Ganoderma lucidum spore oil induces apoptosis of breast cancer cells in vitro and in vivo by activating caspase-3 and caspase-9.
The mushroom Ganoderma lucidum (G. lucidum) is a traditional Chinese medicine reported to have a variety of pharmacological properties, including anti-cancer activity. G. lucidum spore oil (GLSO) is a lipid substance extracted from sporoderm-broken spore of G. lucidum. However, the effect of GLSO on breast cancer and the underlying molecular mechanism remain unclear. The aim of this study was to identify the effects of GLSO on breast cancer cells in vitro and in vivo as well as to investigate the mechanistic basis for the anticancer effect of GLSO. First, in vitro MDA-MB-231 cells were treated with GLSO (0.2, 0.4, and 0.6 μL/mL). The protein levels of B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X (Bax), X-linked inhibitor of apoptosis (XIAP), total poly (ADP-ribose) polymerase (PARP), caspase-3 and caspase-8 were examined using western blotting. The mRNA expression levels of Fas-associated protein with death domain (FADD), TNF receptor-associated factor 2 (TRAF2), caspases-3, -8, -9 and Bax were examined using qRT-PCR. Second, in vivo the anticancer properties of GLSO were assessed by H&E, TUNEL and immunohistochemistry in BALB/c mice injected with 4T1 cells. In addition, the levels of caspase-9/caspase-3 signaling pathway proteins in tumor tissue were evaluated by immunoblotting. Finally, MDA-MB-231 cells were treated with caspase inhibitors to measure cell viability, the protein levels were examined with western blotting. The results in vitro showed that GLSO up-regulated the expression of Bax and caspase-3 in MDA-MB-231 cells, but had no effect on the expression of caspase-8. Moreover, the growth of tumors in vivo was significantly suppressed in the GLSO-treated group. The results of Western blot were consistent with in vitro. In vitro, co-treatment of MDA-MB-231 cells with caspase inhibitors reduced the inhibitory effect of GLSO on cell growth. GLSO inhibits the growth of MDA-MB-231 cells and tumors in vivo by inducing apoptosis, which may be achieved through the mitochondrial apoptotic pathway.


Proposal for the Rapid Reversal of Coagulopathy in Patients with Nonoperative Head Injuries on Anticoagulants and/or Antiplatelet Agents: A Case Study and Literature Review.
Emergency room physicians, trauma teams, and neurosurgeons are seeing increasing numbers of head-injured patients on anticoagulants, many of whom are nonoperative. Head injury and anticoagulation can lead to devastating consequences. These patients need immediate evaluation and often reversal of anticoagulation in order to decrease their high rates of morbidity and mortality. To review data on the prevalence, risks, treatment, and complications of head-injured anticoagulated patients and provide a proposal for their anticoagulant management, and imaging requirements. A PubMed database search was performed for articles on the prevalence, risks, treatment, and complications of patients who have sustained a head injury while on anticoagulant or antiplatelet agents. A total of 1877 articles were found, of which 64 were selected for use based on direct relevance, information quality, and contribution of the article to the current understanding of anticoagulated head injury patients. There are very few guidelines for the management of nonoperative head-injured patients. Rapid reversal guided by international normalized ratio values, Platelet Function Assays, computed tomography imaging of the head, and physical exam is suggested. The proposal presented in this paper enables patient management to begin quickly in a systematic approach, with the goal of achieving a significant decrease in the morbidity and mortality for the anticoagulated head-injured patient. Rapid reversal can potentially decrease mortality by as much as 38%.


Religious socialization of youth involved in child welfare.
Increased religiosity is associated with a variety of improved outcomes, especially for youth in disadvantaged contexts. Although youth involved in child welfare may experience protective effects of religious participation or values, little is known about the impact of maltreatment on religious development. Using the National Survey of Child and Adolescent Well-Being, a nationally representative study of child welfare involved families, correlates of religious attendance and importance of religion for youth were investigated using weighted logistic regression at two waves 18 months apart. Youth self-reports of religious attendance and their ratings of its importance were associated with religious attendance of their caregivers, whether birth-parents or foster parents. Foster parents were more likely to attend religious services than birth parents. Increases in youth attendance from Wave 1 to Wave 2 were associated with high youth religious importance at Wave 1, whereas decreases in attendance were associated with moving between home and foster placements. Increases in religious importance from Wave 1 to Wave 2 were associated with religious attendance at Wave 1 and with the youth being Black.


Multiple comparisons in genetic association studies: a hierarchical modeling approach.
Multiple comparisons or multiple testing has been viewed as a thorny issue in genetic association studies aiming to detect disease-associated genetic variants from a large number of genotyped variants. We alleviate the problem of multiple comparisons by proposing a hierarchical modeling approach that is fundamentally different from the existing methods. The proposed hierarchical models simultaneously fit as many variables as possible and shrink unimportant effects towards zero. Thus, the hierarchical models yield more efficient estimates of parameters than the traditional methods that analyze genetic variants separately, and also coherently address the multiple comparisons problem due to largely reducing the effective number of genetic effects and the number of statistically "significant" effects. We develop a method for computing the effective number of genetic effects in hierarchical generalized linear models, and propose a new adjustment for multiple comparisons, the hierarchical Bonferroni correction, based on the effective number of genetic effects. Our approach not only increases the power to detect disease-associated variants but also controls the Type I error. We illustrate and evaluate our method with real and simulated data sets from genetic association studies. The method has been implemented in our freely available R package BhGLM (http://www.ssg.uab.edu/bhglm/).


Osteomalacia of the mother--rickets of the newborn.
During the last 4 years we observed four cases of neonatal rickets. The mothers of the infants suffered from osteomalacia for 1-3 years prior to its diagnosis shortly after the birth of their children. All four infants were born with craniotabes, and one infant had, in addition, a radial fracture. The diagnoses were confirmed by radiological and laboratory tests which revealed a rarefied bone structure, decreased serum 25-hydroxy-vitamin D and increased alkaline phosphatase levels in all patients. The disorder regressed under low-dose vitamin D3 therapy. As osteomalacia seems to be predominant in oriental women living in Berlin, it is necessary to consider vitamin D deficiency when clinical symptoms of this disease arise and to treat these women at least during pregnancy.


Biofilm in combined sewers: wet weather pollution source and/or dry weather pollution indicator?
In a sewer trunk, three kinds of deposit, acting as potential wet weather sources, be found: the biofilm, the organic layer and the gross bed sediment. This research program, on the "Le Marais" catchment (Paris, France), focused on the biofilm. The objectives were to describe, using a Transmission Electronic Microscope, the architecture of the sewer biofilm and to investigate the contents and the distributions of aliphatic and aromatic hydrocarbons in biofilm. The electron micrographs illustrated a uniform film of bacteria totally covering the surface of a thick organic matrix. A large cohesion of the cell layer and organic matrix complex, due to exopolysaccharides, was noticed. Hence, the hydrocarbon contents were measured not only in the biofilm itself, but in this complex. Our results showed that almost all hydrocarbons were stored in the gross bed sediment and the organic layer and, consequently, the biofilm was not an important potential source of wet weather pollution. Comparison between the hydrocarbon distributions in the biofilm and in the other deposits indicated that the biofilm could be used as an indicator of the aliphatic hydrocarbon pollution in the organic layer.


Prevalence of malnutrition in Kenya.
Prevalence of malnutrition among pre-school children can be used to determine the need for nutrition surveillance, nutritional care, or appropriate nutritional intervention programmes. Such data also indicate the target groups and where interventions are required. To determine the at risk groups, extent and magnitude, and regional distribution of malnutrition. A cross sectional study. The survey was conducted in 14 districts representative of the eight provinces of Kenya. Six thousand, four hundred and nineteen children (3294 males and 3125 females) aged six to 72 months selected using the cluster sampling technique from eight provinces were studied. Anthropometric measures of height/length and weight were used to do the assessment. The prevalence of stunting, wasting and underweight were 37%, 6% and 27% respectively. Stunting was highest among the 12-23 months age group (44.8%). A statistically significant difference (p = < 0.005) was found between boys and girls with regard to stunting. This difference was more remarkable when the two were stratified by age group where 29% of the boys were stunted compared to 20% of the girls. Geographically, it was found that there exists great regional disparities with a low (22.6%) in Kiambu and a high (56.5%) in Kwale districts. These results show that malnutrition is still a serious public health problem in Kenya and requires urgent attention. The problem since the first survey in 1977 shows an upward trend, suggesting deterioration over the years. Well thought out and targeted intervention programmes are long overdue. The results of this survey and others emphasize the importance of having a well established surveillance system which would ensure necessary and timely action.


Case Report: Interferon- γ Rescues Monocytic Human Leukocyte Antigen Receptor (mHLA-DR) Function in a COVID-19 Patient With ARDS and Superinfection With Multiple MDR 4MRGN Bacterial Strains.
CD14+ monocytes present antigens to adaptive immune cells via monocytic human leukocyte antigen receptor (mHLA-DR), which is described as an immunological synapse. Reduced levels of mHLA-DR can display an acquired immune defect, which is often found in sepsis and predisposes for secondary infections and fatal outcomes. Monocytic HLA-DR expression is reliably induced by interferon- γ (IFNγ) therapy. We report a case of multidrug-resistant superinfected COVID-19 acute respiratory distress syndrome (ARDS) on extracorporeal membrane oxygenation (ECMO) support. The resistance profiles of the detected Klebsiella pneumoniae, Pseudomonas aeruginosa, Acinetobacter baumannii and Citrobacter freundii isolates were equipped with resistance to all four antibiotic classes including carbapenems (4MRGN) and Cefiderocol in the case of K. pneumoniae. A causal therapeutic antibiotic strategy was not available. Therefore, we measured the immune status of the patient aiming to identify a potential acquired immune deficiency. Monocyte HLA-DR expression identified by FACS analysis revealed an expression level of 34% positive monocytes and suggested severe immunosuppression. We indicated IFNγ therapy, which resulted in a rapid increase in mHLA-DR expression (96%), rapid resolution of invasive bloodstream infection, and discharge from the hospital on day 70. Superinfection is a dangerous complication of COVID-19 pneumonia, and sepsis-induced immunosuppression is a risk factor for it. Immunosuppression is expressed by a disturbed antigen presentation of monocytes to cells of the adaptive immune system. The case presented here is remarkable as no validated antibiotic regimen existed against the detected bacterial pathogens causing bloodstream infection and severe pneumonia in a patient suffering from COVID-19 ARDS. Possible restoration of the patient's own immunity by IFNγ was a plausible option to boost the patient's immune system, eliminate the identified 4MRGNs, and allow for lung recovery. This led to the conclusion that immune status monitoring is useful in complicated COVID-19-ARDS and that concomitant IFNγ therapy may support antibiotic strategies. After a compromised immune system has been detected by suppressed mHLA-DR levels, the immune system can be safely reactivated by IFNγ.


Youth mortality due to HIV/AIDS in South Africa, 2001-2009: an analysis of the levels of mortality using life table techniques.
South Africa has one of the highest HIV/AIDS prevalence rates in the world. It is estimated that 5.38 million South Africans are living with HIV/AIDS. In addition, new infections among adults aged 15+ were reportedly 316 900 in 2011. New infections among children (0-14 years old) was also high in 2011 at 63 600. This paper examines South Africa's mortality due to HIV/AIDS among the youth (15-34 years old). This age group is of fundamental importance to the economic and social development of the country. However, the challenges of youth development remain vast and incomparable. One of these challenges is the impact of HIV/AIDS on mortality. Life table techniques are used to estimate among others, sex differentials in death rates for the youth population, probability of dying from HIV/AIDS before the age of 35 and life expectancy should HIV/AIDS be eradicated from the population. The study used data from the National Registry of Deaths, as collated by Statistics South Africa from 2001 to 2009. Results show that youth mortality due to HIV/AIDS has remained consistently higher among older youths than in younger ones. By sex, mortality due to this cause has also remained consistent over the period, with mortality due to HIV/AIDS being higher among females than males. Cause-specific mortality rates and proportional mortality ratios reflect the increased mortality of older youth (especially 30-34 years old) and females within the South African population. Probability of dying from HIV/AIDS shows that over the period, fluctuations in likelihood of mortality have occurred, but for both males and females (of all age groups) the chances of dying from this cause decreased in 2007-2009.


Crenarchaeota colonize terrestrial plant roots.
Microorganisms that colonize plant roots are recruited from, and in turn contribute substantially to, the vast and virtually uncharacterized phylogenetic diversity of soil microbiota. The diverse, but poorly understood, microorganisms that colonize plant roots mediate mineral transformations and nutrient cycles that are central to biosphere functioning. Here, we report the results of epifluorescence microscopy and culture-independent recovery of small subunit (SSU) ribosomal RNA (rRNA) gene sequences showing that members of a previously reported clade of soil Crenarchaeota colonize both young and senescent plant roots at an unexpectedly high frequency, and are particularly abundant on the latter. Our results indicate that non-thermophilic members of the Archaea inhabit an important terrestrial niche on earth and direct attention to the need for studies that will determine their possible roles in mediating root biology.


An epidural scoring scale for arm movements (ESSAM) in patients receiving high thoracic epidural analgesia for coronary artery bypass grafting.
Thoracic epidural analgesia appears to improve the outcome of patients undergoing coronary artery bypass graft surgery. Cranial extension of nerve blockade involving the third, fourth and fifth cervical nerve roots can cause apnoea. However, progressive paraesthesia and weakness due to cephalad spread of thoracic epidural analgesia will affect the arms before the diaphragm. A scale was designed to test three active movements of the arms bilaterally: hand grip (T1/C8), wrist flexion (C8/7) and elbow flexion (C6/5). This epidural scoring scale for arm movements (ESSAM) consists of four grades (0-3) based on the number of absent movements, and suggests appropriate action. The reliability of this scale was tested in 40 patients undergoing coronary artery bypass surgery. Twelve of the 40 patients had their epidural infusion reduced on the basis of the scale. Of these 12 patients, eight had a worst ESSAM score of 1, three had a worst score of 2 and one had a worst score of 3. In each patient, motor power returned following the reduction in infusion rate, taking between 30 min and 3 h. This scale appears to be a simple and reliable method for the early detection of the cephalad spread of thoracic epidural analgesia.


Long-term alcohol consumption in relation to all-cause and cardiovascular mortality among survivors of myocardial infarction: the Health Professionals Follow-up Study.
The aim of this study was to examine the association between long-term alcohol consumption, alcohol consumption before and after myocardial infarction (MI), and all-cause and cardiovascular mortality among survivors of MI. The Health Professionals Follow-up Study (HPFS) is a prospective cohort study of 51 529 US male health professionals. From 1986 to 2006, 1818 men were confirmed with incident non-fatal MI. Among MI survivors, 468 deaths were documented during up to 20 years of follow-up. Long-term average alcohol consumption was calculated beginning from the time period immediately before the first MI and updated every 4 years afterward. Cox proportional hazards were used to estimate the multivariable-adjusted hazard ratios (HR) and 95% confidence intervals (CI). Compared with non-drinkers, the multivariable-adjusted HRs for all-cause mortality were 0.78 (95% CI: 0.62-0.97) for 0.1-9.9 g/day, 0.66 (95% CI: 0.51-0.86) for 10.0-29.9 g/day, and 0.87 (95% CI: 0.61-1.25) for ≥30 g/day (P(quadratic)= 0.006). For cardiovascular mortality, the corresponding HRs were 0.74 (95% CI: 0.54-1.02), 0.58 (95% CI: 0.39-0.84), and 0.98 (95% CI: 0.60-1.60), P(quadratic)= 0.003. These findings were consistent when restricted to pre- and post-MI alcohol assessments. In subgroup analyses, moderate alcohol consumption was inversely associated with mortality among men with non-anterior infarcts, and among men with mildly diminished left ventricular function. Long-term moderate alcohol consumption is inversely associated with all-cause and cardiovascular mortality among men who survived a first MI. This U-shaped association may be strongest among individuals with less impaired cardiac function after MI and should be examined further.


Insulin-like growth factors in human breast cancer.
Several protooncogenes and suppressor genes and a variety of growth factors and their receptors have been shown to be mutated, deleted, or activated in human breast cancer. These changes may account for the unregulated growth of breast carcinoma cells. Insulin-like growth factors I and II (IGF-I, IGF-II) belong to a family of polypeptides with growth promoting properties and structural homology to insulin. They exert their mitogenic effects by binding to the IGF-I receptor and activating its tyrosine protein kinase. Other proteins that specifically bind the IGFs include the plasma membrane IGF-II receptor, which also binds lysosomal hydrolases, and several IGF-binding proteins which may serve to modulate IGF interactions with receptors. Breast cancer cell lines express IGF-I and IGF-II receptors and different patterns of binding proteins. IGF-I and IGF-II are each mitogenic for subsets of breast cancer cell lines. This effect is inhibited by antibodies directed against the IGF-I receptor. In breast tumors, IGF-I is expressed by stromal cells, but not carcinoma cells; it is not expressed by breast cancer cell lines. IGF-I is therefore a potential paracrine regulator of breast cancer cell growth. Similarly, IGF-II is expressed in breast tumors, predominantly in stromal cells, but sometimes also in carcinoma cells and in a subset of cell lines. Thus, IGF-II is also a potential paracrine regulator of breast cancer cell growth; in addition, it can be an autocrine regulator in some breast cancer cells.


A longitudinal study of families formed through reproductive donation: Parent-adolescent relationships and adolescent adjustment at age 14.
The aim of the 6th phase of this longitudinal study was to establish whether children born through assisted reproduction involving reproductive donation were at risk for psychological problems following the transition to adolescence at age 14 and, if so, to examine the nature of these problems and the mechanisms involved. Eighty-seven families formed through reproductive donation, including 32 donor insemination families, 27 egg donation families, and 28 surrogacy families, were compared with 54 natural conception families. Standardized interviews, questionnaires, and observational assessments of the quality of parent-adolescent relationships and adolescent adjustment were administered to mothers, adolescents, and teachers. The mothers in surrogacy families showed less negative parenting and reported greater acceptance of their adolescent children and fewer problems in family relationships as a whole compared with gamete donation mothers. In addition, less positive relationships were found between mothers and adolescents in egg donation families than in donor insemination families as rated by both mothers and adolescents. There were no differences between family types for the adolescents themselves in terms of adjustment problems, psychological well-being, and self-esteem. Longitudinal analyses showed no differences between family types in negative parenting from age 7 to age 14, and a weaker association between negative parenting and adjustment difficulties for gamete donation than natural conception and surrogacy families. The findings suggest that the absence of a genetic link between mothers and their children is associated with less positive mother-adolescent relationships whereas the absence of a gestational link does not have an adverse effect. (PsycINFO Database Record


Surgical approach to solid pseudopapillary neoplasms of the proximal pancreas: minimally invasive vs. open.
Solid pseudopapillary neoplasms (SPN) of the pancreas are rare pancreatic neoplasms where complete resection is the cornerstone in management. It has been demonstrated in previous studies that minimally invasive surgical approaches are effective management options in treating SPNs of the distal pancreas. The purpose of this study is to evaluate the feasibility of minimally invasive surgery in treating SPNs of the uncinate, head, and neck of the pancreas. Data from 2005 to 2017 at Severance Hospital of the Yonsei University Health systems in Seoul, South Korea, were retrospectively collected for 25 patients who were diagnosed with SPN of the uncinate, head, and neck of the pancreas and who underwent curative resection. Three groups of patients were considered, depending on the year of surgery, in order to determine trends in the surgical management of SPN. The patients were also divided into two groups corresponding to the type of operation done (minimally invasive surgery vs. open surgery). Perioperative patient data, including age, gender, body mass index (BMI), tumor size, and operation done, were compared and analyzed statistically. Long-term nutritional effects were measured using the Controlling Nutritional Status (CONUT) scoring system. There were no statistically significant differences in age, gender, BMI, symptomatic presentation, operation type, tumor size, and tumor stage between the three time periods. In comparing between minimally invasive and open surgery, there were no statistically significant differences in age, gender, symptomatic presentation, BMI, tumor size, preoperative stage, type of operation, operation time, pancreatic duct size, post-operative pancreatic fistula (POPF) grade, death associated with disease, recurrence, pathological parameters, and change in CONUT score. There was a significant difference in tumor size (4.5 ± 1.8 vs. 2.6 ± 1.0 cm, p = 0.004), blood loss (664.2 ± 512.4 vs. 277.7 ± 250.8 mL, p = 0.024), need to transfuse (33% vs. 0%, p = 0.023), hospital length of stay (27.4 ± 15.3 vs. 11.5 ± 5.3 days, p = 0.002), and complication rate (75% vs. 30.8%, p = 0.027) between the two groups. In appropriately selected patients with SPNs of the uncinate, head, and neck of the pancreas, a minimally invasive surgical approach offers at least equal oncologic and nutritional outcomes, while demonstrating decreased complications and decreased hospital length of stay compared with that of an open surgical approach.


Formulation and characterization of atropine sulfate in albumin-chitosan microparticles for in vivo ocular drug delivery.
The overall study goal was to produce a microparticle formulation containing atropine sulfate for ocular administration with improved efficacy and lower side effects, compared with that of the standard marketed atropine solution. The objective was to prepare an atropine sulfate-loaded bovine serum albumin-chitosan microparticle that would have longer contact time on the eyes as well as better mydriatic and cycloplegic effect using a rabbit model. The microparticle formulation was prepared by method of spray-drying technique. The percent drug loading and encapsulation efficiency were assessed using a USP (I) dissolution apparatus. The particle sizes and zeta potential were determined using laser scattering technique and the surface morphology of the microparticles was determined using a scanning electron microscope. The product yield was calculated from relative amount of material used. In vitro cytotoxicity and uptake by human corneal epithelial cells were examined using AlamarBlue and confocal microscopy. The effects of the microparticle formulation on mydriasis in comparison with the marketed atropine sulfate solution were evaluated in rabbit eyes. The prepared microparticle formulation had ideal physicochemical characteristics for delivery into the eyes. The in vivo studies showed that the microparticles had superior effects on mydriasis in rabbits than the marketed solutions


Purification, optimization and physicochemical properties of collagen from soft-shelled turtle calipash.
The present work was to optimize the purification conditions for soft-shelled turtle (Pelodiscus sinensis) calipash collagen (STCC) isolated by pepsin and to explore collagen physicochemical properties for potential biomaterial applications. Single-factor test and orthogonal method L9 (3(4)) were employed with the STCC recovery yield as indicator. The optimum purification conditions were obtained when NaCl concentration, collagen concentration and purification time were 2M, 8g/L, and 24h, respectively. Purified STCC were characterized by SDS-PAGE, UV scanning, FTIR, solubility, thermal behavior and amino acid analysis. The results showed that STCC contained high hydroxyproline content than that of other fishery skins, belonging to typical type I collagen in form of [α1(I)] 2α2(I). FTIR spectra of STCC were quite similar to other aquatic animals' collagens. It has the lowest solubility at pH 6, and when NaCl concentration decreased from 2% to 6% (w/v), solubility dropped. The denaturation temperature (Td) and melting temperature (Tm) were 35.1°C and 105.14°C, respectively. Morphology of STCC depicted as regular and porous network structure by SEM. In general, the results suggested that turtle calipash can be exploited as alternatives to mammalian collagen and could also be used for biomedical applications as a potential new material.


Use of Ion Exchange To Regulate the Heterogeneous Ice Nucleation Efficiency of Mica.
Heterogeneous ice nucleation (HIN) triggered by mineral surfaces typically exposed to various ions can have a significant impact on the regional atmosphere and climate. However, the dependence of HIN on the nature of the mineral surface ions is still largely unexplored due to the complexity of mineral surfaces. Because K+ on the atomically flat (001) surface of mica can be readily replaced by different cations through ion exchange, muscovite mica was selected; its simple nature provides a very straightforward system that can serve as the model for investigating the effects of mineral surface ions on HIN. Our experiments show that the surface (001) of H+-exchanged mica displays markedly higher HIN efficiencies than that of Na-/K-mica. Vibrational sum-frequency generation spectroscopy reveals that H-mica induces substantially less orientation ordering than Na-/K-mica within the contact water layer at the interface. Molecular dynamics simulations suggest that the HIN efficiency of mica depends on the positional arrangement and orientation of the interfacial water. The formation of the hexagonal ice Ih basal-type structure in the first water layer atop the mica surface facilitates HIN, which is determined by the size of the protruding ions atop the mica surface and by the surface adsorption energy. The orientational distribution is optimal for HIN when 25% of the water molecules in the first water layer atop the mica surface have one OH group pointing up and 25% have one OH group pointing down, which, in turn, is determined by the surface charge distribution.


Bee venom inhibits hepatic fibrosis through suppression of pro-fibrogenic cytokine expression.
Bee venom (BV) has a long tradition of use for the control of pain and inflammation in various chronic diseases. Carbon tetrachloride (CCl4) is known to induce hepatotoxicity after being metabolized to the highly reactive trichloromethyl free radical and its peroxy radical. The purpose of the current study was to examine whether BV regulates the pro-inflammation and fibrosis related genes against a mouse model of hepatic fibrosis induced by CCl4 and ethanol-treated hepatocytes (ETH). Test mice were administered with CCl4 (2 ml/mg) and hepatocytes were treated with 25 mM ethanol. BV was added to the final concentration of 0.05-0.5 mg/kg and 1-100 ng/ml for in vivo and in vitro testing, respectively. Fibrotic livers and ETH were used for the measurement of hepatocyte necrosis, pro-inflammatory cytokines and fibrogenic genes. BV suppressed CCl4-induced hepatocyte necrosis markers of serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT). It also inhibited the secretion of interleukin (IL)-1beta and tumor necrosis factor (TNF)-alpha. Moreover, BV inhibited CCl4-induced expression of transforming growth factor (TGF)-beta1, alpha-smooth muscle actin (SMA) and fibronectin. Similarly, ETH exhibited significant suppression of IL-1beta, TNF-alpha, TGF-beta1 and fibronectin when cultured with BV. These results suggest that BV possesses anti-fibrogenic properties that are mediated by the suppression of pro-inflammatory cytokines and fibrogenic gene expression. BV has substantial therapeutic potential for the treatment of fibrotic diseases.


Clinical predictors of blood pressure response after renal artery stenting.
The Cardiovascular Outcomes in Renal Atherosclerotic Lesions (CORAL) trial, a multicenter randomized controlled trial, failed to demonstrate a benefit of renal artery stenting (RAS) over medical therapy in patients with renal artery stenosis and hypertension. However, there are patients for whom RAS is a consideration because of failure of medical therapy. Unfortunately, selection of patients for RAS is complicated by a lack of validated predictors of blood pressure (BP) response. A previous single-center study identified three preoperative markers of BP response to RAS: requirement for four or more antihypertensive medications, preoperative diastolic BP >90 mm Hg, and preoperative clonidine use. To date, these markers of outcome have not been independently validated. The aim of this study was to validate these markers using data from the CORAL trial. All patients randomized in the CORAL trial to RAS were included. American Heart Association guidelines were used to categorize patients as BP responders or nonresponders to RAS. BP responders were defined by a postoperative BP <160/90 mm Hg with a reduced number of antihypertensive medications or a reduction in diastolic BP to <90 mm Hg with the same medications after RAS. Patients with stable or worsened BP were labeled nonresponders. Variables associated with a favorable BP response were identified by multivariable logistic regression analysis. There were 436 patients who underwent RAS with a median age of 70 years (interquartile range [IQR], 63-76 years). The median systolic and diastolic BPs of the stented cohort at baseline were 149 mm Hg (IQR, 132-164 mm Hg) and 78 mm Hg (IQR, 70-87 mm Hg), respectively. A positive BP response occurred in 284 of 436 (65.1%) stented patients. Multivariable logistic regression analysis identified three independent markers of a positive BP response: requirement for four or more medications (odds ratio, 5.9; P < .001), preoperative diastolic BP >90 mm Hg (odds ratio 13.9; P < .001), and preoperative clonidine use (odds ratio, 4.52; P = .008). The percentage of patients with a positive BP response increased incrementally as the number of markers per patient increased, based on the Cochran-Armitage test for trend (P < .0001). In patients from the CORAL trial who underwent RAS, the previously reported clinical markers of BP response were validated. A prospective trial to validate their utility as predictors of BP response to RAS is warranted.


B-type natriuretic peptide is neither itch-specific nor functions upstream of the GRP-GRPR signaling pathway.
A recent study by Mishra and Hoon identified B-type natriuretic peptide (BNP) as an important peptide for itch transmission and proposed that BNP activates spinal natriuretic peptide receptor-A (NPRA) expressing neurons, which release gastrin releasing peptide (GRP) to activate GRP receptor (GRPR) expressing neurons to relay itch information from the periphery to the brain (Science 340:968-971, 2013). A central premise for the validity of this novel pathway is the absence of GRP in the dorsal root ganglion (DRG) neurons. To this end, they showed that Grp mRNA in DRG neurons is either absent or barely detectable and claimed that BNP but not GRP is a major neurotransmitter for itch in pruriceptors. They showed that NPRA immunostaining is perfectly co-localized with Grp-eGFP in the spinal cord, and a few acute pain behaviors in Nppb-/- mice were tested. They claimed that BNP is an itch-selective peptide that acts as the first station of a dedicated neuronal pathway comprising a GRP-GRPR cascade for itch. However, our studies, along with the others, do not support their claims. We were unable to reproduce the immunostaining of BNP and NPRA as shown by Mishra and Hoon. By contrast, we were able to detect Grp mRNA in DRGs using in situ hybridization and real time RT-PCR. We show that the expression pattern of Grp mRNA is comparable to that of GRP protein in DRGs. Pharmacological and genetic blockade of GRP-GRPR signaling does not significantly affect intrathecal BNP-induced scratching behavior. We show that BNP inhibits inflammatory pain and morphine analgesia. Accumulating evidence demonstrates that GRP is a key neurotransmitter in pruriceptors for mediating histamine-independent itch. BNP-NPRA signaling is involved in both itch and pain and does not function upstream of the GRP-GRPR dedicated neuronal pathway. The site of BNP action in itch and pain and its relationship with GRP remain to be clarified.


Synthesis of biocompatible Au-ZnTe core-shell nanoparticles.
A novel, solution-based route to biocompatible, cysteine-capped gold-zinc telluride (Au-ZnTe) core-shell nanoparticles with potential in biomedical applications is described. The optical properties of the core-shell nanoparticles show combined beneficial features of the individual parent components. The tunable emission properties of the semiconductor shell render the system useful for imaging and biological labeling applications. Powder X-ray diffraction analysis reveals the particles contain crystalline Au and ZnTe. Transmission electron microscope (TEM) imaging of the particles indicates they are largely spherical with sizes in the order of 2-10 nm. Elemental mapping using X-ray energy dispersive spectroscopy (XEDS) in the scanning transmission electron microscope (STEM) mode supports a core-shell morphology. The biocompatibility and cytotoxicity of the core-shells was investigated on a human pancreas adenocarcinoma (PL45) cell line using the WST-1 cell viability assay. The results showed that the core-shells had no adverse effects on the PL45 cellular proliferation or morphology. TEM imaging of PL45 cell cross sections confirmed the cellular uptake and isolation of the core-shell nanoparticles within the cytoplasm via membrane interactions. The fluorescence properties of the Au-ZnTe core-shell structures within the PL45 cell lines results confirmed their bio-imaging potential. The importance and novelty of this research lies in the combination of gold and zinc telluride used to produce a water soluble, biocompatible nanomaterial which may be exploited for drug delivery applications within the domain of oncology.


Opiate drug receptors on excitable cell membranes.
In drug interaction studies on intact mice it was found that naloxone (3mumoles/kg) antagonized the general central nervous system depressant effects of morphine or meperidine. Higher naloxone doses (0.3 and 0.4 mmoles/kg), like the fullagonists, potentiated the loss of the righting reflex produced by phenobarbital. Naloxone (0.3 to 14 muM) antagonized the depressant effects of morphine or meperidine on the compound action potential of frog's sartorius muscles in vitro. Higher naloxone concentration (ED20=0.3 mM, ED100=3.0mM), like the full agonists, depressed action potential production. These results show that high doses of naloxone can duplicate some effects of morphine or meperidine but at low doses it antagonizes the effects of the full agonists. This would suggest that naloxone is a partial agonist with a very low intrinsic activity. These results also indicate that there are opiate drug receptors on excitable cell membranes and that drug activation of these receptors inhibits action potential production.


How can I motivate you to do it my way?
Want to motivate others? Establish meaningfulness and value to them of what they are supposed to do for you, and provide the tools they need to do it. Until they see the value to them, and that value outweighs their perceived risks or costs of doing it, you may get motion but you won't get motivated behaviors. Without motivated behaviors, you'll waste a lot of time trying to goad them on toward your goal, which they don't share. What we want is bilateral motivation toward a common goal. If we're smart, we don't want to be the only ones who are motivated, and others just move.


Infrared holography: an analysis of the thermal behavior of thin films.
This paper presents an analysis describing the thermal behavior of a thin film subjected to a spatially modulated irradiation field. The analysis shows that it is possible using a cw laser to establish a temperature field in such a film that maps the irradiation pattern with a resolution adequate for recording high quality holograms. Effects of the thermal properties of the film and substrate on such recording characteristics as linearity, sensitivity, and resolution are examined. A high diffraction efficiency recording technique based on the sublimation of a thin film situated on a constant temperature substrate is proposed as an example of the application of the analysis.


Evaluation of Deprescribing Amiodarone After New-Onset Atrial Fibrillation in Critical Illness.
Recent studies have shed light on the continued prescription of inpatient medications upon hospital discharge, despite the original intent of short-term inpatient therapy. Amiodarone, an antiarrhythmic associated with significant adverse effects with long-term use, is commonly used for new-onset atrial fibrillation in critical illness (NAFCI). Although it is often preferred in this setting of hemodynamic instability, a prescription for long-term use should be carefully considered, preferably by a cardiologist. This study was conducted to evaluate the incidence of patients discharged on amiodarone without a cardiology consult or referral after being initiated on amiodarone for NAFCI. We conducted a retrospective review of all patients newly prescribed amiodarone for NAFCI over a 2-year period. The primary outcome was the percentage of patients who were continued on amiodarone upon hospital discharge without review by or outpatient referral to a cardiologist. Of the 100 patients who met inclusion criteria, 59 patients were prescribed amiodarone upon hospital discharge. Of these, 48 patients (81.4%) had converted to normal sinus rhythm with the resolution of critical illness. Of 100 patients, 23 received prescriptions for amiodarone upon discharge without a cardiology consult or referral. Amiodarone was frequently continued upon discharge without referral to a cardiologist in patients initiated on this therapy for NAFCI. This may contribute to unnecessary long-term therapy, thereby increasing the risk for significant side effects, drug interactions, and increased healthcare costs. This study suggests that careful medication reconciliation through all transitions of care, including discharge, is essential.


Down syndrome: analysis of airway size and a guide for appropriate intubation.
The purpose of this study is to prospectively evaluate the airway size of children with Down syndrome (DS). Previous studies have observed an increase in postintubation stridor in children with DS. Anesthetic literature suggests using a smaller endotracheal tube in children with DS, but more specific recommendations are not offered. With this study, recommendations are presented for the appropriate endotracheal tube size to use in children with DS undergoing intubation. A prospective, nonrandomized study was performed on a cohort of 42 children with DS and 32 control subjects. Sizing of the airway was assessed through measurement of an air leak around the endotracheal tube at intubation. The size of the airway was also evaluated through measurements of the tracheal diameter at the "tracheotomy point" on magnetic resonance imagine (MRI) studies of the head and neck which were performed on a group of children with DS. These were compared with normative values of the tracheal diameter in children. The proper size of endotracheal tube in a population of children with DS and in a group of normal controls was determined. The "proper size" of an endotracheal tube was defined as that size of tube which allowed an audible air leak around the tube between 10 and 30 cm of H2O pressure. Anesthetic technique was controlled and identical for all study subjects. Participants had no previous history of airway compromise, stridor, or previous intubation. Weight and age were recorded and evaluated for their influence on the results. A retrospective evaluation was made of MRI studies of the neck that were performed on children with DS. Using measurement techniques described by Reed et al., the tracheal diameters at the "tracheostomy point" were compared with normative values for children. Measurements were both obtained by the author and confirmed by a pediatric radiologist. Using this prescribed method to determine the proper size of endotracheal tube, the control group used endotracheal tubes that were predicted from established anesthesia charts and formulas. However, children with DS required endotracheal tubes at least two sizes smaller. Age was found to be a more reliable factor in predicting the endotracheal tube size. A table of endotracheal tube sizes for intubation in children with DS is presented. Evaluation of the tracheal diameter at the tracheotomy point revealed that children with DS have a smaller trachea when compared with control children. It is not only the subglottis that is smaller; the tracheal diameter as well must be assumed to be of a smaller diameter in children with DS. Children with DS have smaller airways than other children. This is because of an overall decrease in the diameter of the tracheal lumens. Initial intubation of a child with DS should be performed with an endotracheal tube at least two sizes smaller than would be used in a child of the same age without DS, to avert potential trauma to the airway.


The combination of dynapenia and abdominal obesity as a risk factor for worse trajectories of IADL disability among older adults.
The concept of dynapenic obesity has been gaining great attention recently. However, there is little epidemiological evidence demonstrating that dynapenic abdominal obese individuals have worse trajectories of disability than those with dynapenia and abdominal obesity alone. Our aim was to investigate whether dynapenia combined with abdominal obesity can result in worse trajectories of instrumental activities of daily living (IADL) among English and Brazilian older adults over eight and ten years of follow-up, respectively. We used longitudinal data from 3374 participants from the English Longitudinal Study of Ageing (ELSA) and 1040 participants from the Brazilian Health, Well-being and Aging Study (SABE) who were free from disability as assessed by IADL at baseline. IADL disability was defined herein as a difficulty to perform the following: preparing meals, managing money, using transportation, shopping, using the telephone, house cleaning, washing clothes, and taking medications according to the Lawton IADL modified scale. The study population in each country was categorized into non-dynapenic/non-abdominal obese (reference group), abdominal obese, dynapenic and dynapenic abdominal obese according to their handgrip strength (<26 kg for men and <16 kg for women) and waist circumference (>102 cm for men and >88 cm for women). We used generalized linear mixed models with IADL as the outcome. The estimated change over time in IADL disability was significantly higher for participants with dynapenic abdominal obesity compared to those with neither condition in both cohorts (ELSA: +0.023, 95% CI = 0.012-0.034, p < 0.001; SABE: +0.065, 95% CI = 0.038-0.091, p < 0.001). Abdominal obesity was also associated with changes over time in IADL disability (ELSA: +0.009, 95% CI = 0.002-0.015, p < 0.05; SABE: +0.021, 95% CI = 0.002-0.041, p < 0.05), which was not observed for dynapenia. Abdominal obesity is an important risk factor for IADL decline but participants with dynapenic abdominal obesity had the highest rates of IADL decline over time among English and Brazilian older adults.


Brain schistosomiasis in mice experimentally infected with Schistosoma mansoni.
Human neuroschistosomiasis has been reported in the literature, but the possibility of modeling neuroschistosomiasis in mice is controversial. In two research laboratories in Brazil that maintain the Schistosoma mansoni life cycle in rodents, two mice developed signs of brain disease (hemiplegia and spinning), and both were autopsied. S. mansoni eggs, both with and without granuloma formation, were observed in the brain and meninges of both mice by optical microscopy. This is the first description of eggs in the brains of symptomatic mice that were experimentally infected with S. mansoni. An investigation of experimental neuroschistosomiasis is now feasible.


Approaches Towards Professional Studies and Spare-time Activities Among Preclinical and Clinical Year Medical Students.
Objective This study aims at a recognition of the differences in the study habits, approach to teaching resources, and spare-time activities of medical students in the preclinical and clinical training periods at King Abdulaziz University (KAU) Jeddah, Saudi Arabia (SA). Methods Study sampling was carried out in 2017 at the Faculty of Medicine, KAU, Jeddah, SA. Students from both genders were included and further subdivided to preclinical (2nd and 3rd years) and clinical groups (4th, 5th, and 6th years). Students were asked to respond to an online questionnaire. SPSS-Version 21 (IBM Corp., Armonk, NY, US) was utilized for statistical analysis of the collected data, Results Of the 347/500 (response rate 69.4%) medical students, 85 (24.5%) were from the preclinical students (2nd and 3rd years), and 262 (64.5%) were enrolled in the clinical group (4th to 6th years of MBBS). The majority of students 330 (94.1%) were unmarried, only 17 of them, i.e., 4.9%, were married. Analysis of the data revealed that medical textbooks, essential versions of basic medical books, online resources, and online version of books were used more frequently by the clinical group as compared to the preclinical students. Teacher-provided lecture handouts and lecture notes taken during classes were being equally used by both groups. There was a significant difference in the opinion on the usefulness of different resources between both groups. Students faced difficulty in understanding the English language, observed more in the pre-clinical years as compared to relatively groomed clinical students. The preclinical group could not understand the teaching material in books due to a weaker understanding of the English language. Social media software was used for keeping both groups busy, but clinical students also used social media for academic purposes. More than half of the participants from the preclinical and almost one-third from the clinical years admitted that their teachers recommended them for relevant medical textbooks. An encouraging trend was observed in most preclinical group students: they found teaching modalities, such as problem-based learning (PBL) and other academic activities, as a trigger to promote book reading. Conclusion Our results show that the students in the clinical phase had a more methodical approach to professional studies and a difference in spare-time activities.


Postoperative jaundice in children. The influence of halothane.
At the Hospital for Sick Children, Great Ormond Street, during the 23-year period 1957 to 1979, 165400 anaesthetics were administered. Almost all of the patients anaesthetised during this time would have been exposed to halothane. Seventy-four patients became jaundiced for the first time in the post-operative period. Halothane-associated hepatitis was excluded as the cause of the postoperative jaundice in all but two of the 74 patients. In these two patients in whom the diagnosis of halothane-associated hepatitis was possible the hepatitic illness was mild and both patients made an uneventful recovery. In this survey the risk of a patient becoming jaundiced due to halothane associated hepatitis was greater than 1 in 82000. It would seem that in children halothane can be used whenever it is warranted and can be used repeatedly.


Oral Supplementation of Parturient Mothers with Vitamin D and Its Effect on 25OHD Status of Exclusively Breastfed Infants at 6 Months of Age: A Double-Blind Randomized Placebo Controlled Trial.
Exclusively breastfed infants are at increased risk of vitamin D deficiency and many lactating mothers have been found deficient in 25OHD stores. To compare serum vitamin D levels in exclusively breastfed infants at 6 months of age with or without oral supplementation of 600,000 IU of vitamin D3 to mothers in early postpartum period. Exclusively breastfeeding term parturient mothers were randomized 24-48 hours following delivery to receive either 600,000 IU of vitamin D3 (Cholecalciferol) over 10 days in a dose of 60,000 IU/day or placebo. 25OHD levels were measured by Radio Immuno Assay method at recruitment and after 6 months in all mothers and their infants. Urinary calcium and creatinine ratio was measured to monitor adverse effects of vitamin D3 in both mothers and infants at 14 weeks and 6 months of age. X-ray of both wrists in anteroposterior view and serum alkaline phosphatase of infants were done in both groups at 6 months of age to look for evidence of rickets. Maternal profile was similar in intervention (A) and control (B) groups. Mothers' serum 25OHD levels at recruitment were also similar being 16.2 ± 9.3 ng/mL in group A and 14.1 ± 7.1 ng/mL in group B. After 6 months, 25OHD levels were 40.3 ± 21.6 and 22.9 ± 20.1 ng/mL in group A and group B mothers (p ≤ 0.00), respectively. The serum 25OHD levels in cord blood were 9.9 ± 5.7 and 8.9 ± 5.1 ng/mL, respectively, in infants born to mothers in intervention and control groups (p = 0.433). At 6 months of age, the serum 25OHD levels significantly (p < 0.00) raised to 29.1 ± 14.6 ng/mL in infants of group A compared to those of group B (15.7 ± 17.7 ng/mL). Four infants developed radiological rickets at 6 months of age, two infants each in intervention group and study group. As against 10 infants in the control group (16.94%), no infant in the study group had biochemical rickets. Urinary calcium and creatinine ratio in mothers and infants at 14 weeks and 6 months of age in both intervention and study group was within normal limits, indicating there was no adverse effects of oral administration of 600,000 IU of vitamin D3. Serum 25OHD levels of exclusively breastfed infants significantly rise at 6 months of age when their mothers are orally supplemented with 60,000 IU of vitamin D3 daily for 10 days in the early postpartum period in comparison to infants of vitamin D3 unsupplemented mothers.


Characterization of soybean seed coat peroxidase: resonance Raman evidence for a structure-based classification of plant peroxidases.
Electronic absorption and resonance Raman spectra of ferric and ferrous forms of a peroxidase from soybean seed coat (SBP) at neutral and alkaline pH values together with the spectra of the ferric-fluoride complex are reported. At neutral pH a quantum mechanically mixed spin state, resulting from the admixture of intermediate spin, S = 3/2, and high spin, S = 5/2, configurations, has been identified which coexists with five- and six-coordinate high-spin hemes. A complete conversion to a fluoride-ligated six-coordinate high-spin and a hydroxy-ligated six-coordinate low-spin heme are observed at acid pH in the presence of fluoride and at alkaline pH, respectively. The spectral features suggest that both the fluoride and hydroxo ligands are stabilized by hydrogen-bond interactions with the distal Arg residue and through a water molecule with the distal His residue. The ferrous form shows a single nu(Fe-Im) at 246 cm(-1) at neutral pH. The data indicate that SBP shares many characteristics with peroxidases belonging to class III of the "plant peroxidase" superfamily.


The unfoldomics decade: an update on intrinsically disordered proteins.
Our first predictor of protein disorder was published just over a decade ago in the Proceedings of the IEEE International Conference on Neural Networks (Romero P, Obradovic Z, Kissinger C, Villafranca JE, Dunker AK (1997) Identifying disordered regions in proteins from amino acid sequence. Proceedings of the IEEE International Conference on Neural Networks, 1: 90-95). By now more than twenty other laboratory groups have joined the efforts to improve the prediction of protein disorder. While the various prediction methodologies used for protein intrinsic disorder resemble those methodologies used for secondary structure prediction, the two types of structures are entirely different. For example, the two structural classes have very different dynamic properties, with the irregular secondary structure class being much less mobile than the disorder class. The prediction of secondary structure has been useful. On the other hand, the prediction of intrinsic disorder has been revolutionary, leading to major modifications of the more than 100 year-old views relating protein structure and function. Experimentalists have been providing evidence over many decades that some proteins lack fixed structure or are disordered (or unfolded) under physiological conditions. In addition, experimentalists are also showing that, for many proteins, their functions depend on the unstructured rather than structured state; such results are in marked contrast to the greater than hundred year old views such as the lock and key hypothesis. Despite extensive data on many important examples, including disease-associated proteins, the importance of disorder for protein function has been largely ignored. Indeed, to our knowledge, current biochemistry books don't present even one acknowledged example of a disorder-dependent function, even though some reports of disorder-dependent functions are more than 50 years old. The results from genome-wide predictions of intrinsic disorder and the results from other bioinformatics studies of intrinsic disorder are demanding attention for these proteins. Disorder prediction has been important for showing that the relatively few experimentally characterized examples are members of a very large collection of related disordered proteins that are wide-spread over all three domains of life. Many significant biological functions are now known to depend directly on, or are importantly associated with, the unfolded or partially folded state. Here our goal is to review the key discoveries and to weave these discoveries together to support novel approaches for understanding sequence-function relationships. Intrinsically disordered protein is common across the three domains of life, but especially common among the eukaryotic proteomes. Signaling sequences and sites of posttranslational modifications are frequently, or very likely most often, located within regions of intrinsic disorder. Disorder-to-order transitions are coupled with the adoption of different structures with different partners. Also, the flexibility of intrinsic disorder helps different disordered regions to bind to a common binding site on a common partner. Such capacity for binding diversity plays important roles in both protein-protein interaction networks and likely also in gene regulation networks. Such disorder-based signaling is further modulated in multicellular eukaryotes by alternative splicing, for which such splicing events map to regions of disorder much more often than to regions of structure. Associating alternative splicing with disorder rather than structure alleviates theoretical and experimentally observed problems associated with the folding of different length, isomeric amino acid sequences. The combination of disorder and alternative splicing is proposed to provide a mechanism for easily "trying out" different signaling pathways, thereby providing the mechanism for generating signaling diversity and enabling the evolution of cell differentiation and multicellularity. Finally, several recent small molecules of interest as potential drugs have been shown to act by blocking protein-protein interactions based on intrinsic disorder of one of the partners. Study of these examples has led to a new approach for drug discovery, and bioinformatics analysis of the human proteome suggests that various disease-associated proteins are very rich in such disorder-based drug discovery targets.


Evidence for rapid gut clearance of microplastic polyester fibers fed to Chinook salmon: A tank study.
Marine and freshwater plastic pollution is a challenging issue receiving large amounts of research and media attention. Yet, few studies have documented the impact of microplastic ingestion to aquatic organisms. In the Pacific Northwest, Chinook salmon are a culturally and commercially significant fish species. The presence of marine and freshwater microplastic pollution is well documented in Chinook salmon habitat, yet no research has investigated the impacts to salmon from microplastic ingestion. The majority of the marine microplastics found in the Salish Sea are microfibers, synthetic extruded polymers that come from commonly worn clothing. To understand the potential impacts of microfiber ingestion to fish, we ran a feeding experiment with juvenile Chinook salmon to determine if ingested fibers are retained or digestion rates altered over a 10 day digestion period. The experiment was completed in two trials, each consisted of 20 control and 20 treatment fish. Treatment fish were each fed an amended ration of 12 food pellets spiked with 20 polyester microfibers and control fish were fed the same ration without added microfibers. Fish were sampled at day 0, 3, 5, 7, and 10 to assess if fibers were retained in their gastrointestinal tract and to determine the rate of digestion. Fibers for the experiment came from washing a red polyester fleece jacket in a microfiber retention bag. Fibers had a mean length of 4.98 mm. Results showed fish were able to clear up to 94% of fed fibers over 10 days. Differences in mean gastrointestinal mass were not statistically significant at any sampled time between treatment and controls, suggesting that the ingestion of microfibers did not alter digestion rates. Further work is needed to understand if repeated exposures, expected in the environment, alter digestion or food assimilation for growth.


A novel method for multiple labeling combining in situ hybridization with immunofluorescence.
In situ hybridization (ISH) is a particularly useful method to investigate de novo mRNA expression in tissue sections. High specificity and sensitivity of this technique combined with the great preservation of tissue and cellular morphology conferred by fixatives such as 4% paraformaldehyde, pH 9.5, make ISH a tool of choice for detecting genes of interest in individual cells in the central nervous system (CNS). Here we describe a novel method that combines radioactive ISH with immunofluorescence on the same tissue section to identify cell populations expressing selected mRNA transcripts. This novel method has several major advantages over previously described double-labeling light microscopic methods combining enzymatic immunohistochemistry and ISH including (1) complete protection against loss of hybridization signal that normally occurs during the immunoenzymatic reaction, (2) improved immunolabeling sensitivity due to the proteinase K digestion step during ISH, (3) detection of several proteins specific for different cell populations on the same tissue section, and (4) counterstaining of tissue sections without affecting visualization of immunolabeling. This new method will be particularly useful for investigators looking to identify cell populations producing mRNAs expressed in low abundance such as cytokines, chemokines, and growth factors in the intact and/or injured mammalian CNS.


[Significance of segmentary reversal defects in the myocardial SPECT with 99mTC-tetrofosmin myocardial SPECT].
To evaluate segmentary reverse defects (RD) (uptake higher in exercise than in rest) in 99mTc-tetrofosmin SPECT. 1,124 consecutive SPECT studies were reviewed and 80 (7%) segmentary RD were identified. Thirty-eight patients with RD attributed to artifact (extra cardiac uptake) were excluded. Thus, 42 patients (3.6%), 21 with and 21 without previous infarct, were studied. Thirteen out of 21 RD in patients without previous infarct corresponded to inferior region and 8 to the anterior region. In three out of 8 patients in whom the coronary angiography was performed, the coronary arteries were angiographically normal and 5 had stenosis of between 50% to 70% of coronary arteries corresponding to RD. Of the 21 RD in patients with previous infarct, the RD site corresponded to the same region of the necrosis (15 inferior and 6 anterior). All had viability criteria (uptake higher than 40% in more than 50% of the region) in rest uptake SPECT quantification. In nine out of 11 patients in whom a coronary angiography was carried out, patency of the artery responsible for the infarct was verified. 3.6% of segmentary RD, which were not attributed to the artifact, were observed in myocardial perfusion 99mTc-tetrofosmin SPECT studies. Half of these cases corresponded to regions without previous infarct and with normal coronary arteries or non-severe coronary stenosis. The remaining corresponded to regions with previous infarct and with viability criteria.


Plasma growth hormone concentration in corticosteroid-treated children.
Endogenous plasma growth hormone concentrations were measured in 23 children who were receiving daily corticosteroid therapy and in 10 control asthmatic children who had not received steroids for at least 8 months. The growth hormone concentrations were similar in the two groups of patients both during the fasting state and after insulin-induced hypoglycemia. 12 children, who were studied while receiving a large dose of prednisone and again 2 wk after steroid withdrawal, also showed no change in growth hormone concentration in relation to corticosteroid therapy. These findings suggest that deficiency of growth hormone is not the major mechanism responsible for the dwarfism of corticosteroid-treated children.


Self-assembly of azobenzene bilayer membranes in binary ionic liquid-water nanostructured media.
Anionic azobenzene-containing amphiphile 1 (sodium 4-[4-(N-methyl-N-dodecylamino)phenylazo]benzenesulfonate) forms ordered bilayer membranes in binary ionic liquid (1-ethyl-3-methylimidazolium ethyl sulfate, [C2mim][C2OSO3])-water mixtures. The binary [C2mim][C2OSO3]-water mixture is macroscopically homogeneous at any mixing ratio; however, it possesses fluctuating nanodomains of [C2mim][C2OSO3] molecules as observed by dynamic light scattering (DLS). These nanodomains show reversible heat-induced mixing behavior with water. Although the amphiphile 1 is substantially insoluble in pure water, it is dispersible in the [C2mim][C2OSO3]-water mixtures. The concentration of [C2mim][C2OSO3] and temperature exert significant influences on the self-assembling characteristics of 1 in the binary media, as shown by DLS, transmission electron microscopy (TEM), UV-vis spectroscopy, and zeta-potential measurements. Bilayer membranes with rod- or dotlike nanostructures were formed at a lower content of [C2mim][C2OSO3] (2-30 v/v %), in which azobenzene chromophores adopt parallel molecular orientation regardless of temperature. In contrast, when the content of [C2mim][C2OSO3] is increased above 60 v/v %, azobenzene bilayers showed thermally reversible gel-to-liquid crystalline phase transition. The self-assembly of azobenzene amphiphiles is tunable depending on the volume fraction of [C2mim][C2OSO3] and temperature, which are associated with the solvation by nanoclusters in the binary [C2mim][C2OSO3]-water media. These observations clearly indicate that mixtures of water-soluble ionic liquids and water provide unique and valiant environments for ordered molecular self-assembly.


[Nutritional value of soya milk in the treatment of malnourished alcoholic patients].
The malnourished alcoholic patient requires frequently hospitalization for treatment and an adequate nutritional support is necessary for recovery of their health. The objective of the present study was to evaluate the nutritional value of an enteral diet based on "soya milk", corn sugar, coconut oil and water. Seven alcoholics, males, with 36.4 year mean age, without any clinical evidence of hepatic cirrhosis and/or pancreatitis, were submitted to three periods of metabolic nitrogen balance (NB), with multiple levels of protein intake (0.4, 0.6 and 0.8 grams of proteins/kg of body weight/day). The nitrogen intake (NI), the fecal nitrogen (FN) and the urinary nitrogen (UN) were determined, and the NB and protein digestibility value were calculated. The net protein utilization (NPU) was calculated by correlation studies between the NI and NB, with a value of 101.3%. The mean true digestibility was 100.1% and the mean requirement for that population was 0.5g protein/kg of body weight/day. Using a 97.5% confidence limit, the protein requirement of the enteral diet was calculated to be 0.8g protein/kg of body weight/day. The enteral diet based on "soya milk" can be profitable for this group of patients. It is a good alternative for use in enteral nutrition, easily available, well tolerable, and of high biological value.


Treatment of cervical artery dissection: a systematic review and meta-analysis.
Cervical dissection is an important cause of stroke in the young. This paper presents a systematic review and a meta-analysis to assess the effectiveness of different treatment approaches: antithrombotic drugs, thrombolysis and stenting. Medline and PubMed were searched from 1966 to 8 April 2007. Reference lists were reviewed. Separate searches were performed for treatment with anticoagulation and antiplatelet therapy during the acute phase (within 1 month of symptoms), thrombolysis and stenting. There were only sufficient data for meta-analysis for the comparison of antiplatelet versus anticoagulation therapy. No randomised trials were identified. 34 non-randomised studies included 762 patients. There was no significant difference in risk of death (antiplatelet 5/268 (1.8%), anticoagulation 9/494 (1.8%), p = 0.88); stroke (antiplatelet 5/268 (1.9%), anticoagulant 10/494 (2.0%), p = 0.66), or stroke and death. Four non-randomised studies of thrombolysis provided insufficient data for assessment of efficacy but complication rates were no greater than thrombolysis for other ischaemic stroke. Six studies included 96 patients undergoing stenting for both acute dissection and chronic complications, providing insufficient data for assessment of efficacy, although complication rates appeared similar to those published for carotid atherosclerosic stenosis. There are no data to support the therapeutic superiority of anticoagulants over antiplatelet agents. Thrombolysis in dissection appears safe but more data on efficacy are required. Stenting is technically possible but there are no data to demonstrate efficacy. There is little evidence to support current treatment approaches in cervical dissection. Randomised controlled prospective trials, particularly assessing anticoagulation versus antiplatelet agents, are required.


Identification of models of heterogeneous cell populations from population snapshot data.
Most of the modeling performed in the area of systems biology aims at achieving a quantitative description of the intracellular pathways within a "typical cell". However, in many biologically important situations even clonal cell populations can show a heterogeneous response. These situations require study of cell-to-cell variability and the development of models for heterogeneous cell populations. In this paper we consider cell populations in which the dynamics of every single cell is captured by a parameter dependent differential equation. Differences among cells are modeled by differences in parameters which are subject to a probability density. A novel Bayesian approach is presented to infer this probability density from population snapshot data, such as flow cytometric analysis, which do not provide single cell time series data. The presented approach can deal with sparse and noisy measurement data. Furthermore, it is appealing from an application point of view as in contrast to other methods the uncertainty of the resulting parameter distribution can directly be assessed. The proposed method is evaluated using artificial experimental data from a model of the tumor necrosis factor signaling network. We demonstrate that the methods are computationally efficient and yield good estimation result even for sparse data sets.


Comparison of digitoxin and its major glucuronidated metabolite: inhibition of Na-K-ATPase and reactivity with the radioimmunoassay.
The metabolism of digitoxin is known to occur through several major pathways including oxidation and glucuronidation. Several studies have compared the behavior of the various unconjugated metabolites with respect to reactivity toward Na-K-ATPase and toward the radioimmunoassay (RIA). Other studies with conjugated products synthesized chemically have also been performed. However, the activity of the conjugated products produced in vivo has not been reported and these metabolites are generally assumed to be inactive. In the present studies we have prepared and purified the glucuronide conjugate of digitoxigenin monodigitoxoside formed by rat liver microsomes and determined the activity of this metabolite as measured by inhibition of Na-K-ATPase and by the RIA. The concentration of the conjugated product needed to cause a fifty per cent inhibition of Na-K-ATPase was 5.40 microM compared to 0.68 for digitoxin and 0.08 for digitoxigenin monodigitoxoside. However, the conjugated product had a two-fold greater affinity for the antibody in the RIA procedure than did either digitoxin or digitoxigenin monodigitoxoside. Although these data cannot be extrapolated to the effects of these drugs on cardiac contractility, the results suggest that the contribution of the glucuronide conjugate to the therapeutic or toxic effect of digitoxin may be minimal. This metabolite may, however, lead to inaccurate estimation of blood levels by the RIA.


Classroom Based Intensive Toilet Training for Children with Autism Spectrum Disorder.
The purpose of this study was to investigate the effects of an intensive toilet training program on continence and self-initiation for elementary children with autism spectrum disorder (ASD). Researchers used a non-concurrent multiple baseline design (Watson and Workman in J Behav Ther Exp Psychiatry 12:257-259, 1981, https://doi.org/10.1016/0005-7916(81)90055-0 ) with regulated randomization (Koehler and Levin in Psychol Methods 3(2):206, 1998, https://doi.org/10.1037/1082-989X.3.2.206 ) to evaluate the effects of the intensive protocol with four students with ASD in the classroom where they received special education services. The protocol included increased access to fluids, contingent time intervals for sit schedules, programmed reinforcement, and dry checks. All four participants met mastery criteria and maintained independent toileting after the study's completion. Three participants began self-initiating to use the restroom. The implications and recommendations for future research are discussed.


[Frequency of diagnosis of postmenopausal osteoporosis of the spine, distant radius and extravertebral fractures in women with normal body mass, overweight and obesity].
To assess features and peculiarities of postmenopausal osteoporosis (OP) in women with normal body mass, overweight and obesity. Dual energy X-ray absorptiometry of the lumbal spine (Lunar DPX) and distal radius X-ray absorptiometry (DTX 200) were performed during cross-section study of 730 symptomatic postmenopausal women. OP was diagnosed in 253 (34.7%) women, 30.5% of them had normal body mass, 43.2% had overweight and 26.3% were obese. Among them 227 had atraumatic fractures at the age over 50 years. Obese OP patients had significantly higher frequency of arterial hypertension, chronic heart failure, osteoarthritis and glucose metabolism disorders than osteoporotic patients with normal body mass. Fracture frequency did not differ between groups with normal body mass, overweight and obesity. Excessive body mass did not decrease fracture risk in women with postmenopausal OP.


[Groups with the risk of tuberculosis].
A specially developed screening was used to examine 652 workers of an assembly shop of a watch plant whose work is characterized by their being in a constrained position for hours which leads of general inactivity and hypoventilation. Disturbances of external respiratory function were found in 180 (27.6%) subjects, which is associated with their working conditions rather than with smoking. These subjects deserve special care since the pre-clinical obstructive bronchial changes can be the precursors of broncho-pulmonary diseases and later of tuberculosis.


Khat (Catha edulis)-induced apoptosis is inhibited by antagonists of caspase-1 and -8 in human leukaemia cells.
Khat chewing is a widespread habit that has a deep-rooted sociocultural tradition in Africa and the Middle East. The biological effects of khat are inadequately investigated and controversial. For the first time, we show that an organic extract of khat induces a selective type of cell death having all morphological and biochemical features of apoptotic cell death. Khat extract was shown to contain the major alkaloid compounds cathinone and cathine. The compounds alone and in combination also induced apoptosis. Khat-induced apoptosis occurred synchronously in various human cell lines (HL-60, NB4, Jurkat) within 8 h of exposure. It was partially reversed after removal of khat and the effect was dependent on de novo protein synthesis, as demonstrated by cotreatment with cycloheximide. The cell death was blocked by the pan-caspase inhibitor Z-VAD-fmk, and also by submicromolar concentrations of Z-YVAD-fmk and Z-IETD-fmk, inhibitors of caspase-1 and -8, respectively. The 50% inhibition constant (IC(50)) for khat (200 microg ml(-1))-induced apoptosis by Z-VAD-fmk, Z-YVAD-fmk and Z-IETD-fmk was 8 x 10(-7) M as compared to 2 x 10(-8) M and 8 x 10(-8) M, respectively. Western blot analysis showed a specific cleavage of procaspase-3 in apoptotic cells, which was inhibited by Z-VAD-fmk. The cell death by khat was more sensitively induced in leukaemia cell lines than in human peripheral blood leukocytes. It is concluded that khat induces a rather swift and sensitive cell death by apoptosis through mechanisms involving activation of caspase-1, -3 and -8.


Oceanic islands are not sinks of biodiversity in spore-producing plants.
Islands have traditionally been considered as migratory and evolutionary dead ends for two main reasons: island colonizers are typically assumed to lose their dispersal power, and continental back colonization has been regarded as unlikely because of niche preemption. The hypothesis that islands might actually represent dynamic refugia and migratory stepping stones for species that are effective dispersers, and in particular, for spore-producing plants, is formally tested here, using the archipelagos of the Azores, Canary Islands, and Madeira, as a model. Population genetic analyses based on nuclear microsatellite variation indicate that dispersal ability of the moss Platyhypnidium riparioides does not decrease in the island setting. The analyses further show that, unlike island populations, mainland (southwestern Europe and North Africa) populations underwent a severe bottleneck during the last glacial maximum (LGM). Our results thus refute the traditional view of islands as the end of the colonization road and point to a different perception of North Atlantic archipelagos as major sources of biodiversity for the postglacial recolonization of Europe by spore-producing plants.


Long-term survival in young adults with colorectal cancer: a population-based study.
This study compares the long-term survival of young adults with colorectal cancer who lived a minimum of 5 years after diagnosis with a cancer-free control population. A population-based study was conducted using cancer registry and administrative data. Persons aged 20 to 44 years in whom colorectal cancer was diagnosed between 1992 and 1999 and who lived at least 5 years after diagnosis were identified using the Ontario Cancer Registry. Patients with colorectal cancer were matched 1:5 to randomly selected controls (who were cancer free at the corresponding date of diagnosis) by use of the Registered Persons Database of Ontario based on age, sex, and geographic location. Time-to-death was compared between patients with colorectal cancer and controls by use of Kaplan-Meier estimates and Cox proportional hazard regression. Nine hundred seventeen young adults with colorectal cancer who lived at least 5 years after diagnosis and 4585 controls were identified. The median follow-up after achieving 5-year survivor status was 6.2 years; 9.5% (87) of patients with colorectal cancer died compared with 1.2% (56) of controls (P < .0001). 62.1% of deaths In the colorectal cancer patient population were attributed to malignant disease. Colorectal cancer patients were significantly more likely to die over time than controls (hazard ratio, 8.2; 95% CI (5.8, 11.6)). Those patients with no evidence of disease recurrence within the first 5 years after diagnosis also remained at an increased risk of death (hazard ratio, 2.0, 95% CI (1.2, 3.6)). Young adult 5-year survivors of colorectal cancer remain at a higher risk of long-term death than age-matched controls.


Patient safety: where is nursing education?
Patient safety is receiving unprecedented attention among clinicians, researchers, and managers in health care systems. In particular, the focus is on the magnitude of systems-based errors and the urgency to identify and prevent these errors. In this new era of patient safety, attending to errors, adverse events, and near misses warrants consideration of both active (individual) and latent (system) errors. However, it is the exclusive focus on individual errors, and not system errors, that is of concern regarding nursing education and patient safety. Educators are encouraged to engage in a culture shift whereby student error is considered from an education systems perspective. Educators and schools are challenged to look within and systematically review how program structures and processes may be contributing to student error and undermining patient safety. Under the rubric of patient safety, the authors also encourage educators to address discontinuities between the educational and practice sectors.


A call to action for comprehensive HIV services for men who have sex with men.
Where surveillance has been done, it has shown that men (MSM) who have sex with men bear a disproportionate burden of HIV. Yet they continue to be excluded, sometimes systematically, from HIV services because of stigma, discrimination, and criminalisation. This situation must change if global control of the HIV epidemic is to be achieved. On both public health and human rights grounds, expansion of HIV prevention, treatment, and care to MSM is an urgent imperative. Effective combination prevention and treatment approaches are feasible, and culturally competent care can be developed, even in rights-challenged environments. Condom and lubricant access for MSM globally is highly cost effective. Antiretroviral-based prevention, and antiretroviral access for MSM globally, would also be cost effective, but would probably require substantial reductions in drug costs in high-income countries to be feasible. To address HIV in MSM will take continued research, political will, structural reform, community engagement, and strategic planning and programming, but it can and must be done.


Long lasting effects of rTMS and associated peripheral sensory input on MEPs, SEPs and transcortical reflex excitability in humans.
We tested the effect of repetitive transcranial magnetic stimulation (rTMS) over the motor cortex on the size of transcortical stretch and mixed nerve reflexes. Fourteen healthy subjects were investigated using either 25 min of 1 Hz rTMS or 30 min of 0.1 Hz rTMS paired with electrical stimulation of the motor point of the first dorsal interosseous muscle (FDI). Following treatment, we measured the effect on the size of: (1) EMG responses evoked in FDI by transcranial magnetic stimulation (MEPs), (2) somatosensory evoked potentials (SEPs) evoked by ulnar nerve stimulation, and (3) transcortical stretch or electrically elicited reflexes. rTMS at 1 Hz reduced the amplitude of both MEPs and long latency reflexes by 20-30 % for about 10 min after the end of stimulation. Short latency reflexes were unaffected. SEPs were not studied, as it has been shown previously that they are also suppressed. rTMS at 0.1 Hz paired with motor point stimulation (interstimulus interval of 25 ms) increased the amplitude of the MEP and the cortical components of the SEP (N20/P25 and later peaks) for up to 10 min. Long latency reflexes were facilitated with the same time course. We conclude that rTMS over the motor cortex either alone or in conjunction with peripheral inputs can decrease or increase the excitability of the sensory and motor cortex for short periods after the end of stimulation. These changes affect not only MEPs and SEPs but also EMG responses to more 'natural' inputs involved in transcortical stretch reflexes.


Expression and Content of Terminal Oxidases in Azotobacter Vinelandii Grown with Excess NH4+ are Modulated by O2 Supply.
The influence of the rate of O2 supply to batch cultures on the contents of cytochromes bd and 'o' in NH4 +-grown Azotobacter vinelandii has been investigated. Difference spectra at room temperature (reduced + CO minus reduced) were recorded for whole cells of a wild-type strain and mutants which either lacked or over-produced the cytochrome bd-type terminal oxidase encoded by cydAB. A Tn5-B20 insertion in cydB in the former mutant also provided a means of monitoring cydAB gene expression from measurements of β-galactosidase activity. The content of cytochrome d in the wild-type, and the expression of cydAB-lacZ, in the mutant, increased as the O2 supply was raised, suggesting that O2 regulates cydAB expression even in the absence of diazotrophy. In a strain carrying a mutation in cydR, a regulatory gene upstream of cydAB, and which over-produces cytochrome bd, the responses to O2 supply during growth at different O2 supply rates were reversed. Changes in the content of a haemoprotein detectable in low temperature photodissociation spectra, and attributed to cytochrome b 595 -the high-spin cytochrome b component of the cytochrome bd complex - followed the changes in cytochrome d levels. CO difference spectra of both the wild-type strain and the cytochrome bd-deficient mutant revealed a haemoprotein with spectral characteristics similar to cytochrome o, the levels of which increased as the O2 supply was raised. These results are discussed with reference to previous reports of cytochrome changes in cells grown under N2-fixing conditions.


Comparison of two approaches to performing an inferior alveolar nerve block in the horse.
To compare two approaches to performing the inferior alveolar nerve block in the horse and to evaluate the consistency of described topographical landmarks. Experimental cadaver model. Eleven cadaver heads were positioned to mimic a standing sedated horse and the position of the mandibular foramen approximated. The vertical approach to the approximate location of the mandibular foramen was undertaken and red dye was deposited. The angled approach was then undertaken and blue ink was used to identify it. The heads were then dissected to determine the location of the dye. Placement was categorised as a hit or a miss for each technique for each side of the head. The distance of the dye from the nerve was recorded. Straight lateral radiographs of the sectioned heads were taken to evaluate the topographical landmarks for performing this nerve block. Each method was performed 22 times. A hit was achieved 16 times (73%) for the angled approach and 13 times (59%) for the vertical approach. There was no significant difference between the two approaches (P = 0.34). Radiographs revealed that the topographical landmarks used to approximate the mandibular foramen were relatively accurate. Both methods were found to be equivalently accurate. The previously reported topographic landmarks for locating the approximate position of the mandibular foramen on the medial aspect of the mandible were found to be accurate, but currently recommended doses of local anaesthetic may be excessive.


Effects of small latex particle uptake on the surface connected canalicular system of blood platelets: a freeze-fracture and cytochemical study.
Recent investigations have suggested that channels of the surface connected open canalicular system are the major source of membrane contributing to increased surface area of platelets following activation or uptake of particulates. However, study of large latex particle phagocytosis suggested that channels filled with spherules become dilated and lose connections with the outer surface, but do not become extruded onto the platelet membrane. The present study has employed electron dense tracers, freeze-fracture and transmission electron microscopy to follow the uptake of small latex spherules by blood platelets. Small particles were rapidly incorporated into the numerous channels without causing significant changes in surface or internal morphology. Intramembranous particles on both E and P faces in replicas of freeze-fractured platelets were unaffected by ingestion of latex spherules. Prolonged exposure to small latex particles caused platelets to lose their discoid form. The irregular spheres contained two or three dilated vacuoles filled with latex and a reduced number of single channels. Results of this and previous studies suggest that channels of the open canalicular system are internalized in platelets after phagocytosis, and are not extruded onto the platelet surface.


Generation of an Alagille syndrome (ALGS) patient-derived induced pluripotent stem cell line (TRNDi032-A) carrying a heterozygous mutation (p.Cys682Leufs*7) in the JAG1 gene.
Alagille syndrome (ALGS) is an autosomal dominant, multisystemic disorder due to haploinsufficiency in either the JAG1 gene (ALGS type 1) or the NOTCH2 gene (ALGS type 2). The disease has been difficult to diagnose and treat due to its muti-system clinical presentation, variable expressivity, and prenatal onset for some of the features. The generation of this iPSC line (TRNDi032-A) carrying a heterozygous mutation, p.Cys682Leufs*7 (c.2044dup), in the JAG1 gene provides a means of studying the disease and developing novel therapeutics towards patient treatment.


Second Trimester Maternal Leptin Levels Are Associated with Body Mass Index and Gestational Weight Gain but not Birth Weight of the Infant.
Obesity is increasing among the pregnant population. Leptin has an important role in the regulation of energy balance and hunger. The aim of this study was to investigate the association between maternal leptin levels with maternal obesity, gestational weight gain (GWG), single nucleotide polymorphisms (SNPs) within the leptin gene, and the age-adjusted birth weight of the child. Maternal leptin levels (n = 740) and SNPs (n = 504) were analyzed in blood samples taken within the Uppsala Biobank of Pregnant women at pregnancy weeks 16-19. Maternal leptin levels differed significantly between body mass index (BMI) groups. Normal weight women had the lowest median leptin levels and levels increased with each BMI group. Leptin SNP genotype was not associated with leptin levels or BMI. There was also no association between maternal leptin levels and age-adjusted birth weight of the child except for a negative association between leptin levels and birth weight in the morbid obese group. Maternal BMI was identified as the best positive explanatory factor for maternal leptin levels. Leptin was a strong positive explanatory factor for GWG. Birth weight of children of uncomplicated pregnancies was, however, dependent on maternal height, BMI, GWG, and parity but not leptin levels, except for in morbid obese women where a negative association between maternal leptin levels and birth weight was found. We speculate that this indicates altered placental function, not manifested in pregnancy complication. We conclude that maternal leptin levels do not affect the birth weight of the child more than BMI, GWG, and parity.


Cardiac nerve blockade by infusion of procaine into the pericardial space of conscious dogs.
A technique was developed to produce acute, reversible cardiac nerve blockade (CNB) in the conscious dog by infusion of 2% procaine into the pericardial (PC) space. During CNB, reflex changes in heart rate (HR) in response to intravenous bolus injections of phenylephrine (100 micrograms) and nitroglycerin (300 micrograms) and the reflex tachycardia and hypotension after a 50-micrograms bolus injection of veratridine into the left atrium were abolished. In response to CNB, HR increased from 79 +/- 10 to 142 +/- 10 beats/min and mean arterial pressure (MAP) increased from 101 +/- 5 to 117 +/- 6 mmHg. Baseline values for plasma arginine vasopressin (AVP), plasma renin activity (PRA), and plasma norepinephrine (NE) were unchanged by CNB, but there was a small increase in plasma cortisol levels (1.4 +/- 0.3 to 2.3 +/- 0.3 micrograms/dl) during CNB. There was no significant change in the baseline levels of any of these hormones during PC infusion of 0.9% saline. To control for the possibility that procaine leaked into the systemic circulation, identical amounts of procaine were infused intravenously. Systemic administration of procaine caused a rise in MAP but had no effect on HR and did not alter plasma levels of AVP, PRA, NE, or cortisol. The relationship between plasma osmolality and plasma AVP, as well as the drinking response to a 60-min infusion of hypertonic NaCl, was unaltered by CNB. We conclude that PC procaine infusion is an effective technique for producing acute, reversible blockade of the cardiac nerves in the conscious dog.


Optical acceptance function of modified compound parabolic concentrators with linear corrugated reflectors.
For reflective cylindrical concentrators the acceptance function, as determined in the meridian plane, remains constant for more oblique planes of incidence. However, if the reflective surface has a linear corrugated structure, it is possible to increase the acceptance in the meridian plane at the expense of reduced acceptance at a more oblique incidence. A ray-tracing study has been performed on the optical properties of troughlike compound parabolic concentrators (CPC's) with linear corrugated reflectors. Calculations of angular acceptance for a modified CPC with concentration C = x is presented. A possible application of this new concentrator is as a secondary concentrator for tracking parabolic troughs.


Giant zirconium-bisphosphonate nano-ribbons and their liquid crystalline phase behaviour in water.
In decimolar aqueous solutions, zirconium oxychloride octahydrate forms several micrometer long and approximately 15 nm wide thin ribbons through the reaction with excess amounts of the sodium salt of 1-hydroxyethane-1,1-diphosphonic acid (HEDP, known as etidronic acid). Primarily deduced from SAXS, TEM, EXAFS and solid-state NMR analyses, a consistent structural model enables congruous explanations for the colloidal behaviour of the purified ribbons as well as of their reaction products with ammonia and amines, respectively. Properties of the lyotropic, liquid crystalline phases are discussed in the light of potential applications in aqueous coatings.


qTeller: a tool for comparative multi-genomic gene expression analysis.
Over the last decade, RNA-Seq whole-genome sequencing has become a widely used method for measuring and understanding transcriptome-level changes in gene expression. Since RNA-Seq is relatively inexpensive, it can be used on multiple genomes to evaluate gene expression across many different conditions, tissues and cell types. Although many tools exist to map and compare RNA-Seq at the genomics level, few web-based tools are dedicated to making data generated for individual genomic analysis accessible and reusable at a gene-level scale for comparative analysis between genes, across different genomes and meta-analyses. To address this challenge, we revamped the comparative gene expression tool qTeller to take advantage of the growing number of public RNA-Seq datasets. qTeller allows users to evaluate gene expression data in a defined genomic interval and also perform two-gene comparisons across multiple user-chosen tissues. Though previously unpublished, qTeller has been cited extensively in the scientific literature, demonstrating its importance to researchers. Our new version of qTeller now supports multiple genomes for intergenomic comparisons, and includes capabilities for both mRNA and protein abundance datasets. Other new features include support for additional data formats, modernized interface and back-end database and an optimized framework for adoption by other organisms' databases. The source code for qTeller is open-source and available through GitHub (https://github.com/Maize-Genetics-and-Genomics-Database/qTeller). A maize instance of qTeller is available at the Maize Genetics and Genomics database (MaizeGDB) (https://qteller.maizegdb.org/), where we have mapped over 200 unique datasets from GenBank across 27 maize genomes. Supplementary data are available at Bioinformatics online.


Primary care management of chronic obstructive pulmonary disease to reduce exacerbations and their consequences.
Exacerbations of chronic obstructive pulmonary disease (COPD)-acute worsenings of dyspnea, cough and/or sputum production beyond daily symptom variations, necessitating a change in treatment-account for most COPD-related morbidity, care burden and direct costs. Frequent exacerbations (especially those requiring emergency, inpatient or intensive care) reduce physical activity, accelerate lung function decline and increase mortality. This review profiles exacerbation diagnosis, treatment and reduction measures for primary care physicians. Chronic maintenance pharmacotherapy is important to reduce exacerbations. Tiotropium, a long-acting anticholinergic, and salmeterol/fluticasone, a long-acting β-agonist/inhaled corticosteroid combination, are Food and Drug Administration-approved maintenance therapies to reduce exacerbations of COPD. Influenza and pneumonia vaccinations reduce infectious triggers; pulmonary rehabilitation reduces exacerbation recurrence. Acute exacerbation treatment (short-acting bronchodilators, systemic corticosteroids and/or antibiotics) should be complemented by long-term COPD maintenance therapy to reduce future exacerbations. Recognition of a COPD exacerbation signals primary care physicians to establish long-term COPD management to reduce morbidity, disability and mortality.