Owner perceptions of radiotherapy treatment for veterinary patients with cancer.
Veterinary clients may have trepidation about treating their pet with radiotherapy because of concerns about radiation side effects or repeated anaesthetics. The purpose of this study is to assess whether owners' attitudes towards veterinary radiotherapy, including concerns over side effects, change during the course of treatment, and whether radiotherapy was perceived to affect pets' quality of life (QOL). A prospective cohort study of clients from 2012 to 2015 was performed. Pets received palliative or definitive radiotherapy for various tumours. Clients completed questionnaires before, during and after radiotherapy. Questions assessed owner preconceptions before treatment, including side effect expectations, actual side effects experienced and overall satisfaction with the process. In addition, at each time point, the owners assessed their pet's QOL using a simple numerical scale. Forty-nine patients were included. After completing treatment, owners were significantly less concerned about potential side effects of radiotherapy (P < 0.001), side effects associated with repeat anaesthetics (P < 0.001), and about radiotherapy in general (P < 0.001). QOL did not show a significant change at any point during or after treatment. Following treatment, 94% reported that the experience was better than expected and 100% supported the use of radiotherapy in pets. This is the first prospective study evaluating client attitudes and satisfaction before and after radiotherapy treatment in pets. The results indicate that radiotherapy is well tolerated, and the anxiety associated with radiotherapy is significantly alleviated after experiencing the process. These results will help veterinarians allay client concerns, and will hopefully lead to an increase in clients pursuing radiotherapy in pets.


Neuroserpin.
Neuroserpin is a member of the serpin family of serine protease inhibitors. Tissue distribution analysis reveals a predominantly neuronal expression during the late stages of neurogenesis and, in the adult brain, in areas where synaptic changes are associated with learning and memory (synaptic plasticity). In vitro studies revealed complex formation between neuroserpin and different serine proteases, i.e. tPA, uPA, and plasmin. The neuroserpin-target complex has so far not been characterized in vivo. However, some investigations help to understand the functional role of this serpin. Neuroserpin was shown to be involved in the regulation of the morphology of neuroendocrine cells in culture, possibly by modulating the degradation of the extracellular matrix by proteolytic enzymes such as tPA. Moreover, a role of neuroserpin in mood regulation has been deduced from the over- and underexpression of neuroserpin in genetically modified mice, which showed increased anxiety and novelty-induced hypo-locomotion. In pathological conditions of the central nervous system (i.e. stroke and seizures), neuroserpin plays a neuroprotective role, probably by blocking the deleterious effects of tPA. A familial form of a neurodegenerative disease, termed familial encephalopathy with neuroserpin inclusion bodies, is caused by point mutations in the neuroserpin gene. This condition is characterized by the intracellular polymerization and accumulation of mutated neuroserpin, leading to neuronal death and dementia.


Curative efficacy of penehyclidine combined with edaravone on acute cerebral infarction and their effects on serum TNF-α and NDS score in rats.
To investigate the effects of penehyclidine combined with edaravone on acute cerebral infarction (ACI) in rats. A rat model of middle cerebral artery infarction was created. The rats were randomly divided into sham, model and treatment group. After grouping, rats in the treatment groups were treated with edaravone combined with phenecyclidine. The rats in the sham and model group were given an equal volume of phosphate-buffered saline (PBS). The therapeutic effects on rats at 3 d and 7 d after treatment were observed, the levels of serum TNF-α, interleukin-6 (IL-6) and high-mobility group box 1 protein (HMGB1) before and after treatment were compared, and the NDS scores were recorded. After treatment, the effective rate in treatment groups was higher than that in control group. The expression levels of serum TNF-α, HMGB1 and IL-6 in treatment groups showed gradually decreasing trends after treatment, and there were significant differences in the levels before and after treatment (p<0.05). At 3 d, the decrease ranges of expression levels of TNF-α, HMGB1, and IL-6 in model and treatment groups were larger than those in control group; there were statistically significant differences in the expression levels between the two groups (p<0.05). The NDS score was gradually decreased after treatment, while the activities of daily living (ADL) score were gradually increased after treatment. There were significant differences in the scores between the two groups at each time point (p<0.05). There were positive correlations of the expression levels of serum IL-6 and HMGB1 with the expression level of TNF-α (correlation coefficient=0.8731 and 0.9084, p<0.01), and there was also a positive correlation between the TNF-α level and the NDS score (correlation coefficient=0.8331, p<0.01). Penehyclidine combined with edaravone has a better clinical treatment effect on ACI rats, which can significantly reduce the levels of serum TNF-α, IL-6 and HMGB1 and the NDS score, so it is worthy of popularization in clinical application.


Molecular diagnosis of Acanthamoeba keratitis: evaluation in rat model and application in suspected human cases.
Acanthamoeba keratitis (AK) is a progressive corneal infection that demands rapid and sensitive techniques for diagnosis to avoid risk of visual impairment. We evaluated two DNA extraction techniques and a semi-nested-PCR (snPCR) targeting the 18S rRNA gene to detect Acanthamoeba cysts and trophozoites. The most effective protocol was evaluated in samples of corneal scrapings and biopsies from an AK rat model and applied to diagnosis of human cases of AK. DNA extraction performed with a commercial kit based on DNA binding to magnetic beads was more efficient than a method based on alkaline lysis, allowing the detection of one trophozoite and one cyst of Acanthamoeba in samples prepared from cultures. This technique and sn-PCR were applied in corneal scrapings of rats experimentally infected with Acanthamoeba (n = 6), resulting in 100% of positivity, against 16.7% (n = 6) of positive identification in culture method using non-nutrient agar (NNA) with Escherichia coli. Corneal biopsies from rats were also tested (n = 6) and resulted in positivity in all samples in both molecular and culture methods. Eight out of ten presumptive human cases of Acanthamoeba keratitis were also confirmed by sn-PCR of scrapping samples, while the culture method was positive in only four cases. We discuss that animal model of AK can be an efficient tool to validate diagnostic methods and conclude that DNA extraction with the kit and snPCR protocol described here is an effective alternative for diagnosis of AK.


Direct measurement of molecular mobility in actively deformed polymer glasses.
When sufficient force is applied to a glassy polymer, it begins to deform through movement of the polymer chains. We used an optical photobleaching technique to quantitatively measure changes in molecular mobility during the active deformation of a polymer glass [poly(methyl methacrylate)]. Segmental mobility increases by up to a factor of 1000 during uniaxial tensile creep. Although the Eyring model can describe the increase in mobility at low stress, it fails to describe mobility after flow onset. In this regime, mobility is strongly accelerated and the distribution of relaxation times narrows substantially, indicating a more homogeneous ensemble of local environments. At even larger stresses, in the strain-hardening regime, mobility decreases with increasing stress. Consistent with the view that stress-induced mobility allows plastic flow in polymer glasses, we observed a strong correlation between strain rate and segmental mobility during creep.


Identifying Barriers to and Facilitators of Using a Mobile Fruit and Vegetable Market Intervention Delivered to Low-Income Housing Sites: A Concept Mapping Study.
Mobile fruit and vegetable (F&V) markets may be a promising strategy to improve F&V intake among low-income and racial/ethnic minority groups. However, challenges remain in terms of maximizing the reach and utilization of such markets. Therefore, this study identifies perceived barriers to and facilitators of utilizing a mobile F&V market among residents who lived in low-income housing that received the markets. Specifically, this article reports the results of the follow-up acceptability study of the "Live Well, Viva Bien" (LWVB) intervention. We conducted concept mapping with residents in housing communities that received the Fresh to You (FTY) markets. Participants generated, sorted, and rated statements concerning barriers to and facilitators of market use. We compared the rating data by residents' level of market utilization and created a map representing how statements clustered into conceptual themes. We retained 66 unique participant-generated statements. Eight thematic clusters emerged; four pertained to barriers: financial/promotion, produce-related, scheduling/knowledge, and logistic/awareness barriers, and four related to facilitators: produce/staffing, promotion, accessibility, and multilevel market facilitators. There was a strong correlation in ratings between participants who more frequently versus less frequently shopped at the markets (r = 0.94). Participants identified financial barriers, market promotion, ease of market accessibility, produce variety and quality, and staffing as key factors influencing FTY market use. This study highlights the importance of identifying the perceived barriers to and facilitators of mobile F&V market use among target populations to inform future efforts to scale up such approaches.


Nutrition Facts Panels: Who Uses Them, What Do They Use, and How Does Use Relate to Dietary Intake?
Nutrition labels are a low-cost tool with the potential to encourage healthy eating habits. To investigate correlates of frequent Nutrition Facts label use, describe the types of label information most often used, and measure how label use relates to dietary intake in young adults. Cross-sectional population-based study of young adults participating in Project Eating and Activity in Teens and Young Adults-IV. Surveys and food frequency questionnaires were completed during 2015-2016 by young adults (N=1,817; weighted sample=49% women) aged 25 to 36 years. Nutrition Facts label use, frequency of using specific information on labels, and dietary intake. Relative risks and adjusted means were used to examine how demographic, behavior, and weight-related factors were associated with Nutrition Facts panel use, and how label use related to dietary outcomes. Associations with P values <0.05 were considered statistically significant. Approximately one-third (31.4%) of participants used Nutrition Facts labels "frequently." Use was significantly higher for women; for participants with high education and income; among those who prepared food regularly; among those who were physically active; among those with a weight status classified as overweight; and among those who were trying to lose, gain, or maintain weight. Label components used most often included sugars (74.1%), total calories (72.9%), serving size (67.9%), and the ingredient list (65.8%). Nutrition Facts label users consumed significantly more fruits, vegetables, and whole grains and fewer sugar-sweetened beverages, compared with nonusers. Nutrition Facts label users ate significantly more frequently at sit-down restaurants but less frequently at fast-food restaurants compared with nonusers. Although Nutrition Facts label use was associated with markers of better dietary quality in a population-based sample of young adults, only one-third of participants used labels frequently. Methods to improve label use should be studied, particularly through leveraging weight- or health-related goals (eg, interest in making healthier food choices), and meeting consumer preferences concerning label content.


Two types of neurones lacking synaptic input in the submucous plexus of guinea-pig small intestine.
Intracellular recordings were made from neurones in the submucous plexus of guinea-pig small intestine. Approximately 20% of all neurones studied appeared to lack synaptic input; two types of neurones without synaptic input were identified. The action potential recorded from one of these types of ganglion cells was followed by a prolonged after-hyperpolarization. The after-hyperpolarization was abolished by Co2+ or Mn2+. A Ca2+ component of the evoked action potential was demonstrated after the Na+ component had been abolished by tetrodotoxin (TTX). The other type of neurone was characterized by a high input resistance (220-320 M omega) and spontaneous action potentials which were unaffected by hexamethonium, curare, atropine or TTX. The ionic basis of the action potentials evoked from spontaneously active cells differed from other enteric neurones. These action potentials exhibited a TTX-insensitive Na+ component as well as a Ca2+ component. It is suggested the spontaneously active neurones may be responsible for the ongoing synaptic activity recorded from many submucous plexus neurones in the absence of stimulation.


Maleic hydrazide: sprout suppression of potatoes in the field.
In 2005, the active substance maleic hydrazide was released on the Belgian market. Maleic hydrazide is authorized in potatoes as foliar treatment for instore sprout suppression and control of volunteers. The mode of action is based on blocking cell division whilst cell elongation is not affected. The product must be applied at once during the growing season, only after at least 80% of the tubers have reached 25 mm diameter and not later than 3 weeks before haulm killing. The first 24 h after application, no meaningful precipitation should occur to insure sufficiently uptake of the product by the crop. Field trials were set up for 4 years (2005-2008) and 4 locations per year with application of maleic hydrazide in four different cultivars (Bintje, Fontane, Asterix and Cilena). After application, the cultivar Asterix showed almost every year a temporarily phytotoxicity (bronze discoloration). On the first place yield was determined. When maleic hydrazide was applied too early (80% tubers % 25mm diameter) yield was negatively affected (3 years on 4) except for the cultivar Cilena (fresh market). Internal quality (dry matter and fry quality) was not influenced by the application of maleic hydrazide. Only Fontane had a slightly lower dry matter content. Maleic hydrazide also influenced appearance of secondary growth. However, the results were very variable depending on cultivar, location and time of application. After harvest, the tubers were kept in storage and assessed monthly on germination. Potatoes treated late in the growing season, showed a shorter dormancy period. A part of the tubers was replanted the following spring to verify volunteer control. Additional trials were set up by the Flemish government for two years (2010-2011). The results of previous trials were confirmed. Additional, the influence of maleic hydrazide on internal germination during storage was examined on the cultivar Innovator. The tests clearly showed a positive effect for this parameter.


No significant effect of 7,8-dihydroxyflavone on APP processing and Alzheimer-associated phenotypes.
It is reported that 7,8-dihydroxyflavone (DHF), a TrkB agonist, has beneficial effects on neuronal excitotoxicity, stroke, and Parkinson disease in animal models by enhancing axon regeneration, muscle reinnervation and neuromuscular transmission. The effect of DHF on AD neuropathology remains not well defined. In this study we examined whether DHF affects APP processing and cognitive functions in vitro and in vivo. We found that DHF had no significant effect on amyloid β precursor protein (APP), BACE1 and amyloid β protein (Aβ). DHF had little effect on APP processing in cell cultures. DHF treatment did not reduce the deposition of Aβ to form neuritic plaques in the brain of AD model mice APP23/PS45. Furthermore, DHF did not alleviate learning and memory impairments in the AD model mice. Our study suggest that further extensive and careful studies are warranted for considering DHF as a new therapeutic agent for reducing amyloid pathology and alleviating cognitive deficits for AD treatment.


Understanding germ-line mutations in BRCA1.
Germ-line mutations in BRCA1 account for the majority of familial breast and ovarian cancer cases and development of cancer in individuals who carry such mutations requires somatic inactivation of the normal allele. BRCA1 is highly polymorphic with more than 1,200 distinct documented variants. Approximately 70% of reported variants lead to absence of full-length BRCA1 protein, through loss of expression or protein truncation, and are suspected to predispose to cancer. These include regulatory mutations, splice site alterations, large rearrangements, large and small deletions or insertions, and nonsense mutations. However, characterizing the remaining missense alterations as either deleterious (cancer-associated mutations) or neutral variants is more complex, as the functional significance of the respective amino acid substitution is not straightforward to evaluate. In addition, many missense variants have been identified only once in defined ethnic groups and represent alleles with very low frequency. Most often, little information is available about segregation of the variant with disease in families, and assessment of disease risk for low frequency alleles through association studies is problematic, requiring a large number of samples stratified and matched by ethnicity. The fact that a significant proportion of BRCA1 variants remain unclassified represents a gap in risk assessment, such that individuals undergoing genetic testing will receive noninformative test results. An approach for assessing the potential clinical significance of missense variants is to combine available genetic data with functional and structural studies. Here we review the available information on BRCA1 variants and explore ways in which we can analyze unclassified variants.


[Pharmacological and molecular aspects of the regulation of eating behavior. With special reference to the role of catecholamines and effects of amphetamine].
Among the numerous endogenous substances involved in the regulation of feeding behaviours, the catecholamines are in the front rank. The numerous studies devoted to this aspect of catecholamines emphasize the importance and complexity of their intervention. Depending on the cerebral structures on which they act and on whether noradrenaline or dopamine are concerned, orexigenic or anorexigenic effects have been described. Alpha-2 and beta adrenergic receptors as well as D1 and D2 dopaminergic receptors participate in these effects. Amphetamine, which is an indirect catecholaminergic agonist, mobilizes neuronal catecholamines and fosters their various effects. Moreover, it exercises direct effects by its association with sites borne by glycaemia-sensitive neurons. This target seems to be common to a wide variety of anorectic agents. They are thought to reproduce on this hypothalamic "glucostat" the effect of a high blood glucose level, thus triggering off signals of satiety. In this unifying hypothesis, the diverse pharmacological profiles these agents are known to possess would result from associated properties.


Metabolite Profiling Reveals Developmental Inequalities in Pinot Noir Berry Tissues Late in Ripening.
Uneven ripening in Vitis vinifera is increasingly recognized as a phenomenon of interest, with substantial implications for fruit and wine composition and quality. This study sought to determine whether variation late in ripening (∼Modified Eichhorn-Lorenz stage 39) was associated with developmental differences that were observable as fruits within a cluster initiated ripening (véraison). Four developmentally distinct ripening classes of berries were tagged at cluster véraison, sampled at three times late in ripening, and subjected to untargeted HPLC-MS to measure variation in amino acids, sugars, organic acids, and phenolic metabolites in skin, pulp, and seed tissues separately. Variability was described using predominantly two strategies. In the first, multivariate analysis (Orthogonal Projections to Latent Structures-Discriminant Analysis, OPLS-DA) was used to determine whether fruits were still distinguishable per their developmental position at véraison and to identify which metabolites accounted for these distinctions. The same technique was used to assess changes in each tissue over time. In a second strategy and for each annotated metabolite, the variance across the ripening classes at each time point was measured to show whether intra-cluster variance (ICV) was growing, shrinking, or constant over the period observed. Indeed, berries could be segregated by OPLS-DA late in ripening based on their developmental position at véraison, though the four ripening classes were aggregated into two larger ripening groups. Further, not all tissues were dynamic over the period examined. Although pulp tissues could be segregated by time sampled, this was not true for seed and only moderately so for skin. Ripening group differences in seed and skin, rather than the time fruit was sampled, were better able to define berries. Metabolites also experienced significant reductions in ICV between single pairs of time points, but never across the entire experiment. Metabolites often exhibited a combination of ICV expansion, contraction and persistence. Finally, we observed significant differences in the abundance of some metabolites between ripening classes that suggest the berries that initiated ripening first remained developmentally ahead of the lagging fruit even late in the ripening phase. This presents a challenge to producers who would seek to harvest at uniformity or at a predefined level of variation.


Liver stellate cells suppress dendritic cells through IL-10.
Liver allografts can be spontaneously accepted across an MHC class I disparity, the mechanism of which is still not known. Since the liver has a large amount of immature dendritic cells, these elements may contribute to transplant acceptance. However, the reason why liver dendritic cells are immature status is unknown. In this study, bone marrow-derived dendritic cell progenitors were cocultured with liver stellate cells, which produce the immunosuppressive cytokines IL-10 and TGF-beta. The results revealed that dendritic cells cocultured with liver stellate cells express low levels of costimulatory molecules with decreased allostimulatory capacity. Addition of anti-IL-10 antibody to the culture media to neutralize IL-10 effects reversed the allostimulatory function of dendritic cells cocultured with stellate cells. In conclusion, liver dendritic cells are conditioned by stellate cells to maintain an immature status, which may contribute to the low immunity of liver. One of the mechanisms that stellate cells may influence dendritic cells is through IL-10.


Inhibition of dog and human gastric lipases by enantiomeric phosphonate inhibitors: a structure-activity study.
The crystal structures of gastric lipases in the apo form [Roussel, A., et al. (1999) J. Biol. Chem. 274, 16995-17002] or in complex with the (R(P))-undecyl butyl phosphonate [C(11)Y(4)(+)] [Roussel, A., et al. (2002) J. Biol. Chem. 277, 2266-2274] have improved our understanding of the structure-activity relationships of acid lipases. In this report, we have performed a kinetic study with dog and human gastric lipases (DGL and HGL, respectively) using several phosphonate inhibitors by varying the absolute configuration of the phosphorus atom and the chain length of the alkyl/alkoxy substituents. Using the two previously determined structures and that of a new crystal structure obtained with the other (S(P))-phosphonate enantiomer [C(11)Y(4)(-)], we constructed models of phosphonate inhibitors fitting into the active site crevices of DGL and HGL. All inhibitors with a chain length of fewer than 12 carbon atoms were found to be completely buried in the catalytic crevice, whereas longer alkyl/alkoxy chains were found to point out of the cavity. The main stereospecific determinant explaining the stronger inhibition of the S(P) enantiomers is the presence of a hydrogen bond involving the catalytic histidine as found in the DGL-C(11)Y(4)(-) complex. On the basis of these results, we have built a model of the first tetrahedral intermediate corresponding to the tristearoyl-lipase complex. The triglyceride molecule completely fills the active site crevice of DGL, in contrast with what is observed with other lipases such as pancreatic lipases which have a shallower and narrower active site. For substrate hydrolysis, the supply of water molecules to the active site might be achieved through a lateral channel identified in the protein core.


[Research evolvement of postmortem diagnosis of early myocardial infarction in forensic pathology].
The cardiac sudden death occupies primacy among the cause of death in adult. Myocardial infarction is one of the main mechanisms of sudden death of coronary heart disease. Because of early myocardial infarction happened abruptly and might die in a short time, and the typical or special changes in morphology is absent, so it is the focus of medico legal research forensic fulfill all long. This paper reviewed the characters of myocardial infarction, applications and limits in forensic fields, and prospected feasibility of new clinical markers in forensic practice, and expected to enhance accuracy of postmortem diagnosis in MI.


Lingual ulceration in disseminated histoplasmosis.
Histoplasmosis is a rare systemic fungal infection commonly presenting as mucosal ulceration of the oral cavity. It has been increasingly reported in India as disseminated disease with lesions in the oral cavity as a consequence of rapid spread of HIV infection. The authors report a case of disseminated histoplasmosis with oral manifestation in a 40-year-old male patient.


Efficiency of bioaugmentation in the removal of organic matter in aquaculture systems.
Several techniques are currently used to treat effluents. Bioaugmentation is a new bioremediation strategy and has been employed to improve effluent quality by treating the water during the production process. This technology consists basically of the addition of microorganisms able to degrade or remove polluting compounds, especially organic matter and nutrients. The objective of this study was to assess the effects of bioaugmentation on some parameters of organic matter and on the performance of juvenile tilapias in an intensive aquaculture production system. The combination of two bacterial consortiums in a complete randomized design was employed in a factorial analysis with two factors. Statistical differences between treatments were analyzed by the analysis of variance (ANOVA) and Tukey test at the 5% level. One of the treatments, heterotrophic bacterial supplementation, was able to reduce biochemical oxygen demand (BOD) by 23%, dissolved organic carbon (DOC) by 83.7% and phytoplanktonic biomass by 43%. On the other hand, no damage was done to either the physical-chemical indicators of water quality or to the growth performance of juvenile tilapias assessed in this study.


Theory and associated phenomenology for intrinsic mortality arising from natural selection.
Standard evolutionary theories of aging and mortality, implicitly based on assumptions of spatial averaging, hold that natural selection cannot favor shorter lifespan without direct compensating benefit to individual reproductive success. However, a number of empirical observations appear as exceptions to or are difficult to reconcile with this view, suggesting explicit lifespan control or programmed death mechanisms inconsistent with the classic understanding. Moreover, evolutionary models that take into account the spatial distributions of populations have been shown to exhibit a variety of self-limiting behaviors, maintained through environmental feedback. Here we extend recent work on spatial modeling of lifespan evolution, showing that both theory and phenomenology are consistent with programmed death. Spatial models show that self-limited lifespan robustly results in long-term benefit to a lineage; longer-lived variants may have a reproductive advantage for many generations, but shorter lifespan ultimately confers long-term reproductive advantage through environmental feedback acting on much longer time scales. Numerous model variations produce the same qualitative result, demonstrating insensitivity to detailed assumptions; the key conditions under which self-limited lifespan is favored are spatial extent and locally exhaustible resources. Factors including lower resource availability, higher consumption, and lower dispersal range are associated with evolution of shorter lifespan. A variety of empirical observations can parsimoniously be explained in terms of long-term selective advantage for intrinsic mortality. Classically anomalous empirical data on natural lifespans and intrinsic mortality, including observations of longer lifespan associated with increased predation, and evidence of programmed death in both unicellular and multicellular organisms, are consistent with specific model predictions. The generic nature of the spatial model conditions under which intrinsic mortality is favored suggests a firm theoretical basis for the idea that evolution can quite generally select for shorter lifespan directly.


Increased expression of acetylcholinesterase T and R transcripts during hematopoietic differentiation is accompanied by parallel elevations in the levels of their respective molecular forms.
Differentiation of hematopoietic cells is known to be accompanied by profound changes in acetylcholinesterase (AChE) enzyme activity, yet the basic mechanisms underlying this developmental regulation remain unknown. We initiated a series of experiments to examine the molecular mechanisms involved in regulating AChE expression during hematopoiesis. Differentiation of murine erythroleukemia (MEL) cells using dimethyl sulfoxide resulted in a 5- and 10-fold increase in intracellular and secreted AChE enzyme activity, respectively. Interestingly, these increases resulted from a preferential induction of the globular molecular form G1 and a slight increase in G4 instead of an increase in the levels of the G2 membrane-bound form, a molecular form expressed in mature erythrocytes. Concomitantly, expression of the two predominant AChE transcripts (R and T, for read-through and tail, respectively) in MEL cells was induced to a similar extent with differentiation. Nuclear run-on assays performed with nuclei isolated from induced versus uninduced MEL cells revealed that in contrast to the large increases seen in the transcription of the beta-globin gene, the transcriptional activity of the AChE gene remained largely unaffected after differentiation. Determination of the half-lives of the R and T transcripts demonstrated that they both exhibited an increase in stability in induced MEL cells. Taken together, results from these studies indicate that post-transcriptional regulatory mechanisms account for the increased expression of AChE in differentiated hematopoietic cells.


[Absorption, distribution and excretion of 14C-josamycin and 14C-josamycin propionate in rats (author's transl)].
Abosrption, distribution and excretion of 14C-josamycin (JM) and 14C-josamycin propionate (JM-P) were studied in rats by measuring both antibacterial activity and radioactivity. 1. In antibacterial activity, plasma and tissue concentrations of JM-P showed a similar tendency to those of JM. Those concentrations of JM reached a peak at 1 hour after administration with a subsequent rapid decrease, while the peak level of JM-P appeared 2 approximately 4 hours after administration and then fell down very slowly. 2. In radioactivity, oral administration of JM-P rapidly produced a very high plasma and tissue concentrations which were in lung, liver, kidney and spleen more than twice those of JM. These results showed that when given orally, JM-P is well absorbed with distributions at high concentrations especially in lung, liver, and kidney and spleen. 3. The ratios of bioactivity/radioactivity in JM administration were the highest in lung and the lowest in liver at 1 hour after. But those of JM-P were generally much lower than those of JM because of higher distribution of JM-P radioactivity into tissues. 4. Four days after oral administration of JM and JM-P, 23.1% and 21.8% of the given radioactivity were recovered respectively from urine. However, the antibacterial activities recovered were 0.40% for JM and 0.65% for JM-P. 5. Biliary recoveries of JM and JM-P were 17.2% and 12.1% of administered radioactivity 2 days after oral administration. On the other hand, 0.47% of JM and 0.17% of JM-P were excreted into bile as antibacterial activity. These results showed that JM and JM-P were excreted into rat urine and bile as some metabolites with less biological activity. 6. The amounts of JM and JM-P recovered from feces were 75.7% and 60.2%, respectively, of the orally given radioactivity. The amount of radioactivity recovered from expiration air was about 1% of either orally given JM or JM-P.


The murine 3beta-hydroxysteroid dehydrogenase (3beta-HSD) gene family: a postulated role for 3beta-HSD VI during early pregnancy.
The enzyme 3beta-hydroxysteroid dehydrogenase/isomerase (3beta-HSD) is essential for the biosynthesis of all active steroid hormones. The 3beta-HSD enzyme consists in multiple isoforms, each the product of a distinct gene. In the mouse, six tissue-specific isoforms have been identified. These isoforms are expressed in a tissue- and temporal specific manner. Mouse 3beta-HSD VI is the only isoform expressed in decidua and giant trophoblast cells during the first half of mouse pregnancy. The tissue- and temporal-specific expression of 3beta-HSD VI during mouse pregnancy, as determined by in situ hybridization and immunohistochemistry, shows that 3beta-HSD is expressed exclusively in the antimesometrial decidua on E6.5 and E7.5. By E9.5, expression of 3beta-HSD is observed in giant trophoblast cells with a marked increase in expression by E10.5. No expression of 3beta-HSD is seen in decidua after E7.5 and no expression of 3beta-HSD is seen in the embryo at any of the times investigated. Giant trophoblast cells in culture from E9.5 and E10.5 synthesize progesterone with cells from E10.5 producing about 3.5-fold more progesterone during the first 24 h in culture. Western blot analysis of 3beta-HSD VI protein demonstrates that the amount of 3beta-HSD VI protein correlates with the amount of progesterone biosynthesis in giant trophoblast cells from E9.5 and E10.5. We propose that progesterone produced during the first half of mouse pregnancy in decidua and giant trophoblast cells acts as an immunosuppressant at the fetal maternal interface to prevent rejection of the fetus.


Hygienic behavior of the honey bee (Apis mellifera) is independent of sucrose responsiveness and foraging ontogeny.
Hygienic behavior in honey bees is a behavioral mechanism of disease resistance. Bees bred for hygienic behavior exhibit an increased olfactory sensitivity to odors of diseased brood, which is most likely differentially enhanced in the hygienic line by the modulatory effects of octopamine (OA), a noradrenaline-like neuromodulator. Here, we addressed whether the hygienic behavioral state is linked to other behavioral activities known to be modulated by OA. We specifically asked if, during learning trials, bees from hygienic colonies discriminate better between odors of diseased and healthy brood because of differences in sucrose (reward) response thresholds. This determination had to be tested because sucrose response thresholds are susceptible to OA modulation and may have influenced the honey bee's association of the conditioned stimulus (odor) with the unconditioned stimulus (i.e., the sucrose reward). Because the onset of first foraging is also modulated by OA, we also examined whether bees from hygienic colonies differentially forage at an earlier age compared to bees from non-hygienic colonies. Our study revealed that 1-day- and 15- to 20-day-old bees from the hygienic line do not have lower sucrose response thresholds compared to bees from the non-hygienic lines. In addition, hygienic bees did not forage at an earlier age or forage preferentially for pollen as compared to non-hygienic bees. These results support the idea that OA does not function in honey bees simply to enhance the detection of all chemical cues non-selectively or control related behaviors regardless of their environmental milieu. Our results indicate that the behavioral profile of the hygienic bee is sculpted by multiple factors including genetic, neural, social and environmental systems.


Control of c-myc mRNA stability by IGF2BP1-associated cytoplasmic RNPs.
The RNA-binding protein IGF2BP1 (IGF-II mRNA binding protein 1) stabilizes the c-myc RNA by associating with the Coding Region instability Determinant (CRD). If and how other proteins cooperate with IGF2BP1 in promoting stabilization of the c-myc mRNA via the CRD remained elusive. Here, we identify various RNA-binding proteins that associate with IGF2BP1 in an RNA-dependent fashion. Four of these proteins (HNRNPU, SYNCRIP, YBX1, and DHX9) were essential to ensure stabilization of the c-myc mRNA via the CRD. These factors associate with IGF2BP1 in a CRD-dependent manner, co-distribute with IGF2BP1 in non-polysomal fractions comprising c-myc mRNA, and colocalize with IGF2BP1 in the cytoplasm. A selective shift of relative c-myc mRNA levels to the polysomal fraction is observed upon IGF2BP1 knockdown. These findings suggest that IGF2BP1 in complex with at least four proteins promotes CRD-mediated mRNA stabilization. Complex formation at the CRD presumably limits the transfer of c-myc mRNA to the polysomal fraction and subsequent translation-coupled decay.


[Analysis of risk factors of radiation-induced toxicity in limited-stage small cell lung cancer treated with hypofractionated intensity-modulated radiotherapy].
Objective: To compare the incidence of radiation-related toxicities between conventional and hypofractionated intensity-modulated radiation therapy (IMRT) for limited-stage small cell lung cancer (SCLC), and to explore the risk factors of hypofractionated radiotherapy-induced toxicities. Methods: Data were retrospectively collected from consecutive limited-stage SCLC patients treated with definitive concurrent chemoradiotherapy in Cancer Hospital of Chinese Academy of Medical Sciences from March 2016 to April 2022. The enrolled patients were divided into two groups according to radiation fractionated regimens. Common Terminology Criteria for Adverse Events (CTCAE, version 5.0) was used to evaluate the grade of radiation esophagus injuries and lung injuries. Logistic regression analyses were used to identify factors associated with radiation-related toxicities in the hypofractionated radiotherapy group. Results: Among 211 enrolled patients, 108 cases underwent conventional IMRT and 103 patients received hypofractionated IMRT. The cumulative incidences of acute esophagitis grade ≥2 [38.9% (42/108) vs 35.0% (36/103), P=0.895] and grade ≥ 3 [1.9% (2/108) vs 5.8% (6/103), P=0.132] were similar between conventional and hypofractionated IMRT group. Late esophagus injuries grade ≥2 occurred in one patient in either group. No differences in the cumulative incidence of acute pneumonitis grade ≥2[12.0% (13/108) vs 5.8% (6/103), P=0.172] and late lung injuries grade ≥2[5.6% (6/108) vs 10.7% (11/103), P=0.277] were observed. There was no grade ≥3 lung injuries occurred in either group. Using multiple regression analysis, mean esophageal dose ≥13 Gy (OR=3.33, 95% CI: 1.23-9.01, P=0.018) and the overlapping volume between planning target volume (PTV) and esophageal ≥8 cm(3)(OR=3.99, 95% CI: 1.24-12.79, P=0.020) were identified as the independent risk factors associated with acute esophagitis grade ≥2 in the hypofractionated radiotherapy group. Acute pneumonitis grade ≥2 was correlated with presence of chronic obstructive pulmonary disease (COPD, P=0.025). Late lung injuries grade ≥2 was correlated with tumor location(P=0.036). Conclusions: Hypofractionated IMRT are tolerated with manageable toxicities for limited-stage SCLC patients treated with IMRT. Mean esophageal dose and the overlapping volume between PTV and esophageal are independently predictive factors of acute esophagitis grade ≥2, and COPD and tumor location are valuable factors of lung injuries for limited-stage SCLC patients receiving hyofractionated radiotherapy. Prospective studies are needed to confirm these results.


Clinical Manifestation and Mutation Spectrum of 53 Unrelated Pedigrees with Protein S Deficiency in China.
Protein S (PS) deficiency is associated with a 10-fold increased risk of venous thromboembolism (VTE), but its diagnosis is quite difficult and complicated. In this study, we identified 53 unrelated pedigrees with PS deficiency in China. Data of their clinical characteristics and laboratory examinations were collected. Genetic analysis of PROS1 including direct sequencing, copy number variant detection and messenger ribonucleic acid analysis was performed in probands and related family members. Of these 53 probands, 52.8% (28/53) experienced multi-site and/or recurrent thrombotic episodes, mainly manifested as deep venous thrombosis and/or pulmonary embolism (82.7%). Additional risk factors of VTE were observed in 39.6% (21/53) probands who exhibited a significantly higher rate of recurrent VTE compared with those not, in which 7 probands were complicated by anti-phospholipid syndrome. Most probands and family members exhibited quantitative PS deficiency with impairment of both activated protein C and tissue factor pathway inhibitor cofactor activities. Note that 87.2% (34/39) PROS1 detectable mutation rate was obtained through comprehensive phenotypic and genetic analysis. A total of 36 PROS1 causative mutations including 16 novel mutations were identified in 48 probands, whereas no PROS1 mutations were detected in the other 5 probands. Three hotspot mutations (Glu67Ala, Arg561Trp and Tyr560*) were identified in the Chinese population for the first time. This article provides a framework for correlating the clinical pathogenesis of PS deficiency to genetic backgrounds in the Chinese population.


Transition-Metal-Catalyzed Regiodivergent and Stereoselective Access to Branched and Linear Allylated 4-Pyridones.
A regiodivergent and stereoselective transition-metal-catalyzed addition of 4-pyridones to allenes furnishing N-allylated pyridones is reported. Employing a commercially available chiral rhodium catalyst enabled enantioselective branched-selective allylation. Conversely, an achiral palladium catalyst led to linear-selective N-allylation in high E-selectivities. A wide range of functional groups was tolerated and assorted synthetic transformations of the N-allylated pyridones demonstrated their utility for the syntheses of medicinally relevant heterocyclic scaffolds.


Immunoglobulin gene organization and the mechanism of repertoire development.
Recombinant DNA technology has made it possible to comparatively examine the immunoglobulin (Ig) gene constitution of numerous species. These studies reveal that many species diverge from the pattern seen in rodents and primates while revealing a number of interesting correlations involving Ig gene organization, B-cell lymphogenesis and the mechanism of repertoire development; many of these fail to correlate with traditional phylogenetic relationships. These correlates pose new questions regarding repertoire developments, which suggest that considerable diversity exists in the process. These findings also allow new questions to emerge regarding the role of IgD, the size of the B-cell repertoire, and the role that antigen may or may not play in repertoire development. These issues are discussed with the intention of stimulating experimentation to test a number of speculative hypotheses regarding B-cell and repertoire development.


Log odds of positive lymph nodes is superior to the number- and ratio-based lymph node classification systems for colorectal cancer patients undergoing curative (R0) resection.
The metastatic lymph node status (N classification) is an important prognostic factor for patients with colorectal cancer (CRC). The aim of the present study was to evaluate and compare the prognostic assessment of three different lymph node staging methods, namely standard lymph node (pN) staging, metastatic lymph node ratio (LNR) and log odds of positive lymph nodes (LODDS) in CRC patients who undergo curative resection (R0). Data were retrospectively collected from 192 patients who had undergone R0 resection. Kaplan-Meier survival curves, Cox proportional hazards model and accuracy of the three methods (pN, LNR and LODDS) were compared to evaluate the prognostic effect. Univariate analysis demonstrated that pN, LNR and LODDS were all significantly correlated with survival (P=0.001, P<0.001 and P<0.001, respectively). The final result of the 3-step multivariate analysis demonstrated that LODDS was superior to the other two N categories. Patients in the same pN or LNR classifications may be classified into different LODDS stages with different prognoses. Thus, LODDS may be a meaningful prognostic indicator and superior to the pN and LNR classifications in CRC patients who undergo curative (R0) resection.


A multidimensional scaling analysis of tone discrimination ability in Cantonese-speaking children using a cochlear implant.
Tone discrimination testing with two groups of profoundly hearing-impaired children using a cochlear implant and one group of normally hearing children suggests that pitch level is perceptually more salient than pitch contour. In this paper, the discrimination results from these children are submitted to a multidimensional scaling analysis to determine what differences if any exist between the children in the information they use to discriminate between tone types. Through the multidimensional scaling analysis it is shown that, 'average pitch height' and 'pitch direction' are the most salient acoustic features in tone with pitch height being perceptually more important than pitch level. Furthermore, these acoustic features are similarly salient for all three groups of children despite differences in the source of auditory information and linguistic experience. Finally, the two groups of cochlear implant users who employ different speech processing strategies with their implant are shown to be distinguishable by differences in the relative salience of pitch direction.


The specific heat of the electron-doped La-1038 compound (Ca0.85La0.15)10(FeAs)10(Pt3As8).
The specific heat of polycrystalline (Ca0.85La0.15)10(FeAs)10(Pt3As8), an electron-doped iron-based superconductor (T(c)(onset) = 34.6 K) with Ca/La ions and Pt3As8 separating the FeAs layers, was measured between 0.4 and 48 K.This compound has been recently reported to represent an electron-doped variant of the non-superconducting 10-3-8 phase, featuring a superconducting transition in the range of that of the 10-4-8 phase. This family of compounds is unique among the iron pnictide superconductors discovered to date due to the second metal pnictide layer, Pt3As8, present in the structure competing with the familiar FeAs layer for the electron from the Ca/La. This superconductor is further unusual in that it has a rather low crystalline symmetry (triclinic) for such a high superconducting transition temperature. The specific heat γ is found to be approximately 26 mJ/(Ca/La mol)K(2), comparable to 122 iron-based superconductors electron-doped on the Fe sites and a factor of two smaller than 122 compounds hole-doped on the cation site, e.g., Ba(1-x)K(x)Fe2As2. The present work also investigates the discontinuity in the specific heat at T(c), ΔC, to compare with the global trend, established by Bud'ko, Ni and Canfield (BNC), of ΔC/T(c) versus T(c) found for essentially all iron-based superconductors. The result is a value lower than the BNC trend by a factor of ten, consistent with a severely broadened superconducting transition.


[Relation between the clinical effect and plasma concentration of midazolam in volunteers].
In 12 healthy volunteers, the pharmacological effects of midazolam were investigated following intravenous (0.15 mg X kg-1 and 12.5 mg in 6 subjects each), intramuscular (12.5 mg in 6 subjects) and oral administration (20 mg in 6 subjects and 10 mg in 4 subjects). The findings were correlated with the plasma concentrations of midazolam and its alpha-hydroxy metabolite. The effects were assessed using objective and subjective methods (reaction time, memory test and subjects' self-assessment with an analog scale covering the degree of sedation). Plasma samples were assayed for midazolam and its alpha-hydroxy metabolite by gas chromatography. The results of the memory test showed that mnemonic retention and recall of a number remained intact for the period preceding intravenous or intramuscular administration. The maximum impairment occurred at 30 min after injection for recall of a number presented at the 15th min. The impairment was no longer detectable 4 h after injection. The plasma concentration time course was similar to that of the reaction time after administration of an identical intravenous or intramuscular dose. The maximum effect was attained within 15 min and 30 min after intravenous and intramuscular administration respectively. Within 2 to 4 h after parenteral administration, the reaction time had returned to normal. At identical plasma concentrations of midazolam, the reaction time was slightly longer in the period immediately following oral administration than after parenteral administration. This result suggested that the alpha-hydroxy metabolite contributed actively to the effect of midazolam. After its intravenous injection, this metabolite's sedative effects attained their maximum with 15 min, having disappeared 4 h later.


Drugs and the kidney.
Renal insufficiency affects every organ system and every aspect of drug disposition by the body. Because the kidney is the organ responsible for the elimination of most drugs or their metabolites from the body, renal dysfunction results in substantial changes in drug therapy. Furthermore, the kidney is often a target organ for the expected physiological effects of the drugs that are given or for their toxicity. Finally, our therapeutic options for treating uremia complicate drug therapy by further changing drug disposition. This article reviews recent work aimed at understanding these processes.


[Cardiac rupture secondary to left ventricular venting].
The cases of two patients with cardiac rupture secondary to left ventricular venting are reported. In the first patient, who had an aortocoronary bypass grafting, rupture was found in the posterolateral wall of the left ventricle just before closing the chest. It was successfully managed by placing sutures. The cause of rupture was thought to be the advancing venting cannula tip introduced into the left ventricle from the superior right pulmonary vein. In the second patient, who had MVR, AVR, and VSD and ASD closure, rupture occurred in the posterior wall of the left atrium on the 4th postoperative day. The patient died instantly because of profound hemorrhagic shock. Rupture of the left atrium was thought to have occurred secondary to distension of the left atrial wall incurred by lifting the unusually large heart for inserting and removing the venting cannula. These experiences made us decide to abandon routine left ventricular venting.


High-intensity re-warm-ups enhance soccer performance.
The effects of high-intensity, short-duration, re-warm-ups on team-sport-related performance were investigated. In a randomised, cross-over study, participants performed 2×26-min periods of an intermittent activity protocol (IAP) on a non-motorized treadmill, interspersed by 15-min of passive recovery (CON); 3-min small-sided game (SSG); or a 5RM leg-press. Measures included counter-movement jump, repeated-sprint, the Loughborough soccer passing test (LSPT), blood lactate concentration, heart-rate, and perceptual measures. Data were analyzed using effect size (90% confidence intervals), and percentage change; determining magnitudes of effects. A 5RM re-warm-up improved flight-time to contraction-time ratio when compared to SSG (9.8%, ES; 0.5±0.3) and CON (ES: 9.4%, 0.7±0.5) re-warm-ups, remaining higher following the second IAP (8.8%, ES; 0.5±0.3 and 10.2%, ES; 0.6±0.6, respectively). Relative-maximum rate-of-force development was greater in the 5RM condition following the second IAP compared to SSG (29.3%, ES; 0.7±0.5) and CON (16.2%, ES; 0.6±0.6). Repeated-sprint ability during the second IAP improved in the 5RM re-warm-up; peak velocity, mean velocity, and acceleration were 4, 3, and 18% greater, respectively. Within groups, the SSG re-warm-up improved LSPT performance post-intervention; 6.4% (ES: 0.6±0.8) and following the second IAP 6.2% (ES: 0.6±0.6), compared to pre-intervention. A 5RM leg-press re-warm-up improved physical performance, while a SSG re-warm-up enhanced skill execution following standardized intermittent exercise.


Efficacy of single-dose mebendazole, polymorphic forms A and C, in the treatment of hookworm and Trichuris infections.
A therapeutic trial of single mebendazole, 300 mg polymorph A, 300 mg polymorph C and 500 mg polymorph C, in the treatment of hookworm and Trichuris infections was carried out at primary schools in Southern Thailand. The total of 958 children were randomly allocated in seven treatment groups including the placebo control and the standard dose control (100 mg polymorph C bid for 3 days). The egg reduction rates and the cure rates of 300 mg and 500 mg polymorph C were similar, but inferior to those of the standard dose in both hookworm and Trichuris infections. The efficacy of single dose 300 mg polymorph A was not different from that of the placebo control (alpha = 0.05) in both infections.


Diffusion-controlled reactions: hydrodynamic interaction between charged, uniformly reactive spherical reactants.
In this work, different models of hydrodynamic interaction (HI) are examined in the diffusion-controlled reaction between uniformly reactive charged spherical particles. In addition to Oseen "stick" and "slip" models of HI, one is considered that accounts for the disturbance of fluid flow by the ions around one reactive partner as they interact with a neighboring reactive species. This interaction is closely related to the "electrophoretic effect" in electrokinetics and can be described by a fairly simple electrophoretic, or E-tensor. These models are applied to the electron-transfer quenching reaction of Ru(bpy)3(2+) and methyl viologen (MV2+) over a wide range of NaCl concentrations (Chiorboli, C. et al., J. Phys. Chem. 1988, 92, 156). The back reaction is also considered. From a comparison of the salt dependence of the model and experimental rates, it is concluded that the "E-tensor" model works best and ignoring HI altogether works worst. The Oseen "stick" and "slip" models fall between these.


Cerebral artery mass in the rabbit is reduced by chronic sympathetic denervation.
Weights of matching right and left middle or posterior cerebral arteries and their main branches from the same animal were compared 8-10 weeks after unilateral denervation by superior cervical ganglionectomy. When compared in pairs, the denervated arterial systems weighed significantly less (mean 85%) than their innervated counterparts. This suggests that the sympathetic innervation exerts a trophic influence on extracerebral arteries.


Carbon monoxide and human disease.
Carbon monoxide is produced endogenously in humans through the breakdown of hemoglobin by heme oxygenase. Although originally thought to be a superfluous by-product of heme catabolism, carbon monoxide is now known to play a central role in many aspects of human health and disease. The functions of carbon monoxide that have been described to date are myriad, including blood pressure regulation, maintenance of organ-specific vascular tone, neurotransmission, stress response, platelet activation, and smooth muscle relaxation. This review outlines what is known to date about carbon monoxide as it relates to human disease.


Acral Lentiginous Melanoma, Indolent Subtype Diagnosed by En Bloc Excision: A Case Report.
Nail unit melanoma is a type of acral lentiginous melanoma and requires histopathologic examination for a confirmed diagnosis. However, inadequate biopsy techniques make definitive diagnosis difficult. A 61-year-old man presented with progressive nail pigmentation for 15 years, which was clinically highly suspicious for malignancy. Acral lentiginous melanoma was not detected in punch and longitudinal biopsy specimens, but en bloc excision tissue revealed melanoma. Acral lentiginous melanoma is known to have a heterogeneous pathologic manifestation depending on the pigmented region and the time it takes to progress. In this regard, en bloc excision can be considered as a first-line biopsy technique to diagnose acral lentiginous melanoma, indolent subtype.


High Glucose Concentration Impairs 5-PAHSA Activity by Inhibiting AMP-Activated Protein Kinase Activation and Promoting Nuclear Factor-Kappa-B-Mediated Inflammation.
Recently, the endogenous fatty acid palmitic acid-5-hydroxystearic acid (5-PAHSA) was found to increase insulin sensitivity and have anti-inflammatory effects in mice with high-fat diet (HFD)-induced diabetes. However, it is unknown if 5-PAHSA affects glucose and lipid metabolism in db/db mice, which are characterized by extreme hyperglycemia. Here, we aim to determine the effect of continued 5-PAHSA administration on glucose and lipid metabolism in db/db mice. We also used 3T3-L1 cells and HepG2 cells to investigate the mechanism behind this effect. HepG2 cells and 3T3-L1 cells were induced to become models of insulin resistance. The models were used to test the effect of 5-PAHSA on insulin signaling. 5-PAHSA was administered orally to db/db mice for 1 month to assess its effects on glucose and lipid metabolism. We also exposed HepG2 cells to high glucose concentrations to investigate the influence on 5-PAHSA's effects on hepatic lipid metabolism and inflammation. 5-PAHSA improved glucose uptake and insulin signaling in HepG2 cells and 3T3-L1 cells. However, after 1 month of treatment, 5-PAHSA did not reduce blood glucose levels, but increased inflammation and promoted fatty liver in db/db mice. In HepG2 cells under normal glucose conditions, 5-PAHSA treatment reduced lipogenesis and increased lipid oxidation. Notably, a high glucose concentration in cell media abolished the positive effects of 5-PAHSA treatment. These changes were associated with: decreased phosphorylation of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC); upregulation of sterol-regulatory element-binding protein 1c (SREBP1c), and fatty acid synthase (FAS); and downregulation of carnitine palmitoyltransferase 1 (CPT1). Besides, the anti-inflammatory effect of 5-PAHSA was also impaired by high glucose conditions. Thus, high glucose concentrations impaired 5-PAHSA action by inhibiting the AMPK signaling pathway and promoting nuclear factor-kappa-B (NF-κB) mediated inflammation.


Reflectance Confocal Microscopy: A Powerful Tool for Large Scale Characterization of Ordered/Disordered Morphology in Colloidal Photonic Structures.
The development of appropriate methods to correlate the structure and optical properties of colloidal photonic structures is still a challenge. Structural information is mostly obtained by electron, X-ray, or optical microscopy methods and X-ray diffraction, while bulk spectroscopic methods and low resolution bright-field microscopy are used for optical characterization. Here, we describe the use of reflectance confocal microscopy as a simple and intuitive technique to provide a direct correlation between the ordered/disordered structural morphology of colloidal crystals and glasses, and their corresponding optical properties.


Cancer related fatigue: implementing guidelines for optimal management.
Cancer-related fatigue (CRF) is a key concern for people living with cancer and can impair physical functioning and activities of daily living. Evidence-based guidelines for CRF are available, yet inconsistently implemented globally. This study aimed to identify barriers and enablers to applying a cancer fatigue guideline and to derive implementation strategies. A mixed-method study explored the feasibility of implementing the CRF guideline developed by the Canadian Association for Psychosocial Oncology (CAPO). Health professionals, managers and consumers from different practice settings participated in a modified Delphi study with two survey rounds. A reference group informed the design of the study including the surveys. The first round focused on guideline characteristics, compatibility with current practice and experience, and behaviour change. The second survey built upon and triangulated the first round. Forty-five health practitioners and managers, and 68 cancer survivors completed the surveys. More than 75% of participants endorsed the CAPO cancer related fatigue guidelines. Some respondents perceived a lack of resources for accessible and expert fatigue management services. Further barriers to guideline implementation included complexity, limited practical details for some elements, and lack of clinical tools such as assessment tools or patient education materials. Recommendations to enhance guideline applicability centred around four main themes: (1) balancing the level of detail in the CAPO guideline with ease of use, (2) defining roles of different professional disciplines in CRF management, (3) how best to integrate CRF management into policy and practice, (4) how best to ensure a consumer-focused approach to CRF management. Translating current knowledge on optimal management of CRF into clinical practice can be enhanced by the adoption of valid guidelines. This study indicates that it is feasible to adopt the CAPO guidelines. Clinical application may be further enhanced with guideline adaptation, professional education and integration with existing practices.


An experimental and theoretical framework for manufacturing prosthetic sockets for transtibial amputees.
Selective laser sintering (SLS) is a powerful manufacturing technology that does not require part-specific tooling or significant human intervention and provides the ability to easily generate parts with complex geometric designs. The present work focuses on developing a manufacturing framework using this technology to produce subject-specific transtibial amputee prosthetic sockets made of Duraform PA, which is a nylon-based material. The framework includes establishing an overall socket design (using the patellar-tendon bearing approach), performing a structural analysis using the finite element method (FEM) to ensure structural reliability during patient use, and validating the results by comparing the model output with experimental data. The validation included quantifying the failure conditions for the socket through a series of bending moment and compression tests. In the case study performed, the FEM results were within 3% of the experimental failure loads for the socket and were considered satisfactory.


Do team processes really have an effect on clinical performance? A systematic literature review.
There is a growing literature on the relationship between team processes and clinical performance. The purpose of this review is to summarize these articles and examine the impact of team process behaviours on clinical performance. We conducted a literature search in five major databases. Inclusion criteria were: English peer-reviewed papers published between January 2001 and May 2012, which showed or tried to show (i) a statistical relationship of a team process variable and clinical performance or (ii) an improvement of a performance variable through a team process intervention. Study quality was assessed using predefined quality indicators. For every study, we calculated the relevant effect sizes. We included 28 studies in the review, seven of which were intervention studies. Every study reported at least one significant relationship between team processes or an intervention and performance. Also, some non-significant effects were reported. Most of the reported effect sizes were large or medium. The study quality ranged from medium to high. The studies are highly diverse regarding the specific team process behaviours investigated and also regarding the methods used. However, they suggest that team process behaviours do influence clinical performance and that training results in increased performance. Future research should rely on existing theoretical frameworks, valid, and reliable methods to assess processes such as teamwork or coordination and focus on the development of adequate tools to assess process performance, linking them with outcomes in the clinical setting.


Soft lubrication.
We consider some basic principles of fluid-induced lubrication at soft interfaces. In particular, we quantify how a soft substrate changes the geometry of and the forces between surfaces sliding past each other. By considering the model problem of a symmetric nonconforming contact moving tangentially to a thin elastic layer, we determine the normal force in the small and large deflection limit, and show that there is an optimal combination of material and geometric properties which maximizes the normal force. Our results can be generalized to a variety of other geometries which show the same qualitative behavior. Thus, they are relevant in the elastohydrodynamic lubrication of soft elastic and poroelastic gels and shells, and in the context of biolubrication in cartilaginous joints.


The role of cognition, affect, and resources in the influence of unreasonable tasks on work engagement: A moderated chain mediation model.
Some studies have concentrated on the adverse effects of unreasonable tasks on work engagement. So far, however, the underlying mechanisms and boundary conditions of the relationship have not been adequately discussed. Based on the cognitive-affective systems theory and the job demands-resources model, this study constructs a chain mediation model in which unreasonable tasks influence work engagement through work alienation and negative affect and explores the moderating role of supervisor support in the model. An analysis of 427 questionnaires from multiple types of organizations shows that: Unreasonable tasks have a negative impact on work engagement; work alienation and negative affect play both separate and chain mediating roles in the negative effect of unreasonable tasks on work engagement, and supervisor support negatively moderates chain mediation by moderating the positive effect of unreasonable tasks on work alienation. This study re-investigates the relationship between unreasonable tasks and work engagement from cognitive, affective, and resource perspectives, which could be a valuable addition to established research and provide suggestions and assistance for management practice.


Temporal clusters of Salmonella serovars in humans in Alberta, 1990-2001.
Temporal clusters of salmonellosis are believed to occur but have not been quantitatively explored, thus, our objectives were to describe trends, seasonal patterns, and clusters of salmonellosis in humans in Alberta by examining isolates reported through passive surveillance systems. Cases of salmonellosis reported through Notifiable Disease Records between January 1990 and December 2001 were obtained from Alberta Health and Wellness. Least squares regression was used to characterize the distribution (long-term trends and seasonal patterns) of isolates. A cluster detection test was used to determine if and when isolates of specific serovars aggregated in time, over and above the background distribution. Comparisons were made to temporal patterns in Alberta livestock and to known outbreaks in humans. S. Typhimurium, Enteritidis, Hadar, Heidelberg, and Thompson were the five most common serovars of the 9,188 isolates reported. The annual number of isolates was relatively stable over time, with a distinct summertime seasonal pattern. Clusters were observed in 23 of 32 serovars examined. More clusters occurred in September and October than in other months, and in 1998 through 2001 than in the early to mid-1990s. Also, more clusters were of short duration than long. Short-duration clusters likely indicate a point source of infection, while long-duration clusters may indicate exposure to a persistent common source or the occurrence of secondary infections. A sharp increasing trend and a large cluster of S. Heidelberg may have public health implications. Surveillance activities focussed on similarities between common serovars, trends, and temporal clusters in humans and animals, and studies on factors associated with autumn clusters may be useful in preventing outbreaks in humans.


Drosophila suzukii (Diptera: Drosophilidae) and its Potential Impact to Wine Grapes During Harvest in Two Cool Climate Wine Grape Production Regions.
Drosophila suzukii (Matsumura) is a global pest attacking various berry crops. D. suzukii lays eggs in damaged and in intact wine grape berries of the most soft-skinned varieties. Here, we describe the relative host utilization of different wine grape cultivars grown in Northern Italy and Oregon. Assessments of host berry utilization were performed in both field and laboratory settings. Results were correlated to physiological changes occurring during grape berry development starting at véraison and concluding during harvest. We found that oviposition increased with an increase in sugar content and a decrease of acidity levels. Oviposition increased with a decrease of penetration force. Penetration force, as a measure of skin hardness, is a critical component of host selection among the D. suzukii-exposed cultivars. We demonstrated that incised berries are more favorable for D. suzukii oviposition and as a nutrient substrate. Increased presence on wine grapes, as indicated by egg laying and increased longevity, was observed for flies that were exposed to incised berries as opposed to fully intact berries. D. suzukii flies can be found feeding on damaged wine grapes during the harvest period, especially when the skins of berries are negatively impacted due to cracking, disease, hail injury, and bird damage. Such an increase of feeding and oviposition may increase the likelihood of spoilage bacteria vectoring due to D. suzukii.


Electronic anesthesia versus topical anesthesia for the control of injection pain.
The ability of a dental transcutaneous electronic nerve stimulator to control pain from injection of local anesthesia was compared to the pain-controlling ability of topical anesthesia. Two maxillary infiltration injections were completed on 21 patients, one injection after electronic anesthesia, the other after topical anesthesia. Patients reported the level of pain caused when the needle pierced their tissue and the solution was injected and their overall evaluation of the injection. No difference was reported for piercing of the tissue; however, the level of pain was very low. Significantly less pain was reported for the injection of local anesthesia solution and the overall evaluation of the injection was more favorable when electronic anesthesia was used. The patients preferred the electronic technique three to one over the topical anesthesia.


Prescription error in an orthopaedic practice.
A retrospective review of 17,833 prescription items was undertaken at the National Orthopaedic Hospital, Lagos, Nigeria with the aim of determining the prevalence and types of prescription error. The percentage prescription error was 4.5 with type C (minor nuisance) being the most common prescription error. Incomplete prescription was the reason for these errors in 71% of cases. Our results revealed that the higher the professional status of the prescriber, the lower the prescription error. Even though the errors were recognised and corrected at the dispensing point, there was no indication that the prescriber was informed of his mistakes. We suggest, amongst others, regular clinical meeting of Doctors and Pharmacists where various aspects of rational drug could be discussed.


Research issues: the food environment and obesity.
"Research Issues: The Food Environment and Obesity" is an article series commissioned by the American Society for Nutrition and The Obesity Society in an attempt to consider the state of understanding on this topic and identify key knowledge gaps. Roberts and Karl focus on the role of energy density in the regulation of energy intake and body weight and offer recommendations for prioritizing research. Finkelstein et al examine food and beverage purchases as a function of price changes and conclude that targeted food taxes and subsidies alone are unlikely to substantially affect obesity. Pereira points out the difficulty in establishing the strength of the association between intake of sugar-sweetened beverages and weight gain and obesity. Johnson and Wardle review the effects of palatability and variety on eating behavior and weight. Livingstone and Pourshahidi examine the impact of portion size manipulations on energy intake and weight management and find that consumers generally tend to eat proportionally more as portion size increases. Kant focuses on the efficacy and effectiveness of eating frequency manipulation for body weight management and finds that such manipulation has consistently yielded null results. Finally, Gordon-Larsen identifies several limitations of the existing literature regarding neighborhood access to healthy foods.


Time, place, and people: composition of the EPIET Alumni Network and its contribution to the European public health resource in 2013.
The EPIET Alumni Network (EAN) is an association of professionals who have completed field epidemiology or public health microbiology training programmes in the European Union. In 2013, we conducted a survey of EAN members to investigate this network's role within European public health. We distributed an online questionnaire to members registered at the time, collecting data on demographics, professional background, and attitudes towards EAN. Out of 362 registered members, 189 (52%) responded; 97% were from Europe; 65% were female. Their mean age was 39 years. The highest academic qualification was PhD for 44% and Master's degree for 55%. The majority (60%) worked in public health institutes. They were especially satisfied with having access to job offers and professional networking via EAN, but requested more learning opportunities and knowledge-sharing between members. EAN is a unique platform where highly skilled professionals can connect to control infectious diseases locally and internationally. Having a network of professionals that know each other, speak the same 'language', and can easily access each other's expertise, represents an important resource for European and global public health, which should be nurtured by encouraging more collaborations devoted to professional development.


Isoelectric focusing of an anti-HL-A2 antiserum cross-reacting with W28.
The cytotoxicity activity of an anti-HL-A2 antiserum cross-reactive with W28 appeared in three distinct peaks after the serum was subjected to isoelectric focusing. The pH at which the peaks formed was reproducible using pH 5-8 or pH 3.5-10 gradients. Anti-HL-A2 activity occurred in each peak, but the cross-reactive anti-W28 cytotoxicity appeared to be largely confined to the second and third peaks. The first peak was exclusively IgG, the second contained IgG and IgM, and the third contained IgG, IgA, and IgM.


Separating Bacteria by Capsule Amount Using a Discontinuous Density Gradient.
Capsule is a key virulence factor in many bacterial species, mediating immune evasion and resistance to various physical stresses. While many methods are available to quantify and compare capsule production between different strains or mutants, there is no widely used method for sorting bacteria based on how much capsule they produce. We have developed a method to separate bacteria by capsule amount, using a discontinuous density gradient. This method is used to compare capsule amounts semi-quantitatively between cultures, to isolate mutants with altered capsule production, and to purify capsulated bacteria from complex samples. This method can also be coupled with transposon-insertion sequencing to identify genes involved in capsule regulation. Here, the method is demonstrated in detail, including how to optimize the gradient conditions for a new bacterial species or strain, and how to construct and run the density gradient.


D-Tailor: automated analysis and design of DNA sequences.
Current advances in DNA synthesis, cloning and sequencing technologies afford high-throughput implementation of artificial sequences into living cells. However, flexible computational tools for multi-objective sequence design are lacking, limiting the potential of these technologies. We developed DNA-Tailor (D-Tailor), a fully extendable software framework, for property-based design of synthetic DNA sequences. D-Tailor permits the seamless integration of multiple sequence analysis tools into a generic Monte Carlo simulation that evolves sequences toward any combination of rationally defined properties. As proof of principle, we show that D-Tailor is capable of designing sequence libraries comprising all possible combinations among three different sequence properties influencing translation efficiency in Escherichia coli The capacity to design artificial sequences that systematically sample any given parameter space should support the implementation of more rigorous experimental designs. Source code is available for download at https://sourceforge.net/projects/dtailor/ CONTACT: email@example.com or email@example.com Supplementary information: Supplementary data are available at Bioinformatics online (D-Tailor Tutorial).


The Discrepancy of Parents' Theories of Intelligence and Parental Involvement.
In families, mothers and fathers may hold the same or different levels of theories of intelligence. This congruence and discrepancy may influence parental involvement in children's education. The current study examined how both parents' theories of intelligence and the direction and degree of the discrepancy of parents' intelligence theories influence maternal and paternal involvement separately. We measured 1,694 matched pairs of parents' theories of intelligence and educational involvement, and examined the relationships using linear regressions and polynomial regressions with response surface analysis. The results showed that (1) the mother's intelligence theory positively related to both paternal involvement and maternal involvement, but the father's intelligence theory only positively related to paternal involvement; (2) when the parents' theories of intelligence reached congruence, the parents' theories of intelligence are positively related to both maternal and paternal involvement; (3) when the parents' theories of intelligence have discrepancy, the maternal involvement is higher while the mother's intelligence theory's level is more incremental than father's; and (4) when the parents' theories of intelligence have discrepancy, more discrepancy of parents' theories of intelligence is related to more paternal involvement. This study revealed the significance of mother's role in education, highlighted the importance of parents' congruence and discrepancies in beliefs, examined how parents' beliefs impact their own behavior and their couple's behavior.


Anti-inflammatory strategies to reduce acute kidney injury in cardiac surgery patients: a meta-analysis of randomized controlled trials.
Acute kidney injury (AKI) after cardiac operations is a serious complication associated with postoperative mortality. Multiple factors contribute to AKI development, principally ischemia-reperfusion injury and inflammatory response. It is well proven that glucocorticoid administration, leukocyte filter application, and miniaturized extracorporeal circuits (MECC) modulate inflammatory response. We conducted a systematic review of randomized controlled trials (RCTs) in which one of these inflammatory system modulation strategies was used, with the aim to evaluate the effects on postoperative AKI. MEDLINE and Cochrane Library were screened through November 2011 for RCTs in which an inflammatory system modulation strategy was adopted. Included were trials that reported data about postoperative renal outcomes. Because AKI was defined by different criteria, including biochemical determinations, urine output, or dialysis requirement, we unified renal outcome as worsening renal function (WRF). We identified 14 trials for steroids administration (931 patients, WRF incidence [treatment vs. placebo]: 2.7% vs. 2.4%; OR: 1.13; 95% CI: 0.53-2.43; P = 0.79), 9 trials for MECC (947 patients, WRF incidence: 2.4% vs. 0.9%; OR: 0.47; 95% CI: 0.18-1.25; P = 0.13), 6 trials for leukocyte filters (374 patients, WRF incidence: 1.1% vs. 7.5%; OR: 0.18; 95% CI: 0.05-0.64; P = 0.008). Only leukocyte filters effectively reduced WRF incidence. Not all cardiopulmonary bypass-related anti-inflammatory strategies analyzed reduced renal damage after cardiac operations. In adult patients, probably other factors are predominant on inflammation in determining AKI, and only leukocyte filters were effective. Large multicenter RCTs are needed in order to better evaluate the role of inflammation in AKI development after cardiac operations.


Identification and occurrence of beta-carboline alkaloids in raisins and inhibition of monoamine oxidase (MAO).
Monoamine oxidase (MAO) is a mitochondrial enzyme involved in the oxidative catabolism of neurotransmitters and xenobiotic amines, including vasopressor and neurotoxic amines, and a current target for antidepressant and neuroprotective drugs. Raisin extracts and homogenates exhibited reversible in vitro inhibition of MAO isozymes, particularly MAO-A, suggesting the presence of MAO-inhibiting substances. Chromatographic and spectrometric studies showed the occurrence of aromatic beta-carboline alkaloids in raisins, and norharman and harman were identified as the key contributors to MAO inhibition. On average, harman ranged from 6 to 644 ng/g and norharman from 2 to 120 ng/g. Several technological variables appeared to determine the presence of these compounds in raisins. Dark-brown raisins (i.e., sun-dried) contained much higher levels than golden raisins. Tetrahydro-beta-carboline-3-carboxylic acid compounds that are direct precursors of aromatic beta-carbolines were also identified in raisins and appeared in a higher amount, reaching up to 50 microg/g. beta-Carbolines were isolated from raisins and acted as good competitive inhibitors of MAO-A (harman) and MAO-B (norharman) isozymes. These results suggest that beta-carboline alkaloids and perhaps raisins containing a high level of beta-carbolines might exhibit potential activity as MAO inhibitors. The results also show that some raisins can be a source of dietary exposure to bioactive beta-carbolines.


Disgust and contamination: a cross-national comparison of ghana and the United States.
The emotion of disgust, with feelings of revulsion and behavioral withdrawal, make it a prime emotion to aid in the avoidance of sources of contamination, including sources of potential infectious disease. We tested the theory that living in a region with a historically high prevalence of infectious diseases would promote higher levels of disgust and contamination sensitivity as a protective measure. A sample of undergraduates from Ghana (n = 103, 57 women), a country with a historically high prevalence of infectious diseases, showed significantly higher scores on scales assessing disgust, contamination, and disease susceptibility than a sample of undergraduates from the United States (n = 96, 58 women), a country with lower levels of disease threat. Contamination sensitivity mediated the national differences in disgust. Disgust connoting contamination also produced larger cross-national effect sizes than other types of disgust. Finally, a factor analysis on the Ghanaian responses to one of the disgust scales did not resemble the usual three-factor solution found in West. Taken together, the results were consistent with the hypothesis that a region with a higher prevalence of infectious disease threats would produce greater sensitivity to disgust and contamination than seen in lower disease threat regions. This first study on disgust in Africa showed that disgust sensitivity could differ considerably from that in the West.


Myelin Breakdown in Human Huntington's Disease: Multi-Modal Evidence from Diffusion MRI and Quantitative Magnetization Transfer.
Huntington's disease (HD) leads to white matter (WM) degeneration that may be due to an early breakdown in axon myelination but in vivo imaging correlates of demyelination remain relatively unexplored in HD compared to other neurodegenerative diseases. This study investigated HD-related effects on a putative marker of myelin, the macromolecular proton fraction (MMPF) from quantitative magnetization transfer and on fractional anisotropy, axial and radial diffusivity from diffusion tensor MR-imaging. Microstructural differences were studied in WM pathways of the basal ganglia and motor systems known to be impaired in HD: the corpus callosum, the cortico-spinal tract, the anterior thalamic radiation, fibers between prefrontal cortex and caudate and between supplementary motor area and putamen. Principal component analysis was employed for dimensionality reduction. Patients showed reductions in a component with high loadings on MMPF in all WM pathways and a trend for increases in a component loading on axial and radial diffusivities but no differences in a component loading on fractional anisotropy. While patients' performance in executive functioning was impaired, their working memory span was preserved. Inter-individual differences in the diffusivity component correlated with patients' performance in clinical measures of the United Huntington Disease Rating Scale. In summary, HD-related reductions in MMPF suggest that myelin breakdown contributes to WM impairment in human HD and emphasize the potential of quantitative MRI metrics to inform about disease pathogenesis. Disease severity in manifest HD, however, was best captured by non-specific diffusivity metrics sensitive to multiple disease and age-related changes.


Prevalence of temporomandibular dysfunction and its association with malocclusion in children and adolescents: an epidemiologic study related to specified stages of dental development.
A sample of 4724 children (2353 girls and 2371 boys) (5-17 years old) were grouped not only by chronological age but also by stage of dental development (deciduous, early mixed, late mixed, and permanent dentition). The registrations included functional occlusion (anterior and lateral sliding, interferences), dental wear, mandibular mobility (maximal opening, deflection), and temporomandibular joint and muscular pain recorded by palpation. Headache was the only symptom of temporomandibular dysfunction (TMD) reported by the children. The results showed that one or more clinical signs were recorded in 25% of the subjects, most of them being mild in character. The prevalences increased during the developmental stages. Girls were in general more affected than boys. Significant associations were found between different signs, and TMD was associated with posterior crossbite, anterior open bite, Angle Class III malocclusion, and extreme maxillary overjet.


Discovery and refinement of a new structural class of potent peptide deformylase inhibitors.
New classes of antibiotics are urgently needed to counter increasing levels of pathogen resistance. Peptide deformylase (PDF) was originally selected as a specific bacterial target, but a human homologue, the inhibition of which causes cell death, was recently discovered. We developed a dual-screening strategy for selecting highly effective compounds with low inhibition effect against human PDF. We selected a new scaffold in vitro that discriminated between human and bacterial PDFs. Analyses of structure-activity relationships identified potent antibiotics such as 2-(5-bromo-1H-indol-3-yl)-N-hydroxyacetamide (6b) with the same mode of action in vivo as previously identified PDF inhibitors but without the apoptotic effects of these inhibitors in human cells.


Prescription for excellence: an ostomy clinic.
Individuals scheduled for ostomy surgery and those with a new or established stoma benefit from the services of a Certified Ostomy Care Nurse or Certified Wound Ostomy Continence Nurse provided in an ostomy clinic. The clinic can provide pre- and postoperative services as well as long-term holistic care. Developing a clinic requires an organized and well thought-out plan that identifies unmet patient needs to justify the importance of this ambulatory service to facility administrators. The plan should include configuring and preparing the area where care will be provided, advertising the services offered, and determining hours, staff, policies, and procedures with particular attention paid to facility and regulatory specifications. After establishing a clinic in a large, urban, acute care hospital, patient visits averaged 33 per month and the scheduled 6 hours per week of clinic time needed to be expanded to meet the needs of those requesting appointments. Once established, patient outcomes and provider satisfaction should be recorded. Certified Ostomy Care Nurses and Certified Wound Ostomy Continence Nurses have a responsibility to inform their patients about the ostomy clinic option when it is available and clinic clinicians should continue to share the results of their efforts to proliferate the ostomy clinic concept.


The relationship between child anthropometry and mortality in developing countries: implications for policy, programs and future research.
The prevention of child mortality is a commonly stated health goal in developing countries and the target of much international assistance in the health sector. Over the past decade the primary strategy for accelerating the reduction in child mortality has been the dissemination of simple, low-cost technologies, such as immunization, oral rehydration therapy and antibiotics, that target specific diseases (Huffmann and Steel 1994). This is done despite the knowledge that malnutrition and disease have a synergistic relationship (Scrimshaw et al. 1968) and that the optimal strategy may involve a combination of health and nutrition interventions. In the 1970s, for instance, it was estimated that malnutrition (notably protein-energy malnutrition--PEM) was the underlying or contributing cause of death for roughly half of all deaths to children aged 1-4 years in several Latin American countries (Puffer and Serrano 1973). Apart from this early study, however, there has been little effort to quantify the contribution of malnutrition to child mortality in other regions of the world in ways which are meaningful to policy. This paper reviews the results of 28 community-based, prospective studies, in 12 Asian and Sub-Saharan African countries, which examined the relationship between anthropometric indicators of malnutrition and child mortality. One purpose is to estimate the contribution of malnutrition to child mortality--distinguishing the effects of severe malnutrition from mild-to-moderate malnutrition--and to examine a number of related issues relevant to policy, programs and research in this area. The accumulated results are consistent in showing that the risk of mortality is inversely related to anthropometric indicators of nutritional status and that there is elevated risk even in the mild-to-moderate range of malnutrition. This latter result contradicts the findings from an earlier, landmark study which suggested that mild-to-moderate malnutrition was not associated with an increased risk of mortality (Chen et al. 1980). The present results indicate that somewhere between 20% and 75% of child deaths are statistically attributable to anthropometric deficits, with most estimates falling in the range 25-50%. When taking account of the relative proportions of severe versus mild-to-moderate malnutrition in the population, the results show further than 16-80% of all nutrition-related deaths are associated with mild-to-moderate malnutrition rather than severe malnutrition. In most studies 46-80% of all nutrition-related deaths are in the mild-to-moderate category.(ABSTRACT TRUNCATED AT 400 WORDS)


The eye in systemic vasculitis.
The term 'vasculitis' includes a wide range of disorders characterised by inflammation of the wall of blood vessels, sometimes with necrosis, leading to ischaemia of the affected organ. The exact pathogenesis of most of these vasculitides is not fully understood and although the presence of circulating auto-antibodies seems to be a common feature among them, each vasculitis has its unique pathogenesis and a predilection for vessels of a defined size. Systemic vasculitis may be associated with ocular complications which include scleritis, keratitis, uveitis and optic neuropathy. These can precede the symptoms/signs of the systemic disease and therefore their recognition may lead to detection of the underlying disorder. The eye may also be affected by the treatment required to control the systemic disease.


Stereoelectronic Switches of Single-Molecule Junctions through Conformation-Modulated Intramolecular Coupling Approaches.
Stereoelectronic effects in single-molecule junctions have been widely utilized to achieve a molecular switch, but high-efficiency and reproducible switching remain challenging. Here, we demonstrate that there are three stable intramolecular conformations in the 9,10-diphenyl-9,10-methanoanthracen-11-one (DPMAO) systems due to steric effect. Interestingly, different electronic coupling approaches including weak coupling (through-space), decoupling, and strong coupling (through-bond) between two terminal benzene rings are accomplished in the three stable conformations, respectively. Theoretical calculations show that the molecular conductance of three stable conformations differs by more than 1 order of magnitude. Furthermore, the populations of the three stable conformations are highly dependent on the solvent effect and the external electric field. Therefore, an excellent molecular switch can be achieved using the DPMAO molecule junctions and external stimuli. Our findings reveal that modulating intramolecular electronic coupling approaches may be a useful manner to enable molecular switches with high switching ratios. This opens up a new route for building high-efficiency molecular switches in single-molecular junctions.


Enhanced increases in cytosolic Ca2+ in ADP-stimulated platelets from patients with delta-storage pool deficiency--a possible indicator of interactions between granule-bound ADP and the membrane ADP receptor.
The possible involvement of secreted platelet substances in agonist-induced [Ca2+]i increases was investigated by comparing these increases in aspirin-treated, fura-2-loaded normal platelets and platelets from patients with storage pool deficiencies (SPD). In the presence and absence of extracellular calcium, the [Ca2+]i response induced by 10 microM ADP, but not those induced by 0.1 unit/ml thrombin, 3.3 microM U46619, or 20 microM serotonin, was significantly greater in SPD platelets than in normal platelets, and was increased to the greatest extent in SPD patients with Hermansky-Pudlak syndrome (HPS), in whom the dense granule deficiencies are the most severe. Pre-incubation of SPD-HPS and normal platelets with 0.005-5 microM ADP produced a dose-dependent inhibition of the [Ca2+]i response induced by 10 microM ADP, but did not alter the [Ca2+]i increases induced by thrombin or U46619. Within a limited range of ADP concentrations, the dose-inhibition curve of the [Ca2+]i response to 10 microM ADP was significantly shifted to the right in SPD-HPS platelets, indicating that pre-incubation with greater amounts of ADP were required to achieve the same extent of inhibition as in normal platelets. These results are consistent with a hypothesis that the smaller ADP-induced [Ca2+]i increases seen in normal platelets may result from prior interactions of dense granule ADP, released via leakage or low levels of activation, with membrane ADP receptors, causing receptor desensitization. Addition of apyrase to platelet-rich plasma prior to fura-2 loading increased the ADP-induced [Ca2+]i response in both normal and SPD-HPS platelets, suggesting that some release of ADP derived from both dense granule and non-granular sources occurs during in vitro fura-2 loading and platelet washing procedures. However, this [Ca2+]i response was also greater in SPD-HPS platelets when blood was collected with minimal manipulation directly into anticoagulant containing apyrase, raising the possibility that release of dense granule ADP resulting in receptor desensitization may also occur in vivo. Thus, in addition to enhancing platelet activation, dense granule ADP could also act to limit the ADP-mediated reactivity of platelets exposed in vivo to low levels of stimulation.