant perforators that exited the fascia greater than 8 cm below the IGF. In cadaver dissections, the mean distance from the pubic tubercle to the fascial exit of all the dominant perforators was 10.17 cm. Nine cadaver specimens (50%) demonstrated perforators that exited the fascia greater than 8 cm below the estimated IGF. The dominant perforator can often be missed in the traditional tPAP design. The vPAP incorporates multiple perforators with a long pedicle, excellent vessel diameter, and favorable donor-site.


Maturation of a Trypanosoma brucei infection to the infectious metacyclic stage is enhanced in nutritionally stressed tsetse flies.
We report on the effect of tsetse fly starvation on the maturation of an established Trypanosoma brucei brucei midgut infection, i.e., the development of procyclic infection into the infectious metacyclic parasites in the tsetse fly salivary glands. Glossina morsitans morsitans flies were nutritionally stressed 10 d after the uptake of a T. b. brucei-infected bloodmeal by depriving these flies from feeding for seven consecutive days, whereas the control fly group (nonstarved group) continued to be fed three times a week. After this period, both fly groups were again fed three times per week on uninfected rabbit. Thirty days after the infected bloodmeal, all surviving flies were dissected and examined for the presence of an immature midgut and a mature salivary gland trypanosome infections. Results showed a significantly increased proportion of flies with salivary gland infection in the nutritionally stressed fly group suggesting an enhanced maturation of the trypanosome infection. These data suggest that environmental factors that cause nutritional stress in a tsetse population do not only make tsetse flies significantly more susceptible to establish a midgut infection as was shown previously but also boost the maturation of these midgut infections.


Does the Effort Meet the Challenge in Promoting Low-Carbon City?-A Perspective of Global Practice.
Global warming caused by carbon emissions has been recognized as a challenge to human sustainable development, and low-carbon city development is widely considered as an effective strategy to address this challenge. Numerous emission reduction measures have been implemented, and considerable efforts have been devoted in promoting low-carbon city. This paper examines whether sufficient efforts have been paid to these typical emission sectors, including Building, Industry, Energy Transformation, and Transportation by referring to the shared responsibility of each sector. The shared responsibility of individual emission sector is calculated by applying energy consumption data in 2014 World Energy Balance. The efforts contributed in emission reduction by each sector are examined by analyzing the low-carbon city work plans of 24 representative sample cities, which are selected globally. The research results demonstrate that sufficient emission reduction efforts have been paid in the Building sector and Transportation sector. But the Industry sector and Energy Transformation sector are less-attended in addressing emission reduction. The reason for the sufficient efforts paid in the Building sector and Transportation sector is considered as that the efforts for emission reduction in these two sectors can bring more co-benefits. However, emission reduction in Industrial sector is generally considered to have the effects of holding back economic growth, and the emission reduction in the sector of Energy Transformation will need enormous investment for advanced technologies. Policy for emission reduction in the Industry sector and Energy Transformation sector is indispensable to promote low-carbon city. This study appeals that (1) low-carbon city can be effectively implemented only if carbon reduction policy is adopted to all industrial activities; (2) multiple channels of financial resources should be established to support cities to mitigate carbon emissions in Industry sector; (3) cooperation on the development of clean energy technology between cities should be promoted; and (4) efforts should be paid to reduce carbon emission from using traditional energy transformation equipment by improving their efficiency.


Cancer-associated alterations of blood group antigen expression in human colorectal polyps.
Human colorectal carcinoma tissues may exhibit several patterns of altered blood group substance (BGS) expression: reappearance of A, B, H, or Lewisb antigens in distal colon; deletion of BGS in the proximal colon with or without precursor substance accumulation; and incompatible BGS expression in proximal or distal colon. The present study evaluated these cancer-associated alterations in colorectal polyps with different malignant potential. With respect to ABH antigens, hyperplastic polyps (HPs), considered to have no malignant potential, did not exhibit incompatibility and only a few cases demonstrated BGS reappearance or deletion. Adenomatous polyps (APs) however, frequently reexpressed ABH antigens or expressed incompatible BG-A or B in 27% of polyps; one specimen demonstrated BG-B deletion. Precursor expression was not found in HPs but was frequently observed in APs. Reappearance of ABH in distal polyps was significantly correlated with increasing grade of dysplasia, but was not significantly correlated with polyp size or histological type. With respect to Lewis antigen expression, Lewisb reappearance occurred in almost every distal polyp, and Lewisa-Lewisb coexpression was also quite common. Lea deletion was frequently noted, especially in HP, but the significance of this finding is unclear. This study indicates that several antigenic alterations that occur in colorectal cancer tissues also appear in premalignant polyps, and often in early stages of the neoplastic process. The observation that incompatible expression of BG-A or B occurs only in AP and cancer tissues (as well as mucosa adjacent to cancer) but not in fetal colonic mucosa, adult normal colonic mucosa, or HP, suggests that this may be a cancer-specific phenomenon.


Influence of resistance breeding in common bean on rhizosphere microbiome composition and function.
The rhizosphere microbiome has a key role in plant growth and health, providing a first line of defense against root infections by soil-borne pathogens. Here, we investigated the composition and metabolic potential of the rhizobacterial community of different common bean (Phaseolus vulgaris) cultivars with variable levels of resistance to the fungal root pathogen Fusarium oxysporum (Fox). For the different bean cultivars grown in two soils with contrasting physicochemical properties and microbial diversity, rhizobacterial abundance was positively correlated with Fox resistance. Pseudomonadaceae, bacillaceae, solibacteraceae and cytophagaceae were more abundant in the rhizosphere of the Fox-resistant cultivar. Network analyses showed a modular topology of the rhizosphere microbiome of the Fox-resistant cultivar, suggesting a more complex and highly connected bacterial community than in the rhizosphere of the Fox-susceptible cultivar. Metagenome analyses further revealed that specific functional traits such as protein secretion systems and biosynthesis genes of antifungal phenazines and rhamnolipids were more abundant in the rhizobacterial community of the Fox-resistant cultivar. Our findings suggest that breeding for Fox resistance in common bean may have co-selected for other unknown plant traits that support a higher abundance of specific beneficial bacterial families in the rhizosphere with functional traits that reinforce the first line of defense.


Evil, Constructed: A Salient Part of an Emerging Spiritual Veteran Identity.
This article investigated constructions of evil among deployed Swedish veterans. Six cases were used to demonstrate common themes of these constructions: humans are capable of everything; anyone can be violated, even killed; evil and cruelty comes in many forms; coldness/cynicism; exhausting to witness suffering and pain; and existential rumination. The impact of these can affect a veteran's identity and their notions of self. However, processing encounters with evil is seen, in some Christian perspectives, as an essential prerequisite for spiritual growth, and this might be potentially important to supporting the emergence of spiritual veteran identities. A pastoral care giver or military chaplain can serve as an existential conversation partner who can assist veterans when approaching such experiences and their potential impact. This may be especially fertile in secular contexts, where pastoral wisdom and ontological approaches can be hard to find in the everyday lives of veterans.


Effects of a Ginkgo biloba extract on two models of cortical hemiplegia in rats.
To screen drugs potentially useful in the pharmacological treatment of subjects with brain lesions, we studied the effects of chronic (7 and 30 days) treatments with a Ginkgo biloba extract (EGb761-IPSEN; EGb) in two animal models of cortical hemiplegia: one induced by motor cortex aspiration and another using a reversible inactivation of the motor cortex through chronic, localized infusion of y-aminobutyric acid (GABA), via osmotic minipumps. The elevated beam test was used in water-deprived animals trained to drink saccharin-sweetened solutions (with or without EGb) and to perform to criteria before the surgical procedures. From the day after surgery, the rats were administered 100 mg/kg of EGb daily for 7 or 30 days. In all groups with motor impairment in which the extract was administered, a faster and more complete recovery was observed, which was significantly different from that of rats which received only saccharin solutions. The salutary effect of EGb was more marked in ablation-induced hemiplegia than in the GABA-treated group. In the former injury model, EGb-treated animals had smaller ventricular diameters than non-treated rats. No differences concerning sensory deficits were detected among groups. EGb was also acutely administered during the epileptic syndrome that follows interruption of chronic GABA infusions (the GABA-withdrawal syndrome). No anticonvulsant effects of EGb were observed. These results suggest a potential use of EGb in brain-injured patients as this product shows little toxicity in animals and man after chronic administration. The active principles among terpenes (ginkgolides, bilobalides and flavonolheterosides present in the EGb) and the mechanisms for this beneficial effects remain to be elucidated.


[Making progress in the use of health policies and practices informed by evidence: the Piripiri-Piauí experience].
Evidence-informed decision making (EIDM) can optimize health services and systems. EIDM involves defining problems, identifying measures to tackle them, assessing the quality of global and local evidence and translating it for the main stakeholders in line with social values and laws. Brazil encourages the use of EIDM in health policy in Piripiri, a municipality of 61,840 inhabitants in the country's poorest region, and launched Brazil's first Evidence Use in Health Care (NEv) center in 2010. The development and preliminary results of the NEv center are reported and its vision, composition, mandate, and activities are presented. The NEv center experience has the support of the Evidence-Informed Policy Network, the Latin American and Caribbean Center of Information on Health Sciences and federal and municipal governments. The decentralization of financing and the provision of healthcare services, the expansion of EIDM in management, and the local political context illustrate the progress of the experiment. Its activities include the production and dissemination of deliberative briefs and dialogues with opinion shapers, workers and health service users. Monitoring and evaluation are underway and the results will help to broaden the scale of activities in Brazil and abroad.


Pharmacokinetic model-driven infusion of fentanyl: assessment of accuracy.
Computer-assisted continuous infusion (CACI) is a pharmacokinetic model-driven infusion device that enables physicians to administer intravenous (iv) drugs in a quantitative fashion, specifying a theoretical blood or plasma concentration. This study evaluated the accuracy of CACI administration of fentanyl using a newly developed CACI device programmed with a well-known set of pharmacokinetic parameters for fentanyl. Patients received diazepam 1 or 2 h before surgery. Anesthesia was induced by a combination of 70% N2O and fentanyl administered by CACI to a predicted concentration of 15-25 ng.ml-1. After neuromuscular blockade and tracheal intubation, the desired plasma fentanyl concentration (setpoint) entered into CACI was 3-6 ng.ml-1, and then the setpoint fentanyl concentration was titrated according to strict criteria of adequate or inadequate anesthesia. Plasma samples for subsequent assay of fentanyl concentration then were taken: at predefined stimuli, when inadequate anesthesia occurred, or 5 min before an anticipated decrease in the fentanyl setpoint. The predictive accuracy of CACI was assessed by calculating for each patient the tenth, 50th, and 90th percentile of the performance error and absolute performance error from each measured and predicted plasma sample pair. Cumulative probability functions for each of these were then plotted. Precision was defined as the dispersion of the tenth to 90th percentile of the median percent performance error for the population and was found to be -31-26%. The median population performance error was -4%, and the median population absolute performance error was 21%.(ABSTRACT TRUNCATED AT 250 WORDS)


[Proposal of a novel dosing schedule of docetaxel by using alpha1-acid glycoprotein as an index].
This study was aimed to propose a novel dosing schedule of docetaxel based on alpha(1)-acid glycoprotein (AGP)as an index. For this purpose, we performed Monte Carlo simulation using a population pharmacokinetic/pharmacodynamic (PPK/PPD) model, which we previously developed to estimate the ANC Nadir distribution after docetaxel administration. AGP values, which were incorporated in PPK/PPD, were sampled from normal distributions (S.D. 44, range from 19 to 259), as various mean levels of 125, 150, 175 and 200 (mg/dl). Monte Carlo simulation was conducted using docetaxel doses of 40, 50 and 60 (mg/m(2)) for each AGP distribution. Simulation was performed 200 times, and distributions of ANC Nadir median were obtained from simulations. We accepted a dose when 20 percentile of the distribution of ANC Nadir median was greater than 500 (counts/microl), in order to avoid the grade 4 neutropenia. From the results of simulations, 40, 50, 60 and 60 doses (mg/m(2)) were recommended for 125, 150, 175, and 200 AGP mean (mg/dl) respectively. Secondly, to evaluate this dosing schedule, we adopted these recommended doses to 16 patients whose ANC Nadir observed is lesser than 500, and simulated the ANC Nadir. The number of patients whose simulated time below ANC=500 was higher than 6 days decreased from 8 to 2, implying that this dosing schedule might be effective to avoid neutropenia induced by docetaxel. In conclusion, we proposed a novel dosing schedule of docetaxel using AGP as an index, which might be effective to avoid neutropenia induced by docetaxel.


Virtual reality simulators for dermatologic surgery: measuring their validity as a teaching tool.
Surgical simulation is increasingly being considered for training, testing, and possibly credentialing in medicine and surgery. At the University of Washington we have been developing a virtual reality (VR) suturing simulator. In the course of development it must be realized that expensive new technologies should bear the burden of proof of their effectiveness and reliability before they are put into training programs. The purpose of this article is to define the concept of surgical skill and to discuss how it can be measured in the context of validating VR surgical simulators. Specific measures of validity and reliability are reviewed and discussed.


Modulation of postjunctional alpha-adrenergic responsiveness by local changes in temperature.
In canine cutaneous veins, local moderate warming (37 degrees-41 degrees C) augments the responsiveness to postjunctional alpha 1-adrenergic stimulation but depresses that to postjunctional alpha 2-adrenergic activation. Moderate cooling (37 degrees-24 degrees C) has the opposite effect. The effects of warming and cooling on alpha 1-adrenergic responses are buffered by a large receptor reserve, allowing for the predominance of alterations in alpha 2-adrenergic responsiveness.


Effects of multiple daily nicotine administrations on pre- and post-nicotine circadian activity episodes in rats.
Administration of a single daily dose of nicotine has been shown to entrain circadian activity episodes both preceding and following the administration time that persist for several days after drug administration ceases. The present study tested the effects of multiple daily nicotine administrations on circadian activity episodes in adult female rats kept under constant light and rate-limited food access. Eight rats received 7 separate 7-day nicotine injection series, each followed by a 3-day test phase without injections. Subcutaneous nicotine was administered once a day during the 1st and 7th series, twice daily during the 2nd and 6th series, three times daily during the 3rd and 5th series, and four times daily during the 4th series. To control the cumulative daily dose throughout the study, 1.0 mg/kg nicotine was evenly divided among the injections within a single day. Pre- and post-administration effects of nicotine declined across the day, and significant entrainment of both pre- and post-nicotine episodes occurred for only one daily injection in each series. Additionally, post-nicotine episodes showed a different dose-response curve than the pre-nicotine episodes: post-nicotine wheel turns increased as the dose decreased, whereas pre-nicotine wheel turns remained relatively constant as the dose changed. These results provide evidence that nicotine-induced circadian entrainment to a single administration time does occur when the drug is administered multiple times a day, and pre- and post-nicotine circadian episodes are mediated at least partially by separate mechanisms.


Single nucleotide polymorphisms in K(ATP) channels: muscular impact on type 2 diabetes.
ATP-sensitive K+ channels (K(ATP) channels) play an important role in glucose homeostasis. A single nucleotide polymorphism (SNP) in the Kir6.2 subunit causes a point mutation of Glu23 to lysine and reduces the ATP sensitivity of pancreatic K(ATP) channels. The SNP found in 58% of Caucasians accounts for 15% of type 2 diabetes. Here we show evidence for dysregulations of muscular K(ATP) channels with the E23K variation. We were particularly interested in the channel modulation by intracellular protons, as pH changes widely and frequently in skeletal muscles. Surprisingly, we found that the defect of the E23K variant was more related to pH than ATP. A level of intracellular acidification seen during exercise not only activated the E23K channel more readily than the wild type, but also relieved the channel inhibition by ATP, leading to a vast increase in the channel open-state probability by approximately sevenfold at pH 6.8 over the wild-type channel at pH 7.4. Considering the reduction in sarcolemmal excitability, muscle fatigue, and impairment of muscular glucose uptake found previously by genetically disrupting K(ATP) channels, it is likely that the E23K variant in muscular K(ATP) channels affects systemic glucose homeostasis and poses an important risk factor for type 2 diabetes and obesity.


Glaciological Mass balance of Znosko Glacier, King George Island.
The present article objective is to determine the net mass balance of the glacier Znosko for periods 2018-2019 and 2019-2020. It is situated on King George Island which belongs to the groups Shetland of the South, Antarctic Peninsula region. For this objective, during February 2018 a net of 19 stakes (which were controlled once during February 2019 and 2020) were installed on the glacier ablation zone, drilling in the accumulation zone and about flights using unmanned aerial vehicles (UAV) to control the glacier zone and geomorphological changes. For the year 2020, it was determined a glacier area of 1.71 ± 0.02 km2, moreover, using five different methods of interpolation, it was obtained on average, as a result, a specific net balance of -590.7 ± 46.6 mm w.e (in water equivalent) for 2018-2019 and -686.7 ± 28.2 mm w.e for 2019-2020, being the ELA altitude 146.5 ± 18.2 m and 144.2 ± 8.3 m respectively. The two consecutive years represent negative net mass balances which are in accordance with other similar studies on this region, also glacier data were obtained on a zone that is characterized by its difficult access.


Wastewater Purification with Nutrient and Carbon Recovery in a Mobile Resource Container.
Water reuse from wastewater treatment plants can significantly reduce freshwater demand. Additionally municipal sewage and some industrial wastewaters could be used as sources of nutrients and carbon more effectively than they are used today. Biological treatments have attracted the most attention in wastewater purification, whereas, so far, only a little attention has been paid to the physico-chemical technologies. These technologies could, however, have great potential to recover nutrients when purifying wastewater. In this study, the main emphasis was to study the possibilities to utilize existing physico-chemical unit operations for wastewater purification and nutrients as well as carbon recovery. Unit operations were selected so that they could produce exploitable circular economy products from wastewaters and be assembled in a mobile container for carrying out recovery anywhere that is suitable. The results showed that in a mobile container, solids could be successfully separated from the studied wastewaters by flocculation-assisted solid/liquid separation and then processed into hydrochar by hydrothermal carbonization. Phosphate was precipitated using lime milk as calcium phosphate, and ammonium nitrogen was captured from the wastewater using membrane contactor technology resulting in ammonium sulphate for fertilizer use. Additionally, reverse osmosis retained residual impurities well, producing good quality water for reuse. The techno-economic feasibility seems promising.


Acute In Vivo Administration of Compound 21 Stimulates Akt and ERK1/2 Phosphorylation in Mouse Heart and Adipose Tissue.
The angiotensin II type 2 (AT2) receptor has a role in promoting insulin sensitivity. However, the mechanisms underlying the AT2 receptor-induced facilitation of insulin are still not completely understood. Therefore, we investigated whether acute in vivo administration of AT2 receptor agonist compound 21 (C21) could activate insulin signaling molecules in insulin-target tissues. We report that, in male C57BL/6 mice, an acute (5 min, 0.25 mg/kg; i.v.) injection of C21 induces the phosphorylation of Akt and ERK1/2 at activating residues (Ser473 and Thr202/Tyr204, respectively) in both epididymal white adipose tissue (WAT) and heart tissue. In WAT, the extent of phosphorylation (p) of Akt and ERK1/2 induced by C21 was approximately 65% of the level detected after a bolus injection of a dose of insulin known to induce maximal activation of the insulin receptor (IR). In the heart, C21 stimulated p-Akt to a lesser extent than in WAT and stimulated p-ERK1/2 to similar levels to those attained by insulin administration. C21 did not modify p-IR levels in either tissue. We conclude that in vivo injection of the AT2 receptor agonist C21 activates Akt and ERK1/2 through a mechanism that does not involve the IR, indicating the participation of these enzymes in AT2R-mediated signaling.


Percutaneous absorption of thirty-eight organic solvents in vitro using pig skin.
Percutaneous absorption is highly variable between chemicals but also within chemicals depending on exposure conditions and experimental set up. We tested a larger number of organic solvents with the same experimental set up, using skin from new-born piglets and static diffusion cells. Thirty-six common organic solvents were studied neat (and 31 of them also in water dilution): acetone, acetonitrile, n-butanol 2-butanone 2-butoxyethanol, 1-butoxy-2-propanol, n-butyl acetate, butyl acrylate, cyclohexane, cyclohexanone, 1,2-dichloroethane, dichloromethane, ethanol, 2-ethoxyethanol, ethyl acetate, ethyl acrylate, ethylbenzene, furfuryl alcohol, n-hexane, 2-hexanone, 2-isopropoxyethanol, methanol, 1-methoxy-2-propanol, methyl acrylate, 3-methyl-1-butanol, methyl tertiary butyl ether, 4-metyl-2-pentanol, methyl methacrylate, 2-propanol, 2-propen-1-ol, 2-propoxyethanol, 1-propoxy-2-propanol, styrene, trichloromethane, toluene and m-xylene. In addition, a mixture of 2-methylbutyl acetate and n-pentyl acetate was tested. For most of the solvents, little or no percutaneous absorption data have been published. Lag times, steady-state fluxes and apparent permeability coefficients were obtained from the time courses of solvent appearance in the receptor medium, as measured by gas chromatography. The use of the same methodology and kind of skin resulted in small variability within experiments, underlining the need for consistent methodology for useful results for developing predictive models. Furthermore, a comparison of the neat and diluted data shows that water dilution affects all these variables and that the direction and magnitude of the effects vary between chemicals. This comparison strongly supports that prediction of percutaneous absorption of neat and water diluted chemicals requires different models.


Porcine xenografts in Parkinson's disease and Huntington's disease patients: preliminary results.
The observation that fetal neurons are able to survive and function when transplanted into the adult brain fostered the development of cellular therapy as a promising approach to achieve neuronal replacement for treatment of diseases of the adult central nervous system. This approach has been demonstrated to be efficacious in patients with Parkinson's disease after transplantation of human fetal neurons. The use of human fetal tissue is limited by ethical, infectious, regulatory, and practical concerns. Other mammalian fetal neural tissue could serve as an alternative cell source. Pigs are a reasonable source of fetal neuronal tissue because of their brain size, large litters, and the extensive experience in rearing them in captivity under controlled conditions. In Phase I studies porcine fetal neural cells grafted unilaterally into Parkinson's disease (PD) and Huntington's disease (HD) patients are being evaluated for safety and efficacy. Clinical improvement of 19% has been observed in the Unified Parkinson's Disease Rating Scale "off" state scores in 10 PD patients assessed 12 months after unilateral striatal transplantation of 12 million fetal porcine ventral mesencephalic (VM) cells. Several patients have improved more than 30%. In a single autopsied PD patient some porcine fetal VM cells were observed to survive 7 months after transplantation. Twelve HD patients have shown a favorable safety profile and no change in total functional capacity score 1 year after unilateral striatal placement of up to 24 million fetal porcine striatal cells. Xenotransplantation of fetal porcine neurons is a promising approach to delivery of healthy neurons to the CNS. The major challenges to the successful use of xenogeneic fetal neuronal cells in neurodegenerative diseases appear to be minimizing immune-mediated rejection, management of the risk of xenotic (cross-species) infections, and the accurate assessment of clinical outcome of diseases that are slowly progressive.


Large A-V fistula: pathophysiological consequences and therapeutic perspectives.
Large Arteriovenous Fistulae (AVF) can increase cardiac output. This may result in the development of congestive heart failure, a clinical situation associated with increased activity of Vasoconstrictor neurohormonal systems: the Renin-angiotensin system (RAS), Sympathetic nervous system (SNS), the Endothelin system and Arginine vasopressin (AVP). At the same time there is compensatory activation of systemic and vasodilating systems: Atrial natriuretic peptide (ANP) and Nitric oxide (NO). Previous data from our laboratory and other groups suggest that urinary sodium excretion in this situation is largely determined by the balance between two antagonistic hormonal systems: the vasoconstrictor/sodium-retaining factors such as RAS, endothelin, and SNS, and vasodilatory/natriuretic substances such as ANP and NO. In decompensated patients, enhanced activities of the sodium-retaining systems overwhelm the effects of vasodilatory/natriuretic systems, which lead to a net reduction in sodium and water excretion. For compensation to occur, the effects of natriuretic mechanisms must prevail over those of the opposing systems, resulting in renal sodium/water excretion. This notion is supported by clinical and experimental studies where pharmacological intervention corrected the imbalance present in AVF. Thus, a shift in the balance in favor of natriuresis may be achieved either by increasing the activity of natriuretic factors or reducing the influence of the antinatriuretic systems. Based on that, the use of angiotensin converting enzyme (ACE) inhibitors and/or angiotensin II (ATII) blockers may be beneficial in the management of patients with large AVF.


Reading difficulty after stroke: ocular and non ocular causes.
Ocular causes of reading impairment following stroke include visual field loss, eye movement impairment and poor central vision. Non ocular causes may include cognitive errors or language impairment. The purpose of this study was to identify all patients referred with suspected visual impairment who had reported reading difficulty to establish the prevalence of ocular and non ocular causes. Prospective, multicentre, observation study with standardised referral and assessment forms across 21 sites. Visual assessment included visual acuity measurement, visual field assessment, ocular alignment, and movement and visual inattention assessment. Multicentre ethical approval and informed patient consent were obtained. A total of 915 patients were recruited, with a mean age of 69·18 years (standard deviation 14·19). Reading difficulties were reported by 177 patients (19·3%), with reading difficulty as the only symptom in 39 patients. Fifteen patients had normal visual assessment but with a diagnosis of expressive or receptive aphasia. Eight patients had alexia. One hundred and nine patients had visual field loss, 85 with eye movement abnormality, 27 with low vision and 39 patients with visual perceptual impairment. Eighty-seven patients had multiple ocular diagnoses with combined visual field, eye movement, low vision or inattention problems. All patients with visual impairment were given targeted treatment and/or advice including prisms, occlusion, refraction, low vision aids and scanning exercises. Patients complaining of reading difficulty were mostly found to have visual impairment relating to low vision, eye movement or visual field loss. A small number were found to have non ocular causes of reading difficulty. Treatment or advice was possible for all patients with visual impairment.


A prospect on the use of antiviral drugs to control local outbreaks of COVID-19.
Current outbreaks of COVID-19 are threatening the health care systems of several countries around the world. Control measures, based on isolation, contact tracing, and quarantine, can decrease and delay the burden of the ongoing epidemic. With respect to the ongoing COVID-19 epidemic, recent modeling work shows that these interventions may be inadequate to control local outbreaks, even when perfect isolation is assumed. The effect of infectiousness prior to symptom onset combined with asymptomatic infectees further complicates the use of contact tracing. We aim to study whether antivirals, which decrease the viral load and reduce infectiousness, could be integrated into control measures in order to augment the feasibility of controlling the epidemic. Using a simulation-based model of viral transmission, we tested the efficacy of different intervention measures to control local COVID-19 outbreaks. For individuals that were identified through contact tracing, we evaluate two procedures: monitoring individuals for symptoms onset and testing of individuals. Additionally, we investigate the implementation of an antiviral compound combined with the contact tracing process. For an infectious disease in which asymptomatic and presymptomatic infections are plausible, an intervention measure based on contact tracing performs better when combined with testing instead of monitoring, provided that the test is able to detect infections during the incubation period. Antiviral drugs, in combination with contact tracing, quarantine, and isolation, result in a significant decrease of the final size and the peak incidence, and increase the probability that the outbreak will fade out. In all tested scenarios, the model highlights the benefits of control measures based on the testing of traced individuals. In addition, the administration of an antiviral drug, together with quarantine, isolation, and contact tracing, is shown to decrease the spread of the epidemic. This control measure could be an effective strategy to control local and re-emerging outbreaks of COVID-19.


Femtosecond broadband time-resolved fluorescence and transient absorption study of the intramolecular charge transfer state of methyl 4-dimethylaminobenzoate.
A combined application of femtosecond broadband time-resolved fluorescence (fs-TRF), fluorescence anisotropy (fs-TRFA) and fs to microsecond (μs) transient absorption (TA) have been used to probe directly the dynamics, nature, formation and decay paths of the singlet intramolecular charge transfer ((1)ICT) state of methyl 4-dimethylaminobenzoate (1a) in acetonitrile. The result reveals explicit evidence for a common electronic origin (the L(a) nature) of the (1)ICT state and its precursor the locally excited ((1)LE) state to account jointly for the dual florescence known to this system. It also shows that the ICT reaction from the (1)LE to (1)ICT state occurs with time constant of ~0.8 ps and the (1)ICT state formed decays with a ~1.9 ns time constant leading mainly to a ππ* natured triplet state ((3)T(1)). The (3)T(1) then relaxes with a ~4 μs lifetime under deoxygenated condition resulting in full recovery of the ground state (S(0)). As a case study, this work contributes novel experimental data for improved understanding of the mechanism of ICT reaction; it also reveals a distinct deactivation pattern for this prototype para-amino substituted aromatic carbonyl compound in acetonitrile.


Structural basis for the thermostability of ferredoxin from the cyanobacterium Mastigocladus laminosus.
Plant-type ferredoxins (Fds) carry a single [2Fe-2S] cluster and serve as electron acceptors of photosystem I (PSI). The ferredoxin from the thermophilic cyanobacterium Mastigocladus laminosus displays optimal activity at 65 degrees C. In order to reveal the molecular factors that confer thermostability, the crystal structure of M.laminosus Fd (mFd) was determined to 1.25 A resolution and subsequently analyzed in comparison with four similar plant-type mesophilic ferredoxins. The topologies of the plant-type ferredoxins are similar, yet two structural determinants were identified that may account for differences in thermostability, a salt bridge network in the C-terminal region, and the flexible L1,2 loop that increases hydrophobic accessible surface area. These conclusions were verified by three mutations, i.e. substitution of L1,2 into a rigid beta-turn ((Delta)L1,2) and two point mutations (E90S and E96S) that disrupt the salt bridge network at the C-terminal region. All three mutants have shown reduced electron transfer (ET) capabilities and [2Fe-2S] stability at high temperatures in comparison to the wild-type mFd. The results have also provided new insights into the involvement of the L1,2 loop in the Fd interactions with its electron donor, the PSI complex.


The role of a low erythropoietin level for the polycythemia vera diagnosis.
A low erythropoietin (EPO) level is a minor diagnostic criterion for polycythemia vera (PV). Controversies exist regarding the diagnostic value of a low EPO level when considering increasing availability of advanced molecular testing. We assessed the role of low EPO level for PV diagnosis in the context of positive JAK2 mutation status as well as other diagnostic parameters. Of 138 patients, 75 patients had PV and 63 had secondary erythrocytosis. Of the 75 patients with PV, 32% had EPO levels within the normal range. EPO level positively correlated with obesity and smoking status, making it an unreliable diagnostic marker in those patients. Although EPO level below normal as a standalone diagnostic modality was significantly associated with PV (odds ratio [OR] 0.857; p < 0.001), when JAK2V617F mutation status was included in the prediction model, the association of low EPO was not statistically significant (OR 0.962, p = 0.269). Positive JAK2V617F demonstrated a strong predictive value for PV (OR 670.5, p = 0.006) either alone or in combination with other variables. Results show that EPO level is not a reliable diagnostic marker due to physiologic variation in association with obesity and smoking.


Relation of FEV(1) to clinical outcomes during exacerbations of chronic obstructive pulmonary disease. Department of Veterans Affairs Cooperative Study Group.
FEV(1) is an objective measure of airflow obstruction used in clinical practice and in therapeutic trials. The precise relationship of FEV(1) to clinical outcomes is generally uncertain. As part of a randomized trial to assess systemic corticosteroid efficacy, we obtained serial FEV(1) measurements in patients hospitalized for exacerbations of chronic obstructive pulmonary disease (COPD). Over the first 14 Study Days at least one FEV(1) value was obtained in 261 subjects. Sixty-four of these subjects experienced treatment failure, defined as death, intubation, readmission for COPD, or intensification of drug therapy, by Study Day 30. After adjustment, both FEV(1) at entry into the study (odds ratio [OR] for a 100-ml increase, 0.87; 95% confidence interval [CI], 0.79 to 0.96) and change in FEV(1) over the first two Study Days (OR for a 100 ml increase, 0.80; 95% CI, 0.69 to 0.92) predicted treatment failure. We identified no baseline characteristic that was significantly related to FEV(1) at entry into the study. Assignment to the systemic corticosteroid treatment arm was associated with a significantly larger FEV(1) at Study Day two (p = 0.01). We conclude that FEV(1) measurements at admission and over the first several days of hospitalization are highly predictive of clinical outcomes during exacerbations of COPD.


The Albany Two-Way Radio Conferences, 1955-1981: a retrospective look at a program providing interactive continuing medical education at a distance.
Despite early widespread recognition of the necessity of continuing medical education (CME) for practicing physicians and surgeons, medical schools and national medical organizations were slow to mobilize to address the need. One pioneering program, developed by the Albany Medical College in New York, not only provided CME, but did so in a live distance education format that allowed for interaction between the participants and the faculty presenters. The Albany Program commenced in 1955 using what was then state-of-the-art technology; it exemplified principles and practices that can be seen as the precursors for the distance education approaches used to reach physicians today. This short article describes the contributions of the Albany Two-Way Radio Conferences and places them in the context of developments in national organizations and policies in the 20th century.


Preparation of polyetherol-appended sulfur porphyrazines and investigations of peripheral metal ion binding in polar solvents.
We describe the complete synthesis and characterization of a new family of peripherally functionalized porphyrazines (pz's) with four, three, or two (in a trans conformation) bis[thioethoxy(ethoxy)ethanol] moieties appended at the pyrroles. These "polyetherol" groups serve as weak exocyclic binding sites for a number of metal ions and also provide solubility of the pz's in low molecular-weight alcohols and water. Electronic spectra of the modified porphyrazines exhibit distinct changes in the visible region (both absorbance and fluorescence) in response to treatment with Ag+, Pb2+, Cd2+, Cs+, and Ni2+ in solution. Such properties make these compounds intriguing candidates for incorporation into the transducer layers in optically based chemical sensors.


Basic principles and clinical applications of biochemical markers of bone metabolism: biochemical and technical aspects.
The interest in and the need for effective measures to be used in the screening, diagnosis, and follow-up of disorders of connective tissue, bone, and mineral metabolism has markedly grown. Next to clinical and imaging techniques, indices of bone turnover have come to play an important role in the assessment of metabolic bone disease. In osteoporosis, recent research has shown that bone markers may also be used to predict future bone loss and hip fractures (in larger cohorts of older patients), identify individuals at risk for osteoporosis, select therapy, and predict and monitor the therapeutic response in individual patients. The development of new markers of bone metabolism has greatly enriched the spectrum of serum and urine analytes used in the assessment of skeletal pathologies. Besides total alkaline phosphatase, other markers such as bone-specific alkaline phosphatase, osteocalcin, or the collagen propeptides are being used to measure bone formation. Bone resorption, previously assessed only by the measurement of urinary calcium and hydroxyproline, may now be detected more precisely by a number of new serum and urine markers. Among these, the pyridinium crosslinks and the telopeptides of collagen type I are presently considered the most specific markers of bone resorption. More recently, bone sialoprotein has also been suggested as a marker of bone resorption in serum. Tartrate-resistant acid phosphatase is now measurable by immunoassay. This article surveys the biochemistry and relevant technical aspects of the currently available markers of bone metabolism.


Ganciclovir treatment of systemic cytomegalovirus in an immunocompetent host.
Cytomegalovirus (CMV) infects a significant number of otherwise healthy individuals. Although most cases are subclinical and therefore not diagnosed, some patients present with a mononucleosis-type illness. Ganciclovir, an agent effective against CMV, has primarily been studied for use in immunocompromised patients. No formal studies have been done in immunocompetent individuals. We report a case of an otherwise healthy adult female with severe heterophile negative infectious mononucleosis. Her symptoms included high fever, malaise, myalgias, cough, and abdominal pain. Work-up revealed an acute CMV infection. Intravenous ganciclovir was given with dramatic clinical and laboratory improvement.


Short communication: Effects of dietary deoiled soy lecithin supplementation on circulating choline and choline metabolites, and the plasma phospholipid profile in Holstein cows fed palm fat.
Dietary lecithin is a source of choline. Our objective was to evaluate the effects of dietary deoiled soy lecithin feeding on circulating choline, choline metabolites, and the plasma phospholipid profile in lactating dairy cows fed fractionated palm fatty acids. In a split-plot Latin square design, 16 Holstein cows (160 ± 7 d in milk; 3.6 ± 1.2 parity) were randomly allocated to a main plot receiving a corn silage and alfalfa haylage-based diet with palm fat containing either moderate or high palmitic acid content at 1.75% of ration dry matter (moderate and high palmitic acid containing 72 or 99% palmitic acid in fat supplement, respectively; n = 8/palm fat diet). Within each palm fat group, deoiled soy lecithin was top-dressed at 0, 0.12, 0.24, or 0.36% of ration dry matter in a replicated 4 × 4 Latin square design with 14-d experimental periods. A 14-d covariate period was used to acclimate cows to palm fat feeding without lecithin supplementation. Blood sampling occurred during the final 3 d of each experimental period. Plasma choline and choline metabolites were quantified using liquid chromatography and mass spectrometry. Plasma phospholipids were profiled using time-of-flight mass spectrometry. Whereas no effects of treatments were detected for plasma choline or methionine, lecithin feeding increased the plasma concentrations of choline metabolites trimethylamine N-oxide and dimethylglycine (24 and 11%, respectively). Plasma phosphatidylcholine (PC) and sphingomyelin (SM) concentrations increased with deoiled lecithin feeding (e.g., PC 16:0/22:6 and SM d18:1/18:3). Lecithin supplementation also increased plasma lysophosphatidylcholine (LPC) concentrations (e.g., LPC 18:0) while reducing plasma phosphatidylethanolamine (PE) concentrations (e.g., PE 16:0/20:5). Although increases in microbial-derived trimethylamine N-oxide suggest gastrointestinal lecithin degradation, elevations in plasma dimethylglycine, PC, LPC, and SM suggest that choline availability was improved by lecithin feeding in cows, thus supporting enhanced endogenous phospholipid synthesis.


The effect of oral contraceptive use on salivary testosterone concentrations and athlete performance during international field hockey matches.
To investigate the effect of oral contraceptive (OC) use on salivary testosterone (sal-T) concentrations and performance-related statistics in international field hockey matches. A cohort observational study with repeated measures. Twenty-three elite female athletes were monitored across four international field hockey matches over a nine-day period. Salivary T was assessed 45min before each match and several match performance statistics were collated; load (i.e. ratings of perceived exertion×playing time), video-derived positive actions (PA) and negative actions (NA), plus coach and player ratings of performance. The sal-T and match performance profiles of OC (n=7) and Non-OC (n=16) players were compared and predictive relationships tested. Pre-match sal-T concentrations were 35% higher in the Non-OC than the OC group (p=0.001), representing a large effect size (ES) difference of 0.96. The OC and Non-OC groups did not differ on any performance statistic (p≥0.348) with ES differences from -0.22 to 0.11. Salivary T was positively related to the number of PA during match play (p=0.017). Additional linkage between sal-T and NA emerged, but with opposing slopes (p=0.008) in the OC (B=-1.783, p=0.030) and Non-OC (B=0.692, p=0.127) groups. OC usage by elite women athletes was accompanied by lower sal-T concentrations, but the performance outputs of the OC and Non-OC groups were similar. This suggests that the T differences had no impact on match performance. On an individual (population-averaged) level, sal-T was associated with PA and NA during these matches, though the response curves predicting NA differed for OC and Non-OC athletes.


Engaging Cold to Upregulate Cell Proliferation in Alginate-Encapsulated Liver Spheroids.
For many years, the impact of hyper- and hypothermia on mammalian cells has been examined. With the exception of short, low temperature storage, which has uses in areas such as preservation for transplantation or regenerative medicine, advantages for the use of low temperature treatment in hepatocytes have not been previously reported. We have observed that alginate-encapsulated HepG2 liver spheroids that are cryopreserved or experience a cold reduction in temperature (≤10°C) for periods between 1 and 90 min display an enhanced cell proliferation during culture 7-16 days post-treatment compared with untreated samples. Following 8-12 days post-treatment, alginate-encapsulated liver spheroids experienced a cell density of 1.71 ± 0.35 times that of control samples (p < 0.001). This effect occurred in samples with a variety of cold treatments. This low temperature treatment offers a simple method to rapidly increase cell proliferation rates for extended culture systems, such as bioartificial liver devices. This would allow the manufacture of required biomass more rapidly, and to a higher cell density, reducing final required biomass volume. This could enable bioartificial liver devices to be prepared more cheaply, making them a more cost effective treatment.


Tuberculosis of the sternum and clavicle: imaging findings in 15 patients.
To describe the imaging findings in sterno-clavicular tubercular involvement. Fifteen patients with pathologically proven tuberculosis of the sternum and clavicle were retrospectively evaluated. Routine radiography, computed tomography (CT) and magnetic resonance imaging (MRI) were used in some or all of the patients. Clinical information and imaging features were evaluated in each case. Eight patients had sternoclavicular joint (SCJ) involvement, five had isolated sternal involvement and two had isolated clavicular involvement. Seven patients were evaluated with only CT, six with only MRI and two with both. There were eight male and seven female patients, varying in age between 16 and 78 years. Fever, swelling and pain were common presenting symptoms. Two patients were HIV positive. Radiographs were positive in only eight patients. Destruction and signal intensity (SI) changes of the sternum and clavicle, destruction of the cartilage, soft tissue changes representing granulation tissue/abscess, displacement of the adjacent structures (vessels, trachea, etc.) and inflammatory changes in the adjacent structures in the form of cellulitis and myositis were common imaging features. All imaging methods can provide complementary information regarding sterno-clavicular tubercular involvement that is helpful for determination of the therapy. MRI is useful in determining the extent of the lesion, particularly marrow involvement and soft tissue extent.


Nucleolin modulates compartmentalization and dynamics of histone 2B-ECFP in the nucleolus.
Eukaryotic cells have 2 to 3 discrete nucleoli required for ribosome synthesis. Nucleoli are phase separated nuclear sub-organelles. Here we examined the role of nuclear Lamins and nucleolar factors in modulating the compartmentalization and dynamics of histone 2B (H2B-ECFP) in the nucleolus. Live imaging and Fluorescence Recovery After Photobleaching (FRAP) of labelled H2B, showed that the depletion of Lamin B1, Fibrillarin (FBL) or Nucleostemin (GNL3), enhances H2B-ECFP mobility in the nucleolus. Furthermore, Nucleolin knockdown significantly decreases H2B-ECFP compartmentalization in the nucleolus, while H2B-ECFP residence and mobility in the nucleolus was prolonged upon Nucleolin overexpression. Co-expression of N-terminal and RNA binding domain (RBD) deletion mutants of Nucleolin or inhibiting 45S rRNA synthesis reduces the sequestration of H2B-ECFP in the nucleolus. Taken together, these studies reveal a crucial role of Nucleolin-rRNA complex in modulating the compartmentalization, stability and dynamics of H2B within the nucleolus.


Posttraumatic stress disorder and self-reported physical health status among U.S. Military personnel serving during the Gulf War period: a population-based study.
The objective of this study was to investigate the relation between posttraumatic stress disorder (PTSD) and perceived physical health. Participants included 3,682 Gulf War veterans and control subjects of the same era who completed a telephone survey about their health status. PTSD was assessed using the PTSD Checklist-Military Version. Veterans screening positive for PTSD reported significantly more physical health symptoms and medical conditions than did veterans without PTSD. They were also more likely to rate their health status as fair or poor and to report lower levels of health-related quality of life. The results of this study are consistent with studies of other combat veterans and provide further support for an association between PTSD and adverse physical health outcomes. Stressful or traumatic life events, such as those encountered during a rapid military deployment and conflict, are associated with a variety of adverse health effects. These health effects may manifest themselves in both psychological and physical outcomes. Health care providers must be attentive to recognize and evaluate both of these dimensions.


Vitamin D, effects on brain development, adult brain function and the links between low levels of vitamin D and neuropsychiatric disease.
Increasingly vitamin D deficiency is being associated with a number of psychiatric conditions. In particular for disorders with a developmental basis, such as autistic spectrum disorder and schizophrenia the neurobiological plausibility of this association is strengthened by the preclinical data indicating vitamin D deficiency in early life affects neuronal differentiation, axonal connectivity, dopamine ontogeny and brain structure and function. More recently epidemiological associations have been made between low vitamin D and psychiatric disorders not typically associated with abnormalities in brain development such as depression and Alzheimer's disease. Once again the preclinical findings revealing that vitamin D can regulate catecholamine levels and protect against specific Alzheimer-like pathology increase the plausibility of this link. In this review we have attempted to integrate this clinical epidemiology with potential vitamin D-mediated basic mechanisms. Throughout the review we have highlighted areas where we think future research should focus.


Newer aspects of inflammatory bowel disease and its cutaneous manifestations: a selective review.
Idiopathic inflammatory bowel disease (IBD) denotes several types of gastrointestinal disorders characterized by protracted inflammation of the large or small bowel, and a tendency toward relapse or recurrence. The two major groups of IBD are identified as chronic nonspecific ulcerative colitis (UC) and Crohn's disease (CD). Extraintestinal manifestations of IBD are diverse and may antedate, occur with, or postdate the onset of the disease process itself. Cutaneous diseases such as erythema nodosum or pyoderma gangrenosum are not infrequent, and test the clinician's ability to recognize the underlying bowel pathology and institute appropriate treatment. This selective review will address the immunological pathogenesis of IBD, new or rarely reported skin markers in IBD, drug therapy and side effects, zinc deficiency, management of osteotomy patients, and cutaneous cancer complicating IBD. Although the prognosis of IBD has improved, the role of the dermatologist as a consultant remains invaluable in reducing the attendant cutaneous morbidity.


Results of a multicenter open-label randomized trial evaluating infusion duration of zoledronic acid in multiple myeloma patients (the ZMAX trial).
Zoledronic acid, an intravenous (IV) bisphosphonate, is a standard treatment for multiple myeloma (MM) but may exacerbate preexisting renal dysfunction. The incidence of zoledronic acid-induced renal dysfunction may correlate with infusion duration. In this randomized, multicenter, open-label study, 176 patients with MM, at least one bone lesion, and stable renal function with a serum creatinine (SCr) level < 3 mg/dL received zoledronic acid 4 mg (in 250 mL) as a 15- or 30-minute IV infusion every 3-4 weeks. At month 12, 20% (17 patients) in the 15-minute and 16% (13 patients) in the 30-minute arm experienced a clinically relevant but nonsignificant SCr-level increase (P = 0.44). By 24 months, the proportion of patients with a clinically relevant SCr-level increase was similar between arms (15-minute 28% [24 patients] vs 30-minute 27% [23 patients], P = 0.9014). Median zoledronic acid end-of-infusion concentrations were higher with the shorter infusion (15-minute 249 ng/mL vs 30-minute 172 ng/mL), and prolonging the infusion beyond 15 minutes did not influence adverse events related to zoledronic acid. For patients with MM, the safety profile of IV zoledronic acid is similar between those receiving a 15- or 30-minute infusion; therefore, determining the appropriate infusion duration of zoledronic acid should be based on individual patient considerations.


Predicting Chikungunya disease personal protective behaviors: Results of a cross-sectional survey of US-Caribbean travelers.
Background: Incidents of vector-borne disease have recently tripled in the United States. Chikungunya disease is a particularly common disease in the Caribbean, posing a threat to international tourists. However, the relationship between psychological variables derived from the protection motivation theory (PMT), and adoption of protective behaviors against the disease, is uncertain. This study sought to identify the psychological predictors of travelers' protective health behaviors, specifically (1) appropriate clothing use, and (2) indoor spatial repellent use. Methods: An online, retrospective survey of U.S. international travelers to Caribbean destinations measured the five constructs of the PMT in the context of Chikungunya disease: Perceived severity, perceived vulnerability, perceived response efficacy, perceived self-efficacy, and knowledge. Hierarchical logistic regression analyzed whether these five theoretical constructs predicted the two protective behaviors in respondents who met study criteria (n = 184). Results: Results suggest that the interaction between chikungunya knowledge and perceived chikungunya severity predicts both appropriate clothing use (odds ratio [OR]: 1.95, CI: 1.18-3.25, P =0.010) and indoor spatial repellent use (OR: 1.55, CI: 1.05-2.29, P =0.029). In the cases of appropriate clothing use, the interaction between perceived chikungunya severity and perceived vulnerability was also a significant predictor (OR: 9.67, CI:1.23-75.80, P =0.031). Additionally, indoor spatial repellent use was also predicted by the interaction of chikungunya knowledge and perceived vulnerability (OR: 1.88, CI:1.18-3.02, P =0.009). Conclusion : Two-pronged educational approaches may be most efficacious in increasing protective health behaviors. Such efforts could reduce incidents of chikungunya disease and other vectorborne diseases in travel destinations featuring high exposure risks.


Reduced DNA repair during differentiation of a myogenic cell line.
Repair synthesis induced by 4-nitroquinoline-1-oxide (4NQO) in L6 myoblasts before and after cellular fusion was measured by [3H] thymidine incorporation into unreplicated DNA. The level of repair synthesis was reuced after the cells had fused into myotubes. The terminal addition of radioactive nucleotides into DNA strands occurred only to a minor extent, and the dilution of [3H] thymidine by intracellular nucleotide pools was shown not to be responsible for the observed difference in repair synthesis, Both the initial rate and the overall incorporation of [3H] thymidine were found to be 50% lower in the myotubes. 4NQO treatment of myoblasts and myotubes induced modifications in the DNA which were observed as single-strand breaks during alkaline sucrose sedimentation. After the myoblasts were allowed a post-treatment incubation, most of the single-strand breaks were not longer apparent. In contrast, a post-treatment incubation of myotubes did not change the extent of single-strand breakage seen. Both myoblasts and myotubes were equally effective in repairing single-strand breaks induced by X radiation. It would appear that when myoblasts fuse, a repair enzyme activity is lost, probably an endonuclease that recognizes one of the 4 NQO modifications of DNA. The result observed is a partial loss of repair synthetic ability and a complete loss of ability to remove the modification that appears as a single-strand break in alkali.


A study of tribendimidine effects in vitro and in vivo on the liver fluke Opisthorchis felineus.
The food-borne liver fluke Opisthorchis felineus is an epidemiologically important species and the causative agent of opisthorchiasis across an extensive territory of Eurasia. For decades, treatment of opisthorchiasis has been based on praziquantel. Tribendimidine could be an alternative drug that has been successfully tested for Opisthorchis viverrini and Clonorchis sinensis infections. We aimed to assess tribendimidine effects in comparison with praziquantel in vivo and in vitro against the liver fluke Opisthorchis felineus. In this study we (i) calculated half-maximal inhibitory concentrations (IC50) by motility tests against O. felineus adults and newly excysted metacercarie after tribendimidine treatment in vitro; (ii) determined whether tribendimidine and PZQ effects on adult liver flukes are dependent on or mediated by white blood cells; and (iii) tested in vivo the anthelmintic activity of tribendimidine on juvenile and adult worms. We found that the efficiency of tribendimidine in vitro was similar (IC50 = 0.23 μM for newly excysted metacercariae and 0.19 μM for adult worms) to that of praziquantel (IC50 0.98 μM for newly excysted metacercariae and 0.47 μM for adult worms). The treatment of adult worms in vivo with praziquantel or tribendimidine at 400 mg/kg resulted in a 76% and 77.2% reduction, respectively, in the worm burden during chronic infection. The differences between WBR values after PZQ and TBN treatment were not significant, thus tribendimidine was as effective as praziquantel against O. felineus liver flukes. Given the broad-spectrum activity of tribendimidine and efficacy against O. felineus, this drug may be a promising candidate for the treatment of opisthorchiasis felinea and other liver fluke infections.


A-type and B-type Epstein-Barr virus differ in their ability to spontaneously enter the lytic cycle.
In this study replication of A-type and B-type Epstein-Barr virus (EBV) strains has been assessed. A-type and B-type type lymphoblastoid cell lines (LCLs) were established by infecting B lymphocytes, isolated from five EBV-seropositive donors, with different A-type and B-type virus isolates. The presence of viral capsid antigens (VCA) in these LCLs was determined by immunofluoresence assay and by immunoblotting. All of the B-type EBV strains were capable of spontaneously generating virus regardless of the origin of the donor cells. In contrast the A-type strains, other than strain IARC-BL36, did not readily produce VCA in any of the different donor lymphocytes used. This study demonstrates another biological difference between the two virus types: their ability to spontaneously enter the lytic cycle.


Spatiotemporal heterogeneity of CNS radial glial cells and their transition to restricted precursors.
Radial glia are among the first cells that develop in the embryonic central nervous system. They are progenitors of glia and neurons but their relationship with restricted precursors that are also derived from neuroepithelia is unclear. To clarify this issue, we analyzed expression of cell type specific markers (BLBP for radial glia, 5A5/E-NCAM for neuronal precursors and A2B5 for glial precursors) on cortical radial glia in vivo and their progeny in vitro. Clones of cortical cells initially expressing only BLBP gave rise to cells that were A2B5+ and eventually lost BLBP expression in vitro. BLBP is expressed in the rat neuroepithelium as early as E12.5 when there is little or no staining for A2B5 and 5A5. In E13.5-15.5 forebrain, A2B5 is spatially restricted co-localizing with a subset of the BLBP+ radial glia. Analysis of cells isolated acutely from embryonic cortices confirmed that BLBP expression could appear without, or together with, A2B5 or 5A5. The numbers of BLBP+/5A5+ cells decreased during neurogenesis while the numbers of BLBP+/A2B5+ cells remained high through the beginning of gliogenesis. The combined results demonstrate that spatially restricted subpopulations of radial glia along the dorsal-ventral axis acquire different markers for neuronal or glial precursors during CNS development.


Hierarchical nanostructures of metal oxides for enhancing charge separation and transport in photoelectrochemical solar energy conversion systems.
Photoelectrochemical solar energy conversion systems, including photoelectrochemical water splitting and photoelectrochemical solar cells (dye-sensitized solar cells, DSSCs), are under intensive development aiming at efficiently harvesting and utilizing solar energy. Metal oxides carved into hierarchical nanostructures are thought to be promising for improving photoelectrochemical performance by enhancing charge separation and transport. Herein, we review the recent progress in the research on the design and applications of metal oxide hierarchical nanostructures in water splitting and DSSC systems with a view to understanding how they improve the device performance in terms of enhanced charge separation and transport properties. This review will end with a conclusion on metal oxide hierarchical nanostructures together with potential future research directions thereof.


Enhancing hydrophobicity, strength and UV shielding capacity of starch film via novel co-cross-linking in neutral conditions.
Starch films are developed as the biodegradable packaging materials to replace the petroleum-based materials in recent years. Thus, it is extremely beneficial to improve the hydrophobicity and mechanical strength of starch films, through a novel approach of co-cross-linking in neutral conditions, with glyoxal and AZC. In this work, systematic studies have been conducted to assess the performance of the co-cross-linked starch along with the control starch and starch cross-linked by glyoxal or AZC alone. Results showed that the co-cross-linked starch films exhibited significantly improved hydrophobicity and strength and the wet stress reached 1.53 MPa, compared to the control, glyoxal or AZC cross-linked starch films. More interestingly, the co-cross-linked film also demonstrated excellent UV shielding capacity and transmittance at visible wavelength range. The reaction mechanism was revealed based on the findings from UV, FT-IR and NMR spectra. This work established an innovative approach to improving the performance of starch film in neutral conditions for packaging applications.


Physiologic, histologic, and neurologic responses to simultaneous bilateral cerebral vessel Doppler imaging at high beam intensity.
This study evaluates physiological fluid heating during continuous bilateral insonation at 530 mW/cm2 for 8 h in a bench simulation. It also examines the physiologic, histopathologic, and neurologic effects of bilateral Doppler imaging of middle cerebral artery (MCA) blood flow velocity using ultrasonic beams with 530 mW/cm2 intensity in a canine model immediately after and 2 weeks after insonation. In saline-filled containers, instrumented with opposing Doppler probes angled 10 degrees off axis, temperature was recorded at 15-min intervals for approximately 8 h at the intersection of the Doppler probe axes. Three conditions were tested: 1) an ambient control, 2) continuous bilateral insonation at 530 mW/cm2 per channel with the thermistor in position, and 3) intermittent thermistor insertion. In one group of canines, physiopathologic responses during continuous bilateral insonation of the MCAs for 8 h at 2 MHz and 530 mW/cm2 were studied. Brains were prepared for histologic examination immediately after insonation. Cerebral temperature; arterial, venous, pulmonary artery, and capillary wedge pressures; electrocardiogram; cardiac output; MCA velocity; and arterial blood gases were monitored. In a second group of canines, a neurologic evaluation was performed before and after insonation and again after 2 weeks. Brain tissue was evaluated histologically after the last neurologic examination. Light microscopic study was used for all histologic evaluations. In the bench experiments, a net temperature rise in the fluid of the simulation amounted to 0.0075 degrees C/h in the overlap region after correction for ambient temperature effects and artifact thermistor heating. In canines, brain temperature (after correction for core body temperature changes and artifact heating of the thermistor) rose a mean of 0.2 degrees C (p < 0.05) by the first hour, thereafter unchanging. No significant changes in the physiologic, neurologic, or histologic evaluations were observed in either of the experimental groups.


Lack of involvement of haemocytes in the establishment and spread of infection in Spodoptera frugiperda larvae infected with the baculovirus Autographa californica M nucleopolyhedrovirus by intrahaemocoelic injection.
It is thought that insect haemocytes, or blood cells, play an important role in baculovirus pathogenesis by amplifying and helping to spread the infection within the insect. Here, infection is described of the lepidopteran noctuid species Spodoptera frugiperda with the baculovirus Autographa californica M nucleopolyhedrovirus (AcMNPV). Late instar S. frugiperda larvae were infected by intrahaemocoelic injection using a recombinant of AcMNPV expressing the enhanced green fluorescent protein gene to visualize infected cells. Approximately 1000-fold higher doses of injected virus were required to initiate infection in S. frugiperda larvae than in another permissive noctuid species, Trichoplusia ni. Infected S. frugiperda larvae survived twice as long as T. ni larvae and exhibited a slower build-up of virus in the haemolymph. In S. frugiperda, infection of fat body and epithelium was observed prior to significant infection of haemocytes, even though the virus was delivered by intrahaemocoelic injection. Expression of eGFP was first detected 12-18 h post-injection within the fat body and, by 24 h, infection had spread to the tracheal and body wall epithelium. In contrast, only 5% of haemocytes were infected at 24 h and the proportion of infected haemocytes increased slowly to only around 50% at 5 days post-infection, when most larval death occurred. Thus, in S. frugiperda, haemocytes do not appear to have a primary role in AcMNPV pathogenesis. This relative lack of infection of haemocytes may in part explain why S. frugiperda larvae are more resistant to AcMNPV infection than T. ni larvae.


Analysis of twitter users' sharing of official new york storm response messages.
Twitter is a social network where users read, send, and share snippets of text ("tweets"). Tweets can be disseminated through multiple means; on desktop computers, laptops, and mobile devices, over ethernet, Wi-Fi or cellular networks. This redundancy positions Twitter as a useful tool for disseminating information to the public during emergencies or disasters. Previous research on dissemination of information using Twitter has mostly investigated the characteristics of tweets that are most effective in raising consumer awareness about a new product or event. In particular, they describe characteristics that increase the chance the messages will be shared ("retweeted") by users. In comparison, little has been published on how information from municipal or state government agencies spreads on Twitter during emergency situations. Retweeting these messages is a way to enhance public awareness of potentially important instructions from public officials in a disaster. The aim of this study is to (1) describe the tweets of select New York State and New York City agencies by public officials surrounding two notable recent winter storms that required a large-scale emergency response, and (2) identify the characteristics of the tweets of public officials that were most disseminated (retweeted). For one week surrounding Superstorm Sandy (October 2012) and the winter blizzard Nemo (February 2013), we collected (1) tweets from the official accounts for six New York governmental agencies, and (2) all tweets containing the hashtags #sandy (or #nemo) and #nyc. From these data we calculated how many times a tweet was retweeted, controlling for differences in baseline activity in each account. We observed how many hashtags and links each tweet contained. We also calculated the lexical diversity of each tweet, a measure of the range of vocabulary used. During the Sandy storm, 3242 shared (retweeted) messages from public officials were collected. The lexical diversity of official tweets was similar (2.25-2.49) and well below the average for non-official tweets mentioning #sandy and #nyc (3.82). Most official tweets were with substantial retweets including a link for further reading. Of the 448 tweets analyzed from six official city and state Twitter accounts from the Nemo blizzard, 271 were related to the storm, and 174 had actionable information for the public. Actionable storm messages were retweeted approximately 24x per message, compared to 31x per message for general storm information. During two weather emergencies, New York public officials were able to convey storm-related information that was shared widely beyond existing follower bases, potentially improving situational awareness and disaster response. Official Sandy tweets, characterized by a lower lexical diversity score than other city- and Sandy-related tweets, were likely easier to understand, and often linked to further information and resources. Actionable information in the Nemo blizzard, such as specific instructions and cancellation notices, was not shared as often as more general warnings and "fun facts," suggesting agencies mix important instructions with more general news and trivia, as a way of reaching the broadest audience during a disaster.


[Arterial impedance in transient modes of the performance of the circulation system].
The authors consider transient processes for modifying arterial impedance, peripheral and elastic resistances of the arterial system, as well as some major hemodynamic parameters early in muscular performance. The analysis was made by applying experimental findings from 74 athletes. The transient processes were derived by using the mathematical modelling techniques on a computer. The termination of transient processes of arterial impedance and its determinants was shown to be asynchronous. Whether the values of arterial impedance at rest and during exercises of unlimited power are comparatively invariant is also discussed in the paper.


Effects of growth hormone therapy on glucose metabolism and insulin sensitivity indices in prepubertal children with Prader-Willi syndrome.
In Prader-Willi syndrome (PWS) growth hormone therapy (GHT) improves height, body composition, agility and muscular strength. In such patients it is necessary to consider the potential diabetogenic effect of GHT, since they tend to develop type 2 diabetes, particularly after the pubertal age. The aim of our study was to investigate the effects of GHT on glucose and insulin homeostasis in PWS children. An oral glucose tolerance test (OGTT) was performed in 24 prepubertal PWS children (15 male, 9 female, age: 5.8 +/- 2.8 years), 16 were obese (group A) and 8 had normal weight (group B), before and after 2.7 +/- 1.3 years GHT (0.22 +/- 0.03 mg/kg/week) and, only at baseline, in 35 prepubertal children with simple obesity (19 male, 16 female) (group C). Fasting glucose and insulin, glucose tolerance, insulin sensitivity index (ISI), homeostasis model assessment of insulin resistance (HOMA-IR), quick insulin check index (QUICKI), area under the curves (AUC) of glucose and insulin were estimated. At the start of GHT, all PWS children were normoglycaemic and normotolerant but two developed impaired glucose tolerance after 2.2 and 1.9 years of therapy, respectively. At baseline, group A showed lower fasting insulin levels, HOMA-IR and AUC of insulin, higher ISI, QUICKI and AUC of glucose than group C. Comparing groups A and B, AUC of insulin was higher and ISI lower in group A. During GHT, a significant increase of fasting insulin and glucose, a worsening of insulin resistance (HOMA-IR) and insulin sensitivity (QUICKI) was found only in group A while ISI did not change. The AUC of glucose decreased in both groups instead AUC of insulin did not change. BMI-SDS decreased in group A and increased in group B. The increased insulin resistance and decreased insulin sensitivity in obese PWS patients, as well as the occurrence of impaired glucose tolerance during GHT, suggest that a close monitoring of glucose and insulin homeostasis is mandatory, especially in treated obese PWS children.


Teenage health and the practice nurse: choice and opportunity for both?
Teenage health issues and the means to address them have caused increasing concern over recent years. This study investigated the involvement and training of practice nurses, the topics raised during consultations with teenagers, and the comfort of the practice nurses in dealing with these topics. Data were collected using a postal questionnaire survey (response rate 80.6%). Expansion of the role of the practice nurse in teenage health may be appropriate but needs to be supported by training.


The growth of Vibrio vulnificus and the habitat of infected patients in Kumamoto.
In Japan, Vibrio vulnificus (V. vulnificus) infection is very rare, and most infections have occurred in Kumamoto Prefecture (1), and especially around the Ariake and Yatsushiro seas. To investigate the relationship between the occurrence of V. vulnificus infection and environmental factors, including the salinity of seawater and the amount of rain in the Ariake and Yatsushiro seas, we measured the most probable number (MPN) of V. vulnificus in seawater and sea mud. In the Ariake Sea, we also observed the temperature and salinity of seawater at one site located on an estuary where the salinity is easily affected by river water and another site located offshore where seawater is little affected by river water. Furthermore, we investigated the MPN of V. vulnificus and observed the temperature and the salinity of seawater in 25 sites in the Ariake and Yatsushiro seas from July to August 2003 and 2004. In addition, we collected data on patients with V. vulnificus infections in Kumamoto from 1990 to 2006. The MPN of V. vulnificus differed by sampling site. More V. vulnificus were detected around the inland sea than the open sea, and the increase in V. vulnificus levels was affected by rainfall around inland sea areas with many rivers. V. vulnificus increases significantly in brackish water areas, and the salinity of seawater was as important as the seawater temperature. In other words, an area's topography and amount of rain are believed to be important factors for the occurrence of V. vulnificus infection. V. vulnificus infection has been regarded as an infection of hot districts. However, the salinity of seawater may be more important than temperature for the growth of V. vulnificus. Therefore, investigating these geographical and meteorological factors can help predict areas with a higher number of V. vulnificus infection outbreaks.


Conversion of human placental alkaline phosphatase from a high Mr form to a low Mr form during butanol extraction. An investigation of the role of endogenous phosphoinositide-specific phospholipases.
Alkaline phosphatase in a wide range of tissues has been shown to be anchored in the membrane by a specific interaction with the polar head group of phosphatidylinositol. It has previously been suggested that the production of low Mr alkaline phosphatase during the commonly used butanol extraction procedure may result from the activation of an endogenous phosphoinositide-specific phospholipase C which removes the 1,2-diacylglycerol responsible for membrane anchoring. This conversion process was investigated in greater detail with human placenta used as the source of alkaline phosphatase. Mr and hydrophobicity of the alkaline phosphatase were determined by gel filtration on TSK-250 and partitioning in Triton X-114, respectively. Alkaline phosphatase extracted from human placental particulate fraction with butanol at pH 5.4 or released by incubation with Staphylococcus aureus phosphatidylinositol-specific phospholipase C produced a form of alkaline phosphatase of Mr approx. 170,000 and relatively low hydrophobicity. By contrast, the butanol extract prepared at pH 8.3 was an aggregated form of Mr approx. 600,000 and was relatively hydrophobic. The effect of a variety of inhibitors and activators on the amount of low Mr alkaline phosphatase produced during butanol extraction revealed that it was a Ca2+- and thiol-dependent process. Proteinase inhibitors had no effect. [3H]Phosphatidylinositol hydrolysis by the particulate fraction, unlike low Mr alkaline phosphatase production, was relatively sensitive to heat inactivation, indicating that the phosphoinositide-specific phospholipases C from cytosol and lysosomes were unlikely to be responsible for conversion. A butanol-stimulated activity which removed the [3H]myristic acid from the variant surface glycoprotein ( [3H]mfVSG) of Trypanosoma brucei was detectable in the human placental particulate fraction. Since this activity was acid active, Ca2+- and thiol-dependent and relatively heat stable, it may be the same as that responsible for production of low Mr alkaline phosphatase. The only 3H-labelled product identified was phosphatidic acid, suggesting that the [3H]mfVSG-cleaving activity is a phospholipase D. These data strongly support the proposal that production of low Mr alkaline phosphatase during butanol extraction is an autolytic process occurring as the result of an endogenous phospholipase. However, they also suggest that the lysosomal and cytosolic phosphoinositide-specific phospholipases C that have previously been described in many mammalian tissues are not responsible for this process.


Relation between different treatment modalities and genomic damage of end-stage renal failure patients.
Patients with end-stage renal disease display enhanced genomic damage. We investigated the relation between genomic damage and different treatment modalities. In a longitudinal study two groups of patients were analyzed in monthly intervals. We assessed the initiation of hemodialysis in 5 conservatively treated patients, and a switch from hemodialysis to hemodiafiltration in 7 patients. DNA damage was investigated in peripheral blood lymphocytes by micronucleus frequency and by comet assay analysis. With regard to potential genotoxicity of advanced glycation end products (AGEs), levels of imidazolone A and AGE-associated fluorescence (AGE-FL) were determined. The initiation of hemodialysis did not alter the genomic damage. In patients who switched from hemodialysis to hemodiafiltration, a small but significant reduction in the comet assay but not in the micronucleus frequency was observed. Elevated plasma levels of imidazolone A and AGE-FL were not influenced by the treatment modalities. In our small patient group no major reduction of the elevated genomic damage could be reached. Disease factors not influenced by altered dialysis modalities may have contributed considerably in our patient group. The persisting high levels of DNA damage suggest a need for further improvement. Inhibiting AGE formation may be one promising way for the future.


Hemidystonia as an initial manifestation of leptomeningeal metastasis.
A 76-year-old woman gradually developed action dystonia of the left hand and foot. Leptomeningeal metastasis of the right fronto-parietal area associated with gastric adenocarcinoma was found on the brain magnetic resonance imaging (MRI) and positron emission tomography (PET) studies. We discuss the mechanisms involved in the development of secondary hemidystonia and review dystonia associated with cortical lesions.


Tranquillization of cane rats (Thryonomys swinderianus) with a depot neuroleptic (pipothiazine palmitate).
Stress-induced self-trauma is a major cause of mortality among captive cane rats (Thryonomys swinderianus). Six subadult female cane rats were injected with a long-acting neuroleptic drug (pipothiazine palmitate 25 mg/kg), and an equal number were injected with isotonic saline. Their behaviour and reactions to stimuli were recorded daily. After 5 weeks, treated animals continued to display significantly less stress-related behaviour than the control group. In addition, two abbreviated studies were conducted. Eleven subadult males were treated identically to the females. Their behaviour was recorded for 1 week. Subsequently, 11 indocile animals on a commercial cane rat farm were tested for calmness, treated with pipothiazine and retested after 2.5 weeks. The results of these studies were similar to those in the female study. A significant taming effect was seen 30 days after a single treatment for all invasive or aggressive tests in treated cane rats, and no extrapyramidal effects were noted. Pipothiazine affected neither their alertness nor weight gain. However, substantial behavioural alteration requires the exposure of the animal to stressful stimuli during the treatment period. Pipothiazine palmitate decreases the stress experienced by cane rats, eases their transition to a new environment, makes them easier to handle and less likely to injure themselves.


Total brachial artery reactivity and incident heart failure and heart failure subtypes: multi-ethnic study of atherosclerosis.
Endothelial dysfunction may be a phenotypic expression of heart failure (HF). Total brachial artery reactivity (TBAR) is a non-invasive measurement of endothelial function that has been associated with increased risk of cardiovascular outcomes. Limited information is currently available on the impact of TBAR on incident HF and its subtypes. The aim of this study was to investigate whether TBAR is associated with overall incident HF, and the two HF subtypes, HF with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction (HFpEF) in a community-based study. The sample included 5499 participants (45-84 years of age) from the Multi-Ethnic Study of Atherosclerosis who were free of cardiovascular disease at baseline. Brachial artery was imaged via ultrasound after five minutes of cuff occlusion at the right forearm. TBAR was calculated as the difference between maximum and minimum brachial artery diameters following cuff release, divided by the minimum diameter multiplied by 100%. A dichotomous TBAR variable was created based on the median value (below or above 7.9%). Participants with EF ≤ 40% were considered HFrEF and those with EF ≥ 50% were considered HFpEF. Cox proportional hazards regression models were used to calculate hazard ratios (HR) and 95% confidence intervals (CI). Over a mean follow-up period of 12.5 years, incident HF was diagnosed in 250 participants: 98 classified as HFrEF, 106 as HFpEF, and 46 with unknown or borderline EF (41-49%). Crude analysis revealed that those with TBAR below the median had a significantly greater risk of HF (HR 1.46; 95% CI 1.13-1.88, p < 0.01) and HFrEF (HR 1.61; 95% CI 1.07-2.43, p < 0.05). Following adjustment for known HF risk factors (e.g., age, sex, race, blood pressure), the strength of these relationships was attenuated. Borderline significant results were revealed in those with HFpEF (HR 1.43; 95% CI 0.97-2.12, p = 0.06). Kaplan-Meier curves suggest significantly lower risks of developing HF and HFrEF in those with TBAR above the median (log-rank p ≤ 0.05 for both). When examined as a continuous variable, with a cut point of 50% for EF, every 1-standard deviation (9.7%) increase in TBAR resulted in a 19 and 29% decrease in risk of HF (p < 0.05) and HFrEF (p = 0.05), respectively. Lower TBAR values were associated with higher rates of incident HF and HFrEF, suggesting a possible role of endothelial dysfunction in HF pathogenesis. The impact of other known HF risk factors may mediate this relationship, thus further research is warranted.


A novel synthetic odorant blend for trapping of malaria and other African mosquito species.
Estimating the biting fraction of mosquitoes is of critical importance for risk assessment of malaria transmission. Here, we present a novel odor-based tool that has been rigorously assessed in semi-field assays and traditional African villages for estimating the number of mosquitoes that enter houses in search of a blood meal. A standard synthetic blend (SB) consisting of ammonia, (S)-lactic acid, tetradecanoic acid, and carbon dioxide was complemented with isovaleric acid, 4,5 dimethylthiazole, 2-methyl-1-butanol, and 3-methyl-1-butanol in various combinations and concentrations, and tested for attractiveness to the malaria mosquito Anopheles gambiae. Compounds were released through low density polyethylene (LDPE) material or from nylon strips (nylon). Studies were done in a semi-field facility and two traditional villages in western Kenya. The alcohol 3-methyl-1-butanol significantly increased the attraction of SB. The other compounds proved less effective or inhibitory. Tested in a village, 3-methyl-1-butanol, released from LDPE, increased the attraction of SB. Further studies showed a significantly enhanced attraction of adding 3-methyl-1-butanol to SB compared to previously-published attractive blends both under semi-field and village conditions. Other mosquito species with relevance for public health were collected with this blend in significantly higher numbers as well. These results demonstrate the advent of a novel, reliable odor-based sampling tool for the collection of malaria and other mosquitoes. The advantage of this odor-based tool over existing mosquito sampling tools is its reproducibility, objectiveness, and relatively low cost compared to current standards of CDC light traps or the human landing catch.


Physicochemical and Functional Properties of 2S, 7S, and 11S Enriched Hemp Seed Protein Fractions.
The hemp seed contains protein fractions that could serve as useful ingredients for food product development. However, utilization of hemp seed protein fractions in the food industry can only be successful if there is sufficient information on their levels and functional properties. Therefore, this work provides a comparative evaluation of the structural and functional properties of hemp seed protein isolate (HPI) and fractions that contain 2S, 7S, or 11S proteins. HPI and protein fractions were isolated at pH values of least solubility. Results showed that the dominant protein was 11S, with a yield of 72.70 ± 2.30%, while 7S and 2S had values of 1.29 ± 0.11% and 3.92 ± 0.15%, respectively. The 2S contained significantly (p < 0.05) higher contents of sulfhydryl groups at 3.69 µmol/g when compared to 7S (1.51 µmol/g), 11S (1.55 µmol/g), and HPI (1.97 µmol/g). The in vitro protein digestibility of the 2S (72.54 ± 0.52%) was significantly (p < 0.05) lower than those of the other isolated proteins. The intrinsic fluorescence showed that the 11S had a more rigid structure at pH 3.0, which was lost at higher pH values. We conclude that the 2S fraction has superior solubility, foaming capacity, and emulsifying activity when compared to the 7S, 11S, and HPI.


Medical abortion and manual vacuum aspiration for legal abortion protect women's health and reduce costs to the health system: findings from Colombia.
The majority of abortions in Colombia continue to take place outside the formal health system under a range of conditions, with the majority of women obtaining misoprostol from a thriving black market for the drug and self-administering the medication. We conducted a cost analysis to compare the costs to the health system of three approaches to the provision of abortion care in Colombia: post-abortion care for complications of unsafe abortions, and for legal abortions in a health facility, misoprostol-only medical abortion and vacuum aspiration abortion. Hospital billing records from three institutions, two large maternity hospitals and one specialist reproductive health clinic, were analysed for procedure and complication rates, and costs by diagnosis. The majority of visits (94%) were to the two hospitals for post-abortion care; the other 6% were for legal abortions. Only one minor complication was found among the women having legal abortions, a complication rate of less than 1%. Among the women presenting for post-abortion care, 5% had complications during their treatment, mainly from infection or haemorrhage. Legal abortions were associated not only with far fewer complications for women, but also lower costs for the health system than for post-abortion care. We calculated based on our findings that for every 1,000 women receiving post-abortion care instead of a legal abortion within the health system, 16 women experienced avoidable complications, and the health system spent US $48,000 managing them. Increasing women's access to safe abortion care would not only reduce complications for women, but would also be a cost-saving strategy for the health system.