Alterations in pancreatic islet function produced by carcinogenic nitrosamines in the Syrian hamster.
Exposure of hamsters to 5 daily doses of 20 mg/kg N-nitrosobis(2-oxopropyl)amine (BOP) or 76 mg/kg N-nitroso(2-hydroxypropyl)(2-oxopropyl)amine (HPOP), resulted in reduced insulin secretion in freshly isolated pancreatic islets. These treatments also reduced plasma insulin and glucose levels, and were hepatotoxic. The inhibition of insulin secretion, however, was transient. Islets isolated from treated hamsters that were then placed in culture secreted elevated levels of insulin for many months. When cultured islets were directly exposed to the nitrosamines for 3 days, there was also a transient reduction of insulin secretion that was subsequently normalized after removal of the nitrosamine from the medium. These results show that BOP and HPOP modify beta-cell function both directly, and possibly indirectly, via damage to the liver. Furthermore, the lack of immediate inhibition of insulin secretion when islets were incubated in the presence of BOP or HPOP as well as glucose, suggests that the nitrosamines do not bind to the glucose receptor.


A moral life after a suicide death in Taiwan.
In this article we present the findings of a qualitative study exploring what suicide survivors in Taiwan experienced after a family member's suicide and how they adjusted to the perceived stigma. Fifteen suicide survivors participated in this study. We found that when a family member's suicide death occurred, survivors first kept a low profile when holding the funeral, and then tried to expel the dead person from their family. They also wished that their grief and painful, shameful feelings could be buried with the dead person. These findings suggest that health care professionals need to work more closely with suicide survivors through understanding the survivors' fear and pain from a sociocultural perspective, and to help them construct a new moral life.


Amniotomy for shortening spontaneous labour.
Intentional artificial rupture of the amniotic membranes during labour, sometimes called amniotomy or 'breaking of the waters', is one of the most commonly performed procedures in modern obstetric and midwifery practice. The primary aim of amniotomy is to speed up contractions and, therefore, shorten the length of labour. However, there are concerns regarding unintended adverse effects on the woman and baby. To determine the effectiveness and safety of amniotomy alone for routinely shortening all labours that start spontaneously. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (30 November 2010). Randomised controlled trials comparing amniotomy alone versus intention to preserve the membranes. We excluded quasi-randomised trials. Two authors assessed identified studies for inclusion, assessed risk of bias and extracted data. Primary analysis was by intention to treat. We have included 15 studies in this updated review, involving 5583 women. In the current review, data for women with spontaneous normal labour were pooled with data from one trial (involving 61 women) where women had spontaneous, but prolonged labour.There was no clear statistically significant difference between the amniotomy and control groups in length of the first stage of labour (mean difference (MD) -20.43 minutes, 95% confidence interval (CI) -95.93 to 55.06), caesarean section (risk ratio (RR) 1.27, 95% CI 0.99 to 1.62), maternal satisfaction with childbirth experience (standardised mean difference (SMD) 0.27, 95% CI -0.49 to 1.04) or low Apgar score less than seven at five minutes (RR 0.57, 95% CI 0.31 to 1.06). There was no consistency between papers regarding the timing of amniotomy during labour in terms of cervical dilatation. On the basis of the findings of this review, we cannot recommend that amniotomy should be introduced routinely as part of standard labour management and care. We recommend that the evidence presented in this review should be made available to women offered an amniotomy and may be useful as a foundation for discussion and any resulting decisions made between women and their caregivers.


Improvement in quality of life among women and men aged 60 years and older following treatment for alcohol use disorder.
Previous studies have yielded mixed results on the association between gender and alcohol use disorder (AUD) treatment outcomes. Thus, additional research is needed to determine the effect of gender on AUD treatment outcomes, including quality of life (QoL), particularly among older adults. In a clinical sample of older adults with DSM-5 AUD, we examined changes in QoL from the beginning of AUD treatment through 1 year of follow-ups. We also examined the effect of gender and explored interaction effects with gender on QoL. We utilized data from the "Elderly Study," a multi-national, single-blind, randomized, controlled trial of 693 adults aged 60+ with DSM-5 AUD. Alcohol use was assessed with the Form-90, and QoL with the brief version of the World Health Organization QoL measure. Information was collected at treatment initiation and at 4-, 12-, 26-, and 52-week follow-ups. Multilevel mixed-effects logistic and linear regression models were used to examine QoL changes and the effect of gender on changes in QoL. Following treatment, small, but significant improvements were seen over time in overall perceived health (p < 0.05). Improvements that persisted over the 1-year follow-up period were seen in the QoL domains of physical health (β: 2.6, 95% CI: 1.4-3.9), psychological health (β: 3.5, 95% CI: 3.3-3.8), social relationships (β: 4.0, 95% CI: 2.5-5.6), and environmental health (β: 1.4, 95% CI: 0.4-2.4). No significant changes were seen over time in overall perceived QoL (p = 0.58). Gender was not associated with changes in any of the QoL outcome measures (all p ≥ 0.05). Among 60+ year-old adults receiving treatment for DSM-5 AUD, improvements in QoL were achievable and maintained over time, but were not associated with gender.


Genetic and epigenetic susceptibility to early life infection.
This review aims to interpret the current literature on the role of genetic and epigenetic factors in susceptibility to neonatal infection, a leading cause of early life mortality and morbidity. Epidemiological data indicate that the differential susceptibility to infection is partly heritable. To date there have been relatively few studies on genetic determinants of susceptibility to neonatal infection and many of these have methodological shortcomings. Most studies predominantly focus on the innate immune system. There is growing interest in the potential role of epigenetic mechanisms in disease susceptibility and data are emerging on the role of epigenetics in the maturation of the immune system in early life. Infection is a leading cause of morbidity and mortality, especially in preterm infants, but it remains unclear why neonates are so susceptible or what mediates differential risk. Genetic and epigenetic epidemiologic studies may assist in the identification of critical protective and pathogenic pathways. Despite the current relative lack of robust data, such studies may facilitate the development of interventions that ultimately decrease the significant morbidity and mortality of this highly vulnerable population.


User Beware: Concerning Findings from the Post 2011-2012 U.S. Internal Revenue Service Migration Data.
The U.S. Internal Revenue Service (IRS) makes publicly and freely available period migration data at the state and county levels. Among their uses, these data inform estimates of net-migration as part of the U.S. Census Bureau's Population Estimates Program, which, in turn, are used for producing other annual statistics, survey design, business and community planning, and federal funding allocations. Building on and extending prior research, we devote this Research Brief to documenting from multiple new angles a highly concerning and apparently systemic problem with the IRS migration data since the IRS took over responsibilities for preparing these data from the U.S. Census Bureau in 2011. As we then discuss, despite the fact that the IRS provides documentation detailing changes that it made to how it prepares these data relative to how the U.S. Census Bureau prepared them, it is not clear why or how these changes would result in the problem detailed in our analysis. Given that this problem appears to be an internal one within the IRS, we conclude by suggesting that the post 2011-12 IRS migration data not be used until this problem is resolved, and we encourage the IRS to do so quickly, transparently, and collaboratively.


Minocycline attenuates sevoflurane-induced cell injury via activation of Nrf2.
Minocycline has been demonstrated to exert neuroprotective effects in various experimental models. In the present study, we investigated the mechanisms underlying the protective effects of minocycline on cell injury induced by the inhalation of the anesthetic, sevoflurane. In our in vivo experiments using rats, minocycline attenuated sevoflurane-induced neuronal degeneration and apoptosis in the rat hippocampus, and this effect was associated with the minocycline-mediated suppression of oxidative stress in the hippocampus. In in vitro experiments, minocycline inhibited sevoflurane-induced apoptosis and the production of reactive oxygen species (ROS) in H4 human neuroglioma cells. In addition, minocycline suppressed the sevoflurane-induced upregulation of interleukin (IL)-6 and the activation of the nuclear factor-κB (NF-κB) signaling pathway in H4 cells. Furthermore, we found that nuclear factor E2-related factor 2 (Nrf2), an activator of the stress response, was upregulated and activated upon sevoflurane treatment both in the rat hippocampus and in H4 cells. In addition, minocycline further augmented the upregulation and activation of Nrf2 when used in conjunction with sevoflurane. Moreover, the knockdown of Nrf2 in H4 cells by small interfering RNA (siRNA) diminished the cytoprotective effect of minocycline, and attenuated the inhibitory effect of minocycline on ROS production, IL-6 upregulation and the activation of the NF-κB signaling pathway. On the whole, our findings indicate that minocycline may exert protective effects against sevoflurane-induced cell injury via the Nrf2-modulated antioxidant response and the inhibition of the activation of the NF-κB signaling pathway.


A review of multidomain interventions to support healthy cognitive ageing.
The risk for cognitive decline and for developing Alzheimer's disease increases with age. The aetiology is assumed to be of multi-factorial origin, and treatment opportunities are lacking. Despite the multi-factorial origin, many intervention studies focused on single factors to influence cognitive health with inconsistent findings. In this view, more and more intervention studies aim to intervene on multiple factors simultaneously to affect or slow down cognitive decline. The purpose of this paper is to give an overview of these multidomain intervention trials. We conducted a non-systematic literature search in Medline, Scopus, Cochrane Library, and clinical trials databases up to October 2011 to review multidomain interventions that investigated effects of combined lifestyle-related factors on cognitive decline and the progression of dementia. Interest in multidomain interventions increased over the past years. We identified six completed and published trials and eight ongoing or not yet published studies that investigated effects on cognitive outcomes. First completed trials yielded promising results for the combination of exercise and mental training and diet and behavioural weight management. Results of ongoing multidomain trials are awaited. Some evidence suggests that strategies which target multiple factors simultaneously may prove more effective than those focusing on a single mechanism or domain. Larger high-quality randomized controlled trials are required to systematically investigate the cognitive effect of programs comprising physical and mental activity as well as nutritional aspects.


Arabidopsis PHOSPHATE TRANSPORTER1 genes PHT1;8 and PHT1;9 are involved in root-to-shoot translocation of orthophosphate.
In plants, the uptake from soil and intercellular transport of inorganic phosphate (Pi) is mediated by the PHT1 family of membrane-spanning proton : Pi symporters. The Arabidopsis thaliana AtPHT1 gene family comprises nine putative high-affinity Pi transporters. While AtPHT1;1 to AtPHT1;4 are involved in Pi acquisition from the rhizosphere, the role of the remaining transporters is less clear. Pi uptake and tissue accumulation studies in AtPHT1;8 and AtPHT1;9 knock-out mutants compared to wild-type plants showed that both transporters are involved in the translocation of Pi from the root to the shoot. Upon inactivation of AtPHT1;9, changes in the transcript profiles of several genes that respond to plant phosphorus (P) status indicated a possible role in the regulation of systemic signaling of P status within the plant. Potential genetic interactions were found among PHT1 transporters, as the transcript profile of AtPHT1;5 and AtPHT1;7 was altered in the absence of AtPHT1;8, and the transcript profile of AtPHT1;7 was altered in the Atpht1;9 mutant. These results indicate that AtPHT1;8 and AtPHT1;9 translocate Pi from the root to the shoot, but not from the soil solution into the root. AtPHT1;8 and AtPHT1;9 are likely to act sequentially in the interior of the plant during the root-to-shoot translocation of Pi, and play a more complex role in the acclimation of A. thaliana to changes in Pi supply than was previously thought.


A cultural side effect: learning to read interferes with identity processing of familiar objects.
Based on the neuronal recycling hypothesis (Dehaene and Cohen, 2007), we examined whether reading acquisition has a cost for the recognition of non-linguistic visual materials. More specifically, we checked whether the ability to discriminate between mirror images, which develops through literacy acquisition, interferes with object identity judgments, and whether interference strength varies as a function of the nature of the non-linguistic material. To these aims we presented illiterate, late literate (who learned to read at adult age), and early literate adults with an orientation-independent, identity-based same-different comparison task in which they had to respond "same" to both physically identical and mirrored or plane-rotated images of pictures of familiar objects (Experiment 1) or of geometric shapes (Experiment 2). Interference from irrelevant orientation variations was stronger with plane rotations than with mirror images, and stronger with geometric shapes than with objects. Illiterates were the only participants almost immune to mirror variations, but only for familiar objects. Thus, the process of unlearning mirror-image generalization, necessary to acquire literacy in the Latin alphabet, has a cost for a basic function of the visual ventral object recognition stream, i.e., identification of familiar objects. This demonstrates that neural recycling is not just an adaptation to multi-use but a process of at least partial exaptation.


Effects of acute coronary occlusion and previous ischaemic injury on left ventricular wall motion in humans.
To assess the acute effects of single and repeated coronary artery occlusions, during percutaneous transluminal coronary angioplasty (PTCA), on left ventricular long axis function in patients with stable and unstable angina. Prospective examination of ventricular systolic and diastolic long axis function using M mode echocardiography and transmitral Doppler in patients with significant coronary artery stenosis and either stable or unstable angina, during routine PTCA. A tertiary referral centre for heart disease with cardiac catheterisation and echocardiographic facilities. 36 patients, age (SD) 60 (8) years, with significant coronary artery disease undergoing PTCA (mean duration 100-130 seconds) to the left anterior descending coronary artery (LAD) in 18 patients, native LAD or its vein graft in eight, and right coronary artery in 10. Controls were 21 normal subjects, age 58 (11) years. RESULTS-AT BASELINE: in systole, total long axis excursion was reduced at septal, posterior, and right sites in patients with LAD disease, at right site in those with vein grafts, and at septal and right sites in patients with right coronary artery disease. Peak shortening rate was often reduced in all patients and onset of shortening delayed with respect to the Q wave in patients with LAD disease. In diastole, onset of lengthening was always delayed, peak lengthening rate reduced, and relative A wave amplitude increased in all patients. There was a consistent abnormal shortening of the long axis during the isovolumic relaxation period in the 14 patients with unstable angina, not seen in the others. Transmitral A wave velocity was also increased and the onset of E wave delayed with respect to A2. At first balloon inflation: the extent of pre-existing systolic and particularly diastolic abnormalities consistently increased in patients with LAD or right coronary artery occlusion. This was associated with further delay in the onset of the transmitral Doppler E wave as its peak velocity fell and E/A ratio increased. In unstable angina, balloon inflation caused minor changes only in systolic function and no change in diastolic function. At second balloon inflation: systolic changes were the same as with the first inflation, while diastolic changes were attenuated by 10-15%. In stable angina intracoronary balloon inflation aggravated pre-existing systolic and diastolic abnormalities in the territory of the occluded vessel, indicating the dependence of both on coronary flow. In unstable angina balloon inflation caused only minor deterioration in systolic function, and diastolic changes-including the characteristic abnormal shortening during isovolumic relaxation-were unaffected. Thus resting abnormalities of left ventricular function in unstable angina are effectively dissociated from acute changes in coronary flow. Overall, the severity of systolic disturbances was unaltered by a second balloon inflation, but diastolic disturbances were attenuated by 10-15%, compatible with ischaemic preconditioning or recruitment of collaterals.


TBE--update on vaccination recommendations for children, adolescents, and adults.
Vaccines against tick-born encephalitis (TBE) are well established in Europe. Two highly immunogenic and safe products are available, FSME-IMMUN and Encepur. Extensive research has been published regarding all aspects of standard and rapid immunization schedules, covaccination, and vaccine interchangeability. Long-term effectiveness and resulting recommendations for booster intervals remain topics of discussion. Vaccination is recommended in Switzerland and in Germany for adults and children living in, or travelling to, endemic areas. Austria has recommended universal vaccination since 1981. It is noteworthy that Austria is the only country in Europe that has experienced a decrease in caseload during the last 20 years. This is almost certainly due to the very high vaccine coverage rate of 86 %.


Microbiome Transmission During Sexual Intercourse Appears Stochastic and Supports the Red Queen Hypothesis.
Microbes inhabit virtually everywhere on and/or in our bodies, including the seminal and vaginal fluids. They have significant importance in maintaining reproductive health and protecting hosts from diseases. The exchange of microbes during sexual intercourse is one of the most direct and significant microbial transmissions between men and women. Nevertheless, the mechanism of this microbial transmission was little known. Is the transmission mode stochastic, passive diffusion similar to the random walk of particles, or driven by some deterministic forces? What is the microbial transmission probability? What are the possible evolutionary implications, particularly from the perspective of sexual reproduction (selection)? We tackle these intriguing questions by leveraging the power of Hubbell's unified neutral theory of biodiversity, specifically implemented as the HDP-MSN (hierarchical Dirichlet process approximated multi-site neutral model), which allows for constructing truly multi-site metacommunity models, simultaneously including vaginal and semen microbiomes. By reanalyzing the microbiome datasets of seminal and vaginal fluids from 23 couples both before and after sexual intercourses originally reported by Mändar and colleagues, we found that the microbial transmission between seminal and vaginal fluids is a stochastic, passive diffusion similar to the random walk of particles in physics, rather than driven by deterministic forces. The transmission probability through sexual intercourse seems to be approximately 0.05. Inspired by the results from the HDP-MSN model, we further conjecture that the stochastic drifts of microbiome transmissions during sexual intercourses can be responsible for the homogeneity between semen and vaginal microbiomes first identified in a previous study, which should be helpful for sexual reproduction by facilitating the sperm movement/survival and/or egg fertilization. This inference seems to be consistent with the classic Red Queen hypothesis, which, when extended to the co-evolutionary interactions between humans and their symbiotic microbiomes, would predict that the reproductive system microbiomes should support sexual reproduction.


Oxygen for children and newborns in non-tertiary hospitals in South-west Nigeria: A needs assessment.
Oxygen is important for the treatment of hypoxaemia associated with pneumonia, malaria, and other medical, obstetric, and surgical conditions. Access to oxygen therapy is limited in many of the high mortality settings where it would be of most benefit. A needs assessment of 12 non-tertiary hospitals in south-west Nigeria, assessing structural, technical and clinical barriers to the provision of safe and effective oxygen therapy. Oxygen supply was reported to be a major challenge by hospital directors. All hospitals had some access to oxygen cylinders, which were expensive and frequently ran out. Nine (75%) hospitals used oxygen concentrators, which were limited by inadequate power supply and lack of maintenance capacity. Appropriate oxygen delivery and monitoring devices (nasal prongs, catheters, pulse oximeters) were poorly available, and no hospitals had clinical guidelines pertaining to the use of -oxygen for children. Oxygen was expensive to patients (median US$20/day) and to hospitals. Estimated oxygen demand is reported using both a constant mean-based estimate and adjustment for seasonal and other variability. Making oxygen available to sick children and neonates in Nigerian hospitals will require: improving detection of hypoxaemia through routine use of pulse oximetry; improving access to oxygen through equipment, training, and maintenance structures; and commitment to building hospital and state structures that can sustain and expand oxygen initiatives.


Metastatic pericardial tumors in a dog with equivocal pericardial cytological findings.
A metastatic tumor associated with pericardial effusion was diagnosed in a 6-year-old, female, mixed-breed dog. Echocardiography identified multiple echogenic masses adherent to both visceral and parietal pericardium, while results of pericardial fluid cytology were non-diagnostic. The distribution pattern of the masses is remarkable in that they protruded from both pericardial surfaces, rather than one, and demonstrated an oscillatory motion during the cardiac cycle. Pathological examination confirmed the diagnosis of multiple metastatic tumors of the pericardium, with the primary tumor being an anaplastic gastric adenocarcinoma.


Relationship between obesity and depression in Korean adults: Korea National Health and Nutrition Examination Survey 2014.
Previous studies on the relationship between obesity and depression have produced conflicting results. And only a limited number of studies have been conducted in Asians, and few large-scale nationwide studies have been conducted in Korean populations.We investigated the relationship between obesity and depression in Korean adults using data from a population-based sample from the 2014 Korea National Health and Nutritional Examination Survey (KNHANES) by cross-sectional study.In total, 4026 subjects (1692 men, 2334 women) aged 19 to 69 years participated in the 2014 KNHANES. Current depression was defined as a score ≥10 on the 9-item Patient Health Questionnaire. Height and weight were measured and the body mass index (BMI) was calculated. The participants were asked to complete questionnaires about socio-demographic factors and disease comorbidities, and health-related behaviors. The chi-squared test and multivariate logistic regression analyses were performed to examine the relationship between obesity and depression.Depression was diagnosed in 5.7% of the study participants (3.9% of men, 7.0% of women). According to body weight status, there was a significant difference in the prevalence of depression (underweight: 16.2%, normal weight: 5.5%, overweight: 4.3%, obese [BMI ≥30]: 6.9%). Compared with the normal weight group, the underweight group had a higher adjusted odds ratio (OR) for depression (OR = 3.27, 95% confidence interval [CI]: 1.22, 8.75 in men; OR = 2.00, 95% CI: 1.12, 3.57 in women). Overweight (OR = 0.60, 95% CI: 0.32, 1.13) and obese (OR = 0.62, 95% CI: 0.17, 2.27) men had lower ORs for depression, but this trend was not significant. Compared with normal weight women, obese women had higher adjusted ORs for depression (OR = 1.75, 95% CI: 0.79, 3.88), while overweight women had lower ORs for depression (OR = 0.90, 95% CI: 0.56, 1.45), but these trends were not significant.This study shows differences in the risk of depression depending upon body weight status. Being underweight was correlated with a high risk of developing depression in both men and women, but obesity cannot be ruled out as a risk factor for this condition.


Quantum confinement of hot image-potential state electrons.
Discrete image-potential state (IS) resonances at Co nanoislands on Au(111) are probed using scanning tunneling microscopy and spectroscopy. We observe particle-in-box-type standing wave patterns, which is surprising in view of the high energy of the IS electrons when compared to the confining potential imposed by the island edges. The weak confining potential experienced by the IS electrons results in electronic interaction effects between closely spaced islands. Probing high-energy ISs hence provides a novel route to investigate electronic coupling between nanoislands on surfaces.


Universal Unitarity Triangle 2016 and the tension between [Formula: see text] and [Formula: see text] in CMFV models.
Motivated by the recently improved results from the Fermilab Lattice and MILC Collaborations on the hadronic matrix elements entering [Formula: see text] in [Formula: see text]-[Formula: see text] mixing, we determine the universal unitarity triangle (UUT) in models with constrained minimal flavour violation (CMFV). Of particular importance are the very precise determinations of the ratio [Formula: see text] and of the angle [Formula: see text]. They follow in this framework from the experimental values of [Formula: see text] and of the CP-asymmetry [Formula: see text]. As in CMFV models the new contributions to meson mixings can be described by a single flavour-universal variable S(v), we next determine the CKM matrix elements [Formula: see text], [Formula: see text], [Formula: see text] and [Formula: see text] as functions of S(v) using the experimental value of [Formula: see text] as input. The lower bound on S(v) in these models, derived by us in 2006, implies then upper bounds on these four CKM elements and on the CP-violating parameter [Formula: see text], which turns out to be significantly below its experimental value. This strategy avoids the use of tree-level determinations of [Formula: see text] and [Formula: see text], which are presently subject to considerable uncertainties. On the other hand, if [Formula: see text] is used instead of [Formula: see text] as input, [Formula: see text] are found to be significantly above the data. In this manner we point out that the new lattice data have significantly sharpened the tension between [Formula: see text] and [Formula: see text] within the CMFV framework. This implies the presence of new physics contributions beyond this framework that are responsible for the breakdown of the flavour universality of the function S(v). We also present the implications of these results for [Formula: see text], [Formula: see text] and [Formula: see text] within the Standard Model.


Reduced insulin suppression of glucose appearance is related to susceptibility to dietary obesity in rats.
To examine the relationship between insulin action and body weight regulation in male rats, the following studies were performed. In study 1, rats (n = 31) were fed a low-fat diet (LFD) for 4 wk, and then glucose kinetics were estimated under basal and hyperinsulinemic conditions using the glucose clamp. After clamps, these same rats were placed on a high-fat diet (HFD) for 5 wk. In study 2, rats (n = 30) were fed an LFD for 3 wk and then a high-sucrose diet for 1 wk to produce selective hepatic insulin resistance. Clamps were then performed, and after clamps, these same rats were placed on an HFD for 5 wk. In study 3, rats (n = 30) were fed an LFD for 1 wk and then a high-sucrose diet for 3 wk to produce widespread insulin resistance. Clamps were then performed, and after clamps, these same rats were placed on an HFD for 5 wk. The rate of glucose appearance (R(a)) during the hyperinsulinemic clamps was the only pre-HFD variable that correlated (r = 0.49, P < 0.01 in study 1; r = 0.51, P < 0.001 in study 2) with weight gain on the HFD. Clamp R(a) also correlated with energy intake on the HFD in study 1 (r = 0.64, P < 0.001) and study 2 (r = 0.59, P < 0.001). Clamp R(a) and energy intake on the HFD accounted for similar portions of the variance in body weight gain on the HFD. Weight gain and fat-pad mass were increased (P < 0.05) in study 2 compared with study 1. In study 3, pre-HFD glucose kinetics were not correlated with energy intake or weight gain on the HFD. Widespread insulin resistance did not significantly reduce the rate of weight gain on the HFD. Thus insulin action on R(a) can influence body weight gain on an HFD. The effects of R(a) on body weight gain appear to be mediated via effects on energy intake. Selective hepatic insulin resistance can increase body weight gain on an HFD, but widespread insulin resistance does not significantly reduce HFD-induced weight gain.


Gait-Cycle-Driven Transmission Power Control Scheme for a Wireless Body Area Network.
In a wireless body area network (WBAN), walking movements can result in rapid channel fluctuations, which severely degrade the performance of transmission power control (TPC) schemes. On the other hand, these channel fluctuations are often periodic and are time-synchronized with the user's gait cycle, since they are all driven from the walking movements. In this paper, we propose a novel gait-cycle-driven transmission power control (G-TPC) for a WBAN. The proposed G-TPC scheme reinforces the existing TPC scheme by exploiting the periodic channel fluctuation in the walking scenario. In the proposed scheme, the user's gait cycle information acquired by an accelerometer is used as beacons for arranging the transmissions at the time points with the ideal channel state. The specific transmission power is then determined by using received signal strength indication (RSSI). An experiment was conducted to evaluate the energy efficiency and reliability of the proposed G-TPC based on a CC2420 platform. The results reveal that compared to the original RSSI/link-quality-indication-based TPC, G-TPC reduces energy consumption by 25% on the sensor node and reduce the packet loss rate by 65%.


Pope John Paul II and the neurological standard for the determination of death: A critical analysis of his address to the Transplantation Society.
The introduction of the "brain death" criterion constitutes a significant paradigm shift in the determination of death. The perception of the public at large is that the Catholic Church has formally endorsed this neurological standard. However, a critical reading of the only magisterial document on this subject, Pope John Paul II's 2000 address, shows that the pope's acceptance of the neurological criterion is conditional in that it entails a twofold requirement. It requires that certain medical presuppositions of the neurological standard are fulfilled, and that its philosophical premise coheres with the Church's teaching on the body-soul union. This article demonstrates that the medical presuppositions are not fulfilled, and that the doctrine of the brain as the central somatic integrator of the body does not cohere either with the current holistic understanding of the human organism or with the Church's Thomistic doctrine of the soul as the form of the body. The concept of "brain death" (the neurological basis for legally declaring a person dead) has caused much controversy since its inception. In this regard, it has been generally perceived that the Catholic Church has officially affirmed the "brain death" criterion. The address of Pope John Paul II in 2000 shows, however, that he only gave it a conditional acceptance, one which requires that several medical and philosophical presuppositions of the "brain death" standard be fulfilled. This article demonstrates, taking into consideration both the empirical evidence and the Church's Thomistic anthropology, that the presuppositions have not been fulfilled.


Bacterial colonization of the nose and external ear canal in newborn infants.
The bacterial flora of the nose and external ear canal of 132 newborn infants, aged 3 days and 4 to 7 days, was examined. Cultures taken from the nose showed the following pattern of bacterial colonization: normal flora (39%); potentially pathologic gram-positive microorganisms (23%); gram-negative enteric rods (16%); and sterile cultures (22%). The most frequent bacterial cultures from nostrils were Staphylococcus epidermidis (39%); Staph. aureus (11%) and Escherichia coli (8%). The cultures from the external ear canal showed normal flora (37%); potentially pathologic gram-positive microorganisms (5%); gram-negative enteric rods (24%); and sterile cultures (34%). The most frequent bacteria cultured from the ear canal were: Staph. epidermidis (37%); E. coli (8%); and Klebsiella pneumoniae (7.5%). Of several factors studied, the type of delivery, Apgar score and the duration of hospitalization were found to have a significant influence on the pattern of bacterial colonization.


More senior BME nurses on agenda for new chief.
The new chief executive at the Florence Nightingale Foundation, Ursula Ward, is keen to promote black and minority ethnic (BME) issues and tackle systemic problems in nursing.


Paucity of CD4+ natural killer T (NKT) lymphocytes in sooty mangabeys is associated with lack of NKT cell depletion after SIV infection.
Lack of chronic immune activation in the presence of persistent viremia is a key feature that distinguishes nonpathogenic simian immunodeficiency virus (SIV) infection in natural hosts from pathogenic SIV and HIV infection. To elucidate novel mechanisms downmodulating immune activation in natural hosts of SIV infection, we investigated natural killer T (NKT) lymphocytes in sooty mangabeys. NKT lymphocytes are a potent immunoregulatory arm of the innate immune system that recognize glycolipid antigens presented on the nonpolymorphic MHC-class I-like CD1d molecules. In a cross-sectional analysis of 50 SIV-negative and 50 naturally SIV-infected sooty mangabeys, ligand alpha-galactosylceramide loaded CD1d tetramers co-staining with Valpha24-positive invariant NKT lymphocytes were detected at frequencies >or=0.002% of circulating T lymphocytes in approximately half of the animals. In contrast to published reports in Asian macaques, sooty mangabey NKT lymphocytes consisted of CD8(+) and CD4/CD8 double-negative T lymphocytes that were CXCR3-positive and CCR5-negative suggesting that they trafficked to sites of inflammation without being susceptible to SIV infection. Consistent with these findings, there was no difference in the frequency or phenotype of NKT lymphocytes between SIV-negative and SIV-infected sooty mangabeys. On stimulation with alpha-galactosylceramide loaded on human CD1d molecules, sooty mangabey NKT lymphocytes underwent degranulation and secreted IFN-gamma, TNF-alpha, IL-2, IL-13, and IL-10, indicating the presence of both effector and immunoregulatory functional capabilities. The unique absence of CD4(+) NKT lymphocytes in sooty mangabeys, combined with their IL-10 cytokine-secreting ability and preservation following SIV infection, raises the possibility that NKT lymphocytes might play a role in downmodulating immune activation in SIV-infected sooty mangabeys.


To biopsy or not to biopsy? Should we screen the histology of stable renal grafts?
Chronic allograft dysfunction is currently the main cause of late allograft failure. Recent encouraging evidence suggests that it may be possible to delay the development of graft damages if adequate management is initiated early in the course of the disease. These observations have renewed interest in the performance of protocol biopsies as routine follow-up procedure for the screening of renal transplants. In the present review, we summarize the available data from the literature to determine the pros and cons of protocol renal allograft biopsies. On the basis of this evidence, we discuss the ethical concerns raised by this procedure.


Ayahuasca in adolescence: a neuropsychological assessment.
The purpose of the study was to evaluate neuropsychologically adolescents who use ayahuasca in a religious context. A battery of neuropsychological tests was administered to adolescents who use ayahuasca. These subjects were compared to a matched control group of adolescents who did not use ayahuasca. The controls were matched with regards to sex, age, and education. The neuropsychological battery included tests of speeded attention, visual search, sequencing, psychomotor speed, verbal and visual abilities, memory, and mental flexibility. The statistical results for subjects from matched controls on neuropsychological measures were computed using independent t-tests. Overall, statistical findings suggested that there was no significant difference between the two groups on neuropsychological measures. Even though, the data overall supports that there was not a difference between ayahuasca users and matched controls on neuropsychological measures, further studies are necessary to support these findings.


Targeting and Regulating of an Oncogene via Nanovector Delivery of MicroRNA using Patient-Derived Xenografts.
In precision cancer nanomedicine, the key is to identify the oncogenes that are responsible for tumorigenesis, based on which these genetic drivers can be each specifically regulated by a nanovector-directed, oncogene-targeted microRNA (miRNA) for tumor suppression. Fibroblast Growth Factor Receptor 3 (FGFR3) is such an oncogene. The molecular tumor-subtype harboring FGFR3 genomic alteration has been identified via genomic sequencing and referred to as the FGFR3-driven tumors. This genomics-based tumor classification provides further rationale for the development of the FGFR3-targeted miRNA replacement therapy in treating patients with FGFR3 gene abnormity. However, successful miRNA therapy has been hampered by lacking of an efficient delivery vehicle. In this study, a nanovector is developed for microRNA-100 (miR-100) -mediated FGFR3 regulation. The nanovector is composed of the mesoporous magnetic clusters that are conjugated with ternary polymers for efficient miRNA in-vivo delivery. The miRNA-loading capacity of the nanovector is found to be high due to the polycation polymer functionalized mesoporous structure, showing excellent tumor cell transfection and pH-sensitive miRNA release. Delivery of miR-100 to cancer cells effectively down-regulates the expression of FGFR3, inhibits cell proliferation, and induces cell apoptosis in vitro. Patient-derived xenografts (PDXs) are used to evaluate the efficacy of miRNA delivery in the FGFR3-driven tumors. Notably, sharp contrasts are observed between the FGFR3-driven tumors and those without FGFR3 genomic alteration. Only the FGFR3-driven PDXs are significantly inhibited via miR-100 delivery while the non-FGFR3-driven PDXs are not affected, showing promise of precision cancer nanomedicine.


Independent developmental programs for two estrogen-regulated genes.
Measurement of hepatic apolipoprotein II and vitellogenin II messenger RNA during chicken embryogenesis showed that these genes acquire estrogen responsiveness at different stages of development. Sensitive solution hybridization assays with excess complementary DNA showed that apolipoprotein II transcripts were induced to 500 molecules per cell at day 9, whereas induction of vitellogenin II messenger RNA was not found until day 11. Thus, two estrogen regulated genes of common function and coordinately regulated in the adult may be on independent developmental programs.


Profiling core proteomes of human cell lines by one-dimensional PAGE and liquid chromatography-tandem mass spectrometry.
Protein expression profiles vary considerably between human cell lines and tissues, which is in part a reflection of their specialized roles within an organism. It is of considerable practical use to establish which proteins constitute the primary components of the respective proteomes. When compiled into databases, such information can facilitate the assessment of selectivity and specificity of a wide range of proteomic experiments. Here we describe the major constituents of proteomes of six human immortalized cell lines. By employing a combination of one-dimensional SDS-PAGE and nanocapillary liquid chromatography-tandem mass spectrometry (LC-MS/MS), we identified up to 1785 non-redundant cytoplasmic and nuclear proteins from a single cell line using 50 and 30 microg of total protein from the corresponding fractions. Up to 38 proteins could be identified from a single band in one liquid chromatography-MS/MS experiment. When combined with systematic gridding of gel lanes into 48 slices, a dynamic range for protein identification of approximately 1:2000 can be envisaged for this approach. Identified proteins range from 4-553 kDa in size, cover the pI range between 3.4 and 12.8, and include 255 proteins with predicted transmembrane domains. Repeated analysis of peptides derived from the same gel band showed that the reproducibility of nanocapillary liquid chromatography-MS/MS of such complex mixtures is about 60-70% suggesting that a particular analytical experiment would need to be repeated about three times to arrive at a representative estimate of the set of highly abundant proteins in a given proteome. Given its technical simplicity, sensitivity, and wealth of generated information, we have adopted this experimental approach to characterize every cell line and tissue that is the subject of experimentation in our laboratory. The combined dataset for the six cell lines consists of 2341 non-redundant human proteins and thus constitutes one of the largest collections of human proteomic data published to date.


A novel dysphagia diet improves the nutrient intake of institutionalized elders.
Dysphagia affects 35% to 60% of the institutionalized elderly population. This study aimed at evaluating the nutrient intake of frail institutionalized elderly persons with dysphagia and to assess the impact of Sainte-Anne's Hospital Advanced Nutritional Care program on dietary intake and weight. A 12-week intervention study. Ninety-three individuals residing in a Montreal, Canada, long-term care facility who were aged at least 65 years were evaluated. Seventeen subjects with a body mass index (BMI; calculated as kg/m(2)) <24 or weight loss >7.5% within 3 months and with dysphagia were included. The treated group (n=8; aged 82.5+/-4.41 years, weight 55.9+/-12.1 kg, BMI 22.4+/-3.93) received Sainte-Anne's Hospital reshaped minced- or pureed-texture foods with thickened beverages where required. The control group (n=9; aged 84.6+/-3.81 years, weight 54.3+/-7.49 kg, BMI 21.2+/-2.31) maintained traditional nourishment. Macronutrient and micronutrient intake, weight, and BMI were measured at baseline, 6 weeks, and 12 weeks. Student t tests were performed to evaluate change within and between groups. The treatment and control groups were similar at baseline, having a mean age of 82.5+/-4.41 years vs 84.6+/-3.81 years and BMI of 22.4+/-3.93 vs 21.2+/-2.31, respectively. The average weight in the treated group increased compared to the control group (3.90+/-2.30 vs -0.79+/-4.18 kg; P=0.02). Similarly, the treated group presented an increased intake of energy, proteins, fats, total saturated fats, monounsaturated fats, potassium, magnesium, calcium, phosphorus, zinc, vitamin B-2, and vitamin D compared to control subjects (P<0.05). Institutionalized elderly patients with dysphagia can eat better and increase body weight via a diversified, modified in texture, and appealing oral diet that meets their nutrition needs.


HER Family Receptors are Important Theranostic Biomarkers for Cervical Cancer: Blocking Glucose Metabolism Enhances the Therapeutic Effect of HER Inhibitors.
Persistent HPV infection alone is not sufficient for cervical cancer development, which requires additional molecular alterations for tumor progression and metastasis ultimately leading to a lethal disease. In this study, we performed a comprehensive analysis of HER family receptor alterations in cervical adenocarcinoma. We detected overexpression of HER protein, mainly HER2, which was an independent prognostic marker for these patients. By using in vitro and in vivo approaches, we provided evidence that HER inhibitors, allitinib and lapatinib, were effective in reducing cervical cancer aggressiveness. Furthermore, combination of these drugs with glucose uptake blockers could overcome the putative HIF1-α-mediated resistance to HER-targeted therapies. Thus, we propose that the use of HER inhibitors in association with glycolysis blockers can be a potentially effective treatment option for HER-positive cervical cancer patients.


Normal human chorionic gonadotropin regression curves in uneventful postmolar patients.
To review current follow-up measures of human chorionic gonadotropin (hCG) in uneventful postmolar patients, and to evaluate criteria for initiating chemotherapy. Between 1993 and 2011 hCG data from 395 patients with uneventful complete moles (CMs) (195 patients) and partial moles (PMs) (205 patients) were obtained at 4 hospitals in Japan. All patients had been followed regularly at various intervals based on the preceding hCG titers and normal hCG regression curve. All patients achieved hCG normalization spontaneously (range, 3.1-29.7 weeks). Approximately half of the patients with CM and PM had attained an undetectable hCG level at 9.3 and 8.3 weeks after evacuation of mole, respectively. The reconstructed normal hCG regression curve consisted of hCG levels of 1,000 mIU/mL at 5 weeks, 100 mIU/mL at 8 weeks and nondetectable hCG levels at 24 weeks. Plotting preceding hCG titers on this hCG regression curve, the intervals of visits to measure hCG were changing, and the real number of visits was significantly fewer than that of recommended weekly measurement of hCG (p<0.0001). The use of the present hCG regression curve after evacuation of a molar pregnancy can aid in estimation of the risk of developing gestational trophoblastic neoplasia, especially in women who have suboptimal compliance and follow-up.


Effects of swimming training on bone mass and the GH/IGF-1 axis in diabetic rats.
The aim of this study was to examine the influence of moderate swimming training on the GH/IGF-1 growth axis and tibial mass in diabetic rats. Male Wistar rats were allocated to one of four groups: sedentary control (SC), trained control (TC), sedentary diabetic (SD) and trained diabetic (TD). Diabetes was induced with alloxan (35 mg/kg b.w.). The training program consisted of a 1h swimming session/day with a load corresponding to 5% of the b.w., five days/week for six weeks. At the end of the training period, the rats were sacrificed and blood was collected for quantification of the serum glucose, insulin, GH, and IGF-1 concentrations. Samples of skeletal muscle were used to quantify the IGF-1 peptide content. The tibias were collected to determine their total area, length and bone mineral content. The results were analyzed by ANOVA with P<0.05 indicating significance. Diabetes decreased the serum levels of GH and IGF-1, as well as the tibial length, total area and bone mineral content in the SD group (P<0.05). Physical training increased the serum IGF-1 level in the TC and TD groups when compared to the sedentary groups (SC and SD), and the tibial length, total area and bone mineral content were higher in the TD group than in the SD group (P<0.05). Exercise did not alter the level of IGF-1 in gastrocnemius muscle in nondiabetic rats, but the muscle IGF-1 content was higher in the TD group than in the SD group. These results indicate that swimming training stimulates bone mass and the GH/IGF-1 axis in diabetic rats.


Modulation of motor learning by a paired associative stimulation protocol inducing LTD-like effects.
Paired associative stimulation (PAS) induces long-term potentiation (LTP)-like effects when interstimulus intervals (ISIs) between electrical peripheral nerve stimulation and transcranial magnetic stimulation (TMS) to M1 are approximately 21-25 ms (PASLTP). It was previously reported that two forms of motor learning (i.e., mode-free and model-based learning) can be differentially modulated by PASLTP depending on the different synaptic inputs to corticospinal neurons (CSNs), which relate to posterior-to-anterior (PA) or anterior-to-posterior (AP) currents induced by TMS (PA or AP inputs, respectively). However, the effects of long-term depression (LTD)-inducing PAS with an ISI of approximately 10 ms (PASLTD) on motor learning and its dependency on current direction have not yet been tested. To investigate whether, and how, PASLTD affects distinct types of motor learning. Eighteen healthy volunteers participated. We adopted the standard PAS using suprathreshold TMS with the target muscle relaxed, as well as subthreshold PAS during voluntary contraction, which was suggested to selectively recruit PA or AP inputs depending on the orientation of the TMS coil. We examined the effects of suprathreshold and subthreshold PASLTD on the performance of model-free and model-based learning, as well as the corticospinal excitability, indexed as the amplitudes of motor evoked potentials (MEPs). PASLTD inhibited model-free learning and MEPs only when subthreshold AP currents were applied. The PASLTD protocols tested here showed no effects on model-based learning. PASLTD affected model-free learning, presumably by modulating CSN excitability changes, rather than PA inputs, which are thought to be related to model-free learning.


Verification and validation of bioinformatics software without a gold standard: a case study of BWA and Bowtie.
Bioinformatics software quality assurance is essential in genomic medicine. Systematic verification and validation of bioinformatics software is difficult because it is often not possible to obtain a realistic "gold standard" for systematic evaluation. Here we apply a technique that originates from the software testing literature, namely Metamorphic Testing (MT), to systematically test three widely used short-read sequence alignment programs. MT alleviates the problems associated with the lack of gold standard by checking that the results from multiple executions of a program satisfy a set of expected or desirable properties that can be derived from the software specification or user expectations. We tested BWA, Bowtie and Bowtie2 using simulated data and one HapMap dataset. It is interesting to observe that multiple executions of the same aligner using slightly modified input FASTQ sequence file, such as after randomly re-ordering of the reads, may affect alignment results. Furthermore, we found that the list of variant calls can be affected unless strict quality control is applied during variant calling. Thorough testing of bioinformatics software is important in delivering clinical genomic medicine. This paper demonstrates a different framework to test a program that involves checking its properties, thus greatly expanding the number and repertoire of test cases we can apply in practice.


Persistently high IgA serum levels are a marker of immunological or virological failure of combined antiretroviral therapy in children with perinatal HIV-1 infection.
Non-expensive and low-complexity surrogate markers for monitoring the response to combined antiretroviral therapy (combined-ART) are needed in poor-resource settings where routine assessment of CD4+ T-lymphocyte count and viral load can not be afforded. We longitudinally evaluated Ig serum levels in 234 HIV-1 infected children receiving combined-ART with > or = 3 drugs. Since Ig levels physiologically vary with age, differences at different age periods were evaluated as differences in z-scores calculated using the mean and standard deviation of the normal population for each age period. Data from 17 (7.3%) children with immunological failure and from 54 (23.1%) children with virological failure of combined-ART were compared with data from not-failed children. At baseline children with immunological failure showed higher IgM z-scores (P = 0.042) than children without. After 3-12 months of therapy immunologically failed children displayed higher viral loads (P < 0.0001) and IgA (P = 0.043) z-scores than not-failed children. Similarly, at the same follow-up time, children with virological failure showed lower CD4(+) T-lymphocyte percentages (P = 0.005) and higher IgA z-scores (P < 0.0001) than not-failed children. No difference in IgG or IgM z-scores was evidenced between failed and not-failed children after 3-12 months of therapy. In conclusion, IgA serum level is a cheap and low-complexity marker of immunological or virological failure of combined-ART which might be adopted in poor-resource settings.


Pancreatic extragastrointestinal stromal tumor invading the duodenum.
Extragastrointestinal stromal tumors that arise in the pancreas are extremely rare and managing them can be difficult, particularly if located in the head of pancreas. This case report aims to contribute to the existing data in the literature regarding extragastrointestinal stromal tumors with rare and unusual locations. We present a 56-year-old man who presented with recurrent mild right upper quadrant abdominal pain. Abdominal computed tomography and magnetic resonance imaging revealed a mass lesion with a diameter of 10 cm localized in the head of pancreas. Pancreaticoduodenectomy with complete tumor excision was performed. He was discharged on the postoperative day 14. Only 15 extragastrointestinal stromal tumors cases have been reported. Of these 15 cases, tumors were located in the head of pancreas in six cases. Here we report the seventh case of pancreatic extragastrointestinal stromal tumor arising in the head of pancreas and also the largest of these seven tumors.


GRASP v2.0: an update on the Genome-Wide Repository of Associations between SNPs and phenotypes.
Here, we present an update on the Genome-Wide Repository of Associations between SNPs and Phenotypes (GRASP) database version 2.0 (http://apps.nhlbi.nih.gov/Grasp/Overview.aspx). GRASP is a centralized repository of publically available genome-wide association study (GWAS) results. GRASP v2.0 contains ∼ 8.87 million SNP associations reported in 2082 studies, an increase of ∼ 2.59 million SNP associations (41.4% increase) and 693 studies (48.9% increase) from our previous version. Our goal in developing and maintaining GRASP is to provide a user-friendly means for diverse sets of researchers to query reported SNP associations (P ≤ 0.05) with human traits, including methylation and expression quantitative trait loci (QTL) studies. Therefore, in addition to making the full database available for download, we developed a user-friendly web interface that allows for direct querying of GRASP. We provide details on the use of this web interface and what information may be gleaned from using this interactive option. Additionally, we describe potential uses of GRASP and how the scientific community may benefit from the convenient availability of all SNP association results from GWAS (P ≤ 0.05). We plan to continue updating GRASP with newly published GWAS and increased annotation depth.


Emergent surgical removal of a migrated left atrial appendage occluder.
Occlusion of the left atrial appendage (LAA) in patients with atrial fibrillation has become a standard therapy to prevent thromboembolic complications. We aim to present 3 cases of LAA occluder embolization after percutaneous WATCHMAN™ device implantation, which required emergent surgical retrieval. The device was dislocated in the left atrium, introducing LAA perforation and resulting in pericardial effusion and later tamponade in 1 patient who developed multiorgan failure and died 8 days postoperatively. Other patients were successfully operated and discharged. Hence, LAA occluder embolization may occur asymptomatically with immediate/late serious complications, which indicates emergent surgery.


α-fur, an antisense RNA gene to fur in the extreme acidophile Acidithiobacillus ferrooxidans.
A large non-coding RNA, termed α-Fur, of ~1000 nt has been detected in the extreme acidophile Acidithiobacillus ferrooxidans encoded on the antisense strand to the iron-responsive master regulator fur (ferric uptake regulator) gene. A promoter for α-fur was predicted bioinformatically and validated using gene fusion experiments. The promoter is situated within the coding region and in the same sense as proB, potentially encoding a glutamate 5-kinase. The 3' termination site of the α-fur transcript was determined by 3' rapid amplification of cDNA ends to lie 7 nt downstream of the start of transcription of fur. Thus, α-fur is antisense to the complete coding region of fur, including its predicted ribosome-binding site. The genetic context of α-fur is conserved in several members of the genus Acidithiobacillus but not in all acidophiles, indicating that it is monophyletic but not niche specific. It is hypothesized that α-Fur regulates the cellular level of Fur. This is the fourth example of an antisense RNA to fur, although it is the first in an extreme acidophile, and underscores the growing importance of cis-encoded non-coding RNAs as potential regulators involved in the microbial iron-responsive stimulon.


Biliary system architecture: experimental models and visualization techniques.
The complex architecture of the liver biliary network represents a structural prerequisite for the formation and secretion of bile as well as excretion of toxic substances through bile ducts. Disorders of the biliary tract affect a significant portion of the worldwide population, often leading to cholestatic liver diseases. Cholestatic liver disease is a condition that results from an impairment of bile formation or bile flow to the gallbladder and duodenum. Cholestasis leads to dramatic changes in biliary tree architecture, worsening liver disease and systemic illness. Recent studies show that the prevalence of cholestatic liver diseases is increasing. The availability of well characterized animal models, as well as development of visualization approaches constitutes a critical asset to develop novel pathogenetic concepts and new treatment strategies.


Adsorptive characteristics of the siloxane surfaces of reduced-charge bentonites saturated with tetramethylammonium cation.
To elucidate interactions of neutral organic contaminants (NOCs) with siloxane surfaces (often referred to hydrophobic nanosites)found between cations in 2:1 phyllosilicates, adsorption of aliphatic and aromatic compounds onto both internal and external siloxane surfaces oftetramethylammonium-intercalated bentonite with a cation exchange capacity (CEC) of 108 cmol/kg (108TMA) and its reduced-charge bentonite (CEC = 65 cmol/ kg, 65TMA) were investigated. Reduction of the layer charge and saturation of bentonite interlayers with TMA+ modify the interlayer microenvironments, which dramatically promote adsorption of NOCs. Specific mechanisms (i.e., steric restriction and phenyl-effect) control the adsorption of NOCs onto internal siloxane surfaces of TMA+ -bentonites from water. The adsorption sites of 108TMA can not provide sufficient space to accommodate NOCs, hence hindering adsorption. Adsorption mechanism on 65TMA varies with solute-loadings, from polarity-selective at low loadings to aromaticity-preferable at high loadings. Significant contribution of phenyl-effect between adsorbed-solutes to aromatics adsorption on 65TMA is found. Solvent polarity effect on the aggregation of TMA+ -bentonites and aniline adsorption demonstrated that the contribution of external siloxane surfaces to favor adsorption in n-hexane are actually exploited but generally omitted. These observations provide significant insights into distinguishing different uptake mechanisms as well as the potential means for the rational design of better organic sorbents.


Oxidations at Sulfur Centers by Aqueous Hypochlorous Acid and Hypochlorite: Cl+ Versus O Atom Transfer.
Sulfur-containing compounds are known to be susceptible to oxidation by aqueous HOCl, but the factors affecting the rates of these reactions are not well-established. Here we report on the kinetics of oxidation of thiosulfate, thiourea, thioglycolate, (methylthio)acetate, tetrathionate, dithiodiglycolate, and dithiodipropionate at 25 °C and 0.4 M ionic strength. These reactions obey the general rate law -d[OCl-]/dt = (kOCl-[OCl-] + kHOCl[HOCl])[substrate] with some exceptions: tetrathionate and the two disulfides undergo rate-limiting hydrolysis at high pH, and dithiodiglycolate has an additional term in the rate law that is second order in [substrate]. The reactions of HOCl are believed to have a Cl+ transfer mechanism, and in the case of thiosulfate the rate of hydrolysis of the ClS2O3- intermediate was determined. In the case of thiourea evidence was obtained for thiourea monoxide as a long-lived product. It is shown that sulfite and species with terminal sulfur atoms have kHOCl values in the vicinity of 1 × 109 M-1 s-1, while SCN- and thioethers react somewhat more slowly; tetrathionate, trithionate, and disulfides react much more slowly. Comparison of the rate constants with those for oxidation of these sulfur substrates by H2O2 and [Pt(CN)4Cl2]2- shows that HOCl reacts a few orders of magnitude more rapidly than [Pt(CN)4Cl2]2- and ∼9 orders of magnitude more rapidly than H2O2. Many of the kHOCl values are leveled by the high electrophilicity of HOCl. It is proposed that the kOCl- values correspond to oxygen-atom transfer mechanisms, as supported by LFERS (linear free energy relationships) relating these rate constants to those for reactions of H2O2 and [Pt(CN)4Cl2]2-.


Predictors of reading fluency in Italian orthography: evidence from a cross-sectional study of primary school students.
This study investigates the role of linguistic and visuospatial attentional processes in predicting reading fluency in typical Italian readers attending primary school. Tasks were administered to 651 children with reading fluency z scores > -1.5 standard deviation to evaluate their phonological awareness, rapid automatized naming (RAN), verbal short-term memory, vocabulary, visual search skills, verbal-visual recall, and visual-spatial attention. Hybrid models combining confirmatory factor analysis and path analysis were used to evaluate the data obtained from younger (first and second grade) and older (third-fifth grade) children, respectively. The results showed that phonological awareness and RAN played a significant role among younger children, while also vocabulary, verbal short-term memory, and visuospatial attention were significant factors among older children.


Novel leukaemia markers.
Using synthetic peptide or recombinant protein as immunising antigens we have produced monoclonal antibodies and polyclonal antisera directed against targets of particular interest in leukaemia diagnosis. In this way we have prepared reagents which recognise all T or all B lymphocytes in routinely fixed paraffin sections which are unique in this respect. We have also produced monoclonal antibodies to molecules potentially involved in specific neoplastic transformations, implicated by virtue of the involvement of their genes in chromosomal defects in these neoplasms. In particular, we have produced antibodies recognising bcl-2, involved in follicular lymphoma, tal-1, involved in T-cell acute leukaemias and HRX involved in a variety of hematologic disorders. The application of these reagents to diagnosis has so far proved useful. In addition their use outside the field of leukaemia diagnosis has proved to be even more important in some cases.


[Systemic embolism of cholesterol crystals].
Systemic cholesterol crystal emboli (SCCE) are no longer a rare complication of severe atheroma. Sixty-year old men, with many vascular problems are typically involved. SCCE, released from atheromatous ulcerated "plaques", invade one or more arteriolar beds. Clinical presentation is polymorphic: skin, muscle, kidney, digestive tract and other abdominal organs, retina, bone narrow ... may be embolized. SCCE are associated with triggering conditions: vascular surgery, anticlotting agents and fibrinolysis, femoral retrograd catheterization by radiologists or cardiologists. This last factor is presently predominant. Clinical signs depend on atheroma localization, intensity and repetition of embols and topography of arteriolar beds susceptible to be embolized: livedo reticularis, acute renal failure with high blood pressure, limbs or abdominal pain, periarteritis nodosa-like syndrome. Diagnosis is based on the discovery of ocular fundi (cholesterol crystals in arterioles) and evidence of cholesterol crystals in various biopsies: skin, muscle, kidneys. Prognosis and curative treatment are poor. Mortality is greater than 80% in systemic forms. Surgical palliative treatment was recently proposed (bypass). Prevention is essential: triggering manipulations i.e. retrograd femoral catheterism have to be avoided by radiologists or cardiologists in exposed patients. In high risk atheromatous patients symptomatic treatment including repetitive dialysis is able to induce significative survival.


Human glycinamide ribonucleotide transformylase: active site mutants as mechanistic probes.
Human glycinamide ribonucleotide transformylase (GART) (EC 220.127.116.11) is a validated target for cancer chemotherapy, but mechanistic studies of this therapeutically important enzyme are limited. Site-directed mutagenesis, initial velocity studies, pH-rate studies, and substrate binding studies have been employed to probe the role of the strictly conserved active site residues, N106, H108, and D144, and the semiconserved K170 in substrate binding and catalysis. Only two conservative substitutions, N106Q and K170R, resulted in catalytically active enzymes, and these active mutant enzymes gave pH-rate profiles and a steady-state kinetic mechanism essentially identical to those of the native enzyme. All inactive mutants were able to bind both substrates, ruling out disrupted formation of the ternary complex as the source of inactivity. Differences between human and Escherichia coli GART, previously used as a model for the human enzyme, were evident.


Primary retroperitoneal teratoma in an adult: ultrasonographic, computer tomographic and magnetic resonance imaging demonstrations.
A 25-year-old male patient with a primary retroperitoneal teratoma is described. The chief complaint was right hypochondralgia during exercise for seven days. Various diagnostic imagings disclosed an expansive, heterogeneous and fat-rich mass associated with multiple cystic lesions in the right suprarenal fossa. Sagittal, transaxial and coronal magnetic resonance imaging scan visualized the extent and character of the tumor very clearly. Histological examination of the tumor removed through a thoracoabdominal approach showed cystic teratoma with out malignant transformations.


Supported Decision-Making: The Expectations Held by People With Experience of Mental Illness.
Supported decision-making (SDM) is a principle guiding mental health service provision, which aims to improve people's ability to make informed decisions about their care. Understanding diverse individual needs is vital to its success. Based on 29 narrative interviews with people diagnosed with mental illness in Australia, we examine how participants reflected on their own experiences of SDM. We find that participants' conceptualization of mental health expertise, their own experiences and sense of agency, and their varying needs for dependence and independence influenced their relationships with mental health practitioners. These factors in turn shaped their expectations about SDM. Four narrative positions emerged: the "Inward Expert," the "Outward Entrustor," the "Self-Aware Observer," and the "Social Integrator." These positionings influenced the type or style of support that participants expected and considered most useful. Our findings are relevant to developing effective approaches to SDM that take into account service users' needs and preferences.


The Insulin-Like Growth Factor 2 mRNA Binding Protein IMP2/IGF2BP2 is Overexpressed and Correlates with Poor Survival in Pancreatic Cancer.
The insulin-like growth factor 2 (IGF2) mRNA binding protein IMP2 (IGF2BP2) is an oncogenic protein known to be overexpressed in different tumor types. Pancreatic cancer is a very lethal cancer that requires early diagnosis and new treatment options. The aim of our study was to investigate the role of IMP2 in the initiation and progression of pancreatic ductal adenocarcinoma (PDAC). IMP2 was significantly overexpressed in a human precursor (PanIN) lesions suggesting IMP2 as a marker for early stages of PDAC. In a PDAC cohort of matched normal and tumor samples IMP2 showed overexpression in tumor tissues compared with normal pancreatic tissue. Strict correlation analysis (threshold R2 > 0.75) revealed 22 genes highly positively and 9 genes highly negatively correlating with IMP2. Besides genes involved in the inhibition of apoptosis (Bcl-XL), especially factors involved in ubiquitination were strongly correlated with IMP2 expression: SMURF1 and FBXO45. Moreover, protein kinase C (PKC) signaling pathway was distinctly affected: DXS1179E encoding PKC iota, PKC substrate PLEK2, and inositol triphosphate receptor IP3R3 were positively correlated with IMP2 expression. Besides tumor initiation, IMP2 also seemed to have an impact on tumor progression. TGF-β treatment of Panc-1 pancreatic cancer cells to induce epithelial-mesenchymal transition (EMT) was accompanied by increased IMP2 expression. EMT is important for cancer cells to gain migratory and invasive potential, which is essential for metastasis. Concordantly, circulating tumor cells showed higher IMP2 levels as compared with normal tissue from tumor origin and with normal hematological cells. Accordingly, IMP2 protein levels correlated with poor survival. In conclusion, as IMP2 seems to promote tumor progression of PDAC, it might be an interesting diagnostic and prognostic marker as well as a novel target for the treatment of PDAC.


Volume-outcome relationship in balloon aortic valvuloplasty: results of a consecutive, patient-level data analysis from a Japanese nationwide multicentre registry (J-SHD).
Transcatheter balloon aortic valvuloplasty (BAV) remains an important alternative treatment for severe, symptomatic aortic stenosis. With increasing numbers of BAVs being performed, the need for large-scale volume-outcome relationship assessments has become evident. Here, we aimed to explain such relationships by analysing consecutive, patient-level BAV data recorded in a prospective Japanese nationwide multicentre registry. Prospective study. Data of 1920 BAVs performed in 200 Japanese hospitals from January 2015 to December 2019. The mean patient age was 85 years, and 36.9% of procedures involved male patients. The efficacy of BAV was assessed by reducing the mean transaortic valve gradient after the procedure. We also assessed in-hospital complication rates, including in-hospital death, bleeding, urgent surgery, distal embolism, vessel rupture and contrast-induced nephropathy. Based on the distribution of case volume (median 20, IQR 10-46), we divided the patients into high-volume (≥20) and low-volume (<20) groups. In-hospital complication risk was assessed with adjustment by logistic regression modelling. Indications for BAV included palliative/destination (44.2%), bridge to transcatheter aortic valve replacement (34.5%), bridge to surgical aortic valve replacement (7.4%) and salvage (9.7%). Reduction of the mean transaortic valve gradient was similar between the high-volume and low-volume groups (20 mm Hg vs 20 mm Hg, p=0.12). The proportion of in-hospital complications during BAV was 4.2%, and the incidence of complications showed no difference between the high-volume and low-volume groups (4.2% vs 4.1%, p=1.00). Rather than hospital volume, salvage procedure was an independent predictor of in-hospital complications (OR, 4.04; 95% CI, 2.03 to 8.06; p<0.001). The current study demonstrated that procedural outcomes of BAV were largely independent of its institutional volume.


Cutaneous reactions to topical application of hydroquinone. Results of a 6-year investigation.
The investigation was designed to assess the safety of hydroquinone in cosmetic skin-lightening products, and to determine the optimal concentration for the purpose. The 840 volunteers who took part in the 6-year trial were drawn from various race groups with skins varying from very fair to very dark. They were subjected to open tests, "normal usage" tests, and standard 48-hour closed-patch tests. In all, over 7,000 test areas were examined. The results show that concentrations of hydroquinone of 3% and less produced negligible adverse effects, irrespective of the base or the colour of the user's skin. It is stressed that any confusion of hydroquinone with the hazardous monobenzyl ether of of hydroquinone (monobenzone, MBH) should be avoided.


Fatigue: a prevalent symptom in gastroparesis.
Fatigue is seen in many medical conditions. Patients with gastroparesis may complain of fatigue. The aim of this work is to first assess the prevalence and severity of fatigue in patients with gastroparesis, and secondly to correlate fatigue with symptoms, quality of life, and factors that may contribute to fatigue. One hundred and fifty-six patients with gastroparesis filled out questionnaires including the fatigue assessment instrument (FAI), patient assessment of upper gastrointestinal symptom severity index, patient assessment of upper gastrointestinal disorders-quality of life and hospital anxiety, and depression scale to evaluate for fatigue, symptoms, quality of life, and depression. Gastric emptying test and laboratory studies for hemoglobin, glycosylated hemoglobin, thyroid function (TSH), and inflammatory markers (CRP and ESR) were obtained. Fatigue was reported by 93 % of patients. The mean total FAI score was 3.71 ± 0.2, with 51 % of patients having a score above 4, indicating severe fatigue. There were moderate correlations between fatigue and many symptoms of gastroparesis: upper abdominal discomfort (r = 0.446), upper abdominal pain (r = 0.422), loss of appetite (r = 0.329), bloating (r = 0.297), and abdominal distention (r = 0.265). Fatigue in patients using metoclopramide (3.5 ± 0.4) was similar to patients using domperidone (3.7 ± 0.5) or neither medicine (3.8 ± 0.3). Fatigue severity correlated with a decreased quality of life (r = -0.694, p < 0.001), increased depression (r = 0.339, p = 0.009), lower anxiety (r = -0.441, p < 0.001), and lower hemoglobin levels (r = -0.258, p = 0.005), but not to glycosylated hemoglobin, ESR, CRP, TSH, or gastric emptying. Fatigue is an important significant symptom in patients with gastroparesis with a high prevalence and severity. Fatigue is correlated with many symptoms of gastroparesis, low hemoglobin, depression, inflammation, decreased quality of life, but not to severity of delayed gastric emptying or to medication use.


[Vasculitis syndrome--clinical classification and diagnostic approaches].
Vasculitis syndrome comprises a broad spectrum of diseases associated with vasculitis, which is characterized by inflammation and damage to blood vessels. Clinical features associated with vasculitis usually appear depending upon size of damaged vessels, but rarely correlate with primary disease itself. Vasculitis must be considered in the differential diagnosis for therapeutic approaches, particularly in patients with serious vasculitis occurring irreversible organ damage due to rapidly progressive systemic vasculitis, such as Wegener's granulomatosis, polyarteritis nodosa. These patients require prompt and aggressive treatment and the optimal treatment at the early stage of disease process can induce complete remission. Vasculitis syndrome have been classified by clinical, pathologic and immunological findings and these classifications and criteria are helpful for diagnostic and appropriate therapeutic approaches.


Pharmacogenomics and Implications for Nursing Practice.
This article aims to introduce the nurse to pharmacogenomics and its implications for clinical practice with regard to drug therapy. Pharmacogenomics is discussed with regard to the basic tenets, relationships to common health conditions, education and practice resources, and implications for nursing practice. Peer-reviewed literature, websites, and expert professional guidelines were reviewed with relation to pharmacogenomics and nursing practice. The genetic-genomic literature has grown significantly since the completion of the Human Genome Project in 2003. This information is now being translated into practice with regard to the patient's genetic profile and the impact on drug therapy, which is pharmacogenomics. The utilization of the patient genetic-genomic profile is beginning to have an impact on patient drug therapy in clinical practice. Nurses are in the position to make sure, with the increased translation of pharmacogenomics into clinical practice, that adverse drug reactions are avoided and doses are optimized.


Molecular cloning of three distinct forms of the Na+,K+-ATPase alpha-subunit from rat brain.
Rat brain and kidney cDNA libraries were constructed and screened with a cDNA insert corresponding to the mRNA for the sheep kidney Na+,K+-ATPase catalytic subunit. The alpha-subunit cDNAs isolated from the kidney library were derived from a single class of messenger RNA, and the brain cDNAs were derived from three classes of messenger RNA. The most abundant brain cDNA, which spans 5.1 kilobases, encodes the alpha(+) form of the enzyme. The second most abundant brain cDNA, which spans 3.65 kilobases, is identical with that of the kidney form and therefore encodes the alpha isoform. The third class of cDNA, which spans 3.55 kilobases, was present at low abundance and encodes an isoform of the alpha-subunit, designated alpha III, which has not been identified previously. The complete nucleotide sequence and deduced amino acid sequence for each of the brain and kidney cDNAs have been determined. In addition, we have identified a lysine-rich sequence that may function as a movable, ion-selective gate during cation binding and occlusion and have also identified several amino acid sequence variations that appear to explain some of the well-known species and tissue differences in cardiac glycoside sensitivity.


Pharmacokinetics, pharmacodynamics, and safety of cinacalcet hydrochloride in hemodialysis patients at doses up to 200 mg once daily.
Cinacalcet hydrochloride (HCl) can be used to manage the secondary hyperparathyroidism of patients with chronic kidney disease. This study investigated the pharmacokinetics, pharmacodynamics, safety, and tolerability of cinacalcet HCl over a dose range of 25 to 300 mg/d in patients receiving dialysis. Hemodialysis patients were randomly assigned 4:1 to receive cinacalcet HCl or placebo in this double-blind study. Cinacalcet HCl doses were escalated weekly in 25-mg increments from 25 to 300 mg/d. Noncompartmental methods were used to analyze the pharmacokinetic parameters of cinacalcet (the free-base). The effects of cinacalcet concentration on plasma parathyroid hormone (PTH) and serum calcium levels were evaluated. Of 23 patients enrolled (17 patients, cinacalcet HCl; 6 patients, placebo), 10 patients (8 patients, cinacalcet HCl; 2 patients, placebo) completed the study. Plasma concentration, median area under the plasma concentration-time curve from time 0 to 24 hours after dosing, and maximal plasma concentration (Cmax ) of cinacalcet increased with doses up to 200 mg once daily. Median oral clearance ranged from 222 to 599 L/h, and median time after dosing when C max occurred ranged from 2 to 3 hours across all doses. The pharmacokinetics were linear over the 25- to 200-mg once-daily dose range, with no substantial increase in exposure at greater than 200 mg. Changes in plasma PTH concentrations correlated inversely with cinacalcet concentration. The concentration-effect relationship was well described by an inhibitory maximal effect model. Cinacalcet HCl was reasonably tolerated, and the incidence of adverse events was similar between groups (76%, cinacalcet; 80%, placebo). Gastrointestinal events were noted at greater doses and may be dose related. Cinacalcet HCl shows a dose-proportional increase in exposure over the range of 25 to 200 mg once daily in patients on hemodialysis therapy, and kinetics were linear up to 200 mg once daily. The incidence of adverse events was similar between groups.


[A comparative study on the radiographs of spiral CT and cone-beam CT in temporomandibular joint osteoarthrosis].
Objective: To observe and compare the radiographs of spiral CT and cone-beam CT (CBCT) in the imaging of temporomandibular joint osteoarthrosis (TMJOA) and to explore the difference between CBCT and spiral CT in detection accuracy so as to provide references for clinical diagnosis and treatment. Methods: A total of 52 patients with TMJOA diagnosed in the Department of Oral and Maxillofacial Surgery, General Hospital of Chinese PLA, from January 2018 to December 2019 were selected. There were 10 males and 42 females, with an average age of 38.6 years (21-70 years). All patients underwent spiral CT and CBCT examinations. Two oral radiologists and two oral and maxillofacial surgeons measured and evaluated the joint spaces and condylar bone lesions of each side of temporomandibular joint. According to the presence or absence of osteoarthrosis, the patients were divided into osteoarthrosis group (92 sides) and non osteoarthrosis group (12 sides). The mean size of joint spaces and the detection rate of lesions were compared between the two groups. SPSS 20.0 was used to analyze the data. Results: There was no significant difference between the measurements of joint space size and joint position in the spiral CT group and the CBCT group (P>0.05). The mean size of the anterior space and the ratio of the posterior condyle in the osteoarthrosis side were larger than that in the normal side. The LR index was smaller in the osteoarthrosis side than that in the normal side indicating that the position of the posterior condyle in the osteoarthrosis side was deviated. However, the difference was not statistically significant (P>0.05). Both spiral CT and CBCT showed good consistency in displaying condylar osteopathy. The most common types of condylar osteopathy was surface defect. The detection rates of defects by spiral CT were surface erosion (85.6%, 89/104), articular surface flattening and shortening (82.7%, 86/104), subcortical sclerosis (40.4%, 42/104), osteophyte (40.4%, 42/104) and subcortical cyst (11.5%, 12/104) respectively. The detection rates of defects by CBCT were surface erosion (88.5%, 92/104), articular surface flattening and shortening (86.5%, 90/104), subcortical sclerosis (35.6%, 37/104), osteophyte (41.3%, 43/104) and subcortical cyst (11.5%, 12/104). There was no statistical difference between the two groups (P>0.05), respectively. Conclusions: Both spiral CT and CBCT showed good accuracies in displaying the osteopathy of TMJOA and the sizes of the joint spaces measured by spiral CT and CBCT were basically the same. Both spiral CT and CBCT could be used as a routine diagnostic method for TMJOA.


Human hepatoma cells expressing MHC antigens display accessory cell function: dependence on LFA-1/ICAM-1 interaction.
Malignant transformation of human hepatocytes is often accompanied by an increased expression of major histocompatibility complex (MHC) molecules, but whether this phenomenon is related to an enhanced immunogenicity remains unknown. In this study, we tested the capacity of a series of human hepatoma cell lines to induce proliferation of allogeneic T cells in primary mixed lymphocyte tumour cultures (MLTC). These cell lines were positive for class I molecules, whereas class II molecule expression was either constitutive or inducible by treatment with interferon-gamma (IFN-gamma). We found that HA22T/VGH cells expressing class II molecules constitutively stimulated high proliferative responses of purified CD4+ T lymphocytes, whereas class II-negative Li7A cells stimulated CD4+ T-cell responses only when induced by treatment with IFN-gamma. HA22T/VGH and Li7A cells also exerted a significant stimulatory activity for purified CD8+ T cells whereas HepG2 cells, in which MHC class II molecules are neither constitutive IFN-gamma-inducible, were unable to induce CD4+ and CD8+ T-cell proliferative responses. Phenotypical analysis revealed that HA22T/VGH and Li7A expressed high levels of intracellular adhesion molecule-1 (ICAM-1) and experiments with blocking monoclonal antibodies (mAb) demonstrated that this molecule played a key role in mediating the co-stimulatory function of hepatoma cells. In addition, HA22T/VGH cells were found to produce mRNA for interleukin-1 (IL-1) beta and IL-6, while Li7a only produced IL-1 beta, yet both these cytokines were found to play a small part, if any, in T-cell co-activation. On the whole, these results show tht hepatoma cells expression MHC antigens and ICAM-1 are able to deliver signals necessary for activation of resting CD4+ and CD8+ T cells and suggest that they may actively participate in the anti-tumour immune response.


Aldehyde dehydrogenase induction by glutamate in Escherichia coli. Role of 2-oxoglutarate.
In Escherichia coli, an aldehyde dehydrogenase that catalyzes the oxidation of L-lactaldehyde to L-lactate is induced not only by L-fucose, L-rhamnose or D-arabinose, but also by growth in the presence of glutamate or amino acids yielding glutamate, with the exception of proline. Induction by these amino acids requires glutamate accumulation. 4-Aminobutyric acid also induces this aldehyde dehydrogenase through its transamination to glutamate. Growth on 2-oxoglutarate, the tricarboxylic acid cycle intermediate with which glutamate is in equilibrium, also induces this aldehyde dehydrogenase. Conditions in which the conversion of 2-oxoglutarate into glutamate is highly restricted displayed unchanged rates of induction by 2-oxoglutarate, indicating that glutamate induces the aldehyde dehydrogenase through 2-oxoglutarate formation. Evidence is presented showing that L-fucose- and 2-oxoglutarate-inducing systems share the same regulatory protein. Induction by growth on either of these two compounds is repressed both by glucose and by glycerol. Addition of cAMP to these cultures partially recovers the glucose-repressed aldehyde dehydrogenase activity, while this nucleotide has no effect on the glycerol-mediated repression. These results indicate that ald is under carbon regulation mediated by at least two different mechanisms.


Management of BMI Is a Potential New Approach for the Prevention of Idiopathic Pulmonary Fibrosis.
Aims: Current idiopathic pulmonary fibrosis (IPF) therapies usually show a poor outcome or treatment efficacy. The search for new risk factors has significant implications in preventing, delaying, and treating IPF. The association between obesity and the risk of IPF is not clear. This study aimed to investigate the role of different obesity types in IPF risk, which provides the possibility of weight loss as a new approach for IPF prevention. Methods: We conducted a two-sample Mendelian randomization (MR) analysis to assess the causal effect of obesity on IPF risk. We collected summary data of genetically determined obesity-related traits, including body mass index (BMI), waist circumference (WC), and waist-to-hip ratio (WHR) from large-scale consortia (the sample size ranging from 232,101 to 681,275), and genetic association with IPF from one of the largest meta-analyses including 2,668 cases. A total of 35-469 single nucleotide polymorphisms were selected as instrumental variables for obesity-related traits. We further performed multivariable MR to estimate the independent effect of BMI and WC on the risk of IPF. Results: Increased BMI and WC were associated with higher risk of IPF [odds ratio (OR) = 1.51, 95% confidence interval (CI) (1.22-1.87), p = 1.27 × 10-4, and OR = 1.71, 95% CI (1.08-2.72), p = 2.33 × 10-2, respectively]. Similar results for the BMI and WC were obtained in the replicated analysis. Subsequently, only the result for BMI survived following the multiple testing correction and showed good consistency with the weighted median estimator. Sensitivity analyses indicated that there was no heterogeneity or horizontal pleiotropy for MR estimations. Further multivariable MR suggested that the BMI showed the same direction and similar magnitude with that in the univariable MR analysis. There was little evidence to support the causal role of WHR on the risk of IPF in this study. Conclusion: Genetically determined BMI demonstrates a causal risk for IPF, which offers a novel insight into probing potential mechanisms. Meanwhile, these results also suggest that weight loss may be beneficial to IPF prevention.


Response of a pregnancy-dependent mouse mammary tumor to hormones.
A transplantable, pregnancy-dependent, mouse mammary tumor line (TPDMT-4) showed a pregnancy-dependent growth in DDD breeders. The tumors grew during pregnancy, regressed rapidly after parturition, and reached ascending peaks in subsequent pregnancies. Growth without regression occurred in animals with pituitary isografts (PI), but not after the hosts were ovariectomized. The effects of ovariectomy was negated by sc injections of both 17beta-estradiol (E) and progesterone (P), but single injections of E or P did not abolish the effect of the ovariectomy. The tumors also grew in virgins given sc implants of E and P or deoxycorticosterone acetate (DCA) pellets. Adrenalectomy had no influence on the tumor growth in PI-bearing animals, but DCA injections stimulated secretion production by both tumor cells and normal mammary cells. The hormonal conditions that produced tumor growth caused in the host mammary glands the full lobulo-alveolar development seen in mid- to late-pregnant animals. In the hosts without tumor growth, the mammary glands had small clusters of acini at most. The tumors were classified as type A morphologically. Our results suggest that the growth of TPDMT-4, like that of normal mammary glands, is controlled by prolactin, E, and P.


Surface modification affect the biodistribution and toxicity characteristics of iron oxide magnetic nanoparticles in rats.
Various surface modifications of iron oxide magnetic nanoparticles (IOMNs) can improve their stability and long-term retention time in vivo, expanding applications of biomedical fields. However, whether the long-term retention of IOMNs coated with different surface modifications has toxic effects remains poorly understood. Here, the toxicity of IOMNs modified with polyethylene glycol (PEG), bovine serum albumin (BSA), and carboxyl group (COOH), forming PEG-IOMNs, BSA-IOMNs, and COOH-IOMNs, respectively, were evaluated in the rats. The high accumulation of PEG-IOMNs and COOH-IOMNs both in the liver and lung, and the high accumulation BSA-IOMNs in blood after 24 day recovery were observed by elemental content analysis. Except individual neutrophils in the local portal area, PEG-IOMNs can also induce cytoplasmic vacuolisation in partial liver cells by histopathological examination. Furthermore, the results of RT-qPCR showed that PEG-IOMNs, BSA-IOMNs, and COOH-IOMNs can change the transcript levels of most genes related to iron homeostasis, mitochondria apoptosis, inflammatory response, but <2-fold alteration. COOH-IOMNs seemed to induce normal cell apoptosis more easily than BSA-IOMNs and PEG-IOMNs. In conclusion, BSA-IOMNs had longer-term retention time in blood. IOMNs coated with PEG and BSA can still induce side effects on the liver.


Simulated analysis of patient waiting time in an outpatient pharmacy.
The cost of various options for reducing patient waiting time in an outpatient pharmacy was studied through computer simulation. The time required to complete prescription filling tasks was recorded for a baseline of five pharmacy employees: technicians A, B, and C, a typist , and a pharmacist. A fixed factorial design of 12 configurations was used in which the number of pharmacy employees was varied (one, two, or three technician As; one or two typists ; and one or two technician Bs). Patient waiting time for each configuration was determined through computer simulation. Pharmacy employee salaries were used to calculate the relative cost of six of the configurations that were predicted to reduce waiting time to less than 10 minutes. Configurations with additional technician Bs or typists , or both, exhibited reductions in total waiting time of comparable magnitude. One of these configurations was identified as the least expensive per daily hours saved. Without disturbing the operation of the pharmacy, computer simulation was found useful in identifying the least expensive method of reducing patient waiting time in an outpatient pharmacy.


Factors influencing the publishing efforts of graduate students in nursing.
The purposes of this study were to identify factors influencing publication efforts of graduate students in nursing and determine the extent to which graduate students' scholarly activities contribute to the creation and dissemination of knowledge in nursing, as evidenced by publication in a professional journal. Authors of articles in Nursing Research were surveyed to assess their status as graduate students during the conceptualization, development, and publication of nursing research studies. The sample consisted of 633 authors of manuscripts published in Nursing Research from 1987 to 1991. The study design was descriptive. A survey questionnaire elicited data on graduate student status and factors that influenced the initiation and completion of the project. The data were analyzed using descriptive statistical techniques. The results of the study suggest that graduate students in nursing make important contributions to the advancement and dissemination of nursing knowledge. Factors that influence graduate students to engage in the process include academic requirements (e.g., thesis, dissertation, coursework), faculty involvement and support, and the ability to self-select the research topic.


Adenosine 3'5'-monophosphate: inhibition of complement-mediated cell lysis.
An increase in adenosine 3',5'-monophosphate (cyclic AMP) in rat mast cells, achieved by stimulating the cells with prostaglandin E(1), by preventing cyclic AMP breakdown with aminophylline, or by adding exogenous dibutyryl cyclic AMP, prevented complement-mediated cytolysis as assessed by both histamine release and vital dye exclusion. Dibutyryl cyclic AMP also suppressed water-induced osmotic lysis.


Heterocyclic Iminoquinones and Quinones from the National Cancer Institute (NCI, USA) COMPARE Analysis.
This review uses the National Cancer Institute (NCI) COMPARE program to establish an extensive list of heterocyclic iminoquinones and quinones with similarities in differential growth inhibition patterns across the 60-cell line panel of the NCI Developmental Therapeutics Program (DTP). Many natural products and synthetic analogues are revealed as potential NAD(P)H:quinone oxidoreductase 1 (NQO1) substrates, through correlations to dipyridoimidazo[5,4-f]benzimidazoleiminoquinone (DPIQ), and as potential thioredoxin reductase (TrxR) inhibitors, through correlations to benzo[1,2,4]triazin-7-ones and pleurotin. The strong correlation to NQO1 infers the enzyme has a major influence on the amount of the active compound with benzo[e]perimidines, phenoxazinones, benz[f]pyrido[1,2-a]indole-6,11-quinones, seriniquinones, kalasinamide, indolequinones, and furano[2,3-b]naphthoquinones, hypothesised as prodrugs. Compounds with very strong correlations to known TrxR inhibitors had inverse correlations to the expression of both reductase enzymes, NQO1 and TrxR, including naphtho[2,3-b][1,4]oxazepane-6,11-diones, benzo[a]carbazole-1,4-diones, pyranonaphthoquinones (including kalafungin, nanaomycin A, and analogues of griseusin A), and discorhabdin C. Quinoline-5,8-dione scaffolds based on streptonigrin and lavendamycin can correlate to either reductase. Inhibitors of TrxR are not necessarily (imino)quinones, e.g., parthenolides, while oxidising moieties are essential for correlations to NQO1, as with the mitosenes. Herein, an overview of synthetic methods and biological activity of each family of heterocyclic imino(quinone) is provided.