Molecular biology of atherosclerosis.
At least 468 individual genes have been manipulated by molecular methods to study their effects on the initiation, promotion, and progression of atherosclerosis. Most clinicians and many investigators, even in related disciplines, find many of these genes and the related pathways entirely foreign. Medical schools generally do not attempt to incorporate the relevant molecular biology into their curriculum. A number of key signaling pathways are highly relevant to atherogenesis and are presented to provide a context for the gene manipulations summarized herein. The pathways include the following: the insulin receptor (and other receptor tyrosine kinases); Ras and MAPK activation; TNF-α and related family members leading to activation of NF-κB; effects of reactive oxygen species (ROS) on signaling; endothelial adaptations to flow including G protein-coupled receptor (GPCR) and integrin-related signaling; activation of endothelial and other cells by modified lipoproteins; purinergic signaling; control of leukocyte adhesion to endothelium, migration, and further activation; foam cell formation; and macrophage and vascular smooth muscle cell signaling related to proliferation, efferocytosis, and apoptosis. This review is intended primarily as an introduction to these key signaling pathways. They have become the focus of modern atherosclerosis research and will undoubtedly provide a rich resource for future innovation toward intervention and prevention of the number one cause of death in the modern world.


[The microbial spectrum of urine and bladder bioptic samples in women with chronic recurrent cystitis].
The evaluation of urine and bladder bioptic samples (bacteriological examination and polymerase chain reaction) of 28 women with chronic cystitis was performed. In 85.7% of cases, mixed infections with predominance of nonclostridial anaerobes in the urine was detected. Herpes simplex virus type 1 was detected in 7.1% of cases. In the same manner as in urine, predominance of nonclostridial anaerobes in bladder bioptic samples (85.7%) was observed. Identical bacteria in urine and bladder bioptic samples were revealed in 64.3% of patients. Herpes viruses and papillomaviruses were frequently registered (p < 0.05) in the bioptic samples.


O2 and Other High-Energy Molecules in Photosynthesis: Why Plants Need Two Photosystems.
The energetics of photosynthesis in plants have been re-analyzed in a framework that represents the relatively high energy of O2 correctly. Starting with the photon energy exciting P680 and "loosening an electron", the energy transfer and electron transport are represented in a comprehensive, self-explanatory sequence of redox energy transfer and release diagrams. The resulting expanded Z-scheme explicitly shows charge separation as well as important high-energy species such as O2, TyrZ˙, and P680+˙, whose energies are not apparent in the classical Z-scheme of photosynthesis. Crucially, the energetics of the three important forms of P680 and of P700 are clarified. The relative free energies of oxidized and reduced species are shown explicitly in kJ/mol, not encrypted in volts. Of the chemical energy produced in photosynthesis, more is stored in O2 than in glucose. The expanded Z-scheme introduced here provides explanatory power lacking in the classical scheme. It shows that P680* is energetically boosted to P680+˙ by the favorable electron affinity of pheophytin and that Photosystem I (PSI) has insufficient energy to split H2O and produce O2 because P700* is too easily ionized. It also avoids the Z-scheme's bewildering implication, according to the "electron waterfall" concept, that H2O gives off electrons that spontaneously flow to chlorophyll while releasing energy. The new analysis explains convincingly why plants need two different photosystems in tandem: (i) PSII mostly extracts hydrogen from H2O, producing PQH2 (plastoquinol), and generates the energetically expensive product O2; this step provides little energy directly to the plant; (ii) PSI produces chemical energy for the organism, by pumping protons against a concentration gradient and producing less reluctant hydrogen donors. It also documents that electron transport and energy transfer occur in opposite directions and do not involve redox voltages. The analysis makes it clear that the high-energy species in photosynthesis are unstable, electron-deficient species such as P680+˙ and TyrZ˙, not putative high-energy electrons.


Incidence, cumulative mortality and factors affecting the outcome of COVID-19-associated mucormycosis from Western India.
To report the incidence, cumulative mortality, and factors influencing the outcomes from a large series of COVID-19-associated mucormycosis (CAM) from western India. Consecutive patients with CAM between March 1 and May 10, 2021, with a minimum follow-up of 1 month were included. We recorded the presence of diabetes, use of steroids, and need for non-invasive ventilation (NIV) from the case files. The features of orbital involvement, treatment administered, and outcomes, i.e., death, orbital exenteration, or recovery were noted. Cumulative probability of adverse outcomes, defined as either death or exenteration, was reported using survival analysis. We treated 67 cases of CAM and found an incidence of 13.6 cases per 1,000 patients post-moderate to severe COVID-19. Uncontrolled diabetes (90%) with ketoacidosis (40%) and prior systemic steroids (84%) were the strongest predispositions. The onset of CAM was 15.1 ± 9.5 days (range: 6-42 days) after recovery from COVID-19. The cumulative probability of an adverse outcome was 38% (95% confidence intervals [CI] = 23.7-56.9%) on day 20. The patients who required NIV during COVID-19 were at seven times higher risk of experiencing an adverse outcome (hazard ratios [HR] = 6.92, 95% CI = 2.9-16.2) while those who received amphotericin- -B had a 61% lower risk (HR = 0.39, 95% CI = 0.16-0.97). The current outbreak of CAM was seen predominantly in uncontrolled diabetics, especially with ketoacidosis and steroid intake. The cumulative probability of death or orbital exenteration was 38% at day 20 of the infection and those who required NIV and did not receive amphotericin-B were at a high risk of these outcomes.


Resistance of leukemic stem-like cells in AML cell line KG1a to natural killer cell-mediated cytotoxicity.
Leukemic stem cells (LSCs) play the central role in the relapse and refractory of acute myeloid leukemia (AML) and highlight the critical need for the new therapeutic strategies to directly target the LSC population. However, relatively little is known about the unique molecular mechanisms of drug and natural killer cells (NK)-killing resistance of LSCs because of very small number of LSCs in bone marrow. In this study, we investigated whether established leukemia cell line contains LSCs. We showed that KG1a leukemia cell line contained leukemic stem-like cells, which have been phenotypically restricted within the CD34(+)CD38(-) fractions. CD34(+)CD38(-) cells could generate CD34(+)CD38(+) cells in culture medium and had renewal function. Moreover, CD34(+)CD38(-) cells had self-renewal potential. We found that leukemic stem-like cells from KG1a cells were resistant to chemotherapy and NK-mediated cytotoxicity. NKG2D ligands involve in protecting LSCs from NK-mediated attack. Taken together, our studies provide a novel cell model for leukemic stem cells research. Our data also shed light on mechanism of double resistant to chemotherapy and NK cell immunotherapy, which was helpful for developing novel effective strategies for LSCs.


9,9-Di-n-octyl-9H-fluorene.
The title compound, C29H42, crystallizes from the melt as a triclinic crystal. The unit cell contains three crystallographically independent molecules. The three fluorene ring systems are oriented such that two non-equivalent ring systems related by a roto-translation are separated by a third ring system oriented orthogonally to them. The octyl chains of all three molecules are perpendicular to the fluorene ring system and force a 7.4 angstroms separation between the two coplanar molecules, thereby preventing molecular pi-stacking.


[Sucessful pregnancy outcome following three severe placental abruptions and intrauterine fetal death in the patient--heterozygous carrier of R506Q mutation of factor V (Leiden)].
A case of successful pregnancy outcome is reported in a patient with 3 preceding severe placental abruptions with intrauterine fetal death and caesarean deliveries. In the course of the current pregnancy heterozygosity for R506Q mutation of factor V (Leiden) was diagnosed in 26 weeks of gestation [w.g.] and low molecular weight heparin [LMWH] therapy initiated. Maternal condition was stable until delivery and all laboratory findings were within normal range. The fetus was followed up by ultrasound biometry and Doppler blood flow studies. From 28 w.g. on NST and biophysical profile were included. An emergency caesarean section was performed in 34 w.g. because of contractions not responding to tocolysis. The newborn was in good condition with weight and length corresponding to the 10th centile for gestational age [g.a]. Histologic study of the placenta showed anemic infarctions and recent haemorrhages in the basal and the chorionic plate. The initiation of LMWH therapy in the case reported was late (26 w.g.). By that moment there was already evidence of impaired fetal growth with fetal biometry corresponding to the 10th centile for g.a. After LMWH therapy was started no further slow down of fetal growth was registered. Successful pregnancy outcome may be related not only to LMWH therapy but also to other factors like active fetal monitoring after 28 w.g. and the emergency caesarian delivery immediately after the onset of uterine contractions. Patients with past obstetric history of severe preeclampsia, placental abruption or fetal growth restriction have to be screened for hereditary or acquired thrombophilia. If a thrombophillic state is present early LMWH therapy has to be considered. It is aimed to prevent anaemic placental infarctions and thrombotic complications.


[Laparoscopic cholecystectomy with single incision laparoscopic surgery].
For the last seventeen years laparoscopic cholecystectomy has remained the gold standard procedure for gallbladder surgery The single incision laparoscopic surgery (SILS) approach is a step toward less invasive surgery and the intraumbilical access improves the cosmetic effect (no scar surgery). The aim of the study was to present our preliminary experience in laparoscopic cholecystectomy through single intraumbilical incision. Three patients with gallbladder symptoms (2 female, 1 male) underwent surgery through single intraumbilical incision. In two cases the procedure was performed with three 5 mm Dexide port approach and in one, with a flexible rubber/gel SILSTM-Port (Covidien, USA) access. A simple 5 mm optics was employed. In two procedures the following disposable instruments were used: roticulator Endo dissect, roticulator Endo grasp, mini Sears scissors as well as standard hook and clips while for the third procedure, a conventional multi-use grasp and roticular Endo dissect. The gallbladder was elevated to the integuments by two sutures to expose Calot's triangle and bladder site. Following exposure, the bile duct and the vesical artery were clipsed and cut routinely to remove the gallbladder in a plastic bag through the bell-button. After procedures no drains were left in the peritoneal cavities. In all three cases the laparoscopic procedure was performed. The median operative time was 88 min. In one female patient, bleeding into the peritoneal cavity was reported and called for laparotomy within a few hours of laparoscopic procedure. Intraoperatively, the branch of vesical artery was sutured to arrest bleeding. The median hospital stay following procedure was 3, 8 and 5 days respectively. After the procedure, the last female patient was observed to have pharyngitis and enlarged jugular lymph nodes that abated after antibiotic therapy. Single-incision laparoscopic cholecystectomy should be performed by experienced laparoscopic surgeons. For adequate evaluation of the efficacy and safety of this procedure it is necessary to perform further clinical studies on a larger number of patients.


[Modular PC-based data acquisition and processing system for biological signals].
The data acquisition system described here is designed for biomedical research and permits the recording of up to eight biological signals simultaneously. A personal computer using the Windows 95 operating system is employed for data monitoring, data processing and analysis during experiments. The system has been designed for reliability, economy, flexibility and ease of handling, with the aim of achieving universal application. To avoid interface incompatibility, problems with transfer protocols and the data formats of commercially available products, analog signals are used for further processing. The individual input channels are electrically isolated from one another and the PC to avoid ground loops, and for reasons of safety. An isolated voltage supply is available for pre-amplifiers and bridges. A bandwidth of 0-5 kHz and the maximum sampling rate of 12.5 kHz suffice to pick up higher frequency signals such as EMG and ENG. The modular software and hardware concepts permit the use of almost any desktop or laptop PC as a central processing unit. The PC handless documentation, data acquisition, data analysis and the preparation of publications. If needed, further analytical functions can be added in modular form. Finally, the option of saving data in the ASCII format permits processing of results with such standard software packages as Excel, Access, Matlab and Origin.


Endoscopic mucosal resection: an improved diagnostic procedure for early gastroesophageal epithelial neoplasms.
Endoscopic mucosal resection (EMR), which is advocated for the treatment of early (superficial) gastroesophageal neoplasms, has also been alluded to represent a superior diagnostic and staging modality. We compared the diagnostic concordance of preceding biopsies with EMR specimens in 31 gastric and 10 esophageal EMRs consisting of 6 low-grade and 12 high-grade dysplasias, 21 intramucosal adenocarcinomas, and 2 submucosal invasive adenocarcinomas. Discrepancies were considered as either major or minor if the histologic grades differed by 2 or more, or by only 1, respectively. Discrepant and concordant cases were compared with regard to the size of lesion (maximum dimension and surface area), number of biopsy fragments, and extent of biopsy sampling (ratio between lesion size and number of biopsy fragments). These same variables were used to evaluate the differences seen between gastric and esophageal cases. Of the 41 cases, 16 (39%) had discrepant diagnoses, including 14 gastric and 2 esophageal neoplasms. A major discrepancy was seen in 2% of the cases (n = 1, gastric) and a minor discrepancy, in 15 cases. All but 2 of the discrepant cases were found to have a higher grade on EMR. The average number of biopsy fragments was 4.4 in both concordant and discrepant groups. The maximal dimension, surface area, and biopsy sampling ratios of the lesion were significantly greater in the discrepant cases than in the concordant cases. The esophageal cases trended toward having smaller size and a significantly extensive biopsy sampling. We conclude that EMR is superior to biopsy for diagnosing superficial gastroesophageal tumors. Discrepancies between the specimens occur in larger lesions (>10 mm) with less extensive biopsy sampling. EMR can substantially modify the diagnostic grade of a lesion and therefore facilitate optimal therapeutic decisions by avoiding undertreatment and overtreatment based on inaccurate grading and staging.


An accessory gene, lipB, required for the production of active Pseudomonas glumae lipase.
Pseudomonas glumae PG1 is able to secrete lipase into the extracellular medium. The lipase is produced as a precursor protein, with an N-terminal signal sequence. A second open reading frame (ORF) was found immediately downstream of the lipase structural gene, lipA, a situation found for the lipases of some other Pseudomonas species. Inactivation of this ORF resulted in a lipase-negative phenotype, indicating its importance in the production of active extracellular lipase. The ORF, lipB, potentially encodes a protein of 353-amino-acid residues, having a hydrophobic N-terminal (amino acids 1 to 90) and a hydrophilic C-terminal part. As a first step in determining the role of LipB, its subcellular location was determined. The protein was found to fractionate with the inner membranes. The expression of fusions of lipB fragments with phoA revealed an N(in)-C(out) topology for the LipB protein, which was confirmed by protease accessibility studies on EDTA-permeabilized cells and on inverted inner membrane vesicles. These and other results indicate that most of the LipB polypeptide is located in the periplasm and anchored to the inner membrane by an N-terminal transmembrane helix, located between amino acids 19 and 40.


Use of Apixaban in Atrial Fibrillation With Ritonavir-Boosted Antiretroviral Therapy: A Case Report.
Purpose: Direct oral anticoagulants (DOACs) pose a challenge when given with potent CYP3A4 and P-gp inhibitors, such as the commonly prescribed pharmacokinetic booster ritonavir. As per the manufacturer, apixaban offers a dose reduction when administered concurrently with ritonavir; thus, we explore the clinical indication and safety of apixaban when given with ritonavir-boosted highly active antiretroviral therapy (HAART) in an HIV patient. Summary: We describe a 73-year-old male with extensive cardiac history, including a past medical history of resolved left ventricular thrombus, newly diagnosed non-valvular atrial fibrillation treated with warfarin, and HIV infection treated with ritonavir-boosted HAART. The patient presented to the emergency department with bleeding from multiple sites, necessitating the use of vitamin K. Consequently, his hospital course was complicated by episodes of minor bleeding and labile INR. Due to the complicated nature of his condition and the potential for drug-drug interactions (DDIs), he was transitioned from warfarin to apixaban. Since there is little readily available data to support the use of rivaroxaban and dabigatran with ritonavir, our patient was safely started on dose-reduced apixaban for stroke prophylaxis in atrial fibrillation due to the predictable nature of apixaban pharmacokinetics and proven superiority regarding adverse effects, as compared to other DOACs. Conclusion: Dose-reduced apixaban is a safe and viable choice in patients with atrial fibrillation warranting stroke prophylaxis while concurrently receiving ritonavir-boosted HAART.


Calcium concentration during anoxic perfusion modifies post-ischemic hypercontraction in the canine heart.
The purpose of this study was to clarify the role of calcium flux in the pathogenesis of transient overshoot in regional myocardial contractile function after brief ischemia (post-ischemic hypercontraction). Six open-chest anesthetized dogs were examined. The left anterior descending coronary artery (LAD) was cannulated with a bypass system from the left carotid artery. Two minutes of total coronary occlusion of the LAD resulted in a post-ischemic hypercontraction 1 minute after reperfusion. Post-ischemic hypercontraction was abolished after reperfusion following 2 minutes of perfusion with anoxic Krebs-Henseleit solution containing 2.5 mM calcium. Post-ischemic hypercontraction occurred after calcium-free anoxic perfusion. The regional myocardial contractile function remained depressed 1 minute after reperfusion following anoxic perfusion with 5.0 mM calcium solution. Thus, post-ischemic hypercontraction was modified by the calcium concentration during anoxia. Alteration in transsarcolemmal calcium influx during reperfusion, which was modified by alterations in the calcium environment during anoxia, could be responsible for this phenomenon.


Brain neurochemical and hemodynamic findings in the NY1DD mouse model of mild sickle cell disease.
To characterize the cerebral profile associated with sickle cell disease (SCD), we used in vivo proton MRI and MRS to quantify hemodynamics and neurochemicals in the thalamus of NY1DD mice, a mild model of SCD, and compared them with wild-type (WT) control mice. Compared with WT mice, NY1DD mice at steady state had elevated cerebral blood flow (CBF) and concentrations of N-acetylaspartate (NAA), glutamate (Glu), alanine, total creatine and N-acetylaspartylglutamate. Concentrations of glutathione (GSH) at steady state showed a negative correlation with BOLD signal change in response to 100% oxygen, a marker for oxidative stress, and mean diffusivity assessed using diffusion-tensor imaging, a marker for edematous inflammation. In NY1DD mice, elevated basal CBF was correlated negatively with [NAA], but positively with concentration of glutamine ([Gln]). Immediately after experimental hypoxia (at reoxygenation after 18 hours of 8% O2 ), concentrations of NAA, Glu, GSH, Gln and taurine (Tau) increased only in NY1DD mice. [NAA], [Glu], [GSH] and [Tau] all returned to baseline levels two weeks after the hypoxic episode. The altered neurochemical profile in the NY1DD mouse model of SCD at steady state and following experimental hypoxia/reoxygenation suggests a state of chronic oxidative stress leading to compensatory cerebral metabolic adjustments.


Novel Phenobarbital-Loaded Nanostructured Lipid Carriers for Epilepsy Treatment: From QbD to In Vivo Evaluation.
Pharmacological treatments of central nervous system diseases are always challenging due to the restrictions imposed by the blood-brain barrier: while some drugs can effectively cross it, many others, some antiepileptic drugs among them, display permeability issues to reach the site of action and exert their pharmacological effects. The development of last-generation therapeutic nanosystems capable of enhancing drug biodistribution has gained ground in the past few years. Lipid-based nanoparticles are promising systems aimed to improve or facilitate the passage of drugs through biological barriers, which have demonstrated their effectiveness in various therapeutic fields, without signs of associated toxicity. In the present work, nanostructured lipid carriers (NLCs) containing the antiepileptic drug phenobarbital were designed and optimized by a quality by design approach (QbD). The optimized formulation was characterized by its entrapment efficiency, particle size, polydispersity index, and Z potential. Thermal properties were analyzed by DSC and TGA, and morphology and crystal properties were analyzed by AFM, TEM, and XRD. Drug localization and possible interactions between the drug and the formulation components were evaluated using FTIR. In vitro release kinetic, cytotoxicity on non-tumoral mouse fibroblasts L929, and in vivo anticonvulsant activity in an animal model of acute seizures were studied as well. The optimized formulation resulted in spherical particles with a mean size of ca. 178 nm and 98.2% of entrapment efficiency, physically stable for more than a month. Results obtained from the physicochemical and in vitro release characterization suggested that the drug was incorporated into the lipid matrix losing its crystalline structure after the synthesis process and was then released following a slower kinetic in comparison with the conventional immediate-release formulation. The NLC was non-toxic against the selected cell line and capable of delivering the drug to the site of action in an adequate amount and time for therapeutic effects, with no appreciable neurotoxicity. Therefore, the developed system represents a promising alternative for the treatment of one of the most prevalent neurological diseases, epilepsy.


Additional risk factors associated with thrombosis and pregnancy morbidity in a unique cohort of antiphospholipid antibody-positive patients.
Antiphospholipid syndrome (APS) is an autoimmune prothrombotic condition with significant morbidity. The objective of this study was to identify additional clinical and epidemiological risks of arterial thrombosis, venous thrombosis, and pregnancy morbidities in a large cohort of persistent antiphospholipid antibodies (aPLs)-positive carriers. This was a cross-sectional cohort study of 453 consecutive patients with a documented positive aPL who attended Peking University People's Hospital. Among 453 patients screened, 297 patients had persistent positive aPL. We compared asymptomatic aPL carriers with thrombotic and obstetric APS patients. And the univariate analysis and multivariable logistic regression were used to evaluate the association between different risk factors and APS clinical manifestations. The levels of circulating markers of neutrophil extracellular traps (NETs) (cell-free DNA and citrullinated histone H3 [Cit-H3]) were assessed and compared among aPL-positive carriers with or without autoimmune disease and APS patients. Additional risk factors associated with arterial thrombosis among aPL-positive carriers included: smoking (odds ratio [OR] = 6.137, 95% confidence interval [CI] = 2.408-15.637, P = 0.0001), hypertension (OR = 2.368, 95% CI = 1.249-4.491, P = 0.008), and the presence of underlying autoimmune disease (OR = 4.401, 95% CI = 2.387-8.113, P < 0.001). Additional risks associated with venous thrombosis among aPL carriers included: smoking (OR = 4.594, 95% CI = 1.681-12.553, P = 0.029) and the presence of underlying autoimmune disease (OR = 6.330, 95% CI = 3.355-11.940, P < 0.001). The presence of underlying autoimmune disease (OR = 3.301, 95% CI = 1.407-7.744, P = 0.006) is the additional risk, which demonstrated a significant association with APS pregnancy morbidity. Higher circulating levels of cell-free DNA and Cit-H3 were observed among APS patients and aPL patients with autoimmune diseases compared with those aPL carriers without underlying autoimmune diseases. Furthermore, control neutrophils that are conditioned with APS patients'sera have more pronounced NET release compared with those treated with aPL carriers'sera without underlying autoimmune diseases. We identified several potential additional risk factors for APS clinical manifestations among a large cohort of Chinese aPL carriers. Our data may help physicians to risk stratify aPL-positive Asian patients.


Increased plasma-soluble tumor necrosis factor-alpha receptor 2 level in lean nondiabetic offspring of type 2 diabetic subjects.
Tumor necrosis factor-alpha (TNF-alpha) is one of the proposed mediators of insulin resistance, upregulated in human obesity. Insulin resistance, however, might precede the development of obesity, especially in subjects with a family history of type 2 diabetes. Therefore, the aim of the present study was to assess plasma levels of TNF-alpha and soluble forms of its receptors (soluble TNF-alpha receptors 1 [sTNFR1] and 2 [sTNFR2]) and to evaluate the relationship of the TNF-alpha system with insulin resistance in lean, nondiabetic offspring of type 2 diabetic patients. We compared 20 lean offspring (BMI <25 kg/m(2), 8 men and 12 women) of type 2 diabetic patients with 20 lean subjects with no family history of diabetes, matched for age, sex, and BMI (control group). Anthropometry and blood biochemical parameters were measured, and insulin sensitivity was evaluated with the euglycemic-hyperinsulinemic clamp technique. Both men and women in the offspring group were markedly more insulin-resistant and had higher plasma levels of sTNFR2 (all P < 0.05). TNF-alpha, sTNFR1, and other examined parameters did not differ between the studied groups. Both TNF-alpha receptors were related to waist-to-hip ratio (WHR), fat-free mass (FFM), plasma total cholesterol, HDL cholesterol, LDL cholesterol, and nonesterified fatty acids (NEFAs). sTNFR2, but not sTNFR1, was also associated with insulin sensitivity (r = -0.49, P = 0.001). This relationship remained significant after adjustment for WHR, FFM, plasma insulin, and NEFA. TNF-alpha system might be involved in modulating insulin action before the onset of obesity in subjects at high risk for type 2 diabetes.


A comparison of corpus callosum development in the BALB/cCF and C57BL/6J inbred mouse strains.
Series of fetuses from two inbred mouse strains, BALB/cCF and C57BL/6J, were collected at the time during which the corpus callosum (CC) crosses midline. Fetuses from each strain were matched initially with respect to chronological age, then morphological age and finally brain weight, and in each case the CC was assessed for presence at midline. The results indicated that CC development was retarded in the BALB animals relative to C57 animals of the same developmental status as measured by either morphological age or brain weight.


Reduction of a tris(picolyl)amine copper(ii) complex by a polymeric flavo-reductase model in water.
Dioxygen activation at copper(i) centres is of primary importance for the development of sustainable oxidation catalysis, but regeneration of copper(i) centres after each catalytic cycle remains a major problem for multi-turn-over catalysis. This work demonstrates that an artificial reductase, made of flavin cofactors incorporated into a water soluble polymer, efficiently reduces a Cu(ii)TPA complex in the presence of NADH in water.


[Epidemiology and control of injury].
Injury has recently become a major world-wide health problem. Injury related deaths occur in many actively working young people and produce major social and economical losses. However health related specialists do not recognize the importance of injury and there have not been many studies related to this problem. This research studied the trends of injury related research in Korea, mortality rate and prevalence rate, socio-economical losses and control in Korea and out of the country, based on literature from Korea and without such as statistical yearly reports on causes of deaths and OECD health reports, as well as WHO web sites. Studies in Korea about injury were very few, with 9 in the 1960's, 5 in the 1980's, 4 in the 1990's and 5 in 2000's. Mortality rate of injury was higher in Korea than in England, USA or Japan, especially in car accidents, suicide and falls. In Korea, the yearly trends in mortality rates were highest in car accidents but those rates are falling, suicide is steadily rising, with highest rate in 2003. Falls is in second rank with no change in rates. In 2003, the ten causes of death in Korea were suicide in 5th rank, transport accidents in 7th rank, and falls in 10th rank. Considering age groups, in the teens, transport accidents were 1st rank, in the 20's and 30's, suicide was 1st rank, and although there were some differences, falls, drowning, assault, fire were in the top 10. Prevalence rates of injury could not be known, but in 2001, according to the National Health and Nutrition Survey, lifelong injury was 10%, and yearly major injury was 1.3%, major injury for two weeks was 0.1%, and minor injury was 10%. In other foreign countries, injury has become to be recognized as a major health related problem, and much programs are being set up to reduce injury related deaths and injuries. WHO is putting much effort in prevention of violence and transport accidents, and in the USA, Canada and Europe, there are injury surveillance systems. Recently, as suicide is increasing rapidly and providing much problems, each country are managing suicide prevention programs. In Korea, Ministry of Construction and Transportation is managing and guiding the policies for prevention of transport accidents. In September of 2004, the Ministry of Health and Welfare has set up a 5 year plan of suicide prevention.


In-cell NMR in E. coli to monitor maturation steps of hSOD1.
In-cell NMR allows characterizing the folding state of a protein as well as posttranslational events at molecular level, in the cellular context. Here, the initial maturation steps of human copper, zinc superoxide dismutase 1 are characterized in the E. coli cytoplasm by in-cell NMR: from the apo protein, which is partially unfolded, to the zinc binding which causes its final quaternary structure. The protein selectively binds only one zinc ion, whereas in vitro also the copper site binds a non-physiological zinc ion. However, no intramolecular disulfide bridge formation occurs, nor copper uptake, suggesting the need of a specific chaperone for those purposes.


Effect of limited proteolysis in the 8th loop of the barrel and of antibodies on porcine pancreas amylase activity.
The porcine pancreatic alpha-amylase is a (beta/alpha)8-barrel protein, containing domains A and B (peptide sequence 1-403) and a distinct C-domain (peptide sequence 404-496). Separation of the terminal C-domain from the A and B domains has been attempted by limited proteolysis in the hinge region. Subtilisin was found to hydrolyse amylase between residues 369 and 370 situated in the loop between the eighth beta-strand and alpha-helix. The cleaved amylase was isolated by chromatofocusing and found to retain about 60% of the activity of the native enzyme, while the isolated fragments were inactive. Antigen binding fragments prepared from polyclonal antibodies to native amylase and the CNBr-fragment P1 (peptide sequence 395-496) respectively, were tested for influence on the enzyme activity. Antibodies directed against P1 had no effect whereas antibodies against the peptide sequence 1-394 and amylase respectively inhibited hydrolysis of substrates having four or more glucose residues but not of shorter oligomaltosides. Crystallographic analysis revealed that changes in the region of residue 369 might affect the conformation of the active site as well as of a second binding site. This site, located on the enzyme surface, is proposed to be required for the hydrolysis of larger substrates.


Assessment of donor limb hemodynamics in femorofemoral bypass for claudication.
During a 5-year period (1975 to 1980), 44 patients underwent femorofemoral bypass for unilateral disabling claudication caused by iliac atheroocclusive disease. All patients had complete Doppler arterial examination performed pre- and postoperatively, including segmental thigh and ankle pressure and calculation of an ankle/brachial (A/B) index for each limb. In 37 patients, standard treadmill exercise testing was performed before and after femorofemoral grafting. Hemodynamic improvement in the symptomatic limb was evidenced by an increase in resting A/B index from a mean of 0.54 +/- 0.14 before to 0.76 +/- 0.22 after operation (P less than 0.001). Exercise tests which were abnormal in all 37 recipient limbs preoperatively were improved. Six of the seven unimproved recipient limbs had associated femoropopliteal occlusion. Donor limb mean resting ankle/brachial index fell from 0.93 +/- 0.22 before to 0.83 +/- 0.22 after surgery (P less than 0.05). However, in 13 of 23 donor limbs, exercise response which had been normal before surgery became abnormal. Additionally, in 14 patients with abnormal donor limb exercise response before grafting, seven limbs had a significantly worsening of the exercise response postoperatively. These findings were not related to the patency of the superficial femoral artery in the donor limb. Deterioration in donor limb hemodynamics noted in 20 (45%) of the 44 patients in this series suggests that strict patient selection criteria should be maintained. Unlike in healthy subjects, an arteriographically patent atherosclerosis iliac artery may not support flow requirements of bilateral lower limb exercise.


Left-sided liver and right sided Polysplenia: a 77-year-old patient with hetrotaxy syndrome.
Hetrotaxy syndrome is defined as an abnormality where the internal thoraco-abdominal organs demonstrate abnormal arrangement across the left-right axis of the body. Although it is a known condition among physicians taking care of pediatric patients, it is rarely seen in adult day-to-day medicine and most physicians involved in care of adult patients are unaware of it. It is important to recognize this anomaly based on clinical findings,due to its reported association with various medical conditions. We report a case of a 77-year-old patient diagnosed with Hetrotaxy syndrome.


Plant sources of provitamin A and human nutriture.
Hypovitaminosis A is a problem in many parts of the developing world. Beyond the stop-gap measures of capsule distribution and food fortification, increased consumption of accessible sources of vitamin A, specifically of the carotenoid provitamin A in yellow, orange, and green plants, has been promoted as the sustainable, long-term solution. However, a search of the available literature reveals few examples of human studies to support the effectiveness of this solution. Evidence from feeding studies shows an almost universally poorer uptake of intact carotenoids from plant sources as opposed to pure, chemical sources. With notable exceptions, the bioconversion of plant carotenoids to preformed vitamin A also seems to be inefficient. Epidemiologic observations in poor Third World populations and in vegetarians in an industrialized nation indicate a relatively greater potency for animal sources of vitamin A. In developing countries, low fat intakes, intestinal roundworms, recurrent diarrhea, and tropical enteropathy all may contribute to reduced utilization of plant provitamin A. The accepted 6:1 equivalency of beta-carotene to preformed vitamin A must be challenged and reexamined in the context of dietary plants. The consequences of operating on a miscalculation could be serious indeed for public health programs designed to alleviate and eradicate hypovitaminosis A.


Programmed Delay of a Virulence Circuit Promotes Salmonella Pathogenicity.
Signal transduction systems dictate various cellular behaviors in response to environmental changes. To operate cellular programs appropriately, organisms have sophisticated regulatory factors to optimize the signal response. The PhoP/PhoQ master virulence regulatory system of the intracellular pathogen Salmonella enterica is activated inside acidic macrophage phagosomes. Here we report that Salmonella delays the activation of this system inside macrophages using an inhibitory protein, EIIANtr (a component of the nitrogen-metabolic phosphotransferase system). We establish that EIIANtr directly restrains PhoP binding to its target promoter, thereby negatively controlling the expression of PhoP-activated genes. PhoP furthers its activation by promoting Lon-mediated degradation of EIIANtr at acidic pH. These results suggest that Salmonella ensures robust activation of its virulence system by suspending the activation of PhoP until a sufficient level of active PhoP is present to overcome the inhibitory effect of EIIANtr Our findings reveal how a pathogen precisely and efficiently operates its virulence program during infection.IMPORTANCE To accomplish successful infection, pathogens must operate their virulence programs in a precise, time-sensitive, and coordinated manner. A major question is how pathogens control the timing of virulence gene expression during infection. Here we report that the intracellular pathogen Salmonella controls the timing and level of virulence gene expression by using an inhibitory protein, EIIANtr A DNA binding master virulence regulator, PhoP, controls various virulence genes inside acidic phagosomes. Salmonella decreases EIIANtr amounts at acidic pH in a Lon- and PhoP-dependent manner. This, in turn, promotes expression of the PhoP-activated virulence program because EIIANtr hampers activation of PhoP-regulated genes by interfering with PhoP binding to DNA. EIIANtr enables Salmonella to impede the activation of PhoP-regulated gene expression inside macrophages. Our findings suggest that Salmonella achieves programmed delay of virulence gene activation by adjusting levels of an inhibitory factor.


Rabies in two privately owned domestic rabbits.
Two privately owned domestic rabbits (Oryctolagus cuniculus) in Maryland were found to be infected with the raccoon variant of the rabies virus in 1998. Both rabbits had an acute onset of anorexia and paralysis or paresis of the left forelimb; 1 also developed head tremors and a head tilt. One of the rabbits became ill 25 days after being attacked by a raccoon (Procyon lotor) and was euthanatized 3 days after onset of illness. The other rabbit, which was housed in an outdoor hutch, died 4 days after onset of clinical signs; the source of infection in that rabbit remains unknown. Currently, there is not a rabies vaccine approved for use in rabbits; thus, the only way to prevent the infection in rabbits is to prevent exposure. Veterinarians in rabies-enzootic areas should be familiar with the clinical signs of rabies in rabbits and should caution rabbit owners about the need to protect their pets from contact with wildlife.


DisProt in 2022: improved quality and accessibility of protein intrinsic disorder annotation.
The Database of Intrinsically Disordered Proteins (DisProt, URL: https://disprot.org) is the major repository of manually curated annotations of intrinsically disordered proteins and regions from the literature. We report here recent updates of DisProt version 9, including a restyled web interface, refactored Intrinsically Disordered Proteins Ontology (IDPO), improvements in the curation process and significant content growth of around 30%. Higher quality and consistency of annotations is provided by a newly implemented reviewing process and training of curators. The increased curation capacity is fostered by the integration of DisProt with APICURON, a dedicated resource for the proper attribution and recognition of biocuration efforts. Better interoperability is provided through the adoption of the Minimum Information About Disorder (MIADE) standard, an active collaboration with the Gene Ontology (GO) and Evidence and Conclusion Ontology (ECO) consortia and the support of the ELIXIR infrastructure.


Single-step acid-catalyzed synthesis of luminescent colloidal organosilica nanobeads.
We present a single-step, room-temperature synthesis of fluorescent organosilica nanobeads (FOS NBs). The FOS NBs were synthesized under aqueous conditions using (3-aminopropyl)triethoxysilane (APTES) as the silicon source in the presence of L-ascorbic acid (L-AA). In the APTES/L-AA/water ternary phase, the hydrolysis and condensation reaction of APTES occurred under acidic conditions to form spherical FOS NBs with an average diameter of 426.8 nm. FOS NBs exhibit excellent colloidal stability in aqueous media. The formation of FOS NBs was complete within a 10 min reaction time, which indicates potential for large-scale mass-production synthesis of luminescent colloidal NBs. The FOS NBs exhibited blue photoluminescence (PL) under UV excitation in the absence of an additional high temperature calcination process or with the incorporation of any fluorophores. This phenomenon is attributed to the presence of carbon-containing defects, which act as luminescent centers formed by the reaction between amino groups in the APTES and L-ascorbic acid reductant. Finally, the results of a cytotoxicity test and cellular uptake experiments revealed that the FOS NBs showed potential as optical contrast agents for bioimaging.


Gene Therapy for Inherited Bleeding Disorders.
Decades of preclinical and clinical studies developing gene therapy for hemophilia are poised to bear fruit with current promising pivotal studies likely to lead to regulatory approval. However, this recent success should not obscure the multiple challenges that were overcome to reach this destination. Gene therapy for hemophilia A and B benefited from advancements in the general gene therapy field, such as the development of adeno-associated viral vectors, as well as disease-specific breakthroughs, like the identification of B-domain deleted factor VIII and hyperactive factor IX Padua. The gene therapy field has also benefited from hemophilia B clinical studies, which revealed for the first time critical safety concerns related to immune responses to the vector capsid not anticipated in preclinical models. Preclinical studies have also investigated gene transfer approaches for other rare inherited bleeding disorders, including factor VII deficiency, von Willebrand disease, and Glanzmann thrombasthenia. Here we review the successful gene therapy journey for hemophilia and pose some unanswered questions. We then discuss the current state of gene therapy for these other rare inherited bleeding disorders and how the lessons of hemophilia gene therapy may guide clinical development.


Effect of protein on the absorption of phenytoin through everted gut preparations.
The transfer of phenytoin across everted gut membrane has been measured both from solutions and from media where the drug is dissolving at different pH. Introduction of protein into the mucosal medium caused varying effects. Protein binding in the mucosal solution causes a decrease in the apparent transfer rate. However, in accord with previous findings, at pH 4 both the solubility and dissolution rate of phenytoin increase in the presence of protein, and this can lead to increased transfer rates. Effects such as these may account for the effect of food on phenytoin bioavailability.


A comparative study on the effect of radial keratotomy in patients who live at sea level and high altitude.
To compare the refractive and keratometric results of matched pairs of patients who underwent radial keratotomy (RK) at sea level and high altitude. The results of 30 eyes that underwent RK procedures in two clinical centres at different altitude were analysed. One centre was at sea level (Istanbul) and the other at an altitude of 1720 m (Van). The patients in the two centres were matched regarding gender, age, degree of myopia, number of incisions and optic zone size. There were 15 eyes in each group. All operations were performed with a diamond blade using a Russian technique by the same surgeon. The mean pre-operative spherical equivalent cycloplegic refractions (SECR) were -6.33 +/- 1.15 D and -6.32 +/- 1.01 D in the Istanbul and Van groups, respectively (p = 0.96). The mean post-operative SECRs were -1.93 +/- 1.03 D and -0.28 +/- 0.57 D in the Istanbul and Van groups, respectively (p < 0.001). The mean SECR changes were 4.40 +/- 0.92 D and 6.03 +/- 1.13 D in subjects who had undergone RK at sea level and at 1720 m, respectively (p < 0.001). These results show that a higher myopic correction can be provided in patients who undergo RK at high altitude compared with those operated on at sea level. The RK nomograms used by refractive surgeons performing RK surgery at high altitude may need to be redesigned in the light of future studies with long-term follow-up.


Radiation therapy to a primary tumor accelerates metastatic growth in mice.
The surgical removal of a primary tumor can result in the rapid growth of metastases. The production of angiogenesis inhibitors by the primary tumor is one mechanism for the inhibition of metastatic tumor growth. The effect of curative radiotherapy to a primary tumor known to make an inhibitor of angiogenesis and the effects on distant metastases has not been studied. We here show that the eradication of a primary Lewis lung carcinoma (LLC-LM), which is known to generate angiostatin, is followed by the rapid growth of metastases that kill the animal within 18 days after the completion of radiation therapy. The right thighs of C57BL/6 mice (n = 25) were injected s.c. with 1 x 10(6) LLC-LM cells. Animals were randomized to one of five groups: no irradiation, 40 Gy in one fraction, 30 Gy in one fraction, 40 Gy in two 20 Gy fractions, or 50 Gy in five 10 Gy fractions. Tumors were clinically eradicated in each treatment group. All of the surviving animals became dyspneic and were killed within 14-18 days after the completion of radiation therapy. Examination of their lungs revealed >46 (range, 46-62) surface metastases in the treated animals compared with 5 (range, 2-8) in the untreated animals. The lung weights had increased from 0.2 g (range, 0.19-0.22 g) in the controls to 0.58 g (range 0.44-0.84) in the experimental animals. The most effective dose regimen was 10 Gy per fraction for five fractions, and serial experiments were conducted with this fractionation scheme. Complete response of the primary tumor was seen in 25 of 35 (71%) mice. The average weight of the lungs in the nonirradiated animals was 0.22 g (range, 0.19-0.24 g) and in the irradiated animals was 0.66 g (range, 0.61-0.70 g). The average number of surface metastases increased from five per lung (range, 2-13) in the control animals to 53 per lung (range, 46-62) in the irradiated animals. Both differences were statistically significant with P < 0.001. If the nontumor-bearing leg was irradiated or the animals were sham-irradiated, no difference in the number of surface metastases or lung weights was observed between the control group and the treated group. Urinary levels of matrix metalloproteinase 2, the enzyme responsible for angiostatin processing in this tumor model, were measured and correlated with the viability and size of the primary tumor. Administration of recombinant angiostatin prevented the growth of the metastases after the treatment of the primary tumor. In this model, the use of radiation to eradicate a primary LLC-LM tumor results in the growth of previously dormant lung metastases and suggests that combining angiogenesis inhibitors with radiation therapy may control distant metastases.


Juvenile Vogt-Koyanagi-Harada Disease in Which Good Visual Prognosis Was Derived from Swift and Definitive Diagnosis.
We report an 8-year-old girl who manifested Vogt-Koyanagi-Harada (VKH) disease. At the first visit, conjunctival hyperemia, inflammation in the anterior chamber, serous retinal detachment, and papillitis were observed in both eyes. Fluorescein angiography (FA) revealed bilateral subretinal fluid and papillitis. Ocular computed tomography (OCT) showed subretinal fluid and choroidal hypertrophy underneath macula in both eyes. Cerebrospinal fluid examination indicated aseptic meningitis. Systemic data did not suggest the other systemic diseases. Therefore, she was diagnosed with incomplete VKH disease. After corticosteroid pulse therapy, oral prednisolone was administered for seven months. Eighteen days after the induction of the treatments, inflammation in the anterior chamber and serous retinal detachment of both eyes disappeared completely. For seven months after the induction of the treatments, she had no relapses of any symptoms. Cerebrospinal fluid examination and FA for children are difficult to conduct, since it is difficult to get informed consent of these examinations from their parents. However, those thorough examinations enable us to make a swift and definitive diagnosis of VKH disease, thus assuring good visual prognosis. We have to bear in mind that juvenile VKH disease is very rare, yet when it occurs, ophthalmologic examinations help us diagnose and treat it.


The case for conservative management of venous angiomas.
Venous angiomas (developmental venous anomalies) are vascular malformations increasingly recognized in general neurosurgical or neurological practice. They are associated with intracranial hemorrhage, seizures, or progressive neurological deficits or found as incidental findings in patients who present with headaches or have neuroimaging studies for investigation of unrelated neurological disorders. Since venous angiomas drain normal cerebral tissue within a functionally normal arterial territory, resection can lead to venous infarction. This report studies 27 patients with venous angiomas, all of whom had conservative treatment. The venous angioma was considered to be responsible for the onset of neurological symptoms in 14 patients (7 with hemorrhage, 3 with hemorrhage and seizures, 2 with seizures, one with an extrapyramidal movement disorder, and one with motor deficit). Thirteen patients had incidental lesions (8 with headache, and 5 with unrelated neurological symptoms). Ten venous angiomas were in the posterior fossa; seven in the cerebellum. Location did not correlate with symptomatic presentation. No patient with hemorrhage required surgical evacuation of the hematoma. No patient died or had significant morbidity during the follow-up interval (mean of 3.7 years). Venous angiomas are low flow, low resistance vascular malformations, many of which are not associated with neurological sequelae. Our series supports the concept that surgical removal or radiosurgical obliteration should not be performed unless a patient has a second life threatening hemorrhage.


The Ever-Important Role of Ethics in Plastic Surgery Today.
As the field of plastic surgery continues to advance, so too do the number and complexity of ethical challenges faced by plastic surgeons. There is a paucity of literature, however, focusing on ethics in plastic surgery. Therefore, the authors offer a timely special topic series discussing ethical issues relevant to the field of plastic surgery. The goals of this series are four-fold: (1) to increase awareness of both frequently and less commonly encountered ethical issues in plastic surgery, (2) to foster discussion and debate of relevant and significant ethical issues, (3) to facilitate clinical ethics education and scholarship in plastic surgery, and (4) to apply an understanding and analysis of ethical issues in a way that optimizes clinical decision-making and delivery of patient care. In this introductory article, the authors discuss the current state of medical ethics scholarship in plastic surgery and introduce the first of several topics that will be detailed in the series. Ultimately, the hope is that increased awareness of the ethical challenges faced by surgeons and patients will improve the practice of plastic surgery.


Lipid-Activatable Fluorescent Probe for Intraoperative Imaging of Atherosclerotic Plaque Using In Situ Patch.
The surgical removal of lesions is among the most common and effective treatments for atherosclerosis. It is often the only curative treatment option, and the ability to visualize the full extent of atherosclerotic plaque during the operation has major implications for the therapeutic outcome. Fluorescence imaging is a promising approach for the inspection of atherosclerotic plaques during surgery. However, there is no systematic strategy for intraoperative fluorescent imaging in atherosclerosis. In this study, the in situ attachment of a lipid-activatable fluorescent probe (CN-N2)-soaked patch to the outer arterial surface is reported for rapid and precise localization of the atherosclerotic plaque in ApoE-deficient mouse during surgery. Stable imaging of the plaque is conducted within 5 min via rapid recognition of abnormally accumulated lipid droplets (LDs) in foam cells. Furthermore, the plaque/normal ratio (P/N) is significantly enhanced to facilitate surgical delineation of carotid atherosclerotic plaques. Visible fluorescence bioimaging using lipid-activatable probes can accurately delineate plaque sizes down to diameters of <0.5 mm, and the images can be swiftly captured within the stable plaque imaging time window. These findings on intraoperative fluorescent imaging of plaques via the in situ attachment of the CN-N2 patch hold promise for effective clinical applications.


Increased fracture rate in women with breast cancer: a review of the hidden risk.
Women with breast cancer, particularly individuals diagnosed at a relatively early age, have an increased incidence of fractures. Fractures can have serious clinical consequences including the need for major surgery, increased morbidity and mortality, increased cost of disease management, and reduced quality of life for patients. The primary cause of the increased fracture risk appears to be an accelerated decrease in bone mineral density (BMD) resulting from the loss of estrogenic signaling that occurs with most treatments for breast cancer, including aromatase inhibitors. However, factors other than BMD levels alone may influence treatment decisions to reduce fracture risk in this setting. Our purpose is to review current evidence for BMD loss and fracture risk during treatment for breast cancer and discuss pharmacologic means to reduce this risk. Fracture risk during treatment for breast cancer may be influenced by the rate of BMD loss and the consequent rapid alterations in bone microarchitecture, in addition to the established fracture risk factors in postmenopausal osteoporosis. The rapid decrease in BMD during adjuvant chemoendocrine therapy for breast cancer may necessitate more aggressive pharmacotherapy than is indicated for healthy postmenopausal women who develop osteoporosis. Over the last few years, clinical trials have established the effectiveness of bisphosphonates and other antiresorptive agents to preserve BMD during adjuvant therapy for early breast cancer. In addition, some bisphosphonates (eg, zoledronic acid) may also delay disease recurrence in women with hormone-responsive tumors, thereby providing an adjuvant benefit in addition to preserving BMD and potentially preventing fractures. It is likely that a combined fracture risk assessment (eg, as in the WHO FRAX algorithm) will more accurately identify both women with postmenopausal osteoporosis and women with breast cancer who require bone-protective therapy.


The use of low doses of dopamine in intensive care medicine.
The dopamine alpha- and beta-adrenoceptor dose-response curves are investigated in four patients who are exempt from cardiovascular disease. A dose-related increase in CO, HR and SV is observed with infusion rates of up to 3 micrograms kg-1 min-1. With concentrations greater than 10 micrograms kg-1 min-1, both BP and SVR increase. Low-dose dopamine infusion less than 3 micrograms kg-1 min-1 is investigated in ten other patients. With this infusion rate, a selective renal vasodilation is induced without peripheral or cardiac beta-adrenoceptor activation. Dopamine is responsible for an increase in diuresis FENa, GFR and RBF. These properties are indicated in renal failure, and when haemodynamic support is required in cardiac failure, if an infusion rate of up to 10 micrograms kg-1 min-1 is able to reverse cardiac insufficiency.


Peritoneal solitary fibrous tumour (SFT): long-term survival of recurrent and metastasised SFT treated with cytoreductive surgery and intraperitoneal chemotherapy.
This study reports a case of a SFT of the peritoneum in a 44-year-old white man that recurred 3 years after the initial surgical removal of the tumour. The patient recurred diffusely, developing a pattern of sarcomatosis and hepatic metastasis and was treated by surgical cytoreduction followed by intraoperative peritoneal hyperthermic chemotherapy (IPHC). Subsequently, he developed pulmonary metastases and was treated with palliative chemotherapy. The patient persisted with recurrent and distant disease, although it was reduced and stabilised, allowing his survival for the last 3 years since the extended surgery. New treatment strategies for a rare disease such as this one have first to be described in order to improve patient follow-up.


A3 CLNN: Spatial, Spectral and Multiscale Attention ConvLSTM Neural Network for Multisource Remote Sensing Data Classification.
The problem of effectively exploiting the information multiple data sources has become a relevant but challenging research topic in remote sensing. In this article, we propose a new approach to exploit the complementarity of two data sources: hyperspectral images (HSIs) and light detection and ranging (LiDAR) data. Specifically, we develop a new dual-channel spatial, spectral and multiscale attention convolutional long short-term memory neural network (called dual-channel A3 CLNN) for feature extraction and classification of multisource remote sensing data. Spatial, spectral, and multiscale attention mechanisms are first designed for HSI and LiDAR data in order to learn spectral- and spatial-enhanced feature representations and to represent multiscale information for different classes. In the designed fusion network, a novel composite attention learning mechanism (combined with a three-level fusion strategy) is used to fully integrate the features in these two data sources. Finally, inspired by the idea of transfer learning, a novel stepwise training strategy is designed to yield a final classification result. Our experimental results, conducted on several multisource remote sensing data sets, demonstrate that the newly proposed dual-channel A 3 CLNN exhibits better feature representation ability (leading to more competitive classification performance) than other state-of-the-art methods.


Anticoagulant-free Genius haemodialysis using low molecular weight heparin-coated circuits.
Regional citrate anticoagulation or saline flushes are often used in haemodialysis patients at high risk of bleeding. In an alternative approach we evaluated the effects of covalent circuit coating with low molecular weight heparin (LMWH) for intermittent haemodialysis. In vitro, we compared the thrombogenicity of an uncoated polyvinylchloride (PVC) tubing set with LMWH-coated tubing (AOThel) and a reference tubing with end-point attached heparin coating (Carmeda Bioactive surface) under dynamic blood contact. In vivo, five chronic haemodialysis patients were studied using the Genius dialysis system and F60S filters. Each patient underwent three dialysis sessions separated by a standard haemodialysis each: (1) standard dialysis (uncoated circuit and regular dalteparin dosage), (2) dialysis with LMWH-coated circuit and regular dalteparin dosage and (3) dialysis with a completely LMWH-coated circuit without anticoagulant use. In vitro, both coated tubings showed significantly reduced thrombin-antithrombin (TAT) complex levels compared with PVC. The reference coating (Carmeda) released substantial antifactor Xa (antiXa) activity into the plasma. The LMWH coating (AOThel) released low antiXa activity only during the initial rinsing. In vivo, all dialysis sessions were well tolerated and completed without major clotting. Antithrombin levels and platelet counts were similar in all groups. P-selectin and D-dimer levels increased similarly in all groups. TAT levels were comparable in all groups during the first 3 h and significantly increased in the anticoagulant-free group after the fourth hour. LMWH surface coating reduces thrombogenicity in vitro without releasing significant amounts of heparin from the surface. In vivo, anticoagulant-free haemodialysis using a completely LMWH-coated circuit is feasible and safe in stable chronic dialysis patients with normal coagulation.


Air-liquid biofilm formation is dependent on ammonium depletion in a Saccharomyces cerevisiae flor strain.
Air-liquid biofilm formation appears to be an adaptive mechanism that promotes foraging of Saccharomyces cerevisiae flor strains in response to nutrient starvation. The FLO11 gene plays a central role in this phenotype as its expression allows yeast cells to rise to the liquid surface. Here, we investigated the role of ammonium depletion in air-liquid biofilm formation and FLO11 expression in a S. cerevisiae flor strain. The data obtained show that increasing ammonium concentrations from 0 to 450 m m reduce air-liquid biofilm in terms of biomass and velum formation and correlate with a reduction of FLO11 expression. Rapamycin inhibition of the TOR pathway and deletion of RAS2 gene significantly reduced biofilm formation and FLO11 expression. Taken together, these data suggest that ammonium depletion is a key factor in the induction of air-liquid biofilm formation and FLO11 expression in S. cerevisiae flor strains.


Radial Shaft Reconstruction With an Intercalary Endoprosthesis Following Resection of Metastatic Tumor.
Improvements in imaging and treatment of musculoskeletal tumors have increased the variety of options for reconstruction following joint-sparing diaphyseal resection. The purpose of this case series was to show that reconstruction of malignant tumors of the radial shaft with an intercalary prosthesis may be an option for patients with segmental bone loss. Three consecutive patients underwent wide resection of the radial diaphysis followed by reconstruction with a custom intercalary prosthesis. A custom intercalary prosthesis with lap joint design was used in all 3 cases. Mean follow-up was 18 months (range, 9-25 months). All patients were weight bearing as tolerated 1 week postoperatively. At the most recent follow-up, patients' mean elbow flexion and extension arc was 137° (range, 130°-140°). At the forearm, mean supination was 60° (range, 30°-90°) and mean pronation was 70° (range, 60°-90°). At the wrist, mean palmar flexion was 80° (range, 70°-90°) and mean dorsiflexion was 80° (range, 70°-90°). All patients reported minimal to no pain and no significant functional limitations. Mean Musculoskeletal Tumor Society score was 26/30 (87%). Reconstruction with an intercalary prosthesis is a viable option for patients with metastatic disease of the radial shaft. All patients had satisfactory results and early return to function; none required return to the operating room. Possible advantages of reconstruction with an intercalary prosthesis compared with reconstruction with a bone graft or polymethylmethacrylate osteosynthesis include early return to function and minimal weight-bearing restrictions postoperatively. [Orthopedics. 2017; 40(2):e242-e247.].


HIV-1 indicator cell lines.
A simple quantitative bioassay for infectious HIV-1 has been developed. The assay is based on adherent CD4+ HeLa cell lines stably transfected with episomal vectors carrying the Escherichia coli beta-galactosidase gene under the control of the HIV long terminal repeat (LTR) promoter. HIV infection of these cell lines transactivates the LTR promoter inducing beta-galactosidase production. Infected cells and virus foci can be stained dark blue by the addition of the chromogenic substrate X-Gal. Alternatively, a readily automatable quantitative enzyme assay can be performed on the infected cultures. Because of its simplicity the bioassay may be useful for routine quantification of HIV-infected cultures, plaque purification, virus neutralization studies and for the screening of antiviral agents.


[Myeloid sarcoma in uterine leiomyoma].
In this case report we present a 44-year-old woman with a 2-weekhistory of vaginal bleeding. Gynaecological examination revealed the presence of a polypoid neoformation in the endometrial cavity with a maximum diameter of 4 cm. Histological analysis showed a classic leiomyoma infiltrated by a second monomorphic, highly undifferentiated neoplasia. Immunohistochemical analysis revealed a negative reaction for cytokeratin, CD10, inhibin, CD99, CD20, CD3, TdT and CD34, and positivity for CD45, MPO, CD68 and CD117. A diagnosis of myeloid sarcoma in myometrial leiomyoma was made. The following days the patient showed the onset of an acute myeloid leukaemia M5a. Forty days after diagnosis the patient died for complications related to immunodeficiency caused by therapy. Especially when a common antibody panel reveals negativity for epithelial, mesenchymal and lymphoid markers, this case underlines the importance of considering myeloid sarcoma in differential diagnosis of undifferentiated tumours arising in an extramedullary site in order to avoid errors and permit optimal therapeutic management.


A study of the relationship among body position, bladder function and urine variables in spinal cord injured subjects.
Clinical observations of nurses working with spinal cord patients describe positional changes affecting diuresis. Research has not documented this phenomenon in detail. Knowledge of the timing of diuresis may allow more control over bladder management. The purpose of this descriptive pilot study was to determine the relationship among body position, timing of diuresis, urine volume, and fluid intake in spinal cord injured subjects. A convenience sample of six subjects with varying levels of spinal cord injury were studied. For five consecutive days, positional changes were determined during bed, wheelchair, and tilt activities. Fluid intake and urine volume, specific gravity, and colony count were measured. Data analysis using correlation and regression statistics revealed head and foot elevation and fluid intake may account for some variance but do not predict total variance in urine output. Future research to validate findings in a controlled setting may provide a scientific basis for bladder management.


Circumstances and Consequences of Violence-Related Injuries Presenting at Hospital. A Study at the Pediatric Emergency and Forensic Medicine Units of Maputo Central Hospital, Mozambique.
Rates of violence against children are high in Sub-Saharan Africa and information is scarce on the resulting injuries. This study investigates sex-related differences in the circumstances and consequences of sexual and physical violence in the Mozambican context. Hospital records from 2019 at the pediatric emergency and forensic medicine units of Maputo Central Hospital were scrutinized using a standardized form. Of the 321 cases identified, 60% resulted from sexual violence. Girls represented 86.4% of the victims of sexual violence and boys, 66.1% of those from physical violence. Being injured in a familiar environment and by a parent, a relative, or someone known was strikingly common. The injury pattern varied by form of violence and sex of the child. About half of the injuries sustained by physical violence were minor/superficial. Severe injuries requiring hospitalization (33% in total) and some specialized care (27% in total) were mainly sustained by girl victims of sexual violence. While circumstances and consequences of violence-related injuries have several similarities, being severely injured is more typical of girl victims of sexual violence. Besides medical care, hospital services in Mozambique must be prepared to offer pediatric victims of violence the necessary social care.


Dispersive Liquid-Liquid Semi-Microextraction of Сu(II) with 6,7-dihydroxy-2,4-diphenylbenzopyrylium Chloride for its Spectrophotometric Determination.
A novel dispersive liquid-liquid semi-microextraction (DLLsME) procedure for copper(II) preconcentration is proposed. The system containing copper(II) and 6,7-dihydroxy-2,4-diphenylbenzopyrylium chloride (DHDPhB), after addition a mixture of chloroform and methanol becomes cloudy and the formation of the organic phase was observed immediately. The optimal conditions of DLLsME were found to be: pH 5, absorption band maximum was 570 nm, 1 cm3 of 1×10-3 mol/dm3ofDHDPhB, and mixed extractant containing 1 cm3 of chloroform and 1 cm3 of methanol. Under optimal conditions, the calibration plot was linear in the range of copper(II) concentration 4.32-65 µg/dm3 and the limit of detection was 1.29 µg/dm3. The rocks and tap water samples were successfully analyzed according to the suggested procedure with RSD no more than 4.9%.


Carbon monoxide induces relaxation of human internal thoracic and radial arterial grafts.
Carbon monoxide is produced by the degradation of heme by intracellular heme-oxygenase. The aim of our study was to evaluate, in vitro, the vasodilating effect of carbon monoxide and its mechanisms of action on human internal thoracic and radial artery grafts. Segments of human internal thoracic artery and radial artery, obtained from isolated coronary artery bypass surgery patients, were studied in organ chambers. The arterial rings were precontracted with norepinephrine then submitted to carbon monoxide. Inhibitors of nitric oxide synthase and of soluble guanylate cyclase were added to some arterial rings. Carbon monoxide induced significant relaxation in precontracted human internal thoracic artery and radial artery rings. This relaxation was independent of the presence of functional endothelium in internal thoracic artery. Blocking soluble guanylate cyclase partially inhibited this relaxation, while blocking nitric oxide synthase had no effect. Carbon monoxide has a relaxing effect on human internal thoracic artery and radial artery grafts in vitro, partially via cyclic guanylate monophosphate (cGMP) pathway activation. Inducing carbon monoxide production at the cellular level in vivo in human arterial grafts might help prevent vasospasm.


[Roles of nuclear receptors in the gene expression of drug-metabolizing enzymes under various physiological conditions].
The nuclear receptor constitutive androstane receptor (CAR), a key transcription factor for the expression of cytochrome P450 (CYP) 2B genes, resides in the cytoplasm under untreated conditions and translocates into the nucleus upon xenobiotic exposure. CAR forms a multiprotein complex including heat shock protein 90 in the cytoplasm as the glucocorticoid receptor, and it is likely that protein phosphatase 2A plays a critical role in the first step of CAR nuclear translocation. In addition to the xenobiotic induction of CYP2Bs, our recent studies have indicated that CAR is important for sex and strain differences and obesity/diabetes-associated changes in the expression of CYP2B genes. These results have raised the hypothesis that the expression of nuclear receptors varies depending on the physiologic condition, leading to the dysregulation of CYP expression. In obese mice fed a high-fat diet, however, hepatic CYP3A levels are drastically decreased without any significant changes in the expression of nuclear receptors including the pregnane X receptor and hepatocyte nuclear factor-4, which are known to be key transcription factors in the expression of CYP3A genes. These results indicate that it is important to investigate the mechanism of the transcriptional regulation of nuclear receptor genes as well as the activation of nuclear receptors to understand the CYP expression system fully.


[Valvular heart disease in patients with anti-phospholipid syndrome].
Anti-phospholipid antibodies (APA) may involve heart and valvular heart disease seems to be the most common clinical manifestation. To study the prevalence and characteristics of valvular heart disease in a large patient population with anti-phospholipid syndrome (APS) and also to analyze the clinical and immunological profile of patients with valvular involvement compared with those without involvement. Patients and methods. Retrospective analysis of 113 patients diagnosed of APS. Eighty-one percent were females and the mean age was 39 years (SD:14). Sixty-two percent of patients were diagnosed of primary APS (70 patients) and the remaining 38% (43 patients) corresponded to patients with APS associated with systemic lupus erythematosus (SLE). The median follow-up of patients was 55 months (range: 7-144 months). The cardiologic assessment was performed by means of transthoracic echocardiogram. The study of anti-lupus anticoagulant (AL) was performed by means of coagulometric assays and measurement of anticardiolipin antibodies (aCL), anti-beta2 glycoprotein I (abeta2-PGI) and anti-prothrombin (aPT) by ELISA. The prevalence of valvular heart disease was 19%. The mitral valve was mostly involved (91%) and the most common structural abnormality corresponded to mitral insufficiency. Valvular replacement was required in 24% of patients. In the subgroup of patients with valvular heart disease, a significantly higher prevalence was observed in the following parameters: total thrombosis (71% versus 49%; p = 0.05), arterial thrombosis (57% versus 23%; p = 0.002), stroke (38% versus 13%; p = 0.01), trombocitopenia (71% versus 45%; p = 0.02), hemolytic anemia (29% versus 9%; p = 0.02), and livedo reticularis (48% versus 3%; p < 0.0001). As for immunological differences, only a higher prevalence of LA was found (81% versus 59%; p= 0.04) and abeta2-GPI (IgG isotype) (43% versus 22%; p = 0.05) in patients with valvular heart disease. Valvular heart disease is more frequent in pa-tients with APS and mitral insufficiency is the most common lesion. In a patient with the diagnosis of APS, an echocar-digram should be obtained in his/her initial assessment and regular controls should be obtained in the follow-up.


Mechanosensitive Channel Currents Recorded in Rat Brain Microvascular Endothelial Cells with Whole-cell Mode.
Using the whole-cell patch-clamp technique, delayed outward currents were recorded in rat brain microvascular endothelial cells(RBMECs), which were nearly completely inhibited by extracellular TEA-Cl at a concentration of 20 mmol/L. Whole-cell currents were elicited by 2 100 ms depolarizing voltage pulses applied every 7 s between -100 mV to +90 mV, with 10 mV increment, from a holding potential of -100 mV. The currents were similar with delayed rectified K(+) currents (IKv)which were inhibited in a concentration-dependent manner by both application of TEA-Cl, with an IC(50) approximately 2.0 mmol/L. In the presence of mechanical force, outward currents were increased in amplitude as compared with controls. These mechanical force-induced currents were also defined as IKv, which were different from previous described mechanosensitive currents induced by mechanical force with characteristic of inward rectifier.


Maternal chronic infection as a risk factor in preterm low birth weight infants: the link with periodontal infection.
In the past decade, there has been mounting scientific evidence suggesting that periodontal disease may play an important role as a risk factor for adverse pregnancy outcomes. This article focuses on the definition, incidence, risk factors associated with preterm low birthweight infants (PLBW), the evidence linking chronic infections and PLBW, and the scientific evidence linking periodontal infections with adverse pregnancy outcomes. Additionally, this review summarizes the current epidemiological studies on the PLBW/infection relation and makes conclusions based on these results. Data from a limited number of studies available support the hypothesis that periodontal disease may act as a risk factor for PLBW infants. The fetal exposure to different periodontal pathogens needs to be confirmed, the mechanisms associated with the potential passage of periodontal bacteria across the placental barrier, and the efficacy of different periodontal treatments in reducing the risk for PLBW need to be studied further.


An emergency pursuit game: a method for teaching emergency decision-making skills.
Continuing education programs are used to enhance nurses' emergency decision-making knowledge and skills. Often, these programs are viewed as necessary but boring. An Emergency Pursuit game was developed to provide a novel, challenging, motivating, and cost-effective teaching/learning method. The game is played by teams of nurses who compete for points by answering questions concerning emergency drugs, cardiac arrhythmias, emergency policies and procedures, and non-arrest medical emergencies. Many benefits are realized from a continuing educational program using the Emergency Pursuit game. Of greatest importance is the improved proficiency and performance by nurses during clinical emergency situations.


[Effects of exposure to altitude on neuropsychology aspects: a literature review].
Discuss the effects of altitude exposure on neuropsychological functions. We have conducted a literature review using as source indexed articles at Pubmed in the period from 1921 to 2008, using the following key words: 'cognition and hypoxia', 'hypoxia and neuropsychology', 'acute hypoxia', 'chronic hypoxia', and 'acclimatization and hypoxia', as well as specific books on the subject. Acute and chronic effects of Hypoxia can alter many of the neuropsychological functions in different altitudes due to physiological changes resulted by the oxygen (O2) partial decrease that can lead to neuropsychological alterations in individuals exposed to high altitudes. Individuals exposed to high altitudes must use an O2 supplementation and the practice of acclimatization, among other strategy ways that can be used in order to minimize the negative effects of hypoxia on neuropsychological aspects.


A Straight Skeleton Based Connectivity Restoration Strategy in the Presence of Obstacles for WSNs.
Connectivity has significance in both of data collection and aggregation for Wireless Sensor Networks (WSNs). Once the connectivity is lost, relay nodes are deployed to build a Steiner Minimal Tree (SMT) such that the inter-component connection is reestablished. In recent years, there has been a growing interest in connectivity restoration problems. In previous works, the deployment area of a WSN is assumed to be flat without obstacles. However, such an assumption is not realistic. In addition, most of the existing strategies chose the representative of each component, which serves as the starting point of relay node deployment during the connectivity restoration, either in a random way or in the shortest-distance based manner. In fact, both ways of representative selection could potentially increase the length of the SMT such that more relay nodes are required. In this paper, a novel connectivity restoration strategy is proposed-Obstacle-Avoid connectivity restoration strategy based on Straight Skeletons (OASS), which employs both the polygon based representative selection with the presence of obstacles and the straight skeleton based SMT establishment. The OASS is proved to be a 3- o p t approximation algorithm with the complexity of O ( n log n ) , and the approximation ratio can reduce to 3 3 2 while it satisfies a certain condition. The theoretical analysis and simulations show that the performance of the OASS is better than other strategies in terms of the relay count and the quality of the established topology (i.e., distances between components, delivery latency and balanced traffic load) as well.


Thrombomodulin promotes focal adhesion kinase activation and contributes to angiogenesis by binding to fibronectin.
Angiogenesis promotes tumor growth and metastasis. Cell adhesion molecules interact with the extracellular matrix (ECM) and increase cell adhesion and migration during angiogenesis. Thrombomodulin (TM) is a cell surface transmembrane glycoprotein expressed in endothelial cells. However, the function and significance of TM in cell-matrix interactions and angiogenesis remain unclear. Here, we first demonstrated that recombinant lectin-like domain of TM interacts with an ECM protein, fibronectin, and identified the N-terminal 70-kDa domain of fibronectin as the TM-binding site. Exogenous expression of TM in TM-deficient A2058 melanoma cells enhanced cell adhesion and migration on fibronectin and invasion on Matrigel. In addition, TM increased focal adhesion kinase (FAK) phosphorylation and matrix metalloproteinase-9 production. In mice bearing subcutaneous B16F10 melanoma tumors, immunofluorescence analysis indicated that TM was highly expressed and co-localized with fibronectin on the tumor vasculature. The interaction between TM and fibronectin in tumor blood vessels was also validated by the proximity ligation assay. In human umbilical vein endothelial cells, up-regulation of TM by vascular endothelial growth factor (VEGF), a tumor angiogenic factor, promoted cell adhesion and tube formation, whereas TM knockdown by RNA interference attenuated VEGF-induced cell adhesion and tube formation. In summary, TM promotes angiogenesis by enhancing cell adhesion, migration, and FAK activation through interaction with fibronectin. TM may represent a novel target for inhibiting tumor angiogenesis.


Letrozole Versus Clomiphene Citrate and Natural Cycle: Endometrial Receptivity During Implantation Window in Women With Polycystic Ovary Syndrome.
Numerous studies have reported on ovulation and pregnancy rates in patients with polycystic ovary syndrome (PCOS). However, relevant data on endometrial receptivity are limited. This study was conducted to compare endometrial receptivity during implantation windows among letrozole (LE), clomiphene citrate (CC), and natural cycle, and to assess the predictive value for pregnancy of observed indicators. This randomized controlled trial study enrolled 270 patients with PCOS. Patients were given LE (n=90) at a dose of 2.5mg/day or CC (n=90) at a dose of 50 mg/day on cycle days 5-9 for ovulation induction. Patients in the natural cycle group (n=90) did not receive any drug for ovulation induction. Endometrial ultrasonic parameters, integrin αvβ3, and vascular endothelial growth factor (VEGF) concentrations in uterine secretion were detected during the implantation window. The endometrial receptivity, ovulation rate, pregnancy rates, and predictive value of observed indicators for pregnancy were analyzed. The successful ovulation rate did not differ between the LE group and CC group (P>0.05). Endometrial ultrasonic parameters [endometrial thickness (ET), endometrial volume (EV), vascularization index (VI), flow index (FI), vascularization flow index (VFI)], integrin αvβ3, and VEGF concentrations in uterine fluid were significantly higher in the LE group compared with the CC group and natural cycle group (P<0.05). The clinical pregnancy and ongoing pregnancy rates of the LE group were significantly higher than in the CC group (P<0.05). Endometrial ultrasonic parameters (VI, FI, and VFI), integrin αvβ3, and VEGF concentrations in uterine fluid of all pregnancy groups were significantly higher compared with the no pregnancy group (P<0.05), and the above parameters in ongoing pregnancy were significantly higher than in biochemical pregnancy (P<0.05). The endometrial FI during the implantation window had the highest predictive value for pregnancy (AUC=0.889). The integrin αvβ3 in uterine fluid had better predictive value (AUC=0.876) than VEGF. Endometrial receptivity during the implantation window of LE is superior to CC in PCOS women, which may be related to higher clinical pregnancy and ongoing pregnancy rates. Endometrial FI examined by 3-D power Doppler, and integrin αvβ3 in uterine secretion during the implantation window, could be preferable non-invasive predictor markers for pregnancy. www.chictr.org.cn, ChiCTR1900023423.


Seroprevalence of Trypanosoma cruzi in kidney transplant donors and recipients in Mexico City.
Infectious diseases are common causes of morbidity and mortality among kidney transplant recipients. Chagas disease (CD) has been recognized as an emerging infectious complication of transplantation caused by the parasite Trypanosoma cruzi. CD is prevalent in Mexico, particularly in the southern coastal region. The impact on Mexican kidney transplant programs has not been previously studied prospectively. From 2009 through 2010, serum samples from 59 kidney transplant donors and 405 renal transplant recipients were screened for antibodies against T. cruzi. Serum was initially screened using a locally developed ELISA test; positive results were confirmed by an indirect immunofluorescense test, in accordance with Panamerican Health Organization/World Health Organization guidelines. None of the donors were seropositive for T. cruzi, while 8 (1.97%) kidney transplant recipients were confirmed to be seropositive for T. cruzi. None of them have developed clinical manifestations of CD, although specific screening of recipients was not performed. A prospective study is planned to define the epidemiology and outcome of CD among kidney transplant donors and recipients in Mexico more thoroughly.


Factors Associated with Disposable Menstrual Absorbent Use Among Young Women in India.
Hygienic use of absorbent products during menstruation is a challenge for young women in India, especially among the underprivileged, who lack knowledge and access to resources. Reuse of menstrual absorbents can be unhygienic and result in adverse health and other outcomes. Data from the 2015-2016 National Family Health Survey-4 for 233,606 menstruating women aged 15-24 were used to examine levels and correlates of exclusive use of disposable absorbents during menstruation. Bivariate and logistic regression analyses were conducted to identify disparities in exclusive use by such characteristics as caste, mass media exposure and interaction with health workers. Exclusive use of disposable absorbents was low among young women overall (37%), and varied substantially by caste and other characteristics. Compared with women from general castes, those from scheduled castes, scheduled tribes and other backward classes had reduced odds of exclusive disposable absorbent use (odds ratios, 0.8-0.9). Disposable absorbent use was negatively associated with lower levels of education and household wealth, and rural residence. Compared with women who reported daily media exposure, those exposed less frequently had reduced odds of disposable absorbent use (0.7-0.9). Among those who recently met with a health worker, odds of use were lower if menstrual hygiene had not been discussed (0.9). Promoting awareness of proper menstrual hygiene-through education, media campaigns and discussion with reproductive health workers-and targeted interventions to disseminate and subsidize the purchase of disposable sanitary napkins should be pursued to address health disparities.


Commentary: Oversight of engineered nanomaterials in the workplace.
Research and business investment in emerging nanotechnologies is leading to a diverse range of new substances and products. As workers are faced with handling new materials, often with novel properties, the robustness of current workplace health and safety regulatory frameworks is being brought into question. Here, 12 characteristics of the U.S. occupational safety regulatory framework identified by Choi and Ramachandran are considered in the context of emerging nanotechnologies. The assessment suggests that, as the number of new materials entering the workplace continues to increase, OSHA will need to develop flexible approaches to identifying and reducing potential risks. Relying on conventional approaches in the face of unconventional challenges will increase the probability of otherwise avoidable heath impacts. If the potential for engineered nanomaterials to cause harm is to be understood and managed, the agency will need to look at new approaches to generating, sharing, and using information.


Cryptococcus neoformans VNII as the Main Cause of Cryptococcosis in Domestic Cats from Rio de Janeiro, Brazil.
Cryptococcosis is a systemic fungal disease acquired from contaminated environments with propagules of the basidiomycetous yeasts of the Cryptococcus neoformans and C. gattii species complexes. The C. neoformans species complex classically comprises four major molecular types (VNI, VNII, VNIII, and VNIV), and the C. gattii species complex comprises another four (VGI, VGII, VGIII, and VGIV) and the newly identified molecular type VGV. These major molecular types differ in their epidemiological and ecological features, clinical presentations, and therapeutic outcomes. Generally, the most common isolated types are VNI, VGI, and VGII. The epidemiological profile of cryptococcosis in domestic cats is poorly studied and cats can be the sentinels for human infections. Therefore, the present study aimed to determine the molecular characterization of Cryptococcus spp. isolated from domestic cats and their dwellings in the metropolitan area of Rio de Janeiro, Brazil. A total of 36 Cryptococcus spp. strains, both clinical and environmental, from 19 cats were subtyped using multilocus sequence typing (MLST). The ploidy was identified using flow cytometry and the mating type was determined through amplification with specific pheromone primers. All strains were mating type alpha and 6/36 were diploid (all VNII). Most isolates (63.88%) were identified as VNII, a rare molecular type, leading to the consideration that this genotype is more likely related to skin lesions, since there was a high percentage (68.75%) of cats with skin lesions, which is also considered rare. Further studies regarding the molecular epidemiology of cryptococcosis in felines are still needed to clarify the reason for the large proportion of the rare molecular type VNII causing infections in cats.


Optical vortex knots - one photon at a time.
Feynman described the double slit experiment as "a phenomenon which is impossible, absolutely impossible, to explain in any classical way and which has in it the heart of quantum mechanics". The double-slit experiment, performed one photon at a time, dramatically demonstrates the particle-wave duality of quantum objects by generating a fringe pattern corresponding to the interference of light (a wave phenomenon) from two slits, even when there is only one photon (a particle) at a time passing through the apparatus. The particle-wave duality of light should also apply to complex three dimensional optical fields formed by multi-path interference, however, this has not been demonstrated. Here we observe particle-wave duality of a three dimensional field by generating a trefoil optical vortex knot - one photon at a time. This result demonstrates a fundamental physical principle, that particle-wave duality implies interference in both space (between spatially distinct modes) and time (through the complex evolution of the superposition of modes), and has implications for topologically entangled single photon states, orbital angular momentum multiplexing and topological quantum computing.


Security Control of Multiagent Systems Under Denial-of-Service Attacks.
Security control aims to guarantee the consensus of multiagent systems (MASs) in the presence of the denial-to-service attacker. Most of the existing distributed controllers are invalid during the attack interval due to the paralyzed communication channels. In order to overcome this difficulty, a novel hybrid distributed control protocol is designed. Here, the controller uses the latest information saved in the buffers in the presence of malicious attacks, which will further enhance the security of MASs. Some sufficient conditions on the coupled strength and attack parameters are derived to achieve the leader-following consensus of MASs. Furthermore, we estimate the upper bounds of denial-of-service (DoS) frequency and DoS duration which the MASs can tolerate before losing consensus. Notice that we also reduce the computational complexity via the property of the Kronecker product. Besides, an observer-based model is proposed and the corresponding consensus criterion is established to reduce the effects of attackers on the controller. Finally, the efficiency of our theoretical results is illustrated by a numerical example.


Effect of whey storage on biogas produced by co-digestion of sewage sludge and whey.
Biogas production from municipal anaerobic digesters could potentially be boosted via co-digestion with organic wastes such as whey. The challenge is that whey production is seasonal. This research examined the effect of storing whey at ambient temperature on: (1) whey composition; (2) biogas production from co-digestion of the stored whey with municipal primary sludge. Whey storage resulted in acidification with formation of acetate, propionate and butyrate and a 9% reduction in total chemical oxygen demand (COD) over the 9-month trial. A control digester fed with primary sludge produced 0.18-0.23 m3 CH4/kgCOD(added). Co-digestion of fresh whey and sludge increased biogas production and the methane contribution from the whey was 0.29 m3CH4/kgCOD(added). When the fresh whey was substituted with stored whey, methane production by the whey remained at 0.29 m3CH4/kgCOD(added). The ability to store whey at ambient temperature and allow co-digestion year round will significantly improve the economics of biogas production from whey.


Moiré structures in twisted bilayer graphene studied by transmission electron microscopy.
We investigate imaging of moiré structures in free-standing twisted bilayer graphene (TBG) carried out by transmission electron microscopy (TEM) in diffraction and in-line Gabor holography modes. Electron diffraction patterns of TBG acquired at typical TEM electron energies of 80-300 keV exhibit the diffraction peaks caused by diffraction on individual layers. However, diffraction peaks at the scattering angles related to the periodicity of the moiré structure have not been observed in such diffraction patterns. We show that diffraction on moiré structure can create intense diffraction peaks if the energy of the probing electrons is very low, in the range of a few tens of eV. Experimental diffraction patterns of TBG acquired with low-energy electrons of 236 eV exhibiting peaks attributed to the moiré structure periodicity are shown. In holography mode, the intensity of the wave transmitted through the sample and measured in the far-field can be enhanced or decreased depending on the atomic arrangement, as for example AA or AB stacking. Thus, a decrease of intensity in the far-field must not necessarily be associated with some absorption inside the sample but can simply be a result of a particular atomic arrangement. We believe that our findings can be important for exploiting graphene as a support in electron imaging.


Stunted growth and mortality associated with sodium deficiency.
We investigated reports of stunted growth and high mortality occurring among young poultry in 38 small privately owned flocks in Vermont and New Hampshire. Tests for infectious agents including avian influenza and Newcastle disease viruses were negative, as were toxicologic tests for mycotoxins, heavy metals, pesticides, and monensin in feed samples. Analysis of 6 samples of implicated feed revealed 330-870 ppm of sodium (median level 350 ppm), whereas the recommended minimum level for chick feed is 1200-2000 ppm. A case-control study included 38 affected and 23 unaffected flocks. Statistical analysis showed that affected flocks were 29 times more likely to have consumed a particular brand of poultry feed (odds ratio = 29.2, 95% confidence interval = 3.2-675.8) but did not show any association between clinical signs and hatchery, location of chick purchase, chick purchase date, or years of producer experience.