Oligosaccharide structures of isolated human colonic mucin species.
Purified human colonic mucin contains six distinct components which may be separated by DEAE-cellulose chromatography. Past studies defined the structure of oligosaccharide side chains from the most abundant species III, IV, and V which elute at intermediate salt concentrations. In these studies the structures of oligosaccharide side chains liberated from the remaining early and late eluting species I, II, and VI were determined after isolation by sequential conventional and high performance liquid chromatography through combination of gas chromatography, methylation analysis, and sequential glycosidase digestion. Mucin species I, II, and VI contained a less varied array of discrete oligosaccharide structures than that observed in the major mucin components. Mucin species I and II contained five and 10 structures, respectively, which account for 68 and 71% of total oligosaccharide content in these fractions. The predominant oligosaccharides of mucin species I included three neutral structures: a disaccharide GlcNAc beta (1-3)GalNAc-ol, a trisaccharide Gal beta (1-4)GlcNAc beta (1-3)GalNAc-ol, and a tetrasaccharide GlcNAc beta (1-4)Gal beta (1-4)GlcNAc beta (1-3)GalNAc-ol as well as two acidic components representing the sialylated forms of two of these oligosaccharides. Mucin species II contained these same oligosaccharides as well as four additional acidic structures, notably a disaccharide Neu alpha (2-6)GalNAc-ol and a hexasaccharide Gal beta (1-4)GlcNAc beta (1-3)Gal beta (1-4)GlcNAc beta (1-3) (NeuAc alpha (2-6))-GalNAc-ol, not identified in any other mucin species. The late eluting mucin species VI contained at least five discrete neutral oligosaccharides and six major acidic structures. While the majority of these structures had been previously isolated from the earlier eluting mucin species IV and V, species VI also contained di- and trisialylated oligosaccharides not identified in other mucin species. In conjunction with earlier studies of the major mucin species III, IV, and V, these data define the range of oligosaccharide structures present in human colonic mucin. These studies demonstrate that human colonic mucin possesses species with characteristic and distinguishable combinations of oligosaccharides which reflect variations of common core structures.


Does the association between birth weight and blood pressure increase with age? A longitudinal study in young adults.
To assess whether the association between birth weight and blood pressure (BP) increases with age using three different statistical methods. A representative sample of 1232 study participants born between 1974-1978 in Limache, Chile were assessed in 2000-2002, of whom 796 were reassessed in 2010-2012. An 'amplification effect' was assessed by the change in the β coefficient in the two periods, the association between birth weight and the difference of BP overtime, and the interaction between birth weight and BP in the two periods. Birth weight was negatively associated with SBP in 2000-2002 (β = -2.46, 95% confidence interval (CI) -3.77 to -1.16) and in 2010-2012 (β = -3.64, 95% CI -5.20 to -2.08), and with DBP in 2000-2002 (β = -1.26, 95% CI -2.23 to -0.29) , and 2010-2012 (β = -1.64, 95% CI -2.84 to -0.45) after adjustment for sex, physical activity, and BMI. There was no association between birth weight and the difference in BP between the two periods or the interaction between birth weight, BP, and time interval. Birth weight is a factor associated with BP in adults. This association increased with age, but amplification was shown only with one of the three methods.


Nursing workloads: the results of a study of Queensland Nurses.
This paper reports the findings of a survey undertaken in Queensland, Australia in October 2001. The participants were registered and enrolled nurses and assistants in nursing who were members of the industrial body - the Queensland Nursing Union (QNU), and who were in paid employment in nursing in Queensland. Participants were selected by random sampling from each of the three major employment groups - the aged care, public and private acute sectors. Of the 2800 invited participants, 1477 responded resulting in an overall response rate of 53%. The findings indicate that over 50% of nurses in the aged-care sector, 32% of nurses in the public and 30% of nurses in the private acute sector experience difficulties in meeting patient needs because of insufficient staffing levels. The nurses in this study also believed that there was poor skills-mix, mostly caused by lack of funding, too few experienced staff or too many inexperienced staff. Many nurses in this study expressed their anger and frustration about their inability to complete their work to their professional satisfaction in the paid time available. Further, many nurses also expressed the view that because of this inability they were planning to leave the nursing profession. These findings are consistent with other research into the nursing workforce both within Australia and internationally.


Peripherally inserted central catheters and the incidence of candidal sepsis in VLBW and ELBW infants: is sepsis increased?
Peripherally inserted central catheters (PICCs) have been widely used in neonatal clinics. However, the complications such as infection after PICC treatment are also confronting neonatologists especially in developing countries. This study was undertaken to investigate whether PICCs is a safe treatment for very low birth weight (VLBW) infants and extremely low birth weight (ELBW) infants. Fifty-nine VLBW and ELBW infants receiving PICCs and 89 VLBW and ELBW infants receiving peripheral intravenous catheters (PIVCs) were included in this study. The incidence of sepsis and mortality were compared retrospectively between the two groups. There was no difference in the total sepsis incidence and mortality between the PICCs and PIVCs groups (P=0.11 and P=0.61 respectively). However, the candidal sepsis incidence was higher in the PICCs group than in the PIVCs group [6/59 (10.2%) vs 2/89 (2.2%); P=0.044 (Exat Sig. 1-sided), OR=4.93, 95% CI 0.96-25.3]. Placement and indwelling of PICCs are a potential risk factor for candidal sepsis among VLBW and ELBW infants.


The legacy of early childhood violence exposure to adulthood intimate partner violence: Variable- and person-oriented evidence.
This study examined prospective pathways from exposure to interparental violence (EIPV) during infancy (ages 0-24 months) and toddlerhood/preschool (ages 25-64 months) to intimate partner violence (IPV) perpetration and victimization in adulthood (ages 23, 26, and 32 years) using 2 complementary approaches. Building on past findings, a variable-oriented approach was used to examine the effects of developmental timing of EIPV in infancy versus toddlerhood/preschool to IPV involvement in early adulthood, at age 23 years. A person-oriented approach next examined whether continuity and change in IPV (persisting, increasing, and decreasing vs. nonviolent patterns) across the transition from early adulthood to adulthood (ages 26 to 32 years) were predicted by developmental timing of EIPV within early childhood and/or contemporaneous adulthood factors (life stress and behavior problems). In this fully prospective longitudinal study beginning at birth, mothers reported on EIPV in infancy and toddlerhood/preschool, and participants (N = 179) reported on IPV and contemporaneous stress and behavior in early adulthood and adulthood. Results indicated that according to the variable-oriented approach, EIPV in toddlerhood/preschool but not in infancy predicted both IPV perpetration and victimization at age 23. The person-oriented approach revealed that, along with life stress and externalizing behavior, EIPV in toddlerhood/preschool, but not in infancy, also differentiated patterns of IPV from ages 26 to 32. Findings converge on toddlerhood/preschool as a particular promising developmental period to intervene and deter long-term effects of EIPV on IPV across the transition from early adulthood to adulthood. (PsycINFO Database Record


[A rare complication after surgical correction of the rupture of Valsalva's sinus aneurysm into the right heart ventricle].
Postsurgical myocardial infarction in a 68-year-old female was observed after occasional compression of the coronary artery by a teflon gasket when P-like suture was applied on the anterior wall of the right ventricle in the course of surgical intervention for closure of the aortic-right-ventricular fistula. The latter had formed after the rupture of Valsalva's sinus aneurysm into the right ventricle this being the cause of the surgery. The authors propose how to document the diagnosis and medical death certificate in similar cases.


[Changes in excitability in the motor cortex of the dog during switching-over conditioned escape and avoidance reflexes].
Excitability of the motor cortex (projection of the foreleg), judged by the threshold of flexion reaction to its stimulation during elaboration of conditioned transswitching (CT), was studied in dogs. CT was elaborated for instrumental reflexes of escape (1-st CT variant) and avoidance (2-nd CT variant). In the 1-st variant the dog escaped from the hydrochloric acid solution, if during its administration it produced an active flexion of the foreleg in situation A and an active extension of the same leg in situation B, with a permanent action of a switch (a fan). In the 2-nd CT variant, the dog avoided the acid, if in situation A, in response to a tone of 250 Hz, it actively lifted its foreleg, and if in situation B, it actively resisted a passive lift in response to the same stimulus. In escape CT as well as in avoidance CT, there was a statistically significant difference between the thresholds of flexion reaction. The threshold was lower in situation of instrumental flexion reflex formation in comparison to the situation of extension reflex formation.


Bridging the Information Gap in Polycystic Ovary Syndrome: A Narrative Review with Systematic Approach.
Polycystic ovary syndrome (PCOS) is a complex endocrinopathy with wide-ranging implications for affected individuals. Literature has shown that patients with PCOS are dissatisfied with the health information provided to them and that healthcare professionals lack adequate knowledge. In this narrative review with systematic approach, we explored the unmet information needs in PCOS care for both patients and healthcare professionals. A comprehensive search of databases yielded 41 relevant studies, predominantly of observational and qualitative design. Adults and adolescents with PCOS desire wide ranging health information and express a keen desire for weight management guidance. Importantly, discussions surrounding weight should be addressed knowledgeably and without weight bias. Therefore, healthcare professionals should facilitate access to comprehensive evidence-based resources. Lack of information drives PCOS-related online searches. Referral to support groups that promote individual agency in the self-management aspects of PCOS can furthermore guide patient resource acquisition. Patients prefer guidance from professionals that understand the psychosocial complexity of PCOS and can empathize with experiences of stigmatization or even marginalization depending on the cultural context of the individual. The findings informed the 2023 International Evidence-Based PCOS Guideline, recommending patient-centered communication, evidence-based information resources, and culturally sensitive approaches to optimize PCOS care.


Social capital, income inequality and self-rated health in Chita peninsula, Japan: a multilevel analysis of older people in 25 communities.
The effect of social capital on one's health has drawn researchers' attention. In East-Asian countries, however, such an effect has been less studied than in Western countries. Mindful of this background, this study aimed to investigate the linkage between social capital and health at the level of a small area in Japan, and also to examine whether social capital mediates the relation between income inequality and health. The main survey targeted 34,374 people aged 65 years and older from 25 communities who were without the need of nursing care. We collected 17,269 questionnaires (response rate 50.2%), from which we used 15,225 (response rate 44.3%) which had complete information on self-rated health, age, and sex. The main outcome measure was self-rated health status (1=fair/poor; 0=very good/good). The individual-level variables of age, sex, equivalised income, marital status, educational attainment, and type of housing were included to control for compositional effects. Average income, social capital and the Gini coefficient were used as community-level variables. The variable of social capital was calculated as the percentage of individuals in the community samples who reported "yes" or "it depends" to the question "Generally speaking, would you say that most people can be trusted?" When the individual-level variables and the average equivalised income at the community level were controlled for, we found that high social capital and a decreased Gini coefficient were significantly associated with good self-rated health using a multilevel model. The association between social capital and self-rated health was insignificant after adjustment for the Gini coefficient. However, in other series of models, we also detected a statistically significant linkage between the increased Gini coefficient and negative responses to the question of individual-level trust using multilevel models. This suggests that people who live in conditions of high-income inequality tend to exhibit low trust levels, and that social capital mediates the relation between income inequality and health. This study is, to our knowledge, the first investigation of the linkage between social capital and health in Japan using multilevel analysis, and reports the first supported result of the relative income hypothesis in Japan. Additionally, the statistically significant linkage between the increased Gini coefficient and low trust observed in this study provides additional evidence to support the social cohesion and collective social pathway between income inequality and health.


Endoscopic Submucosal Dissection in Patients with Ulcerative Colitis.
Patients with ulcerative colitis have an increased risk of developing colorectal cancer. This risk has been estimated to reach about 7% at 20 years of disease, 7-14% at 25 years, and as high as 30% after 35 years. The guidelines for the management of inflammatory bowel disease recommend endoscopic resection of circumscribed dysplasia and ongoing colonoscopic surveillance as a reasonable strategy in patients with ulcerative colitis. Submucosal fibrosis due to background inflammation could hamper adequate lifting and endoscopic treatment. Endoscopic mucosal resection (EMR) is difficult for dysplasia within colitic mucosa due to the non-lifting sign. Although endoscopic submucosal dissection (ESD) generally has higher risks of perforation and bleeding compared to EMR, the technique can achieve complete en bloc resection regardless of the lesion size or severity of submucosal fibrosis. Several studies have shown that ESD for circumscribed dysplasia in ulcerative colitis is feasible. While ESD can avert unnecessary surgery, submucosal fibrosis makes the intervention technically demanding in cases of ulcerative colitis. ESD should be performed by expert endoscopists using the most suitable equipment and devices available.


Suicide among regular-duty military personnel: a retrospective case-control study of occupation-specific risk factors for workplace suicide.
The purpose of this study was to examine the epidemiology, phenomenology, and occupation-specific risk factors for suicide among regular-duty military personnel as a model for other professions at risk for workplace suicide. Suicide incidence and methods were determined in a retrospective military cohort comprising all deaths (N=732) of regular-duty military personnel in the Irish Defence Forces between 1970 and 2002. A retrospective, case-control study using pair-matched military comparison subjects was conducted to determine occupation-specific risk factors for suicide, particularly by firearm, among military personnel. Risk factors were subjected to chi-square analysis or independent t tests and entered into a binary logistic regression analysis model. The period-averaged suicide rate for the cohort was 15.3/100,000. Firearm suicides accounted for 53% of the cases. Suicides that took place on duty occurred predominantly when personnel were alone shortly after duty commencement in the morning. Bivariate and logistic regression analyses identified psychiatric illness and a past history of deliberate self-harm, morning duty (shortly after duty assumption and consequent access to firearms), and a recent medical downgrading as independent risk factors predicting firearm suicide among military personnel. Occupation influences suicide method. Access to and opportunity to use lethal means in the workplace are distinct but related occupation-specific suicide risk factors in the military and in other at-risk professions. In professions where access to lethal means is inevitable, moderating opportunity for suicide is crucially important. In regular-duty military personnel, a medical downgrading, combined with risk factors established in civilians such as younger age, male gender, psychiatric illness, and past self-harm, increases the risk of suicide. The findings may be used to guide military harm-reduction strategies and have applicability in strategies for other professions at risk for workplace suicide.


[Threshold value for reimbursement of costs of new drugs: cost-effectiveness research and modelling are essential links].
There is increasing discussion in the Netherlands about the introduction of a threshold value for the costs per extra year of life when reimbursing costs of new drugs. The Medicines Committee ('Commissie Geneesmiddelen'), a division of the Netherlands National Healthcare Institute ('Zorginstituut Nederland'), advises on reimbursement of costs of new drugs. This advice is based upon the determination of therapeutic value of the drug and the results of economic evaluations. Mathematical models that predict future costs and effectiveness are often used in economic evaluations; these models can vary greatly in transparency and quality due to author assumptions. Standardisation of cost-effectiveness models is one solution to overcome the unwanted variation in quality. Discussions about the introduction of a threshold value can only be meaningful if all involved are adequately informed, and by high quality in cost-effectiveness research and, particularly, economic evaluations. Collaboration and discussion between medical specialists, patients or patient organisations, health economists and policy makers, both in development of methods and in standardisation, are essential to improve the quality of decision making.


The CDK regulators Cdh1 and Sic1 promote efficient usage of DNA replication origins to prevent chromosomal instability at a chromosome arm.
Robustness and completion of DNA replication rely on redundant DNA replication origins. Reduced efficiency of origin licensing is proposed to contribute to chromosome instability in CDK-deregulated cell cycles, a frequent alteration in oncogenesis. However, the mechanism by which this instability occurs is largely unknown. Current models suggest that limited origin numbers would reduce fork density favouring chromosome rearrangements, but experimental support in CDK-deregulated cells is lacking. We have investigated the pattern of origin firing efficiency in budding yeast cells lacking the CDK regulators Cdh1 and Sic1. We show that each regulator is required for efficient origin activity, and that both cooperate non-redundantly. Notably, origins are differentially sensitive to CDK deregulation. Origin sensitivity is independent on normal origin efficiency, firing timing or chromosomal location. Interestingly, at a chromosome arm, there is a shortage of origin firing involving active and dormant origins, and the extent of shortage correlates with the severity of CDK deregulation and chromosome instability. We therefore propose that CDK deregulation in G1 phase compromises origin redundancy by decreasing the number of active and dormant origins, leading to origin shortage and increased chromosome instability.


Dialogue and Dominance in Couple Therapy for Depression: Exploring Therapists' Responses in Creating Collaborative Moments.
Previous investigations have found specific communication patterns in couples dealing with depression, specifically when depression concurs with conjugal conflicts. The presence of these patterns can reflect couples' difficulties in engaging in collaborative communication during their sessions, posing a real challenge for therapists. This exploratory study uses a dialogical approach to examine issues of dominance and type of dialogue in two couples who differed in terms of their levels of dyadic adjustment. The therapists' reactions were explored in order to detect the kinds of responses that were most effective at engendering a collaborative attitude in therapy sessions. The method used to analyze the dialogue was Dialogical Investigations of Happenings of Change (DIHC). Results on dominance indicated that the degree of quantitative and semantic dominance displayed by a different member of the couple in each case was illustrative of their relational dynamics, while in both cases interactional dominance was exercised by the therapists. Results on dialogue revealed that dialogic dialogue might help to coconstruct new shared meanings of depression. The findings indicated that certain responses by therapists as part of the dialogue could be useful in bringing about a reduction in hostility between the members of a couple, provided that the responses are maintained over the course of the session. Some research and clinical implications that emerge from the results are discussed.


[Diagnosis and clinical picture of oligophrenia among students with cerebral palsy].
A clinico-psychological examination covered 112 children aged 7-9 years with cerebral paralysis. The authors consider the diagnosis of intellectual disorders using traditional clinico-psychological techniques and an original technique of prediction ("Ugadaika" and Raven's matrices). the latter two methods, when combined with clinical examination, were shown to be highly informative in diagnosing oligophrenia in junior schoolchildren. Characteristics of oligophrenia in different forms of infantile cerebral paralysis are described.


The conservation of redundancy in genetic systems: effects of sexual and asexual reproduction.
The relationship between probability of survival and the number of deleterious mutations in the genome is investigated using three different models of highly redundant systems that interact with a threatening environment. Model one is a system that counters a potentially lethal infection; it has multiple identical components that act in sequence and in parallel. Model two has many different overlapping components that provide threefold coverage of a large number of vital functions. The third model is based on statistical decision theory: an ideal detector, following an optimum decision strategy, makes crucial decisions in an uncertain world. The probability of a fatal error is reduced by a redundant sampling system, but the chance of error rises as the system is impaired by deleterious mutations. In all three cases the survival profile shows a synergistic pattern in that the probability of survival falls slowly and then more rapidly. This is different than the multiplicative or independent survival profile that is often used in mathematical models. It is suggested that a synergistic profile is a property of redundant systems. Model one is then used to study the conservation of redundancy during sexual and asexual reproduction. A unicellular haploid organism reproducing asexually retains redundancy when the mutation rate is very low (0.001 per cell division), but tends to lose high levels of redundancy if the mutation rate is increased (0.01 to 0.1 per cell division). If a similar unicellular haploid organism has a sexual phase then redundancy is retained for mutation rates between 0.001 and 0.1 per cell division. The sexual organism outgrows the asexual organism when the above mutation rates apply. If they compete for finite resources the asexual organism will be extinguished. Variants of the sexual organism with increased redundancy will outgrow those with lower levels of redundancy and the sexual process facilitates the evolution of more complex forms. There is a limit to the extent that complexity can be increased by increasing the size of the genome and in asexual organisms this leads to progressive accumulation of mutations with loss of redundancy and eventual extinction. If complexity is increased by using genes in new combinations, the asexual form can reach a stable equilibrium, although it is associated with some loss of redundancy. The sexual form, by comparison, can survive, with retention of redundancy, even if the mutation rate is above one per generation. The conservation and evolution of redundancy, which is essential for complexity, depends on the sexual process of reproduction.


Classification of retinal ganglion cells in the southern hemisphere lamprey Geotria australis (Cyclostomata).
Lampreys are one of two extant representatives of the earliest group of vertebrates, the agnathans or jawless fishes. The single species of the southern hemisphere lamprey family Geotriidae, Geotria australis, possesses the potential for pentachromatic color discrimination opposed to the mono- or dichromacy found in other lampreys. However, little is known of the retinal ganglion cell types that contribute to visual processing in G. australis. A quantitative morphological approach was used to distinguish and describe retinal ganglion cell types in G. australis. The morphology of retinal ganglion cells was revealed by retrograde biocytin labeling from the optic disc. Cells were digitally reconstructed, and somatic area and position and dendritic field size, density, tortuosity, and stratification were subjected to quantitative morphometric analyses. Cluster analysis, in conjunction with similarity profile analysis (SIMPROF), statistically identified five discrete monostratified retinal ganglion cell types, one of which may comprise two subtypes. Two bistratified types were identified separately, including a biplexiform and a bistratified subtype. The use of cluster analysis with SIMPROF provided a robust statistical technique for objectively identifying cell types whose characteristics were similar and significantly different from those of other types and thus provides an objective resolution of the problems posed by "lumpers vs. splitters" when designating cell types. The diversity of retinal ganglion cells suggests that visual information in the lamprey G. australis is processed in parallel streams, as in gnathostomes. These findings, together with the results of previous studies, indicate that the visual system of the lamprey G. australis represents the upper limit of visual complexity in extant agnathans.


Calcium ion-stimulated phosphorylation of myelin proteins.
Myelin isolated from the central and peripheral nervous system contains a Mg2+-dependent protein kinase that catalyses phosphorylation of myelin-specific proteins. This phosphorylation is markedly stimulated by Ca2+ but not by cyclic AMP. Evidence was obtained that suggested an involvement of calmodulin-like protein in the stimulatory effects of Ca2+ on myelin phosphorylation.


Tgf-Beta pathway as a therapeutic target in bone metastases.
Breast and prostate cancer frequently metastasizes to the skeleton and causes bone destruction. In skeletal tissue, transforming growth factor-beta (TGF-beta) is a major bone-derived factor responsible for driving a feed-forward vicious cycle of breast cancer growth in bone. TGF-beta is released from bone in active form by osteoclastic resorption and increases the tumor secretion of factors, which stimulate osteolytic destruction of the bone adjacent to the tumor. Moreover it activates epithelial-mesenchymal transition and tumor cell invasion, increases angiogenesis and induces immunosuppression. Blocking the TGF-beta signaling pathway to interrupt this vicious cycle between tumor and bone offers a target for therapeutic intervention to decrease skeletal metastasis. Here we summarize the current knowledge of TGF-beta in bone metastases, the use of TGF-beta inhibitors and its potential for clinical use and consequences.


Y-Doped Sb2Te3 Phase-Change Materials: Toward a Universal Memory.
The disadvantages of high power consumption and slow operating speed hinder the application of phase-change materials (PCMs) for a universal memory. In this work, based on a rigorous experimental scheme, we synthesized a series of YxSb2-xTe3 (0 ≤ x ≤ 0.333) PCMs and demonstrated that Y0.25Sb1.75Te3 (YST) is an excellent candidate material for the universal phase-change memory. This YST PCM, even being integrated into a conventional T-shaped device, exhibits an ultralow reset power consumption of 1.3 pJ and a competitive fast set speed of 6 ns. The ultralow power consumption is attributed to the Y-reduced thermal and electrical conductivity, while the maintained crystal structure of Sb2Te3 and the grain refinement provide the competitive fast crystallization speed. This work highlights a novel way to obtain new PCMs with lower power consumption and competitive fast speed toward a universal memory.


Autosomal genomic scan for loci linked to obesity and energy metabolism in Pima Indians.
An autosomal genomic scan to search for linkage to obesity and energy metabolism was completed in Pima Indians, a population prone to obesity. Obesity was assessed by percent body fat (by hydrodensitometry) and fat distribution (the ratio of waist circumference to thigh circumference). Energy metabolism was measured in a respiratory chamber as 24-h metabolic rate, sleeping metabolic rate, and 24-h respiratory quotient (24RQ), an indicator of the ratio of carbohydrate oxidation to fat oxidation. Five hundred sixteen microsatellite markers with a median spacing of 6.4 cM were analyzed, in 362 siblings who had measurements of body composition and in 220 siblings who had measurements of energy metabolism. These comprised 451 sib pairs in 127 nuclear families, for linkage analysis to obesity, and 236 sib pairs in 82 nuclear families, for linkage analysis to energy metabolism. Pointwise and multipoint methods for regression of sib-pair differences in identity by descent, as well as a sibling-based variance-components method, were used to detect linkage. LOD scores >=2 were found at 11q21-q22, for percent body fat (LOD=2.1; P=.001), at 11q23-q24, for 24-h energy expenditure (LOD=2.0; P=.001), and at 1p31-p21 (LOD=2.0) and 20q11.2 (LOD=3.0; P=.0001), for 24RQ, by pointwise and multipoint analyses. With the variance-components method, the highest LOD score (LOD=2.3 P=.0006) was found at 18q21, for percent body fat, and at 1p31-p21 (LOD=2.8; P=.0003), for 24RQ. Possible candidate genes include LEPR (leptin receptor), at 1p31, and ASIP (agouti-signaling protein), at 20q11.2.


Synthesizing Methuselah: The Question of Artificial Agelessness.
As biological organisms, we age and, eventually, die. However, age's deteriorating effects may not be universal. Some theoretical entities, due to their synthetic composition, could exist independently from aging-artificial general intelligence (AGI). With adequate resource access, an AGI could theoretically be ageless and would be, in some sense, immortal. Yet, this need not be inevitable. Designers could imbue AGIs with artificial mortality via an internal shut-off point. The question, though, is, should they? Should researchers curtail an AGI's potentially endless lifespan by deliberately making it mortal? It is this question that this article explores. First, it considers what type of AGI is under discussion before outlining how such beings could be ageless. Then, after clarifying the type of immortality under discussion and arguing that imbuing an AGI with synthetic aging would be person-affecting, the article explores four core conundrums: (i) deliberately causing a morally significant being's death; (ii) immortality's associated harms; (iii) concerns about immortality's unequal assignment; and (iv) the danger of immortal AGI overlords. The article concludes that while prudence requires we create an aging AGI, in the face of the material harm such an action would constitute, this is an insufficient reason to justify doing so.


Antimicrobial dispensing practices and determinants of antimicrobial resistance: a qualitative study among community pharmacists in Pakistan.
There are concerns with the extent of dispensing of antibiotics among community pharmacists in Pakistan often without a prescription adding to antimicrobial resistance (AMR) rates. To explore the determinants of AMR and the pattern of antimicrobial dispensing among community pharmacists. In this qualitative study design, a semistructured interview guide was developed based on an in-depth review of published papers. Audio-recorded interviews with transcripts were analysed by thematic content analysis. Interviews were conducted among community pharmacists in Lahore, Pakistan. In order to obtain individual points of view, in-depth face-to-face interviews with purposively selected pharmacists were conducted. A total of 12 pharmacists were interviewed for the study. After analysis, four major themes emerged: (1) knowledge and perception of community pharmacists about antimicrobials, (2) antimicrobial dispensing practices of community pharmacists, (3) determinants of AMR, (4) potential interventions to control AMR. Most of the pharmacists have limited knowledge about AMR, antimicrobial stewardship programmes and related guidelines. However, all the pharmacists strongly agreed that different appropriate actions should be taken in order to rationalise future antimicrobial use. The results indicated that irrational antimicrobial dispensing and use is common among community pharmacists in Pakistan owing to lack of knowledge. The community pharmacists perceived that behaviour of patients and the societal environment contributed to irrational antimicrobial use and subsequent development of AMR. They suggested a need for a multidisciplinary framework in order to improve future antimicrobial use and reduce AMR in Pakistan.


Nitrogen Self-Doped Activated Carbons Derived from Bamboo Shoots as Adsorbent for Methylene Blue Adsorption.
Bamboo shoots, a promising renewable biomass, mainly consist of carbohydrates and other nitrogen-related compounds, such as proteins, amino acids and nucleotides. In this work, nitrogen self-doped activated carbons derived from bamboo shoots were prepared via a simultaneous carbonization and activation process. The adsorption properties of the prepared samples were evaluated by removing methylene blue from waste water. The factors that affect the adsorption process were examined, including initial concentration, contact time and pH of methylene blue solution. The resulting that BSNC-800-4 performed better in methylene blue removal from waste water, due to its high specific surface area (2270.9 m2 g-1), proper pore size (2.19 nm) and relatively high nitrogen content (1.06%). Its equilibrium data were well fitted to Langmuir isotherm model with a maximum monolayer adsorption capacity of 458 mg g-1 and a removal efficiency of 91.7% at methylene blue concentration of 500 mg L-1. The pseudo-second-order kinetic model could be used to accurately estimate the carbon material's (BSNC-800-4) adsorption process. The adsorption mechanism between methylene blue solution and BSNC-800-4 was controlled by film diffusion. This study provides an alternative way to develop nitrogen self-doped activated carbons to better meet the needs of the adsorption applications.


Cholinergic Capsules and Academic Admonitions.
Herein, I intend to capture highlights shared with my academic and research colleagues over the 60 years I devoted initially to my graduate and postdoctoral training and then to academic endeavors starting as an assistant professor in a new medical school at the University of California, San Diego (UCSD). During this period, the Department of Pharmacology emerged from a division within the Department of Medicine to become the first basic science department, solely within the School of Medicine at UCSD in 1979. As part of the school's plans to reorganize and to retain me at UCSD, I was appointed as founding chair. Some years later in 2002, faculty, led largely within the Department of Pharmacology and by practicing pharmacists within UCSD Healthcare, started the independent Skaggs School of Pharmacy and Pharmaceutical Sciences with a doctor of pharmacy (PharmD) program, where I served as the founding dean. My career pathway, from working at my family-owned pharmacy to chairing a department in a school of medicine and then becoming the dean of a school of pharmacy at a research-intensive, student-centered institution, involved some risky decisions. But the academic, curricular, and accreditation challenges posed were met by a cadre of creative faculty colleagues. I offer my experiences to individuals confronted with a multiplicity of real or imagined opportunities in academic health sciences, the related pharmaceutical industry, and government oversight agencies.


Whole-epigenome analysis in multiple myeloma reveals DNA hypermethylation of B cell-specific enhancers.
While analyzing the DNA methylome of multiple myeloma (MM), a plasma cell neoplasm, by whole-genome bisulfite sequencing and high-density arrays, we observed a highly heterogeneous pattern globally characterized by regional DNA hypermethylation embedded in extensive hypomethylation. In contrast to the widely reported DNA hypermethylation of promoter-associated CpG islands (CGIs) in cancer, hypermethylated sites in MM, as opposed to normal plasma cells, were located outside CpG islands and were unexpectedly associated with intronic enhancer regions defined in normal B cells and plasma cells. Both RNA-seq and in vitro reporter assays indicated that enhancer hypermethylation is globally associated with down-regulation of its host genes. ChIP-seq and DNase-seq further revealed that DNA hypermethylation in these regions is related to enhancer decommissioning. Hypermethylated enhancer regions overlapped with binding sites of B cell-specific transcription factors (TFs) and the degree of enhancer methylation inversely correlated with expression levels of these TFs in MM. Furthermore, hypermethylated regions in MM were methylated in stem cells and gradually became demethylated during normal B-cell differentiation, suggesting that MM cells either reacquire epigenetic features of undifferentiated cells or maintain an epigenetic signature of a putative myeloma stem cell progenitor. Overall, we have identified DNA hypermethylation of developmentally regulated enhancers as a new type of epigenetic modification associated with the pathogenesis of MM.


Ligamentous injuries of the knee.
Among the most potentially debilitating injuries to the athlete's knee are those injuries involving the ligaments. The unhappy sequelae of instability and premature osteoarthritis may be avoided by prompt, accurate recognition of the injury, appropriate delivery of treatment, and subsequent maintenance of rehabilitation.


Clinical implications of identifying non-B subtypes of human immunodeficiency virus type 1 infection.
Although human immunodeficiency virus type 1 (HIV-1) infection in the United States has predominantly involved subtype B, increasing global travel is leading to wider dissemination of genetically heterogeneous subtypes. While physicians depend on HIV-1 viral load measurements to guide antiretroviral therapy, commonly used molecular assays may underestimate the viral load of patients with non-B subtypes. Nine patients with non-B subtypes of HIV-1 were identified by physicians who suspected a non-B subtype on the basis of a low or undetectable HIV-1 viral load, by the Amplicor HIV-1 Monitor test, version 1.0, in conjunction with either a declining CD4 cell count or history of travel outside the United States. Use of version 1.5 of the Amplicor HIV-1 Monitor test detected a median HIV-1 viral load that was 2.0 log(10) RNA copies/mL higher than was determined with version 1.0. Clinical management was altered in all cases after diagnosis of a non-B-subtype infection. These cases demonstrate that it is critical for physicians to suspect and diagnose non-B subtypes of HIV-1 so that an assay with reliable subtype performance can be used to guide antiretroviral therapy.


Overexpression of salusin‑β downregulates adipoR1 expression to prevent fatty acid oxidation in HepG2 cells.
Salusin‑β and adiponectin receptor 1 (adipoR1) serve important roles in the development of certain cardiovascular diseases and lipid metabolism. However, to the best of our knowledge, the relationship between salusin‑β and adipoR1, and their underlying mechanisms of action, currently remain unclear. In the present study, lentiviral vectors designed to overexpress salusin‑β or knock down salusin‑β expression were used in 293T and HepG2 cells. Semi‑quantitative PCR was performed to investigate the relationship between salusin‑β and adipoR1 mRNA expression in 293T cells. Western blotting was used to assess the protein expression levels of adipoR1, adenosine monophosphate‑activated protein kinase (AMPK), acetyl‑CoA carboxylase (ACC) and carnitine palmitoyl transferase 1A (CPT‑1A) in transfected HepG2 cells. Simultaneously, HepG2 cells were treated with an adipoR1 inhibitor (thapsigargin) or agonist (AdipoRon) and the resultant changes in the expression levels of the aforementioned proteins were observed. Oil Red O staining and measurements of cellular triglyceride levels were performed to assess the extent of lipid accumulation in HepG2 cells. The results demonstrated that salusin‑β overexpression downregulated adipoR1 expression and inhibited the phosphorylation of AMPK and ACC, which led to decreased CPT‑1A protein expression. By contrast, salusin‑β knockdown increased adipoR1 expression and promoted the phosphorylation of AMPK and ACC, which conversely enhanced CPT‑1A protein expression. Treatment with adipoR1 agonist, AdipoRon, reversed the effects of salusin‑β overexpression. In addition, salusin‑β overexpression enhanced intracellular lipid accumulation in HepG2 cells induced by free fatty acid treatment. These findings highlighted the potential regulatory role of salusin‑β in adipoR1‑mediated signaling pathways. To conclude, the present study provided insights into the regulation of fatty acid metabolism by the liver. In particular, salusin‑β may serve as a potential target for the therapeutic intervention of metabolic disorders of lipids.


Evaluation of finger blood pressure monitoring instruments.
Self-blood pressure monitoring can be critical in the management of hypertension, but it is often awkward and cumbersome. One attempt to improve the ease with which such measurements are made was the development of electronic, digital, automatic monitors for measurement of blood pressure in the finger. The purpose of this study was to evaluate the accuracy, reliability, failure rate, and ease of operation of these devices. While these finger devices were found easier to use than the traditional brachial-artery methods, their accuracies and reliabilities were lower. The greater responsiveness of the digital arteries to changes in local conditions is suggested as the cause of the lesser accuracy and reliability. The author concludes that blood pressure in the digital arteries of the finger is not sufficiently representative of general systemic blood pressure for clinical purposes.


Host oxidative folding pathways offer novel anti-chikungunya virus drug targets with broad spectrum potential.
Alphaviruses require conserved cysteine residues for proper folding and assembly of the E1 and E2 envelope glycoproteins, and likely depend on host protein disulfide isomerase-family enzymes (PDI) to aid in facilitating disulfide bond formation and isomerization in these proteins. Here, we show that in human HEK293 cells, commercially available inhibitors of PDI or modulators thereof (thioredoxin reductase, TRX-R; endoplasmic reticulum oxidoreductin-1, ERO-1) inhibit the replication of CHIKV chikungunya virus (CHIKV) in vitro in a dose-dependent manner. Further, the TRX-R inhibitor auranofin inhibited Venezuelan equine encephalitis virus and the flavivirus Zika virus replication in vitro, while PDI inhibitor 16F16 reduced replication but demonstrated notable toxicity. 16F16 significantly altered the viral genome: plaque-forming unit (PFU) ratio of CHIKV in vitro without affecting relative intracellular viral RNA quantities and inhibited CHIKV E1-induced cell-cell fusion, suggesting that PDI inhibitors alter progeny virion infectivity through altered envelope function. Auranofin also increased the extracellular genome:PFU ratio but decreased the amount of intracellular CHIKV RNA, suggesting an alternative mechanism of action. Finally, auranofin reduced footpad swelling and viremia in the C57BL/6 murine model of CHIKV infection. Our results suggest that targeting oxidative folding pathways represents a potential new anti-alphavirus therapeutic strategy.


Secondary Students' Reasoning on Pedigree Problems.
Pedigree problems are typical genetics tasks in schools. They are well suited to help students learn scientific reasoning, representing realistic genetic problems. However, pedigree problems also pose complex requirements, especially for secondary students. They require a suitable solution strategy and technical knowledge. In this study, we examined the approaches used by N = 89 secondary school students when solving two different pedigree problems. In our qualitative analysis of student responses, we examined how two groups of secondary students with varying degrees of experience in genetics constructed arguments to support their decisions. To do so, we categorized I = 516 propositions from students' responses using theory- and data-driven codes. Comparison between groups revealed that "advanced genetics" students (n = 44) formulated more arguments, referred more frequently to specific family constellations, and considered superficial pedigree features less often. Conversely, "beginning genetics" students did not use a conclusive approach of step-by-step falsification but argued for the mode of inheritance they believed was correct. Advanced genetics students, in contrast to beginners, to some extent used a falsification strategy. Finally, we demonstrate which family members students used in their decisions and discuss a variety of typical but unreliable arguments.


National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: III. The 2014 Biomarker Working Group Report.
Biology-based markers to confirm or aid in the diagnosis or prognosis of chronic graft-versus-host disease (GVHD) after allogeneic hematopoietic cell transplantation or monitor its progression are critically needed to facilitate evaluation of new therapies. Biomarkers have been defined as any characteristic that is objectively measured and evaluated as an indicator of a normal biological or pathogenic process, or of a pharmacologic response to a therapeutic intervention. Applications of biomarkers in chronic GVHD clinical trials or patient management include the following: (1) diagnosis and assessment of chronic GVHD disease activity, including distinguishing irreversible damage from continued disease activity; (2) prognostic risk to develop chronic GVHD; and (3) prediction of response to therapy. Sample collection for chronic GVHD biomarkers studies should be well documented following established quality control guidelines for sample acquisition, processing, preservation, and testing, at intervals that are both calendar and event driven. The consistent therapeutic treatment of subjects and standardized documentation needed to support biomarker studies are most likely to be provided in prospective clinical trials. To date, no chronic GVHD biomarkers have been qualified for use in clinical applications. Since our previous chronic GVHD Biomarkers Working Group report in 2005, an increasing number of chronic GVHD candidate biomarkers are available for further investigation. This paper provides a 4-part framework for biomarker investigations: identification, verification, qualification, and application with terminology based on Food and Drug Administration and European Medicines Agency guidelines.


Recombinant BCG Expressing LTAK63 Adjuvant induces Superior Protection against Mycobacterium tuberculosis.
In order to develop an improved BCG vaccine against tuberculosis we have taken advantage of the adjuvant properties of a non-toxic derivative of Escherichia coli heat labile enterotoxin (LT), LTAK63. We have constructed rBCG strains expressing LTAK63 at different expression levels. Mice immunized with BCG expressing low levels of LTAK63 (rBCG-LTAK63lo) showed higher Th1 cytokines and IL-17 in the lungs, and when challenged intratracheally with Mycobacterium tuberculosis displayed a 2.0-3.0 log reduction in CFU as compared to wild type BCG. Histopathological analysis of lung tissues from protected mice revealed a reduced inflammatory response. Immunization with rBCG-LTAK63lo also protected against a 100-fold higher challenge dose. Mice immunized with rBCG-LTAK63lo produced an increase in TGF-β as compared with BCG after challenge, with a corresponding reduction in Th1 and Th17 cytokines, as determined by Real Time RT-PCR. Furthermore, rBCG-LTAK63lo also displays protection against challenge with a highly virulent Beijing isolate. Our findings suggest that BCG with low-level expression of the LTAK63 adjuvant induces a stronger immune response in the lungs conferring higher levels of protection, and a novel mechanism subsequently triggers a regulatory immune response, which then limits the pathology. The rBCG-LTAK63lo strain can be the basis of an improved vaccine against tuberculosis.


Evidence-Based Evaluation of eHealth Interventions: Systematic Literature Review.
Until now, the use of technology in health care was driven mostly by the assumptions about the benefits of electronic health (eHealth) rather than its evidence. It is noticeable that the magnitude of evidence of effectiveness and efficiency of eHealth is not proportionate to the number of interventions that are regularly conducted. Reliable evidence generated through comprehensive evaluation of eHealth interventions may accelerate the growth of eHealth for long-term successful implementation and help to experience eHealth benefits in an enhanced way. This study aimed to understand how the evidence of effectiveness and efficiency of eHealth can be generated through evaluation. Hence, we aim to discern (1) how evaluation is conducted in distinct eHealth intervention phases, (2) the aspects of effectiveness and efficiency that are typically evaluated during eHealth interventions, and (3) how eHealth interventions are evaluated in practice. A systematic literature review was conducted to explore the evaluation methods for eHealth interventions. Preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines were followed. We searched Google Scholar and Scopus for the published papers that addressed the evaluation of eHealth or described an eHealth intervention study. A qualitative analysis of the selected papers was conducted in several steps. We intended to see how the process of evaluation unfolds in distinct phases of an eHealth intervention. We revealed that in practice and in several conceptual papers, evaluation is performed at the end of the intervention. There are some studies that discuss the importance of conducting evaluation throughout the intervention; however, in practice, we found no case study that followed this. For our second research question, we discovered aspects of efficiency and effectiveness that are proposed to be assessed during interventions. The aspects that were recurrent in the conceptual papers include clinical, human and social, organizational, technological, cost, ethical and legal, and transferability. However, the case studies reviewed only evaluate the clinical and human and social aspects. At the end of the paper, we discussed a novel approach to look into the evaluation. Our intention was to stir up a discussion around this approach with the hope that it might be able to gather evidence in a comprehensive and credible way. The importance of evidence in eHealth has not been discussed as rigorously as have the diverse evaluation approaches and evaluation frameworks. Further research directed toward evidence-based evaluation can not only improve the quality of intervention studies but also facilitate successful long-term implementation of eHealth in general. We conclude that the development of more robust and comprehensive evaluation of eHealth studies or an improved validation of evaluation methods could ease the transferability of results among similar studies. Thus, the resources can be used for supplementary research in eHealth.


The Collision of Mental Health, Substance Use Disorder, and Suicide.
Suicide is the 10th leading cause of death, and, in women, nearly half of all suicide deaths occur during their reproductive years. Suicide is associated with psychiatric illness, especially mood and anxiety disorders. Childhood adversities, such as physical, emotional, and sexual abuse, and intimate partner violence increase the risk of suicide. Having more than one psychiatric disorder or comorbid substance use disorder also increases the risk of suicide. Substance use disorders can be the triggering factor for a suicide attempt among those who have a psychiatric condition and suicidal thoughts. Women attempt suicide three times more often than men, although they are less likely to complete suicide. Although the rate of suicide decreases in the perinatal period, pregnant women are more likely to use violent means. Women who complete suicide in the perinatal period are also more likely to be younger, married, and experiencing a depressive episode. For many women, the only encounter with the medical system they have might be in reproductive health care clinics. This means that their obstetrician-gynecologist has a unique opportunity to address women's mental health and enhance suicide prevention. The American College of Obstetricians and Gynecologists recommends screening for depression among perinatal women. Clinicians need to be aware that women with severe perinatal depression are at increased risk of suicide and that women with suicidal thoughts need careful monitoring, evaluation, and treatment.


Randomized phase II study of BR96-doxorubicin conjugate in patients with metastatic breast cancer.
BMS-182248-1 (BR96-doxorubicin immunoconjugate) is a chimeric human/mouse monoclonal antibody linked to approximately eight doxorubicin molecules. The antibody is directed against the Lewis-Y antigen, which is expressed on 75% of all breast cancers but is limited in expression on normal tissues. Preclinical xenograft models demonstrated significant antitumor activity, including cures. A randomized phase II design was chosen to estimate the activity of the BR96-doxorubicin conjugate in metastatic breast cancer in a study population with confirmed sensitivity to single-agent doxorubicin. Patients with measurable metastatic breast cancer and immunohistochemical evidence of Lewis-Y expression on their tumor received either BR96-doxorubicin conjugate 700 mg/m2 IV over 24 hours or doxorubicin 60 mg/m2 every 3 weeks. Patients were stratified on the basis of prior doxorubicin exposure, visceral disease, and institution. Cross-over to the opposite treatment arm was allowed with progressive or persistently stable disease. Twenty-three patients who had received a median of one prior chemotherapy regimen were assessable. There was one partial response (7%) in 14 patients receiving the BR96-doxorubicin conjugate and one complete response and three partial responses (44%) in nine assessable patients receiving doxorubicin. No patient experienced a clinically significant hypersensitivity reaction. The toxicities were significantly different between the two treatment groups, with the BR96-doxorubicin conjugate group having limited hematologic toxicity, whereas gastrointestinal toxicities, including marked serum amylase and lipase elevations, nausea, and vomiting with gastritis, were prominent. The BR96-doxorubicin immunoconjugate has limited clinical antitumor activity in metastatic breast cancer. The gastrointestinal toxicities likely represent binding of the agent to normal tissues expressing the target antigen and may have compromised the delivery of the immunoconjugate to the tumor sites.


Automated detection of clustered microcalcifications on mammograms: CAD system application to MIAS database.
To investigate the detection performance of our automated detection scheme for clustered microcalcifications on mammograms, we applied our computer-aided diagnosis (CAD) system to the database of the Mammographic Image Analysis Society (MIAS) in the UK. Forty-three mammograms from this database were used in this study. In our scheme, the breast regions were firstly extracted by determining the skinline. Histograms of the original images were used to extract the high-density area within the breast region as the segmentation from the fatty area around the skinline. Then the contrast correction technique was employed. Gradient vectors of the image density were calculated on the contrast corrected images. To extract the specific features of the pattern of the microcalcifications, triple-ring filter analysis was employed. A variable-ring filter was used for more accurate detection after the triple-ring filter. The features of the detected candidate areas were then characterized by feature analysis. The areas which satisfied the characteristics and specific terms were classified and displayed as clusters. As a result, the sensitivity was 95.8% with the false-positive rate at 1.8 clusters per image. This demonstrates that the automated detection of clustered microcalcifications in our CAD system is reliable as an aid to radiologists.


Doubling of world population unlikely.
Most national and international agencies producing population projections avoid addressing explicitly the issue of uncertainty. Typically, they provide either a single projection or a set of low, medium and high variants, and only very rarely do they give these projections a probabilistic interpretation. Probabilistic population projections have been developed for specific industrialized countries, mostly the United States, and are based largely on time-series analysis. On a global level, time-series analysis is not applicable because there is a lack of appropriate data, and for conceptual reasons such as the structural discontinuity caused by the demographic transition. Here we report on a new probabilistic approach that makes use of expert opinion on trends in fertility, mortality and migration, and on the 90 per cent uncertainty range of those trends in different parts of the world. We have used simulation techniques to derive probability distributions of population sizes and age structures for 13 regions of the world up to the year 2100. Among other things, we find that there is a probability of two-thirds that the world's population will not double in the twenty-first century.


Hydrogen bonding induced protein adsorption on polymer brushes: a Monte Carlo study.
Using Monte Carlo simulations, we investigate the protein adsorption behaviors on polymer brushes in the presence of hydrogen bonding between proteins and polymer brushes. It is interesting to observe in simulation that as a function of grafting density, the amount of protein adsorbed passes through a minimum, that is, a critical grafting density with the minimum amount of adsorbed protein exists. The existence of a critical grafting density uncovers two different driving forces of protein adsorption. The driving force of protein adsorption is mainly the hydrogen bonding between proteins and polymer brushes when the grafting density is above the critical value, whereas the driving force is the attraction between proteins and the hydrophobic substrate when the grafting density is below the critical value. It is extraordinary that at the critical grafting density, increasing the hydrophilicity of the polymer brushes will lead to an increase in protein adsorption, even when the formation of hydrogen bonding between the proteins and polymer brushes is suppressed by the increasing hydrophilicity of the polymer brushes. This mainly results from the conformational transition of the polymer chains from collapsed to stretched when the hydrophilicity is increased. It is noteworthy that the relationship between protein adsorption and grafting density reported in this study is quite consistent with our previous experimental work. Beyond that, the simulation results also provide detailed information about protein adsorption location and grafting chain conformation, which helps us to better understand the protein adsorption behaviors on polymer brushes induced by hydrogen bonding.


[Development of various types of muscle fibers in the quadriceps femoris and the soleus during human ontogenesis].
By means of histological methods for revealing adenosine triphosphatase of myosin (pH 4.6) and succinate dehydrogenase activity, using postmortem material, development of various muscle fibers of the femoral m. quadriceps and m. soleus has been studied in human ontogenesis. The first stage of rearrangements lasts from the 5th-6th month of the uterine development up to 2 years of age and is characterized by formation (from non-differentiated) of oxidative, glycolytic and oxidative-glycolytic fibers. During the period from 2 up to 7-8 years of age the ratio in the types changes slightly, but transversal section size of the muscle fiber increases intensively. Then from 11 up to 17 years of age, together with maximal increment of the fibers transversal section, there is an essential change in the type relation. By the 17th years of age, in the femoral m. quadriceps the part of the fibers with glycolytic type of energy supply increases, while in the m. soleus the oxidative fibers become more numerous. By the 70th years of age in the femoral m. quadriceps relative amount of intermediate fibers increases.


House sparrows do not exhibit a preference for the scent of potential partners with different MHC-I diversity and genetic distances.
MHC genes play a fundamental role in immune recognition of pathogens and parasites. Therefore, females may increase offspring heterozygosity and genetic diversity by selecting males with genetically compatible or heterozygous MHC. In birds, several studies suggest that MHC genes play a role in mate choice, and recent evidence suggests that olfaction may play a role in the MHC-II discrimination. However, whether olfaction is involved in MHC-I discrimination in birds remains unknown. Previous studies indicate that house sparrow females with low allelic diversity prefer males with higher diversity in MHC-I alleles. Here, we directly explored whether female and male house sparrows (Passer domesticus) could estimate by scent MHC-I diversity and/or dissimilarity of potential partners. Our results show that neither females nor males exhibit a preference related to MHC-I diversity or dissimilarity of potential partners, suggesting that MHC-I is not detected through olfaction. Further studies are needed to understand the mechanisms responsible for mate discrimination based on MHC-I in birds.


[Model of conditioned relex formation and analysis of the functional significance of the electrographic correlates of learning].
The formation of a conditioned reflex was studied on the basis of a net model in which the main data on the interconnection between cortical units were brought. In the course of learning the model reproduced practically the entire complex of electrographic manifestations of conditioning known from experiments. The mechanisms of emergence of theta-activity and spatial synchronization of biopotentials were studied. Attention is drawn to the fundamentally different dynamics of excitability change in the cortical projections of conditioned stimuli and conditioned reaction. The forms of participation of subcortical structures in the formation of conditioned connection are discussed.


Effect of L-buthionine-(S,R)-sulphoximine, an inhibitor of gamma-glutamylcysteine synthetase on peroxynitrite- and endotoxic shock-induced vascular failure.
1. Peroxynitrite, a cytotoxic oxidant formed from the reaction of nitric oxide (NO) and superoxide is a mediator of cellular injury in ischaemia/reperfusion injury, shock and inflammation. Here we investigated whether L-buthionine-(S,R)-sulphoximine (BSO), an inhibitor of gamma-glutamylcysteine synthetase, alters endothelial and vascular smooth muscle injury in response to peroxynitrite in vitro and during endotoxic shock in vivo. 2. In human umbilical vein endothelial cells and in rat aortic smooth muscle cells, BSO (1 mM, for 24 h) enhanced, whereas glutathione (3 mM) or glutathione ethyl ester (3 mM) attenuated the peroxynitrite (100-1000 microM)-induced suppression of mitochondrial respiration (measured by the conversion of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) to formazan), formation of nitrotyrosine (detected by Western blotting), protein oxidation (measured by detection of 2,4 dinitrophenylhydrazine-reactive carbonyls), and DNA single strand breakage and activation of the nuclear enzyme poly (ADP-ribose) synthetase (PARS) (measured by the incorporation of radiolabelled NAD+ into nuclear proteins and by the alkaline unwinding assay, respectively). Glutathione ethyl ester treatment reduced the BSO-induced enhancement of peroxynitrite-induced cytotoxicity. 3. In rat isolated thoracic aortic rings, BSO treatment (in vivo, at 1 g kg(-1) intraperitoneally (i.p.) for 24 h) enhanced, whereas pretreatment with glutathione (in vitro, 3 mM) attenuated the peroxynitrite-induced reduction of the contractions to noradrenaline, and the peroxynitrite-induced impairment of the endothelium-dependent relaxations to acetylcholine. 4. In BSO-pretreated rats, treatment with bacterial lipopolysaccharide (LPS, 15 mg kg(-1), i.p., for 6 h) caused a more pronounced vascular hyporeactivity and endothelial dysfunction ex vivo. BSO pretreatment also increased the degree of nitrotyrosine staining (detected by imunohistochemistry) in the aorta after LPS treatment. 5. In conclusion, our results demonstrate that L-buthionine-(S,R)-sulphoximine, an inhibitor of gamma-glutamylcysteine synthetase enhances peroxynitrite- and endotoxic shock-induced vascular failure. Based on these findings, we suggest that endogenous glutathione plays an important protective role against peroxynitrite- and LPS-induced vascular injury.


Analysis of inorganic nitrogen and related anions in high salinity water using ion chromatography with tandem UV and conductivity detectors.
Over 97% of the Earth's water is high salinity water in the form of gulfs, oceans, and salt lakes. There is an increasing concern for the quality of water in bays, gulfs, oceans, and other natural waters. These waters are affected by many different sources of contamination. The sources are, but not limited to, groundwater run-off of nitrogen containing fertilizer, pesticides, cleaning agents, solid wastes, industrial waters, and many more. The final destinations of these contaminants are rivers, lakes, and bayous that eventually will lead to bays, gulfs, and oceans. Many industries depend on the quality of these waters, such as the fishing industry. In addition to wild marine life, there are large aquariums and fish and shrimp farms that are required to know the quality of the water. However, the ability of these industries to monitor their processes is limited. Most analytical methods do not apply to the analysis of high salinity waters. They are dependent on wet chemistry techniques, spectrophotometers, and flow analyzers. These methods do not have the accuracy, precision, and sensitivity when compared to ion chromatography (IC). Since the inception of IC, it has become a standard practice for determining the content of many different water samples. Many IC methods are limited in the range of analytes that can be detected, as well as the numerous sample sources of which the methods are applicable. The main focus of current IC methods does not include high salinity waters. This research demonstrates an ion chromatographic method that has the ability to determine low level concentrations of inorganic nitrogen and related anions (nitrite-N, nitrate-N, phosphorous-P, sulfate, bromide, chloride, sulfide, fluoride, ammonia, calcium, and magnesium) in a single run using a combination of UV and conductivity detectors. This method is applicable to various waters, and uses both freshwater and high salinity water samples.


Protein phosphorylation sites regulate the function of the bipartite NLS of nucleolin.
Nucleolin is a major component of the nucleolus. In Xenopus laevis, a maternal store of nucleolin is accumulated in the multiple nucleoli generated during oogenesis. This maternal nucleolin is distributed throughout the cytoplasm of the egg during oocyte maturation and after fertilization it is gradually reaccumulated in the nuclei of the embryo. Cytoplasmic localization of nucleolin coincides with massive phosphorylation by p34cdc2 kinase, and nuclear translocation is accompanied by net dephosphorylation. Multiple phosphorylation consensus sites for the cell cycle-dependent p34cdc2 kinase and for protein kinase CK2 are clustered in the N-terminal domain of nucleolin. To assess the efficiency of the bipartite nuclear localization signal, we have constructed fusion proteins consisting of maltose binding protein (MBP) and the nuclear localization signal of nucleolin. In addition, either an acidic domain of nucleolin without phosphorylation sites, or an acidic domain containing 4 CK2 sites, or a cluster of 5 cdc2 sites was fused to the MBP-nuclear localization signal (MBP-NLS). Nuclear translocation of these constructs was tested in an in vitro system consisting of Xenopus egg extract and sperm nuclei. Nuclear targetting of MBP by the bipartite nuclear localization signal of nucleolin became significantly more efficient after addition of either CK2 sites or cdc2 sites to the MBP-NLS construct. Yet the cdc2 sites play a dual role. They enhance nuclear translocation exclusively in their dephosphorylated state and promote cytoplasmic localization when phosphorylated, thereby providing a powerful cell cycle-dependent regulatory element of the nuclear localization signal.


Collisions, caging, thermodynamics, and jamming in the barrier hopping theory of glassy hard sphere fluids.
An ultralocal limit of the microscopic single particle barrier hopping theory of glassy dynamics is proposed which allows explicit analytic expressions for the characteristic length scales, energy scales, and nonequilibrium free energy to be derived. All properties are shown to be controlled by a single coupling constant determined by the fluid density and contact value of the radial distribution function. This parameter quantifies an effective mean square force exerted on a tagged particle due to collisions with its surroundings. The analysis suggests a conceptual basis for previous surprising findings of multiple inter-relationships between characteristics of the transient localized state, the early stages of cage escape, non-Gaussian or dynamic heterogeneity effects, and the barrier hopping process that defines the alpha relaxation event. The underlying physical picture is also relevant to fluids of nonspherical molecules and sticky colloidal suspensions. The possibility of a unified view of liquid dynamics is suggested spanning the range from dense gases to the zero mobility jammed state.


Assessment and management of acute pain in the older person with cognitive impairment: A qualitative study.
Older Australians experience health disparities in pain management compared to other groups. This article is focused on understanding the emergency nurses' perceptions of pain and pain management for older persons with cognitive impairment and presenting with a long bone fracture. This article is part of a larger study focusing on emergency nurses' pain management practices for older Australians with cognitive impairment. The aim of the study was to understand emergency nurses' perceptions of the management of pain for older persons with cognitive impairment and presenting with a long bone fracture. This is part of a larger multicentre programme of research exploring pain management in older persons with cognitive impairment and who are experiencing pain from a long bone fracture. This study had a qualitative research design, with data collected through focus group interviews and a thematic method of analysis. The study is framed by a constructivist's paradigm, which enabled multiple realities to surface and be interpreted. Eighty emergency nurses participated, with 67 (84%) females and 13 (16%) males, in 16 focus groups across four emergency departments. Nurses had an average of 12.5 years as a Registered Nurse (SD ± 10.06) and 8.6 years (SD ± 8.64) emergency experience. Five themes emerged from data analysis and included: 1) Belief in championing pain management; 2) Pain management and the ageing processes; 3) Lack of pain assessment tools for the cognitively impaired older person; 4) Delivering analgesia--a balancing act; and 5) Policy barriers to nurse initiated pain management. This study makes clear the challenges clinicians' face in managing pain in older patients presenting to emergency departments. More specifically, older persons with cognitive impairment face substantially greater obstacles in receiving effective pain relief given the lack of any standardised pain assessment screening tool within emergency departments. To improve pain management practices emergency clinicians need to test the utility of behavioural pain assessment tools for cognitively impaired older persons within the emergency context.


Receiving maternity care during the COVID-19 pandemic: Experiences of women's partners and support persons.
In Australia, the provision of maternity care during the COVID-19 pandemic was significantly altered to limit transmission of the virus. Many hospitals limited face-to-face appointments to only the pregnant woman and restricted the number of support people present during labour, birth, and postnatal visits to one person. How these restrictions were experienced by partners and support persons of childbearing women are unknown. To explore the experiences of partners and support persons of women receiving maternity care during the COVID-19 pandemic. A two-phased qualitative study including an online survey and interviews. Analysis was undertaken using content analysis. Partners and support persons experienced a sense of 'missing out' from the pregnancy and maternity care experience because of changes in the provision of care during the pandemic. They reported feelings of isolation, psychological distress, and reduced bonding time with babies. Conflicting information and processes within and across maternity services contributed to feelings of uncertainty and a perceived reduction in the quality of care. Partners and support persons were negatively impacted by restrictions on maternity wards, however they also perceived these to be of benefit to women. Many partners and support persons were negatively impacted by restrictions in maternity services during the pandemic; strategies to ensure their active involvement in maternity care are needed. This study offers insights from the unique perspective of partners and support people of women receiving maternity care during the pandemic. Policies and processes that exclude partners and support persons need to be reconsidered.


Inhibition of beta-adrenergic response in cultured epidermal cells by phorbol myristate acetate.
Treatment of cultured epidermal cells with the tumor promoter, phorbol myristate acetate (PMA), results in a 75% inhibition of the normal isoproterenol stimulated 7-fold increase in cAMP accumulation. Maximum inhibition occurred 3 h after PMA treatment. The effect of phorbol ester on the beta-adrenergic system in mouse epidermis thus appears to be due to its action on the epidermal cell membrane and does not require mediation by macrophages.


Apolipoprotein E4: a causative factor and therapeutic target in neuropathology, including Alzheimer's disease.
The premise of this review is that apolipoprotein (apo) E4 is much more than a contributing factor to neurodegeneration. ApoE has critical functions in redistributing lipids among CNS cells for normal lipid homeostasis, repairing injured neurons, maintaining synapto-dendritic connections, and scavenging toxins. In multiple pathways affecting neuropathology, including Alzheimer's disease, apoE acts directly or in concert with age, head injury, oxidative stress, ischemia, inflammation, and excess amyloid beta peptide production to cause neurological disorders, accelerating progression, altering prognosis, or lowering age of onset. We envision that unique structural features of apoE4 are responsible for apoE4-associated neuropathology. Although the structures of apoE2, apoE3, and apoE4 are in dynamic equilibrium, apoE4, which is detrimental in a variety of neurological disorders, is more likely to assume a pathological conformation. Importantly, apoE4 displays domain interaction (an interaction between the N- and C-terminal domains of the protein that results in a compact structure) and molten globule formation (the formation of stable, reactive intermediates with potentially pathological activities). In response to CNS stress or injury, neurons can synthesize apoE. ApoE4 uniquely undergoes neuron-specific proteolysis, resulting in bioactive toxic fragments that enter the cytosol, alter the cytoskeleton, disrupt mitochondrial energy balance, and cause cell death. Our findings suggest potential therapeutic strategies, including the use of "structure correctors" to convert apoE4 to an "apoE3-like" molecule, protease inhibitors to prevent the generation of toxic apoE4 fragments, and "mitochondrial protectors" to prevent cellular energy disruption.


[High prevalence of hepatitis C in the district of Botafogo, municipality of Bebedouro, São Paulo State, Brazil, 2007].
This article aimed to estimate the prevalence of hepatitis C in Botafogo, a district of Bebedouro, São Paulo State, Brazil, and investigate possible risk factors. One individual over 18 years of age was selected from each household to answer a questionnaire on socio-demographic variables and factors associated with hepatitis C. Blood samples were also drawn for immunoenzymatic tests. Positive HCV-antibody samples were submitted to viral RNA detection. HCV prevalence was 8.8% (95%CI: 5.8-11.7), and independent variables associated with risk of infection were: male gender, time of local residence > 30 years, and history of injected medication using non-disposable material, sterilized by boiling. The high prevalence of hepatitis C infection in this relatively isolated rural population appears to result from previous exposure to injections with inadequately sterilized material, with some evidence suggesting a specific elderly pharmacy employee who customarily applied such injections and may have been a chronic HCV carrier.


The Central Cord Score: A Novel Classification and Scoring System Specific to Acute Traumatic Central Cord Syndrome.
Acute traumatic central cord syndrome (ATCCS) is the most common form of spinal cord injury in the United States. Treatment remains controversial, which is a consequence of ATCCS having an inherently different natural history from conventional spinal cord injury, thus requiring a separate classification system. We devised a novel Central Cord Score (CCscore), which both guides treatment and tracks improvement over time with symptoms specific to ATCCS. Medical records of patients with a diagnosis of ATCCS were retrospectively reviewed at a single institution. The CCscore was devised based on signs, symptoms, and imaging findings we believed to be critical in assessing severity of ATCCS. Numeric values were assigned for distal upper extremity motor strength, upper extremity sensation, ambulatory status, magnetic resonance imaging cord signal, and urinary retention. We identified 51 patients with follow-up data; there were 17 cases of mild injury (CCscore 1-5), 23 moderate cases (CCscore 6-10), and 11 severe cases (CCscore 11-15). Patients treated surgically had significantly greater improvement in upper extremity motor scores and total CCscore only up to 3 months. In terms of timing of surgery, patients treated <24 hours after injury had significantly improved upper extremity motor scores and overall CCscores at last follow-up of ≥3 months. Based on these data and their alignment with past literature, the CCscore is able to objectively and specifically categorize the severity and outcome of ATCCS, which represents a step forward in the quest to determine the ultimate efficacy and timing of surgery for ATCCS.


An intrinsic microRNA timer regulates progressive decline in shoot regenerative capacity in plants.
Plant cells are totipotent and competent to regenerate from differentiated organs. It has been shown that two phytohormones, auxin and cytokinin, play critical roles within this process. As in animals, the regenerative capacity declines with age in plants, but the molecular basis for this phenomenon remains elusive. Here, we demonstrate that an age-regulated microRNA, miR156, regulates shoot regenerative capacity. As a plant ages, the gradual increase in miR156-targeted SQUAMOSA PROMOTER BINDING PROTEIN-LIKE (SPL) transcription factors leads to the progressive decline in shoot regenerative capacity. In old plants, SPL reduces shoot regenerative capacity by attenuating the cytokinin response through binding with the B-type ARABIDOPSIS RESPONSE REGULATORs, which encode the transcriptional activators in the cytokinin signaling pathway. Consistently, the increased amount of exogenous cytokinin complements the reduced shoot regenerative capacity in old plants. Therefore, the recruitment of age cues in response to cytokinin contributes to shoot regenerative competence.


Upregulated transcription of plasmid and chromosomal ribulose monophosphate pathway genes is critical for methanol assimilation rate and methanol tolerance in the methylotrophic bacterium Bacillus methanolicus.
The natural plasmid pBM19 carries the key mdh gene needed for the oxidation of methanol into formaldehyde by Bacillus methanolicus. Five more genes, glpX, fba, tkt, pfk, and rpe, with deduced roles in the cell primary metabolism, are also located on this plasmid. By using real-time PCR, we show that they are transcriptionally upregulated (6- to 40-fold) in cells utilizing methanol; a similar induction was shown for two chromosomal genes, hps and phi. These seven genes are involved in the fructose bisphosphate aldolase/sedoheptulose bisphosphatase variant of the ribulose monophosphate (RuMP) pathway for formaldehyde assimilation. Curing of pBM19 causes higher methanol tolerance and reduced formaldehyde tolerance, and the methanol tolerance is reversed to wild-type levels by reintroducing mdh. Thus, the RuMP pathway is needed to detoxify the formaldehyde produced by the methanol dehydrogenase-mediated conversion of methanol, and the in vivo transcription levels of mdh and the RuMP pathway genes reflect the methanol tolerance level of the cells. The transcriptional inducer of hps and phi genes is formaldehyde, and not methanol, and introduction of multiple copies of these two genes into B. methanolicus made the cells more tolerant of growth on high methanol concentrations. The recombinant strain also had a significantly higher specific growth rate on methanol than the wild type. While pBM19 is critical for growth on methanol and important for formaldehyde detoxification, the maintenance of this plasmid represents a burden for B. methanolicus when growing on mannitol. Our data contribute to a new and fundamental understanding of the regulation of B. methanolicus methylotrophy.


Genetic and biochemical analysis of TGF beta signal transduction.
TGF beta-like ligands are involved in many different developmental processes that pattern a variety of tissues in invertebrates and vertebrates. In the last few years, rapid progress has been made toward elucidating the developmental roles of the TGF beta-like pathways and identifying the novel components involved in transducing their signals, particularly the newly discovered Smads. This rapid progress has been the result of a synergy between classical genetic approaches and biochemical approaches, and this combined approach is likely to propel future understanding of the signaling pathway used by TGF beta.


Diagnostic accuracy of fungal identification in histopathology and cytopathology specimens.
Tools to diagnose fungal infection are microscopic examination, antigen or antibody-based detection tests, molecular diagnostics, and culture, with culture being the "gold standard" for species-level identification. Although these methods are commonly used in concert and yield concordant results, in some cases tissue is not available for culture, and/or different methodologies yield discrepant results. These discrepancies may be clinically significant, causing confusion and inappropriate or delayed initiation of antifungals. This study evaluates the correlation between microscopic examination and the results of laboratory studies, and identifies clinical scenarios and specimen characteristics associated with tissue sent for microscopic examination without concomitant laboratory studies. We performed an 18-year retrospective review at a tertiary-care, academic medical center in the Midwest United States of all fungal infection diagnoses made by microscopic examination. Only 16% of samples with fungal infection diagnosed by microscopic examination had a concomitant sample submitted for laboratory studies. Of these cases, 36% had no growth on culture and/or had a negative laboratory study. Among cases in which fungal infections were diagnosed and laboratory studies were positive, the accuracy of histopathologic identification was 95%. The most common cause for incorrect morphologic diagnoses was misidentification of Aspergillus spp. and Mucorales. Our results underscore the importance of educating pathologists with regard to appropriate terminology and increasing knowledge of mycology, particularly in relation to organisms forming hyphae in tissue. Species-level diagnosis of fungi cannot be made by microscopic examination of tissue alone. Anatomic pathology reports should recommend correlation with laboratory studies, and provide a differential diagnosis based on morphology.


[Antioxidative and membranotropic activities of rosmarinic acid].
The metabolic damages and inflammatory diseases are closely connected with high increase of the contents of the reactive oxygen species (ROS) and lipid peroxidation products in organism. In connection with this natural antioxidants are actively used for efficient fight with oxidative stress. In current work we have estimated an antioxidative potential of rosmarinic acid (RA), which is broadly wide-spread amongst plants and possesses the useful spectrum of biological activities. It has been shown that RA noticeably exceeded known antioxidants in test on antioxidant activities in Hb-H2O2-luminol and 2,2'-azo bis (2-methylpropionamidine) dihydrochloride-luminol systems, as well as on inhibition of linoleic acid peroxidation. On antioxidant activities the investigated substances can be arranged in the following order: RA > dihydroquercetin > trolox > ascorbic acid. RA molecules are localized mainly in the lipid bilayer of polar groups, but have no significant effect on its structural and functional properties: RA does not cause significant changes in permeability of planar bilayer membranes in a dose range of 0.5 to 10 microg/ml. Spontaneous incorporating of 1 mol% of RA into the lipid bilayer is sufficient for the complete prevention of lipid peroxidation. Thus, the antioxidant activity of RA is based on its ability to inhibit the initiation stage of free radical reactions of lipid peroxidation, largely caused by the formation of ROS. In this regard RA, as a powerful and effective inhibitor of ROS and lipid peroxidation, has great potential for wide use not only in medicine but also in the food industry to preserve the quality of perishable food products.


Consensus miRNA expression profiles derived from interplatform normalization of microarray data.
Eukaryotic gene expression is controlled at the post-transcriptional level by small noncoding RNAs called microRNAs (miRNA). miRNAs play important roles during early development and participate in gene regulatory circuits in the cell. Different high-throughput expression analysis methods including microarrays, bead-based detection, and small RNA cloning have been applied to quantitatively detect miRNAs in various tissues, cell types, and biological conditions. High-throughput expression data was collected from public repositories and processed to create a database of miRNA expression profiles. Several commonly used normalization methods were compared to identify suitable methods for cross-platform comparison of high-throughput miRNA expression data. The database provides interlaboratory and interplatform validated reference expression levels for miRNAs. The normalized expression profiles were validated by querying for well-established features of miRNA expression. Firstly, expression profiles of several tissue-specific miRNAs showed good agreement between the database and previously reported profiles. We have also identified a set of miRNAs that are constitutively expressed across mammalian tissues. Secondly, we used the database to compare the expression patterns of miRNAs belonging to the let-7 family, where the divergence in expression patterns implies that they may have diversified functionally. Lastly, we compared expression profiles of intronic and clustered miRNAs. Expression profiles of intronic miRNAs and clustered miRNAs showed either very good, or in certain cases, very poor correlation with the host gene. Interplatform comparison of miRNA expression profiles thus provides a resource of consensus expression profiles that can be used in the future for studying miRNA function and regulation.


Super toner and ink repellent superoleophobic surface.
Offset of imaging material from a fuser surface to paper during fusing is highly undesirable in printing. Here the wetting and repellent characteristics of three imaging materials (a solid wax ink, a waxy polyester toner, and a polyester toner) in their molten states have been studied on three model print surfaces: a transparency (surrogate for paper), a PTFE film, and a model superoleophobic surface, with the aim of assessing their performance in fusing. The superoleophobic surface, with water and hexadecane contact angles of ∼156° and sliding angles at ∼10°, comprises 3 μm diameter pillar arrays on silicon wafer and was fabricated by photolithography followed by surface modification with a fluorosilane. The contact angles of the three imaging materials range from 40 to 79° on the transparency and the sessile drops do not slide even at 90° tilted angle, indicating that they all wet, adhere, and pin on the transparency. Although the contact angles of the three imaging materials are slightly higher (63-85°) on PTFE, the sessile drops do not slide on PTFE either. Because PTFE is widely used as a fuser surface material in combination with different waxy imaging materials commercially, we attribute the successful implementation of PTFE to the use of the wax additive. With the superoleophobic surface, there is a dramatic increase in advancing and static contact angles for all three imaging materials. The advancing and static contact angles are in the 150-168° range for waxy toner, indicative of superhigh repellency. Although the advancing and static contact angles for the polyester toner decrease slightly at 147 and 130°, respectively, the repellency is still very high. More importantly, the sessile drops of all three imaging materials are mobile upon tilting and they all have high receding contact angles. The overall results suggest that the adhesion between the superoleophobic surface and the ink and toner materials are very small relative to those with paper and PTFE. The important of high repellency and low adhesion to offset performance is discussed.


Accumulation of viral transcripts and DNA during establishment of latency by herpes simplex virus.
Latent infection of mice with wild-type herpes simplex virus is established during an acute phase of ganglionic infection in which there is abundant viral replication and productive-cycle gene expression. Thymidine kinase-negative mutants establish latent infections but are severely impaired for acute ganglionic replication and productive-cycle gene expression. Indeed, by in situ hybridization assays, acute infection by these mutants resembles latency. To assess events during establishment of latency by wild-type and thymidine kinase-negative viruses, we quantified specific viral nucleic acid sequences in mouse trigeminal ganglia during acute ganglionic infection by using sensitive PCR-based assays. Through 32 h postinfection, viral DNA and transcripts representative of the three kinetic classes of productive-cycle genes accumulated to comparable levels in wild-type- and mutant-infected ganglia. At 48 and 72 h, although latency-associated transcripts accumulated to comparable levels in ganglia infected with wild-type or mutant virus, levels of DNA accumulating in wild-type-infected ganglia exceeded those in mutant-infected ganglia by 2 to 3 orders of magnitude. Coincident with this increase in DNA, wild-type-infected ganglia exhibited abundant expression of productive-cycle genes and high titers of infectious progeny. Nevertheless, the levels of productive-cycle RNAs expressed by mutant virus during acute infection greatly exceeded those expressed by wild-type virus during latency. The results thus distinguish acute infection of ganglia by a replication-compromised mutant from latent infection and may have implications for mechanisms of latency.


Current status of immunoscintigraphy in the detection of thrombosis and thromboembolism.
This review describes the use of monoclonal antibodies (MoAbs) for immunoscintigraphic detection of thrombosis and thromboembolism. Two major groups of MoAbs have been tested: Antibodies directed against platelets and antibodies directed against fibrin. Several antiplatelet antibodies have been developed that are directed against either the platelet membrane glycoprotein complex, IIb/IIIa, which binds fibrinogen, or against two different proteins, alpha granule membrane protein GMP-140 and thrombospondin (TSP) that are expressed during platelet activation. Platelets labeled with radioactive antibody or antibody fragments have characteristics similar to platelets labeled in vitro with lipophilic complexes. Studies in animal models indicate that antiplatelet antibody and antiactivated platelet factor antibody imaging have a high sensitivity for clots less than 24 hours old and that images can be positive as early as one to two hours after antibody administration. A limited number of antiplatelet antibody studies have been performed in patients. This technique appears to yield accurate results provided that active platelet deposition is occurring at the time of the study. Several antifibrin MoAbs, specific for fibrin monomers, have been developed. Compared with antiplatelet antibodies, antifibrin antibodies and antibody fragments appear to be capable of detecting older experimental clots (up to five days old). Images in experimental thrombosis models are routinely positive within two hours of antibody administration. Recently reported clinical trials indicate a high sensitivity in all anatomic locations within the extremities whether or not patients were receiving heparin.


Writing a grant proposal--part 2: research methods--part 2.
As part of a Spotlight series on grant writing by members of the Center for Clinical Investigation of the Wound Ostomy and Continence Nursing (WOCN) Society, this article completes an explanation about writing the Methods section of a grant proposal. The aim of this series is to enhance the skills of WOC nurses to increase submissions of high-quality grants related to WOC nursing science and success in garnering funding, particularly from foundation grants, such as that of the WOCN. In this article, writing about the sample and setting, power analysis, sampling and recruitment procedures, implementation and data collection procedures, statistical analysis plan, and ethical considerations are described.