Changing Population Size in McDonald-Kreitman Style Analyses: Artifactual Correlations and Adaptive Evolution between Humans and Chimpanzees.
It is known that methods to estimate the rate of adaptive evolution, which are based on the McDonald-Kreitman test, can be biased by changes in effective population size. Here, we demonstrate theoretically that changes in population size can also generate an artifactual correlation between the rate of adaptive evolution and any factor that is correlated to the strength of selection acting against deleterious mutations. In this context, we have investigated whether several site-level factors influence the rate of adaptive evolution in the divergence of humans and chimpanzees, two species that have been inferred to have undergone population size contraction since they diverged. We find that the rate of adaptive evolution, relative to the rate of mutation, is higher for more exposed amino acids, lower for amino acid pairs that are more dissimilar in terms of their polarity, volume, and lower for amino acid pairs that are subject to stronger purifying selection, as measured by the ratio of the numbers of nonsynonymous to synonymous polymorphisms (pN/pS). All of these correlations are opposite to the artifactual correlations expected under contracting population size. We therefore conclude that these correlations are genuine.


Transient Fanconi Syndrome After Treatment with Firocoxib, Cefadroxil, Tramadol, and Famotidine in a Maltese.
Fanconi syndrome is a renal proximal tubulopathy characterized by excessive urinary loss of glucose, amino acids, several electrolytes, and bicarbonate. Here, we report the case of transient Fanconi syndrome in a dog following administration of firocoxib, cefadroxil, tramadol, and famotidine. A 10 mo old Maltese was presented with lethargy, anorexia, vomiting, and weight loss. Transient Fanconi syndrome without azotemia was associated with firocoxib, cefadroxil, tramadol, and famotidine treatment. The dog received supportive care including IV fluids, gastroprotectants, and oral nutritional supplements. Two months after initial diagnosis and treatment, the dog showed complete resolution of glucosuria and aminoaciduria. The unique features of Fanconi syndrome in this case emphasize the potential renal tubular toxicity of this widely used multiple-drug combination.


Enhanced detection of visual targets on the hand and familiar tools.
This study investigated whether or not the simple detection of visual stimuli is better when those stimuli are presented on the hand than on other objects, and whether or not detection on other objects improves when people are trained to use them as tools. Participants performed a speeded visual detection task to targets presented on either side of their own left hand, a fake left hand, and a small garden rake. They were then trained to use either the fake hand or the rake as a tool with their left hand. Participants initially responded faster to stimuli projected onto their real hand than to stimuli presented on the fake hand or the tool, but they did not respond faster to stimuli on one side of the hand than on the other. After training, participants showed better detection of the visual stimuli presented on the object that they had been trained to use than they did for stimuli presented on the other object. Moreover, participants responded faster to stimuli presented on the upper side of the object that they had been trained to use than they did to stimuli on the other side. These findings demonstrate that an enhanced visual detection can be induced for stimuli presented on tools and other inanimate objects with training, suggesting that these objects have been incorporated into the body schema.


The P2X7-nonmuscle myosin membrane complex regulates phagocytosis of nonopsonized particles and bacteria by a pathway attenuated by extracellular ATP.
Phagocytosis of nonopsonized bacteria is central to innate immunity, but its regulation is less defined. We show that overexpression of the P2X(7) receptor greatly augments the phagocytosis of nonopsonized beads and heat-killed bacteria by transfected HEK-293 cells, whereas blocking P2X(7) expression by siRNA significantly reduces the phagocytic ability of human monocytic cells. An intact P2X(7)-nonmuscle myosin complex is required for phagocytosis of nonopsonized beads because activation of P2X(7) receptors by adenosine triphosphate (ATP), which dissociates myosin IIA from the P2X(7) complex, inhibits this phagocytic pathway. Fresh human monocytes rapidly phagocytosed live and heat-killed Staphylococcus aureus and Escherichia coli in the absence of serum, but the uptake was reduced by prior incubation with ATP, or P2X(7) monoclonal antibody, or recombinant P2X(7) extracellular domain. Injection of beads or bacteria into the peritoneal cavity of mice resulted in their brisk phagocytosis by macrophages, but injection of ATP before particles markedly decreased this uptake. These data demonstrate a novel pathway of phagocytosis of nonopsonized particles and bacteria, which operate in vivo and require an intact P2X(7)-nonmuscle myosin IIA membrane complex. The inhibitory effect of ATP on particle uptake by the macrophage is regulated by the P2X(7) receptor and defines this phagocytic pathway.


Association between dietary patterns and socioeconomic factors and food environment in a city in the South of Brazil.
The aim of this study was to investigate the association between dietary patterns and demographic and socioeconomic factors and the food environment among adults and older persons in a city in the south of Brazil. We conducted a cross-sectional study with people of both sexes aged between 20 and 70 years. Dietary patterns were identified using principal component analysis. Poisson regression was used to estimate crude and adjusted prevalence ratios and 95% confidence intervals. Four dietary patterns were identified: Healthy; Traditional; Refined Carbs and Sugars; and Fast Food. Positive associations were found between being female and higher income and the Healthy dietary pattern; being black or brown and living in a household with at least six members and the Traditional and Refined Carbs and Sugars patterns; and higher education and the fast-food dietary pattern. Having main meals at home was associated with the Traditional pattern and having lunch or dinner away from home was the associated with Refined Carbs and Sugars and fast-food patterns. Lower socioeconomic status leads to higher consumption of the Traditional and/or Refined Carbs and Sugars dietary patterns, while higher socioeconomic status appears to enable individuals to choose between healthy or fast-food patterns.


Impact analysis of COVID-19 responses on energy grid dynamics in Europe.
When COVID-19 pandemic spread in Europe, governments imposed unprecedented confinement measures with mostly unknown repercussions on contemporary societies. In some cases, a considerable drop in energy consumption was observed, anticipating a scenario of sizable low-cost energy generation, from renewable sources, expected only for years later. In this paper, the impact of governmental restrictions on electrical load, generation and transmission was investigated in 16 European countries. Using the indices provided by the Oxford COVID-19 Government Response Tracker, precise restriction types were found to correlate with the load drop. Then the European grid was analysed to assess how the load drop was balanced by the change in generation and transmission patterns. The same restriction period from 2020 was compared to previous years, accounting for yearly variability with ad hoc statistical technique. As a result, generation was found to be heavily impacted in most countries with significant load drop. Overall, generation from nuclear, and fossil coal and gas sources was reduced, in favour of renewables and, in some countries, fossil gas. Moreover, intermittent renewables generation increased in most countries without indicating an exceptional amount of curtailments. Finally, the European grid helped balance those changes with an increase in both energy exports and imports, with some net exporting countries becoming net importers, notably Germany, and vice versa. Together, these findings show the far reaching implications of the COVID-19 crisis, and contribute to the understanding and planning of higher renewables share scenarios, which will become more prevalent in the battle against climate change.


The control of EGF signaling and cell fate in the Drosophila abdomen.
How cells integrate both patterning and signaling information to select between distinct cell fates is a fundamental problem in developmental biology. In this short review, I focus on recent findings of how the Hox and senseless patterning genes regulate epidermal growth factor (EGF) signaling and cell fate within the Drosophila abdomen. In Li-Kroeger et al., we described how a Hox and Senseless transcription factor competition functions as a molecular switch on a cis-regulatory element in the rhomboid (rho) gene to control EGF signaling within the peripheral nervous system (PNS). Here, I discuss an additional implication of these findings: that rho contains at least two cis-regulatory elements to control EGF secretion from the PNS, each to induce a different cell fate.


Renal cell carcinoma.
In addition to the known risk factors for renal cell carcinoma, hypertension, obesity, and tobacco use, a diet high in consumption of fried or sautéed meat and the frequent consumption of poultry may increase the risk for renal cell carcinoma. A diet high in consumption of fruits and vegetables appears to have a protective effect. Molecular markers, in particular markers of cell proliferation, may have prognostic value and be of assistance in identifying patients who would benefit from more aggressive therapy. Surgery continues to the mainstay of treatment of localized disease, and may be the optimal treatment for patients with isolated solitary metastatic disease. Response rates to systemic therapy with cytokines vary from 5% to 20% with significant adverse effects.


Dream recall and the full moon.
There is ongoing debate on whether the full moon is associated with sleep and dreaming. The analysis of diaries kept by the participants (N = 196) over 28 to 111 nights showed no association of a full moon and dream recall. Psychological factors might explain why some persons associate a full moon with increased dream recall.


An analysis of stakeholder views on children's mental health services.
The purpose was to examine the perspectives of mental health stakeholders as a means to guide the adaptation of evidence-based treatments. The Mental Health System Ecological (MHSE) model was used to organize therapist, administrator, and parent perspectives gathered using qualitative methods. The MHSE model posits the influences of client-level, provider-level, intervention-specific, service delivery, organizational, and service system characteristics on implementation. Focus groups and interviews were conducted with community mental health stakeholders and included parents, therapists, and administrators (N = 21). Participants included 11 primarily Caucasian (90.48%) female participants, ranging in ages between 31 and 57 years. Data were analyzed according to the MHSE model. Frequency counts were tabulated for each theme and stakeholder group differences were determined using the Mann-Whitney test. Stakeholder groups mentioned needs at each level of the MHSE model. Stakeholder group differences most notably emerged with child and family themes, which included complexity of mental health issues, parenting differences, and family stressors. Stakeholders identified challenges for optimal mental health services for children across multiple levels of an ecological model. Implications of the findings are discussed, including the continued relevance of adapting mental health interventions by increasing their flexible application across multiple target problems and the promise of partnership approaches.


Vaccination against hepatitis B in a general hospital in Israel: antibody level before vaccination and immunogenicity of vaccine.
We offered hepatitis B vaccine (Heptavax B) to 809 of the health care personnel of a 650-bed regional hospital; 290 accepted the offer. Anti-HBs measurement was done by enzyme immunoassay (AUSAB EIA, Abbott, UK) and expressed in mIU/ml. Seroconversion was determined at a level of 2.1 mIU/ml. Of 290 employees 58 (20%) were found positive for hepatitis B antibodies before vaccination. Of the laboratory technicians, 40.9% were found positive for antibodies before vaccination, as were 26.5% of nurses and 10.9% of physicians. Among vaccine recipients 35.8% responded after the first dose, 86.6% after the second and 92.7% after the third. Seventeen workers (7.3%) were nonresponders, of whom 14 received the whole vaccine series. There was no difference in immune responses to the vaccine between men and women. The present study confirms the relatively high prevalence of HBV infection in health care workers. Furthermore, vaccination of employees has been highly effective and well tolerated. The present data, therefore, support the introduction of active vaccination against HBV in health care workers in Israel.


Newly discovered landscape traps produce regime shifts in wet forests.
We describe the "landscape trap" concept, whereby entire landscapes are shifted into, and then maintained (trapped) in, a highly compromised structural and functional state as the result of multiple temporal and spatial feedbacks between human and natural disturbance regimes. The landscape trap concept builds on ideas like stable alternative states and other relevant concepts, but it substantively expands the conceptual thinking in a number of unique ways. In this paper, we (i) review the literature to develop the concept of landscape traps, including their general features; (ii) provide a case study as an example of a landscape trap from the mountain ash (Eucalyptus regnans) forests of southeastern Australia; (iii) suggest how landscape traps can be detected before they are irrevocably established; and (iv) present evidence of the generality of landscape traps in different ecosystems worldwide.


Modulation of the Photophysical, Photochemical, and Electrochemical Properties of Re(I) Diimine Complexes by Interligand Interactions.
The photophysical and photochemical properties of transition metal complexes have attracted considerable attention because of their recent applications as photocatalysts in artificial photosynthesis and organic synthesis, as light emitters in electroluminescent (EL) devices, and as dyes in solar cells. The general control methods cannot be always used to obtain transition metal complexes with photochemical properties that are suitable for the above-mentioned applications. In the fields of solar energy conversion, strong metal-to-ligand charge-transfer (MLCT) absorption of redox photosensitizers and/or photocatalysts in the visible region with long wavelength is essential. However, the usual methods, i.e., introduction of electron-withdrawing groups into the electron-accepting ligand and/or weak-field ligands into the central metal, have several drawbacks, including shorter excited-state lifetime, lower emission efficiency, and lower oxidation and reduction power. Herein we describe a new method to control the photophysical, photochemical, and electrochemical properties of Re(I) diimine carbonyl complexes that have been widely used in various fields such as photocatalysts for CO2 reduction and emitters in EL devices and sensors. This method involves the introduction of interligand interactions (π-π and CH-π interactions) into the Re(I) complexes; the aromatic diimine ligand coordinating to the Re center approaches the aryl groups on the phosphine ligand or ligands at the cis position, which "compulsorily" induces a weak interaction between these aromatic groups. As a result of this interligand interaction, the Re complexes with the aromatic diimine ligand and the arylphosphine ligand(s) exhibit red-shifted 1MLCT absorption but afford blue-shifted emission from the triplet metal-to-ligand charge-transfer (3MLCT) excited state. This increases the oxidation power and lifetime of the 3MLCT excited state. These unique property changes are favorable, particularly for redox photosensitizers. The interligand interaction is strongly expressed by the ring-shaped multinuclear Re(I) complexes (Re-rings). In the case of Re-rings with high steric hindrance due to a small inner cavity, the lifetime of the 3MLCT excited state is up to 8 μs and the emission quantum yield is up to 70%. These properties cannot be obtained by the corresponding mononuclear Re(I) complexes, which generally exhibit shorter lifetimes (<1 μs) and lower emission quantum yields (<10%). Some of the Re-rings could be successfully applied as efficient photosensitizers in photocatalytic systems for CO2 reduction; the highest quantum yields for CO2 reduction were achieved by using photocatalytic systems composed of Re-rings as the photosensitizers and Re(I) (82%), Ru(II) (58%), and Mn(I) (48%) complexes as catalysts. This interligand interaction potentially provides unique and useful methods for controlling the photophysical, photochemical, and electrochemical functions of various metal complexes, paving the way to create new functions for metal complexes.


Solid state bioconversion of oil palm biomass for ligninase enzyme production.
A laboratory-scale study of bioconversion of local lignocellulosic material, oil palm biomass (OPB) was conducted by evaluating the enzyme production through microbial treatment in solid state bioconversion (SSB). OPB in the form of empty fruit bunches (EFB) was used as a solid substrate and treated with the white-rot fungus, Phanerochaete chrysosporium, to produce ligninase. The results showed that the highest ligninase activity of 400.27 U/liter was obtained at day 12 of fermentation. While the optimum study indicated the enzyme production of 1472.8 U/liter with moisture content of 50%, 578.7 U/liter with 10% v/w of inoculum size, and 721.8 U/liter with co-substrate concentration of 1% (w/w) at days 9, 9 and 12 of fungal treatment, respectively. The parameters glucosamine and reducing sugar were observed to evaluate the growth and substrate utilization in the experiment.


Effect of flavonoids from Exellodendron coriaceum (Chrysobalanaceae) on glucose-6-phosphatase.
From the n-butanol extract of the aerial parts of Exellodendron coriaceum (Benth.) Prance the flavonoids quercetin-3-O-beta-D-galactopyranoside (1), quercetin-3-O-alpha-L-arabinopyranoside (2), quercetin-3-O-alpha-L-rhamnopyranosyl-(1-->2)-alpha-L-rhamnopyranoside (3), and quercetin-3-O-alpha-L-rhamnopyranosyl-(1-->6)-beta-D-galactopyranoside (4) were isolated. Additionally from this extract three flavonoids were isolated and partially characterized as quercetin glycosides. All these compounds were tested for their hypoglycemic activity using the glucose-6-phosphatase microsomal hepatic system. The flavonoids inhibited the activity of the enzyme when intact microsomes were used, the highest percentage of inhibition being 65%. To the best of our knowledge, this is the first report of chemical and biological activity of E. coriaceum.


How the pediatric autopsy yields valuable information in a vertically integrated health care system.
Although autopsy rates have declined significantly in recent decades, studies continue to validate the autopsy as an important source of clinically relevant information, a teaching tool, and a quality assurance measure. A recent review of autopsy series showed a decline in the number of serious errors likely to have affected clinical outcome detected at autopsy during the past 46 years, with a current major error rate of 8.4% to 24.4%. Our hypothesis was that the pediatric autopsy would uncover a significant number of major unexpected findings at the high end of the spectrum predicted by a recent review. This study assesses the unexpected findings at a pediatric hospital whose autopsy service handles both in-house (tertiary care) and referral (mostly perinatal) cases for a vertically integrated health care system. Data were analyzed from an autopsy effectiveness report completed for all autopsies performed in 2000. The data from this series include concordance of premortem and postmortem diagnoses, with the autopsy considered the criterion standard. The autopsy effectiveness report also provided logistic information, such as problems with consents, medical records, specimen identification, and prosection. Pediatric autopsies were performed by members of the Pediatric Pathology Division in a freestanding children's hospital in the Intermountain West of the United States with a large rural catchment area. This hospital is part of a large health maintenance organization serving the surrounding urban and rural areas. A sample of all in-house and referral autopsies for the year 2000 was examined. The percentage of cases with a major or minor diagnostic discrepancy or unexpected pathologic finding using the autopsy as the criterion standard. The overall autopsy rate was 40% (39 hospital autopsies and 15 forensic autopsies per 135 total deaths) and was 32% excluding forensic cases. Twenty-two additional referral autopsies from outside institutions were performed. Of 61 autopsies, 12 (20%) revealed a major diagnostic discrepancy or unexpected pathologic finding, 17 (28%) had a minor unexpected finding or additional diagnosis, 41 (67%) clarified the differential diagnosis, 46 (75%) confirmed or verified a major diagnosis, and 21 (34%) provided information regarding treatment effects. Additionally, 3 (5%) had problems with identification, and 12 (20%) had problems with consent, all of which were resolved prior to initiation of the autopsy. These data confirm the value of the pediatric autopsy in a children's hospital and a vertically integrated health care system. It is an important medical and quality assurance procedure for assessing the accuracy of diagnoses, clarifying differential diagnoses, yielding unexpected findings, and providing feedback regarding therapeutic outcomes.


[Pandora's Box: pathogens in Ixodes ricinus ticks in Central Europe].
Among the various species of hard ticks, Ixodes ricinus is the most frequently found tick throughout Europe. As with other ixodid ticks, the developmental cycle runs through three stages. In each stage a blood meal is required in order to develop to the next stage. Ixodes ricinus has been found to feed on more than 300 different vertebrate species. Usually, larval ticks feed on small mammals such as mice and become infected with various microorganisms and viruses, of which some are substantial pathogens to humans. The pathogens remain in the tick during molting and are thus transstadially transmitted to the next developmental stage. Pathogens transmitted to humans are the agents of Lyme borreliosis, the tick-borne encephalitis virus, Rickettsia species, Anaplasma phagocytophilum, occasionally Francisella tularensis, and protozoal Babesia species. Within the scope of an EU project Ixodes ricinus ticks from all federal states of Austria were searched by means of PCR methods for bacterial pathogens such as Anaplasma phagocytophilum, Borrelia burgdorferi sensu lato, Coxiella burnetii, Ehrlichia spp., Francisella tularensis, Rickettsia spp., and protozoal Babesia. Additionally, the prevalence of Bartonella spp. in this tick species was also determined. Besides the singular detection of Coxiella burnetii and Francisella tularensis in one tick collection site the overall prevalence of Anaplasma phagocytophilum, borreliae, rickettsae and babesiae in Ixodes ricinus amounted to 15%, 14%, 6% and surprising 36% and 51%, respectively. Bartonellae were detected in about 7%.


Howship-Romberg Sign and Bowel Obstruction: A Case Report.
Small bowel obstruction (SBO) is associated with high morbidity and mortality in acute care surgery practice, with hernias constituting a significant portion of the underlying etiology. Physical examination and maneuvers such as changing the extremity position of the patient can further improve clinician's diagnostic acumen to identify the cause of the disease. We present a case of SBO in an 83-year-old female whose physical exam was consistent with an underlying obturator hernia.


Adjunctive Use of Phage Sb-1 in Antibiotics Enhances Inhibitory Biofilm Growth Activity versus Rifampin-Resistant Staphylococcus aureus Strains.
Effective antimicrobials are crucial for managing Staphylococcus aureus implant-associated bone infections (IABIs), particularly for infections due to rifampin-resistant S. aureus (RRSA). Failure to remove the implant results in persistent infection; thus, prolonged suppressive antibiotic therapy may be a reasonable alternative. However, a high incidence of adverse events can necessitate the discontinuation of therapy. In this scenario, commercial Staphylococcal bacteriophage Sb-1 combined with antibiotics is an option, showing a promising synergistic activity to facilitate the treatment of biofilm infections. Therefore, we evaluated the efficacy of the inhibitory activity of five antibiotics (doxycycline, levofloxacin, clindamycin, linezolid, and rifampin) alone or combined with phage Sb-1 (106 PFU/mL) in a simultaneous and staggered manner, to combat five clinical RRSA strains and the laboratory strain MRSA ATCC 43300 in 72 h by isothermal microcalorimetry. The synergistic effects were observed when phage Sb-1 (106 PFU/mL) combined with antibiotics had at least 2 log-reduction lower concentrations, represented by a fractional biofilm inhibitory concentration (FBIC) of <0.25. Among the antibiotics that we tested, the synergistic effect of all six strains was achieved in phage/doxycycline and phage/linezolid combinations in a staggered manner, whereas a distinctly noticeable improvement in inhibitory activity was observed in the phage/doxycycline combination with a low concentration of doxycycline. Moreover, phage/levofloxacin and phage/clindamycin combinations also showed a synergistic inhibitory effect against five strains and four strains, respectively. Interestingly, the synergistic inhibitory activity was also observed in the doxycycline-resistant and levofloxacin-resistant profile strains. However, no inhibitory activity was observed for all of the combinations in a simultaneous manner, as well as for the phage/rifampin combination in a staggered manner. These results have implications for alternative, combined, and prolonged suppressive antimicrobial treatment approaches.


A proximate perspective on reciprocal altruism.
The study of reciprocal altruism, or the exchange of goods and services between individuals, requires attention to both evolutionary explanations and proximate mechanisms. Evolutionary explanations have been debated at length, but far less is known about the proximate mechanisms of reciprocity. Our own research has focused on the immediate causes and contingencies underlying services such as food sharing, grooming, and cooperation in brown capuchin monkeys and chimpanzees. Employing both observational and experimental techniques, we have come to distinguish three types of reciprocity. Symmetry-based reciprocity is cognitively the least complex form, based on symmetries inherent in dyadic relationships (e.g., mutual association, kinship). Attitudinal reciprocity, which is more cognitively complex, is based on the mirroring of social attitudes between partners and is exhibited by both capuchin monkeys and chimpanzees. Finally, calculated reciprocity, the most cognitively advanced form, is based on mental scorekeeping and is found only in humans and possibly chimpanzees.


A study of early pregnancy factor activity in the sera of women with trophoblastic tumor.
To detect whether or not the early pregnancy factor (EPF)-like activity, or chaperonin 10, could be in the sera of patients with trophoblastic tumor in order to find another more efficient means to diagnose this kind of tumor. The rosette inhibition assay was used to detect EPF-like activity in 216 sera, collected from patients with gestational trophoblastic tumor, including 47 sera of patients with choriocarcinoma, 68 sera of patients bearing invasive mole, and 101 sera of patients with vesicular mole. The accuracy of diagnosing malignant trophoblastic tumor by detecting EPF-like activity is 91.3% (105/115), with a false positive rate of 14.58% and a false negative rate of 4.8% by this method. Furthermore, the rosette inhibition titer (RIT) values have significant difference (P < 0.001) between the sera in patients with malignant trophoblastic tumor before treatment and those after treatment. This study demonstrated that diagnosis of malignant trophoblastic tumor could be made with an accuracy of 91.3% by detecting EPF-like activity and that EPF-like activity could be used as an indicator to distinguish benign from malignant trophoblastic tumor.


Cryogenic target design considerations for the production of [18F]fluoride from enriched [18O]carbon dioxide.
Four cryogenic target designs are described for the production of fluorine-18 in the chemical form of fluoride using oxygen-18-enriched carbon dioxide gas utilizing the (18)O(p,n)18F nuclear reaction. The targets are conical in shape and made of copper or silver and the carbon dioxide is frozen into the cone at liquid nitrogen temperatures. Three of the targets (2 copper and 1 silver) have four cooling fins extending radially and are different lengths, and one target has only a single heat sink at the rear of the cone. The targets with four cooling fins could be run with 17.4 MeV protons incident on the target material at a beam current of 25 microA with no detectable volatilization of the target material, although yields did decrease slightly when compared with lower current runs. The target with the single cooling block showed volatilization at about 8 microA. The two copper targets of different lengths did not show a difference in the volatilization of the target material at the beam current limit of our cyclotron (25 microA). The shorter target did maintain production with a lower amount of gas frozen into the target, while the longer target maintained production at higher beam currents. Targets of this type are compatible with low energy, high current accelerators because very thin windows may be used.


Polar day syndrome: differences in growth, photosynthetic traits and sink-size patterns between northern and southern Finnish silver birch (Betula pendula Roth) provenances in native and non-native photoperiods.
Continuous light (CL) is available throughout the polar day for plants in the Arctic during the growing season, whereas provenances of the same species experience a very different environment with non-CL (NCL) just a few latitudes to the south. Both provenances need to acclimate to climate warming, yet we lack comprehensive understanding of how their growth, photosynthesis and leaf traits differ. Further, the provenances presumably have morphological and physiological adaptations to their native environments and therefore differ in response to photoperiod. We tested the height growth, leaf longevity, biomass accumulation, biomass allocation and rates of gas exchange of northern (67°N) and southern (61°N) Finnish silver birch (Betula pendula Roth) origins in CL- and NCL-treatments in a 4-month chamber experiment. Irrespective of photoperiod, 67°N had higher area-based photosynthetic rate (Anet), stomatal conductance (gs) and relative height growth rate (RGR), but lower stomatal density and fewer branches and leaves than 61°N. Photoperiod affected height growth cessation, biomass and photosynthetic traits, whereas leaf longevity and many leaf functional traits remained unchanged. In CL, both provenances had lower gs, higher RGR, increased shoot:root ratio and increased sink sizes (more branching, more leaves, increased total plant dry weight) compared with NCL. In NCL, 67°N ceased height growth earlier than in CL, which altered biomass accumulation and distribution patterns. Northern conditions impose challenges for plant growth and physiology. Whether a provenance inhabits and is adapted to an area with or without CL can also affect its response to the changing climate. Northern birches may have adapted to CL and the short growing season with a 'polar day syndrome' of traits, including relatively high gas exchange rates with low leaf biomass and growth traits that are mainly limited by the environment and the earlier growth cessation (to avoid frost damage).


Metabolic pathway alterations that support cell proliferation.
Proliferating cells adapt metabolism to support the conversion of available nutrients into biomass. How cell metabolism is regulated to balance the production of ATP, metabolite building blocks, and reducing equivalents remains uncertain. Proliferative metabolism often involves an increased rate of glycolysis. A key regulated step in glycolysis is catalyzed by pyruvate kinase to convert phosphoenolpyruvate (PEP) to pyruvate. Surprisingly, there is strong selection for expression of the less active M2 isoform of pyruvate kinase (PKM2) in tumors and other proliferative tissues. Cell growth signals further decrease PKM2 activity, and cells with less active PKM2 use another pathway with separate regulatory properties to convert PEP to pyruvate. One consequence of using this alternative pathway is an accumulation of 3-phosphoglycerate (3PG) that leads to the diversion of 3PG into the serine biosynthesis pathway. In fact, in some cancers a substantial portion of the total glucose flux is directed toward serine synthesis, and genetic evidence suggests that glucose flux into this pathway can promote cell transformation. Environmental conditions can also influence the pathways that cells use to generate biomass with the source of carbon for lipid synthesis changing based on oxygen availability. Together, these findings argue that distinct metabolic phenotypes exist among proliferating cells, and both genetic and environmental factors influence how metabolism is regulated to support cell growth.


Cephalometric analysis of pharyngeal airway space dimensions in Turner syndrome.
Turner syndrome (TS) that is due to a total or partial lack of an X chromosome affects about 1 in 2000 girls. The syndrome is characterized by short stature and gonadal dysgenesis. Its documented craniofacial features include retrognathic jaws, a short mandible, and a large cranial base angle. Our aim was to find out whether the syndrome also has an effect on the pharyngeal airway space. We retrospectively analysed lateral cephalograms of 35 TS subjects whose age ranged from 6.5 to 21 years and of 35 healthy female controls matched for age. On those, we did 7 linear and 10 angular cephalometric measurements and 9 pharyngeal measurements. Differences between the subjects with TS and their controls were assessed by paired two-tailed T-test. In the girls with TS, both the maxilla and the mandible were more retrognathic (SNA, P = 0.015 and SNB, P < 0.001), the mandible was shorter (TM-Pgn, P = 0.016), and the cranial base angle was larger (SNBa, P = 0.025) than in the controls, confirming the results of earlier studies. Notably, all six pharyngeal airway measurements were smaller in girls with TS. Two of them, PNS-ad2 and PAS, were statistically significantly smaller (P = 0.019 and P = 0.012, respectively). Thus, a narrow pharynx, either as a primary finding or as a consequence of the maxillo-mandibular retrognathism, further delineates the phenotype. This may imply an elevated risk of sleep apnoea in females with TS.


Research and application of non-traditional chemical stabilizers on bauxite residue (red sand) dust control, a review.
Bauxite residue is a by-product of aluminium processing. It is usually stored in large-scale residue drying area (RDA). The bauxite residue is highly alkaline and contains a large percentage of metal oxides which are hazardous to the environment and human health. Therefore, the generated dust is a major environmental concern that needs to be addressed and efficiently managed. One of the major dust generation sources is from the coarse fraction of the bauxite residue named red sand. To minimize the environmental and health impacts, non-traditional chemical stabilizers can be applied to construct a binding surface crust with certain hardness and strength. Dust emission is reduced due to the increased moisture retention capacity and strong cohesion between sand particles. There are limited number of refereed publications that discuss the application of this method to alleviate dust generation from red sand. By critically reviewing the literature and the application of non-traditional chemical stabilizers to sand-like materials in other fields, this paper introduces some non-traditional chemical stabilizers that can be potentially used for controlling red sand dust. Commonly used evaluation methods in various studies are compared and summarized; the stabilization mechanisms are examined; and the performance of three types of stabilizers are compared and evaluated. This review potentially serves as a reference and guide for further studies in red sand dust control. The findings are especially useful for developing suitable quantitative methods for evaluating the dust suppression efficiency of soil stabilizers, and for determining the appropriate additive quantities that achieve both economic and performance effectiveness.


Elucidation of Photoisomerization-Related Structural Changes in an Acrylamide-Bridged Binaphthalene-Diazene Macrocyclic Chiroptical Switch by Experimental Electronic Circular Dichroism Spectra Simulation: Role of Dispersion Corrections.
Nondestructive readout of light-driven molecular memory devices can be achieved by monitoring the alterations in the chiroptical properties of 1,1'-binaphthalene as a conformationally responsive chiral group. In our system, this signaling unit is connected via acrylamide linkers to the receiving diphenyldiazene fragment, which undergoes significant geometrical changes upon (E)/(Z)-photoisomerization. The compound functions as a stable photochromic switch by alternating irradiation at 365/465 nm, with fully reversible modulation of circular dichroism (CD) signal intensity (up to 1:3) and extended thermal stability of the (Z)-isomer. According to molecular modeling, the acrylamide spacers are due to the imposed cyclic strain upon photoisomerization forced to switch amide conformations, which is markedly reflected in the CD spectra, whereas binaphthalene conformational changes are mostly neglected both by theory and by experiment. In CD simulation by TD-DFT, CAM-B3LYP outperforms B3LYP and M06 by means of similarity analysis, whereas the last mentioned functional also delivers satisfactory performance qualitatively. The inclusion of dispersion corrections during geometry optimization was crucial to retain consistency with the measured spectra. By carefully considering all relevant conformations of this 20-membered macrocycle, reasonable agreement with the experiment is reached not only for the CD simulation of the individual conformers but also of the photoisomerization process of their admixture.


Osmotic induction of stress-responsive gene expression in the lobster Homarus americanus.
The American lobster, Homarus americanus, encounters osmotic stress throughout its life cycle. To understand the molecular basis of osmotic stress responses in vivo, we used homologous cDNA probes to characterize the mRNA patterns of lobster HSP70 (=70-kDa heat-shock protein), HSP90 (=90-kDa heat-shock protein), and polyubiquitin during hypo- and hyper-osmotic stress in abdominal muscle and hepatopancreas (a digestive tissue) at 30, 60, and 120 min of osmotic stress. Hypo- and hyper-osmotic stress significantly increased the levels of the mRNAs encoding HSP70 and HSP90 in abdominal muscle. Hyper-osmotic stress increased HSP90 mRNA levels in hepatopancreas, but hypo-osmotic stress did not. Both abdominal muscle and hepatopancreas exhibited significant changes in polyubiquitin gene expression during osmotic stress. In abdominal muscle, polyubiquitin mRNA levels increased during both hypo- and hyper-osmotic stress. Hepatopancreas, however, showed a significant elevation in polyubiquitin mRNA only during hypo-osmotic stress.


Risk assessment of the introduction of Rift Valley fever from the Horn of Africa to Yemen via legal trade of small ruminants.
Rift Valley fever (RVF) is a mosquito-borne viral zoonosis of increasing global importance. Occurring since 1930 across Africa, it was detected for the first time in Saudi Arabia and Yemen in September 2000, leading to human deaths and major losses in livestock populations. Assuming the virus has not survived in Yemen or has been circulating at a low level, authors qualitatively assessed the likelihood of "re-introduction" of RVF into Yemen through the legal importation of small ruminants from the Horn of Africa. The overall probability of introduction was assessed very low to medium, increasing during festival periods and higher when considering a direct transmission exposure as compared to a vectorial transmission exposure. The uncertainty was considered to be medium underlining important gaps in information that need to be fulfilled in the region. Options to reduce the risk are proposed and discussed, including possible improvements of the current Yemeni quarantine system.


Subthreshold Nano-Second Laser Treatment and Age-Related Macular Degeneration.
The presence of drusen is an important hallmark of age-related macular degeneration (AMD). Laser-induced regression of drusen, first observed over four decades ago, has led to much interest in the potential role of lasers in slowing the progression of the disease. In this article, we summarise the key insights from pre-clinical studies into the possible mechanisms of action of various laser interventions that result in beneficial changes in the retinal pigment epithelium/Bruch's membrane/choriocapillaris interface. Key learnings from clinical trials of laser treatment in AMD are also summarised, concentrating on the evolution of laser technology towards short pulse, non-thermal delivery such as the nanosecond laser. The evolution in our understanding of AMD, through advances in multimodal imaging and functional testing, as well as ongoing investigation of key pathological mechanisms, have all helped to set the scene for further well-conducted randomised trials to further explore potential utility of the nanosecond and other subthreshold short pulse lasers in AMD.


Immunohistochemical mapping of neuropeptide Y in the tree shrew brain.
Day-active tree shrews are promising animals as research models for a variety of human disorders. Neuropeptide Y (NPY) modulates many behaviors in vertebrates. Here we examined the distribution of NPY in the brain of tree shrews (Tupaia belangeri chinensis) using immunohistochemical techniques. The differential distribution of NPY-immunoreactive (-ir) cells and fibers were observed in the rhinencephalon, telencephalon, diencephalon, mesencephalon, metencephalon, and myelencephalon of tree shrews. Most NPY-ir cells were multipolar or bipolar in shape with triangular, fusiform, and/or globular perikarya. The densest cluster of NPY-ir cells were found in the mitral cell layer of the main olfactory bulb (MOB), arcuate nucleus of the hypothalamus, and pretectal nucleus of the thalamus. The MOB presented a unique pattern of NPY immunoreactivity. Laminar distribution of NPY-ir cells was observed in the MOB, neocortex, and hippocampus. Compared to rats, the tree shrews exhibited a particularly robust and widespread distribution of NPY-ir cells in the MOB, bed nucleus of the stria terminalis, and amygdala as well as the ventral lateral geniculate nucleus and pretectal nucleus of the thalamus. By contrast, a low density of neurons were scattered in the striatum, neocortex, polymorph cell layer of the dentate gyrus, superior colliculus, inferior colliculus, and dorsal tegmental nucleus. These findings provide the first detailed mapping of NPY immunoreactivity in the tree shrew brain and demonstrate species differences in the distribution of this neuropeptide, providing an anatomical basis for the participation of the NPY system in the regulation of numerous physiological and behavioral processes.


Short-term impact of tension-free vaginal tape obturator procedure on sexual function in women with stress urinary incontinence.
The tension-free vaginal tape obturator (TVT-O) procedure is one of the most commonly used anti-incontinence surgeries, but little is known about its impact on sexual function. To evaluate sexual function after the TVT-O procedure at 6 months postoperatively. Fifty-six sexually active women who underwent the TVT-O procedure for severe stress urinary incontinence (SUI) were evaluated using the short form of the Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire (PISQ-12) before and 6 months after surgery. The perception of incontinence-related quality-of-life were also evaluated by the short form of the Urogenital Distress Inventory (UDI-6) and the Incontinence Impact Questionnaire (IIQ-7) to assess the effect of surgery on incontinence. Total score and score for each PISQ-12 item. The mean total PISQ-12 score did not differ significantly before (24.0 + or - 12.2) and after (23.0 + or - 13.2) (P = 0.194) the TVT-O procedure. Scores for individual items on the PISQ-12 varied, with incontinence-related items improving but others, such as the frequency of achieving orgasm deteriorating for some women. The scores of UDI-6 and IIQ-7 were significantly improved by 6-month follow-up, indicating that the operation successfully resolved the incontinence. Despite successful amelioration of SUI by the TVT-O procedure, sexual function does not necessarily improve in the first 6 months after surgery.


Adenosine receptor A2B mediates alcoholic hepatitis by regulating cAMP levels and the NF-KB pathway.
Alcoholic hepatitis is a serious form of liver damage. Inflammation is a key factor in alcoholic hepatitis and plays a key role in the progression of alcoholic liver disease. Adenosine receptor A2B (A2BAR) is a member of the adenosine receptor family and generally considered to be a negative regulator of the inflammatory response. We found that A2BAR was the most highly expressed adenosine receptor in ETOH-fed mouse liver tissue and was also highly expressed in primary Kupffer cells and ETOH-induced RAW264.7 cells. In addition, injection of BAY 60-6583 stimulated A2BAR, induced upregulation of the expression levels of cAMP, and reduced ETOH-induced steatosis and inflammation in mice. At the same time, knockdown of A2BAR in vitro increased the inflammatory response in RAW264.7 cells triggered by ETOH. After knockdown of A2BAR in vitro, the release of the inflammatory cytokines IL-6, IL-1β and TNF-α was increased. After overexpression of A2BAR in vitro, the cAMP level was significantly increased, PKA expression was increased, the expression of phosphorylated proteins in the NF-kB signal transduction pathway was significantly affected, and the expression of the key phosphorylated protein p-P65 was decreased. However, after the simultaneous overexpression of A2BAR and inhibition of PKA, the expression of the key phosphorylated protein p-P65 was still significantly decreased. In addition, after the expression of A2BAR increased or decreased in RAW264.7 cells, AML-12 cells were cultured in the supernatant of RAW264.7 cells stimulated by ETOH, and the apoptosis rate was significantly changed by flow cytometry. These results suggest that A2BAR can reduce alcoholic steatohepatitis by upregulating cAMP levels and negatively regulating the NF-kB pathway. Overall, these findings suggest the significance of A2BAR-mediated inflammation in alcoholic liver disease.


The nonparasitic phase of Dermacentor nitens under field conditions in southeastern Brazil.
Dermacentor nitens is a one-host tick that uses domestic equids as main hosts. Herein, the nonparasitic phase of D. nitens was evaluated under field conditions in Pirassununga, São Paulo state, Southeastern Brazil. By exposing engorged females of D. nitens to field conditions (grass plots) for 24 consecutive months, this tick species was able to complete its nonparasitic phase by producing host-seeking larvae in the pasture throughout the year. Preoviposition and egg incubation periods were longer during autumn and winter months than during the other months. The number of larvae generated by engorged females was in most of the times lower during autumn and winter months, as demonstrated by lower egg hatching values. Such conditions could be linked to lower mean temperatures and rainfall. Larvae with the longest longevity hatched from the eggs with the shortest incubation periods. An apparent synchronism of larval hatching during spring was observed from the eggs laid by females during late winter and autumn, which is consistent with the phenomenon of "spring rise". The results indicate that D. nitens can complete up to five generations per year in southeastern Brazil, providing baseline data to develop future protocols for the appropriate control of D. nitens on horses.


Prospection by Any Other Name? A Response to Seligman et al. (2013).
We stand in agreement with Seligman et al. (2013, this issue) that prospection is an important psychological process, but we disagree that it has been neglected within the psychological literature. We further question some of the broader claims made by the authors regarding conscious decision making and free will. We argue that future-oriented cognition is fully consistent with deterministic accounts of cognition, including automaticity, and that prospection does little to advance the position of free will.


Blood pressure control in patients with chronic kidney disease according to office and home blood pressures.
The aim of this study was to assess blood pressure (BP) control in patients with chronic kidney disease (CKD) according to office and home BP and to assess the prevalence of normal BP, white-coat uncontrolled hypertension (WUCH), masked uncontrolled hypertension (MUCH) and elevated BP. Patients with renal failure with or without proteinuria were included in this multicenter observational study. Office BP was first measured by the physician using a self-monitoring BP device (three automatic readings), then by the patient at home (morning and evening) over 3 consecutive days. WUCH was defined as a systolic BP (SBP)/diastolic BP (DBP) ≥140/90 mmHg in the clinic and SBP/DBP<135/85 mmHg at home. MUCH was defined as SBP/DBP <140/90 mmHg in the clinic and SBP/DBP ≥135/85 mmHg at home. Among the 243 included subjects, data of 225 patients were analyzed. Mean estimated glomerular filtration rate was 37.7 ± 15.7 mL/min/1.73 m and mean office SBP/DBP was 154 ± 19/83 ± 13 mmHg. Mean office SBP/DBP was significantly higher than home SBP/DBP (+9.0 ± 15.1/+7.0 ± 10.0 mmHg, P < 0.01). Normal BP (office and home BP), WUCH, MUCH and elevated BP (office and home BP) rates were 12.0, 14.2, 6.7 and 67.1%, respectively. The patients were taking, on average, 2.8 ± 1.5 antihypertensive drugs/day. BP control in patients with CKD was poor. Routine use of 'out-of-office' BP measurement, in addition to office BP by which we can identify patients with WUCH or MUCH, should be recommended based on the current findings.


Cloning and tissue expression of chicken heart fatty acid-binding protein and intestine fatty acid-binding protein genes.
Fatty acid-binding proteins (FABPs) are members of a superfamily of lipid-binding proteins, occurring intracellularly in invertebrates and vertebrates. This study was designed to clone and characterize the genes of heart fatty acid-binding protein and intestine fatty acid-binding protein in the chicken. PCR primers were designed according to the chicken EST sequences to amplify cDNA of H-FABP and I-FABP genes from chicken heart and intestinal tissues. Analysis of sequence showed that the cDNA of the chicken H-FABP gene is 75 to 77% homologues to human, mouse, and pig H-FABP genes, and the chicken I-FABP gene is 71 to 72% homologues to human, mouse, and pig I-FABP genes. In addition, Northern blot analysis indicated that of the two genes, similar to the copartner of the mammal, H-FABP gene was expressed in a wide variety of tissues, and I-FABP gene was expressed only in intestinal tissues. The expression levels of the chicken H-FABP mRNA in heart and I-FABP mRNA in intestine had significant differences between the broilers from fat line and Bai'er layers at six weeks of age. The results of this study provided basic molecular information for studying the role of two FABPs in the regulation of fatty acid metabolism in avian species.


Shrink-wrapped isosurface from cross sectional images.
This paper addresses a new surface reconstruction scheme for approximating the isosurface from a set of tomographic cross sectional images. Differently from the novel Marching Cubes (MC) algorithm, our method does not extract the iso-density surface (isosurface) directly from the voxel data but calculates the iso-density point (isopoint) first. After building a coarse initial mesh approximating the ideal isosurface by the cell-boundary representation, it metamorphoses the mesh into the final isosurface by a relaxation scheme, called shrink-wrapping process. Compared with the MC algorithm, our method is robust and does not make any cracks on surface. Furthermore, since it is possible to utilize lots of additional isopoints during the surface reconstruction process by extending the adjacency definition, theoretically the resulting surface can be better in quality than the MC algorithm. According to experiments, it is proved to be very robust and efficient for isosurface reconstruction from cross sectional images.


Refinement of the primary hydration shell model for molecular dynamics simulations of large proteins.
A realistic representation of water molecules is important in molecular dynamics simulation of proteins. However, the standard method of solvating biomolecules, that is, immersing them in a box of water with periodic boundary conditions, is computationally expensive. The primary hydration shell (PHS) method, developed more than a decade ago and implemented in CHARMM, uses only a thin shell of water around the system of interest, and so greatly reduces the computational cost of simulations. Applying the PHS method, especially to larger proteins, revealed that further optimization and a partial reworking was required and here we present several improvements to its performance. The model is applied to systems with different sizes, and both water and protein behaviors are compared with those observed in standard simulations with periodic boundary conditions and, in some cases, with experimental data. The advantages of the modified PHS method over its original implementation are clearly apparent when it is applied to simulating the 82 kDa protein Malate Synthase G.


A toddler SHIME® model to study microbiota of young children.
The 'first 1000 days of life' determine the gut microbiota composition and can have long-term health consequences. In this study, the simulator of the human intestinal microbial ecosystem (SHIME®) model, which represents the main functional sections of the digestive tract, was chosen to study the microbiota of young children. The aim of this study was to reproduce the digestive process of toddlers and their specific colonic environment. The ascending, transverse and descending colons of SHIME® model were inoculated with feces from three donors aged between 1 and 2 years-old, in three separate runs. For each run, samples from colon vessels were collected at days 14, 21 and 28 after microbiota stabilization period. Short chain fatty acid concentrations determined by HPLC showed that microbiota obtained in SHIME® model shared characteristics between adults and infants. In addition, microbial diversity and bacterial populations determined by 16S rRNA amplicon sequencing were specific to each colon vessel. In conclusion, the SHIME® model developed in this study seemed well adapted to evaluate prebiotic and probiotic impact on the specific microbiota of toddlers, or medicine and endocrine disruptor metabolism. Moreover, this study is the first to highlight some biofilm development in in vitro gastrointestinal modelling systems.


The effect of ingested macronutrients on postprandial ghrelin response: a critical review of existing literature data.
Ghrelin is a powerful orexigenic gut hormone with growth hormone releasing activity. It plays a pivotal role for long-term energy balance and short-term food intake. It is also recognized as a potent signal for meal initiation. Ghrelin levels rise sharply before feeding onset, and are strongly suppressed by food ingestion. Postprandial ghrelin response is totally macronutrient specific in normal weight subjects, but is rather independent of macronutrient composition in obese. In rodents and lean individuals, isoenergetic meals of different macronutrient content suppress ghrelin to a variable extent. Carbohydrate appears to be the most effective macronutrient for ghrelin suppression, because of its rapid absorption and insulin-secreting effect. Protein induces prolonged ghrelin suppression and is considered to be the most satiating macronutrient. Fat, on the other hand, exhibits rather weak and insufficient ghrelin-suppressing capacity. The principal mediators involved in meal-induced ghrelin regulation are glucose, insulin, gastrointestinal hormones released in the postabsorptive phase, vagal activity, gastric emptying rate, and postprandial alterations in intestinal osmolarity.


Maternal mental health and adverse birth outcomes.
Recent research in economics emphasizes the role of in utero conditions for the health endowment at birth and in early childhood and for social as well as economic outcomes in later life. This paper analyzes the relation between maternal mental health during pregnancy and birth outcomes of the child. In particular, we analyze the relationship between maternal mental health during pregnancy and the probability of giving birth preterm (PT), having a newborn at low birth weight (LBW) or being small for gestational age (SGA). Based on large population-representative data from the German Socio-Economic Panel (SOEP) and cohort data from the National Educational Panel Study (NEPS), we present extensive descriptive evidence on the relationship between maternal mental health and preterm birth by carrying out OLS estimates controlling for a wide range of socioeconomic characteristics. In addition, we apply matching estimators and mother fixed effects models, which bring us closer toward a causal interpretation of estimates. In summary, the results uniformly provide evidence that poor maternal mental health is a risk factor for preterm birth and low birth weight in offspring. In contrast, we find no evidence for an relationship between maternal mental health and small for gestational age at birth.


Evidence that the plastid translocon Tic40 components possess modulating capabilities.
The transport of proteins into the plastid is a process that faces changing cellular needs such as the situation found in different plant organs or developing tissues. The plastid translocon must therefore be responsive to the changing cell environment to deliver efficiently different arrays of structurally diverse proteins. Although the Tic40-related envelope proteins appear to be translocon components designed to address the varying needs of protein translocation, details of their involvement remain elusive. This study was thus designed to combine plant-based experiments and yeast mitochondrion-based approaches for unveiling clues related to how the Tic40 components may behave during the protein translocation process. The main findings related to how Tic40 proteins may work are: 1) natural fluctuations are apparent in developing tissues, in different organs of the same plant, and in different species; 2) transgenic Arabidopsis seedlings can tolerate functionally a wide range of variations in Tic40 levels, from partial suppression to excessive production; 3) the Tic40 proteins themselves exhibit configurational changes in their association with yeast mitochondria in response to different carbon sources; 4) the presence of Tic40 proteins in yeast mitochondria influences regulatory aspects of the mitochondrial translocon; and 5) the Tic40 proteins associate with mitochondrial translocon components involved in regulatory-like events. The combined data provide evidence that Tic40 proteins possess modulating capabilities.


Imipenem/Cilastatin/Relebactam Alone and in Combination against Pseudomonas aeruginosa in the In Vitro Pharmacodynamic Model.
Combination therapy may enhance imipenem/cilastatin/relebactam's (I/R) activity against Pseudomonas aeruginosa and suppress resistance development. Human-simulated unbound plasma concentrations of I/R at 1.25 g every 6 h (h), colistin at 360 mg daily, and amikacin at 25 mg/kg daily were reproduced alone and in combination against six imipenem-nonsusceptible P. aeruginosa isolates in an in vitro pharmacodynamic model over 24 h. For I/R alone, the mean reductions in CFU ± the standard errors by 24 h were -2.52 ± 0.49, -1.49 ± 0.49, -1.15 ± 0.67, and -0.61 ± 0.10 log10 CFU/ml against isolates with MICs of 1/4, 2/4, 4/4, and 8/4 μg/ml, respectively. Amikacin alone also resulted in 24 h CFU reductions consistent with its MIC, while colistin CFU reductions did not differ. Resistant subpopulations were observed after 24 h in 1, 4, and 3 I/R-, colistin-, and amikacin-exposed isolates, respectively. The combination of I/R and colistin resulted in synergistic (n = 1) or additive (n = 2) interactions against three isolates with 24-h CFU reductions ranging from -2.62 to -4.67 log10 CFU/ml. The combination of I/R and amikacin exhibited indifferent interactions against all isolates, with combined drugs achieving -0.51- to -3.33-log10 CFU/ml reductions. No resistant subpopulations were observed during I/R and colistin combination studies, and when added to amikacin, I/R prevented the emergence of amikacin resistance. Against these six multidrug-resistant P. aeruginosa, I/R alone achieved significant CFU reductions against I/R-susceptible isolates. Combinations of I/R plus colistin resulted in additivity or synergy against some P. aeruginosa, whereas the addition of amikacin did not provide further antibacterial efficacy against these isolates.


Detection of inherited metabolic disorders via tandem mass spectrometry in Thai infants.
From a retrospective study in Medical Genetics Unit, Department of Pediatrics, Siriraj Hospital Faculty of Medicine, Mahidol University in Bangkok (1983-1988), the estimated pediatric patients with clinically suspected IEM are approximately 2-4% of total annual pediatrics admission of 5,000 or more. This is, a low estimation since survey from all teaching hospitals in the country including the largest Children's Hospital in Bangkok indicated the presence of numerous IEM. However, most IEM were clinically diagnosed with limited laboratory facilities. We started a collaboration with Magee Womens Hospital of Pittsburgh and NeoGen Screening, USA; using tandem mass spectrometry to diagnose high risk infants and children for IEM from July 1993 to March 1998. Of total 146 samples sent, we detected numerous metabolic disorders (11.2%) eg phenylketonuria, organic acidemia, maple syrup urine disease, isovaleric acidemia, methylmalonic acidemia, albinism, translocase/carnitine palmitoyltransferase type II, G6PD deficiency and lysinuric protein intolerance.


Protective effects of BiP inducer X (BIX) against diabetic cardiomyopathy in rats.
Diabetic cardiomyopathy (DC) is associated with impaired endoplasmic reticulum (ER) function, development of ER stress, and induction of cardiac cell apoptosis. Preventive effects of BiP inducer X (BIX) were investigated against DC characteristic changes in a type 2 diabetes rat model. To establish diabetes, a high-fat diet and a single dose of streptozotocin were administered. Then, animals were assigned into the following groups: control, BIX, diabetic animals monitored for one, two, and three weeks. Diabetic rats were treated with BIX for one, two, and three weeks. Expressions of various ER stress and apoptotic markers were assessed by immunoblotting method. CHOP gene expression was assessed by Real-time PCR. Tissue expression of BiP was evaluated by immunohistochemistry method. Hematoxylin and eosin and Masson's trichrome staining were performed to assess histological changes in the left ventricle. Cardiac cell apoptosis was examined using TUNEL assay. BIX administration suppressed the activation of the ER stress markers and cleavage of procaspase-3 in the diabetic rats. Likewise, tissue expression of BiP protein was increased, while CHOP mRNA levels were decreased. These results were accompanied by reducing cardiac fibrosis and myocardial cell apoptosis suggesting protective effects of BIX against the development of DC by decreasing cardiomyocyte apoptosis and fibrosis.


Interferon gamma (IFNgamma) gene transfer of an EMT6 tumor that is poorly responsive to IFNgamma stimulation: increase in tumor immunogenicity is accompanied by induction of a mouse class II transactivator and class II MHC.
Abstract Interferon gamma (IFNgamma) is an important cytokine with immunomodulatory properties that include activation of immune cells and induction of class I and class II major histocompatibility complex antigens. In this study a retroviral vector was used to introduce the IFNgamma gene into EMT6 tumor cells to assess the effect of IFNgamma gene expression on tumor immunogenicity. Transfectants were selected in G418-containing tissue-culture medium and were determined to express the inserted IFNgamma gene by reverse transcriptase/polymerase chain reaction. Flow-cytometric analysis revealed that parental unmodified EMT6 cells constitutively expressed only class I MHC and were poorly responsive to exogenous IFNgamma stimulation, whereas class II MHC was induced in IFNgamma-transfected cells. The induction of class II MHC in IFNgamma-transfected cells correlated with the expression of a mouse class II transactivator gene that was dormant in unmodified or mock-transfected cells. In addition, IFNgamma-gene-transfected tumor cells were found to secrete up to 17 ng IFN (equivalent to 75 units/10(6) cells) by enzyme-linked immunosorbent assay (ELISA). Whereas parental EMT6 cells grew unchecked, the growth of genetically modified tumor cells was significantly inhibited in immunocompetent mice. Rechallenge of animals that rejected an IFNgamma-transfected EMT6 clone (EMT6-B17) with parental EMT6 cells resulted in tumor rejection, suggesting that IFNgamma-transfected EMT6 cells were able to induce long-term immunity. Mixing experiments using gene-transfected and unmodified tumor cells demonstrated that 10% of IFNgamma-transfected cells in the population was sufficient to protect mice against subsequent challenge with tumorigenic EMT6 cells. These studies demonstrate that the immunogenicity of tumor cells that are poorly responsive to exogenous IFNgamma can be enhanced by inserting and expressing the IFNgamma transgene. These findings also suggest a role for class II MHC in reducing tumorigenicity of the EMT6 tumor and inducing long-term tumor immunity.


Characteristics and risk profile of psoriasis patients included in the Czech national registry BIOREP and a comparison with other registries.
BIOREP is a Czech registry of psoriatic patients on biological treatment in a clinical setting. We describe the characteristics of patients with psoriasis at the time of enrollment and present comparisons with published data from other national registries. We analyzed the cohort of patients treated with biologics between May 2005 and May 2015. Demographic data, previous therapies, comorbidities, and severity of psoriasis were compared with data from other registries - DERMBIO, BIOBADADERM, BADBIR, and PSOBEST. A total of 1412 psoriatic patients initiating biological treatment were included with a predominance of males (63.4%). The mean patient age was 50.2 years, and approximately 70.5% of patients were either overweight or obese. The mean baseline Psoriasis Area and Severity Index was 19.8, and the Dermatology Life Quality Index was 16.6. More than one-third of patients (41.0%) reported a history of psoriatic arthritis, and a high proportion of patients (49.5%) with cardiovascular risk factors (hypertension [35.2%], hyperlipidemia [27.7%], diabetes mellitus [11.4%], coronary heart disease [4.9%], and obesity [15.2%]) were observed. Most of the patients had been previously treated with phototherapy (85.4%), acitretin (74.0%), methotrexate (65.7%), or cyclosporine (53.1%). BIOREP is one of the first registries of patients with psoriasis treated with biologics in Central and Eastern Europe. Our results found a similar or higher prevalence of comorbidities, long disease duration, and high impact on the quality of life among patients included in Western European registries.


Musculoskeletal problems among workers of an Iranian sugar-producing factory.
Assessment of the level of exposure to work-related musculoskeletal disorders (WMSDs) risk factors can be an appropriate basis for planning and implementing an interventional ergonomics program in the workplace. This study was conducted among workers of an Iranian sugar-producing factory to determine WMSD prevalence rate among production workers and to assess the level of exposure to WMSD risks. In total, 116 workers were randomly selected from production workshops and included in the study. The Nordic musculoskeletal questionnaire was used to study prevalence of WMSDs and a quick exposure check (QEC) was used to assess physical exposure to risks. Required data were videotaped. Most workers (87.1%) suffered from some kind of MSD symptoms during the 12 months prior to the study. The highest prevalence was reported in knees (58.6%) and the lower back (54.3%). In 99.1% of the workers, the level exposure to MSD risks established with QEC was high and very high. Awkward postures, manual material handling, and long hours of standing were the major ergonomics problems. There was a high rate of WMSDs in this factory. The level of exposure to WMSD risk factors was high and corrective measures for reducing risk level were essential.


[The value of certain parameters in the diagnosis and detection of metabolic X syndrome].
Authors summarise their 5-year long experiences on 343 patients about diagnostic methods of metabolic syndrome X and offer a simple possibility for screening of the jeopardized individuals. In a group of patients with hypertension and central obesity (group I: with 2 insulin resistant condition), 229 (89%) out of 255 cases met the basic criteria of the syndrome X which were hypertension, central obesity and high insulin levels for the corresponding blood sugar levels during oral glucose tolerance test (probable insulin resistance). Dyslipidemia was missing in 20% of these people. Hyperinsulinism occurred in 85%, glucose intolerance in 53%, presumable insulin resistance in 90% of cases. Insulin resistance was characterised by late hyperinsulinism (90 and 120 min.) during oral glucose tolerance test. This was the case in people with "diabetoid" glucose responses too, suggesting an early failure of glucose tolerance and/or insulin secretion. Components of syndrome X were present with a lower frequency in 24 patients with obesity (group II), in 35 patients with hypertension (group III) and in 29 patients without obesity or hypertension (group IV), as well. According to central obesity and hypertension, syndrome X could be screened by a probability of 90%. This can be helpful in prevention of NIDDM and coronary heart disease.


Comparison of four pancreatic islet implantation sites.
Although the liver is the most common site for pancreatic islet transplantation, it is not optimal. We compared kidney, liver, muscle, and omentum as transplantation sites with regard to operative feasibility, and the efficiency of implantation and glycemic control. Islets from C57BL/6 mice were transplanted into diabetic syngeneic recipients. The mean operative time and mortality were measured to assess feasibility. To assess implantation efficiency, the marginal mass required to cure diabetes and the mean time taken to achieve normoglycemia were measured. A glucose tolerance test was performed to assess glycemic control efficiency. The data are listed in the order of the kidney, liver, muscle, and omentum, respectively. The mean mortality rate was 6.7, 20.0, 7.1, and 12.5%; the mean operative time was 10.2, 27.4, 11.2, and 19.8 min; the marginal islet mass was 100, 600, 600, and 200 islet equivalence units and the mean time to reach euglycemia was 3.0, 15.1, 26.6, and 13.9 days. The glucose kinetics of omental pouch islets was the most similar to controls. Thus, a strategic approach is required for deciding on the best transplantation recipient sites after considering donor sources and islet volume. Alternatives can be chosen based on safety or efficacy.


Xenopus Shugoshin 2 regulates the spindle assembly pathway mediated by the chromosomal passenger complex.
Shugoshins (Sgo) are conserved proteins that act as protectors of centromeric cohesion and as sensors of tension for the machinery that eliminates improper kinetochore-microtubule attachments. Most vertebrates contain two Sgo proteins, but their specific functions are not always clear. Xenopus laevis Sgo1, XSgo1, protects centromeric cohesin from the prophase dissociation pathway. Here, we report the identification of XSgo2 and show that it does not regulate cohesion. Instead, we find that it participates in bipolar spindle assembly. Both Sgo proteins interact physically with the Chromosomal Passenger Complex (CPC) containing Aurora B, a key regulator of mitosis, but the functional consequences of such interaction are distinct. XSgo1 is required for proper localization of the CPC while XSgo2 positively contributes to its activation and the subsequent phosphorylation of at least one key substrate for bipolar spindle assembly, the microtubule depolymerizing kinesin MCAK (Mitotic Centromere-Associated Kinesin). Thus, the two Xenopus Sgo proteins have non-overlapping functions in chromosome segregation. Our results further suggest that this functional specificity could rely on the association of XSgo1 and XSgo2 with different regulatory subunits of the PP2A complex.


A child with chronic manganese exposure from drinking water.
The patient's family bought a home in a suburb, but the proximity of the house to wetlands and its distance from the town water main prohibited connecting the house to town water. The family had a well drilled and they drank the well water for 5 years, despite the fact that the water was turbid, had a metallic taste, and left an orange-brown residue on clothes, dishes, and appliances. When the water was tested after 5 years of residential use, the manganese concentration was elevated (1.21 ppm; U.S. Environmental Protection Agency reference, < 0.05 ppm). The family's 10-year-old son had elevated manganese concentrations in whole blood, urine, and hair. The blood manganese level of his brother was normal, but his hair manganese level was elevated. The patient, the 10-year-old, was in the fifth grade and had no history of learning problems; however, teachers had noticed his inattentiveness and lack of focus in the classroom. Our results of cognitive testing were normal, but tests of memory revealed a markedly below-average performance: the patient's general memory index was at the 13th percentile, his verbal memory at the 19th percentile, his visual memory at the 14th percentile, and his learning index at the 19th percentile. The patient's free recall and cued recall tests were all 0.5-1.5 standard deviations (1 SD = 16th percentile) below normal. Psychometric testing scores showed normal IQ but unexpectedly poor verbal and visual memory. These findings are consistent with the known toxic effects of manganese, although a causal relationship cannot necessarily be inferred.


Reticulons Regulate the ER Inheritance Block during ER Stress.
Segregation of functional organelles during the cell cycle is crucial to generate healthy daughter cells. In Saccharomyces cerevisiae, ER stress causes an ER inheritance block to ensure cells inherit a functional ER. Here, we report that formation of tubular ER in the mother cell, the first step in ER inheritance, depends on functional symmetry between the cortical ER (cER) and perinuclear ER (pnER). ER stress induces functional asymmetry, blocking tubular ER formation and ER inheritance. Using fluorescence recovery after photobleaching, we show that the ER chaperone Kar2/BiP fused to GFP and an ER membrane reporter, Hmg1-GFP, behave differently in the cER and pnER. The functional asymmetry and tubular ER formation depend on Reticulons/Yop1, which maintain ER structure. LUNAPARK1 deletion in rtn1Δrtn2Δyop1Δ cells restores the pnER/cER functional asymmetry, tubular ER generation, and ER inheritance blocks. Thus, Reticulon/Yop1-dependent changes in ER structure are linked to ER inheritance during the yeast cell cycle.


Process-oriented training in breastfeeding alters attitudes to breastfeeding in health professionals.
The purpose of the study was to measure the attitudes of antenatal midwives and postnatal nurses to breastfeeding before and after common, process-oriented breastfeeding training. Antenatal centres and child-health centres in 10 municipalities were randomized to either an intervention or a control group. The antenatal midwives and postnatal nurses in the intervention group were together given process-oriented breastfeeding training and were, in addition, asked to develop a common breastfeeding policy. A previously developed instrument was used to measure the effects of a training programme on breastfeeding attitudes among midwives and postnatal nurses. It consisted of four scales measuring a person's attitudes toward breastfeeding in four dimensions: regulating, facilitating, disempowering, and breastfeeding-antipathy attitudes. A mean score was calculated for each individual on these four dimensional scales. The higher the score, the stronger the attitude. After one year, the intervention group reduced their scores on the regulating scale when compared with the control group (p<0.001). The intervention group decreased their scores on the regulating scale and increased their scores on the facilitating scale over the first year after training. The control group also significantly increased their scores on the facilitating scale. When the results were analysed profession-wise, the postnatal nurses in the intervention group decreased their scores on the regulating and disempowering scales and increased their scores on the facilitating scale. In contrast, the midwives in the intervention group decreased their scores only on the breastfeeding antipathy scale. The control group midwives decreased their scores on the disempowering scale. No differences were found among the postnatal nurses in the control group. Process-oriented breastfeeding training made both antenatal midwives and postnatal nurses better disposed to breastfeeding; postnatal nurses in particular improved their attitudes. Attitudes to breastfeeding tended to be stable over time, but process-oriented training lowered the scores a little on the regulating scale, suggesting that after this kind of training counsellors would find it less necessary to schedule and control the mothers' breastfeeding behaviour.


Alternative methods of photosynthetic carbon assimilation in marine macroalgae.
Two green macroalgae, Codium decorticatum and Udotea flabellum, differ photosynthetically. Codium had high O(2)-sensitive, and Udotea low O(2)-insensitive, CO(2) compensation points; Codium showed a Warburg effect at seawater dissolved inorganic carbon levels and had photorespiratory CO(2) release, whereas Udotea did not. Seawater dissolved inorganic carbon levels did not saturate photosynthesis. For Codium, but not Udotea, the Warburg effect was increased by ethoxyzolamide, a carbonic anhydrase inhibitor, at high but not low pH. Isolated chloroplasts from both macroalgae showed a Warburg effect that was ethoxyzolamide-insensitive. In both macroalgae, chloroplastic and extrachloroplastic carbonic anhydrase activity was present. P-enolpyruvate carboxykinase (PEPCK) carboxylating activity in Udotea extracts was equivalent to that of ribulose bisphosphate carboxylase, and enzyme activities for C(4) acid metabolism and P-enolpyruvate regeneration were sufficient to operate a limited C(4)-like system. In Udotea, malate and aspartate were early-labeled photosynthetic products that turned over within 60 seconds. Photorespiratory compounds were much less labeled in Udotea. Low dark fixation rates ruled out Crassulacean acid metabolism. A limited C(4)-like system, based on PEPCK, is hypothesized to be the mechanism reducing photorespiration in Udotea. Codium showed no evidence of photosynthetic C(4) acid metabolism. Marine macroalgae, like terrestrial angiosperms, seem to have diverse photosynthetic modes.


Corrections and clarifications.
The article about the viral hybrid SHIV by Joseph Sidroski and his colleagues that was reported in Jon Cohen's News & Comment article "Monkey-human viral hybrid is new weapon in AIDS fight" (24 July, p. 478), appeared in the July issue of the Journal of Acquired Immune Deficiency Syndrome, not the June issue, as stated.


Autophagy in α-Synucleinopathies-An Overstrained System.
Alpha-synucleinopathies comprise progressive neurodegenerative diseases, including Parkinson's disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA). They all exhibit the same pathological hallmark, which is the formation of α-synuclein positive deposits in neuronal or glial cells. The aggregation of α-synuclein in the cell body of neurons, giving rise to the so-called Lewy bodies (LBs), is the major characteristic for PD and DLB, whereas the accumulation of α-synuclein in oligodendroglial cells, so-called glial cytoplasmic inclusions (GCIs), is the hallmark for MSA. The mechanisms involved in the intracytoplasmic inclusion formation in neuronal and oligodendroglial cells are not fully understood to date. A possible mechanism could be an impaired autophagic machinery that cannot cope with the high intracellular amount of α-synuclein. In fact, different studies showed that reduced autophagy is involved in α-synuclein aggregation. Furthermore, altered levels of different autophagy markers were reported in PD, DLB, and MSA brains. To date, the trigger point in disease initiation is not entirely clear; that is, whether autophagy dysfunction alone suffices to increase α-synuclein or whether α-synuclein is the pathogenic driver. In the current review, we discuss the involvement of defective autophagy machinery in the formation of α-synuclein aggregates, propagation of α-synuclein, and the resulting neurodegenerative processes in α-synucleinopathies.


Expression, localization, and function of transforming growth factor-beta s in embryonic chick spinal cord, hindbrain, and dorsal root ganglia.
We have studied the localizations of transforming growth factor-beta (TGF-beta) 2 and 3 immunohistochemically using isoform-specific antibodies and TGF-beta 3 mRNA by in situ hybridization in the nervous system of the 3- to 15-day-old chick embryo with special reference to spinal cord, hindbrain, and dorsal root ganglia (DRG). At embryonic day (E) 3, TGF-beta 3 mRNA as well as TGF-beta 2 and 3 immunoreactivities (IRs) were most prominent in the notochord, wall of the aorta, and dermomyotome. At E5 and E7, strong TGF-beta 2 and 3 IR were seen in or on radial glia of spinal cord and hindbrain. Radial glia in the floor plate region and ventral commissure gave the most intense signal. In the DRG, fiber strands of intense IRs representing extracellular matrix or satellite cells were seen. Neuronal perikarya did not become IR for TGF-beta 2 and 3 until E11, but even then the moderate signals for TGF-beta 3 mRNA could not be specifically localized to the neuronal cell bodies. In E11 and older embryos, spinal cord glial or glial progenitor cells, but not neuronal cell bodies were labeled for TGF-beta 3 mRNA. Immunocytochemistry and western blot analysis indicated that E8 DRG neurons have the TGF-beta receptor type II, and treatment of these cells with NGF induces expression of TGF-beta 3 mRNA. The TGF-beta isoforms 1, 2, and 3 did not promote survival of E8 DRG neurons in dissociated cell cultures. All three TGF-beta isoforms, however, promoted neurite growth from E8 DRG explants, but were less potent than nerve growth factor. Our data suggest identical localizations of TGF-beta 2 and -beta 3 IR in the developing chick and mammalian nervous systems, underscoring the general importance of TGF-beta s in fundamental events of neural development.


Effect of caffeine on cardiovascular function in the stage 24 chick embryo.
Caffeine is consumed by an estimated 95% of pregnant women. Yet, it is not known if caffeine alters embryonic cardiovascular function. We measured the effect of caffeine on mean and phasic dorsal aortic blood flow and mean vitelline artery pressure with a 20-MHz pulse Doppler velocity meter and a servo-null pressure system, respectively. We calculated vascular resistance, stroke volume index, and heart rate. We injected 5-microliters aliquots of anhydrous caffeine dissolved in chick Ringer's lactate into a vitelline vein in doses from 1.2 X 10(-5) mg (0.15 mg/kg) to 1.2 X 10(-2) mg (150 mg/kg). Control embryos received 5 microliters chick Ringer's lactate. The hemodynamic measurements were continuously recorded from 1 min prior through 5 min after injection. 9 stage 24 chick embryos were studied at each dose. The data were analyzed by one-way analysis of variance and Tukey's HSD test. Caffeine had no effect on heart rate, but a direct dose-related effect on mean dorsal aortic blood flow, stroke volume index, mean pressure, and vascular resistance. The effect of caffeine on stroke volume index at 5 min was a linear log-dose relationship [y = 0.155 + 0.02 1n (dose), p less than 0.001]. In the chick, caffeine acutely affects cardiovascular function by increasing myocardial contractility and dilating resistance vessels. We speculate this action is mediated through direct cellular effects: increase in free Ca++ and cyclic adenosine monophosphate.


TALEN/CRISPR-mediated engineering of a promoterless anti-viral RNAi hairpin into an endogenous miRNA locus.
Successful RNAi applications depend on strategies allowing robust and persistent expression of minimal gene silencing triggers without perturbing endogenous gene expression. Here, we propose a novel avenue which is integration of a promoterless shmiRNA, i.e. a shRNA embedded in a micro-RNA (miRNA) scaffold, into an engineered genomic miRNA locus. For proof-of-concept, we used TALE or CRISPR/Cas9 nucleases to site-specifically integrate an anti-hepatitis C virus (HCV) shmiRNA into the liver-specific miR-122/hcr locus in hepatoma cells, with the aim to obtain cellular clones that are genetically protected against HCV infection. Using reporter assays, Northern blotting and qRT-PCR, we confirmed anti-HCV shmiRNA expression as well as miR-122 integrity and functionality in selected cellular progeny. Moreover, we employed a comprehensive battery of PCR, cDNA/miRNA profiling and whole genome sequencing analyses to validate targeted integration of a single shmiRNA molecule at the expected position, and to rule out deleterious effects on the genomes or transcriptomes of the engineered cells. Importantly, a subgenomic HCV replicon and a full-length reporter virus, but not a Dengue virus control, were significantly impaired in the modified cells. Our original combination of DNA engineering and RNAi expression technologies benefits numerous applications, from miRNA, genome and transgenesis research, to human gene therapy.


Naturally-Derived Amphiphilic Polystyrenes Prepared by Aqueous Controlled/Living Cationic Polymerization and Copolymerization of Vinylguaiacol with R⁻OH/BF₃·OEt₂.
In this study, we investigated direct-controlled/living cationic polymerization and copolymerization of 4-vinylguaiacol (4VG), i.e., 4-hydroxy-3-methoxystyrene, which can be derived from naturally-occurring ferulic acid, to develop novel bio-based amphiphilic polystyrenes with phenol functions. The controlled/living cationic polymerization of 4VG was achieved using the R⁻OH/BF₃·OEt₂ initiating system, which is effective for the controlled/living polymerization of petroleum-derived 4-vinylphenol in the presence of a large amount of water via reversible activation of terminal C⁻OH bond catalyzed by BF₃·OEt₂, to result in the polymers with controlled molecular weights and narrow molecular weight distributions. The random or block copolymerization of 4VG was also examined using p-methoxystyrene (pMOS) as a comonomer with an aqueous initiating system to tune the amphiphilic nature of the 4VG-derived phenolic polymers. The obtained polymer can be expected not only to be used as a novel styrenic bio-based polymer but also as a material with amphiphilic nature for some applications.


Confounding effect of biologic maturation on sex differences in physical activity and sedentary behavior in adolescents.
Sex differences in physical activity (PA) through pubertal maturation and the growth spurt are often attributed to changing interests. The contribution of sex differences in biological maturation to the adolescent decline has received limited attention. This study examined the contribution of somatic maturation to sex differences in objective assessments of sedentary behavior and PA in Portuguese adolescents (N = 302, aged 13-16 years). Maturation was estimated from the percentage of predicted mature stature and physically active and inactive behaviors assessed with Actigraph GT1M accelerometers. The influence of age, sex and their interaction on body size, maturation and physical behaviors were examined using factorial ANOVA and, subsequently, ANCOVA (controlling for maturation) tested the effect of sex. Males spent more time in MVPA and less time in sedentary behavior than females. However, sex differences were attenuated when maturation was controlled; thus suggesting that maturity may play an important role in adolescent behaviors.


How we treat febrile neutropenia in patients receiving cancer chemotherapy.
Although improved supportive care has reduced mortality associated with febrile neutropenia, it continues to cause chemotherapy limitations, morbidity, mortality, and cost among patients with cancer.


A note on estimating the cause of death structure in high mortality populations.
Strategies for reducing mortality should be based on an informed assessment of the underlying structure of causes of death. In the absence of an adequate vital registration scheme, cause of death information is generally derived from fragmentary data which are often limited to specific sectors of the population. Using the previous mortality experience of industrialized countries at higher levels of mortality and the cause of death returns of contemporary developing societies with reasonably accurate and complete mortality data, a linear model has been developed to estimate the cause-structure of mortality in a population from knowledge of the crude death rate alone. Through an appropriate weighting of age-cause-specific mortality rates, emphasis is placed on those causes of death likely to be of greatest concern in high mortality populations. Using the model parameters derived in this fashion, the technique is applied to estimate the cause-structure of mortality in Java. The resulting distribution of deaths differs markedly from that suggested by an older age-standard and is much more in accord with epidemiological opinion about likely causes of death based on rural health surveys, hospital records, and other health data. Regression parameters for estimating the cause of death structure during infancy and early childhood are also shown and may be used independently of the all-age regression estimates.


The pulmonary manifestations of AIDS-related non-Hodgkin's lymphoma.
To describe the clinical, radiographic, and autopsy features of AIDS-related non-Hodgkin's Iymphoma (NHL) with pulmonary involvement. Retrospective series of patients with HIV infection and NHL with pathologically documented lung or pleural involvement. A university and a county hospital in San Francisco. Thirty-eight patients with HIV infection and NHL involving the lungs or pleura. Most patients had respiratory symptoms (87%) and signs (84%). The majority of patients had advanced HIV infection, with a mean CD4 count of 67 (+/- 65). The most common laboratory abnormalities were elevated lactate dehydrogenase value (89%), elevated erythrocyte sedimentation rate (94%), hematologic abnormalities (95%), and widened alveolar-arterial gradient (89%). Thoracic CT revealed pulmonary nodules (50%), lobar infiltrates (27%), and lung mass (19%) as the most common parenchymal abnormalities. Pleural effusion (68%) and thoracic lymphadenopathy (54%) were unexpectedly common. Autopsy confirmed the high prevalence of pulmonary nodules (30%), airspace disease (35%), and lung mass (25%). Pleural effusions (65%) and thoracic lymphadenopathy (60%) were also common at autopsy. The respiratory system was the most common extranodal site (71%) in patients with AIDS-related NHL undergoing autopsy. Of the bronchoscopic procedures performed, transbronchial biopsy had the highest diagnostic yield (58%) for lymphoma. BAL and bronchial brushing were never diagnostic. Pleural fluid cytologic study and open lung biopsy specimens also had high diagnostic yields (75% each). The lung is a common extranodal site in AIDS-related NHL. NHL with pulmonary involvement occurs primarily in patients with advanced HIV infection. Most patients have nodules, infiltrates, or masses by thoracic imaging and autopsy. Thoracic lymphadenopathy is much more common than previously believed. Transbronchial biopsy, pleural fluid cytologic study, and open lung biopsy are the most useful diagnostic procedures.


Improving the management of neuropathic pain.
Neuropathic pain is defined as 'pain arising as a direct consequence of a lesion or disease of the somatosensory system'. It may reflect a widespread neuropathic process (e.g. diabetic neuropathy) or a more focal disorder (e.g. post-herpetic neuralgia). The practical importance of recognising neuropathic pain (as distinct from nociceptive pain) lies in the difference in effective treatments. The patient may be experiencing more than one type of pain. Many long-term disabling neurological disorders, such as multiple sclerosis, as well as causing neuropathic pain, may also give rise to musculoskeletal pains which may be more readily amenable to treatment. Most treatment for long-term pain, including neuropathic pain, should be provided in primary care, with specialist support. When taking the history it is important to elicit information about the site, duration, intensity and character of the pain, or pains, and what precipitates and relieves it. Accompanying somatosensory disturbance in the painful territory (numbness; allodynia; hyperalgesia; paraesthesia and dysaesthesia) is strongly suggestive of neuropathic pain. A specialist opinion should be sought where the diagnosis is uncertain, or the patient's condition is rapidly deteriorating or uncontrolled. This may be a specialist in a particular condition, to address issues of primary diagnosis, or a specialist in pain medicine to advise on, or provide, further treatment. Patients who are struggling with their pain are best served by specialist centres that can endeavour to explain the condition and encourage self-management.


Mouse Embryonic Fibroblasts Isolated From Nthl1 D227Y Knockin Mice Exhibit Defective DNA Repair and Increased Genome Instability.
Oxidative DNA damage as a result of normal cellular metabolism, inflammation, or exposure to exogenous DNA damaging agents if left unrepaired, can result in genomic instability, a precursor to cancer and other diseases. Nth-like DNA glycosylase 1 (NTHL1) is an evolutionarily conserved bifunctional DNA glycosylase that primarily removes oxidized pyrimidine lesions. NTHL1 D239Y is a germline variant identified in both heterozygous and homozygous state in the human population. Here, we have generated a knockin mouse model carrying Nthl1 D227Y (mouse homologue of D239Y) using CRISPR-cas9 genome editing technology and investigated the cellular effects of the variant in the heterozygous (Y/+) and homozygous (Y/Y) state using murine embryonic fibroblasts. We identified a significant increase in double stranded breaks, genomic instability, replication stress and impaired proliferation in both the Nthl1 D227Y heterozygous Y/+ and homozygous mutant Y/Y MEFs. Importantly, we identified that the presence of the D227Y variant interferes with repair by the WT protein, possibly by binding and shielding the lesions. The cellular phenotypes observed in D227Y mutant MEFs suggest that both the heterozygous and homozygous carriers of this NTHL1 germline mutation may be at increased risk for the development of DNA damage-associated diseases, including cancer.