Routine practice in mechanical ventilation in cardiac surgery in Italy.
Management of mechanical ventilation is a key issue in the prevention of postoperative pulmonary complications (PPCs) and the improvement of surgical outcome. This is especially true in cardiac surgery where the use of the cardiopulmonary bypass (CPB) increases the risk of lung injury. In the last years a growing number of studies have shown that protective ventilation has led to excellent results. However, the literature in this regard is lacking in cardiac surgery and there are no univocal guidelines in this sense. The aim of this survey was to investigate the actual clinical practice about ventilation techniques used in the Italian cardiac surgery centers. A questionnaire of 32-item was sent to 69 Italian cardiac surgery centers, 56 of which return a completed form (81.2%). The questionnaire was assembled by three independent researchers and the final version was e-mailed to all members of the SIAARTI (Italian society of anesthesia resuscitation and intensive care medicine) Study Group on Cardiothoracic and Vascular Anesthesia. The answers were collected using a Google Forms sheet. In case of multiple questionnaires returned from the same center (i.e., different physicians from the same center responded) the head of department was asked to give a definite answer. Furthermore, for the 17 centers who reported multiple questionnaires, no large differences were found between the responses of different doctors belonging to the same center (12.3%±4.2% of discordant answers). Intraoperatively, patients were ventilated with a tidal volume (TV) of 6-8 mL/kg (91.1% of centers), a positive end-expiration pressure of 3-5 cmH2O (76.8% of centers) and a fraction of inspired oxygen (FiO2) of 50-80% (60.7% of centers). During the CPB, the "stop ventilation" technique was frequently adopted (73.2%). Before the discharge from the intensive care unit (ICU) non-invasive ventilation (NIV) was never applied in 32.1% of the centers, but it was used in 46.4% of patients with postoperative complications. This study shows a significant heterogeneity in ventilatory techniques among the Italian centers during CPB, whereas in the other surgical time the majority of the responding centers adopted a protective mechanical ventilation strategy.


Gastroplasty in morbid obesity: observations in 300 patients.
Morbid obesity is associated with a number of life-threatening complications. Medical treatment of morbid obesity is rarely successful. Gastric reduction has replaced intestinal bypass as the surgical treatment of choice. Indications for operation are fairly standardized, and complications and results are similar in most large series. In our series of 300 gastroplasties done during the past four years, weight loss compares favorably with that in other reported series. Our hospital complication rate has been low because of short operating time and early ambulation. Postoperative vomiting has been reduced by enlarging the stoma. Revision rate was between 1% and 2% per year. The surgical treatment of morbid obesity requires a great deal of personal contact between surgeon and patient in the preoperative and postoperative periods. Because these patients tend not to comply with the dietary restrictions of the operation, close follow-up care is required.


[Pasta quality in view of its elemental composition].
Concentrations of iron, zinc, copper and manganese were determined in 13 different kinds of pasta available in sale. The concentrations of chemical elements were analysed, after wet mineralization, by flame atomic absorption spectrometry - AAS with deuterium background correction. Reliability of the procedure was checked by analysis of certified reference materials. The average concentrations (mg/100 g) of minerals in pasta were as follows: 16.3 for calcium; 159 for potassium; 1.93 for iron and 1.35 for zinc. These measurements allowed to estimate the realisation of the recommended daily intake of bioelements with the analysed products for an adult person. The highest percentage of realisation was estimated for wholewheat pasta. Statistical analysis has shown a strong influence of the flour type (wholemeal, semolina, wheat) used in pasta production on elements concentrations.


Perceived social support and its impact on depression and health-related quality of life: a comparison between cancer patients and general population.
It is well known that cancer patients' perception of social support is associated with their depressive symptoms and health-related quality of life. However, there have been little studies that compared the variates of cancer patients with the general population. We sought to compare differences in the level of perceived social support and the impact of perceived social support on depressive symptoms and health-related quality of life between cancer survivors and the general population. Data were collected from 1818 cancer patients treated at the National Cancer Center and regional cancer centers in South Korea. The control group of the general population was composed of 2000 individuals without cancer from community. Cancer patients reported significantly higher level of perceived social support than the general population, while they reported lower health-related quality of life and were more susceptible to depression. The positive associations of higher perceived social support with lower depressive symptoms, as well as with higher health-related quality of life, were stronger among cancer patients than among the general population. The interaction effect suggests that the impact of social support would be stronger among cancer patients than the general public. Thus, it would be beneficial to pay attention to providing social support to cancer patients, particularly to those who are more vulnerable. Furthermore, investigation of the most effective and efficient methods to deliver social support interventions would be worthwhile.


Ferritin light chain gene mutations in two Brazilian families with hereditary hyperferritinemia-cataract syndrome.
Hereditary hyperferritinemia-cataract syndrome is an autosomal dominant genetic disorder associated with mutations in the 5'UTR region of the ferritin light chain gene. These mutations cause the ferritin levels to increase even in the absence of iron overload. Patients also develop bilateral cataract early due to accumulation of ferritin in the lens, and many are misdiagnosed as having hemochromatosis and thus not properly treated. The first cases were described in 1995 and several mutations have already been identified. However, this syndrome is still a poorly understood. We report two cases of unrelated Brazilian families with clinical suspicion of the syndrome, which were treated in our department. For the definitive diagnosis, the affected patients, their parents and siblings were submitted to Sanger sequencing of the 5'UTR region for detection of the ferritin light gene mutation. Single nucleotide polymorphism-like mutations were found in the affected patients, previously described. The test assisted in making the accurate diagnosis of the disease, and its description is important so that the test can be incorporated into clinical practice.


Positional dependence of particles in microfludic impedance cytometry.
Single cell impedance cytometry is a label-free electrical analysis method that requires minimal sample preparation and has been used to count and discriminate cells on the basis of their impedance properties. This paper shows experimental and numerically simulated impedance signals for test particles (6 μm diameter polystyrene) flowing through a microfluidic channel. The variation of impedance signal with particle position is mapped using numerical simulation and these results match closely with experimental data. We demonstrate that for a nominal 40 μm × 40 μm channel, the impedance signal is independent of position over the majority of the channel area, but shows large experimentally verifiable variation at extreme positions. The parabolic flow profile in the channel ensures that most of the sample flows through the area of uniform signal. At high flow rates inertial focusing is observed; the particles flow in equal numbers through two equilibrium positions reducing the coefficient of variance (CV) in the impedance signals to negligible values.


A suspected case of bilateral crossed renal ectopia or bilateral jet effect.
Crossed renal ectopia is a relatively unusual congenital anomaly. Bilateral crossed renal ectopia is considered the rarest form of this anomaly. A 19-year-old girl with intermittent flank pain was admitted to our department. Various clinical and laboratory examinations were carried out. Excretory urography showed a normal upper urinary tract anatomy, whereas the distal ends of the ureters crossed each other in the pelvis, which suggested bilateral crossed renal ectopia.


An fNIRS Study of Applicability of the Unity-Diversity Model of Executive Functions in Preschoolers.
Executive function (EF) includes a set of higher-order abilities that control one's actions and thoughts consciously and has a protracted developmental trajectory that parallels the maturation of the frontal lobes, which develop speedily over the preschool period. To fully understand the development of EF in preschoolers, this study examined the relationship among the three domains of executive function (cognitive shifting, inhibitory control, and working memory) to test the applicability of the unity-diversity model in preschoolers using both behavioral and fNIRS approaches. Altogether, 58 Chinese preschoolers (34 boys, 24 girls, Mage = 5.86 years, SD = 0.53, age range = 4.83-6.67 years) were administered the Dimensional Card Change Sort (DCCS), go/no-go, and missing scan task. Their brain activations in the prefrontal cortex during the tasks were examined using fNIRS. First, the behavioral results indicated that the missing scan task scores (working memory) correlated with the DCCS (cognitive shifting) and go/no-go tasks (inhibitory control). However, the latter two did not correlate with each other. Second, the fNIRS results demonstrated that the prefrontal activations during the working memory task correlated with those in the same regions during the cognitive shifting and inhibitory control tasks. However, the latter two still did not correlate. The behavioral and neuroimaging evidence jointly indicates that the unity-diversity model of EF does apply to Chinese preschoolers.


Secondhand smoke and adverse fetal outcomes in nonsmoking pregnant women: a meta-analysis.
To determine the risk of adverse fetal outcomes of secondhand smoke exposure in nonsmoking pregnant women. This was a systematic review and meta-analysis in accordance with Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines. We searched Medline and Embase (to March 2009) and reference lists for eligible studies; no language restrictions were imposed. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were estimated by using random-effect models. Our search was for epidemiologic studies of maternal exposure to secondhand smoke during pregnancy in nonsmoking pregnant women. The main outcome measures were spontaneous abortion, perinatal and neonatal death, stillbirth, and congenital malformations. We identified 19 studies that assessed the effects of secondhand smoke exposure in nonsmoking pregnant women. We found no evidence of a statistically significant effect of secondhand smoke exposure on the risk of spontaneous abortion (OR: 1.17 [95% CI: 0.88-1.54]; 6 studies). However, secondhand smoke exposure significantly increased the risk of stillbirth (OR: 1.23 [95% CI: 1.09-1.38]; 4 studies) and congenital malformation (OR: 1.13 [95% CI: 1.01-1.26]; 7 studies), although none of the associations with specific congenital abnormalities were individually significant. Secondhand smoke exposure had no significant effect on perinatal or neonatal death. Pregnant women who are exposed to secondhand smoke are estimated to be 23% more likely to experience stillbirth and 13% more likely give birth to a child with a congenital malformation. Because the timing and mechanism of this effect is not clear, it is important to prevent secondhand smoke exposure in women before and during pregnancy.


CD98 expression is associated with the grade of malignancy in thymic epithelial tumors.
CD98 has been associated with tumor growth and is highly expressed in human neoplasms. The aim of this study was to evaluate the clinicopathological significance of CD98 expression in thymic epithelial tumors. Forty-nine patients with thymic epithelial tumors were included in this study. Tumor sections were stained by immunohistochemistry for CD98; vascular endothelial growth factor (VEGF); micro-vessels (CD31 and CD34); cell cycle control marker (p53); and apoptosis marker (Bcl-2). CD98 expression for low-risk thymomas, high-risk thymomas, and thymic carcinomas were 1 (4%) of 27, 9 (82%) of 11, and 11 (100%) of 11, respectively. There was positive correlation between CD98 and VEGF (p<0.001), microvessel density (CD31 and CD34) (p<0.001) and p53 (p<0.001). However, Bcl-2 showed no positive correlation with CD98 expression. The expression of CD98 were also significantly associated with the grade of malignancy in thymic epithelial tumors. Multivariate analysis revealed that overexpression of CD98 was a significant independent factor predicting a poor outcome in thymic epithelial tumors. CD98 expression was associated with the grade of malignancy in thymic epithelial tumors. Moreover, CD98 expression was closely correlated with angiogenesis and cell cycle control, and was useful for predicting poor outcome.


AZD7545 is a selective inhibitor of pyruvate dehydrogenase kinase 2.
The PDH (pyruvate dehydrogenase) multi-enzyme complex catalyses a key regulatory step in oxidative glycolysis. Phosphorylation of the E1 subunit of the complex on serine residues results in the inactivation of enzyme activity. A family of four dedicated PDH kinase isoenzymes exists, each of which displays a distinct tissue-specific expression profile. AZD7545 is one of a series of PDH kinase inhibitors developed for the treatment of type 2 diabetes. The isoenzyme-selectivity profile of AZD7545 and related compounds is described and the consequences for their in vivo mode of action are discussed.


Healthy Effects of Plant Polyphenols: Molecular Mechanisms.
The increasing extension in life expectancy of human beings in developed countries is accompanied by a progressively greater rate of degenerative diseases associated with lifestyle and aging, most of which are still waiting for effective, not merely symptomatic, therapies. Accordingly, at present, the recommendations aimed at reducing the prevalence of these conditions in the population are limited to a safer lifestyle including physical/mental exercise, a reduced caloric intake, and a proper diet in a convivial environment. The claimed health benefits of the Mediterranean and Asian diets have been confirmed in many clinical trials and epidemiological surveys. These diets are characterized by several features, including low meat consumption, the intake of oils instead of fats as lipid sources, moderate amounts of red wine, and significant amounts of fresh fruit and vegetables. In particular, the latter have attracted popular and scientific attention for their content, though in reduced amounts, of a number of molecules increasingly investigated for their healthy properties. Among the latter, plant polyphenols have raised remarkable interest in the scientific community; in fact, several clinical trials have confirmed that many health benefits of the Mediterranean/Asian diets can be traced back to the presence of significant amounts of these molecules, even though, in some cases, contradictory results have been reported, which highlights the need for further investigation. In light of the results of these trials, recent research has sought to provide information on the biochemical, molecular, epigenetic, and cell biology modifications by plant polyphenols in cell, organismal, animal, and human models of cancer, metabolic, and neurodegenerative pathologies, notably Alzheimer's and Parkinson disease. The findings reported in the last decade are starting to help to decipher the complex relations between plant polyphenols and cell homeostatic systems including metabolic and redox equilibrium, proteostasis, and the inflammatory response, establishing an increasingly solid molecular basis for the healthy effects of these molecules. Taken together, the data currently available, though still incomplete, are providing a rationale for the possible use of natural polyphenols, or their molecular scaffolds, as nutraceuticals to contrast aging and to combat many associated pathologies.


Hemadsorption-negative plaque test: new assay for rubella virus revealing a unique interference.
A simple and rapid plaque procedure has been developed for detecting and accurately assaying rubella virus in a noncytopathic virus-cell relationship. Plaque-formation is based on the development, in individual cells infected with rubella virus, of a unique type of intrinsic interference to infection with Newcastle disease virus. Rubella virus-infected cells challenged with Newcastle disease virus and tested for hemadsorption 15 hours later stand out as hemadsorption-negative areas. Individual living cells infected with rubella virus can be resolved under conditions allowing standard cloning procedures. In principle, the hemadsorption-negative plaque test can be used to search for a new class of noncytopathic, non-hemadsorbing viruses-those that induce an intrinsic interference to infection by any hemadsorbing virus.


Trait anxiety and salivary cortisol during free living and military stress.
Accumulating evidence suggests that negative affect is associated with elevated cortisol. Limited research has investigated this association in young, highly functioning, and stress-resilient populations. We examined the relation of trait anxiety with total and diurnal salivary cortisol during free-living conditions and during a stressful military exercise in 26 military men ages 19-30 yr (M = 21.6, SD = 2.3). Salivary cortisol was assessed at five time points over 2 consecutive days of free-living measurement, and three time points during a stressful military experience. Trait anxiety was measured with the trait portion of the Spielberger State-Trait Anxiety Inventory 1-3 wk prior to the military exercise. Total cortisol concentrations were similar between men reporting high or low anxiety during free-living conditions (8.6 +/- 3.2 vs. 7.4 +/- 2.8 nmol x L(-1), respectively, P > 0.05), and military stress (21.3 +/- 7.3 vs. 19.0 +/- 7.0 nmol x L(-1), respectively, P > 0.05). The diurnal cortisol profile differed significantly (P = 0.04) between these men during the free-living condition, but not the stressful military experience (P > 0.05). Specifically, during free living, men with low anxiety exhibited a diurnal cortisol pattern that peaked in the early morning, decreased precipitously during the midmorning, and continued to decrease throughout the day, reaching a nadir in the evening. By contrast, the cortisol pattern of high-anxiety men remained elevated and significantly higher than their low-anxiety counterparts during the midmorning, decreased more slowly throughout the day, and reached its lowest level in the evening. Results were not substantially altered following adjustment for sleep duration or wake time. These findings suggest that trait anxiety influences the diurnal cortisol pattern in young, apparently healthy men during free-living conditions, but does not predict the cortisol response to uncontrollable military stress.


Neurologic abnormalities and cerebrospinal fluid changes in horses administered fumonisin B1 intravenously.
The objective of this experiment was to characterize a dose-dependent toxic effect of fumonisin B1 (FB1) and to document initial neurologic signs, clinical progression, and terminal cerebrospinal fluid (CSF) changes in horses administered FB1 IV. Seventeen healthy horses were administered 0.00 (n = 4), 0.01 (n = 3), 0.05 (n = 3), 0.10 (n = 3), or 0.20 mg (n = 4) of purified FB1 IV q24h. When neurologic abnormalities observed by a masked observer became severe, atlanto-occipital CSF taps were performed and CSF pressure, cell count, cytology, protein, albumin and glucose concentrations, and creatine kinase activity were measured. Changes in CSF and number of days to 1st observation of neurologic abnormalities were compared between doses by ANOVA, with the level of significance set at P < .05. Control horses and low-dose horses (0.01 mg/kg) remained neurologically normal. In higher dose FB1-treated horses (n = 10), initial clinical signs (days 4-10) included hindlimb ataxia, delayed forelimb placing, and decreased tongue tone and movement. Hindlimb and trunkal ataxia, depression, hyperesthesia, and intermittent dementia gradually became apparent. When data from all horses with neurologic abnormalities were pooled (0.05-0.20 mg/kg FB1), mild clinical signs (mean day 6.3) occurred significantly earlier than did more severe (mean day 8.9) clinical signs (P = .009). Neurologic horses had high CSF protein, albumin, and IgG concentrations and increased albumin quotients (P < .05). It was concluded that FB1-induced neurologic and CSF changes in a dose-dependent manner, with a no-observable-limit of 0.01 mg FB1/kg IV q24h for 28 days. The neurologic and CSF changes were consistent with vasogenic cerebral edema.


Differential regulation of WASP and N-WASP by Cdc42, Rac1, Nck, and PI(4,5)P2.
The Wiskott-Aldrich syndrome protein (WASP) and neural WASP (N-WASP) are key players in regulating actin cytoskeleton via the Arp2/3 complex. It has been widely reported that the WASP proteins are activated by Rho family small GTPase Cdc42 and that Rac1 acts through SCAR/WAVE proteins. However, a systematic study of the specificity of different GTPases for different Arp2/3 activators has not been conducted. In this study, we have expressed, purified, and characterized completely soluble, highly active, and autoinhibited full-length human WASP and N-WASP from mammalian cells. We show a novel N-WASP activation by Rho family small GTPase Rac1. This GTPase exclusively stimulates N-WASP and has no effects on WASP. Rac1 is a significantly more potent N-WASP activator than Cdc42. In contrast, Cdc42 is a more effective activator of WASP than N-WASP. Lipid vesicles containing PIP2 significantly improve actin nucleation by the Arp2/3 complex and N-WASP in the presence of Rac1 or Cdc42. PIP2 vesicles have no effect on WASP activity alone. Moreover, the inhibition of WASP-stimulated actin nucleation in the presence of Cdc42 and PIP2 vesicles has been observed. We found that adaptor proteins Nck1 or Nck2 are the most potent WASP and N-WASP activators with distinct effects on the WASP family members. Our in vitro data demonstrates differential regulation of full-length WASP and N-WASP by cellular activators that highlights fundamental differences of response at the protein-protein level.


[Ceramic acetabulum for hip endoprostheses. 8: Revisions].
For total hip replacement, ceramic femoral heads and acetabular liners are being used with success. However, reports of revision surgery necessitated by fractures or marked wear of ceramic components are still being published. The revision rate due to fracture is less than 0.01%, and much lower than for other complications. Nevertheless, improvement of safety remains a topic of discussion. This article reviews the results of investigations of explanted ceramic heads and liners, and discusses the problems caused by ceramic wear and chipping. Recommendations for revision surgery in such cases are given.


Allopregnanolone association with psychophysiological and cognitive functions during acute smoking abstinence in premenopausal women.
Nicotine response may predict susceptibility to smoking relapse. Allopregnanolone, a neuroactive steroid metabolized from progesterone, has been shown to be associated with several symptoms of nicotine response. We sought to explore the association between allopregnanolone and response to nicotine during acute smoking abstinence in premenopausal women. Participants completed 2 nicotine-response laboratory sessions, 1 in their follicular (low allopregnanolone) and 1 in their luteal (high allopregnanolone) menstrual phase, on the fourth day of biochemically confirmed smoking abstinence. During the laboratory sessions, participants self-administered a nicotine nasal spray and completed a timed series of cardiovascular, cognitive, and subjective assessments of response to nicotine. The relationships of allopregnanolone with baseline values and change scores of outcome measures were assessed using covariance pattern modeling. Study participants (N = 77) had a mean age of 29.9 (SD = 6.8) years and smoked an average of 12.2 (SD = 4.9) cigarettes per day. Allopregnanolone concentration measured before nicotine administration was positively associated with systolic (β = 0.85, p = .04) and diastolic blood pressure (β = 1.19, p < .001) and self-report of physical symptoms (β = 0.58, p < .001), dizziness (β = 0.88, p < .01), jitteriness (β = 0.90, p = .04), and pleasantness (β = 2.05, p = .04). Allopregnanolone also had significant positive associations with change in cognition following nicotine nasal spray administration, specifically discriminability as a measure of attention (β = 1.15, p = .05) and response bias as a measure of impulsivity (β = 0.13, p = .02). These data suggest that allopregnanolone may be related to cardiovascular and subjective physical state during acute smoking abstinence, as well as cognitive response to nicotine.


Family physician preferences and knowledge gaps regarding the care of adolescent and young adult survivors of childhood cancer.
Childhood cancer survivors are at risk for long-term morbidity and early mortality. Since most adult and some adolescent survivors of childhood cancer will receive their long-term care from a primary care physician, we sought to determine family physicians' comfort with caring for this population. A survey was mailed to 2,520 United States (US) and Canadian family physicians to assess their attitudes and knowledge regarding the care of adolescent and young adult survivors of childhood cancer. One thousand one hundred twenty-four family physicians responded (704 US, 420 Canadian). Median age was 53 years; 63 % were men; 81 % had cared for ≤2 childhood cancer survivors in the past 5 years. Of those who had cared for a survivor, 48 % had never or almost never received a treatment summary from the referring cancer center; 85 % preferred to care for survivors in consultation with a cancer center-based physician or long-term follow-up program. Only 33, 27, and 23 % of respondents were very comfortable caring for survivors of childhood Hodgkin lymphoma, acute lymphoblastic leukemia or osteosarcoma, respectively. Only 16, 10, and 74 % of respondents correctly identified the guideline recommended surveillance for secondary breast cancer, cardiac dysfunction and hypothyroidism in response to a vignette describing a Hodgkin lymphoma survivor. Respondents rated access to clinical care guidelines and receipt of a patient-specific letter from specialists with surveillance recommendations as the modalities most likely to assist them in caring for survivors. Most family physicians are willing to care for childhood cancer survivors in consultation with a cancer center, and with specific tools to facilitate this care. Adult and adolescent survivors of childhood cancer who receive their follow-up care from a family physician must be empowered to choose a physician who is comfortable with caring for survivors. Further, the survivor must ensure that their physician has access to a treatment summary as well as to patient-specific recommendations for surveillance for late effects of cancer therapy.


Analysis of the gut bacterial communities in beef cattle and their association with feed intake, growth, and efficiency.
The impetus behind the global food security challenge is direct, with the necessity to feed almost 10 billion people by 2050. Developing a food-secure world, where people have access to a safe and sustainable food supply, is the principal goal of this challenge. To achieve this end, beef production enterprises must develop methods to produce more pounds of animal protein with less. Selection for feed-efficient beef cattle using genetic improvement technologies has helped to understand and improve the stayability and longevity of such traits within the herd. Yet genetic contributions to feed efficiency have been difficult to identify, and differing genetics, feed regimens, and environments among studies contribute to great variation and interpretation of results. With increasing evidence that hosts and their microbiomes interact in complex associations and networks, examining the gut microbial population variation in feed efficiency may lead to partially clarifying the considerable variation in the efficiency of feed utilization. The use of metagenomics and high-throughput sequencing has greatly impacted the study of the ruminant gut. The ability to interrogate these systems at great depth has permitted a greater understanding of the microbiological and molecular mechanisms involved in ruminant nutrition and health. Although the microbial communities of the reticulorumen have been well documented to date, our understanding of the populations within the gastrointestinal tract as a whole is limited. The composition and phylogenetic diversity of the gut microbial community are critical to the overall well-being of the host and must be determined to fully understand the relationship between the microbiomes within segments of the cattle gastrointestinal tract and feed efficiency, ADG, and ADFI. This review addresses recent research regarding the bacterial communities along the gastrointestinal tract of beef cattle; their association with ADG, ADFI, and feed efficiency; and the potential implications for beef production.


Invited Commentary: Evolution of Social Networks, Health, and the Role of Epidemiology.
Almost 40 years ago, Berkman and Syme demonstrated that social networks were related to the risk of early mortality (Am J Epidemiol. 1979;109(2):186-204). Their study was highly innovative because they directly measured and quantified social networks in a large prospective population-based survey with mortality follow-up. The results of the study showed robust network gradients, whereby those with fewer networks and weaker social ties had significantly higher mortality rates. The important influence of social networks that Berkman and Syme noted many years ago is likely to heighten in the future, as demographic characteristics shift and individuals become more inclined to socialize through online platforms instead of real-world interactions. Berkman and Syme's research in 1979 continues to play a key role in shaping recent efforts to uncover the influence of social networks on health. Looking back on their findings may help epidemiologists better understand the importance of both online and offline networks for population health today.


Structural analysis of diols by electrospray mass spectrometry on boric acid complexes.
A method is presented to characterize diols using negative ion electrospray (ES) mass spectrometry in combination with collision-induced dissociation tandem mass spectrometry (MS/MS). The analyte diol is added to a solution containing an ethylene glycol/boric acid [2:1] complex and then subjected to infusion ES. The following boric acid complexes are formed: (i) a complex with two ethylene glycol molecules, (ii) a mixed ethylene glycol/analyte complex, and (iii) a complex with two analyte molecules. The first complex serves as a reference for the assessment of the extent of complex formation with the analyte. The ES mass spectra of acyclic vicinal diols all feature intense mixed complex signals, indicative of efficient complex formation. Chemical fine tuning is achieved by MS/MS experiments. Thus, although the (2R,3R)-(-)-2,3-butanediol and meso-2,3-butanediol stereo-isomers show the same complexation efficiency, MS/MS experiments reveal pronounced structure characteristic differences. By contrast, 1,3- and 1,4-diols are less prone to complex formation as they give only weak signals relative to the reference. For cyclic vicinal diols only the cis isomer produces an intense mixed complex, whose MS/MS spectrum is characteristically different from that of the trans form. The above procedure does not permit an unambiguous differentiation of acyclic polyhydroxy compounds like mannitol and sorbitol. However, structurally related methyl glycosides show characteristic MS/MS spectra. Our findings indicate that the above simple procedure may be useful to probe the presence and structure of diols and other polyols in aqueous solutions. Copyright 1999 John Wiley & Sons, Ltd.


Compound K Induces Endoplasmic Reticulum Stress and Apoptosis in Human Liver Cancer Cells by Regulating STAT3.
The ginsenoside compound K (20-O-β-d-glucopyranosyl-20(S)-protopanaxadiol; CK) is an intestinal bacterial metabolite of ginseng protopanaxadiol saponin that has been reported to induce apoptosis in many cancer cells; however, the precise mechanisms of its activity in human hepatocellular carcinoma (HCC) cells remain unclear. Herein, we demonstrated that CK inhibited the growth and colony formation of HepG2 and SMMC-7721 cells, phenotypes that were mediated by inducing apoptosis. Meanwhile, CK showed lower toxicity in normal hepatoma cells. After treating HepG2 and SMMC-7721 cells with CK, p-STAT3 levels decreased, the three branches of the unfolded protein response were activated, and levels of endoplasmic reticulum stress (ERS)-related proteins were increased. We also revealed that CK decreased the DNA-binding capacity of STAT3. Moreover, silencing STAT3 with CRISPR/Cas9 technology enhanced CK-induced ERS and apoptosis. Finally, we showed that CK inhibited the growth of liver cancer xenografts with little toxicity. Mice bearing human HCC xenografts that were treated with CK showed increased GRP78 expression and decreased p-STAT3 levels. Taken together, these data showed that CK induced ERS and apoptosis by inhibiting p-STAT3 in human liver cancer cells; thus, CK might be a potential therapeutic candidate for human HCC.


Protocol for cardiac assessment of recreational athletes.
In this work, the development of a database on physical fitness is presented. As initial population to fill this database, people who practice recreational sports at the Universidad Simon Bolivar (USB) were chosen. The goal was studying individual physical fitness in order to structure exercise routines that gives certain benefits without risking the individual health, promoting a less sedentary way of life. Before the study, a low-cost noninvasive protocol was designed to determine the level of physical fitness. The methodology consisted of four steps: a) A review of existing protocols to propose a set of physical fitness (International Physical Activity Questionnaire (IPAQ)), cardiovascular (heart rate variability, heart rate recovery time and arterial blood pressure), anthropomorphic, aerobic (maximum oxygen consumption) and mood state (Profile of Mood State (POMS)) measurements, which allow sketching a complete profile on the sportsman physical fitness. b) Instrumental data collection. c) Electrocardiographic signal processing. d) Data post-processing using multivariate analysis. The database was composed of 26 subject from USB. Ten subjects were soccer players, ten were mountain climbers and six were sedentary people. Results showed that the heart rate recover time after 2-3 min, IPAQ and maximum oxygen consumption have higher weights for classifying individuals according to their habitual physical activity. Heart rate variability, as well as, POMS did not contribute greatly for discriminating recreational sport from sedentary persons.


Electrn microscopic observations on virus-like particles associated with SH antigen.
The structural aspects of SH antigen-containing particles were investigated. These studies confirmed the existence of a large spherical particle (ca. 43 nm) and smaller (ca. 20 nm) rod- and sphere-shaped particles. The large particle consists of an outer and inner membrane and a core of "nucleic acid" as seen by positive staining techniques. The outer membrane of the large particle appears to be similar to that of the 20-nm diameter spheres and rods known to possess the SH antigen.


Genetic essential tremor in gamma-aminobutyric acidA receptor alpha1 subunit knockout mice.
Essential tremor is the most common movement disorder and has an unknown etiology. Here we report that gamma-aminobutyric acidA (GABA(A)) receptor alpha1-/- mice exhibit postural and kinetic tremor and motor incoordination that is characteristic of essential tremor disease. We tested mice with essential-like tremor using current drug therapies that alleviate symptoms in essential tremor patients (primidone, propranolol, and gabapentin) and several candidates hypothesized to reduce tremor, including ethanol; the noncompetitive N-methyl-D-aspartate receptor antagonist MK-801; the adenosine A1 receptor agonist 2-chloro-N6-cyclopentyladenosine (CCPA); the GABA(A) receptor modulators diazepam, allopregnanolone, and Ro15-4513; and the L-type Ca2+ channel antagonist nitrendipine. Primidone, propranolol, and gabapentin reduced the amplitude (power) of the pathologic tremor. Nonsedative doses of ethanol eliminated tremor in mice. Diazepam, allopregnanolone, Ro15-4513, and nitrendipine had no effect or enhanced tremor, whereas MK-801 and CCPA reduced tremor. To understand the etiology of tremor in these mice, we studied the electrophysiological properties of cerebellar Purkinje cells. Cerebellar Purkinje cells in GABA(A) receptor alpha1-/- mice exhibited a profound loss of all responses to synaptic or exogenous GABA, but no differences in abundance, gross morphology, or spontaneous synaptic activity were observed. This genetic animal model elucidates a mechanism of GABAergic dysfunction in the major motor pathway and potential targets for pharmacotherapy of essential tremor.


Molecular cloning and expression of cynomolgus monkey interleukin-1beta cDNA.
The cynomolgus monkey cDNA encoding interleukin-1beta (IL-1beta) was molecularly cloned by the reverse transcription polymerase chain reaction from a cDNA library of adherent splenocytes stimulated with lipopolysaccharides. The sequence analysis showed that the monkey IL-1beta cDNA encodes a protein of 268 amino acids and displays a high degree (90%) of homology with the human counterpart. Substitution of amino acids resides mainly in the leader sequences of IL-1beta when compared with those of human IL-1beta. This cloned monkey IL-1beta cDNA was used to express in Escherichia coli as a fusion protein with thioredoxin and in insect cells infected with a recombinant baculovirus after molecular modification where monkey IL-1beta signal sequences were placed prior to the mature sequences of IL-1beta for efficient secretion in insect cells. Recombinant monkey IL-1beta expressed in both systems was shown to react with rabbit antihuman IL-1beta antiserum by Western blot analysis and to have the biological activity of IL-1beta in a bioassay.


Ultrashort peptide bioconjugates are exclusively antifungal agents and synergize with cyclodextrin and amphotericin B.
Many natural broad-spectrum cationic antimicrobial peptides (AMPs) possess a general mode of action that is dependent on lipophilicity and charge. Modulating the lipophilicity of AMPs by the addition of a fatty acid has been an effective strategy to increase the lytic activity and can further broaden the spectrum of AMPs. However, lipophilic modifications that narrow the spectrum of activity and exclusively direct peptides to fungi are less common. Here, we show that short peptide sequences can be targeted to fungi with structured lipophilic biomolecules, such as vitamin E and cholesterol. The conjugates were active against Aspergillus fumigatus, Cryptococcus neoformans, and Candida albicans but not against bacteria and were observed to cause membrane perturbation by transmission electron microscopy and in membrane permeability studies. However, for C. albicans, selected compounds were effective without the perturbation of the cell membrane, and synergism was seen with a vitamin E conjugate and amphotericin B. Moreover, in combination with β-cyclodextrin, antibacterial activity emerged in selected compounds. Biocompatibility for selected active compounds was tested in vitro and in vivo using toxicity assays on erythrocytes, macrophages, and mice. In vitro cytotoxicity experiments led to selective toxicity ratios (50% lethal concentration/MIC) of up to 64 for highly active antifungal compounds, and no in vivo murine toxicity was seen. Taken together, these results highlight the importance of the conjugated lipophilic structure and suggest that the modulation of other biologically relevant peptides with hydrophobic moieties, such as cholesterol and vitamin E, generate compounds with unique bioactivity.


Tracking the dynamics of the social brain: ERP approaches for social cognitive and affective neuroscience.
Event-related potential (ERP) approaches to social cognitive and affective neuroscience (SCAN) are not as widely used as other neuroimaging techniques, yet they offer several unique advantages. In particular, the high temporal resolution of ERP measures of neural activity make them ideally suited for studying the dynamic interplay of rapidly unfolding cognitive and affective processes. In this article, we highlight the utility of ERP methods for scientists investigating questions of SCAN. We begin with a brief description of the physiological basis of ERPs and discussion of methodological practices. We then discuss how ERPs may be used to address a range of questions concerning social perception, social cognition, attitudes, affect and self-regulation, with examples of research that has used the ERP approach to contribute important theoretical advances in these areas. Whether used alone or in combination with other techniques, the ERP is an indispensable part of the social and affective neuroscientist's methodological toolkit.


Fringe projection profilometry method with high efficiency, precision, and convenience: theoretical analysis and development.
Fringe projector profilometry (FPP) is an important three-dimensional (3D) measurement technique, especially when high precision and speed are required. Thus, theoretical interrogation is critical to provide deep understanding and possible improvement of FPP. By dividing an FPP measurement process into four steps (system calibration, phase measurement, pixel correspondence, and 3D reconstruction), we give theoretical analysis on the entire process except for the extensively studied calibration step. Our study indeed reveals a series of important system properties, to the best of our knowledge, for the first time: (i) in phase measurement, the optimal and worst fringe angles are proven perpendicular and parallel to epipolar line, respectively, and can be considered as system parameters and can be directly made available during traditional calibration, highlighting the significance of the epipolar line; (ii) in correspondence, when two sets of fringes with different fringe orientations are projected, the highest correspondence precision can be achieved with arbitrary orientations as long as these two orientations are perpendicular to each other; (iii) in reconstruction, a higher reconstruction precision is given by the 4-equation methods, while we notice that the 3-equation methods are almost dominatingly used in literature. Based on these theoretical results, we propose a novel FPP measurement method which (i) only projects one set of fringes with optimal fringe angle to explicitly work together with the epipolar line for precise pixel correspondence; (ii) for the first time, the optimal fringe angle is determined directly from the calibration parameters, instead of being measured; (iii) uses 4 equations for precise 3D reconstruction but we can remove one equation which is equivalent to an epipolar line, making it the first algorithm that can use 3-equation solution to achieve 4-equation precision. Our method is efficient (only one set of fringe patterns is required in projection and the speed is doubled in reconstruction), precise (in both pixel correspondence and 3D reconstruction), and convenient (the computable optimal fringe angle and a closed-form 3-equation solution). We also believe that our work is insightful in revealing fundamental FPP properties, provides a more reasonable measurement for practice, and thus is beneficial to further FPP studies.


Orthotopic Ferret Tracheal Transplantation Using a Recellularized Bioengineered Graft Produces Functional Epithelia.
Tracheal grafts may be necessary to bridge long-segment defects after curative resection for airway obstructions. Bioengineered grafts have emerged as an appealing option, given the possibilities of altering the histologic and cellular profile of the conduit. We previously designed a bioreactor capable of luminally decellularizing and recellularizing a ferret trachea with surface airway epithelia (SAE) basal cells (BCs), and we sought to assess the fate of these grafts when transplanted in an orthotopic fashion. As adjuncts to the procedure, we investigated the use of a vascular endothelial growth factor (VEGF)-laden hydrogel and of immunosuppression (IS) in graft revascularization and viability. IS was shown to limit early graft revascularization, but this effect could be counteracted with VEGF supplementation. Submucosal gland (SMG) loss was shown to be inevitable regardless of the revascularization strategy. Lastly, the bioengineered tracheas survived one month after transplant with differentiation of our implanted BCs that then transitioned into a recipient-derived functional epithelium. The work presented in this manuscript has important implications for future cellular and regenerative therapies.


Reduced levels of mercury in first baby haircuts of autistic children.
Reported rates of autism have increased sharply in the United States and the United Kingdom. One possible factor underlying these increases is increased exposure to mercury through thimerosal-containing vaccines, but vaccine exposures need to be evaluated in the context of cumulative exposures during gestation and early infancy. Differential rates of postnatal mercury elimination may explain why similar gestational and infant exposures produce variable neurological effects. First baby haircut samples were obtained from 94 children diagnosed with autism using Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM IV) criteria and 45 age- and gender-matched controls. Information on diet, dental amalgam fillings, vaccine history, Rho D immunoglobulin administration, and autism symptom severity was collected through a maternal survey questionnaire and clinical observation. Hair mercury levels in the autistic group were 0.47 ppm versus 3.63 ppm in controls, a significant difference. The mothers in the autistic group had significantly higher levels of mercury exposure through Rho D immunoglobulin injections and amalgam fillings than control mothers. Within the autistic group, hair mercury levels varied significantly across mildly, moderately, and severely autistic children, with mean group levels of 0.79, 0.46, and 0.21 ppm, respectively. Hair mercury levels among controls were significantly correlated with the number of the mothers' amalgam fillings and their fish consumption as well as exposure to mercury through childhood vaccines, correlations that were absent in the autistic group. Hair excretion patterns among autistic infants were significantly reduced relative to control. These data cast doubt on the efficacy of traditional hair analysis as a measure of total mercury exposure in a subset of the population. In light of the biological plausibility of mercury's role in neurodevelopmental disorders, the present study provides further insight into one possible mechanism by which early mercury exposures could increase the risk of autism.


The pattern of cortical atrophy in patients with Parkinson's disease according to cognitive status.
Cognitive dysfunction is common in Parkinson's disease (PD), and along with PD with dementia (PDD), the concept of mild cognitive impairment in PD (PD-MCI) has been introduced. To identify structural candidates according to cognitive status in PD, we compared gray matter (GM) density across PD-intact cognition (PD-IC, n = 23), PD-MCI (n = 27), and PDD (n = 18) using voxel-based morphometry. The demographic data among PD subjects were similar, however, general cognition and disease duration were more severe in PD-MCI and PDD than in PD-IC. Compared with controls, GM density was significantly decreased in the left occipital area in PD-IC; the bilateral temporal, left prefrontal and insular, and right occipital areas in PD-MCI; and in widespread brain areas in PDD. Compared with PD-IC, patients with PD-MCI had significantly decreased GM density in the right middle frontal area, and those with PDD had decreased GM density in the right parietal, middle frontal, insular, and lentiform areas. GM density in patients with PDD was significantly decreased in the bilateral middle temporal, right inferior temporal, and left middle and superior prefrontal areas. PDD patients with shorter disease duration before dementia (<5 year) showed greater GM atrophy in the posterior cingulate area than did those with longer disease duration (≥5 year). These data suggest that cortical atrophy in PD exhibits a greater extent with increasing levels of cognitive impairment, and different anatomical substrates would correspond to each cognitive status.


Characterizing and predicting pathologic spine fractures in myeloma patients with FDG PET/CT and MR imaging.
To determine if FDG PET/CT scans can be used to discriminate between old and new pathologic spine fractures in myeloma patients and also to determine if there is any combination of PET/CT and MR imaging findings that may indicate an impending spine fracture. Retrospective review, after IRB approval, by two musculoskeletal radiologists and one nuclear medicine physician was done. PET/CT database was searched to identify studies performed in myeloma patients, using the search terms myeloma, plasmacytoma, or plasma cell. Records, for this group of 176 patients, were searched for concurrent spine MR imaging and report of fracture. The SUV(max) was recorded for each vertebral level from C2 through L5. All other imaging studies carried out in each patient (spine radiographs, spine CTs, and spine MRIs) and clinical records also were reviewed. Spine fractures were identified using the Genant system. MR imaging findings noted included signal intensity, pattern of involvement, as well as the size and location, within the vertebral body, of individual focal lesions. 31 of the 176 patients had concurrent spine MR imaging and report of fracture. Five of these 31 patients were excluded because they had no documentation of the age of fracture prior to PET/CT imaging. The 26 remaining patients (598 vertebral levels) included 17 men and 9 women. There were a total of 59 PET/CTs, 104 spine X-ray studies, 25 spine CT exams, and 71 spine MRI exams. There were a total of 134 vertebral body fractures: 27 were determined to be acute/subacute and pathologic due to active myeloma, 1 was determined to be new but owing to simple osteoporosis, and 106 were determined to be old. The mean SUV(max) in the acute/subacute pathologic fractures was 2.9 with a range from 1.1 to 4.3 (standard deviation 0.98). The old fractures had a mean SUV(max) of 1.6 with a range from 0.6 to 3.1 (standard deviation 0.55). This was a statistically significant difference with p value <.0001. The 464 vertebral bodies without fracture had a mean SUV(max) of 1.8. SUV(max) ≥2.5 was seen at 49 vertebral levels, including 27 with a fracture and 22 without a fracture. SUV(max) ≥3.5 was found at 9 vertebral levels, including 6 with a fracture and 3 without a fracture. The combination of diffuse or multifocal MR patterns and SUV > 3.5 was seen at 7 levels, all but one with new pathologic fractures. PET/CT SUV > 3.2 alone can be used in myeloma patients to discriminate between old and new pathologic fractures, just as it has been reported in other types of cancer patients. The combination of PET/CT SUV > 3.5 and MR findings of diffuse or multifocal vertebral body involvement seems to indicate an impending fracture.


Event-Related Potential Correlates of Valence, Arousal, and Subjective Significance in Processing of an Emotional Stroop Task.
The present study is the first to measure event-related potentials associated with the processing of the emotional Stroop task (EST) with the use of an orthogonal factorial manipulation for emotional valence, arousal, and subjective significance (the importance of the current experience for goals and plans for the future). The current study aimed to investigate concurrently the role of the three dimensions describing the emotion-laden words for interference control measured in the classical version of the EST paradigm. The results showed that reaction times were affected by the emotional valence of presented words and the interactive effect of valence and arousal. The expected emotional arousal effect was only found in behavioral results for neutrally valenced words. Electrophysiological results showed valence and subjective significance correlated with the amplitude differences in the P2 component. Moreover, the amplitude of the N450 component varied with the level of subjective significance. This study also demonstrated that exploratory event-related potential analysis provides additional information beyond the classical component-based analysis. The obtained results show that cognitive control effects in the EST may be altered by manipulation in the subjective significance dimension.


Porous Polymersomes as Carriers for Silver Nanoparticles and Nanoclusters: Advantages of Compartmentalization for Antimicrobial Usage.
The global threat to public health posed by antibiotic-resistant bacterial infections requires the exploration of innovative approaches. Nanomaterials, particularly silver nanoparticles (AgNPs) and nanoclusters (AgNCs), have emerged as potential solutions to address the pressing issue of a bacterial healthcare crisis. However, the high cytotoxicity levels and low stability associated with AgNPs and AgNCs limit their applicability. To overcome these challenges, AgNCs and AgNPs were synthesized in the presence of porous polymersomes, resulting in a compartmentalized system that enhances stability, reduces cytotoxicity, and maintains high antimicrobial activity. The encapsulated particles exhibit a distribution of silver components on both the surface and the core, which is confirmed through the analysis of surface charge and center of mass. Moreover, our investigation demonstrates improved stability of the nanoparticles and nanoclusters upon entrapment in the porous system, as evidenced by the ion release assay. The antimicrobial effectiveness of porous polymersomes containing AgNPs and AgNCs was demonstrated by visualizing the biofilms and quantifying the penetration depth. Furthermore, cytotoxicity studies showed that compartmentalization increases cell compatibility for AgNC-based systems, showcasing the many advantages this system holds.


The SUMMIT ambulatory-ICU primary care model for medically and socially complex patients in an urban federally qualified health center: study design and rationale.
Medically complex urban patients experiencing homelessness comprise a disproportionate number of high-cost, high-need patients. There are few studies of interventions to improve care for these populations; their social complexity makes them difficult to study and requires clinical and research collaboration. We present a protocol for a trial of the streamlined unified meaningfully managed interdisciplinary team (SUMMIT) team, an ambulatory ICU (A-ICU) intervention to improve utilization and patient experience that uses control populations to address limitations of prior research. Participants are patients at a Federally Qualified Health Center in Portland, Oregon that serves patients experiencing homelessness or who have substance use disorders. Participants meet at least one of the following criteria: > 1 hospitalization over past 6 months; at least one medical co-morbidity including uncontrolled diabetes, heart failure, chronic obstructive pulmonary disease, liver disease, soft-tissue infection; and 1 mental health diagnosis or substance use disorder. We exclude patients if they have < 6 months to live, have cognitive impairment preventing consent, or are non-English speaking. Following consent and baseline assessment, we randomize participants to immediate SUMMIT intervention or wait-list control group. Participants receiving the SUMMIT intervention transfer care to a clinic-based team of physician, complex care nurse, care coordinator, social worker, and pharmacist with reduced panel size and flexible scheduling with emphasis on motivational interviewing, patient goal setting and advanced care planning. Wait-listed participants continue usual care plus engagement with community health worker intervention for 6 months prior to joining SUMMIT. The primary outcome is hospital utilization at 6 months; secondary outcomes include emergency department utilization, patient activation, and patient experience measures. We follow participants for 12 months after intervention initiation. The SUMMIT A-ICU is an intensive primary care intervention for high-utilizers impacted by homelessness. Use of a wait-list control design balances community and staff stakeholder needs, who felt all participants should have access to the intervention, while addressing research needs to include control populations. Design limitations include prolonged follow-up period that increases risk for attrition, and conflict between practice and research; including partner stakeholders and embedded researchers familiar with the population in study planning can mitigate these barriers. Trial registration ClinicalTrials.gov NCT03224858, Registered 7/21/17 retrospectively registered https://clinicaltrials.gov/ct2/show/NCT03224858.


Wheelchair-mounted robotic arms: a survey of occupational therapists' practices and perspectives.
Despite the benefits of wheelchair-mounted robotic arms (WMRAs), occupational therapists are not yet widely involved in the recommendation or implementation of these assistive devices. The purpose of this study was to investigate and compare the current practices and perspectives of occupational therapists who had and had not recommended a WMRA on the recommendation, training, and implementation of WMRAs. This was a descriptive cross-sectional study. An online survey was sent to Canadian, European, and American occupational therapists who had or had not worked with WMRAs. Respondents were asked close-ended questions about their experience, role, barriers, motivations, and future needs regarding WMRAs. We compared results between respondents who had and had not recommended WMRAs using descriptive statistics. Ninety-three North American and European occupational therapists completed the survey. Of those, 29 (31.2%) had recommended a WMRA, mostly the JACO robotic arm (n = 26, 89.7%) in rehabilitation centres (n = 18, 62.1%). Their perspectives on their role and barriers related to WMRAs were similar to those who had never recommended a WMRA. All respondents recognised the relevance of occupational therapists' contribution, and most reported interest in WMRAs (n = 76, 81.7%). However, many barriers emerged, mainly related to limited funding (n = 49, 76.6%), lack of training and knowledge (n = 38, 59.4%), and resource constraints (n = 37, 54.4%). Future needs identified matched these barriers. This survey provides novel insight into occupational therapists' perspectives on WMRAs. It highlights that health professionals need to have easier access to funding, formal training, and resources to support their involvement with WMRAs.Implications for rehabilitationMost occupational therapists are interested in working with WMRAs, considering the potential of these devices to support individuals with upper extremity impairments in their daily activities. They also recognise their unique contribution to the assessment, recommendation, and implementation process among multidisciplinary teams.WMRA recommendation is relevant in various clinical settings and with a wide range of client populations. Nevertheless, it appears that occupational therapists working with adults, in rehabilitation centres or specialised clinics, may have more opportunities to get involved in this process and to attend formal training on this technology, as compared to other settings.Many barriers remain, impeding occupational therapists' role in the recommendation and implementation of WMRAs. Addressing these barriers may increase the number of devices that are successfully adopted and utilised by individuals with upper extremity impairments. In particular, future research and health policies should focus on access to sufficient funding, formal training, and resources for occupational therapists relative to their role in recommending and implementing WMRAs.


The role of caveolin-1 in blood-brain barrier disruption induced by focused ultrasound combined with microbubbles.
This research was designed to determine whether disrupting the blood-brain barrier (BBB) in rats by applying focused ultrasound (FUS) combined with microbubbles induced changes in the density of caveolae and/or the expression of the structural protein caveolin-1. To this end, two approaches were utilized. First, using enhanced magnetic resonance imaging, characteristics of BBB disruption induced by our specific FUS parameters and dose of microbubble were recorded, and the time after treatment when the BBB was the most permeable was determined. Second, rats were treated with FUS or microbubbles alone, both or neither, and a combination of Evans blue (EB) BBB permeability assays, streptavidin-peroxidase (SP) immunohistochemistry, western blot, and transmission electron microscopy (TEM) was employed to detect any changes in caveolae density and caveolin-1 expression at the previously determined time point when the BBB was the most permeable. The first set of studies revealed that our specific FUS parameters and dose of microbubbles were able to induce a transient, targeted, and reversible BBB opening in rats, and that the BBB was the most permeable 1 h after treatment with FUS and microbubbles. In the second set of experiments, the results of the SP immunohistochemistry, western blot, and TEM, taken together, revealed that caveolae and caveolin-1 were primarily localized in the brain microvascular endothelial cells of all of the rats regardless of treatment, and that caveolin-1 expression was highest in the rats treated with both FUS and microbubbles. In summary, treatment with FUS, in combination with a dose of microbubbles, can enhance BBB permeability through a caveolae-mediated transcellular approach by upregulating the expression level of caveolin-1 and, consequently, the amount of caveolae. This caveolin-1-mediated transcellular transport pathway may cooperate with other transport pathways to induce opening of the BBB. This research sheds light on the mechanism of a transient, targeted, and reversible opening of the BBB induced by FUS combined with microbubbles.


[Age-specific learning ability in Japanese quails (Coturnix coturnix japonica)].
The main question of our investigation is: Do there exist age-specific learning abilities in animals? 120 QUAILS (Coturnix coturnix japonica) of 12 different age groups (between one day and 20 weeks) were tested in a combination apparatus 0y using two training methods. 60 quails were trained with decreasing (1), 60 other quails with increasing learning assistance (2). In each case the learning period lasted 5 days after which the animals were tested in a two-way choice apparatus and in a simple maze. Retention was tested 3 weeks later. - The 2 methods led to different results. In general the younger animals learnt better than the other ones when trained by method 1. No differences in learning performance between the 12 age groups were obtained by method 2.


Synergic Effect of Nanolignin and Metal Oxide Nanoparticles into Poly(l-lactide) Bionanocomposites: Material Properties, Antioxidant Activity, and Antibacterial Performance.
Binary and ternary poly(l-lactide) (PLLA)-based nanocomposites, containing nanolignin (1 wt %) and different metal oxide nanoparticles (0.5 wt %, Ag2O, TiO2, WO3, Fe2O3, and ZnFe2O4), were realized by solvent casting, and their morphological, thermal, surface, optical, antioxidant, and antimicrobial characterizations were performed. The presence of metal oxide nanoparticles at the selected weight concentration affects the surface microstructure of the PLLA polymer, and this outcome is particle-type dependent, according to the shape, morphology, and chemical properties of the selected nanoparticles (NPs). Analogously, wettability of PLLA-based nanocomposites was slightly modified by the presence of hydrophobic lignin nanoparticles and different shaped metal oxides. Results of differential scanning calorimetry (DSC) and X-ray powder diffraction (XRD) tests confirmed that nanoparticle addition confined the mobility of the amorphous phase, increasing at the same time the formation of more numerous but less perfect PLLA crystals. Interestingly, antioxidant activity was also obtained in ternary-based nanocomposites, where a synergic effect of lignin and metal oxide nanoparticles was obtained. Antibacterial tests showed manifest activity of TiO2 and Ag2O nanoparticles containing PLLA films, and the time dependence was more evident for Staphylococcus aureus than for Escherichia coli. Lignin nanoparticles are able to provide protection against UV light while still allowing visible light to pass and even surpass the UV-protection capacity provided by many inorganic nanoparticles. This makes them an attractive renewable additive for the realization of PLLA/metal oxide nanocomposites in the fields of food, drug packaging, and biomedical industry, where antibacterial and antioxidant properties are required.


Abscisic acid: Metabolism, transport, crosstalk with other plant growth regulators, and its role in heavy metal stress mitigation.
Heavy metal (HM) stress is threatening agricultural crops, ecological systems, and human health worldwide. HM toxicity adversely affects plant growth, physiological processes, and crop productivity by disturbing cellular ionic balance, metabolic balance, cell membrane integrity, and protein and enzyme activities. Plants under HM stress intrinsically develop mechanisms to counter the adversities of HM but not prevent them. However, the exogenous application of abscisic acid (ABA) is a strategy for boosting the tolerance capacity of plants against HM toxicity by improving osmolyte accumulation and antioxidant machinery. ABA is an essential plant growth regulator that modulates various plant growth and metabolic processes, including seed development and germination, vegetative growth, stomatal regulation, flowering, and leaf senescence under diverse environmental conditions. This review summarizes ABA biosynthesis, signaling, transport, and catabolism in plant tissues and the adverse effects of HM stress on crop plants. Moreover, we describe the role of ABA in mitigating HM stress and elucidating the interplay of ABA with other plant growth regulators.


Doxorubicin-induced apoptosis enhances monocyte infiltration and adverse cardiac remodeling in diabetic animals.
Diabetic cancer patients were treated with doxorubicin (DOX), a potent chemotherapeutic drug that induces cardiac toxicity; however, molecular mechanisms of cardiac toxicity in this specific disease progression in patients and animal models are completely unknown. Therefore, we designed a study to understand the effects of DOX-induced cardiac toxicity in diabetic animals and the involved pathophysiological mechanisms. C57BL/6 J mice were divided into four DOX- and diabetic (streptozotocin; STZ) - treated groups; control, STZ, DOX, and DOX+STZ. At day 14, animals were sacrificed, echocardiography was used to examine heart function, and heart and blood samples were collected to investigate apoptotic mechanisms (caspase 3, BAX, B-Cell leukemia/lymphoma 2 (Bcl2)), inflammation, and cardiac remodeling. Our data shows a significant (p < 0.05) increase in glucose levels, apoptotic markers, and monocyte infiltration at the site of apoptosis and triggered inflammatory immune response (tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6)), in DOX+STZ animals compared with control and experimental groups. We also observed significant (p < 0.05) increase in myofibrillar area, fibrosis, and significantly decreased (p < 0.05) cardiac function in DOX-treated diabetic animals compared with controls. In conclusion, our data suggest that DOX induces significantly increased apoptosis, fibrosis, and structural alterations in diabetic hearts compared with non-diabetic animals.


[Effect of a multivitamin on insulin resistance, inflammation, and oxidative stress in a Wistar rat model of induced obesity].
Introduction: excessive accumulation of adipose tissue is accompanied by alterations in the inflammatory state and increased oxidative stress, and these variables are associated with insulin resistance and increased glucose and insulin levels. On the other hand, vitamins and minerals reinforce the antioxidant and inflammatory capacity, for this reasons we propose that they could contribute to the control of insulin resistance, glucose and lipid metabolism in a rat model of obesity. Objective: to analyze the effect of a multivitamin supplement on markers of insulin resistance, inflammation, and oxidative stress in obese rats on a cafeteria diet. Methods: thirty-five 28-day-old male Wistar rats were randomly divided into four groups: 1, standard diet control; 2, standard diet plus multivitamin; 3, obese on a cafeteria diet; and 4, obese on a cafeteria diet plus multivitamin. After the treatments, glucose levels, HbA1c, insulin, TNF-α, IL-6, oxidative stress and lipid profile were analyzed by colorimetric methods, as well as the percentage of adipose tissue, Homeostasis Model Assessment (HOMA) index y Quantitative Insulin Sensitivity Check Index (QUICKI). Results: multivitamin supplementation significantly decreased visceral adipose tissue, HOMA index, glucose, HbA1c, oxidant stress, and inflammatory markers in the obese plus multivitamin rat group, compared with the obese cafeteria diet rat group and the standard diet rat control group. However, the group that was administered only the multivitamin without the cafeteria diet had increased levels of total adipose tissue, glucose, and oxidative stress, as well as the QUICKI index relative to the control group with the standard diet. Conclusion: co-administration of a multivitamin supplement may improve insulin sensitivity, glucose metabolism and lipid profile; strengthen antioxidant status; and decrease inflammation during weight gain. However, it was not expected that added sugars in multivitamin supplement can also increase total adipose tissue, oxidative stress and glucose levels, so it is suggested to use sugar-free multivitamins in the future.


Does tardive dysmentia really exist?
Tardive dysmentia has been described as the behavioral equivalent of tardive dyskinesia in patients with schizophrenia. Its association with tardive dyskinesia and psychopathology has been controversial. The authors assessed 123 inpatients with chronic schizophrenia for presence of tardive dysmentia symptoms/signs. Psychopathology and tardive dyskinesia were also assessed. Of the group, 24 patients (19.5%) had at least one tardive dysmentia symptom/sign, whereas only 1 patient (0.8%) fulfilled the syndromal criteria for tardive dysmentia. Those with tardive dysmentia had higher psychopathology scores, higher Abnormal Involuntary Movement Scale total scores, higher number of women and family psychiatric illness, and higher rates of persistent tardive dyskinesia. Tardive dysmentia symptoms/signs are frequently seen in chronic schizophrenia, but the complete syndrome may be rare.


Healthcare providers' treatment of college smokers.
About 28% of college students smoke tobacco, and many will continue smoking into adulthood. Although little is known about how to help college students quit smoking, 1 promising strategy is healthcare providers' advice. To estimate their life-time receipt of brief advice and to identify characteristics that predict who may receive that advice, 348 college students completed a survey about their smoking and related practices. Seventy-seven percent of the smokers (73% of the students) were asked about smoking. Of those smokers, 57% were advised to quit, 22% were given advice about quitting, 5% were helped with setting a quit date, and 4% were offered follow-up. Occasional smokers were less likely than daily smokers to be advised to quit. Although 36.2% of the smokers did not report their smoking accurately, smokers who were accurate were more likely to be advised to quit and to be given advice about quitting.


The oceanic carbonate system: a reassessment of biogenic controls.
Fluxes of biogenic carbonates moving out of the euphotic zone and into deeper undersaturated waters of the North Pacific were estimated with free-drifting sediment traps. Short-duration (1 to 1.5 day) sampling between 100 and 2200 meters points to a major involvement in the oceanic carbonate system by a class of organisms which had been relegated to a secondary role-aragonitic pteropods. Pteropod fluxes through the base of the euphotic zone are almost large enough to balance the alkalinity budget for the Pacific Ocean. Dissolution experiments with freshly collected materials shed considerable light on a mystery surrounding these labile organisms: although plankton collections from net tows almost always contain large numbers of pteropods, these organisms are never a major component of biogenic materials in long-duration sediment trap collections. Their low abundance in long-duration collections results from dissolution subsequent to collection. Shortduration sampling showed significant increases in the ratio of calcitic foraminifera to aragonitic pteropods in undersaturated waters, indicating the more stable mineralogic form, calcite, was preserved relative to aragonite. Approximately 90 percent of the aragonite flux is remineralized in the upper 2.2 kilometers of the water column.


Multipotential marrow stromal cells transduced to produce L-DOPA: engraftment in a rat model of Parkinson disease.
Bone marrow stromal cells can be used as an alternative source of cells for neural transplantation and repair. Here, the efficacy of genetically modified marrow stromal cells was examined in a rat model of Parkinson disease. Rat marrow stromal cells (rMSCs) and human marrow stromal cells (hMSCs) were genetically engineered by transduction with retroviruses encoding tyrosine hydroxylase (TH) and GTP cyclohydrolase I, the enzyme necessary for production of the tetrahydrobiopterin cofactor for TH (BH4). Transduced cells synthesized 3,4-dihydroxyphenylalanine (L-DOPA) in vitro and maintained their multipotentiality after retroviral transduction. To examine the cells in vivo, transduced rMSCs were injected into the striatum of 6-hydroxydopamine-lesioned rats. L-DOPA and metabolites were detected by microdialysis in the denervated striatum of rats that received doubly transduced rMSCs. Also, there was a significant reduction in apomorphine-induced rotation when compared with controls. The cells engrafted and survived for at least 87 days. However, expression of the transgenes ceased at about 9 days, an observation consistent with reports from other laboratories in which similar retroviruses were used to express transgenes in the brain.


Direct contact between sympathetic neurons and rat cardiac myocytes in vitro increases expression of functional calcium channels.
To test the hypothesis that direct contact between sympathetic neurons and myocytes regulates expression and function of cardiac Ca channels, we prepared cultures of neonatal rat ventricular myocytes with and without sympathetic ganglia. Contractile properties of myocytes were assessed by an optical-video system. Contractility-pCa curves showed a 60% greater increase in contractility for innervated myocytes compared with control cells at 6.3 mM [Ca]0 (n = 8, P less than 0.05). Cells grown in medium conditioned by growth of ganglia and myocytes were indistinguishable physiologically from control cells. [Bay K 8644]-contractility curves revealed a 60 +/- 10% enhancement of the contractility response at 10(-6) M for innervated cells compared with control cells. The increased response to Bay K 8644 was not blocked by alpha- or beta-adrenergic antagonists. Moreover, increased efficacy of Bay K 8644 was maintained for at least 24 h after denervation produced by removal of ganglia from the culture. Dihydropyridine binding sites were assessed with the L channel-specific radioligand 3[H]PN200-110. PN200-110 binding sites were increased by innervation (51 +/- 5 to 108 +/- 20 fmol/mg protein, P less than 0.01), with no change in KD. Peak current-voltage curves were determined by whole-cell voltage clamp techniques for myocytes contacted by a neuron, control myocytes, and myocytes grown in conditioned medium. Current density of L-type Ca channels was significantly higher in innervated myocytes (10.5 +/- 0.4 pA/pF, n = 5) than in control myocytes (5.9 +/- 0.3 pA/pF, n = 8, P less than 0.01) or myocytes grown in conditioned medium (6.2 +/- 0.2 pA/pF, n = 10, P less than 0.01). Thus, physical contact between a sympathetic neuron and previously uninnervated neonatal rat ventricular myocytes increases expression of functional L-type calcium channels as judged by contractile responses to Ca0 and Bay K 8644, as well as by electrophysiological and radioligand binding properties.


Pathological calcification and replicating calcifying-nanoparticles: general approach and correlation.
Calcification, a phenomenon often regarded by pathologists little more than evidence of cell death, is becoming recognized to be important in the dynamics of a variety of diseases from which millions of beings suffer in all ages. In calcification, all that is needed for crystal formation to start is nidi (nuclei) and an environment of available dissolved components at or near saturation concentrations, along with the absence of inhibitors for crystal formation. Calcifying nanoparticles (CNP) are the first calcium phosphate mineral containing particles isolated from human blood and were detected in numerous pathologic calcification related diseases. Controversy and critical role of CNP as nidi and triggering factor in human pathologic calcification are discussed.


Virulence of a Salmonella typhimurium OmpD mutant.
An ompD mutation caused by a Tn10 insertion was transduced into Salmonella typhimurium SL1344 and UK-1. The adherence and invasion capabilities of the resultant ompD mutants were examined by tissue culture analysis. The virulence of the S. typhimurium ompD mutants was ascertained by a 50% lethal dose (LD50) study and by determining colonization ability with BALB/c mice. We found no statistically significant difference in adherence and invasion capacities between the S. typhimurium wild type strains and their corresponding ompD mutants. Furthermore, the LD50 and colonization studies revealed that there is no statistically significant difference in virulence between the S. typhimurium wild type strains and their corresponding ompD mutants. These results differ from those reported previously (C. J. Dorman, S. Chatfield, C. F. Higgins, C. Hayward, and G. Dougan, Infect. Immun. 57:2136-2140, 1989).


Cognitive function improvement with astaxanthin and tocotrienol intake: a randomized, double-blind, placebo-controlled study.
We examined the effects of the mixed ingestion of astaxanthin derived from Haematococcus pluvialis and tocotrienols on the cognitive function of healthy Japanese adults who feel a memory decline. Forty-four subjects were randomly but equally assigned to the astaxanthin-tocotrienols or placebo group. An astaxanthin-tocotrienols or placebo capsule was taken once daily before or after breakfast for a 12-week intervention period. The primary outcome was composite memory from the Cognitrax cognitive test, and the secondary outcomes were other cognitive functions and subjective symptoms for memory. Each group included 18 subjects in the efficacy analysis (astaxanthin-tocotrienols group, 55.4 ± 7.9 years; placebo group, 54.6 ± 6.9 years). The astaxanthin-tocotrienols group showed a significant improvement in composite memory and verbal memory in Cognitrax at Δ12 weeks compared with the placebo group. Additionally, the astaxanthin-tocotrienols group showed a significant improvement in the subjective symptom of "During the last week, have you had trouble remembering people's names or the names of things?" compared with the placebo group after 12 weeks. No adverse events were observed in this study. The results demonstrated that taking an astaxanthin-tocotrienols combination improves the composite memory and verbal memory of Japanese adults who feel a memory decline (UMIN 000031758).


Polysaccharide oxidation by lytic polysaccharide monooxygenase is enhanced by engineered cellobiose dehydrogenase.
The catalytic function of lytic polysaccharide monooxygenases (LPMOs) to cleave and decrystallize recalcitrant polysaccharides put these enzymes in the spotlight of fundamental and applied research. Here we demonstrate that the demand of LPMO for an electron donor and an oxygen species as cosubstrate can be fulfilled by a single auxiliary enzyme: an engineered fungal cellobiose dehydrogenase (CDH) with increased oxidase activity. The engineered CDH was about 30 times more efficient in driving the LPMO reaction due to its 27 time increased production of H2 O2 acting as a cosubstrate for LPMO. Transient kinetic measurements confirmed that intra- and intermolecular electron transfer rates of the engineered CDH were similar to the wild-type CDH, meaning that the mutations had not compromised CDH's role as an electron donor. These results support the notion of H2 O2 -driven LPMO activity and shed new light on the role of CDH in activating LPMOs. Importantly, the results also demonstrate that the use of the engineered CDH results in fast and steady LPMO reactions with CDH-generated H2 O2 as a cosubstrate, which may provide new opportunities to employ LPMOs in biomass hydrolysis to generate fuels and chemicals.


Exposure to exogenous enkephalins disrupts reproductive development in the Eastern lubber grasshopper, Romalea microptera (Insecta: Orthoptera).
Enkephalins play a major role in reproductive physiology in crustaceans; however their role in reproductive development in insects is largely unknown. We investigated the effect of exposure to exogenous leucine-enkephalin (Leu-Enk), methionine-enkephalin (Met-Enk), and the opioid antagonist naloxone on gonad development in the Eastern lubber grasshopper, Romalea microptera. Injection of either Leu-Enk or naloxone alone significantly increased the testicular index and testicular follicular diameter in males, and the ovarian index, oocyte length, and oocyte diameter in females. In contrast, injection of Met-Enk inhibited all measures of reproductive development in both sexes. Surprisingly, co-injection of naloxone with either enkephalin enhanced the effect associated with administration of the enkephalin alone. This study clearly demonstrates the ability of enkephalins to disrupt insect sexual development and also suggests the existence of conserved enkephaline-dependent regulatory mechanisms in insects and crustaceans.


Amino acid sequences of Euglena viridis ferredoxin and cytochromes c.
The Order Euglenida comprises many species and perhaps 40 genera, but almost all biochemical and genetic studies have been limited to a single species. Euglena gracilis, because of its ease of growth in the laboratory. Sequence studies of chloroplast and mitochondrial proteins from E. gracilis show that they have diverged widely from other eukaryotic lines. In the present paper we report the sequences of three proteins from another euglenoid, Euglena viridis, using material isolated from a natural bloom. The mitochondrial cytochrome c shows more than 90% sequence identity with that from E. gracilis, and contains the same characteristic features. The chloroplast cytochrome c6 has diverged to a greater extent and shows only 77% identity. The chloroplast ferredoxin from E. viridis is similar in sequence to those of cyanobacteria and algal chloroplasts, with sequence identities of up to 75%. Details of the purification, analysis and sequence determination experiments on the peptides have been deposited as Supplementary Publication SUP 50163 (32 pages) at the British Library Document Supply Centre, Boston Spa, Wetherby, West Yorkshire LS23 7BQ, U.K., from whom copies can be obtained on the terms indicated in Biochem. J. (1991) 273, 5.


Uranyl precipitation by Pseudomonas aeruginosa via controlled polyphosphate metabolism.
The polyphosphate kinase gene from Pseudomonas aeruginosa was overexpressed in its native host, resulting in the accumulation of 100 times the polyphosphate seen with control strains. Degradation of this polyphosphate was induced by carbon starvation conditions, resulting in phosphate release into the medium. The mechanism of polyphosphate degradation is not clearly understood, but it appears to be associated with glycogen degradation. Upon suspension of the cells in 1 mM uranyl nitrate, nearly all polyphosphate that had accumulated was degraded within 48 h, resulting in the removal of nearly 80% of the uranyl ion and >95% of lesser-concentrated solutions. Electron microscopy, energy-dispersive X-ray spectroscopy, and time-resolved laser-induced fluorescence spectroscopy (TRLFS) suggest that this removal was due to the precipitation of uranyl phosphate at the cell membrane. TRLFS also indicated that uranyl was initially sorbed to the cell as uranyl hydroxide and was then precipitated as uranyl phosphate as phosphate was released from the cell. Lethal doses of radiation did not halt phosphate secretion from polyphosphate-filled cells under carbon starvation conditions.


FAM196B acts as oncogene and promotes proliferation of gastric cancer cells through AKT signaling pathway.
Gastric cancer (GC) is the second leading cause of cancer-related deaths worldwide, but the mechanisms remain unknown. Here we report that family with sequence similarity 196 member B (FAM196B) is highly expressed in primary GC tissues and the expression level is correlated with the clinicopathologic characteristics of GC. In this experiment, knockdown of FAM196B suppressed GC cell proliferation and induced G1/G0 to S phase cell cycle arrest by regulating Cyclin D1, Cyclin A and CDK2 expressions. Furthermore, we investigated the molecular mechanism of FAM196B action in GC. The results showed that knockdown of FAM196B inhibited the activation of AKT signaling pathway. We further revealed that activating of AKT rescued the effect of FAM196B knockdown on cell proliferation and drove cell re-enter into the S phase of the cell cycle with SC79 (a AKT activator). Our findings demonstrated that FAM196B may promote GC cell proliferation by activating AKT signaling pathway. Taken together, this study provides a new evidence that FAM196B functions as a novel oncogene and could be a potential therapeutic target in therapy of GC.


Current outcomes of the bi-directional cavopulmonary anastomosis in single ventricle patients: analysis of risk factors for morbidity and mortality, and suitability for Fontan completion.
The bi-directional cavopulmonary anastomosis forms an essential staging procedure for univentricular hearts. This review aims to identify risk factors for morbidity, mortality, and suitability for Fontan completion. A total of 114 patients undergoing cavopulmonary anastomosis between 1992 and 2012 were reviewed to assess primary - mortality and survival to Fontan completion - and secondary outcome endpoints - re-intubation, new drain, and ICU stay. Median age and weight were 8 months and 6.9 kg, respectively. In 83% of patients, 1-3 interventions had preceded. Norwood-type procedures became more prevalent over time. Extubation occurred after a median of 4 hours, median ICU stay was 2 days; 10 patients (8.8%) needed re-intubation and 18 received a new drain. Higher central venous pressure and transpulmonary gradient were risk factors for new drain insertion (p<0.01). Higher pre-operative pulmonary pressure correlated with increased inotropic support and prolonged intubation (p=0.01). Need for re-intubation was significantly affected by younger age at operation (p=0.01). Hospital and pre-Fontan mortality were 11.4 and 5.3%, respectively. Operative mortality was independently affected by younger age (p=0.013), lower weight (p=0.02), longer bypass time (p=0.04), and re-intubation (p=0.004). Interstage mortality was mainly influenced by moderate ventricular function (p=0.03); 82% of survivors underwent or are candidates for Fontan completion. The cavopulmonary anastomosis remains associated with adverse outcomes. Age at operation decreases with rising prevalence of complex univentricular hearts. Considering the important impact of re-intubation on hospital mortality, peri-operative management should focus on optimising cardio-respiratory status. Once this selection step is taken, successful Fontan completion can be expected, provided that ventricular function is maintained.


Oral administration of interferon tau enhances oxidation of energy substrates and reduces adiposity in Zucker diabetic fatty rats.
Male Zucker diabetic fatty (ZDF) rats were used to study effects of oral administration of interferon tau (IFNT) in reducing obesity. Eighteen ZDF rats (28 days of age) were assigned randomly to receive 0, 4, or 8 μg IFNT/kg body weight (BW) per day (n = 6/group) for 8 weeks. Water consumption was measured every two days. Food intake and BW were recorded weekly. Energy expenditure in 4-, 6-, 8-, and 10-week-old rats was determined using indirect calorimetry. Starting at 7 weeks of age, urinary glucose, and ketone bodies were tested daily. Rates of glucose and oleate oxidation in liver, brown adipose tissue, and abdominal adipose tissue, as well as leucine catabolism in skeletal muscle, and lipolysis in white and brown adipose tissues were greater for rats treated with 8 μg IFNT/kg BW/day in comparison with control rats. Treatment with 8 μg IFNT/kg BW/day increased heat production, reduced BW gain and adiposity, ameliorated fatty liver syndrome, delayed the onset of diabetes, and decreased concentrations of glucose, free fatty acids, triacylglycerol, cholesterol, and branched-chain amino acids in plasma, compared with control rats. Oral administration of 8 µg IFNT/kg BW/day ameliorated oxidative stress in skeletal muscle, liver, and adipose tissue, as indicated by decreased ratios of oxidized glutathione to reduced glutathione and increased concentrations of tetrahydrobiopterin. These results indicate that IFNT stimulates oxidation of energy substrates and reduces obesity in ZDF rats and may have broad important implications for preventing and treating obesity-related diseases in mammals.


Defective Bile Acid Signaling Promotes Vascular Dysfunction, Supporting a Role for G-Protein Bile Acid Receptor 1/Farnesoid X Receptor Agonism and Statins in the Treatment of Nonalcoholic Fatty Liver Disease.
Patients with nonalcoholic fatty liver disease are at increased risk to develop atherosclerotic cardiovascular diseases. FXR and GPBAR1 are 2 bile acid-activated receptors exploited in the treatment of nonalcoholic fatty liver disease: whether dual GPBAR1/FXR agonists synergize with statins in the treatment of the liver and cardiovascular components of nonalcoholic fatty liver disease is unknown. Investigations of human aortic samples obtained from patients who underwent surgery for aortic aneurysms and Gpbar1-/-, Fxr-/-, and dual Gpbar1-/-Fxr-/- mice demonstrated that GPBAR1 and FXR are expressed in the aortic wall and regulate endothelial cell/macrophage interactions. The expression of GPBAR1 in the human endothelium correlated with the expression of inflammatory biomarkers. Mice lacking Fxr and Gpbar1-/-/Fxr-/- display hypotension and aortic inflammation, along with altered intestinal permeability that deteriorates with age, and severe dysbiosis, along with dysregulated bile acid synthesis. Vasomotor activities of aortic rings were altered by Gpbar1 and Fxr gene ablation. In apolipoprotein E-/- and wild-type mice, BAR502, a dual GPBAR1/FXR agonist, alone or in combination with atorvastatin, reduced cholesterol and low-density lipoprotein plasma levels, mitigated the development of liver steatosis and aortic plaque formation, and shifted the polarization of circulating leukocytes toward an anti-inflammatory phenotype. BAR502/atorvastatin reversed intestinal dysbiosis and dysregulated bile acid synthesis, promoting a shift of bile acid pool composition toward FXR antagonists and GPBAR1 agonists. FXR and GPBAR1 maintain intestinal, liver, and cardiovascular homeostasis, and their therapeutic targeting with a dual GPBAR1/FXR ligand and atorvastatin holds potential in the treatment of liver and cardiovascular components of nonalcoholic fatty liver disease.


Naso-orbito-ethmoid fractures: perspective and practices of nigerian surgeons.
The study was to appraise the level of expertise in the management of Naso-Orbito-Ethmoid (NOE) fractures and to provide recommendation for necessary improvement in an African population. A questionnaire was designed and electronically mailed to Nigerian Oral & Maxillofacial surgeons, Plastic and Reconstructive surgeons, and Ear, Nose and Throat surgeons to assess their perspectives and practices in the diagnosis and management of NOE fractures. Further administration of questionnaire was done at the AO (Association of Osteosynthesis) principle course in Lagos, January, 2010. Information generated were coded and processed with statistical package for Social Sciences version 15.0, Chicago Illinois, USA. The questionnaire was delivered to 214 surgeons, there were 112 respondents out of which 78 expressed no interest in the management of NOE fractures and 34 had interest and so completed the questionnaire. Diagnosis is largely based on plain radiographs; only 22 surgeons perform NOE trauma surgery, majority (63.9%) use existing laceration or more conservative approaches like Lynch or open sky incisions. Mini and micro-plates are employed by only 31.8% of the surgeons. Bone grafting is rarely performed but when required, the iliac crest is preferred. Repair of the nasolacrimal duct system is rarely done. The management of NOE fractures in Nigeria, falls short of the current best evidence in the world literature. International collaboration for improvement is recommended.


Restricting access to publications from funded research: ethical issues and solutions.
India is becoming one of the hubs of clinical research. Commensurate with these advances, the government funding for biomedical research in thrust areas is also increasing. The Indian Council of Medical Research (ICMR), Department of Biotechnology (DBT), Department of Science and Technology (DST) are some of the government organizations which provide financial support for various research projects. The results of the funded research projects are published in various international journals. Most of these journals have an access to paid subscribers only. Hence it is unethical to use the research grants from government (people's money) and not allow the scientific community free access to the results of the study. To tackle such issues, these agencies should sign the Berlin declaration and create open access repositories. A public access policy should be formulated and listed in JULIET. The funding bodies in India should also join Pubmed Central (PMC) to form PMC India so that every investigator who has received grants would submit the full text of the paper published from his study and these can be made freely accessible to everyone. Universities and research institutions should also develop institutional open access repositories. The public access policy has definitive advantages and should be implemented.


The effect of pelvic floor muscle exercise on women with chronic non-specific low back pain.
Dysfunction of spinal stability seems to be one of the causes of low back pain (LBP). It is thought that a large number of muscles have a role in spinal stability including the pelvic floor muscle (PFM). The purpose of this study was to investigate the effect of PFM exercise in the treatment of chronic LBP. After ethical approval, a randomized controlled clinical trial was carried out on 20 women with chronic LBP. Patients were randomly allocated into two groups: an experimental and a control group. The control group was given routine treatment including electrotherapy and general exercises; and the experimental group received routine treatment and additional PFM exercise. Pain intensity, functional disability and PFM strength and endurance were measured before, immediately after intervention and at 3 months follow-up. In both groups pain and functional disability were significantly reduced following treatment (p<0.01), but no significant difference was found between the two groups (p>0.05). All measurements were improved in both groups (p<0.01) although patients in the experimental group showed greater improvement in PFM strength and endurance (p<0.01). It seems that the PFM exercise combined with routine treatment was not superior to routine treatment alone in patients with chronic LBP.