Suppression and expression as distinct emotion-regulation processes in daily interactions: Longitudinal and meta-analyses.
Emotional suppression and expression both occur frequently in daily social interactions, yet research examining these emotion regulation processes simultaneously in naturalistic contexts remains limited. Although theory and research tend to reflect an implicit assumption that suppression and expression represent opposite sides of the same construct, they are likely to occur independently and exert different influences on intrapersonal and interpersonal experiences. In 4 experience-sampling and longitudinal studies, we assessed the personal and interpersonal consequences of daily emotional suppression and expression within romantic and close relationships. Mixed-model analyses revealed that suppression and expression consistently predicted independent and distinct outcomes across the studies. When individuals suppressed their emotions, they experienced more intrapersonal costs such as greater depressed mood, greater fatigue, lower self-esteem, and lower life satisfaction. Interpersonally, they also felt less acceptance from others, more distancing by others, and less relationship satisfaction. Greater suppression in daily life also predicted increases in depressive symptoms and reductions in relationship satisfaction 3 months later. In contrast, when individuals were more emotionally expressive during daily interactions, they experienced interpersonal benefits such as greater acceptance from others, greater relatedness and relationship satisfaction, and less distancing by others. Greater emotional expression in daily life also predicted increases in self-esteem and relationship satisfaction across time. Meta-analyses of the 4 studies confirmed the reliability and significance of these relationships; |r's| = .12-.33. These studies demonstrate that suppression and expression are distinct processes used to manage emotions within social relationships and operate differently in shaping personal well-being and relationship functioning. (PsycINFO Database Record


Reticulocytes in sports medicine: an update.
Reticulocytes are young red blood cells which develop from erythroblasts and circulate in the bloodstream for about 1-4 days before maturing into erythrocytes. With the introduction of reticulocyte count in equations and statistical models for detecting suspected blood doping, its application to sports medicine has attracted growing interest in reticulocyte behavior during training and competition seasons in athletes and experimental blood doping treatment in healthy volunteers. An update on recent publications is therefore needed to improve the interpretation of reticulocyte analysis and its variability in sportsmen. Reticulocyte count constitutes a robust parameter during the preanalytical phase, but cell stability can be assured only if blood samples are kept at constantly cold temperatures (4 degrees C) and test results will differ depending on the blood analyzer system used. Marked intraindividual variability is the principal finding to be evaluated when exercise-induced changes are observed or illicit procedures suspected. Furthermore, reticulocyte variability is greater than that of other hematological parameters such as hemoglobin or hematocrit. Ideally, any variation should be interpreted against long-term time series for the individual athlete: values obtained from large athlete cohorts ought to be used only for extrapolating outliers that deserve further examination. Reticulocyte distribution in athletes is similar to that found in the general population, and a gender effect in some sports disciplines or selected athlete groups may be seen. Reticulocyte variability is strongly influenced by seasonal factors linked to training and competition schedules and by the type of sports discipline. Published experimental data have confirmed the high sensitivity of reticulocyte analysis in identifying abnormal bone marrow stimulation by either erythropoietin administration or blood withdrawal and reinfusion.


Cervical metastases in advanced ovarian malignancies.
Cervical metastases from ovarian malignancies are a rare event. In order to better define the incidence and pathogenesis of this phenomenon we retrospectively reviewed the charts and pathologic material from 171 Stage III ovarian malignancies. Nine patients (5.3%) were identified with cervical metastases and three patterns of spread to the cervix were recognized: 1) lymphatic permeation only; 2) para-cervical soft tissue extension and 3) direct stromal myometrial invasion. All of the patients with cervical metastases had high grade (Broder's grade III or IV) tumors and extensive abdominal disease at presentation. Although four patients had a positive or suspicious pap smear, none of these had cervical involvement. We conclude that ovarian metastases to the cervix are a rare event, occurring late in the course of the disease and arise from a variety of modes of spread.


Self-reported health behaviour change in adults: analysis of the Canadian Community Health Survey 4.1.
Knowledge of Canadians' experiences in making health behaviour changes (HBCs) in general, and among those at risk due to body mass index (BMI), would help inform health promotion / disease prevention programs. Selected self reported HBCs in the past 12 months by BMI category were examined in this secondary analysis of the Canadian Community Health Survey 4.1. These HBCs included increased sports/exercise, weight loss and improved eating habits. Barriers to HBC were also examined. Descriptive analyses and forward stepwise logistic regression were completed on data from respondents 18 years and older. Self-reported BMI was corrected by the method of Connor Gorber et al. (2008). Our final sample was n = 111 449. Overall, 58% of respondents had made an HBC, with increased sports/exercise as the most important HBC in 29% of the sample, followed by improved eating habits (10%) and weight loss (7%). Half (51%) experienced barriers to HBC; lack of will power was most commonly cited, followed by work and family responsibilities. Obese respondents reported HBC more frequently than normal-weight respondents (60% vs. 55%), but the prevalence of increased sports/ exercise and improved eating habits was similar across BMI categories. Regression models accounted for only 6%-10% of the total variance. That a majority of respondents had made at least one HBC bodes well for positively shifting population health. Additional work to further characterize the population, and to improve on population indicators, is needed to assess the impact of health promotion/disease prevention efforts. These findings provide important first population benchmarks for future work.


Impact of C-reactive protein on treatment of patients with cardiovascular disease.
The impact of C-reactive protein (CRP) on the treatment of patients with cardiovascular disease is described. CRP is a marker of coronary heart disease and other disease states. Its release from the liver activates endothelial dysfunction and contributes to atherothrombosis. In healthy persons, CRP was found to be an independent risk marker for cardiovascular disease when compared with low-density-lipoprotein (LDL) cholesterol. In 2003, the Centers for Disease Control and Prevention and the American Heart Association published a statement regarding CRP's use in clinical practice and public health. In a primary prevention study, statins were shown to reduce CRP, and patients with a low concentration of LDL cholesterol and high CRP may benefit from statin therapy. The results of a secondary prevention study confirmed that CRP reduction was not related to the lipid-lowering effects of the statins and that pravastatin reduced coronary events regardless of inflammation status designated by the CRP value. Another study demonstrated that intensive pharmacotherapy was more effective than moderate therapy in reducing CRP, but it found no difference in clinical outcomes among statin regimens once the goal CRP value was attained. In atheroma ultrasound studies, a reduced CRP level was related to reductions in atheroma volume regardless of the statin regimen used. The correct use of CRP in pharmacotherapeutic monitoring of statins has not been fully elucidated. Until more data regarding CRP and statin use are available, pharmacists must continue to focus on risk factors other than CRP, such as cholesterol levels, medical history, social history, and lifestyle characteristics, when making clinical decisions regarding statin therapy.


[Reduced ex vivo production of superoxide anion by polymorphonuclear leukocytes during therapy with omeprazole. A pharmacological effect?].
Among available drugs, omeprazole is the one that cures gastric acid secretion-related pathologies, including reflux oesophagitis which responds poorly to H2-receptor antagonists, most rapidly and efficaciously. This marked therapeutic action is thought to reflect the drug's capacity to adequately control parietal hydrochloric acid secretion. Our data suggest an omeprazole effect on human neutrophil function too. Neutrophils are more or less a constant, and often conspicuous anatomo-pathological component of the phlogistic processes associated with gastric acid secretion. A direct or indirect effect exerted by omeprazole on leukocyte function would be of great scientific-biological and therapeutic interest. Furthermore, it would contribute to marking the drug superior in terms of more rapid relief of the symptoms and range of therapeutic action.


Combustion-derived nanoparticles: a review of their toxicology following inhalation exposure.
This review considers the molecular toxicology of combustion-derived nanoparticles (CDNP) following inhalation exposure. CDNP originate from a number of sources and in this review we consider diesel soot, welding fume, carbon black and coal fly ash. A substantial literature demonstrates that these pose a hazard to the lungs through their potential to cause oxidative stress, inflammation and cancer; they also have the potential to redistribute to other organs following pulmonary deposition. These different CDNP show considerable heterogeneity in composition and solubility, meaning that oxidative stress may originate from different components depending on the particle under consideration. Key CDNP-associated properties of large surface area and the presence of metals and organics all have the potential to produce oxidative stress. CDNP may also exert genotoxic effects, depending on their composition. CDNP and their components also have the potential to translocate to the brain and also the blood, and thereby reach other targets such as the cardiovascular system, spleen and liver. CDNP therefore can be seen as a group of particulate toxins unified by a common mechanism of injury and properties of translocation which have the potential to mediate a range of adverse effects in the lungs and other organs and warrant further research.


Two-photon photochromism of diarylethene dimer derivatives.
Photochromic diarylethene dimer derivatives with large two-photon absorption (TPA) cross-sections have been designed and synthesized. The derivatives have a D-pi-D structure in which indole rings are used as donor units (D) and 1,4-bis(ethynyl)benzene or 1,4-bis(ethenyl)benzene as a pi-conjugated chain unit (pi). Compound 5 a, which has oxazole rings as one of the aryl groups, showed a TPA cross-section of 23 GM at 820 nm and exhibited efficient two-photon photochromic reactivity.


Seroprevalence rates and transmission of plague (Yersinia pestis) in mammalian carnivores.
Exposure to plague (Yersinia pestis) by flea-bites or consumption of infected rodents is common in mammalian carnivores in North America. Most carnivore species exhibit seroprevalence rates ranging from 3% to 100% in areas where plague occurs. Seroprevalence is highest in mustelids, intermediate in ursids, felids, and canids, and lowest in procyonids, probably reflecting variation in exposure rates as a function of dietary habits. Although conventional wisdom suggests that carnivores may only be important in plague ecology as vectors of infective fleas, animal-to-human (zoonotic) transmission suggests that mammalian carnivores can act as infectious hosts. Furthermore, a review of clinical investigations reveals that plague can be harvested from canid and felid hosts, and suggests the possibility of plague transmission between carnivores. Further study of plague transmission by carnivores in both wild and laboratory conditions is needed to understand the possible role of carnivores as wildlife reservoirs of plague.


Analysis of IgG with specificity for variant surface antigens expressed by placental Plasmodium falciparum isolates.
Pregnancy-associated malaria (PAM) is caused by Plasmodium falciparum-infected erythrocytes that can sequester in placental intervillous space by expressing particular variant surface antigens (VSA) that can mediate adhesion to chondroitin sulfate A (CSA) in vitro. IgG antibodies with specificity for the VSA expressed by these parasites (VSAPAM) are associated with protection from maternal anaemia, prematurity and low birth weight, which is the greatest risk factor for death in the first month of life. In this study, the development of anti-VSAPAM antibodies in a group of 151 women who presented to the maternity ward of Albert Schweitzer Hospital in Lambaréné, Gabon for delivery was analysed using flow cytometry assays. Plasma samples from placenta infected primiparous women were also investigated for their capacity to inhibit parasite binding to CSA in vitro. In the study cohort, primiparous as well as secundiparous women had the greatest risk of infection at delivery as well as during pregnancy. Primiparous women with infected placentas at delivery showed higher levels of VSAPAM-specific IgG compared to women who had no malaria infections at delivery. Placental isolates of Gabonese and Senegalese origin tested on plasma samples from Gabon showed parity dependency and gender specificity patterns. There was a significant correlation of plasma reactivity as measured by flow cytometry between different placental isolates. In the plasma of infected primiparous women, VSAPAM-specific IgG measured by flow cytometry could be correlated with anti-adhesion antibodies measured by the inhibition of CSA binding. Recognition of placental parasites shows a parity- and sex- dependent pattern, like that previously observed in laboratory strains selected to bind to CSA. Placental infections at delivery in primiparous women appear to be sufficient to induce functional antibodies which can both recognize the surface of the infected erythrocytes as well as block their binding to CSA. The correlation between serum reactivities of placental field isolates from different geographic locations and collected at different times is indicative of the conserved nature of the antigen(s) mediating PAM.


Influence of isoleucine upon quinomycin biosynthesis by Streptomyces sp. 732.
When dl-isoleucine was added to an ammonium nitrate-maltose medium during cultivation of Streptomyces sp. 732, quinomycin B formation was selectively enhanced (from 3 to 70% of the quinomycin mixture) and quinomycin C synthesis was inhibited completely. In addition, two new quinomycins, designated quinomycins D and E, were produced in the presence of isoleucine. These compounds were found to contain N-methylalloisoleucine. In experiments with isoleucine enantiomorphs, it was determined that the order of effectiveness for quinomycin B synthesis was dl-isoleucine > d-isoleucine > l-isoleucine. The extent to which quinomycin B synthesis is enhanced depends upon the concentration and the time of addition of isoleucine to the medium. The effect of dl-isoleucine was reduced to some extent by the addition of l-valine. It is conceivable that amino acids which are precursors of the N-methylamino acids in quinomycin can regulate quinomycin formation.


Immunosuppression and modulation in liver transplantation.
Recent advances in immunosuppressive drug regimens have changed the outcome after liver transplantation significantly in the last two decades. However, chronic rejection and long-term graft survival remains a major problem. Side effects like drug-induced nephrotoxicity, hypertension, osteoporosis, hyperlipidaemia and neuropathy of some immunosuppressive agents play an essential role in long-term allograft and patient survival. This review outlines the current treatment of short- and long-term immunosuppression in liver transplanted patients, it summarizes the treatment of acute and chronic rejection, describes the complications and side effects of immunosuppressive therapy and points out the current use of immunosuppressive therapy in living-related liver transplantation.


Activation of Steroidogenesis, Anti-Apoptotic Activity, and Proliferation in Porcine Granulosa Cells by RUNX1 Is Negatively Regulated by H3K27me3 Transcriptional Repression.
H3K27me3 is an epigenetic modification that results in the repression of gene transcription. The transcription factor RUNX1 (the runt-related transcription factor 1) influences granulosa cells' growth and ovulation. This research uses ELISA, flow cytometry, EDU, ChIP-PCR, WB and qPCR to investigate steroidogenesis, cell apoptosis, and the proliferation effect of RUNX1 in porcine granulosa cells (pGCs) as regulated by H3K27me3. Decreased H3K27me3 stimulates the expression of steroidogenesis-related genes, including CYP11A1, PTGS2, and STAR, as well as prostaglandin. H3K27me3 transcriptionally represses RUNX1 here, whereas RUNX1 acts as an activator of FSHR, CYP11A1, and CYP19A1, promoting the production of androgen, estrogen, and prostaglandin, as well as increasing anti-apoptotic and cell proliferation activity, but decreasing progesterone. Both the complementary recovery of the H3K27me3 antagonist with the siRUNX1 signal, and the H3K27me3 agonist with the RUNX1 signal to maintain RUNX1 lead to the activation of CYP19A1, ER1, HSD17β4, and STAR here. Androgen and prostaglandin are significantly repressed but progesterone is markedly increased with the antagonist and siRUNX1. Prostaglandin is significantly promoted with the agonist and RUNX1. Furthermore, H3K27me3-RUNX1 affects the anti-apoptotic activity and stimulation of proliferation in pGCs. The present work verifies the transcriptional suppression of RUNX1 by H3K27me3 during antral follicular development and maturation, which determines the levels of hormone synthesis and cell apoptosis and proliferation in the pGC microenvironment.


CCN1/CYR61-mediated meticulous patrolling by Ly6Clow monocytes fuels vascular inflammation.
Inflammation is characterized by the recruitment of leukocytes from the bloodstream. The rapid arrival of neutrophils is followed by a wave of inflammatory lymphocyte antigen 6 complex (Ly6C)-positive monocytes. In contrast Ly6C(low) monocytes survey the endothelium in the steady state, but their role in inflammation is still unclear. Here, using confocal intravital microscopy, we show that upon Toll-like receptor 7/8 (TLR7/8)-mediated inflammation of mesenteric veins, platelet activation drives the rapid mobilization of Ly6C(low) monocytes to the luminal side of the endothelium. After repeatedly interacting with platelets, Ly6C(low) monocytes commit to a meticulous patrolling of the endothelial wall and orchestrate the subsequent arrival and extravasation of neutrophils through the production of proinflammatory cytokines and chemokines. At a molecular level, we show that cysteine-rich protein 61 (CYR61)/CYR61 connective tissue growth factor nephroblastoma overexpressed 1 (CCN1) protein is released by activated platelets and enables the recruitment of Ly6C(low) monocytes upon vascular inflammation. In addition endothelium-bound CCN1 sustains the adequate patrolling of Ly6C(low) monocytes both in the steady state and under inflammatory conditions. Blocking CCN1 or platelets with specific antibodies impaired the early arrival of Ly6C(low) monocytes and abolished the recruitment of neutrophils. These results refine the leukocyte recruitment cascade model by introducing endothelium-bound CCN1 as an inflammation mediator and by demonstrating a role for platelets and patrolling Ly6C(low) monocytes in acute vascular inflammation.


TMS triflate-catalyzed cleavage of prenyl (3-methylbut-2-enyl) ester.
[reaction: see text] Prenyl (3-methylbut-2-enyl) ester is catalytically cleaved by TMS triflate affording carboxylic acid and isoprene in high yield under mild conditions with high chemoselectivity without causing epimerization of the neighboring chiral center.


Estimating the Impact of Laminar Flow on the Pattern and Rate of Decomposition in Aquatic Environments-Is There a Better Way of Modeling Decomposition?
Determining the Postmortem Submersion Interval (PMSI) is challenging for forensic anthropologists due to the variability of decomposition in aquatic environments. One possible cause of this variability that has received little attention in the literature is the impact of laminar flow. In order to determine whether flow affects the pattern or rate of decomposition, this study analyzed six rabbit carcasses submerged in two different sites: one with slow, laminar flow ("River Site") and one without flow ("Canal Site"). A pulley system was designed in order to periodically bring the carcasses out of the water for sampling, with the pattern of decomposition monitored using visual descriptions of the decomposition process and the rate monitored using the Heaton et al. 2010 method of scoring aquatic decomposition in conjunction with accumulated degree days (ADD). The rate of decomposition was found to be significantly different between the two sites (F(1, 126) = 89.569, p < 0.01). In addition, decomposition was observed to occur in four distinct stages, which were modeled as a series of curves, and a Staged Decomposition Model was created as the possible basis for an improved predictor of PMSI versus the current loglinear approach. While the traditional loglinear approach appears to give a good approximation to the Staged Decomposition Models in environments with laminar flow, this research suggests that it may be less accurate for nonflowing sites.


Characteristics of women with and without breast augmentation.
To compare selected characteristics of women with and without augmentation mammaplasty to identify differences between these 2 groups of women. White women identified as controls in previously conducted population-based, case-control studies formed the study population for the present cross-sectional analysis (N=3570). Interview information on selected characteristics was compared between women who had received augmentation mammaplasty (n=80) and other women (n=3490) using the prevalence odds ratio (pOR) as the measure of association. Women with breast implants were more likely to drink a greater average number of alcoholic drinks per week (for > or =7 drinks vs 0 drinks: pOR=2.9, 95% confidence interval [CI]=1.5-5.5), be younger at first pregnancy (for age <20 years vs age 20-29 years: pOR=1.6, 95% CI=1.0-2.7), be younger at first birth (for age <20 years vs age 20-29 years: pOR=1.9, 95% C1=1.1-3.3), have a history of terminated pregnancies (for > or =1 termination vs 0 terminations: pOR=2.0, 95% CI=1.2-3.4), have ever used oral contraceptives (pOR=2.2, 95% CI=1.0-4.7), have ever used hair dyes (pOR=4.5, 95% CI=1.3-15.4), and have had a greater lifetime number of sexual partners (for > or =14 partners vs < or =4 partners: pOR=8.9, 95% CI=3.1-25.5) than other women. A history of smoking, lactation, high blood pressure, or thyroid disorders, as well as the number of pregnancies, full-term births, or miscarriages, differed little between women with and without implants. Women with breast augmentation were much less likely to be heavy than other women (for > or =74 kg vs <56 kg: pOR=0.1, 95% CI=0.03-0.3). The differences we found between women with and without breast implants suggest that consideration and evaluation of confounding factors in future studies will help to clarify some of the long-term health consequences of having breast implants.


The Effects of Cinnamomum Cassia on Blood Glucose Values are Greater than those of Dietary Changes Alone.
Eighteen type II diabetics (9 women and 9 men) participated in a 12-week trial that consisted of 2 parts, a 3-week control phase followed by a 9-week experimental phase where half of the subjects received 1000 mg of Cinnamomum cassia while the other half received 1000 mg of a placebo pill. All of the subjects that were in the cinnamon group had a statistically significant decrease in their blood sugar levels with a P-value of 3.915 × 10(-10). The subjects in the cinnamon group had an average overall decrease in their blood sugar levels of about 30 mg/dL, which is comparable to oral medications available for diabetes. All subjects were educated on appropriate diabetic diets and maintained that diet for the entire 12 week study. Greater decreases in blood glucose values were observed in patients using the cinnamon compared to those using the dietary changes alone.


Ethical implications of standardization of ICU care with computerized protocols.
Ethical issues related to the use of computerized protocols to control mechanical ventilation of patients with Acute Respiratory Distress Syndrome (ARDS) are identical to the ethical issues surrounding the use of any therapy or intervention. Four ethical principles must be considered: nonmaleficence, beneficence, autonomy, and distributed justice. The major ethical challenges to computerized protocol use as a specific application of clinical decision support tools are found within the principles of nonmaleficence and of beneficence. The absence of credible outcome data on which ARDS patient survival probabilities with different therapeutic options could be based is a constraint common to most ICU clinical decision making. Clinicians are thus deprived of the knowledge necessary to define benefit and are limited to beneficent intention in clinical decisions. Computerized protocol controlled decision making for the clinical management of mechanical ventilation for ARDS patients is ethically defensible. It is as well supported as most ICU therapy options.


Reversibility of unawareness of hypoglycemia in patients with insulinomas.
A lack of appropriate autonomic warning symptoms before the development of neuroglycopenia occurs frequently in patients with diabetes mellitus. The pathogenesis of this phenomenon is unclear, but it is associated with intensive insulin therapy, prolonged duration of diabetes, frequent episodes of hypoglycemia, and impaired glucose counterregulation. Recently, it has been proposed that repeated episodes of hypoglycemia may themselves induce the phenomenon. To test this hypothesis and to determine whether the phenomenon is reversible, we assessed autonomic and neuroglycopenic symptoms, counterregulatory hormonal responses, and cognitive function during stepped hypoglycemic-clamp studies in 6 patients with insulinomas before and approximately six months after curative surgery and in 14 normal subjects matched for age, weight, and sex. Before surgery, the patients with insulinomas had lower scores than the normal subjects for autonomic symptoms (mean [+/- SD], 3.5 +/- 0.8 vs. 9.6 +/- 4.5) and neuroglycopenic symptoms (2.8 +/- 1.5 vs. 8.9 +/- 5.3). The patients also had impaired counterregulatory hormonal responses (their plasma epinephrine, norepinephrine, glucagon, growth hormone, and cortisol responses before surgery were 187 +/- 227 pg per milliliter [1.03 +/- 1.25 nmol per liter], 223 +/- 85 pg per milliliter [1.32 +/- 0.50 nmol per liter], 86 +/- 21 ng per liter, 7.4 +/- 5.2 micrograms per liter, and 12.1 +/- 1.5 micrograms per deciliter [334 +/- 41 nmol per liter], respectively, as compared with 842 +/- 439 pg per milliliter [4.63 +/- 2.41 nmol per liter], 519 +/- 150 pg per milliliter [3.07 +/- 0.89 nmol per liter], 201 +/- 58 ng per liter, 25.3 +/- 13.7 micrograms per liter, and 26.3 +/- 1.2 micrograms per deciliter [726 +/- 33 nmol per liter] in the normal subjects) and less deterioration in cognitive function than the normal subjects during hypoglycemia (sum of z scores for seven tests of cognitive function, 1.7 +/- 1.9 vs. 8.9 +/- 3.5) (P < 0.02 for all comparisons). Surgical cure reversed all these abnormalities (P not significant for all comparisons with the normal subjects). Hypoglycemia itself can induce unawareness of the autonomic and neuroglycopenic symptoms of hypoglycemia and decrease the counterregulatory hormonal responses to hypoglycemia.


Molecular analysis of the SMN1 and NAIP genes in 60 Tunisian spinal muscular atrophy patients.
In this study we examined the deletion of SMN and NAIP genes in 60 Tunisian families. There were 35 patients with type I SMA. 18 with type II SMA. 6 with type III SMA and I with type IV SMA. The age of onset was before 6 months for type I, between 6 months and 2 years for type II, between 2 years and 17 years for type III and 30 years for type IV. Exon 7 of SMNI gene was homozygously deleted in 95% (57/60) of SMA patients. There was a higher frequency of homozygous absence of SMN1 in type I and type II (100% and 94% respectively) than in type III (66,7%). SMN1 exon 8 was undetectable in 88% (53/60) of patients. The case type II patient with homozygous deletion of SMNI exon 7 and not exon 8 was tested for the presence of a hybrid SMN gene. This patient showed in the second PCR a SMN1 exon 8 product by restriction site assay indicating that a gene conversion event had occurred. All parents' individuals retained one copy of their SMN1 gene. Exon 5 of NAIP gene was homozygously deleted in 58% (35/60) of patients (77% in type I (27/35), 27,7% in type II (5/18), 50% (3/6) in type III. No patient had a deletion in NAIP gene without a deletion in the SMN1 gene. Homozygous deletion of NAIP exon 5 was detected in 1 parent. Our results show that the incidence of NAIP deletion is higher in the more severe SMA cases.


Relationships of maternal and paternal anthropometry with neonatal body size, proportions and adiposity in an Australian cohort.
The patterns of association between maternal or paternal and neonatal phenotype may offer insight into how neonatal characteristics are shaped by evolutionary processes, such as conflicting parental interests in fetal investment and obstetric constraints. Paternal interests are theoretically served by maximizing fetal growth, and maternal interests by managing investment in current and future offspring, but whether paternal and maternal influences act on different components of overall size is unknown. We tested whether parents' prepregnancy height and body mass index (BMI) were related to neonatal anthropometry (birthweight, head circumference, absolute and proportional limb segment and trunk lengths, subcutaneous fat) among 1,041 Australian neonates using stepwise linear regression. Maternal and paternal height and maternal BMI were associated with birthweight. Paternal height related to offspring forearm and lower leg lengths, maternal height and BMI to neonatal head circumference, and maternal BMI to offspring adiposity. Principal components analysis identified three components of variability reflecting neonatal "head and trunk skeletal size," "adiposity," and "limb lengths." Regression analyses of the component scores supported the associations of head and trunk size or adiposity with maternal anthropometry, and limb lengths with paternal anthropometry. Our results suggest that while neonatal fatness reflects environmental conditions (maternal physiology), head circumference and limb and trunk lengths show differing associations with parental anthropometry. These patterns may reflect genetics, parental imprinting and environmental influences in a manner consistent with parental conflicts of interest. Paternal height may relate to neonatal limb length as a means of increasing fetal growth without exacerbating the risk of obstetric complications.


Experts Collaboration Learning for Continual Multi-Modal Reasoning.
Multi-modal reasoning, which aims to capture logical and causal structures in visual content and associate them with cues from other modality inputs (e.g., texts) to perform various types of reasoning, is an important research topic in artificial intelligence (AI). Existing works for multi-modal reasoning mainly exploit offline learning, where the training samples of all types of reasoning tasks are assumed to be available at once. Here we focus on continual learning for multi-modal reasoning (i.e., continual multi-modal reasoning), where the model is required to continuously learn to solve novel types of multi-modal reasoning tasks in a lifelong fashion. Continual multi-modal reasoning is challenging since the model needs to be able to effectively learn various types of new reasoning tasks, meanwhile avoiding forgetting. Here we propose a novel brain-inspired exp erts [Formula: see text]llaboration network (Expo), which incorporates multiple learning blocks (experts). When encountering a new task, our network dynamically assembles and updates a set of task-specific experts that are most relevant to learning the current task, by either utilizing learned experts or exploring new experts. This thus enables effective learning of new tasks, and meanwhile consolidates previously learned reasoning skills. Moreover, to automatically find optimal task-specific experts, an effective experts selection strategy is designed. Extensive experiments demonstrate the efficacy of our model for continual multi-modal reasoning.


Acute liver failure in adults: an evidence-based management protocol for clinicians.
With the goal of providing guidance on the provision of optimal intensive care to adult patients with acute liver failure (ALF), this paper defines ALF and describes a protocol for appropriately diagnosing this relatively rare clinical entity and ascertaining its etiology, where possible. This paper also identifies the few known therapies that may be effective for specific causes of ALF and provides a comprehensive approach for anticipating, identifying, and managing complications. Finally, one of the more important aspects of care for patients with ALF is the determination of prognosis and, specifically, the need for liver transplantation. Prognostic tools are provided to help guide the clinician in this critical decision process. Management of patients with ALF is complex and challenging, even in centers where staff members have high levels of expertise and substantial experience. This evidence-based protocol may, therefore, assist in the delivery of optimal care to this critically ill patient population and may substantially increase the likelihood of positive outcomes.


Effect of the physical activity program on the treatment of resistant hypertension in primary care.
Regular physical activity is widely recommended for patients with arterial hypertension as an essential component of lifestyle modification. Much less is known about the impact of physical exercise on the management of treatment of resistant hypertension (RH). The aim was to assess the effect of physical activity program intensified by mobile phone text reminders on blood pressure control in subjects with RH managed in the primary care. In total, 53 patients with primary hypertension were qualified, including 27 who met the criteria for RH and 26 with well-controlled hypertension (WCH). Ambulatory 24-h blood pressure was monitored and body composition evaluated with bioimpedance and habitual physical activity profile was determined continuously over 72 h with accelerometer. All measurements were performed at baseline and after three and six months. The patients were asked to modify their lifestyle according to American Heart Association Guidelines that included regular aerobic physical activity tailored to individual needs.FindingsPhysical activity in RH increased significantly after six months compared with control subjects (P=0.001). Office systolic blood pressure (SBP) and diastolic blood pressure (DBP) in the RH group decreased significantly after three months but after six months only office DBP remained significantly lower. After three months 24-h SBP decreased by 3.1±11 mmHg (P=0.08) and DBP by 2.0±6 mmHg (P=0.17) in RH, whereas in WCH respective changes were +1.2±10 and -0.3±6 mmHg. After six months 24-h BP changes were similar. Individualized structured physical activity program increases physical activity in the treatment of resistant hypertensives in primary care but the effect on 24-h blood pressure is only transient.


Patient-oriented performance measures of diagnostic tests. 3. U-Factor.
When a clinician is faced with the problem of deciding whether to order a specific diagnostic test, the ideal information would be the utility of the "perform test" branch of the decision tree versus the utility of the "do not perform test" branch. This difference in utility is termed the Expected Utility of the Test ( EUT ). We propose a new performance measure of a test called the U-Factor (UF) which is related to EUT by a simple formula. UF depends on the prior probability of disease and on the decision thresholds at which one would be indifferent between any two immediately subsequent management options, and can be presented as a two-dimensional nomogram. UF is useful as a computational aid in a formal decision analysis, and may be useful as an informal measure of the value of a diagnostic test when a formal analysis is not feasible.


[The pathology and genetic background of myeloma].
Plasma cell myeloma is a heterogeneous hematologic malignancy of plasma cells, occurring dominantly in the elderly population. It is now accepted that all myeloma cases are preceded by a clinically silent expansion of clonal plasma cells, known as monoclonal gammopathy of undetermined significance. Our knowledge on the genetics of myeloma is still limited and lags behind other well-characterized hematological malignancies. One of the reasons of this fact is the difficulty to induce metaphases within the malignant plasma cell population. With the development of new molecular techniques (microarrays and next generation sequencing), our understanding of the pathogenesis and progression of myeloma has been highly improved in the past years. This review offers an insight into this newly gained knowledge.


Mutational activation of the K-ras oncogene. A possible pathogenetic factor in adenocarcinoma of the lung.
To define the role of cellular oncogenes in human cancers, we studied the prevalence of mutational activation of ras oncogenes in untreated non-small-cell lung cancer. Genomic DNA was extracted from 39 tumor specimens obtained by thoracotomy and was examined for activating point mutations in codons 12, 13, and 61 of the H-ras, K-ras, and N-ras genes. A novel, highly sensitive assay based on oligonucleotide hybridization following an in vitro amplification step was employed. The K-ras gene was found to be activated by point mutations in codon 12 in 5 of 10 adenocarcinomas. Two of these tumors were less than 2 cm in size and had not metastasized. No ras gene mutations were observed in 15 squamous-cell carcinomas, 10 large-cell carcinomas, 1 carcinoid, 2 metastatic adenocarcinomas from primary tumors outside the lung, and 1 small-cell carcinoma. An approximately 20-fold amplification of the unmutated K-ras gene was observed in a tumor that proved to be a solitary lung metastasis of a rectal carcinoma. We conclude that mutational K-ras activation may be an important early event in the pathogenesis of adenocarcinoma of the lung but that amplification of ras genes or mutational activation of H-ras or N-ras does not play a major part in non-small-cell lung cancer.


Rinsability of orthophthalaldehyde from endoscopes.
Orthophthalaldehyde high level disinfectants are contraindicated for use with urological instruments such as cystoscopes due to anaphylaxis-like allergic reactions during surveillance of bladder cancer patients. Allergic reactions and mucosal injuries have also been reported following colonoscopy, laryngoscopy, and transesophageal echocardiography with devices disinfected using orthophthalaldehyde. Possibly these endoscopes were not adequately rinsed after disinfection by orthophthalaldehyde. We examined this possibility by means of a zone-of-inhibition test, and also a test to extract residues of orthophthalaldehyde with acetonitrile, from sections of endoscope insertion tube materials, to measure the presence of alkaline glutaraldehyde, or glutaraldehyde plus 20% w/w isopropanol, or ortho-phthalaldehyde that remained on the endoscope materials after exposure to these disinfectants followed by a series of rinses in water, or by aeration overnight. Zones of any size indicated the disinfectant had not been rinsed away from the endoscope material. There were no zones of inhibition surrounding endoscope materials soaked in glutaraldehyde or glutaraldehyde plus isopropanol after three serial water rinses according to manufacturers' rinsing directions. The endoscope material soaked in orthophthalaldehyde produced zones of inhibition even after fifteen serial rinses with water. Orthophthalaldehyde was extracted from the rinsed endoscope material by acetonitrile. These data, and other information, indicate that the high level disinfectant orthophthalaldehyde, also known as 1,2-benzene dialdehyde, cannot be rinsed away from flexible endoscope material with any practical number of rinses with water, or by drying overnight.


Evidence for a peripheral component in the sympatholytic effect of clonidine in rats.
In an attempt to assess separately the peripheral and central effects of clonidine on cardiovascular parameters and plasma catecholamine levels, the selective alpha 2-adrenoceptor antagonist idazoxan (RX 781094) was given either intravenously (i.v.) or intracerebroventricularly (i.c.v.) to anaesthetized rats before administration of intravenous clonidine. Plasma noradrenaline and plasma growth hormone concentrations were used as indices of peripheral sympathetic nervous activity and central alpha-adrenoceptor stimulation, respectively. Peripheral and central administration of idazoxan antagonized the cardiovascular responses to i.v. clonidine, 5 micrograms kg-1. However, idazoxan was more effective against the hypotension than the bradycardia induced by clonidine. Idazoxan 300 micrograms kg-1 i.v. and 50 micrograms i.c.v. prevented clonidine-induced falls in plasma noradrenaline and adrenaline. The results suggest that 50 micrograms idazoxan i.c.v. caused some blockade of peripheral as well as central alpha 2-adrenoceptors. Idazoxan, 10 micrograms i.c.v., caused similar inhibition of the hypotensive response to clonidine as 300 micrograms kg-1 i.v. and 50 micrograms i.c.v. but did not significantly inhibit the clonidine-induced fall in plasma noradrenaline concentration. Animals pretreated with i.v. or i.c.v. idazoxan had significantly lower levels of plasma growth hormone than vehicle-treated rats. Idazoxan 10 micrograms and 50 micrograms i.c.v. suppressed growth hormone secretion to the same extent. These results suggest that stimulation of peripheral, prejunctional alpha 2-adrenoceptors in anaesthetized rats may contribute to the fall in plasma catecholamines produced by i.v. clonidine, and confirm that the hypotensive effect is centrally mediated.


Genome shuffling of Zygosaccharomyces rouxii to accelerate and enhance the flavour formation of soy sauce.
The purpose of this study was to achieve rapid improvement of the flavour of soy sauce by increasing the salt stress resistance of Zygosaccharomyces rouxii. Here, we describe genome shuffling to improve the salt tolerance of Z. rouxii while simultaneously enhancing and accelerating flavour formation of soy sauce. A mutant, S3-2, with a stronger resistance to salt, was selected after three rounds of genome shuffling. S3-2 not only grew well in peptone/yeast extract/dextrose medium containing a high salt content with wide range of pH, but also exhibited stronger stress resistance to potassium chloride and lithium chloride. In high-salt liquid fermentation, S3-2 obviously accelerated flavour formation of soy sauce, thus decreasing the total time required for development of the aroma. In addition, S3-2 gave high amino acid nitrogen and good flavour. In particular, the ethyl acetate content was 2.38 times that in the control. S3-2 distinctly improved the formation of 4-hydroxy-2 (or 5) -ethyl-5 (or 2) -methyl-3 (2H) -furanone by up to 75%. Another important flavour component, 4-ethylguaiacol, was also detected. Genome shuffling was successfully used to achieve significant improvements in flavour formation. The selected strain improved the main flavour components and amino acid nitrogen, thereby enhancing the quality of soy sauce.


Usefulness of the endotoxin activity assay as a biomarker to assess the severity of endotoxemia in critically ill patients.
The aim of this study was to investigate the prevalence of endotoxemia in critically ill Japanese patients using the endotoxin activity assay, a newly developed rapid assay of endotoxin. The endotoxin levels (EA levels) in the blood of 314 patients admitted to our university hospital's intensive care unit (ICU) were measured within 24 h of admission, and its correlation with disease severity and outcome examined. In addition, the EA levels in 61 samples from healthy volunteers were measured. EA level was 0.39 ± 0.25 (mean ± SD) in patients admitted to the ICU and 0.10 ± 0.09 in healthy controls. There was less overlap of EA level distribution between patients and controls compared with previous reports measuring EA level in mainly Caucasian populations. Our patients' EA levels were significantly correlated with disease severity criteria and 28-d mortality. When EA and procalcitonin levels were used concomitantly, disease severity could be assessed more precisely than when either marker was used alone. These results suggest that EA level is a useful marker for disease severity assessment and outcome prediction in critically ill patients.


High-resolution genotyping of Lymphogranuloma Venereum (LGV) strains of Chlamydia trachomatis in London using multi-locus VNTR analysis-ompA genotyping (MLVA-ompA).
Lymphogranuloma venereum (LGV) is caused by Chlamydia trachomatis strains with ompA genotypes L1 to L3. An LGV epidemic associated with the L2b genotype has emerged in the past few decades amongst men who have sex with men (MSM). C. trachomatis genotypes can be discriminated by outer membrane protein A gene (ompA) sequencing, however this method has limited resolution. This study employed a high-resolution genotyping method, namely, multi-locus tandem repeat (VNTR) analysis with ompA sequencing (MLVA-ompA), to assess the distribution of LGV MLVA-ompA genotypes amongst individuals attending genitourinary medicine (GUM) clinics in London. Clinical specimens were collected from individuals attending eight London-based GUM clinics. Specimens that tested positive for C. trachomatis by commercial nucleic acid amplification test (NAAT) were confirmed as LGV by pmpH real-time PCR. LGV-positive DNA extracts were subsequently genotyped using MLVA-ompA. Two hundred and thirty DNA extracts were confirmed as LGV, and 162 (70%) yielded complete MLVA-ompA genotypes. Six LGV MLVA-ompA genotypes were identified: 1.9.2b-L2, 1.9.3b-L2b, 1.9.2b-L2b, 1.9.2b-L2b/D, 1.4a.2b-L2b, and 5.9.2b-L1. The following LGV ompA genotypes were identified (in descending order of abundance): L2, L2b, L2b/D, and L1. Eight ompA sequences with the hybrid L2b/D profile were detected. The hybrid sequence was identical to the ompA of a recombinant L2b/D strain detected in Portugal in 2017. The L2 ompA genotype was found to predominate in the London study population. The study detected an unusual hybrid L2b/D ompA profile that was previously reported in Portugal. We recommend further monitoring and surveillance of LGV strains within the UK population.


Reevaluation of human alpha interferons against herpesvirus infection of the rabbit eye.
Because of reported differences in potency, recombinant DNA-derived human alpha interferons (IFNs) were reevaluated for use against acute Herpes Simplex Virus type 1 (HSV-1) infection of the rabbit eye. The IFNs used topically were IFN-alpha 2, (IFN-alpha 2) and a consensus of known human IFN-alpha s, designated IFN-alpha Con1. Prophylactic treatment with IFN-alpha Con1 at 1 or 15 X 10(6) U/eye/day beginning 48 hours before HSV-1 inoculation and therapeutic treatment with 5 or 15 X 10(6) U/eye/day beginning 4 hours after inoculation with either IFN-alpha Con1 or IFN-alpha 2 appeared to prevent or significantly reduce the development of corneal epithelial involvement. The effects were dose dependent with no evidence for decreased activity at the higher dose. The duration of HSV-1 shedding into tear film was not significantly reduced.


Recent Progress in the Preparation, Assembly, Transformation, and Applications of Layer-Structured Nanodisks beyond Graphene.
Layered nanodisks with confined thickness and lateral size have been emerging as a unique type of two-dimensional (2D) nanomaterials in recent years. Inheriting some properties of 2D nanosheets and meanwhile possessing the size-confinement effect, these layered nanodisks exhibit unique optical, electronic, and chemical properties, which endow them with great promise in a wide range of applications. Here, the recent progress of layered nanodisks is introduced. The synthetic strategies, assembly, structural/compositional transformation, and applications of layered nanodisks are systematically described and discussed, with emphasis on their new appealing structures and functions. Finally, some perspectives and future research directions of this promising field are given.


Neuropathy in a rat model of mild diabetes induced by multiple low doses of streptozotocin: effects of the antioxidant stobadine in comparison with a high-dose alpha-lipoic acid treatment.
Hyperglycaemia-induced oxidative stress makes an important contribution to the aetiology of diabetic neuropathy. The aim of our study was to evaluate the effect of the antioxidant stobadine (STB) in comparison with a treatment by a high-dose of alpha-lipoic acid (ALA), on the neurological consequences of chronic hyperglycaemia in an animal model of diabetes in Wistar rats (16 weeks old), made diabetic by streptozotocin (STZ 3 x 20 mg i.v.). Neuropathy was evaluated electrophysiologically by measuring motor nerve conduction velocity (NCV) in the 4th and 8th week in vivo and motor NCV and resistance to ischaemic conduction failure (RICF) of the sciatic nerve in the 10th week of the experiment in vitro. The therapy with ALA (100 mg/kg i.p., 5 times a week) and STB (25 mg/kg i.p., 5 times a week) had a significant effect on NCV in vivo in the 8th week of the experiment and no effect in the 10th week in vitro. The RICF elevated in diabetic animals was significantly modified by ALA. The effect of the antioxidant STB on NCV was comparable with that of ALA, while RICF was affected only by ALA. We conclude that treatment with appropriate antioxidants might partially prevent nerve dysfunction in diabetic rats.


Hemangiomas of the internal auditory canal.
Three patients who presented with symptoms and signs of acoustic tumors are described: one of them had an arteriovenous malformation and the other two had cavernous hemangiomas. The common feature in all these patients was the presence of marked facial weakness with or without fasciculations and a complete loss of hearing in the presence of a small tumor. The cerebrospinal fluid protein was normal in these patients. Polytomography and Pantopaque cisternograms were used to make the diagnosis. Since these lesions are circumscribed, they are suitable for removal using microneurosurgical techniques.


Self-assembly of supra-amphiphiles based on dual charge-transfer interactions: from nanosheets to nanofibers.
With the elaborate engineering of supra-amphiphiles based on dual charge-transfer interactions, the rational design and programmable transformation of well-defined 1D and 2D nanostructures have been demonstrated. First, H-shaped supra-amphiphiles are successfully obtained on the basis of the directional charge-transfer interactions of naphthalene diimide and naphthalene, which self-assemble in water to form 2D nanosheets. Second, by complexation of the H-shaped supra-amphiphiles with pyrene derivatives, the 2D nanosheets transform into ultralong 1D nanofibers. Therefore, this line of research represents a successful example of supramolecular engineering and has enriched its realm.


Globin digest: no evidence for a weight loss mechanism.
This study was designed to document the mechanism through which globin digest, a dietary herbal supplement, might cause weight loss by exploring possible fat malabsorption, calorie malabsorption, energy expenditure, and fat oxidation. Six healthy subjects were placed on an outpatient diet for 14 days and given a meal containing 40.9 g of fat on days 5 and 11, and stools were collected for 72 hours after each meal for analysis of fecal fat content. Four grams of globin digest was given with one meal and placebo with the other. In another separate study, six subjects were placed on a 100-g fat, weight-maintaining diet for 14 days. All food was prepared by the Pennington Center (Baton Rouge, LA) metabolic kitchen. Globin digest (2 g) or placebo was given with each of three meals per day, and stool was collected for calorie determinations during the last 72 hours of each week. Subjects received globin digest during one of the 2 weeks and placebo during the other. Resting metabolic rate and respiratory quotient were measured on the last day of each 1-week period. There was no increase in 72-hour fecal fat or fecal calories by bomb calorimetry during either of the studies. There was no difference in the respiratory quotient. Globin digest did result in an increase in resting metabolic rate. However, this increase was not statistically significant. Globin digest, if effective, does not cause weight loss or fat loss through fat malabsorption or a relative increase in fat oxidation. Future studies are needed to document the efficacy of globin digest for weight loss in humans before further mechanistic investigation is attempted.


Isolation of Acanthamoeba species in surface waters of Gilan province-north of Iran.
We analyzed water samples to determine the prevalence of free-living Acanthamoeba in water sources from Gilan, greater area, Iran. A total of 27 surface water samples were collected from environmental sources, including natural (rivers, lakes, springs, and lagoon) and freshwater source. The samples were filtrated and transferred to non-nutrient agar plates seeded with Escherichia coli and incubated for 2 to 7 days at 30°C or 42°C. The plates were examined by microscopy to morphologically identify Acanthamoeba species. Following DNA extraction, PCR was used to confirm the microscopically identification. A total of 19 out of 27 samples (70.3%) were positive for Acanthamoeba species based on the morphological criteria, and 14 (73.7%) were confirmed by PCR method. The high frequency of Acanthamoeba spp. in different environmental water sources of Gilan is an alert for the public health related to water sources in Iran.


Changes in social participation and life-space mobility in newly enrolled home-based rehabilitation users over 6 months.
[Purpose] This study aimed to examine whether we were able to measure changes in social participation and life-space mobility of newly enrolled home-based rehabilitation (HR) users by using the activities and participation components of the International Classification of Functioning, Disability and Health (ICF) and Life-Space Assessment (LSA) over a 6-months period. [Participants and Methods] We enrolled 47 HR users who had suffered from a stroke or other condition within the previous year. A 6-month prospective cohort study was conducted. The performance qualifiers "d6 domestic life" and "d9 community, social and civic life" in the activities and participation components of the ICF and LSA were used. [Results] We observed significant improvements in the performance qualifier "d9 community, social and civic life" of the ICF over 3 months, and the LSA over a 6-months period. We also identified significant improvements in "d910 community life" and "d920 recreation and leisure" of the ICF. The LSA results showed that HR users had more frequent mobility within the neighborhood. [Conclusion] This study showed that newly enrolled HR users improved their social activities in the community, recreational activities, and life-space mobility over a 6-months period. These were measured using performance qualifiers from the ICF and LSA.


Paradoxical effects of cigarette smoke and COPD on SARS-CoV-2 infection and disease.
How cigarette smoke (CS) and chronic obstructive pulmonary disease (COPD) affect severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infection and severity is controversial. We investigated the effects of COPD and CS on the expression of SARS-CoV-2 entry receptor ACE2 in vivo in COPD patients and controls and in CS-exposed mice, and the effects of CS on SARS-CoV-2 infection in human bronchial epithelial cells in vitro. We quantified: (1) pulmonary ACE2 protein levels by immunostaining and ELISA, and both ACE2 and/or TMPRSS2 mRNA levels by RT-qPCR in two independent human cohorts; and (2) pulmonary ACE2 protein levels by immunostaining and ELISA in C57BL/6 WT mice exposed to air or CS for up to 6 months. The effects of CS exposure on SARS-CoV-2 infection were evaluated after in vitro infection of Calu-3 cells and differentiated human bronchial epithelial cells (HBECs), respectively. ACE2 protein and mRNA levels were decreased in peripheral airways from COPD patients versus controls but similar in central airways. Mice exposed to CS had decreased ACE2 protein levels in their bronchial and alveolar epithelia versus air-exposed mice. CS treatment decreased viral replication in Calu-3 cells, as determined by immunofluorescence staining for replicative double-stranded RNA (dsRNA) and western blot for viral N protein. Acute CS exposure decreased in vitro SARS-CoV-2 replication in HBECs, as determined by plaque assay and RT-qPCR. ACE2 levels were decreased in both bronchial and alveolar epithelial cells from COPD patients versus controls, and from CS-exposed versus air-exposed mice. CS-pre-exposure potently inhibited SARS-CoV-2 replication in vitro. These findings urge to investigate further the controversial effects of CS and COPD on SARS-CoV-2 infection.


Renin-angiotensin System Blockade Therapy for Early Renal Involvement in MYH9-related Disease with an E1841K Mutation.
MYH9-related disease is a rare genetic disorder characterized by macrothrombocytopenia, with frequent proteinuric nephropathy, hearing loss, and cataract. Although proteinuric nephropathy usually progresses to renal failure, there is no established treatment for the nephropathy. We herein describe the case of a 19-year-old man carrying an E1841K MYH9 mutation, who developed persistent proteinuria. The patient was diagnosed with early-stage MYH9-related nephropathy based on the histological examination of a kidney biopsy specimen. The patient was treated with enalapril, which significantly reduced the proteinuria with no decline in his renal function. The early administration of renin-angiotensin system blockade therapy may have beneficial effects on MYH9-related nephropathy in patients with E1841K mutations. We also briefly summarize previously published cases of MYH9-related nephropathy treated with renin-angiotensin system (RAS) blockade therapy.


Hepatic vein reconstruction for resection of hepatic tumors.
Involvement of the hepatic veins requiring reconstruction has traditionally been considered a contraindication to resection for advanced tumors of the liver because the surgical risks are high and the long-term prognosis poor. Recent advances in liver surgery gleaned from split and live donor liver transplantation that necessitate hepatic vein reconstruction can be applied to hepatic resection in some cases. Sixteen patients who underwent hepatic resection requiring hepatic vein reconstruction from 1996-2001 were reviewed. The mean age was 43 years (range 2-61). Nine patients were resected for hepatocellular carcinoma (HCC), five patients for colorectal metastases, and one patient each for hepatoblastoma and cholangiocarcinoma. In six patients with HCC and cirrhosis, the right hepatic vein was reconstructed to provide venous outflow to liver segments not adequately drained by a remaining major hepatic vein. Four of these six patients required the use of Gore-Tex (W. L. Gore & Associates, Inc., Newark, DE) interposition grafts. In the 10 other cases the entire venous outflow from the remnant liver was reconstructed or reimplanted into the inferior vena cava primarily (n = 8) or using segments of the portal vein from the resected side of the liver as a graft (n = 2). Ex-vivo procedures with the use of veno-venous bypass were required in two cases and in-situ cold perfusion of the liver was used in one case. There were two perioperative deaths (12%). One patient died of liver failure 3 weeks after right trisegmentectomy with reconstruction of the left hepatic vein and one patient died at 3 months after resection due to sepsis from a segment of small bowel that perforated into a diaphragmatic hernia. Four patients had evidence of postoperative liver failure that resolved with supportive management and one patient required temporary dialysis. All vascular reconstructions were patent at last followup. With median followup of 23 months, 3 patients have died of recurrent malignancy at 14, 18 and 30 months, while an additional patient went on to die of progressive liver failure at 22 months. Actuarial 1 and 3 year survival was 88% and 50% respectively. Hepatic vein involvement by hepatic malignancy does not necessarily preclude resection. Liver resection with reconstruction of the hepatic veins can be performed in selected cases. The increased risk associated with the procedure appears to be balanced by the possible benefits, particularly when the lack of alternative curative approaches is considered.


Ischemic nephropathy.
Data suggest that ischemic renal disease secondary to atherosclerotic renal artery stenosis is a prevalent health problem. Atherosclerotic renal artery stenosis is a rapidly progressive process that can result in end-stage renal disease. Renal arteriography is the current diagnostic method of choice for the demonstration of renal artery stenosis. Captopril renography, nuclear magnetic resonance angiography, and duplex scanning are promising screening tests for this disorder. Therapeutic options include medical management, percutaneous angioplasty, and surgical revascularization.


Novel concept for a mucosal adhesive ointment.
Conventional adhesive ointments cause irritation to the mucous membranes. Therefore, a novel mucosal adhesive ointment based partly on neutralized polymethacrylic acid methyl ester was formulated. The flow curves of the ointment vehicle showed pseudoplastic properties. The rheological behavior as well as the adhesion on the mucosal membrane could be varied by the type and concentration of the polymer used and the base used for neutralization. During clinical studies, the ointment vehicle as well as a tretinoin (vitamin A acid) preparation for the treatment of lichen planus did not cause any local irritation or systemic side effects. Both vehicle and preparation were found to be pleasant for the patients to use. The new system of the mucosal adhesive ointment is not limited to the incorporation of tretinoin as the active agent; combined with other drugs the system could be applied to all types of mucosal membranes.


Tuboovarian abscess caused by Candida in a woman with an intrauterine device.
Candida infection should be considered in an individual with a pelvic abscess that is unresponsive to conventional antibiotic therapy, particularly in the presence of an intrauterine device. We present a case of a tuboovarian abscess caused by Candida species in a woman with an intrauterine device for >10 years. Surgical intervention followed by antifungal therapy resulted in a favorable outcome.


Painful Discrimination in the Emergency Department: Risk Factors for Underassessment of Patients' Pain by Nurses.
Unrelieved acute musculoskeletal pain continues to be a reality of major clinical importance, despite advancements in pain management. Accurate pain assessment by nurses is crucial for effective pain management. Yet inaccurate pain assessment is a consistent finding worldwide in various clinical settings, including the emergency department. In this study, pain assessments between nurses and patients with acute musculoskeletal pain after extremity injury will be compared to assess discrepancies. A second aim is to identify patients at high risk for underassessment by emergency nurses. The prospective PROTACT study included 539 adult patients who were admitted to the emergency department with musculoskeletal pain. Data on pain assessment and characteristics of patients including demographics, pain, and injury, psychosocial, and clinical factors were collected using questionnaires and hospital registry. Nurses significantly underestimated patients' pain with a mean difference of 2.4 and a 95% confidence interval of 2.2-2.6 on an 11-points numerical rating scale. Agreement between nurses' documented and patients' self-reported pain was only 27%, and 63% of the pain was underassessed. Pain was particularly underassessed in women, in persons with a lower educational level, in patients who used prehospital analgesics, in smokers, in patients with injury to the lower extremities, in anxious patients, and in patients with a lower urgency level. Underassessment of pain by emergency nurses is still a major problem and might result in undertreatment of pain if the emergency nurses rely on their assessment to provide further pain treatment. Strategies that focus on awareness among nurses of which patients are at high risk of underassessment of pain are needed.


Controlled substances in long-term care pharmacy: part 2.
Complying with state and federal requirements for controlled substances is crucial for all pharmacies. Specific regulations regarding how controlled substances are ordered, prescribed, dispensed, and stored, as well as strict requirements for disposal and record-keeping, require specific policies and procedures. For pharmacies that primarily dispense medications to long-term care facilities, there can be some unique challenges.


Development of an epicardial circulatory assist device.
The overall purpose of this project was to develop a circulatory assist device that could be used as a bridge to heart transplantation. Although heart muscle damage was one of the disadvantages with the original epicardial assist devices, as long as no bleeding occurs, such trauma would be of secondary importance in this particular application. The development of the proposed epicardial circulatory assist device (ECAD) was evolutionary in nature, with the second prototype design based on the lessons learned from that of the first. In vivo results from both phases of the project are reported. ECAD prototype 1 (ECAD-1) was composed of a flexible outer housing and two driving balloons. Fixation to the heart was adjustable for various heart sizes using Velcro fasteners. The design of the ECAD prototype 2 (ECAD-2) was based on the results of ECAD-1. Fixation to the heart was accomplished by suturing the outer housing onto the heart along the anterior descending artery and at the posterior atrioventricular groove. Each device was tested in five dogs. ECAD-1 was able to maintain the systemic circulation for 5 hours. However, unstable fixation and myocardial damage due to rubbing were the major problems. ECAD-2 passive effects on natural heart filling were acceptable. Under conditions of severe heart failure, a flow of more than 85% of control was obtained with a driving rate of 90-110 beats/min and 30% systole. The longest pumping was conducted for 8 hours. The ECAD was demonstrated to be a device useful in assisting the failing heart for short periods. Proper design will play a fundamental role in successful extended use.


Are more extensive procedures warranted at the time of aortic arch reoperation?
To determine the early and late outcomes of patients undergoing aortic arch reoperations. The follow-up of 70 patients undergoing a second arch operation (excluding univentricular physiology) between 1979 and 2015 was reviewed. Median age at initial arch operation and second operation was 9 days (interquartile range: 5-35) and 10 months (interquartile range: 3-64), respectively. The most common indication for initial arch operation was coarctation in 79% (55/70). The most common indication for a second arch operation was arch reobstruction in 90% (63/70). There were 2 hospital deaths (2/70, 3%) and 3 early third arch operations (3/70, 4%). Late follow-up was available in 94% (64/68) of hospital survivors. After a mean of 9 ± 7 years, there were 5 late deaths (5/64, 8%). Fifteen-year survival was 90% (95% confidence interval: 75-96). Arch reobstruction (echocardiogram gradient >25 mmHg/third operation for reobstruction) was present in 28% (18/64) and 16% (10/64) required a third arch operation. Fifteen-year freedom from arch reobstruction and third arch operation was 63% (95% confidence interval: 43-78) and 74% (95% confidence interval: 52-87), respectively. On multivariable analysis, hypoplastic arch at initial arch repair (P = 0.03) and interposition graft at second arch operation (P < 0.0001) were risk factors for third arch operation. Patients undergoing a second arch operation have significant rates of arch reobstruction and reoperation. The high rates of arch reobstruction and third arch operation warrant more extensive procedures at the time of second arch operation, especially in patients with a hypoplastic arch. Regular long-term monitoring after arch reoperation is mandatory.


Medicalization vs. adaptive models? Sense-making in magazine framing of menopause.
Women over the age of 40 are largely absent from media imagery. This study examined how magazines have framed menopause over the past two decades, as an increasing number of women have entered the phase. Using a traditional content analysis, we analyzed author and source gender, topics, and photographs in menopause articles in seven news and women's magazines. A computerized content-analysis program was used to determine how the magazines framed menopause. "Framing" refers to the emphasis and theme(s) of an article. Women's magazines provided a broad range of topics to help women prepare and cope; news magazines reported scientific developments, particularly in fertility. More frames, including clearer descriptions of symptoms and effects, occurred in women's magazines. Female authors included menopausal women as sources, but males did not. Photos of menopausal women appeared in a small portion of articles, and the women shown were predominantly white. Findings indicate some consistency with media coverage of other women's health issues, but with greater differences between news and women's magazines.


Dynamic Neutron Scattering by Biological Systems.
Dynamic neutron scattering directly probes motions in biological systems on femtosecond to microsecond timescales. When combined with molecular dynamics simulation and normal mode analysis, detailed descriptions of the forms and frequencies of motions can be derived. We examine vibrations in proteins, the temperature dependence of protein motions, and concepts describing the rich variety of motions detectable using neutrons in biological systems at physiological temperatures. New techniques for deriving information on collective motions using coherent scattering are also reviewed.


Respiratory Symptoms in Young Adults and Future Lung Disease. The CARDIA Lung Study.
There are limited data on factors in young adulthood that predict future lung disease. To determine the relationship between respiratory symptoms, loss of lung health, and incident respiratory disease in a population-based study of young adults. We examined prospective data from 2,749 participants in the CARDIA (Coronary Artery Risk Development in Young Adults) study who completed respiratory symptom questionnaires at baseline and 2 years later and repeated spirometry measurements over 30 years. Cough or phlegm, episodes of bronchitis, wheeze, shortness of breath, and chest illnesses at both baseline and Year 2 were the main predictor variables in models assessing decline in FEV1 and FVC from Year 5 to Year 30, incident obstructive and restrictive lung physiology, and visual emphysema on thoracic computed tomography scan. After adjustment for covariates, including body mass index, asthma, and smoking, report of any symptom was associated with -2.71 ml/yr excess decline in FEV1 (P < 0.001) and -2.18 in FVC (P < 0.001) as well as greater odds of incident (prebronchodilator) obstructive (odds ratio [OR], 1.63; 95% confidence interval [CI], 1.24-2.14) and restrictive (OR, 1.40; 95% CI, 1.09-1.80) physiology. Cough-related symptoms (OR, 1.56; 95% CI, 1.13-2.16) were associated with greater odds of future emphysema. Persistent respiratory symptoms in young adults are associated with accelerated decline in lung function, incident obstructive and restrictive physiology, and greater odds of future radiographic emphysema.


Occurrence of yeasts in psittacines droppings from captive birds in Italy.
Three-hundred twenty five droppings from parrots raised in the premises of 4 breeders and in several private households were cultured for yeasts. One-hundred sixty droppings (49.2%) resulted positive. From these specimens 212 isolates belonging to 27 different species were obtained. Mainly Candida species such as C. albicans, C. catenulata, C. curvata, C. famata, C. glabrata, C. guilliermondi, C. holmii, C. intermedia, C. krusei, C. lambica, C. lusitaniae, C. membranaefaciens, C. parapsilosis, C. pelliculosa, C. sake and C. valida were isolated. Debarvomyces marama, D. polymorphus, Geotrichum sp., Pichia etchelsii, P. ohmeri, Rhodotorula glutinis, R. rubra, Rhodotorula sp., Saccharomyces cerevisiae, S. kluyiveri and Zygosaccharomyces sp. were also obtained. Dark colonies on Staib medium were never observed. The psittacine birds apparently serve as carriers for several Candida species or their perfect states and to a lesser extent for other opportunistic yeasts such as Rhodotorula, Trichosporon and Saccharomyces spp., which are considered part of the transient microbiota of the gastrointestinal tract. The most striking finding was the absence of Cryptococcus spp. among the isolates. The present survey confirms the role of pet birds in carrying potential zoonotic yeasts.


Reappraising the formation of Jaffé's Base: studies of the treatment of imidazolidine-2-thione with mild oxidising agents.
Throughout reports detailing the preparation of Jaffé's Base, which date as far back as 1894, its identity and the nature of an intermediate prior to its formation have been constant points of conjecture. This report presents firm evidence that the oxidation of imidazolidine-2-thione, SCN(H)C2H4N(H), with potassium triiodide yields the 'thiol' condensation product 2,2'-bis(4,5-dihydro-1H-imidazolidine)disulfide (NC2H4N(H)CS)2 (1), which under mild conditions undergoes partial self condensation to yield 1-(4,5-dihydro-1H-imidazolidin-2-yl)imidazolidine-2-thione, Jaffé's Base--SCN(CNC2H4N(H))C2H4NH, (2). Crystallisation of 1 from acetone results in the unexpected formation of heterobicyclic 3-methyl-5,6-dihydroimidazolidin[2,1-b]thiazole, 3. The conversion of 1 to 3 has been studied by 1H NMR spectroscopy, which suggests the concurrent formation of 2 as an unreactive by-product. The solid state structures of 2, its HBr salt (2.HBr) and 3.(HI.I2), the latter being the isolated form of 3 under the conditions employed, have been determined using XRD methods.


Rehabilitation for shoulder instability.
Both structural and non-structural components can contribute to shoulder instability. Classification and therefore management must recognise these factors to achieve functional stability. This paper discusses a classification system proposing three types of shoulder instability recognising the structural and non-structural components and that a continuum exists between pathologies. Structural causes can be addressed with surgical intervention, but non-structural causes such as altered neuromuscular control within the rotator cuff should be addressed conservatively. The purpose of this article is to describe the types of instability and guide appropriate management, helping to avoid surgery in inappropriate cases and ensure that effective rehabilitation has been achieved.


Predicting nodal status using dynamic contrast-enhanced magnetic resonance imaging in patients with locally advanced breast cancer undergoing neoadjuvant chemotherapy with and without sequential trastuzumab.
Dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) is a reliable and accurate method for monitoring primary tumor response in the breast and can be used as a surrogate to predict final axillary nodal status. Retrospective study (October 1, 2004, through February 28, 2006) of 46 patients with clinically staged locally advanced breast cancer. Comprehensive cancer center. Forty-six patients with locally advanced breast cancer. Neoadjuvant chemotherapy (NAC), DCE-MRI, mastectomy and lumpectomy, and axillary lymph node dissection. The DCE-MRI results and pathologic response of the breast and axillary lymph nodes. Forty-six patients underwent NAC with doxorubicin hydrochloride and cyclophosphamide, followed by paclitaxel and carboplatin, with or without trastuzumab based on human epidermal growth factor receptor 2 (HER2/neu) status. Twenty-one patients (46%) had a complete pathologic response. For the HER2/neu-positive patients, the complete pathologic response rate was 70% (14/20). The accuracy, sensitivity, and specificity of the primary tumor response in predicting the axillary nodal status were 78%, 88%, and 72%, respectively. The accuracy, sensitivity, and specificity of the DCE-MRI-measured response in the primary tumor in predicting axillary nodal status were 74%, 62%, and 82%, respectively. For the HER2/neu-positive patients, the accuracy, sensitivity, and specificity improved to 80%, 75%, and 82%, respectively. The results of DCE-MRI of the primary tumor can be predictive of axillary nodal status, especially in patients receiving trastuzumab who are HER2/neu positive. The HER2/neu-positive patients with a complete clinical response on DCE-MRI are highly unlikely to benefit from an axillary lymph node dissection. For HER2/neu-negative patients, sentinel lymph node sampling is warranted.


A rare case of spontaneous live unilateral twin tubal pregnancy with both fetuses presenting with heart activities and a literature review.
Ectopic pregnancy is an extrauterine pregnancy, and 98% of which occur in the fallopian tube. The incidence of twin tubal pregnancy is rare but is increasing due to assisted reproductive technology. Spontaneous unilateral twin tubal pregnancy is extremely rare, and only a small number of case reports have been made. We herein report a rare case of spontaneous unilateral twin tubal pregnancy with both fetuses presenting with heart activities and a literature review. Right salpingectomy was performed in this case. Pathologic and histologic assessment confirmed the 2 distinct pregnancies in the same tube. The twins were dichorionic and diamniotic.


Abnormal Paraventricular Nucleus of Hypothalamus and Growth Retardation Associated with Loss of Nuclear Receptor Gene COUP-TFII.
The paraventricular nucleus of hypothalamus plays important roles in the regulation of energy balance and fetal growth. However, the molecular mechanisms underlying its formation and function have not been clearly elucidated. Various mutations in the human COUP-TFII gene, which encodes a nuclear receptor, result in growth retardation, congenital diaphragmatic hernia and congenital heart defects. Here, we show that COUP-TFII gene is expressed in the developing hypothalamus in mouse. The ventral forebrain-specific RXCre/+; COUP-TFII F/F mutant mice display growth retardation. The development of the paraventricular nucleus of hypothalamus is compromised in the COUP-TFII mutant mainly because of increased apoptosis and mis-migration of the Brn2+ neurons. Moreover, hypoplastic anterior pituitary with blood cell clusters and shrunken posterior pituitary lacking AVP/OT neuron innervations are observed in the mutant, indicating the failure of formation of the hypothalamic-pituitary axis. Mechanistic studies show that the expression of Bdnf and Nrp1 genes is reduced in the mutant embryo, and that Bdnf is a direct downstream target of the COUP-TFII protein. Thus, our findings provide a novel functional validation that COUP-TFII gene promotes the expression of Bdnf and Nrp1 genes to ensure the appropriate morphogenesis of the hypothalamic-pituitary axis, especially the paraventricular nucleus of hypothalamus, and to prevent growth retardation.


[Decrease of Leu7 positive cells in peripheral blood from patients with aseptic meningitis].
In order to clarify the role of natural killer cell in the central nervous system (CNS) infection, we examined Leu7 positive cells in peripheral blood of aseptic meningitis by flow cytometry. We studied 10 patients with aseptic meningitis (5 echo virus type 6 and 5 suspected viral meningitis). Also 3 patients with Japanese encephalitis, 3 with fungal meningitis, each one with bacterial meningitis, tuberculous meningitis and brainstem encephalitis were analyzed. Blood samples of acute phase and after recovery were obtained by the first examination on admission and the latest examination after normalization of cerebrospinal fluid findings, respectively. All aseptic meningitis patients showed decrease of Leu7 positive cells in acute phase (mean +/- SD = 6.8 +/- 3.12%, from 3 to 25 days of illness) and continued after recovery (8.3 +/- 4.27%, from 35 to 503 days of illness) in all but one. The number of the cells found in the aseptic meningitis patients during the acute phase and after recovery was significantly lower than in normal subjects (p less than 0.01). The change did not differ statistically between the acute phase and post recovery. The date suggest that decreased Leu7 positive cells is present before infection. As concerning other CNS infections, the positive cells decreased from acute phase to after recovery in two Japanese encephalitis and one tuberculous patients. But because of small number, it was not decided whether the decrease significantly was low value or not. Since natural killer cells is related to defence mechanism of viral infection in acute phase, it seems that low natural killer activity may develop the viral infection. Therefore the date raises the possibility that the people who has originally less the natural killer cells tend to be susceptible, as far as viral meningitis.


Excision of the proximal end of the femur for hip stiffness in myelomeningocele.
Operation on the hips of patients with myelomeningocele is often followed by stiffness or ankylosis. Excision of the upper end of the femur for this condition frequently fails because of extensive new bone formation. Twelve excisions in eight patients are reported. Six of these patients had recently had spinal fusion operations; the consequent loss of ability to compensate for hip stiffness by spinal flexion had made sitting difficult or impossible. Excision or even re-excision of the upper femur failed in most cases. Careful assessment of hip mobility before spinal operations in these patients is essential and osteotomy rather than excision of the upper femur is advised.


[The role of oxidative stress in pathogenesis of GBS].
Axon degeneration accompanying its demielinization is a main course of neurological insufficiency typical for GBS. The mechanisms of axon degeneration, considered as the secondary result of serve inflammation are not established. We aimed to determine the role of oxidative metabolism in viral polyneuropathy pathogenesis. The activity of pro- and antioxidant systems of the body was studied by electron paramagnetic resonance (EPR) method. In blood and cerebrospinal fluid the intensive EPR signals of nitric oxide (NO), complexes of NO with nonhemic iron (HbNO), lypo- and superoxide radicals content noticeably increases, the signals of free Mn2+ and Fe2+ revealed, the activity of blood antioxidant enzymes, ceruloplasmin and katalasa increases (by 60%), superoxidedismitase's and glutation reductases activity decreases (by 20% and 70% correspondingly). It was considered, that inflammatory damage of nervous system induced by different infectious stimulus is initiated by activated immune cell proinflamatory agents (reactive oxygen and nitrogen species). Subsequently the oxidative stress, as result of accumulation of generators of reactive oxygen species, disordered intracellular metabolism products, contributes to axon demielinization and degeneration.


A metal surface with chiral memory.
Adsorption of maleic acid onto the copper(110) surface in ultrahigh vacuum induces restructuring of the surface such that its original mirror symmetry is locally broken. Scanning tunnelling microscopy performed on areas, which contain no molecules after annealing, reveals that Cu adatoms are still lined up on the surface in a chiral fashion.


Temporal control in the voicing contrast: Evidence from surgery-related apraxia of speech.
The goal of this study was to investigate the phonetic realisation of the voicing feature in two tumour resection-related Spanish speakers with apraxia of speech. Temporal parameters related to the phonological contrast of voicing in Spanish have been analysed for intervocalic voiced and voiceless obstruents embedded in isolated words and nonwords, and compared with data collected from healthy speakers. Results indicate that in devoiced productions, where VOT values fitted the 'voiceless stops' category, vowel duration values matched those of voiced stops and suggested the preservation of contextual voicing cues. An attempt at preserving a consonant/vowel duration ratio consistent with aerodynamic predictions for voicing contrast has been observed in apraxic correct production as well as in devoicing errors, but not in the control group, which could be interpreted as a compensatory mechanism.


Low risk of venous thrombosis in two families with combined type I plasminogen deficiency and factor V R506Q mutation.
Two families with type I plasminogen deficiency and APC resistance are reported. The proposita of family A suffered from ischemic stroke when taking estrogen-progesterone-containing oral contraceptive. Several hemostatic challenges in the past (ovariectomy, appendectomy, and two pregnancies) were without thrombosis. Plasminogen activity and antigen (60 and 58%, normal range 72-136 and 69-135%, respectively) were reduced, and an increased APC resistance (APC-SR= 1.55; normal range 1.8-3.00) associated with G --> A change at 1,691 nucleotide position in exon 10 of FV gene (FV Leiden) was observed. The asymptomatic son had isolated plasminogen deficiency (activity 57% and antigen 60%) whereas the asymptomatic daughter had isolated APC resistance (APC-SR = 1.61) and FV Leiden mutation. The proposita of family B, referred for superficial thrombophlebitis, had low plasminogen levels (activity 55% and antigen 53%) and APC resistance (APC-SR = 1.5) whereas the asymptomatic mother and the brother had isolated APC resistance (APC-SR = 1.62 and 1.8, respectively) and the asymptomatic father isolated plasminogen deficiency (activity 61% and antigen 62%). These data suggest that the combination of plasminogen deficiency and APC resistance probably does not significantly increase the risk of venous thrombosis. However, larger experience with additional cases is needed to definitely assess the magnitude of thrombotic risk in these families.


Heterogeneity of home care assistance needs of people with AIDS.
A multidisciplinary home care service for people with AIDS (PWAs) was started in Rome in September 1990. This paper describes the features of the home care service offered by the Associated Health Care Workers' Co-operative (OSA), an example of the integration of private and state systems. We detail the types and numbers of visits that PWAs have needed, and we explore the possible correlation between demographic and clinical variables and the care required. As of September 1994 service had been provided to 372 PWAs. During the 4-year period, 62,927 home care visits were made (an average of 4.3 visits/patient/week): 66% were made by psychologists, social workers and home helps, and 34% by health professionals. PWAs who, at the outset of their home care, suffered from AIDS-dementia complex (ADC), toxoplasmosis, wasting syndrome or cytomegalovirus retinitis required the highest number of visits. Psychologists, social workers and home care helps made more frequent visits than health professionals for all AIDS-defining conditions except retinitis (for which 63% of visits were for health care). Our study shows that careful assessment of patients receiving home care helps in planning visits and in organizing available resources. A controlled randomized multicentre study is under way with the aim of determining the effectiveness of home care in terms of survival, quality of life and care workload and related costs.


Breast cancer prevention.
We have developed a new approach for breast cancer prevention, capitalizing in the preventive effect of early first full-term pregnancy, hormonally induced differentiation and our ability to identify specific genomic signatures that allow us to predict risk reduction. Early pregnancy imprints in the breast permanent genomic changes or a 'signature' that reduces the susceptibility of this organ to cancer. At cellular level, what we have achieved is the shifting of the Stem Cell 1 population, highly susceptible to cancer, to a population of Stem Cell 2 that is refractory to carcinogenesis. In a case-control study, we have compared the gene expression profile in normal breast tissue from nulliparous and parous postmenopausal women with (case) and without (control) breast cancer. We have determined that early first full-term pregnancy induces a specific genomic signature in the postmenopausal breast that is the biomarker for the Stem cell 2. The Stem cell 2 contains specific genes controlling transcription, RNA processing, immune response, apoptosis and DNA repair. We have further detected in the plasma, using an ELISA assay, the proteins coded by the gene signature. We are developing clinical trials to demonstrate the proof of the principle that r-hCG can induce in the human breast a genomic signature of the Stem cell 2. This is a concept that challenges the currently available chemopreventive agents that need to be given for extended periods for maintaining the suppression of a specific metabolic pathway or the abrogation of the function of an organ.


Nuclear redox-signaling is essential for apoptosis inhibition in endothelial cells--important role for nuclear thioredoxin-1.
The redox regulator thioredoxin-1 (Trx) is a potent antioxidative enzyme and exerts important cellular functions. Physiological concentrations of reactive oxygen species (ROS) and of nitric oxide (NO) act as second messengers. Previously, we demonstrated that ROS and NO reduced apoptosis in a Trx-dependent manner. The aim of this study was to determine the underlying mechanisms. First, we investigated the localization of Trx after H2O2 and NO. Both induced nuclear import of Trx, which required karyopherin-alpha. siRNA against karyopherin-alpha inhibited nuclear import of Trx. Analysis of the Trx amino acid sequence and subsequent immunoprecipitation studies revealed that Trx(K81/82E) is not imported into the nucleus under H2O2 treatment and Trx(K81/82/85E) was retained in the cytosol and induced cell death. Trx(K81/82E) abolished the antiapoptotic capacity of H2O2. Glutathione S-transferase P1 (GST-P1) was identified as one major target regulated by H2O2. siRNA against GST-P1 abolished the antiapoptotic effect of H2O2. Cysteine 69, but not cysteines 32 and 35, which are all required for the complete antiapoptotic function of Trx, is not imported into the nucleus. H2O2-induced nuclear import of Trx depends on karyopherin-alpha and NO. Trx-dependent induction of GST-P1 expression is required for apoptosis inhibition in endothelial cells.


Voice Onset Time Imitation in Teens Versus Adults.
We compare teens' and adults' imitation of sentences with shortened and lengthened voice onset time (VOT), in order to test whether purported age-based advantages in phonetic acquisition may be due to differences in imitative ability. Teens (M age = 13, n = 39) and adults (n = 31) completed an explicit imitation and discrimination task on pairs of sentences characterized by canonical and manipulated (shortened or lengthened) VOT. We assessed extent of imitation using two acoustic metrics (ΔVOT and Proximity), accuracy on the discrimination task, and correlations between imitation and perception. Both age groups modified VOT when imitating stimuli with both lengthened and shortened VOT. Adults, however, showed significantly more lengthening than teens (i.e., higher ΔVOT), as well as VOT values that were slightly but significantly closer to the target stimulus values (i.e., lower proximity). Both age groups showed above-chance discrimination accuracy, and a significant relationship between individual perception and production performance was found for lengthened-VOT sentences. We found no evidence that teens have a greater imitative ability than adults; in fact, adults showed significantly more imitation based on both acoustic metrics. Both age groups showed robust imitation of VOT manipulations in both directions, in contrast to previous work showing lack of imitation for shortened VOT. Extent of imitation was predicted by individual perceptual performance, but only to a limited degree, underscoring the importance of other factors in explaining individual variation in imitative ability.


Preoperative pelvic radiation increases the risk for ileal pouch failure in patients with colitis-associated colorectal cancer.
To evaluate the impact of preoperative radiation on pouch outcomes in patients with colitis-associated cancer (CAC). CAC patients who underwent restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) from 1984 to 2009 were identified from our registry. The impact of preoperative pelvic radiation for CAC or other pelvic cancer on pouch related outcomes was evaluated. Sixty-three pouch patients with confirmed CAC were included (37 male, 58.7%). The mean age at pouch construction was 46.9±10.6 years. Seven patients were excluded due to the presence of persistent diverting ileostomy (n=2) or no follow-up (n=5). The remaining 56 patients were analyzed, including 9 who received pelvic radiation prior to IPAA creation for CRC or other cancers. Preoperative pelvic radiation was significantly associated with chronic pouchitis (P=0.024). There was, however, no correlation between pelvic radiation and pouch/anal transitional zone neoplasia, pouch stricture, pelvic abscess and pouch fistula/sinus. Pouch failure occurred in 13 patients after a median follow-up of 66.4 (range: 2.7-322.2) months. Although a simple statistical analysis based on the number of patients with pouch failure did not achieve significance (4/9 vs. 9/47, P=0.19), Kaplan-Meier analysis showed a strong association between preoperative pelvic radiation and the risk for pouch failure (P<0.001). A subgroup analysis of rectal cancer patients revealed that 3/7 patients (42.9%) with radiation and 3/17 (17.6%) without had pouch failure (P=0.31). Again, the association between pelvic radiation and pouch failure was confirmed using Kaplan-Meier analysis (P=0.02). Pelvic radiation administered prior to IPAA creation appears to be associated with poor pouch outcomes. Oncological benefits and pouch functional outcomes should be carefully balanced before pelvic radiation is considered prior to restorative proctocolectomy.


Risk of liver decompensation with cumulative use of mitochondrial toxic nucleoside analogues in HIV/hepatitis C virus coinfection.
Among patients dually infected with human immunodeficiency virus (HIV) and chronic hepatitis C virus (HCV), use of antiretroviral therapy (ART) containing mitochondrial toxic nucleoside reverse transcriptase inhibitors (mtNRTIs) might induce chronic hepatic injury, which could accelerate HCV-associated liver fibrosis and increase the risk of hepatic decompensation and death. We conducted a cohort study among 1747 HIV/HCV patients initiating NRTI-containing ART within the Veterans Aging Cohort Study (2002-2009) to determine if cumulative mtNRTI use increased the risk of hepatic decompensation and death among HIV-/HCV-coinfected patients. Separate marginal structural models were used to estimate hazard ratios (HRs) of each outcome associated with cumulative exposure to ART regimens that contain mtNRTIs versus regimens that contain other NRTIs. Over 7033 person-years, we observed 97 (5.6%) decompensation events (incidence rate, 13.8/1000 person-years) and 125 (7.2%) deaths (incidence rate, 17.8 events/1000 person-years). The risk of hepatic decompensation increased with cumulative mtNRTI use (1-11 mo: HR, 1.79 [95% confidence interval (CI), 0.74-4.31]; 12-35 mo: HR, 1.39 [95% CI, 0.68-2.87]; 36-71 mo: HR, 2.27 [95% CI, 0.92-5.60]; >71 mo: HR, 4.66 [95% CI, 1.04-20.83]; P = .045) versus nonuse. Cumulative mtNRTI use also increased risk of death (1-11 mo: HR, 2.24 [95% CI, 1.04-4.81]; 12-35 mo: HR, 2.05 [95% CI, 0.68-6.20]; 36-71 mo: HR, 3.04 [95% CI, 1.12-8.26]; >71 mo: HR, 3.93 [95% CI, 0.75-20.50]; P = .030). These findings suggest that cumulative mtNRTI use may increase the risk of hepatic decompensation and death in HIV/HCV coinfection. These drugs should be avoided when alternatives exist for HIV/HCV patients.