Symptoms of depression and anxiety in patients with thalassemia: prevalence and correlates in the thalassemia longitudinal cohort.
Thalassemia is an inherited blood disorder that requires lifelong adherence to a complicated and burdensome medical regimen which could potentially impact emotional functioning of patients. The importance of understanding and promoting healthy emotional functioning is crucial not only to psychological well-being, but also to physical health as it has been shown to impact adherence to medical regimens [1-4]. The current study aimed to [1] determine the prevalence of depressive and anxiety symptoms in adolescent and adult patients with thalassemia; and [2] explore possible demographic, medical, and psychosocial correlates of these symptoms in 276 patients (14-58 years old, M age = 27.83; 52% female). Overall, most patients did not report experiencing significant symptoms of anxiety and depression (33% of participants indicated experiencing symptoms of anxiety and 11% symptoms of depression). Females and older patients were more likely to experience these symptoms than males and younger patients. Symptoms of anxiety and depression were positively associated with self-report of difficulty with adherence and negatively associated with quality of life. Given these findings, regular screening for anxiety and depression symptoms could help to identify at-risk individuals to provide them with appropriate psychological support with the goal of improving both emotional and physical health.


Polyunsaturated fatty acid biosynthesis in Saccharomyces cerevisiae: expression of ethanol tolerance and the FAD2 gene from Arabidopsis thaliana.
The Arabidopsis thaliana delta-12 fatty acid desaturase gene (FAD2) was overexpressed in Saccharomyces cerevisiae by using the GAL1 promoter. S. cerevisiae harboring the FAD2 gene was capable of forming hexadecadienoyl (16:2) and linoleoyl (18:2) residues in the membrane lipid when cultured in medium containing galactose. Gas-liquid chromatography analysis of total lipids indicated that the transformed S. cerevisiae accumulated these dienoic fatty acyl residues and that they accounted for approximately 50% of the total fatty acyl residues. Phospholipid analysis of this strain indicated that the oleoyl (18:1) residue binding phosphatidylcholine (PC) was mostly converted to the 18:2 residue binding PC, whereas 50% of the palmitoleoyl (16:1) residue binding PC was converted to the 16:2 residue binding PC. A marked effect on the unsaturation of 16:1 and 18:1 was observed when S. cerevisiae harboring the FAD2 gene was cultured at 8 degrees C. To assess the ethanol tolerance of S. cerevisiae producing polyunsaturated fatty acids, the cell viability of this strain in the presence of ethanol was examined. The results indicated that S. cerevisiae cells overexpressing the FAD2 gene had greater resistance to 15% (vol/vol) ethanol than did the control cells.


First enzymatic synthesis of an N1-cyclised cADPR (cyclic-ADP ribose) analogue with a hypoxanthine partial structure: discovery of a membrane permeant cADPR agonist.
Nicotinamide 8-Br-hypoxanthine dinucleotide (8-Br-NHD+) was cyclised at the N1 position by the ADP-ribosyl cyclase from Aplysia californica to give cyclic 8-Br-inosine diphosphoribose (8-Br-N1-cIDPR), a novel membrane-permeant agonist of Ca2+ release in human T cells.


Effect of venlafaxine on pineal melatonin and noradrenaline in the male rat.
Studies in vitro indicate that the antidepressant drug, venlafaxine (VEN), inhibits the reuptake of both serotonin (5-hydroxytryptamine, 5-HT) and noradrenaline (NA) but has little activity on other neurotransmitter receptors. There are, however, few studies on the effects of VEN on monoamine neurotransmission in vivo. In the present study we examined the effect of VEN treatment on the melatonin content of the rat pineal gland because the synthesis of melatonin is regulated by the release of NA onto pinealocyte beta-adrenoceptors. Acute treatment with higher doses (15 mg/kg) of VEN significantly increased pineal melatonin and NA but this effect was attenuated by subchronic treatment. These data are consistent with in vitro data suggesting that VEN increases NA neurotransmission at higher doses and that repeated treatment can desensitize pinealocyte beta-adrenoceptors.


Genetic implications and health consequences following the Chernobyl nuclear accident.
It has been almost 25 years since the Chernobyl nuclear accident in Ukraine. We review relevant data derived from published reports originating in the Former Soviet Union. We cite census data from Ukraine and research studies from Western Europe that analyzed the effect of radiation on genetics and health outcome in the exposed populations. We also present philatelic materials that pictorially captured that fateful event in history.


Is osteoporosis a risk factor for osseointegration of dental implants?
The success of osseointegration depends in part on the state of the host bed. Concerns have therefore been raised about osteoporosis, a condition believed to be associated with a decrease in bone quality and quantity. However, the orthopedic literature indicates that osteoporotic fractures heal readily and that the level of bone mass and estimates of the parameters associated with bone remodeling present considerable overlap between patients with osteoporosis and control subjects. It also appears that osteoporosis, as diagnosed at one particular site of the skeleton, is not necessarily seen at another distant site. Although the prevalence of osteoporosis increases among the elderly and after menopause, the results of this study indicate that implant failure rate is not correlated with age and sex. A review of the literature and of results of a series of patients treated does not provide a compelling theoretical or practical basis to expect osteoporosis to be a risk factor for osseointegrated dental implants.


Synergistic enhancement of chemisorption and catalytic conversion in lithium-sulfur batteries via Co3Fe7/Co5.47N separator mediator.
Lithium-sulfur batteries (LSBs) show considerable potential in next-generation high performance batteries, but the heavy shuttle effect and sluggish redox kinetics of polysulfide hinder their further applications. In this paper, to address these shortcomings of LSBs, Co3Fe7/Co5.47N heterostructure were prepared and constructed from their Fe-Co Prussian blue analogue precursors under the condition of high temperature pyrolysis. The obtained Co3Fe7/Co5.47N display excellent immobilization-diffusion-conversion performance for polysulfides by synergistic effect in successfully hindering the shuttle effect of polysulfides. When the Co3Fe7/Co5.47N heterostructure were applied to modify the commercial polypropylene (PP) separator, the batteries displayed fantastic rate capacity and cycling stability. Specifically, the Co3Fe7/Co5.47N-PP batteries exhibit an extremely satisfactory initial specific capacity of 1430 m Ah/g at 0.5C, wonderful rate capacity of around 780 m Ah/g at 3C and superior per cycle decaying rate of 0.08 % for 500 cycles at 0.5C. When the current density reaches to 2C, the batteries still exhibit 501 m Ah/g after 900 cycles with 0.015 % per cycle decay rate. Besides, even in the high loading of sulfur (3.0 mg cm-2) at 0.5C, the superior cycling stability (0.075 % per cycle decay rate after 200 cycles) and high specific capacity (741 mAh/g after 200 cycles) can still be performed. Thus, this work provides a facile method for high-powered and long-life Li-S batteries with eminent entrapping-conversion processes of polysulfides.


Enhanced c-myc gene expression during forelimb regenerative outgrowth in the young Xenopus laevis.
Analysis of the expression of the c-myc protooncogene has been carried out in the forelimb regenerate of the Xenopus laevis froglet. Northern blot hybridization analysis revealed the presence of a 2.5-kilobase c-myc transcript in the regenerate forelimb at a level at least 7-fold more than the one found in nonregenerating forelimbs or stumps of regenerating forelimbs. In situ hybridization analyses confirmed the relative abundance of c-myc RNA in the regenerate forelimb and provided evidence of spatial localization of high levels of c-myc RNA in specific cell layers. The deepest layers of the wound epithelium of epidermal origin showed a strong signal, whereas virtually no c-myc RNA was detected in the outermost layers. Labeling was also observed in mesenchymal cells of the blastema where it was relatively evenly distributed. This pattern of c-myc RNA in the regenerate might indicate that the expression of c-myc plays a role in the regulation of the continued proliferation of specific cells of the regenerate, whereas repression of this gene in the epidermis correlates with terminal differentiation of keratinocytes.


Antidiarrheal activity of Capparis zeylanica leaf extracts.
The antidiarrheal activity of the methanolic extract of the leaves of Capparis zeylanica (Capparidaceae) was investigated by castor oil-induced diarrhea and small intestine transit method on mice. Like loperamide (3 mg/kg body weight), C. zeylanica methanolic extract (100,150,200 mg/kg body weight) produced a significant decrease in the severity of diarrhea. The percentage protection in extract-treated animals showing diarrhea was compared with castor oil-treated and loperamide-treated animals. The activity was found to be dose-dependant. Its effect when evaluated on intestinal transit produced a decrease in intestinal transit (75.97%).The results revealed that the methanolic extract significantly reduced diarrhea in mice with reduction in weight of stools.


[Blood fatty acid transporters in acute pancreatitis].
A relationship between of acute pancreatitis severity and concentrations of blood transporters of nonesterified fatty acids (albumin) and esterified fatty acids (lipoproteins) was studied. In necrotizing pancreatitis, there was a positive correlation between decrease of albumin and lipoprotein concentrations in serum, but no correlation was in edematous pancreatitis. High levels of serum albumin (> 32 g/L) and lipoproteins (cholesterol + triglycerides, CH + TG, > 260 mg/dL) had good prognostic value in terms of favourable development of this disease, whereas lower concentrations indicated unfavourable prognosis. Both albumin and lipoproteins appeared in the peritoneal exsudate where they represented 73 and 53% of the serum concentrations, respectively. Albumin efflux from blood to the exsudate correlated with lipoprotein efflux (r = 0.7) in necrotizing pancreatitis. The latter suggests that proteins penetrated together the tissue barrier blood/peritoneal space. The less albumin and lipoprotein concentrations in serum, the more they are in the exsudate (r = -0.57 and -0.47, respectively); probably, their concentration decrease in blood is due to to their efflux into the exsudate.


Closure of ductus arteriosus determined by cardiac catheterization and angiography in newborn foals.
The physiologic closure of the ductus areteriosus was determined in 4 foals less than 16 hours old. The common carotid artery was catheterized, using local anesthesia and tranquilization, and contrast medium was injected into the ascending aorta. Radiographs were made of heart and great vessels during and after the injection to visualize the pathway of injected contrast medium.


Risk of hematological malignancies from CT radiation exposure in children, adolescents and young adults.
Over one million European children undergo computed tomography (CT) scans annually. Although moderate- to high-dose ionizing radiation exposure is an established risk factor for hematological malignancies, risks at CT examination dose levels remain uncertain. Here we followed up a multinational cohort (EPI-CT) of 948,174 individuals who underwent CT examinations before age 22 years in nine European countries. Radiation doses to the active bone marrow were estimated on the basis of body part scanned, patient characteristics, time period and inferred CT technical parameters. We found an association between cumulative dose and risk of all hematological malignancies, with an excess relative risk of 1.96 (95% confidence interval 1.10 to 3.12) per 100 mGy (790 cases). Similar estimates were obtained for lymphoid and myeloid malignancies. Results suggest that for every 10,000 children examined today (mean dose 8 mGy), 1-2 persons are expected to develop a hematological malignancy attributable to radiation exposure in the subsequent 12 years. Our results strengthen the body of evidence of increased cancer risk at low radiation doses and highlight the need for continued justification of pediatric CT examinations and optimization of doses.


Diet pattern and longevity: do simple rules suffice? A commentary.
Nutritionism reduces dietary advice to statements about a few nutrients, with sometimes unintended implications for science, industry, and the public. Although reductionist questions about nutrition are legitimate scientifically, a nutrient focus in the public arena forces the food industry to compete with the use of nutrient statements. Consumers must interpret information that may not be correct or relevant. The theory of food synergy, which postulates that the many constituents of individual foods and dietary patterns act together on health, leads to the idea that dietary policy would be clearer if it focused on foods. To illustrate this method, the food-based A Priori Diet Quality Score was described in the Iowa Women's Health Study; a substantial total mortality reduction for increasing quartiles of the score was found. The simple food-based rules implied in this a priori score support minimizing meat, salt, added sugar, and heavily processed foods while emphasizing phytochemical-rich foods. These principles could help improve nutrition policy, help industry to supply better food, and help to focus future scientific research. Although an understanding of what foods are best for health is a step forward in nutrition, other major challenges remain, including getting high-quality food to the masses and food sustainability.


Diversity of the effect of recombinant tumor necrosis factors alpha and beta on human myelogenous leukemia cell lines.
In vitro characteristics of response to recombinant tumor necrosis factors alpha (rTNF-alpha) and beta (rTNF-beta) were studied in six human myelogenous leukemia cell lines. Heterogeneity of the response to rTNF was observed, and one line (K562) was resistant. No enhancement of cell growth was noted in any cell line. The dose-response curves for rTNF-alpha were characteristically sigmoid, the maximum inhibitory effect occurring between 25 and 200 ng/mL. Nonresponsiveness within this range indicated resistance that could not be overcome, even with very high doses of rTNF alpha. A similar response of sensitive and resistant lines occurred after exposure to rTNF-beta. The clonogenic cells were more sensitive than the overall population to the action of rTNF alpha, and prolonged exposure was necessary for manifestation of the effect. Concomitant exposure to recombinant interferon-alpha (rIFN-alpha) increased the response of two cell lines to rTNF-alpha, but no clear synergistic action could be demonstrated. The addition of rIFN-gamma was without effect. Variations in the rTNF-alpha-induced proliferative response could not be explained by differences in the number of binding sites per cell or their affinity for rTNF-alpha. That the clonogenic cells showed a higher sensitivity than the whole population might indicate a preferential effect on more primitive, actively proliferating cells with high growth potential.


Time trends in suicide-related behaviours in girls and boys.
To examine the incidence and nature of emergency department (ED) presentations for nonfatal suicide-related behaviours (SRBs) over time, in boys and girls living in Ontario. We hypothesize declining rates (fiscal years [FYs] 2002/03 to 2006/07) ceased thereafter owing to renewed regulatory warnings against prescribing antidepressants and the economic recession. We graphed and tested differences in ED SRB incidence rates for FYs 2002/03 to 2010/11. We estimated rate ratios and 95% confidence intervals using negative binomial regression controlling for changes in the underlying population (age, community size, and neighbourhood income quintile). We examined the nature of the incident (index) presentations over time in terms of the method(s) used and events occurring before and after the index event. ED SRB incidence rates decreased by 30% in boys and girls from FYs 2002/03 to 2006/07, but not thereafter. This trend was most evident in girls who self-poisoned and in girls' presentations to hospital with mental illness in the preceding year. Within a year of the index event, the proportion of girls with a repeat ED SRB presentation also declined by about one-third, but beyond FYs 2005/06 to 2009/10. However, the proportion admitted subsequent to the index event increased by about one-third. In boys, their patterns of presentations to hospital with mental illness and SRB repetition over time were similar to girls, but estimated with greater variability. While the decline in ED SRB rates to FY 2006/07 is encouraging, the lack of decline thereafter and an increase in subsequent admissions merits ongoing monitoring and evaluation.


QTL analysis of proteome and transcriptome variations for dissecting the genetic architecture of complex traits in maize.
In this review, we present some studies on genetic analysis of proteome and transcriptome variations, which exemplify new strategies for a better understanding of the molecular and genetic bases of complex traits. A large genetic variability was revealed at the proteome expression level, which raised the possibility to predict phenotypical performance on the basis of gene product variability. This approach yielded limited results, but could be re-newed by extensive identification of proteins now allowed by mass spectrometry. The dissection of the genetic basis of the variation of individual protein amounts proves very powerful to select 'candidate' proteins, physiologically relevant for a given phenotypical trait, as shown by a study on the effect of water stress in maize. In order to investigate factors of grain quality in maize, we selected a regulatory locus known to control the expression of several storage protein genes, Opaque-2, and investigated the relationships between variability in zein amount and composition and the molecular polymorphism at this locus. Moreover, a QTL analysis revealed that the variability in Opaque-2 transcript abundance was controlled by several polymorphic trans-acting regulators unlinked to the Opaque-2 structural gene. Such genetic approaches should represent additional tools for physiological analysis of the huge amounts of data generated by transcritome and proteome projects.


Relative adrenal insufficiency in a patient with liver disease.
Patients with established cirrhosis are at increased risk of sepsis. Bacterial infections are a frequent cause of morbidity and mortality in patients with advanced liver disease. Mortality for patients admitted to hospital with bacterial infection is approximately 30%, whereas the development of septic shock and multiorgan failure is associated with a mortality of 70-100%. Activation of the hypothalamic-pituitary-adrenal axis is an important feature of a patient's response to severe sepsis and major trauma. An inadequate adrenal response with suboptimal cortisol production has been recognized in patients with septic shock. Patients with septic shock and adrenal insufficiency have reduced response to vasoconstrictor agents, higher rates of refractory shock and high mortality rates. An improvement in survival with administration of hydrocortisone in patients with septic shock and an inadequate adrenal response has been demonstrated. In a more recent study, however, there was no survival benefit in septic shock though reversal of shock was faster with hydrocortisone administration. Recently, adrenal insufficiency has been demonstrated in patients with severe liver disease such as acute liver failure, acute on chronic liver failure, recent liver transplantation and cirrhosis irrespective of the presence of sepsis. Nevertheless survival benefit with administration of hydrocortisone has only been demonstrated in patients with cirrhosis and septic shock. A case report of a patient with cirrhosis and adrenal insufficiency is presented with a review of the literature.


Covalent Immune Recruiters: Tools to Gain Chemical Control Over Immune Recognition.
Unprecedented progress made in the treatment of cancer using the body's own immune system has encouraged the development of synthetic molecule based immunotherapeutics. An emerging class of these compounds, called Antibody Recruiting Molecules (ARMs) or Antibody Engagers (AEs), functions by reversibly binding antibodies naturally present in human serum and recruiting these to cancer cells. The recruited antibodies then engage immune cells to form quaternary complexes that drive cancer erradication. Despite their promise, the requirement to form quaternary complexes governed by multiple equilibria complicates an understanding of their in vivo efficacy. Particularly problematic are low endogenous serum antibody concentrations and rapid clearance of AEs from circulation. Here we describe a new class of trifunctional chemical tools we call covalent immune recruiters (CIRs). CIRs covalently label specific serum antibodies in a selective manner with a target protein binding ligand. CIRs thereby exert well-defined control over antibody recruitment and simplify quaternary complex equilibium, enabling probing of the resultant effects on immune recognition. We demonstrate CIRs can selectively covalently label anti-DNP IgG, a natural human antibody, directly in human serum to drive efficient immune cell recognition of targets. We expect CIRs will be useful tools to probe how quaternary complex stability impacts the immune recognition of cancer in vivo, revealing new design principles to guide the development of future AEs.


Controlled cortical impact model for traumatic brain injury.
Every year over a million Americans suffer a traumatic brain injury (TBI). Combined with the incidence of TBIs worldwide, the physical, emotional, social, and economical effects are staggering. Therefore, further research into the effects of TBI and effective treatments is necessary. The controlled cortical impact (CCI) model induces traumatic brain injuries ranging from mild to severe. This method uses a rigid impactor to deliver mechanical energy to an intact dura exposed following a craniectomy. Impact is made under precise parameters at a set velocity to achieve a pre-determined deformation depth. Although other TBI models, such as weight drop and fluid percussion, exist, CCI is more accurate, easier to control, and most importantly, produces traumatic brain injuries similar to those seen in humans. However, no TBI model is currently able to reproduce pathological changes identical to those seen in human patients. The CCI model allows investigation into the short-term and long-term effects of TBI, such as neuronal death, memory deficits, and cerebral edema, as well as potential therapeutic treatments for TBI.


HIV and sexually transmitted infection risk behaviors and beliefs among Black West Indian immigrants and US-born Blacks.
We compared Black West Indian immigrants' and US-born Blacks' sexual and drug-use risk behaviors and their beliefs related to using condoms and informing partners of sexually transmitted infections (STIs) to identify possible differences in risk. We drew data from the baseline assessment of a clinic-based intervention designed to increase partner STI notification. Black West Indian men were less likely than were US-born Black men to report nonregular partners. There were no differences in condom use. US-born Black women were more likely than were Black West Indian women to be extremely confident that they could convince their regular partners to use condoms (odds ratio [OR] = 2.40; 95% confidence interval [CI] = 1.21, 4.76), whereas there were no differences between Black West Indian and US-born Black men on this measure (interaction P = .06). US-born Black women were more likely than were Black West Indian women to be extremely confident in their ability to discuss STI screening with their regular partners (OR = 1.89; 95% CI = 1.03, 3.47). Black West Indian women's lower levels of confidence that they can discuss STI screening with their regular partners and convince these partners to use condoms may increase their infection risk. Gender-sensitive interventions are warranted for Black West Indian immigrants, especially women.


Ser/Thr phosphorylation of hematopoietic specific protein 1 (HS1): implication of protein kinase CK2.
Hematopoietic lineage cell-specific protein 1 (HS1), a tyrosine multiphosphorylated protein implicated in receptor-mediated apoptosis and proliferative responses, is shown here to become Ser/Thr phosphorylated upon incubation of platelets with radiolabeled inorganic phosphate. The in vivo Ser/Thr phosphorylation of HS1 is enhanced by okadaic acid and reduced by specific inhibitors of casein kinase (CK)2. In vitro, HS1 is an excellent substrate for either CK2 alpha subunit alone (Km = 47 nM) or CK2 holoenzyme, tested in the presence of polylysine (Km = 400 nM). Phosphorylation reaches a stoichiometry of about 2 mol phosphate per mol HS1 and occurs mainly at threonyl residue(s), mostly located in the N-terminal region, but also at seryl residue(s) residing in the central core of the molecule (208-402), as judged from experiments with deleted forms of HS1. Ser/Thr phosphorylation of HS1, either induced in vivo by okadaic acid or catalysed in vitro by CK2, potentiates subsequent phosphorylation at tyrosyl residues. These data indicate the possibility that regulation of HS1 may also be under the control of Ser/Thr phosphorylation, and suggest that in quiescent cells CK2 could play a role in inducing constitutive Tyr phosphorylation of HS1 in the absence of stimuli that activate the protein tyrosine kinase pathway.


Phytochemical profiles and antioxidant activity of wheat varieties.
Whole grain consumption has been associated with reduced risk of chronic diseases, such as cardiovascular diseases and cancer. These beneficial effects have been attributed to the unique phytochemicals of grains that complement those found in fruits and vegetables. Wheat is one of the major grains in the human diet; however, little is known about the inherent varietal differences in phytochemical profiles, total phenolic and carotenoid contents, or total antioxidant activities of different wheat varieties, which ultimately influence the associated nutritional and health benefits of wheat and wheat products. The objectives of this study were to determine the phytochemical profiles and total antioxidant activity for 11 diverse wheat varieties and experimental lines. The profiles included free, soluble-conjugated, and insoluble-bound forms of total phenolics, flavonoids, and ferulic acids and carotenoid content including lutein, zeaxanthin, and beta-cryptoxanthin. The results showed that total phenolic content (709.8-860.0 micromol of gallic acid equiv/100 g of wheat), total antioxidant activity (37.6-46.4 micromol of vitamin C/g), and total flavonoid content (105.8-141.8 micromol of catechin equiv/100 g of wheat) did not vary greatly among the 11 wheat lines. However, significant differences in total ferulic acid content (p < 0.05) and carotenoid content (p < 0.05) among the varieties were observed, with carotenoid content exhibiting the greatest range of values. Carotenoid content among the 11 wheat varieties exhibited 5-fold, 3-fold, and 12-fold differences in lutein, zeaxanthin, and beta-cryptoxanthin, respectively. A synthetic wheat experimental line, W7985, gave the lowest carotenoid concentrations of any of the genotypes in this study. Such large genotypic differences in carotenoid content may open up new opportunities for breeding wheat varieties with higher nutritional value.


Updated results on the karyology of the WI-38, MRC-5 and MRC-9 cell strains.
Data concerning cumulative results obtained from studies of the karyology of the characterized MRC-5 cell strain and the MRC-9 strain at present being characterized, indicate that these cells have karyological characteristics similar to each other and to the extensively studied WI-38 cell strain. The general inference from these studies is that the cells are karyotypically stable and that their karyological characteristics are within the limits recommended for normal cell populations.


[Middle and long-term follow-up of 101 children with giant coronary artery aneurysm of Kawasaki disease].
Objective: To summarize the clinical features, middle-and long-term prognosis of Kawasaki disease (KD) with giant coronary artery aneurysm (GCAA). Methods: In this retrospective cohort study, a cross-sectional analysis was conducted on 101 KD children with GCAA in the KD with GCAA database established by Beijing Children's Hospital, Capital Medical University in 2004. GCAA was diagnosed as coronary artery absolute lumen diameter ≥8.0 mm. All patients were followed up regularly. The endpoint was the time of last follow-up or the death time. T test or χ2 test was used for comparison between groups. Results: A total of 101 KD children with GCAA were enrolled, including 82 males (81.2%) and 19 females (18.8%). The age of disease onset was 2.5 (1.0, 4.5) years. The follow-up duration was 4.5 (2.7, 7.5) years, with a longest of 19 years. All children received routine treatment with aspirin and warfarin, and clopidogrel was added in severe cases. At the end of follow-up, 13 cases (12.9%) had cardiac enlargement, 11 cases (10.9%) developed heart failure, 13 cases (12.9%) experienced myocardial infarction, 2 cases (2.0%) underwent coronary artery bypass graft and 6 cases (5.9%) died. A total of 170 coronary arteries were involved, including 24 (14.1%) GCAAs on the main trunk of left coronary artery, 10 (5.9%) GCAAs on left circumflex, 57 (33.5%) GCAAs on left anterior descending, 78 (45.9%) GCAAs on the middle segments of right coronary artery, and 1 (0.6%) GCAA in the distal segments of right coronary artery. Eleven cases (10.9%) recovered with the coronary artery absolute lumen diameter of all GCAAs below 4.0 mm. Among 170 branches with GCAAs, 28 (16.5%) regressed below 4.0 mm. No significant difference was found in the regression rates between right and left GCAA (18.7% (17/91) vs. 13.9% (11/79), χ²=2.473, P=0.116). There was no statistically significant difference in retraction between unilateral GCAA and bilateral GCAA (16.1% (9/56) vs. 4.4% (2/45), χ2=2.381, P=0.123). Conclusions: GCAA of KD occurred more common in the middle segments of right and left anterior descending coronary arteries. The incidence of adverse cardiac events and the mortality rate in children with GCAA complicated with KD was high. Their long-term prognosis was poor.


Active Intent Disambiguation for Shared Control Robots.
Assistive shared-control robots have the potential to transform the lives of millions of people afflicted with severe motor impairments. The usefulness of shared-control robots typically relies on the underlying autonomy's ability to infer the user's needs and intentions, and the ability to do so unambiguously is often a limiting factor for providing appropriate assistance confidently and accurately. The contributions of this paper are four-fold. First, we introduce the idea of intent disambiguation via control mode selection, and present a mathematical formalism for the same. Second, we develop a control mode selection algorithm which selects the control mode in which the user-initiated motion helps the autonomy to maximally disambiguate user intent. Third, we present a pilot study with eight subjects to evaluate the efficacy of the disambiguation algorithm. Our results suggest that the disambiguation system (a) helps to significantly reduce task effort, as measured by number of button presses, and (b) is of greater utility for more limited control interfaces and more complex tasks. We also observe that (c) subjects demonstrated a wide range of disambiguation request behaviors, with the common thread of concentrating requests early in the execution. As our last contribution, we introduce a novel field-theoretic approach to intent inference inspired by dynamic field theory that works in tandem with the disambiguation scheme.


Polyarteritis Nodosa: Old Disease, New Etiologies.
Polyarteritis nodosa (PAN), also known as panarteritis nodosa, represents a form of necrotizing vasculitis that predominantly affects medium-sized vessels, although it is not restricted to them and can also involve smaller vessels. The clinical presentation is heterogeneous and characterized by a significant number of patients exhibiting general symptoms, including asthenia, fever, and unintended weight loss. Although PAN can involve virtually any organ, it preferentially affects the skin, nervous system, and the gastrointestinal tract. Orchitis is a rare but specific manifestation of PAN. The absence of granulomas, glomerulonephritis, and anti-neutrophil cytoplasmic antibodies serves to distinguish PAN from other types of vasculitis. Major complications consist of hemorrhagic and thrombotic events occurring in mesenteric, cardiac, cerebral, and renal systems. Historically, PAN was frequently linked to hepatitis B virus (HBV) infection, but this association has dramatically changed in recent years due to declining HBV prevalence. Current epidemiological research often identifies a connection between PAN and genetic syndromes as well as neoplasia. This article provides a comprehensive review of PAN, specifically focusing on the progression of its clinical manifestations over time.


Molecular diagnosis of respiratory tract infection in acute exacerbations of chronic obstructive pulmonary disease.
Acute exacerbations are significant events in the course of chronic obstructive pulmonary disease. Modern diagnostic techniques have revealed an infectious cause for the majority of exacerbations. Common respiratory viruses contribute to 25%-50% of exacerbations. Detection of viral nucleic acids in nasopharyngeal swab or sputum samples has become the preferred method to study viral exacerbations instead of viral cultures and serologic examination. Clinical application of such molecular detection requires additional studies to clarify interpretation of a positive result. Bacteria account for 25%-50% of exacerbations. Studies comparing molecular detection of bacteria in sputum with conventional culture techniques have shown that a substantial proportion of bacteria are not detected by the latter method. However, as with molecular viral detection, clinical application of molecular bacterial diagnosis requires additional studies. Although still faced with several challenges and requiring additional development, it is quite likely that molecular methods will become the preferred methods for determining the etiology of exacerbations of chronic obstructive pulmonary disease.


Coinfection with herpes simplex virus type 2 is associated with reduced HIV-specific T cell responses and systemic immune activation.
Chronic coinfection with herpes simplex virus type 2 (HSV-2) and human immunodeficiency virus (HIV) has been associated with an increased HIV viral load and more rapid disease progression, perhaps related to HSV-2-associated alterations in host immunity. Studies were nested within (1) a cross-sectional study of men coinfected with HIV and HSV-2 and (2) women not infected with HIV, both before and after HSV-2 acquisition. HSV-2 infection status was determined by ELISA. HIV-specific CD8(+) T cell epitopes were mapped, and proliferation of HIV-specific cells was also assessed. Systemic inflammatory and regulatory T cell populations were assayed by flow cytometry. The breadth of both the HIV-specific CD8(+) T cell interferon-gamma and proliferative responses was reduced in participants coinfected with HIV and HSV-2, independent of the HIV plasma viral load and CD4(+) T cell count, and the magnitude of the responses was also reduced. HSV-2 infection in this group was associated with increased T cell CD38 expression but not with differences in the proportion of CD4(+) FoxP3(+) regulatory T cells. However, in women not infected with HIV, acquisition of HSV-2 was associated with an increase in the proportion of regulatory T cells. HSV-2 coinfection was associated with reduced HIV-specific T cell responses and systemic inflammation. The immune effects of HSV-2 may underlie the negative impact that this coinfection has on the clinical course of HIV infection.


Ingestion of oxygenated water enhances lactate clearance kinetics in trained runners.
Drinks with higher dissolved oxygen concentrations have in recent times gained popularity as a potential ergogenic aid, despite a lack of evidence regarding their efficacy. The aim of this study was to assess effects of ingestion of an oxygen supplement (OS) on exercise performance and post-exercise recovery in a group of trained runners. Trained male runners (n = 25, mean ± SD; age 23 ± 6 years, mass 70 ± 9 kg, BMI 21.9 ± 2.7 kg.m-2 VO2max 64 ± 6mL.kg-1.min-1), completed a randomised double blinded, crossover study to assess the effect of ingestion of OS solution on exercise performance and recovery. Trials consisted of a 30min rest period, 5min warm-up, a 5000m treadmill time-trial, and a 30min passive recovery. Participants ingested 6x15mL of either OS or a taste matched placebo during the trials (3 during the rest phase, 1 during exercise and 2 during the recovery). Muscle tissue O2 saturation was measured via near infrared spectroscopy. Blood lactate concentrations were measured prior to, mid-way and directly after the finish of the 5000m time trials and every 3-min during the post-exercise recovery. Ingestion of OS did not improve exercise performance. No significant differences were observed for muscle tissue O2 saturation at any time-points. However, lactate clearance was significantly improved during recovery in the OS trials. Both AUC (109 ± 32 vs. 123 ± 38 mmol.min, P < 0.05, d = 0.40) and lactate half-life (λ) (1127 ± 272 vs. 1223 ± 334 s, P < 0.05, d = 0.32) were significantly reduced. Despite no evidence of improved exercise performance, ingestion of OS did enhance post-exercise recovery via increased lactate clearance.


Analysis, occurrence, and toxic potential of pyrethroids, and fipronil in sediments from an urban estuary.
Eight pyrethroids and fipronil and its three major degradates were analyzed in urban estuarine sediments that exhibited a range of toxic effects to an amphipod test species. Sediments from Ballona Creek, an urban estuary in Southern California (USA), collected during three dry season events were analyzed by gas chromatography with electron capture and negative chemical ionization mass spectrometric detection (GC-ECD and GC-NCI-MS). The two detection methods were in agreement for intermediate levels of pyrethroid contamination (10-50 ng/g dry wt) but deviated for both low and high concentrations (< 5 and > 50 ng/g). Sediments contained total pyrethroids as high as 473 ng/g with permethrin, bifenthrin, and cypermethrin as the most abundant compounds. In contrast, fipronil and its desulfinyl, sulfide, and sulfone degradates were detected at much lower levels (<or= 0.18-16 ng/g). Toxic units estimated for these compounds revealed that bifenthrin and cypermethrin were likely contributors to the mortality observed in tests with the estuarine amphipod Eohaustorius estuarius. Although fipronil was not a likely contributor to the observed mortality, the concentrations detected may be of concern for more sensitive crustacean species. Furthermore, the spatial pattern of pyrethroid contamination and potential toxicity was highly correlated with fine-grained substrate, which shifted to downstream stations within a three-month period during the dry season.


Family caregiver constructs and outcome measures in neuro-oncology: A systematic review.
As a first step to reach consensus on the key constructs and outcomes in neuro-oncology caregiver research, we performed a systematic review to evaluate the constructs that are being evaluated in research studies and how these have been assessed. All peer-reviewed publications with primary data reporting on outcomes of family caregivers of adult primary brain tumor patients were eligible. Electronic databases PubMed/Medline, Embase, Web of Science, Emcare, Cochrane Library, and PsycINFO were searched up to September 2021. Using Covidence, title and abstract screening, full-text review, and data extraction were done by two researchers independently, with a third guiding consensus. Constructs as reported in each study, and how these were assessed were the primary result. Searches yielded 1090 unique records, with 213 remaining after title/abstract screening. Of these, 157 publications met inclusion criteria, comprising 120 unique studies. These originated from 18 countries and were published between 1996 and 2022. Most were observational (75%) cross-sectional (61%) studies, reporting on quantitative methods (62%). Twenty-seven different constructs were assessed and mapped along the Caregiver Health Model (CGHM) categories, namely, caregiver health, needs, tasks, beliefs and attitudes, and environment. Seventeen questionnaires were used >2 times to measure the same construct, with the vast majority of questionnaires only used across one or two studies. Neuro-oncology caregiving research is a field gaining traction, but lags behind in clear definition of key constructs, and consistency in assessment of these constructs. Developing consensus or guidance will improve comparability of studies, meta-analyses, and advance the science more quickly.


Diet-induced systemic lupus erythematosus (SLE) in primates.
Ten adult, female cynomolgus macaques were randomly assigned to two equal groups: (1) semipurified diet (SPD); and (2) SPD with 45% ground alfalfa seed (AS). Both groups were studied at monthly intervals after 5 mo on their respective diets. Control animals had a mean hematocrit (Hct) of 43 +/- 2%, negative antiglobulin (AG), antinuclear antibody (ANA) and LE cell tests. Mean values for C3 and C4 were 309 +/- 47 mg/dl and 35 +/- 7 mg/dl, respectively. Mean serum binding to radiolabeled double stranded deoxyribonucleic acid (dsDNA) was 1.9 +/- 0.2%. Three of five animals fed AS developed signs of an SLE-like illness characterized by AG-positive anemia (lowest Hct 30%), positive ANA (highest titer greater than 1:15, 360; rim pattern) and elevated anti-dsDNA binding (highest 96%) with variable degrees of hypocomplementemia. One animal had granular deposition of immunoglobulin and complement at the dermal-epidermal junction of clinically normal skin the presence of immune complex-induced glomerulonephritis.


PLGA Nanoparticles Co-encapsulating NY-ESO-1 Peptides and IMM60 Induce Robust CD8 and CD4 T Cell and B Cell Responses.
Tumor-specific neoantigens can be highly immunogenic, but their identification for each patient and the production of personalized cancer vaccines can be time-consuming and prohibitively expensive. In contrast, tumor-associated antigens are widely expressed and suitable as an off the shelf immunotherapy. Here, we developed a PLGA-based nanoparticle vaccine that contains both the immunogenic cancer germline antigen NY-ESO-1 and an α-GalCer analog IMM60, as a novel iNKT cell agonist and dendritic cell transactivator. Three peptide sequences (85-111, 117-143, and 157-165) derived from immunodominant regions of NY-ESO-1 were selected. These peptides have a wide HLA coverage and were efficiently processed and presented by dendritic cells via various HLA subtypes. Co-delivery of IMM60 enhanced CD4 and CD8 T cell responses and antibody levels against NY-ESO-1 in vivo. Moreover, the nanoparticles have negligible systemic toxicity in high doses, and they could be produced according to GMP guidelines. Together, we demonstrated the feasibility of producing a PLGA-based nanovaccine containing immunogenic peptides and an iNKT cell agonist, that is activating DCs to induce antigen-specific T cell responses.


Antimicrobial resistance: Prevalence, economic burden, mechanisms of resistance and strategies to overcome.
Antibiotic resistance is a major health concern globally and has been estimated to cause 10 million deaths worldwide by year 2050 if the current trend of inappropriate and excessive use of antibiotics continues. Although, the discovery of antibiotics has saved countless of lives for the past 80 years, increasing levels of bacterial resistance to antibiotics would jeopardize the progress in clinical and agricultural sectors and may cause life-threatening situations even for previously treatable bacterial infections. Antibiotic resistance would increase the levels of poverty of low-middle income countries mostly due to extended hospital stays, higher cost of treatment and untimely deaths that directly affect the total productivity rate. Recent incidences of antibiotic resistance have been gradually increasing globally and this may potentiate horizontal transmission of the resistant gene and have been linked with cross-resistance to other antibiotic families as well. This review summarizes the global burden of antibiotic resistance from the economic viewpoint, highlights the recent incidences of antibiotic resistance mainly related to Escherichia coli, Acinetobacter baumannii, Klebsiella pneumoniae, Salmonella spp. and Staphylococcus aureus, describes the common mechanistic actions of antibiotic resistance and potential strategies to overcome antibiotic resistance.


Cyanobacteria and Cyanotoxins Occurrence and Removal from Five High-Risk Conventional Treatment Drinking Water Plants.
An environmental protection agency EPA expert workshop prioritized three cyanotoxins, microcystins, anatoxin-a, and cylindrospermopsin (MAC), as being important in freshwaters of the United States. This study evaluated the prevalence of potentially toxin producing cyanobacteria cell numbers relative to the presence and quantity of the MAC toxins in the context of this framework. Total and potential toxin producing cyanobacteria cell counts were conducted on weekly raw and finished water samples from utilities located in five US states. An Enzyme-Linked Immunosorbant Assay (ELISA) was used to screen the raw and finished water samples for microcystins. High-pressure liquid chromatography with a photodiode array detector (HPLC/PDA) verified microcystin concentrations and quantified anatoxin-a and cylindrospermopsin concentrations. Four of the five utilities experienced cyanobacterial blooms in their raw water. Raw water samples from three utilities showed detectable levels of microcystins and a fourth utility had detectable levels of both microcystin and cylindrospermopsin. No utilities had detectable concentrations of anatoxin-a. These conventional plants effectively removed the cyanobacterial cells and all finished water samples showed MAC levels below the detection limit by ELISA and HPLC/PDA.


Upper airway resistance syndrome--report of three cases.
Patients with the upper airway resistance syndrome are frequently overlooked, and even if clinically suspected, often escape identification by polysomnographic monitoring. Three cases (2 women and a man) with excessive daytime sleepiness and fatigue were confirmed to have the upper airway resistance syndrome after undergoing polysomnography with oesophageal pressure monitoring. Nasal CPAP during sleep was prescribed for 2 cases but 1 case refused all available treatment options. After one month of CPAP therapy, the 2 cases reported improved symptoms and Epworth sleepiness scores. Lower daytime blood pressures were also recorded. Oesophageal pressure monitoring and EEG arousal analysis can greatly enhance the diagnostic accuracy in the upper airway resistance syndrome. Accurate diagnosis and effective treatment of this condition is important because of its sequelae of hypersomnolence and association with other disorders like systemic hypertension.


The impact of multifunctional genes on "guilt by association" analysis.
Many previous studies have shown that by using variants of "guilt-by-association", gene function predictions can be made with very high statistical confidence. In these studies, it is assumed that the "associations" in the data (e.g., protein interaction partners) of a gene are necessary in establishing "guilt". In this paper we show that multifunctionality, rather than association, is a primary driver of gene function prediction. We first show that knowledge of the degree of multifunctionality alone can produce astonishingly strong performance when used as a predictor of gene function. We then demonstrate how multifunctionality is encoded in gene interaction data (such as protein interactions and coexpression networks) and how this can feed forward into gene function prediction algorithms. We find that high-quality gene function predictions can be made using data that possesses no information on which gene interacts with which. By examining a wide range of networks from mouse, human and yeast, as well as multiple prediction methods and evaluation metrics, we provide evidence that this problem is pervasive and does not reflect the failings of any particular algorithm or data type. We propose computational controls that can be used to provide more meaningful control when estimating gene function prediction performance. We suggest that this source of bias due to multifunctionality is important to control for, with widespread implications for the interpretation of genomics studies.


[Socioemotional disorders in children living in Konzo-affected areas, an epidemic paralytic disease associated with cyanide poisoning from food in sub-Saharan Africa].
the aim of this study was to describe the socioemotional profile of children living in Konzo-affected areas, an epidemic toxico-nutritional palsy in sub-Saharan Africa. we evaluated the socioemotional profile of 210 children, 123 with Konzo and 87 presumed to be healthy (4-17 years) based on a structured interview conducted with their parents during an epidemioclinic survey of Konzo in Congo-Kinshasa in 2011. Neurocognitive profile was identified by the KABC-II, the BOT-2 and the global neurological symptom index of Konzo. Associative tests were carried out by using chi-square test, logistic regression and, where applicable, generalized linear model, at the significance threshold of 0.05. in general, irritability, physical violence or inhibition with or without sadness were found in 46.0%, 30.2%, 18.7% of children respectively, with an increased risk of Konzo (OR = 2.6; CI95%: 1.4-4.8; p = 0.001). Socioemotional disorder was associated with underweight (OR: 0.49; CI95%: 0.31-0.78; p = 0.002) and with an elevated global neurological symptom index of Konzo (OR: 1.33; CI 95%: 1.1-1.63; p = 0.019); furthermore it exacerbated cognitive impairment in children with Konzo (interaction neurological status-socioemotional disorders D = 6.297; p = 0.013). High cognitive performances were observed in children without Konzo but with socioemotional disorders. The average concentration (standard deviation ± SD) of urinary thiocyanate was higher (554.8 ± 371.6 µmol/l) among children with Konzo associated with socioemotional disorders. children living in Konzo-affected areas have socioemotional disorders. Their psychopathological status and the effect of Konzo on cognition require in-depth studies.


Uric Acid Puzzle: Dual Role as Anti-oxidantand Pro-oxidant.
Hyperuricemia is known to be associated with the presence of cardiovascular and metabolic syndrome and with the development of incipient kidney disease and an accelerated renal progression. However, an elevated uric acid level was not generally regarded as a true etiology or mediator, but an indicator of these diseases. Uric acid has recently regained the clinical interest and popularity based on emerging data suggesting the causative role of hyperuricemia in cardiovascular and renal disease. Experimental data demonstrates oxidative stress is one of the earliest phenomena observed in vascular, renal, liver cells and adipocytes exposed to uric acid. Since uric acid is one of the major antioxidants of plasma acting as a free radical scavenger and a chelator of transitional metal ion, uric acid-induced oxidative stress seems paradoxical. Data regarding the clinical implication of hyperuricemia is even more confusing, which defines hyperuricemia as a useless parameter to be eliminated from routine follow-up or a major risk factor to be therapeutic target. With a review of experimental and epidemiologic data, the presence of molecular switch to regulate the role of uric acid as anti- or pro-oxidant in different compartment of our body is suggested, which may shed light on understanding the paradoxical role of uric acid and solving the "uric acid debate".


Food refusal as a protest tool. Hunger strikes in Belgian prisons during the interwar period.
In studies on resistance and protest, empirical research tends to concentrate on collective forms of action, those organised within social movements or by resistance groups. As such, research into the protest tactic of hunger strikes suffers from the same ailment. While there is ample historical study into hunger strikes by the suffragettes or the IRA, the actions of individuals without any connection to political movements have mostly been left unnoticed - although they tended to outnumber the former, especially in prisons where hunger strikes are in a way a measure of last resort. This paper investigates hunger strikes of individual detainees in Belgian prisons during the interwar period, a time of transformation in the penitentiary system and changings views on crime and the criminal. Through a critical reading of prisoner files of the prison of Forest, this study analyses the motivations of prisoners to start a hunger strike and the reactions and sanctions of the prison authorities. Findings reveal that going on a hunger strike, or simply not eating, was sufficient to label prisoners as mentally ill and transfer them into the psychiatric ward. If the prisoner could not be convinced to eat, the hunger strike was almost always terminated by forcibly feeding the detainee. As this was done to prisoners whose life was not in danger and with the brutal use of rectal feeding, I argue that force feeding was also a means to discipline detainees.


Uterine adenomyosis in southern three-banded armadillos (Tolypeutes matacus).
Uterine adenomyosis was diagnosed in five southern three-banded armadillos (Tolypeutes matacus) from four different zoological collections in North America between 1995 and 2012. Two cases were diagnosed after ovariohysterectomy and histopathologic evaluation of the uteri, and the remaining cases were identified incidentally at the time of postmortem examination. Animals ranged from 5 to 14 yr of age at the time of diagnosis. Of armadillos diagnosed before postmortem examination, clinical signs included weakness, collapse, anemia, and vulvar discharge. Histopathologic evaluation of the uteri revealed well-developed, irregular endometrial glands extending into the myometrium and occasional hemorrhage within these glands. The two cases diagnosed antemortem were successfully treated with ovariohysterectomy. To the authors' knowledge, this condition has not been previously reported in Xenarthra, including armadillos.


veqtl-mapper: variance association mapping for molecular phenotypes.
Genetic loci associated with the variance of phenotypic traits have been of recent interest as they can be signatures of genetic interactions, gene by environment interactions, parent of origin effects and canalization. We present a fast efficient tool to map loci affecting variance of gene expression and other molecular phenotypes in cis. Results: Applied to the publicly available Geuvadis gene expression dataset, we identify 816 loci associated with variance of gene expression using an additive model, and 32 showing differences in variance between homozygous and heterozygous alleles, signatures of parent of origin effects. Documentation and links to source code and binaries for linux can be found at https://funpopgen.github.io/veqm/ . email@example.com. Supplementary data are available at Bioinformatics online.


Novel Insights on the Three-dimensional Shape of Microgels at Fluid Interfaces.
Mechanically soft colloids (microgels) adsorbed at the interface between two fluids offer superior advantages over hard counterparts for a variety of applications ranging from foams/emulsion stabilization to the assembly of two-dimensional (2D) materials. Particle deformability and compressibility impart additional responses to microgel-laden interfaces that can be controlled on-demand by varying single-particle properties (e.g. crosslinking content and polymer density profile) and/or external parameters (e.g. interfacial compression and tension, temperature, oil polarity). In order to understand how single-particle softness influences the resulting material properties, a detailed quantification of the microgel's 3D conformation when confined at the fluid interface is of utmost importance. This article describes how different methodologies can be used to visualize, and in some case quantify, the conformation of adsorbed microgels, putting particular emphasis on the multiple advantages offered by in situ atomic force microscopy imaging at the fluid interface. The influence of the internal particle architecture, as well as that of temperature, interfacial tension and solubility in the organic phase, will be discussed. Finally, some perspectives on how softness can be exploited to tune the structural and mechanical properties of microgel monolayers will be provided.


Blood pressure abnormalities in children with sickle cell anemia.
Kidney disease is an important cause of morbidity and mortality in patients with sickle cell anemia (SCA). The factors that affect progression of renal disease are unknown, especially in children and adolescents. Alterations in blood pressure, including hypertension and lack of the normal nocturnal dip in blood pressure, are important determinants of diabetic nephropathy and other renal diseases and may play a role in sickle cell nephropathy. Our primary hypothesis was that children with SCA who have microalbuminuria will demonstrate less nocturnal dipping of blood pressure compared to patients without microalbuminuria. We also investigated other potential factors associated with microalbuminuria. This prospective study of 52 adolescents with SCA followed in the Children's Medical Center Dallas Comprehensive Sickle Cell Center characterized 24-hour ambulatory blood pressure profiles and presence of microalbuminuria. Stepwise logistic regression was performed to identify significant independent factors that are associated with microalbuminuria. Thirty-five percent of patients were identified as having previously unrecognized hypertension, and 17% had pre-hypertension (blood pressure greater than the 90th percentile but less than the 95th percentile). Fifty-six percent of patients lacked the normal nocturnal dip in blood pressure. In addition, 21% had microalbuminuria, and their percent nocturnal dip was significantly less than those without microalbuminuria (P = 0.01). Blood pressure abnormalities are common in adolescents with SCA and are a possible modifiable risk factor in the progression of sickle cell nephropathy.


Activation of silent genes by transposons Tn5 and Tn10.
The presence of transposons Tn10 or Tn5 in the genome increases the frequency with which a silent (promoter-less) gene (hisD) is mutationally activated. The activation frequency is increased 5-25-fold by Tn10 and 30-90-fold by Tn5. Activation of the hisD gene is achieved by transposition of the entire transposon or one of its flanking insertion sequences to a region just upstream of the silent gene, between a Rho-dependent termination site in the adjacent hisG gene and the hisD gene. For both Tn5 and Tn10 the component insertion sequences were found to transpose much more frequently than the entire composite element. Transposons Tn5 and Tn10 have previously been shown to carry promoters which direct transcripts into sequences adjacent to their insertion sites.


Does laryngopharyngeal reflux cause intraoral burning sensations? A preliminary study.
Intraoral burning sensations are a common problem in the otolaryngological practice. The aim of this study was to evaluate if laryngopharyngeal reflux can cause intraoral burning sensations by measuring oropharyngeal acid reflux. Patients with recurring intraoral burning sensations underwent oropharyngeal pH monitoring in our outpatient clinic. The pH catheter was placed at the level of the uvula. The catheter contained an externally worn transmitter, which wirelessly sent the data to a monitor. In addition, patients were instructed to indicate meals or the occurrence of burning sensations by pressing provided buttons on the monitor. Corresponding events of burning sensations and a significant decrease in oropharyngeal pH values should be visualized. Twenty two patients suffering from recurring intraoral burning sensations underwent oropharyngeal pH measurement for 21-25 h. We could find oropharyngeal reflux episodes in 11 patients. However, we could not detect any episodes of burning sensations in the mouth corresponding with a decrease in oropharyngeal pH values. Our results suggest that there is no causal connection between LPR episodes and the occurrence of intraoral burning sensations in the examined patients. Although further studies with more patients are necessary in the future, we conclude from our findings that recurring intraoral burning sensations are not an indication for proton pump inhibitor therapy.


Exploring the feasibility and effects of a high-fruit and -vegetable diet in healthy women.
Based on reports that fruits and vegetables may protect against breast cancer, this randomized intervention study tested the feasibility of increasing fruit and vegetable intake among healthy women to 9 daily servings through individual dietary counseling and group activities. Adherence to the dietary recommendations was monitored by 24-h food recalls, log sheets, and plasma carotenoid assessments. To explore possible cancer protective mechanisms of fruits and vegetables, we investigated the treatment effect on plasma phenol levels and on thiobarbituric acid-reactive substances measured as malondialdehyde equivalents, a possible marker of oxidative damage. At baseline, women in the intervention (n = 13) and control (n = 16) group reported an average daily consumption of 3.3 and 3.2 fruit and vegetable servings, respectively. After 3 and 6 months of intervention, intake in the intervention group had increased to 8.3 and 7.4 servings, whereas the control group reported an average of 4.2 and 4.1 daily servings. An increase of plasma carotenoid levels from 1249 microg/liter at baseline to 1854 and 1827 microg/liter after 3 and 6 months confirmed compliance with the dietary recommendations in the intervention group. Plasma carotenoid levels among controls changed slightly from 1165 to 1231 and 1291 microg/liter Whereas total phenol levels did not respond according to our hypothesis, malondialdehyde levels decreased slightly in the intervention group. These results suggest that motivated women can substantially increase their fruit and vegetable intake, which leads to a notable increase in plasma carotenoid levels.


Plasticity of monocyte development and monocyte fates.
Monocytes are circulating myeloid immune precursor cells that are generated in the bone marrow. Mature monocytes are released into the circulation and, in case of need, recruited to peripheral sites of inflammation to differentiate into monocyte-derived effector cells. In absence of overt inflammation, monocytes also extravasate into selected tissues, where they complement tissue-resident macrophage compartments. Adjustment of these homeostatic monocyte infiltrates to local environment is critical to maintain health, as best established for the intestine. Defined gene expression changes that differ between gut segments presumably help strike the fine balance between the crucial function of these monocyte-derived macrophages as tissue rheostats and their detrimental hyperactivation. Environmental factors that dictate local monocyte differentiation remain incompletely understood. Definition of the latter could aid our general understanding of in vivo monocyte functions and their relation to inflammatory disorders. In this review, we summarize recent advances in our understanding of monocyte subsets, their differentiation into tissue macrophages, and selected contributions of monocyte-derived cells to steady-state physiology. Moreover, we will discuss emerging evidence for an intriguing bifurcation of monocyte development in the bone marrow and potential functional implications. Emphasis will be given to points of controversies, but we will largely focus on the healthy organism. For a discussion of monocyte and macrophage contributions to inflammatory conditions, we refer the reader to other dedicated reviews.


Increased mast cell numbers in a calcaneal tendon overuse model.
Tendinopathy is often discovered late because the initial development of tendon pathology is asymptomatic. The aim of this study was to examine the potential role of mast cell involvement in early tendinopathy using a high-intensity uphill running (HIUR) exercise model. Twenty-four male Wistar rats were divided in two groups: running group (n = 12); sedentary control group (n = 12). The running-group was exposed to the HIUR exercise protocol for 7 weeks. The calcaneal tendons of both hind limbs were dissected. The right tendon was used for histologic analysis using Bonar score, immunohistochemistry, and second harmonic generation microscopy (SHGM). The left tendon was used for quantitative polymerase chain reaction (qPCR) analysis. An increased tendon cell density in the runners were observed compared to the controls (P = 0.05). Further, the intensity of immunostaining of protein kinase B, P = 0.03; 2.75 ± 0.54 vs 1.17 ± 0.53, was increased in the runners. The Bonar score (P = 0.05), and the number of mast cells (P = 0.02) were significantly higher in the runners compared to the controls. Furthermore, SHGM showed focal collagen disorganization in the runners, and reduced collagen density (P = 0.03). IL-3 mRNA levels were correlated with mast cell number in sedentary animals. The qPCR analysis showed no significant differences between the groups in the other analyzed targets. The current study demonstrates that 7-week HIUR causes structural changes in the calcaneal tendon, and further that these changes are associated with an increased mast cell density.


Effect of Routine Cytochrome P450 2D6 and 2C19 Genotyping on Antipsychotic Drug Persistence in Patients With Schizophrenia: A Randomized Clinical Trial.
Genetic polymorphism of genes encoding the drug metabolizing enzymes, cytochrome P450 2D6 and 2C19 (CYP2D6 and CYP2C19), is associated with treatment failure of and adverse reactions to psychotropic drugs. The clinical utility of routine CYP2D6 and CYP2C19 genotyping (CYP testing) is unclear. To estimate whether routine CYP testing effects the persistence of antipsychotic drug treatment. This single-masked, 3-group randomized clinical trial included patients aged 18 years or older who had been diagnosed within the schizophrenic spectrum (International Statistical Classification of Diseases and Related Health Problems, Tenth Revision codes, F20-F29) and not previously genotyped. A total of 669 of 1406 potentially eligible patients from 12 psychiatric outpatient clinics in Denmark were approached between July 2008 and December 2009. Overall, 528 patients were genotyped and randomly allocated to 1 of 3 study groups or exclusion in a sequence of 1:1:1:3 using a predictive enrichment design, aiming to double the proportion of poor or ultrarapid metabolizers for CYP2D6 or CYP2C19. Outcome measurements were recorded at baseline and 1-year follow-up. Data analysis was performed in December 2012 and updated March 2019. The trial included 2 intervention groups, where antipsychotic drug treatment was guided by either CYP test (CYP test-guided [CTG]) or structured clinical monitoring (SCM), in which adverse effects and factors influencing compliance were systematically recorded at least once quarterly, and 1 control group. Primary outcome was antipsychotic drug persistence, ie, days to first modification of the initial treatment. Secondary outcomes were number of drug and dose changes, adverse effects, and psychotic symptoms, ie, hallucinations and delusions. A total of 528 participants were genotyped, and 311 (median [interquartile range {IQR} age, 41 [30-50] years; 139 [45%] women; median [IQR] duration of illness, 6 [3-13] years) were randomly allocated to 1 of 3 study groups. Overall, 61 participants (20%) were extreme metabolizers. There was no difference in antipsychotic drug persistence between the CTG group and the control group (hazard ratio [HR], 1.02; 95% CI, 0.71-1.45) or SCM and the control group (HR, 0.88; 95% CI, 0.61-1.26). Subanalyses among extreme metabolizers showed similar results (CTG: HR, 0.99; 95% CI, 0.48-2.03; SCM: HR, 0.93; 95% CI, 0.44-1.96). The results of this randomized clinical trial do not support routine CYP testing in patients with schizophrenia. ClinicalTrials.gov Identifier: NCT00707382.


A tactile cockpit instrument supports the control of self-motion during spatial disorientation.
We investigated the effectiveness of a tactile torso display as a countermeasure to spatial disorientation (SD) and compared inside-out and outside-in codings. SD is a serious threat to military as well as civilian pilots and aircraft. Considerable effort has been put into SD countermeasures such as training programs and advanced cockpit displays. Tactile displays have been considered a promising technology. Twenty-four participants were assigned to the two coding groups (12 per group and matched for age and gender). We used a rotating chair to build up a state of SD by rotating participants around their yaw axis followed by a sudden stop. During the following recovery phase a random disturbance signal was added to the chair's orientation. Participants actively controlled their orientation and were instructed to maintain a stable orientation. Statistical analyses revealed that recovery from SD was improved with support of the tactile instrument, but tracking performance was reduced. The effects were the same whether the instrument was available full time or during the recovery phase only. There were no differences between outside-in and inside-out coding. The present study demonstrates the potential of tactile cockpit instruments in controlling SD, even in the presence of strong but misleading self-motion information from the vestibular sense. Actual or potential applications of this research include spatial disorientation countermeasures for pilots, divers, and astronauts.


Resorcinol 10% as a Promising Therapeutic Option for Mild Hidradenitis Suppurativa: A Prospective, Randomized, Open Study.
Treatment of hidradenitis suppurativa (HS) is challenging, and in Hurley stage I, it is based on topical measures. Our aim was to compare the efficacy and safety of topical resorcinol 10% with topical clindamycin 1% and no therapy, in Hurley stage I HS. In this open, prospective, randomized trial, we studied 60 Hurley stage I patients with IHS4 ≤10. Group A was treated with topical resorcinol 10%; group B with clindamycin lotion 1%; and group C received no treatment. Patients were evaluated by total lesion count, the International Hidradenitis Suppurativa Severity Score System (IHS4) and the Dermatology Life Quality Index (DLQI) at baseline, 12 and 24 weeks. Self-reported number of flares and adverse events (AEs) were recorded. A significant reduction in the mean total lesion count and DLQI scores were observed in group A, compared to group B at week 12 (p = 0.036, p < 0.001, respectively), and in the mean total lesion count, IHS4, and DLQI scores at week 24 (p = 0.034, p = 0.017, p < 0.001, respectively). Resorcinol 10% was well-tolerated with only mild AEs. Resorcinol 10% may represent a useful alternative for the long-term treatment of mild HS, which is superior to topical clindamycin and has a favorable safety profile.


Tips for pandemic response planning for Internal Medicine training programs.
This article was migrated. The article was marked as recommended. The current Coronavirus Disease 2019 (COVID-19) pandemic has strained hospital systems and training programs across the world. As capacity issues mount and trainees are called upon to provide frontline medical care, programs and institutions have had to rapidly evolve to redefine the trainee experience. To that end, there is a paucity of literature regarding how healthcare training programs should operate during a global pandemic. Here, we aim to describe twelve evidence-based recommendations for coordinating a cohesive, systematic approach to pandemic response planning for Internal Medicine residency training programs. These tips encompass inpatient and outpatient practices, provider safety, resuscitation, virtual education programming and resident wellbeing. Though many of these considerations or recommendations were not described during the COVID-19 pandemic, these tips have been described previously in the literature, are applicable to the current pandemic and could be easily extrapolated to future crises.


Phase II study of pegylated liposomal doxorubicin in heavily pretreated epithelial ovarian cancer patients. May a new treatment schedule improve toxicity profile?
Pegylated liposomal doxorubicin (PLD) has shown promising activity in the treatment of recurrent ovarian cancer but skin toxicity remains the dose-limiting toxicity of the drug. The aim of this study was to investigate whether a different treatment schedule may improve the toxicity profile, especially in terms of dermatological and mucosal toxicity. It is an open-label phase II study in a population of heavily pretreated ovarian cancer patients. PLD was administered at the dose of 35 mg/m2 q21 until disease progression or unacceptable toxicity. Thirty-seven heavily pretreated (median number of previous chemotherapy regimens 2, range 1-6) ovarian cancer patients were enrolled. All patients received at least two courses of chemotherapy and all were evaluated for response. No one showed complete response, while five partial responses (13.5%), 16 stabilizations of disease (48.6%) and 14 progressions of disease (37.8%) were observed. The median time to response was 12 weeks (range 8-16). The median duration of response was 22.8 weeks (range 4-68), the median duration of stabilization of disease was 17.6 weeks (range 4-28). Palmar plantar erythrodysesthesia (PPE) occurred in 8 patients (21.6%) and was of grade 3 in one patient (2.8%). Grade 1 stomatitis occurred in 3 patients (8.1%). Grade 3-4 neutropenia occurred in only 4 patients (10.8%). PLD at the dose of 35 mg/m2 q21 seems to translate into an acceptable skin toxicity profile with a response rate comparable to others obtained with a standard schedule.


Maternal HIV does not affect resiliency among uninfected/HIV exposed South African children from birth to 5 years of age.
Examine resiliency among a South African population cohort of children of mothers living with HIV (MLH) and mothers without HIV (MWOH) in low-income townships over the first 5 years of life. A cluster randomized controlled intervention trial evaluating child resiliency and the effects of home visiting in township neighborhoods from pregnancy through 5 years postbirth. The population of pregnant women in 24 matched neighborhoods were recruited and randomized by neighborhood to a standard care condition (n = 594) or a paraprofessional home visiting intervention condition (n = 644). Mothers and children were assessed at 2 weeks, 6, 18, 36, and 60 months postbirth (92-84% follow-up; 10.2% mortality). Resilient children were identified based on consistently meeting global standards for growth, cognitive functioning, and behavior. Maternal HIV status (n = 354 MLH; n = 723 mothers without HIV MWOH), intervention condition, maternal risks, caretaking, sociodemographic characteristics, and neighborhood were examined as predictors of child resiliency over time using analysis of variance, chi-square analyses, and Fisher's exact tests, where appropriate. None of HIV-seropositive children (n = 17) were resilient; 19% of 345 HIV-exposed but uninfected children of MLH were resilient, a rate very similar to the 16% among MWOH. Resiliency was significantly associated with lower income, food security, not having a live-in partner, and the absence of maternal risk (i.e., not being depressed, using alcohol, or being a victim of intimate partner violence). Being randomized to a home visiting intervention, maternal breastfeeding for at least 3 months and attending a preschool crèche were also unrelated to resiliency. Although matched pairs of neighborhoods had similar rates of resilient children, resiliency varied significantly by neighborhood with rates ranging from 9.5 to 27%. We set a new standard to define resiliency, as consistently recommended by theoreticians. Although seropositive children are not resilient, uninfected children of MLH are as resilient as their peers of MWOH. Typical protective factors (e.g., home visiting, breastfeeding, preschool) were unrelated to resiliency over the first 5 years of life. ClinicalTrials.gov registration #NCT00996528.


Serum selenium levels predict survival after breast cancer.
Studies have reported an inverse relationship between serum selenium levels and cancer incidence, but the impact of low serum selenium status on survival after a diagnosis of breast cancer has not been established. We obtained a blood sample from 546 women diagnosed with a first primary invasive breast cancer between 2008 and 2015 in the region of Szczecin, Poland. Blood was collected after diagnosis, but prior to treatment. Serum selenium was quantified by mass spectroscopy and each patient was assigned to one of four categories (quartiles) based on the distribution in the entire cohort. Patients were followed from diagnosis to death over a mean follow-up of 3.8 years. Vital status was obtained by linkage to the Polish National Death Registry. The 5-year overall actuarial survival was 68.1% for women in the lowest (< 64.4 µg/L) and 82.5% for those in the highest (> 81.0 µg/L) quartile of serum selenium. In an adjusted analysis, the hazard ratio for death was 2.49 (95%CI 1.53-4.04; P = 0.0002) for patients in the lowest quartile of serum selenium, compared to those in all other quartiles. The effect of low selenium on breast cancer-specific mortality was stronger for women who were past smokers (HR 6.03; 95%CI 1.96-18.6; P = 0.0002). This study suggests that a selenium level in excess of 64.4 µg//L might be beneficial for women undergoing treatment for breast cancer and that selenium supplementation to achieve this level may favorably impact the outcome. Further studies are needed to confirm this association and to evaluate the impact of selenium supplementation on breast cancer survival among women with low post-diagnostic selenium levels.


Cetylpyridinium chloride produces increased zeta-potential on Salmonella Typhimurium cells, a mechanism of the pathogen's inactivation.
Cetylpyridinium chloride (CPC) is a quaternary ammonium sanitizer approved for fresh poultry animal carcass sanitization from microbial human pathogens, such as Salmonella enterica. Nonetheless, the interactions of CPC with Salmonella cells, and the mechanism of the sanitizer's neutralization by lecithin remains largely unknown. This study aimed to investigate the interaction of CPC with lecithin and Salmonella Typhimurium to determine the interactions of the sanitizer and neutralizer impacting the bacterium's survival. Application of 0.8% CPC is proposed to produce loss of microbial membrane integrity with loss of electrostatic repulsion between individual cells, resulting in the eventual emulsification of membrane lipids with cytoplasmic contents leakage. Our findings point to a two-phase interaction between CPC and lecithin impacting S. Typhimurium survival. The first consists of electrostatic attraction and charge neutralization between oppositely charged components of pathogen cell and CPC. The second involves formation of aggregates between sanitizer and pathogen, or between sanitizer, pathogen membrane lipids, and lecithin.


Effect of skin barrier therapy on neonatal mortality rates in preterm infants in Bangladesh: a randomized, controlled, clinical trial.
Skin barrier therapy during the neonatal period, when the skin barrier is most highly compromised and the risk of death is greatest, has been shown to have a number of potential benefits, including reduced risk of nosocomial sepsis. Topical application of emollients that augment skin barrier function was evaluated as a strategy for improving survival rates among hospitalized preterm infants in Bangladesh. A prospective, randomized, controlled, clinical trial was conducted in the special care nursery at Dhaka Shishu (Children) Hospital, the largest tertiary care children's hospital in Bangladesh. Preterm infants (gestational age: < or = 33 weeks; N = 497) received daily topical applications of sunflower seed oil or Aquaphor ointment. Neonatal mortality rates were compared in an intent-to-treat analysis with a control group that did not receive emollient therapy. Treatment with sunflower seed oil resulted in a statistically significant 26% reduction in mortality rates, compared with infants not receiving topical emollient therapy. Aquaphor therapy also significantly reduced mortality rates, by 32%. Topical therapy with skin barrier-enhancing emollients improved survival rates among preterm hospitalized infants in Bangladesh. This study provides strong evidence for the implementation of topical therapy for high-risk preterm neonates in developing countries.


[FMRI-study of speech perception impairment in post-stroke patients with sensory aphasia].
The aim of the study was to find neurophysiological correlates of the primary stage impairment of speech perception, namely phonemic discrimination, in patients with sensory aphasia after acute ischemic stroke in the left hemisphere by noninvasive method of fMRI. For this purpose we registered the fMRI-equivalent of mismatch negativity (MMN) in response to the speech phonemes--syllables "ba" and "pa" in odd-ball paradigm in 20 healthy subjects and 23 patients with post-stroke sensory aphasia. In healthy subjects active brain areas depending from the MMN contrast were observed in the superior temporal and inferior frontal gyri in the right and left hemispheres. In the group of patients there was a significant activation of the auditory cortex in the right hemisphere only, and this activation was less in a volume and intensity than in healthy subjects and correlated to the degree of preservation of speech. Thus, the method of recording fMRI equivalent of MMN is sensitive to study the speech perception impairment.


[Bibliometric indicators of research in primary care (1988-1992)].
To describe Spanish scientific production in primary care by means of using bibliometric indexes. Spanish scientific production which was published in medical periodicals and indexed in the Indice Médico Español during the years 1988-1992. 446 articles published in thirty-four different medical journals. Descriptive, longitudinal and retrospective study. The number of articles slightly increases over the complete time of the study, principally in 1992. 98.4% were written in Spanish language. The average number of signatures per article is about five. Most of the authors are family doctors or interns of the medical specialty. In 76.46% of the cases, the articles were signed by only one institution. The majority of them (38.56%), were done in teaching units of family medicine. Barcelona is the most important producer of articles (20.2%) and 78% were published in the Atención Primaria periodical. The average number of references slightly increases during the whole period and is about 17 references in the five years studied. The scientific production on primary care seems to have an exponential increase according to Price's Law and it is concentrated in the Atención Primaria periodical. Most of authors are family doctors or interns of such specialty, who work in units of family medicine. Collaborative studies among institutions are uncommon. The number of signatures and the use of references were found to be similar to other medical specialties.


Ewing's sarcoma. A retrospective study of prognostic factors and treatment results.
A material of 87 consecutive patients with Ewing's sarcoma referred for treatment in the period 1962-1983 was retrospectively analysed. Thirteen patients had metastases at the time of diagnosis. Of the remainder, 71 received radiation therapy and 32 adjuvant chemotherapy. Survival rate was not influenced by age, sex or treatment delay. Metastatic disease predictably shortened survival (median 6 months vs. 23 months for localized disease). Tumour site did not significantly influence survival rate, although pelvic localization was associated with a slightly shorter median survival. Both pain and objective impairment of movement at presentation correlated to a poorer prognosis, possibly because of larger tumours or soft tissue extension. Adjuvant chemotherapy prolonged recurrence-free survival from a median of 6 months to 16 months, but survival was not improved significantly. Local failure occurred in about 40 per cent, regardless of radiation dose and tumour site. At the time of evaluation, 13 patients (15%) were alive with no evidence of disease and a median follow-up time of 68 months (range 16-196). So far, 2 patients have developed secondary malignancies in irradiated areas (one malignant fibrous histiocytoma and one osteogenic sarcoma).


Avian influenza overview June - September 2022.
The 2021-2022 highly pathogenic avian influenza (HPAI) epidemic season is the largest HPAI epidemic so far observed in Europe, with a total of 2,467 outbreaks in poultry, 47.7 million birds culled in the affected establishments, 187 outbreaks in captive birds, and 3,573 HPAI virus detections in wild birds with an unprecedent geographical extent reaching from Svalbard islands to South Portugal and Ukraine, affecting 37 European countries. Between 11 June and 9 September 2022, 788 HPAI virus detections were reported in 16 European countries in poultry (56), captive (22) and wild birds (710). Several colony-breeding seabird species exhibited widespread and massive mortality from HPAI A(H5N1) virus along the northwest coast of Europe. This resulted in an unprecedentedly high level of HPAI virus detections in wild birds between June and August 2022 and represents an ongoing risk of infection for domestic birds. HPAI outbreaks were still observed in poultry from June to September with five-fold more infected premises than observed during the same period in 2021 and mostly distributed along the Atlantic coast. Response options to this new epidemiological situation include the definition and rapid implementation of suitable and sustainable HPAI mitigation strategies such as appropriate biosecurity measures and surveillance strategies for early detection in the different poultry production systems. The viruses currently circulating in Europe belong to clade 188.8.131.52b with seven genotypes, three of which identified for the first time during this time period, being detected during summer. HPAI A(H5) viruses were also detected in wild mammal species in Europe and North America and showed genetic markers of adaptation to replication in mammals. Since the last report, two A(H5N6), two A(H9N2) and one A(H10N3) human infections were reported in China. The risk of infection is assessed as low for the general population in the EU/EEA, and low to medium for occupationally exposed people.


[The impact of surgical correction of obesity (laparoscopic gastro-bypass surgery) under metabolic syndrome on the biochemical blood indicators].
In nowadays the wide propagation of surgical treatment of metabolic syndrome using the laparoscopic gastro-bypass surgery can be explained hy severe consequences of clinical manifestation of metabolic syndrome. The risk of the mentioned method has to be clear-cut assessed. The comprehensive analysis of changes in indicators of metabolism has to be applied to patients with metabolic syndrome before and after laparoscopic gastro-bypass surgery. The study was carried out on the sampling of 41 patients, 16 patients before and 25 after laparoscopic gastro-bypass surgery. In patients with metabolic syndrome after laparoscopic gastro-bypass surgery the normalization of concentration of glucose and glycated hemoglobin was established. The level of triglycerides, low density lipoproteins and reactive protein reliably decreased as compared with indicators of in non-operated patients. After laparoscopic gastro-bypass surgery, the positive dynamics of activity of enzymes of blood serum was noted.


Electrospun polystyrene-poly(styrene-co-maleic anhydride) nanofiber as a new aptasensor platform.
Here, we report the use of an aptamer-immobilized electrospun polystyrene-poly(styrene-co-maleic anhydride) (PS-PSMA) nanofiber as a new aptasensor platform for protein detection. Two thrombin-binding aptamers (TBA29 and TBA15) were used as a model platform to facilitate efficient detection of thrombin in a sandwich manner. Thrombin concentration was measured by fluorescence microscopy and spectroscopy, in which aptamers were labeled with either fluorescein dye or quantum dots. The results indicated that thrombin was captured uniformly on the surface of the nanofiber. Using this sandwich-type biosensor, the minimum detectable concentration of thrombin was 10 pM, with a dynamic range of 0.1-50 nM, when quantum dots were used for labeling. In contrast, the limit of detection was 1 nM, with a dynamic range of 10-200 nM, when using fluorescein dye labeling. This aptamers-on-nanofiber-based biosensor showed 2500-fold higher sensitivity than a 96-microwell plate format, attributed mainly to the large surface area of the nanofibers. In addition, this novel platform also exhibited similar high sensitivity in the detection of exogenously added thrombin in diluted human serum. This aptamers-on-nanofiber system, which is competitive with other sensing platforms and clinically meaningful in terms of its detection limit, is expected to be useful for the detection of various other targets because of its ease of application and manipulation.


Functional luminal imaging probe geometric and histomorphologic analysis of abdominal wall wound induced by different trocars in pigs.
This study aimed to investigate wound geometry and tissue damage caused by several different trocar types using a quantitative functional luminal imaging probe (FLIP) geometric profile and histomorphologic analysis. Four pigs were used in this study. After general anesthesia, six different trocars were randomly inserted at preselected locations in the porcine abdominal wall. The hydration status of the animals was monitored and maintained. A bag mounted on a FLIP was used to profile the geometry of the trocar holes during distension. After the FLIP study, the abdominal wall surrounding the trocar holes was harvested. The tissue was fixed in neutral 10% buffered formalin solution for more than 24 h. The samples contained control tissue (undamaged) and test tissue (damaged) through the entire rectangular tissue block. Approximately four to seven slides were cut parallel to the surface from each sample. Each slide was photographed, and the morphometry of the hole and damaged areas were measured and displayed three-dimensionally. The histologic sections were analyzed with regard to acute damage, bleeding, and acute inflammation of the skin, muscle, and fascia. The FLIP study demonstrated differences between the six trocars. These were mainly due to differences between the Versaport Plus V2 bladed trocar with the smooth cannula, the Applied Medical Separator nonbladed access system with threaded cannula, and the VersaStep Plus trocar. The morphometry data showed the smallest hole and damage areas for the Versaport Plus V2 bladed trocar with the smooth cannula. The damaged area divided by the trocar hole area was smallest for the VersaStep plus trocar and the Ethicon Endopath bladed trocar with a stability cannula (p < 0.05). The histologic analysis showed that the VersaStep Plus trocar and the Ethicon Endopath bladed trocar with a stability cannula gave the least bleeding and inflammation (p < 0.05). An agreement was found between the geometric data obtained by FLIP, the morphometric analysis, and the histology.


Spontaneous transmitter release in experimental neuromuscular disorders of the rat.
Examination of spontaneous miniature end-plate potentials (mepps) in rat skeletal muscle has revealed that in conditions such as botulinum poisoning, during nerve terminal regeneration or in the presence of the drug 4-aminoquinoline two types of acetylcholine release are responsible for the mepps. In addition to the mepps that correspond to the quantal component of a nerve impulse evoked end-plate potential, a second type of acetylcholine release occurs. The latter type of transmitter release gives rise to mepps with a more prolonged time to peak and frequently a larger than normal amplitude. It is unaffected by nerve terminal depolarization, transmembrane calcium fluxes, and other procedures known to enhance mepp frequency. In botulinum-poisoned muscles this secretory type of transmitter release dominates, being exclusively present in muscles where nerve stimulation fails to release transmitter. In normal muscle such a release is induced by 4-aminoquinoline, which may cause up to 50% of all the spontaneous mepps to be of that kind. It is suggested that the described secretion of acetylcholine serves a neurotrophic function.


Low-molecular-weight heparin for the treatment of venous thromboembolism.
Unfractionated heparin (UFH) binds to several plasma, platelet, and endothelial proteins, producing a highly variable anticoagulant response. For this reason, frequent anticoagulation monitoring and dosage adjustment are necessary during UFH administration. In contrast, low-molecular-weight heparins (LMWHs) exhibit less protein binding and provide more predictable anticoagulation with reduced need for patient monitoring and dosage adjustment. Therefore, LMWHs are potentially useful for anticoagulation therapy on an outpatient basis. Several recent clinical trials have compared LMWHs (administered primarily on an outpatient basis) and UFH for the treatment of venous thromboembolism. These trials have indicated that LMWHs possess efficacy and safety characteristics similar to intravenous heparin but are easier to administer. LMWH preparations vary considerably in their methods of preparation and pharmacological properties, and the relative efficacies of these various LMWHs remain to be determined by direct comparisons in randomized clinical trials.


A microarray analysis of sex- and gonad-biased gene expression in the zebrafish: evidence for masculinization of the transcriptome.
In many taxa, males and females are very distinct phenotypically, and these differences often reflect divergent selective pressures acting on the sexes. Phenotypic sexual dimorphism almost certainly reflects differing patterns of gene expression between the sexes, and microarray studies have documented widespread sexually dimorphic gene expression. Although the evolutionary significance of sexual dimorphism in gene expression remains unresolved, these studies have led to the formulation of a hypothesis that male-driven evolution has resulted in the masculinization of animal transcriptomes. Here we use a microarray assessment of sex- and gonad-biased gene expression to test this hypothesis in zebrafish. By using zebrafish Affymetrix microarrays to compare gene expression patterns in male and female somatic and gonadal tissues, we identified a large number of genes (5899) demonstrating differences in transcript abundance between male and female Danio rerio. Under conservative statistical significance criteria, all sex-biases in gene expression were due to differences between testes and ovaries. Male-enriched genes were more abundant than female-enriched genes, and expression bias for male-enriched genes was greater in magnitude than that for female-enriched genes. We also identified a large number of genes demonstrating elevated transcript abundance in testes and ovaries relative to male body and female body, respectively. Overall our results support the hypothesis that male-biased evolutionary pressures have resulted in male-biased patterns of gene expression. Interestingly, our results seem to be at odds with a handful of other microarray-based studies of sex-specific gene expression patterns in zebrafish. However, ours was the only study designed to address this specific hypothesis, and major methodological differences among studies could explain the discrepancies. Regardless, all of these studies agree that transcriptomic sex differences in D. rerio are widespread despite the apparent absence of heterogamety. These differences likely make important contributions to phenotypic sexual dimorphism in adult zebrafish; thus, from an evolutionary standpoint, the precise roles of sex-specific selection and sexual conflict in the evolution of sexually dimorphic gene expression are very important. The results of our study and others like it set the stage for further work aimed at directly addressing this exciting issue in comparative genomics.