Comparison of surface proteins of Anaplasma marginale grown in tick cell culture, tick salivary glands, and cattle.
Anaplasma marginale, a tick-borne rickettsial pathogen of cattle, infects bovine erythrocytes, resulting in mild to severe hemolytic disease that causes economic losses in domestic livestock worldwide. Recently, the Virginia isolate of A. marginale was propagated in a continuous tick cell line, IDE8, derived from embryonic Ixodes scapularis. Development of A. marginale in cell culture was morphologically similar to that described previously in ticks. In order to evaluate the potential of the cell culture-derived organisms for use in future research or as an antigen for serologic tests and vaccines, the extent of structural conservation of the major surface proteins (MSPs) between the cell culture-derived A. marginale and the bovine erythrocytic stage, currently the source of A. marginale antigen, was determined. Structural conservation on the tick salivary-gland stage was also examined. Monoclonal and monospecific antisera against MSPs 1 through 5, initially characterized against erythrocyte stages, also reacted with A. marginale from cell culture and tick salivary glands. MSP1a among geographic A. marginale isolates is variable in size because of different numbers of a tandemly repeated 28- or 29-amino-acid peptide. The cell culture-derived A. marginale maintained the same-size MSP1a as that found on the Virginia isolate of A. marginale in bovine erythrocytes and tick salivary glands. Although differences were observed in the polymorphic MSP2 antigen between culture and salivary-gland stages, MSP2 did not appear to vary, by two-dimensional gel electrophoresis, during continuous passage in culture. These data show that MSPs of erythrocyte-stage A. marginale are present on culture stages and may be structurally conserved during continuous culture. The presence of all current candidate diagnostic and vaccine antigens suggests that in vitro cultures are a valuable source of rickettsiae for basic research and for the development of improved diagnostic reagents and vaccines against anaplasmosis.


Maternal physical activity, sitting, and risk of non-cardiac birth defects.
The relationship between maternal physical activity (PA)/sitting and birth defects is largely unexplored. We examined whether pre-pregnancy PA/sitting were associated with having a pregnancy affected by a birth defect. We used data from two United States population-based case-control studies: 2008-2011 deliveries from the National Birth Defects Prevention Study (NBDPS; 9 states) and 2014-2018 deliveries from the Birth Defects Study To Evaluate Pregnancy exposureS (BD-STEPS; 7 states). Cases with one of 12 non-cardiac birth defects (n = 3798) were identified through population-based registries. Controls (n = 2682) were live-born infants without major birth defects randomly sampled using vital/hospital records. Mothers self-reported pre-pregnancy PA/sitting. Unconditional logistic regression models estimated associations between PA/sitting categories and the 12 birth defects. Mothers engaging in pre-pregnancy PA was associated with a reduced odds of five (spina bifida, cleft palate, anorectal atresia, hypospadias, transverse limb deficiency) and a higher odds of two (anencephaly, gastroschisis) birth defects. Mothers spending less time sitting in pre-pregnancy was associated with a reduced odds of two (anorectal atresia, hypospadias) and a higher odds of one (cleft lip with or without cleft palate) birth defect. Reasonable next steps include replication of these findings, improved exposure assessment, and elucidation of biologic mechanisms. Using data from two population-based case-control studies, we found that mothers engaging in different types of physical activity in the 3 months before pregnancy had an infant with a reduced odds of five and a higher odds of two birth defects. Mothers spending less time sitting in the 3 months before pregnancy had an infant with a reduced odds of two and a higher odds of one birth defect. Clarification and confirmation from additional studies are needed using more precise exposure measures, distinguishing occupational from leisure-time physical activity, and elucidation of mechanisms supporting these associations.


Relapsing Kawasaki's disease.
An 18-month-old child with Kawasaki syndrome twice developed severe recurrence of symptoms when the acetylsalicylic acid (Aspirin) dosage was decreased from 80 mg/kg/day. Care of the patient with Kawasaki disease should be directed toward control of symptoms as well as monitoring for cardiac involvement.


Trends of robotic-assisted surgery for thyroid, colorectal, stomach and hepatopancreaticobiliary cancer: 10 year Korea trend investigation.
The current position of robotic surgery in the field of minimally invasive surgery remains ambiguous. We evaluated long-term trends of robotic general surgery and the future direction of its development. Data on robotic cancer surgeries between 2005 and 2014 were retrospectively collected by volunteer institutions in the Republic of Korea. Spearman's correlation and logistic regression analyses were used to compare robotic and laparoscopic surgery trends in general surgery. The odds that robotic surgery was performed instead of laparoscopic surgery significantly decreased in the fields of colorectal, stomach, and hepato-biliary-pancreatic surgery (odds ratio [OR]: 0.95, 95% confidence interval [CI]: 0.93-0.97; OR: 0.90, 95% CI: 0.88-0.92; and OR: 0.71, 95% CI: 0.65-0.78, respectively), except for thyroid surgery (OR: 1.28, 95% CI: 1.25-1.30). Of the total numbers of each procedure, proportions of robotic intersphincteric resections, abdominoperineal resections, and pylorus-preserving surgery performed significantly increased (r = 0.98, P < .001; r = 0.78, P = .01; and r = 0.86, P = .007, respectively). The use of robotic surgery failed to preponderate that of laparoscopic surgery, except for thyroid surgery. Robotic surgery is increasingly preferred for limited fields or complex surgeries, but the use of robotics in simple surgeries has decreased.


Aortic sinotubular junction calcium as a marker of severe aortic atherosclerosis.
Because the significance of calcification of the sinotubular junction is poorly understood, we retrospectively investigated its association with aortic atherosclerosis in 101 patients who underwent transesophageal echocardiography. Such calcification was found to be a marker of more severe aortic atherosclerosis and, specifically, aortic arch disease.


Near-isothermal conditions in the middle and lower crust induced by melt migration.
The thermal structure of the crust strongly influences deformation, metamorphism and plutonism. Models for the geothermal gradient in stable crust predict a steady increase of temperature with depth. This thermal structure, however, is incompatible with observations from high-temperature metamorphic terranes exhumed in orogens. Global compilations of peak conditions in high-temperature metamorphic terranes define relatively narrow ranges of peak temperatures over a wide range in pressure, for both isothermal decompression and isobaric cooling paths. Here we develop simple one-dimensional thermal models that include the effects of melt migration. These models show that long-lived plutonism results in a quasi-steady-state geotherm with a rapid temperature increase in the upper crust and nearly isothermal conditions in the middle and lower crust. The models also predict that the upward advection of heat by melt generates granulite facies metamorphism, and widespread andalusite-sillimanite metamorphism in the upper crust. Once the quasi-steady-state thermal profile is reached, the middle and lower crust are greatly weakened due to high temperatures and anatectic conditions, thus setting the stage for gravitational collapse, exhumation and isothermal decompression after the onset of plutonism. Near-isothermal conditions in the middle and lower crust result from the thermal buffering effect of dehydration melting reactions that, in part, control the shape of the geotherm.


Complementary and alternative medicine use among patients attending a hospital dermatology clinic in Taiwan.
Recent studies have indicated that complementary and alternative medicine (CAM) has been gaining popularity around the world. Previous studies showed that CAM use was common among dermatology patients in Western nations. This study presents the prevalence and types of CAM use among a group of patients in a dermatology clinic in Taiwan. A convenient sample of 198 patients was recruited from the dermatology clinic of Show Chwan Memorial Hospital in Changhua City, Taiwan. Each patient completed a standardized questionnaire. Chi-square tests were used to compare the demographic characteristics of those who did and did not use CAM. Logistic regression analyses were performed to determine the strength of association between correlate variables and CAM use. Forty-one per cent of subjects had used CAM to treat their dermatological conditions. Subjects in the younger (< 30 years) and older (> 50 years) age groups were more likely to use CAM than those in the 30-50-year age group. Those that participated in religious or social groups were more likely to use CAM. CAM users felt a more negative impact of their dermatological conditions on daily living, relationships, emotional well-being and physical health. As in Western nations, CAM use is prevalent among dermatology patients in Taiwan: not only the traditionally popular Chinese CAM, but also Western CAM. With CAM being popular in the younger age group, dermatologists will likely encounter more CAM users in the future. Because some CAM may produce serious side-effects, dermatologists need to help and guide patients to assess the benefits and dangers of using CAM to treat dermatological conditions.


Experimental studies on fluid pathophysiology in small intestinal obstruction in the rat. IV. Effects of intraluminal hyperosmolality and simultaneous intravenous infusions on mucosal micromorphology.
A hyperosmolal glucose solution was introduced into a loop of small intestine of specified length and position while intravenous infusions of varying osmolality were given at the same time. The hyperosmolal solution in the lumen caused damage primarily to the tips of the villi where sloughing of the epithelial cells was frequently seen. These defects were repaired by an increase in surface coverage by neighboring epithelial cells, which thus were reduced in height. A varying degree of edema was generally seen in the epithelial cells. The severity of these lesions was modified by intravenous infusions in inverse relationship to the osmolality of the infusions. Thus the defence mounted by the intestinal mucosa against the hyperosmolal solution in the lumen was impaired by the infusion of hypo-osmolal solutions and improved by hyperosmolal solutions. In the latter cases the mucosa maintained a practically normal histological picture.


Modification of catecholamine and prostaglandin tissue levels in E. coli endotoxin-treated rats.
Epinephrine and norepinephrine adrenal levels were depleted in Escherichia coli endotoxin-treated (10 mg/kg) male Wistar rats from 504 +/- 203 to 119 +/- 77 ng/mg in control and from 200 +/- 97 to 123 +/- 66 ng/mg wet wt, respectively. However dopamine increased from 4.2 +/- 1.9 to 14.9 +/- 3.4 ng/mg. After endotoxin administration, norepinephrine content in peripheral organs, heart 1.27 +/- 0.19 ng/mg, spleen 1.52 +/- 0.59 ng/mg, liver 0.15 +/- 0.05 ng/mg, and kidney 0.24 +/- 0.09 ng/mg wet wt. decreased by 34, 36, 47, and 18%, respectively. Indomethacin treatment kept the catecholamine levels constant in endotoxic rats, but naloxone had no effect. PGF2 alpha tissue levels (12.0 +/- 10.1 pg/mg protein in spleen and 1.85 +/- 0.6 pg/mg protein in liver) were increased twofold by endotoxin treatment: PGE2 content in spleen and liver 0.5 +/- 0.2 pg/mg protein and 2.3 +/- 1.9 pg/mg protein, respectively, increased by only 27 and 26%. In the kidneys of endotoxin-treated animals, PGF2 alpha and PGE2 levels were lower than in control. Indomethacin treatment decreased PGF2 alpha and PGE2 and increased the norepinephrine content in the same organs. It is suggested that prostaglandins play a participative role in the control of norepinephrine tissue levels in endotoxemia.


Ureteral carcinoid tumor.
Most ureteral tumors are transitional cell neoplasms. Neuroendocrine tumors of the genitourinary tract are extremely rare. To our knowledge, only one ureteral carcinoid tumor has been reported before. We report a second case of ureteral carcinoid tumor found in a 70-year-old female.


Osteopenia in transgenic mice with osteoblast-targeted expression of the inducible cAMP early repressor.
ICER is a member of the CREM family of basic leucine zipper transcription factors that acts as a dominant negative regulator of gene transcription. Four different isoforms of ICER (I, Igamma, II and IIgamma) are transcribed from the P2 promoter of the Crem gene. We previously found that each of the ICER isoforms is induced by parathyroid hormone in osteoblasts. The goal of the present study was to assess the function of ICER in bone by overexpressing ICER in osteoblasts of transgenic mice. ICER I and ICER II cDNAs, each containing an N-terminal FLAG epitope tag, were cloned downstream of a fragment containing 3.6 kb of the rat Col1a1 promoter and most of the rat Col1a1 first intron to produce pOBCol3.6-ICER I and pOBCol3.6-ICER II transgenes, respectively. Multiple lines of mice were generated bearing the ICER I and ICER II transgenes. At 8 weeks of age, ICER I and ICER II transgenic mice had lower body weights and decreased bone mineral density of femurs and vertebrae. Further studies were done with ICER I transgenic mice, which had greatly reduced trabecular bone volume and a markedly decreased bone formation rate in femurs. Osteoblast differentiation and osteocalcin expression were reduced in ex vivo bone marrow cultures from ICER I transgenic mice. ICER I antagonized the activity of ATF4 at its consensus DNA binding site in the osteocalcin promoter in vitro. Thus, transgenic mice with osteoblast-targeted overexpression of ICER exhibited osteopenia caused primarily by reduced bone formation. We speculate that ICER regulates the activity and/or expression of ATF/CREB factors required for normal bone formation.


Gastric myoelectrical activity in patients with inflammatory bowel disease.
Inflammatory bowel disease is characterized by the presence of gastrointestinal motility disturbances; however alterations in the gastric myoelectrical activity have not been characterized. In this study we have recorded the gastric myoelectrical activity in patients with ulcerative colitis (UC) and Crohn's disease (CD) during their clinical remission. Gastric activity was assessed using electrogastrography (EGG) in patients with UC (n = 60), CD (n = 40) and healthy controls (n = 40). In each case, their response to water load test, as well as the dominant frequency (DF), dominant power (DP) and the power ratio (PR) of the electrical activity were recorded. In healthy controls, the resting DF was 2.57 ± 1.05 cycles per minute (cpm), which decreased after water ingestion (2.34 ± 0.99 cpm; P = 0.001). Compared to healthy controls, patients with UC had low resting DF (bradygastria) (2.57 ± 1.05 vs. 1.86 ± 1.28 cpm; P = 0.01). The change in DF after water ingestion was insignificant in patients with UC and CD. Post-water ingestion, healthy controls exhibited an increase in the DP as compared to the resting state, (7.1 [2.93, 102.56] vs. 15.94 [3.92, 133.41] μV (2); P = 0.02). Patients with UC (1.26 [0.14, 9.83] vs. 3.27 [0.61, 42.12] μV(2)) and CD (2.54 [0.44, 47.06] vs. 15.8 [0.1, 126.68] μV(2)) also showed a significant increase in the DP post-water ingestion. Patients with ulcerative colitis have altered resting gastric myoelectrical activity during the remission phase of the disease.


The role of antibiotic prophylaxis in endoscopic retrograde cholangiopancreatography; a retrospective single-center evaluation.
Endoscopic retrograde cholangiopancreaticography (ERCP) can be complicated by post-ERCP cholangitis even when performed by experienced endoscopists. Therefore, antibiotic prophylaxis is recommended for certain patients, but controversy exists as to which patient groups really benefit from this strategy. We retrospectively evaluated the use of antibiotics in a primary teaching hospital in the Netherlands with regard to the incidence of post-ERCP cholangitis and cholecystitis. Retrospective single-center evaluation in a primary teaching hospital. All consecutive ERCPs between 2000 and 2006 were studied. Primary end point was the incidence of post-ERCP cholangitis and cholecystitis, divided into four categories: definite, likely, possible and unlikely. Additionally, occurrence of complications such as pneumonia, post-ERCP pancreatitis, perforation of the duodenum, substantial bleeding and the need for re-ERCP within 5 days was scored. Five hundred forty ERCPs in 327 patients were screened. Of these, 292 ERCPs performed in 193 patients were included. Eight ERCPs (2.7%) of all ERCPs were followed by definite cholangitis and two ERCPs (0.7%) by likely cholangitis. The occurrence rate of ERCP-related complications remained low. This study shows that with our current policy of restricted use of antibiotic prophylaxis the overall incidence of biliary tract infections is low.


Chemiluminescent screening of specific hybridoma cells via a proximity-rolling circle activated enzymatic switch.
The mass-production capability of hybridoma technology is bottlenecked by the routine screening procedure which is time-consuming and laborious as the requirement of clonal expansion. Here, we describe a 1-day chemiluminescent screening protocol for specific hybridoma cells on conventional 96-well plate via a proximity-rolling circle activated enzymatic switch (P-RCAES) strategy. The P-RCAES uses a pair of antigen-DNA probes to recognize secreted specific antibody and proximity-induce rolling circle amplification for mass-production of pyrophosphate to activate Cu(II) inhibited horseradish peroxidase and generate a strong chemiluminescent signal. The P-RCAES based homogeneous chemiluminescent assay can detect antibody down to 18 fM, and enables the screening of specific hybridoma cells secreting PCSK9 antibody at single-cell level without tedious cloning process. The proposed fast screening protocol has good expansibility without need of sophisticated instruments, and provides a screening method for greatly improving the efficiency of hybridoma technology.


Antimicrobial substances from aspen tissue grown in vitro.
Isolated aspen tissue, when grown in vitro for 3 weeks on agar medium, yielded antimicrobial substances which produced inhibitory zones when the culture plates were inoculated with Fusarium roseum, Saccharomyces cervisiae, Bacillus subtilis, Bacillus cereus, Penicillium, roqueforti, Torula utilis, Sarcina lutea, Flavobacterium aquatile, Pullularia pullulans, and Staphylococcus aureus.


Application of adsorptive stripping voltammetry to the simultaneous determination of bismuth and copper in the presence of nuclear fast red.
A sensitive and selective method for the simultaneous determination of copper and bismuth by adsorptive stripping was developed using nuclear fast red (2-anthracenesulfonic acid, 4-amino-9,10-dihydro-1,3-dihydroxy-9,10-dioxo-, monosodium salt) as selective complexing agent onto hanging mercury drop electrode. In a single scan both metals gave peaks that were distinctly separated by 85 mV allowing their determination in the presence of each other. Optimal analytical conditions were found to be: nuclear fast red concentration of 80 microM, pH of 2.8 and adsorptive potential of -300 mV versus Ag/AgCl. With accumulation time of 180s the peaks currents are proportional to concentration of copper and bismuth over the 1-100 and 5-60 ng mL(-1) range with detection limits of 0.2 and 1.2 ng mL(-1), respectively. The procedure was applied to simultaneous determination of copper and bismuth in some real samples.


The diagnostic value of pneumoperitoneogram for splenomegaly in chronic liver diseases.
The splenic enlargement is an important symptoms of portal hypertension, and various attempts have been made to objectively describe it. But, endoscopic diagnosis for splenomegaly in chronic liver diseases may be sometimes difficult for these uncharacteristic appearances. The pneumoperitoneography was performed in 141 chronic liver diseases just before laparoscopic procedure, size and form of the spleen on X-ray film were measured and analysed. We have compared these results with the laparoscopic findings (the gross appearance of liver and spleen, the degree of portal hypertension, etc), the patterns on scintigram and the histological findings of the liver. There were fairely good correlation between the splenic findings on radiogram and above factors, especially the size of the spleen was gradually increased according to the degree of portal hypertension and the fibrous change of the liver specimens. In conclusion, the findings of spleen on pneumoperitoneogram were valuable for diagnosis of splenomegaly in chronic liver diseases.


Suppression of Polysulfide Dissolution and Shuttling with Glutamate Electrolyte for Lithium Sulfur Batteries.
The lithium sulfur battery is regarded as a potential next-generation high-energy battery system. However, polysulfides dissolve and shuttle through the electrolytes, causing rapid capacity decay, serious self-discharge, and poor high-temperature performances. Here, we demonstrate that by directly introducing glutamate into commercial electrolytes, these issues can be tackled simultaneously. With abundant negatively charged hydroxyl groups, the glutamate additive electrolyte effectively suppresses the shuttling of negatively charged polysulfide ions through strong repulsive interaction up to 1.54 eV. With glutamate additive electrolyte, the lithium sulfur battery has a capacity retention of 60% after 1000 cycles at 5.95 mA/cm2, a self-discharge rate on the order of one-third that of commercial electrolytes, and stable operation at 60 °C.


Innervation from the entorhinal cortex to the dentate gyrus and the vulnerability to Zn2.
Hippocampal Zn2+ homeostasis is critical for cognitive activity and hippocampus-dependent memory. Extracellular Zn2+ signaling is linked to extracellular glutamate signaling and leads to intracellular Zn2+ signaling, which is involved in cognitive activity. On the other hand, excess intracellular Zn2+ signaling that is induced by excess glutamate signaling is involved in cognitive decline. In the hippocampal formation, the dentate gyrus is the most vulnerable to aging and is thought to contribute to age-related cognitive decline. The layer II of the entorhinal cortex is the most vulnerable to neuronal death in Alzheimer's disease. The perforant pathway provides input from the layer II to the dentate gyrus and is one of the earliest affected pathways in Alzheimer's disease. Medial perforant pathway-dentate granule cell synapses are vulnerable to either excess intracellular Zn2+ or β-amyloid (Aβ)-bound zinc, which induce transient cognitive decline via attenuation of medial perforant pathway LTP. However, it is unknown whether the vulnerability to excess intracellular Zn2+ is involved in region-specific vulnerability to aging and Alzheimer's disease. To discover a strategy to prevent short-term cognitive decline in normal aging process and the pre-dementia stage of Alzheimer's disease, the present paper deals with vulnerability of medial perforant pathway-dentate granule cell synapses to intracellular Zn2+ dyshomeostasis and its possible involvement in differential vulnerability to aging and Alzheimer's disease in the hippocampal formation.


Fibronectin inhibits endocytosis of calcium oxalate crystals by renal tubular cells.
Fibronectin (FN; 230 kDa) is a multifunctional alpha2-glycoprotein distributed throughout the extracellular matrix and body fluids. We recently reported that FN has a protective effect against injury of renal tubular cells by exposure to oxalate and calcium oxalate (CaOX) crystals and inhibits the adhesion of CaOX crystals to renal tubular cells. In the study presented here, we investigated whether FN has inhibitory effect on crystal endocytosis by renal tubular cells. The inhibitory effect of FN on endocytosis of CaOX crystals by MDCK cells was examined by using a radioactivity uptake assay. Also, crystal endocytosis by cells was morphologically assessed by means of transmission electron microscopy (TEM). FN had inhibitory effects on CaOX crystal endocytosis by MDCK cells. The morphological TEM study showed that few crystals were taken into cells when FN was added compared to the number of crystals when FN was not added. We found that FN had the inhibitory effects on the interaction between crystals and renal tubular cells, including the adhesion or endocytosis of crystals by cells.


Severe water intoxication secondary to the concomitant intake of non-steroidal anti-inflammatory drugs and desmopressin: a case report and review of the literature.
Most of the clinical data on the safety profile of desmopressin (DDAVP), which is an effective treatment for both polyuric conditions and bleeding disorders, originate from studies on the tailoring of drug treatment, whereas few reports exist describing severe side effects secondary to drug-drug interaction. We herein describe a case of severe hyponatremia complicated by seizure and coma due to the intake of non-steroidal anti-inflammatory drugs (NSAIDs) in a patient on DDAVP replacement therapy for central diabetes insipidus (DI). A 50-yr-old Caucasian man, with congenital central DI, developed an episode of generalized tonic-clonic seizure, resulting in coma immediately after being admitted to the Emergency Unit for weakness and emesis. Based on his medical history and clinical findings, water intoxication secondary to ketoprofen intake (200 mg/day for the last 3 days) concomitant with DDAVP replacement therapy (Minirin(®) 60 mcg 4 tablets a day) was hypothesized as being the cause of the severe euvolemic hypotonic hyponatremia (natremia 113 mEq/l, plasma osmolality 238 mOsm/Kg). After standard emergency procedures, appropriate gradual restoration of serum sodium levels to the normal range was achieved in 72 hours. Hydratation was maintained according to water excretion and desmopressin therapy was re-introduced. We discuss this case report in the context of the published literature. The present report first highlights the potentially life-threatening side effects associated with over-the-counter NSAIDs during DDAVP replacement therapy for central DI. Risks and benefits of co-treatment should be carefully considered and therapeutic alternatives to NSAIDs should be recommended to patients with central DI in order to improve DDAVP safety.


Flunarizine in the prevention of classical migraine: a placebo-controlled evaluation.
Pharmacological data and early clinical experience have suggested that the calcium entry blocker flunarizine may be a valuable asset in the prophylaxis of migraine. This was supported by a study in twenty patients with classical migraine who were, after a drug-free running-in phase, orally treated with either placebo or flunarizine (10 mg at night) for three to four months. Flunarizine significantly reduced the frequency, duration and severity of the migraine attacks. A corrected migraine index, based on these three variables, was reduced by 82% in the drug group but increased by 66% in the control patients. Only one patient did not clearly benefit from flunarizine, and the response in another illustrated that flunarizine has to be given for at least four months before its efficacy can be judged in some cases. No side effects occurred.


Trace enrichment of biological folates on solid-phase adsorption cartridges and analysis by high-pressure liquid chromatography.
A procedure involving solid-phase adsorption on bonded silica has been developed for trace enrichment and selective recovery of folate monoglutamates from liver tissue. A variety of reverse-phase (ethyl, octyl, octadecyl, phenyl) and anion-exchange (aminopropyl, quaternary amine, primary/secondary amine) cartridges were tested for their potential to adsorb and elute folate monoglutamates from standard solutions (50 nmol each of H4-pteroylglutamic acid (H4PteGlu), 5-CHO-H4PteGlu, 10-CHO-H4PteGlu, PteGlu, and 5-CH3-H4PteGlu). Quantitative recoveries were obtained from aminopropyl (-NH2) and all reverse-phase cartridges. For the analyses of rat liver folates, 20 ml of clear supernatant obtained from 5 g of tissue was treated with conjugase, which released folate monoglutamates from endogenous stores. Folate monoglutamates were then separated from nonfolate material by selective adsorption and recovery from -NH2 extraction cartridges. The procedure also provided a 10-fold concentrate, which allowed direct analysis by HPLC, using C-18 reverse-phase ion-pair columns coupled with uv detection (290 nm). Experiments with standard folates (n = 3) mixed with liver tissue and carried through the extraction, incubation, and trace-enrichment steps showed the following recoveries: 10-CHO-H4PteGlu, 55 +/- 5.0%; H4PteGlu, 80 +/- 5.0%; 5-CHO-H4PteGlu, 123 +/- 12.0%; and 5-CH3-H4PteGlu, 89 +/- 3.0%. Endogenous compositions of liver folates (n = 5) were as follows: 10-CHO-H4PteGlu, 1.03 +/- 0.3 nmol/g (6.7%); H4PteGlu, 5.70 +/- 1.0 (36.4%); 5-CHO-H4Pte Glu, 1.34 +/- 0.4 (8.7%); and 5-CH3-H4PteGlu, 7.34 +/- 1.2 (48.0%). Chromatographic peaks were identified by their retention times and by comparing their spectral profiles (obtained by a diode array detector) with respective pure folates. We found trace enrichment of biological folates on solid-phase extraction cartridges to be rapid and quantitative. The method allowed, for the first time, direct analysis of tissue folates by HPLC/uv methods.


Urinary creatinine excretion in the ICU: low excretion does not mean inadequate collection.
It has been assumed that a urinary creatinine excretion rate of less than 10 mg/kg per day means an inadequately collected urine sample. To determine the frequency of a urinary creatinine excretion rate of less than 10 mg/kg per day in intensive care unit patients with an adequately collected urine sample. In a prospective study of creatinine excretion rates, 24-hour urine samples were evaluated for urinary creatinine in 209 critically ill patients with indwelling Foley catheters. Patients from three adult intensive care units in New York City were divided into two groups. Group 1 patients excreted less than 10 mg/kg per day of urinary creatinine, and group 2 patients excreted at least 10 mg/kg per day. Groups 1 and 2 were first evaluated by dividing the creatinine excretion data by actual body weight. Since actual body weight may overestimate body weight in the critically ill patient, data from groups 1 and 2 were also evaluated using lean body weight. Urinary creatinine excretion was less than 10 mg/kg per day in 36.8% of patients using actual body weight and 29.7% of patients adjusted for lean body weight. The average age of patients in group 1 was 74 +/- 17 years for both actual body weight and lean body weight. The average age of group 2 patients was 60 +/- 19 years for actual body weight and 62 +/- 19 years for lean body weight. There was a significant difference in age between group 1 and group 2 patients for both actual body weight and lean body weight. The proportion of female vs male patients with reduced creatinine excretion was significantly greater, whether the actual body weight or lean body weight adjustment was used. A urinary creatinine excretion rate of less than 10 mg/kg per day occurs in about one third of critically ill patients, who are more likely to be elderly and female.


Capillary electrophoresis and small molecule drug discovery: a perfect match?
Capillary electrophoresis (CE) is an analytical technique based on the separation of the analytes within a capillary owing to their different electrophoretic mobilities. It is widely used in pharmaceutical analyses owing to its versatility and high separation power. However, its penetration into the drug discovery scene has been relatively limited until recent years. Several factors have contributed to this low implementation, including the maturity of liquid chromatography, the scarcity of experienced CE practitioners, and certain limitations intrinsic to the technique. Recently, instrumental improvements and the growing demand for analytical information have lead to a continuously expanding range of routine electrophoretic applications throughout pharmaceutical discovery and development. In this article we review CE fundamentals, review well-established CE methodologies in drug discovery of small molecules and discuss trends that, in our opinion, might emerge in the coming years.


Defining Nano, Nanotechnology and Nanomedicine: Why Should It Matter?
Nanotechnology, which involves manipulation of matter on a 'nano' scale, is considered to be a key enabling technology. Medical applications of nanotechnology (commonly known as nanomedicine) are expected to significantly improve disease diagnostic and therapeutic modalities and subsequently reduce health care costs. However, there is no consensus on the definition of nanotechnology or nanomedicine, and this stems from the underlying debate on defining 'nano'. This paper aims to present the diversity in the definition of nanomedicine and its impact on the translation of basic science research in nanotechnology into clinical applications. We present the insights obtained from exploratory qualitative interviews with 46 stakeholders involved in translational nanomedicine from Europe and North America. The definition of nanomedicine has implications for many aspects of translational research including: fund allocation, patents, drug regulatory review processes and approvals, ethical review processes, clinical trials and public acceptance. Given the interdisciplinary nature of the field and common interest in developing effective clinical applications, it is important to have honest and transparent communication about nanomedicine, its benefits and potential harm. A clear and consistent definition of nanomedicine would significantly facilitate trust among various stakeholders including the general public while minimizing the risk of miscommunication and undue fear of nanotechnology and nanomedicine.


Acute macular neuroretinopathy.
A 24-year-old white woman convalescing from a viral upper respiratory infection suddenly developed three positive scotomas around the fixation point in her left eye. The fundus had three corresponding lesions that appeared to be characteristic of acute macular neuroretinopathy. Situated in the fovea, subtle, reddish-brown, wedge- or tear-shaped lesions were best seen with the direct ophthalmoscope using red-free light. Visual acuity was 6/6 (20/20), and peripheral fields were normal. The patient's reproduction of the scotomas on an Amsler grid sheet mirrored the observed ophthalmoscopic findings. Fluorescein angiograms were normal. She had been taking oral contraceptives for many years. Although viral illness and oral contraceptives have been associated with acute macular neuroretinopathy, no etiology was proven, and no treatment is known. The patient remains symptomatic after a six-month follow-up.


Validation of a sensitive assay for thiocoraline in mouse plasma using liquid chromatography-tandem mass spectrometry.
A sensitive high-performance liquid chromatography-tandem mass spectrometry assay for thiocoraline, an anti-tumor depsipeptide, in mouse plasma is described. Echinomycin, a quinoxaline peptide, was used as an internal standard. Thiocoraline was recovered from the mouse plasma using protein precipitation with acetonitrile and followed by solid-phase extraction of the supernatant. The mobile phase consisted of methanol (0.1% formic acid)-water (0.1% formic acid) (90:10, v/v). The analytical column was a YMC C(18). The standard curve was linear from 0.1 to 50 ng/ml (R(2)>0.99). The lower limit of quantitation was 0.1 ng/ml. The assay was specific based on the multiple reaction monitoring transitions at m/z 1157-->215 and m/z 1101-->243 for thiocoraline and the internal standard, echinomycin, respectively. The mean intra- and inter-day assay accuracies remained below 5 and 12%, respectively, for all calibration standards and quality control (QC) samples. The intra- and inter-day assay precisions were less than 11.4 and 9.5% for all QC levels, respectively. The utility of the assay was demonstrated by a pharmacokinetic study of i.v. (bolus) thiocoraline on CD-1 mice. Thiocoraline was stable in mouse plasma in an ice-water bath for 6 h and for three freeze-thaw cycles. The reconstituted thiocoraline after extraction and drying sample process was stable in the autosampler for over 24 h. The assay was able to quantify thiocoraline in plasma up to 48 h following dose. Pharmacokinetic analysis showed that thiocoraline has distinct pharmacokinetic profiling when dosed in different formulation solutions. The assay is currently used to measure thiocoraline plasma concentrations in support of a project to develop a suitable formulation with a desirable pharmacokinetic profile.


A simple approach for EPID dosimetric calibration to overcome the effect of image-lag and ghosting.
EPID dosimetry has known drawbacks. The main issue is that a measurable residual signal is observed after the end of irradiation for prolonged periods of time, thus making measurement difficult. We present a detailed analysis of EPID response and suggest a simple, yet accurate approach for calibration that avoids the complexity of incorporating ghosting and image-lag using the maximum integrated signal instead of the total integrated signal. This approach is linear with dose and independent of dose rate.


[Epithelioid-cell granulomatous lymphadenitis in a case of parasitic infection in the cervical region (case report) (author's transl)].
A case is reported of epithelioid-cell granulomatous inflammation in the neck with fustula formation and cervical lymph-adenitis, resembling tuberculosis. After neck dissection, histological examination of the removed tissue revealed parasitic infection (organism not identified) as the cause.


A double-blind, randomized, comparative trial of itraconazole versus terbinafine for 2 weeks in tinea capitis.
In this randomized, double-blind study, the efficacy and safety of oral itraconazole (n = 28) and terbinafine (n = 27), each given for 2 weeks, was compared in patients with tinea capitis. Trichophyton violaceum was the major pathogen in both groups (82.1% and 88.9%, respectively). The final evaluation at week 12 showed a cure rate of 85.7% and 77.8%, respectively (P > 0.05). Adverse events noted were mild and did not warrant discontinuation of therapy.


Bioreduction of Cr(VI) by alkaliphilic Bacillus subtilis and interaction of the membrane groups.
Detoxification of Cr(VI) under alkaline pH requires attention due to the alkaline nature of many effluents. An alkaliphilic gram-positive Bacillus subtilis isolated from tannery effluent contaminated soil was found to grow and reduce Cr(VI) up to 100% at an alkaline pH 9. Decrease in pH to acidic range with growth of the bacterium signified the role played by metabolites (organic acids) in chromium resistance and reduction mechanism. The XPS and FT-IR spectra confirmed the reduction of Cr(VI) by bacteria into +3 oxidation state. Chromate reductase assay indicated that the reduction was mediated by constitutive membrane bound enzymes. The kinetics of Cr(VI) reduction activity derived using the monod equation proved (K s = 0.00032) high affinity of the organism to the metal. This study thus helped to localize the reduction activity at subcellular level in a chromium resistant alkaliphilic Bacillus sp.


Capripoxvirus-vectored vaccines against livestock diseases in Africa.
Five different viral diseases of livestock, lumpy skin disease (LSD), sheep pox (SPP), goat pox (GTP), Rift Valley fever (RVF) and peste des petits ruminants (PPR), circulate in the same regions of Africa, imposing a major burden on economic activity and public health. While commercial vaccines against these viruses are available, the cost of implementing regular vaccination regimens against multiple diseases is prohibitive for most African farmers. A single, affordable multivalent vaccine that simultaneously protects against all 5 diseases would therefore be of significant benefit to the livestock sector in Africa. It could also serve as a platform for the development of new vaccines of significance to other developing countries around the world. In this paper, we present an overview of the economic importance of livestock in Africa, the pathogens responsible for RVF, PPR, SPP, GTP and LSD and the vaccination strategies currently used to combat them. We then review experience with the development of attenuated capripoxviruses as vaccines against LSD, SPP and GTP and of recombinant capripoxvirus-vectored vaccines against RVF and PPR. We conclude the article by presenting the rationale for a single, multivalent capripoxvirus-vectored vaccine that would protect against all 5 diseases of livestock, and describe the approach being taken by a consortium of Canadian and South African researchers to develop such a vaccine.


LptD-antigen system on gold nanoparticles: an innovative strategy in the nanovaccine development.
Nanovaccine development is a growing research field in which the development of new carriers and bioconjugation approaches is a priority. In this sense, this report describes for the first time, the development of a novel conjugate that consists of gold nanoparticles (AuNPs) obtained by a one-step synthesis using an immunogenic peptide of the Lipopolysaccharide-assembly protein LptD fromVibrio parahaemolyticusbacteria as a reducing and capping agent. The resultingLptD@AuNPscompounds were fully characterized and the results showed the high capacity of the peptide to form complexes and reduce gold ions. The reaction yield estimated was higher than 83% and the chemical integrity of the peptide on the NP surface revealed a tyrosine amino acid bonding on the AuNP surface. Furthermore, theLptD@AuNPsystem showed high colloidal stability in a wide pH range (3-11 pH values), where the hydrodynamic diameter and Zeta potential behavior were strongly influenced by the functional groups of the antigenic peptide. The cytotoxicity assays showed that the obtained system is safe for mouse leukocytes, while immunized mice withLptD@AuNPsproduced specific IgG antibodies. These encouraging results revealed the efficacy of some antigenic peptides as reducers and capping agents, in addition, opening the path to determine immunogenicity and immunoprotective efficacy of theLptD@AuNPsystem against the disease induced byVibrio parahaemolyticus.


Unprecedented synthesis of alkynylphosphine-boranes through room-temperature oxidative alkynylation.
An original and user-friendly synthesis of alkynylphosphine-boranes, useful building blocks in organic synthesis, based on an oxidative P-alkynylation reaction with readily available copper acetylides is reported. The ability of a secondary phosphine protected with a borane to undergo oxidative coupling without oxidation of the P-moiety is demonstrated for the first time. The reaction, which proceeds at room temperature, is applicable to the preparation of enantioenriched and structurally complex alkynylphosphine-boranes.


Complete ecological isolation and cryptic diversity in Polynucleobacter bacteria not resolved by 16S rRNA gene sequences.
Transplantation experiments and genome comparisons were used to determine if lineages of planktonic Polynucleobacter almost indistinguishable by their 16S ribosomal RNA (rRNA) sequences differ distinctively in their ecophysiological and genomic traits. The results of three transplantation experiments differing in complexity of biotic interactions revealed complete ecological isolation between some of the lineages. This pattern fits well to the previously detected environmental distribution of lineages along chemical gradients, as well as to differences in gene content putatively providing adaptation to chemically distinct habitats. Patterns of distribution of iron transporter genes across 209 Polynucleobacter strains obtained from freshwater systems and representing a broad pH spectrum further emphasize differences in habitat-specific adaptations. Genome comparisons of six strains sharing ⩾99% 16S rRNA similarities suggested that each strain represents a distinct species. Comparison of sequence diversity among genomes with sequence diversity among 240 cultivated Polynucleobacter strains indicated a large cryptic species complex not resolvable by 16S rRNA sequences. The revealed ecological isolation and cryptic diversity in Polynucleobacter bacteria is crucial in the interpretation of diversity studies on freshwater bacterioplankton based on ribosomal sequences.


Intratumoral and peritumoral radiomics analysis for preoperative Lauren classification in gastric cancer.
Preoperative prediction of the Lauren classification in gastric cancer (GC) is very important to the choice of therapy, the evaluation of prognosis, and the improvement of quality of life. However, there is not yet radiomics analysis concerning the prediction of Lauren classification straightly. In this study, a radiomic nomogram was developed to preoperatively differentiate Lauren diffuse type from intestinal type in GC. A total of 539 GC patients were enrolled in this study and later randomly allocated to two cohorts at a 7:3 ratio for training and validation. Two sets of radiomic features were derived from tumor regions and peritumor regions on venous phase computed tomography (CT) images, respectively. With the least absolute shrinkage and selection operator logistic regression, a combined radiomic signature was constructed. Also, a tumor-based model and a peripheral ring-based model were built for comparison. Afterwards, a radiomic nomogram integrating the combined radiomic signature and clinical characteristics was developed. All the models were evaluated regarding classification ability and clinical usefulness. The combined radiomic signature achieved an area under receiver operating characteristic curve (AUC) of 0.715 (95% confidence interval [CI], 0.663-0.767) in the training cohort and 0.714 (95% CI, 0.636-0.792) in the validation cohort. The radiomic nomogram incorporating the combined radiomic signature, age, CT T stage, and CT N stage outperformed the other models with a training AUC of 0.745 (95% CI, 0.696-0.795) and a validation AUC of 0.758 (95% CI, 0.685-0.831). The significantly improved sensitivity of radiomic nomogram (0.765 and 0.793) indicated better identification of diffuse type GC patients. Further, calibration curves and decision curves demonstrated its great model fitness and clinical usefulness. The radiomic nomogram involving the combined radiomic signature and clinical characteristics holds potential in differentiating Lauren diffuse type from intestinal type for reasonable clinical treatment strategy.


Effect of two treatments on changes in serum acute phase protein concentrations in dogs with clinical leishmaniosis.
The objective of this study was to compare changes in serum concentrations of acute phase proteins (APPs) and paraoxanase (PON-1) in response to two treatments in dogs with leishmaniosis (CanL). For this purpose, 20 dogs with CanL were assigned to two treatment groups: antimonial plus allopurinol (Group G, n=12) and miltefosine plus allopurinol (Group M, n=8). Serum concentrations of PON-1 and APPs including C-reactive protein, haptoglobin (Hp), ferritin (Ft) and albumin were monitored over a period of 3 months after treatment. At the beginning of the study (day 0), most of the dogs had APP abnormalities. None of the variables differed significantly between groups in the first or subsequent visits. There was a significantly higher reduction in serum Ft in Group G than in Group M from day 0 to day 30 (P=0.0085), and also from day 0 to day 90 (P=0.0214). There was a higher increase in serum PON-1 in Group G than in than Group M from day 0 to day 30 (P=0.0039), and also from day 0 to day 90 (P=0.0404). This is the first report of APPs in dogs with natural clinical leishmaniosis treated with miltefosine. There was faster resolution of serum APP concentrations in dogs treated with antimonials (P<0.05).


Prediction of in situ exposure to ultrasound: an improved method.
The acoustic output of medical ultrasonic equipment is usually measured in water but to determine the safety (or performance) of a machine it is necessary to know the in situ acoustic pressure levels inside a patient. At present, when estimates of these levels are made, a linear propagation model is used although in practice the propagation is nonlinear. This paper shows that such a model can lead to large errors (80% or more in pressure) and in particular that in situ predictions of the peak-negative acoustic pressure are too low. To describe the field in water and in tissue it is necessary to take account of diffraction, attenuation, and dispersion as well as nonlinear propagation. It is difficult to use acoustic output levels in water to predict in situ values because the amplitude in water approaches a limit, an effect known as saturation. Nevertheless, a method of making such predictions is presented in this paper and is validated by comparison with experiment. The method is relatively time-consuming to implement and has not yet been applied to pulsed fields, so there is a need for more complete and simpler methods.


[Analysis of a series of 44 cases of peritoneal tuberculosis diagnosed in the pathology laboratory of the Tokoin teaching hospital of Lomé (1993-2014)].
It is a descriptive and cross-sectional study on all issues relating to peritoneal tuberculosis histological diagnosed in the pathology department (LAP) of the Lomé Tokoin CHU from January 1993 to December 2014 (20 years). A total of 44 cases of peritoneal tuberculosis were included. They were 18 women and 26 men, with a mean age of 37.6±0.2 years. The circumstances of discovery were dominated by ascites (84.1%), fever (75%), weight loss (63.6%) and abdominal pain (59.1%). The peritoneal involvement was isolated in 31.8% of cases, and associated with pleuropulmonary tuberculosis in 54.5% of cases. Co-infection with HIV was present in 63.9% of cases. Twenty-five patients (69.4%) with information about their social conditions had low socioeconomic level: unemployed (10 cases; 40%), workers (10 cases; 40%) and retired (5 cases; 20%). An increase in cell count was observed in 94.6% of cases. Histology revealed the epithelial giant cell granuloma associated with caseous necrosis in 38 cases (86.4%) and cheesy isolated in 6 patients. Peritoneal tuberculosis is not exceptional in our country. The diagnosis should be considered in febrile ascites, and will be confirmed by laparoscopy with histological samples for a histological diagnosis.


Management of Cystic Conditions.
Cystic conditions are the most common disorder of the breast. Simple cysts are not malignant and do not require intervention. Patients with symptomatic simple cysts can undergo elective aspiration, and typical cyst fluid can be discarded. Bloody fluid should be sent for cytology. Cysts with thick walls, thick septations, or solid components have a risk of malignancy and should undergo biopsy.


Fetal Surgery for Myelomeningocele: Neurosurgical Perspectives.
More than 30 years have elapsed since it was recognised that folic acid supplementation could substantially reduce the risk of open neural tube defects (ONTDs). During that time, many countries have adopted policies of food fortification with demonstrable reduction in the incidence of both cranial and spinal ONTDs. Improved prenatal detection and termination has also resulted in a reduction in the number of affected live births. Nonetheless, in the USA about 1500 children, and in the UK around 500 children are born each year with myelomeningocele (MMC) and so the management of MMC and its complications continues to constitute a significant clinical workload for many paediatric neurosurgical units around the world.Until recently, the options available following antenatal diagnosis of MMC were termination of pregnancy or postnatal repair. As a result of the MOMS trial, prenatal repair has become an additional option in selected cases (Adzick et al., N Engl J Med 364(11):993-1004, 2011). Fetal surgery for myelomeningocele is now offered in more than 30 centres worldwide. The aim of this chapter is to review the experimental basis of prenatal repair of MMC, to critically evaluate the neurosurgical implications of this intervention and to describe the technique of 'open' repair, comparing this with emerging minimally invasive alternatives.


New Practical Aspects of Sweet Syndrome.
Sweet syndrome (SS), or acute febrile neutrophilic dermatosis, is an inflammatory, non-infectious skin reaction characterized clinically by tender, erythematous papules/plaques/pustules/nodules commonly appearing on the upper limbs, trunk, and head and neck; histologically, SS is characterized by dense neutrophilic infiltrate in the dermis. SS is accompanied by fever; an elevation of inflammatory markers (e.g., erythrocyte sedimentation rate, C reactive protein) in serum may also be observed. Although most cases of SS are idiopathic, SS also occurs in the setting of malignancy or following administration of an associated drug. SS has also been reported in association with pregnancy and a burgeoning list of infectious (most commonly upper respiratory tract infections) and inflammatory diseases; likewise, the litany of possible iatrogenic triggers has also grown. Over the past several years, a wider spectrum of SS presentation has been realized, with several reports highlighting novel clinical and histological variants. Corticosteroids continue to be efficacious first-line therapy for the majority of patients with SS, although novel steroid-sparing agents have been recently added to the therapeutic armamentarium against refractory SS. New mechanisms of SS induction have also been recognized, although the precise etiology of SS still remains elusive. Here, we catalogue the various clinical and histological presentations of SS, summarize recently reported disease associations and iatrogenic triggers, and review treatment options. We also attempt to frame the findings of this review in the context of established and emerging paradigms of SS pathogenesis.


The effect of Riluzole on functional recovery of locomotion in the rat sciatic nerve crush model.
Peripheral nerve injury (PNI) is common disorder that represents more than 3 % of all traumatic injury cases. One type of PNI, sciatic nerve injury, leads to considerable motoneuron dysfunction. Because Riluzole is clinically approved for the treatment of motoneuron disease, we evaluated whether Riluzole treatment could enhance the nerve regeneration process and improve functional outcome after sciatic nerve crush in rats. In acute treatment groups, a single dose of Riluzole (6 and 8 mg/kg) was administered intra-peritoneally 15 min after the crush nerve injury. In the chronic treatment groups, animals were treated with Riluzole (4 and 6 mg/kg/d) for 8 days. Sciatic functional index (SFI) was evaluated for 9 weeks after injury. Furthermore, electrophysiological and morphometric evaluations were performed at the 9th week following injury. Acute and chronic administrations of Riluzole immediately after sciatic nerve crush result in significantly delayed regeneration and reduced motor function outcome. These findings suggest that early administration of even a single dose of Riluzole after sciatic nerve crush injury can delay motor function recovery. This effect may not depend on its anti-nociceptive activity.


Glutathione S-transferase activities in African catfish injected with β-naphthoflavone: effects of ploidy, gender, dose, and sampling time.
Glutathione S-transferases (GST) are considered among the most controversial biomarkers of water pollutants in fish with little known about factors influencing their activities. The objective of this study was to investigate how gender, dose, ploidy, and sampling time alter hepatic GST activities in African catfish (Clarias gariepinus) following β-naphthoflavone (β-NF) injection. Newly matured male and female diploid and triploid fish were intraperitoneally (i.p.) injected with 0, 15, or 75 mg/kg of β-NF, and livers were excised 24, 48, and 72 h post-injection. Results showed that hepatic GST activities were significantly inhibited by both doses of β-NF. Inhibition was greater in females than males, but no significant differences were observed between diploid and triploid fish. Enzymatic activities differed over time with lowest levels 72 h post-injection. These results extend our understanding of GST activity in fish and highlight the necessity of considering confounding factors when comparing different studies.


Cytotoxicity profiling of decabromodiphenyl ethane to earthworm (Eisenia fetida): Abnormity-recovery-dysregulation physiological pattern reflects the coping mechanism.
Response of terrestrial invertebrates to decabromodiphenyl ethane (DBDPE) is an emerging field of research nowadays, while cytotoxicity of DBDPE and self-defense strategies of invertebrates are poorly understood. In this study, earthworms (Eisenia fetida) were incubated in the DBDPE-spiked soil system (10, 30, 50, 70, and 100 mg kg-1 dw) for 28-d uptake. The bioaccumulation and distribution of DBDPE, a series of biomarkers associated with lysosomes/mitochondria, and the apoptosis rate of coelomocytes have been evaluated on the 7th, 14th, 21th, and 28th day. At experimental endpoint, the autophagy/apoptosis phenomena have been observed under transmission electron microscopy and the expression levels of six target genes have been explored. Findings in this paper revealed that: bioaccumulation factors decreased with the incremental DBDPE concentrations in the soil. Intestinal ingestion, but not epidermal contact predominated the absorption of DBDPE. The fluctuations of biomarkers and the apoptosis rate were described as the "abnormity-recovery-dysregulation" pattern. Intense oxidative stress, energy demands, membrane-system damage, pathological organelles, and apoptosis were observed in the treated groups. Conclusively, the cytotoxicity of DBDPE initiated the mitochondrial apoptosis pathway which affected the physiological status of lysosomes, autophagy, and the expression of genes. The coping mechanisms of Eisenia fetida to DBDPE included activating mitochondrial electron transport processes, reorganizing actin cytoskeleton, and initiating autophagy. Earthworms resisted the cytotoxicity of DBDPE to a certain extent, while long-term exposure still resulted in apoptosis of coelomocytes. This study works as a laboratory simulation for the environmental safety evaluation of DBDPE and the detoxification mechanisms for earthworm.


Immunodiagnosis of childhood ALL with monoclonal antibodies to myeloid and lymphoid associated antigens.
Sixty-five cryopreserved leukemic samples from children diagnosed and treated as having acute lymphocytic leukemia (ALL) were retrospectively examined for the presence of lymphoid and myeloid associated antigens by indirect immunofluorescence using monoclonal antibodies. Expectedly, the majority of these specimens expressed antigens known to be expressed on lymphoid, and not myeloid malignancies. These included the common acute lymphoblastic leukemia antigen (CALLA), the p32 B-cell associated antigen, and T-cell associated antigens. Leukemic cells from the 8 remaining patients expressed antigens known to be present on both myeloid and lymphoid leukemias. These included HLA/DR, and the antigens identified by BA-1 and BA-2. Cells from 2 of these 8 patients reacted with antibodies that define antigens present on normal and malignant myeloid cells. Both specimens reacted with 1G10, an anti-granulocyte antibody, and one reacted with 5F1 which reacts with monocytes, nucleated red blood cells, megakaryocytes and platelets. One of these patients relapsed while receiving ALL therapy, and the morphology of her leukemic cells became characteristic of acute monocytic leukemia (AMoL). The second patient failed ALL therapy but responded to standard acute nonlymphocytic leukemia (ANLL) therapy, clearing her peripheral blasts. Thus these studies confirm that cell surface phenotyping with monoclonal antibodies can recognize ALL cells that express myeloid rather than lymphoid associated antigens and demonstrate that the malignant cells display a clinical behavior consistent with the diagnosis of ANLL.


Fmoc N-hydroxysuccinimide ester: A facile and multifunctional role in N-glycan analysis.
N-glycans that are fluorescently tagged by glycosylamine acylation have become a promising way for glycan biomarker discovery. Here, we describe a simple and rapid method using Fmoc N-hydroxysuccinimide ester (Fmoc-OSu) to label N-glycans by reacting with their corresponding intermediate glycosylamines produced by microwave-assisted deglycosylation. After optimizing reaction conditions, this derivatization reaction can be effectively achieved under 40 °C for 1 h. Moreover, the comparison of fluorescent intensities for Fmoc-OSu, Fmoc-Cl and 2-AA labeling strategies were also performed. Among which, the fluorescent intensities of Fmoc-OSu labeled glycan derivatives were approximately 5 and 13 times higher than that labeled by Fmoc-Cl and 2-AA respectively. Furthermore, the developed derivatization strategy has also been applied for analyzing serum N-glycans, aiming to screen specific biomarkers for early diagnosis of lung squamous cell cancer. More interestingly, the preparation of free reducing N-glycan standards have been achieved by the combination of HPLC fraction of Fmoc labeled glycan derivatives and Fmoc releasing chemistry. Overall, this proposed method has the potential to be used in functional glycomic study.


Children's reactions to disaster.
Children's reactions to disaster are influenced by their developmental stage, as well as by situational, personal, and family factors. This review describes children's experiences during man-made and natural disasters and uses drawings and narrative to illustrate specific reactions. Mental health outcomes, including post-traumatic stress disorder, are identified, as are approaches to working with children and families after disaster.


Extraction of canine gait characteristics using a mobile gait analysis system based on inertial measurement units.
This study aims to investigate two simple algorithms for extracting gait features from an inertial measurement unit (IMU) based canine gait analysis system. The first algorithm was developed to determine the hip/shoulder extension/flexion range of motion. The second algorithm automatically determines the stance and swing phase per leg. To investigate the accuracy of the algorithms, two dogs were walked on a treadmill and measured simultaneously with an IMU system, an optical tracking system and two cameras. The range of motion estimation was compared to the optical tracking systems, with a total of 280 steps recorded. To test the stance and swing phase detection, a total of 63 steps were manually annotated in the video recordings and compared with the output of the algorithm. The IMU's-based estimation of the range of motion showed an average deviation of 1.4° to 5.6° from the optical reference, while the average deviation in the detection of the beginning and end of the stance and swing phases ranged from -0.01 to 0.09 s. This study shows that even simple algorithms can extract relevant information from inertial measurements that are comparable to results from more complex approaches. However, additional studies including a wider subject pool need to be conducted to investigate the significance of the presented findings.


Encephalitis lethargica.
We report a case of encephalitis lethargica, who presented major intensive care problems, particularly with respect to hyperirritability and convulsions, but who went on to complete recovery. This case would encourage a more aggressive attitude to the management of encephalitis.


Hydrochemical and statistical techniques to decode groundwater geochemical interactions and saline water intrusion along the coastal regions of Tamil Nadu and Puducherry, India.
The study attempts to decipher saline water invasion and aided geochemical influences activated along the coastal zones of Tamil Nadu and Puducherry. Total 76 groundwater samples representing pre- and post-monsoon seasons were collected and examined for various parameters like Ca2+, K+, Na+, Mg2+, Cl-, HCO3-, NO3- and SO42-. Multiple techniques such as hydrochemical ionic changes, hydrochemical facies evolution model and seawater mixing index were incorporated to decipher the salinization process in the study area. Hydrochemical facies suggests 38.00% of groundwater samples representing CaHCO3 facies indicating fresh groundwater, mixed Ca-Cl groundwater by 26.00% of samples and about 36.00% samples suggest Na-Cl indicating saline water. Hydrochemical facies evolution diagram differentiated groundwater facies into freshening and intrusion phase irrespective of seasons. About 23.60% and 21.00% of samples during pre- and post-monsoon suggest samples influenced by seawater intrusion. Hydrochemical ionic changes of samples signify the positive fraction of seawater in both seasons, which shows the mixing of fresh groundwater with saline water. The seawater mixing index confirms a greater percentage of samples during post-monsoon (42.00%) have been influenced by seawater with values greater than one. Principle component analysis extracted three factors with a total variance of 67.31% and 62.03% during pre- and post-monsoon seasons, respectively. Factor 1 replicates the natural processes such as saline water intrusion and ion exchange, whereas factors 2 and 3 signify anthropogenic actions such as improper sewage disposal, use of fertilizers, domestic and industrial waste discharge influencing groundwater chemistry.


Inhibition of glycosylation of herpes simplex virus glycoproteins: identification of antigenic and immunogenic partially glycosylated glycopeptides on the cell surface membrane.
The surface membranes of cells infected with herpes simplex virus type 1 (HSV-1), strain KOS, contain three principal glycoproteins, gC (apparent Mr 129k), gB (apparent Mr 120k), and gD (apparent Mr 58k). Infections carried out in the presence of the glycosylation inhibitor 2-deoxy-D-glucose result in the loss of the mature species with the concurrent appearance of lower-molecular-weight polypeptides which are presumably partially glycosylated forms of the fully processed glycoproteins. Specific immunoprecipitation of radiolabeled cytoplasmic extracts of 2-deoxy-D-glucose-inhibited infections identified partially glycosylated proteins designated DG92, DG88, and DG53, which are antigenically related to the corresponding mature forms gB, gC, and gD. Cell surface radioiodination, in combination with specific immunoprecipitation, revealed that DG88 and DG53 were the principal species transported to the cell surface in 2-deoxy-D-glucose-inhibited infections. DG92 was readily detected in the cytoplasm but not on the plasma membrane. Cells infected with the KOS mutant, syn LD70, did not synthesize glycoprotein gC. In glycosylation-inhibited syn LD70 infections, DG88 was not detected in either the cytoplasm or plasma membrane, demonstrating a genetic relationship between DG88 and gC. Polyclonal and monoclonal antibodies directed against the glycoproteins gC, gB, and gD sensitized infected cells to complement-mediated immune cytolysis. Cells infected in the presence of the inhibitor were sensitized to lysis only by antibody specific for gC and gD. The glycosylation-inhibited cells were insensitive to immunolysis by anti-gB monoclonal antibody. These findings confirm that the glycosylation-deficient forms of gC and gD, but not gB reach the cell surface in the presence of inhibitor and that the inhibitor-induced alterations in glycosylation do not cause a complete loss of antigenicity. Inoculation of mice with syngeneic 3T3 cells infected in the presence or absence of inhibitor-induced cytolytic and neutralizing antibody. A major portion of the cytolytic antibody was directed against gC, but anti-gC antibody appeared to play a minor role in virus neutralization. While the serum induced by the control infected cells contained precipitating antibodies for gC, gB, and gD, the serum derived from mice inoculated with inhibitor-treated infected cells had only weak immunoprecipitating activity against gB. Together, these findings have identified partially glycosylated forms of the major HSV glycoproteins and show that complete glycosylation is not required for transport of some of these partially glycosylated polypeptides to the cell surface. Moreover, complete glycosylation of the glycopeptides is not essential for maintenance of antigenicity or immunogenicity, indicating that at least some determinants recognized by antibodies directed against the mature glycoproteins are not affected by 2-deoxy-D-glucose-induced carbohydrate alterations.


A novel starch from Pongamia pinnata seeds: Comparison of its thermal, morphological and rheological behaviour with starches from other botanical sources.
Pongamia pinnata seed (PPS) starch was studied for its physicochemical, thermal, rheological and morphological properties. As PPS starch is a novel starch, it was compared with corn, mung bean, potato, pearl millet and mango kernel starches. Peak, trough and final viscosity of PPS starch was found the lowest as compared to other starches. Plots of shear stress versus shear rate for starch pastes were plotted and fitted to Herschel-Bulkley model. Yield stress and consistency index value of starch pastes varied between 6.5 and 58.9 Pa and 1.4-10.6 Pa s, respectively. During frequency sweep testing, G' and G'' values of starch pastes varied between 33 and 484 Pa and 18-71 Pa, PPS starch paste had the lowest values. Transition temperatures (Tο, Tp, Tc) for PPS starch was 61.5, 72.1 and 82.9 °C, respectively. Scanning electron microscopy of PPS starch showed small to large and round to oval shape starch granules with small pitches on their surface.


Effect of tachykinin receptor antagonists in experimental neuropathic pain.
The intrathecal effect of 0.1 to 10 microg of RP-67,580 (3aR,7aR)-7,7-diphenyl-2[1-imino-2(2-methoxyphenyl)-ethyl]++ +perhydroisoindol-4-one hydrochloride, CP-96,345 (2S,3S)-cis-(2(diphenylmethyl)-N-[(2-methoxyphenyl) methyl]-1-azabicyclo[2.2.2]octan-3-amine), SR-140,333 (S)-(1-¿2-[3-(3,4-dichlorophenyl)- 1-(3-isopropoxyphenylacetyl)piperidin-3-yl]ethyl¿-4-phenyl-1 -azonia-bicyclo[2.2.2.]-octane,chloride), all neurokinin (NK)1-receptor antagonists, SR-48,968 (S)-N-methyl-N[4-(4-acetylamino-4-[phenylpiperidino)-2-(3,4-dichlorophen yl)-butyl]benzamide, a tachykinin NK2 receptor antagonist and SR-142,801 (S)-(N)-(1-(3-(1-benzoyl-3-(3,4-dichlorophenyl) piperidin-3-yl)propyl)-4-phenylpiperidin-4-yl)-N-methyl acetamide, a tachykinin NK3 receptor antagonist, and of their respective inactive enantiomers on thresholds of vocalization due to a mechanical stimulus in mononeuropathic (sciatic nerve ligature) and diabetic rats, was examined. The tachykinin NK1 and the NK2 receptor antagonists were antinociceptive in both models, with a higher effect of the former in diabetic rats. The tachykinin NK3 receptor antagonist was weakly effective in diabetic rats only. This indicates a differential involvement of the tachykinins according to the model of neuropathic pain, suggesting a potential role for tachykinin receptor antagonists in the treatment of neuropathic pain.


A comprehensive analysis of the triad of frailty, aging, and obesity in spine surgery: the risk analysis index predicted 30-day mortality with superior discrimination.
The United States has experienced substantial shifts in its population dynamics due to an aging population and increasing obesity rates. Nonetheless, there is limited data about the interplay between the triad of frailty, aging, and obesity. To investigate discriminative thresholds and independent associations of the Risk Analysis Index (RAI), Modified Frailty Index-5 (mFI-5), and greater patient age. An observational retrospective cohort study. We analyzed 49,754 spine surgery patients from the American College of Surgeons National Surgical Quality Improvement Program database from 2012 to 2020. A total of 30-day postoperative mortality. Using receiver operating characteristic (ROC) and multivariable (odds ratios [OR] and 95% confidence intervals [CI]) analyses, we compared the discriminative thresholds and independent associations of RAI, mFI-5, and greater patient age in elderly obese patients who underwent spine surgery. There were 49,754 spine surgery patients, with a median age of 71 years (IQR: 68-75), largely white (82.6%) and male (51.9%). The ROC analysis for 30-day postoperative mortality demonstrated superior discrimination for RAI (C-statistic 0.779, 95%CI 0.54-0.805) compared to mFI-5 (C-statistic 0.623, 95% CI 0.594-0.651) and greater patient age (C-statistic 0.627, 95% CI 0.598-0.656). Multivariable analyses revealed a dose-dependent association and a larger effect magnitude for RAI: frail patients OR: 19.52 (95% CI 18.29-20.82) and very frail patients OR: 65.81 (95% CI 62.32-69.50). A similar trend was observed in the interaction evaluating RAI-age-obesity (p<.001). Our study highlights a strong association between frailty and 30-day postoperative mortality in elderly obese spine patients, revealing a dose-dependent relationship. The RAI has superior discrimination than the mFI-5 and greater patient age in predicting 30-day postoperative mortality after spine surgery. Using the RAI in preoperative assessments may improve outcomes and help healthcare providers effectively communicate accurate surgical risks and potential benefits, set realistic recovery expectations, and enhances patient satisfaction.


Being wheelchair-bound and being bedridden: Two concept analyses.
Analysis of the concepts and development of a conceptual definition of being wheelchair-bound and being bedridden. Concept analysis. Walker and Avant´s concept analysis method was used. A thematic analysis guided the determination of the attributes, antecedents and consequences. Being wheelchair-bound and being bedridden are defined as permanent states in which people are bound to an object. Being passively bound to a wheelchair and being bedridden both mean an increasing restriction of the life-space. Being passive wheelchair-bound often represents a preliminary stage to being bedridden. Both concepts have six attributes: in need of help, powerlessness, life-space confinement, mobility limitation, endurance and weakness. They differ in the main feature maintaining an independent sitting position. Physical immobility and physiological instability are antecedents with the following influencing factors: illness, complexity, burden, endogenous/exogenous booster. The consequences are the progression of inactivity and all related physical and psycho-social problems.


Post-operative follow-up following the removal of wisdom teeth.
This article determines whether it is possible to decrease the number of review appointments following wisdom teeth removal without detriment to the patient. A prospective single-centre study was undertaken in a general hospital with 130 consecutive patients undergoing the removal of impacted wisdom teeth.


Flow-injection enhanced chemiluminescence method for determination of ciprofloxacin in pharmaceutical preparations and biological fluids.
A novel rapid and sensitive analytical method, enhanced chemiluminescence with flow-injection sampling, is described for determination of ciprofloxacin. The method is based on the chemiluminescence reaction of the potassium permanganate-sodium thiosulfate-ciprofloxacin system. An enhanced chemiluminescence reaction was developed, and optimum conditions for CL emission were investigated. The chemiluminescence intensity was linearly dependent on ciprofloxacin concentration in the range 1.0 x 10(-8)-1.0 x 10(-5) g mL(-1). The detection limit was 4 x 10(-9) g mL(-1). The relative standard deviation was 1.8% for eleven measurements of 2.0 x 10(-7) g mL(-1) ciprofloxacin standard solution. The new method enables simple, sensitive, and rapid determination of ciprofloxacin and has been successfully used for determination of ciprofloxacin in biological fluids and in ciprofloxacin hydrochloride tablet and injection.


Tracking the structural dynamics of proteins with time-resolved X-ray solution scattering.
Relevant events during protein function such as ligand binding/release and interaction with substrates or with light are often accompanied by out-of-equilibrium structural dynamics. Time-resolved experimental techniques have been developed to follow protein structural changes as they happen in real time after a given reaction-triggering event. Time-resolved X-ray solution scattering is a promising approach that bears structural sensitivity with temporal resolution in the femto-to-millisecond time range, depending on the X-ray source characteristics and the triggering method. Here we present the basic principles of the technique together with a description of the most relevant results recently published and a discussion on the computational methods currently developed to achieve a structural interpretation of the time-resolved X-ray solution scattering experimental data.


Evaluation of a Point-of-care ultrasound (POCUS) workshop for peripheral intravenous cannulation.
Point-of-care ultrasound (POCUS) is increasingly used as a non-invasive vascular access assessment method by clinicians from multiple disciplines worldwide, prior and during vascular access cannulations. While POCUS is a relatively new method to establish a vascular access in patients with complex vascular conditions, it is also essential to train and educate individuals who are novices in the techniques of cannulation so that they become proficient in performing this task subsequently on patients safely and successfully. A simulated environment may be a helpful tool to help healthcare providers establish skills in using POCUS safely and may also help them to successfully establish vascular access in patients. With this project, we sought to determine if participants of a simulated POCUS workshop for vascular access can use this technique successfully in their individual clinical environment after their attendance of a half-day workshop. A mixed-methods longitudinal study design was chosen to evaluate a point-of-care ultrasound workshop for peripheral intravenous cannula insertion. The workshops used simulation models for cannulation in combination with multiple ultrasound devices from various manufacturers to expose participants to a broader variety of POCUS devices as they may also vary in different clinical areas. Participants self-assessed their cannulation skills using questionnaires on a 10-point rating scale prior to and directly after the workshop. A total of 85 Individuals participated in eleven half-day workshops through 2021 and 2022. Workshop participants claimed that attending the workshop had significantly enhanced their clinical skill of using ultrasound for the purpose of cannulating a venous vessel. The level of confidence in using this technique had increased in all participants directly after conclusion of the workshop. Globally, clinicians are increasingly using POCUS to establish vascular access in patients, and it is necessary that they receive sufficient and adequately structured and formal training to successfully apply this technique in their clinical practice. Offering a workshop which uses simulation models in combination with various POCUS devices to demonstrate this technique in a hands-on approach has proven to be useful to establish this newly learned skill in clinicians.


Influenza virus pathogenicity regulated by host cellular proteases, cytokines and metabolites, and its therapeutic options.
Influenza A virus (IAV) causes significant morbidity and mortality. The knowledge gained within the last decade on the pandemic IAV(H1N1)2009 improved our understanding not only of the viral pathogenicity but also the host cellular factors involved in the pathogenicity of multiorgan failure (MOF), such as cellular trypsin-type hemagglutinin (HA0) processing proteases for viral multiplication, cytokine storm, metabolic disorders and energy crisis. The HA processing proteases in the airway and organs for all IAV known to date have been identified. Recently, a new concept on the pathogenicity of MOF, the "influenza virus-cytokine-trypsin" cycle, has been proposed involving up-regulation of trypsin through pro-inflammatory cytokines, and potentiation of viral multiplication in various organs. Furthermore, the relationship between causative factors has been summarized as the "influenza virus-cytokine-trypsin" cycle interconnected with the "metabolic disorders-cytokine" cycle. These cycles provide new treatment concepts for ATP crisis and MOF. This review discusses IAV pathogenicity on cellular proteases, cytokines, metabolites and therapeutic options.


High resolution ECG analysis by an improved signal averaging method and comparison with a beat-to-beat approach.
The aim of this paper is to describe the analysis of a high resolution ECG recorded from the body surface. Standard signal averaging techniques are improved by using a new time delay estimation method which leads to a better alignment accuracy of P and T waves. A second method uses adaptive identification to achieve a beat by beat fine ECG estimation. Information provided by the two methods allows a better interpretation of low and very low level signals.


Characterizing pesticide sorption and degradation in microscale biopurification systems using column displacement experiments.
Biopurification systems treating pesticide contaminated water are very efficient, however they operate as a black box. Processes inside the system are not yet characterized. To optimize the performance, knowledge of degradation and retention processes needs to be generated. Therefore, displacement experiments were carried out for four pesticides (isoproturon, bentazone, metalaxyl, linuron) in columns containing different organic mixtures. Bromide, isoproturon and bentazone breakthrough curves (BTCs) were well described using the convection-dispersion equation (CDE) and a first-order degradation kinetic approach. Metalaxyl and linuron BTCs were well described using the CDE model expanded with Monod-type kinetics. Freundlich sorption, first-order degradation and Monod kinetics coefficients were fitted to the BTCs. Fitted values of the distribution coefficient K(f,column) were much lower than those determined from batch experiments. Based on mobility, pesticides were ranked as: bentazone>metalaxyl-isoproturon>linuron. Based on degradability, pesticides were ranked as: linuron>metalaxyl-isoproturon>bentazone.


Austrian recommendations for the management of essential thrombocythemia.
According to the World Health Organization (WHO) classification, essential (primary) thrombocythemia (ET) is one of several Bcr-Abl negative chronic myeloproliferative neoplasms (MPN). The classical term MPN covers the subcategories of MPN: ET, polycythemia vera (PV), primary myelofibrosis (PMF), and prefibrotic PMF (pPMF). ET is marked by clonal proliferation of hematopoietic stem cells, leading to a chronic overproduction of platelets. At the molecular level a JAK2 (Janus Kinase 2), calreticulin, or MPL mutation is found in the majority of patients. Typical ongoing complications of the disease include thrombosis and hemorrhage. Primary and secondary prevention of these complications can be achieved with platelet function inhibitors and various cytoreductive drugs including anagrelide, hydroxyurea and interferon. After a long follow up, in a minority of ET patients the disease transforms into post-ET myelofibrosis or secondary leukemia. Overall, life expectancy with ET is only slightly decreased.


Role of bronchoalveolar lavage in the assessment of opportunistic pulmonary infections: utility and complications.
We prospectively evaluated the diagnostic role of bronchoalveolar lavage in the assessment of opportunistic pulmonary infections and the incidence of associated complications in 100 immunocompromised patients during a 9-month period. Bronchoalveolar lavage was useful in detecting the presence of Pneumocystis carinii, viruses, fungi, bacteria, and mycobacteria in the lower respiratory tract. P. carinii was diagnosed by bronchoalveolar lavage in 17 patients and by open-lung biopsy in 1. Other organisms detected by lavage, lung biopsy, or both included viruses (eight patients), fungi (four patients), bacteria (six patients), and mycobacteria (three patients). Of the 100 patients studied, 33 had infectious agents detected in the lung; in 6 of these patients, more than one organism was present. Bronchoalveolar lavage detected the infectious organisms in 30 of the patients, in many of whom an open-lung biopsy was likely avoided because of the lavage studies. Although no major complications of bronchoalveolar lavage were noted in this critically ill population, five patients did require short-term mechanical ventilation after bronchoscopy. When correctly used, bronchoalveolar lavage is a safe and useful procedure for the assessment of immunocompromised subjects with suspected opportunistic pulmonary infections.


Gender Differences in Perceived Family Involvement and Perceived Family Control during Emerging Adulthood: A Cross-Country Comparison in Southern Europe.
The aim of the present study was to explore gender differences in perceived parental involvement and perceived psychological and behavioral control during emerging adulthood in two Southern European countries (Spain and Portugal). Data were collected from 491 Portuguese and 552 Spanish undergraduate emerging adults (53.7 % women and 46.3 % men) aged between 18 and 29 years (M = 20.24 and SD = 2.12). Results indicated that women perceived higher levels of parental involvement than men in both countries, and men perceived more behavioral control than women in Portugal. Furthermore, gender was found to moderate the association between perceived parental involvement and perceived psychological and behavioral control differently in each country. Taken together, our findings suggest that gender-differentiated socialization patterns persist during emerging adulthood and that these patterns may be affected by the sociocultural context.


The heme uptake process in Trypanosoma cruzi epimastigotes is inhibited by heme analogues and by inhibitors of ABC transporters.
Heme (iron protoporphyrin IX) is an important molecule involved in many biological reactions, including oxygen transport, respiration, photosynthesis and drug detoxification. Trypanosoma cruzi parasites, the etiological agent of Chagas' disease, take up heme from the environment to supply their nutritional needs because they do not synthesize this cofactor. However, the mechanisms involved in heme transport across biological membranes are poorly understood. Indeed, in T. cruzi, no heme transporter has yet been characterized. In the present work, we evaluate the heme uptake processes by T. cruzi epimastigotes using fluorescent heme-analogues. Heme uptake decreased significantly when cells were pretreated with different concentrations of SnPPIX, PdMPIX or ZnMPIX, this observed competition suggests that they are taken up by the same transport system. We studied the growth behavior of epimastigotes using the same heme-analogues and the treatments with SnPPIX or PdMPIX impaired cell growth but when heme was added to the culture medium the observed inhibition was partially reversed. In addition, we tested how the heme uptake processes are affected by the presence of different transporter inhibitors. When the cells were treated with inhibitors and then incubated with heme, heme uptake decreased significantly for all treatments. These results constitute a strong indication for the existence of a protein associated with porphyrin transport in T. cruzi, possibly ATP-binding cassette transporters (ABC-transporter).


Access to Care, Treatment Ambivalence, Medication Nonadherence, and Long-Term Mortality Among Severely Hypertensive African Americans: A Prospective Cohort Study.
African Americans living in poor neighborhoods bear a high burden of illness and early mortality. Nonadherence may contribute to this burden. In a prospective cohort study of urban African Americans with poorly controlled hypertension, mortality was 47.6% over a median follow-up of 6.1 years. Patients with pill-taking nonadherence were more likely to die (hazard ratio, 1.80; 95% confidence interval [CI], 1.18-2.76) after adjustment for potential confounders. With regard to factors related to nonadherence, poor access to care such as difficulty paying for medications was associated with prescription refill nonadherence (odds ratio [OR], 4.12; 95% CI, 1.88-9.03). Pill-taking nonadherence was not associated with poor access to care; however, it was associated with factors related to treatment ambivalence including lower hypertension knowledge (OR, 2.97; 95% CI, 1.39-6.32), side effects (OR, 3.44; 95% CI, 1.47-8.03), forgetfulness (OR, 3.62; 95% CI, 1.78-7.34), and feeling that the medications do not help (OR, 2.78; 95% CI, 1.09-7.09). These data suggest that greater access to care is a necessary but insufficient remedy to the disparities experienced by urban African Americans with hypertension. To achieve its full promise, health reform must also address treatment ambivalence.


Diabetes and hearing impairment in Mexican American adults: a population-based study.
Reports on the relationship between diabetes and hearing loss have been controversial. The present study examined this relationship in 1,740 Mexican American adults using data from the Hispanic Health and Nutrition Examination Survey. Hearing threshold levels were obtained for each participant at the following frequencies: 500, 1000, 2000, and 4000 Hertz (Hz). The thresholds from the worse hearing ear were used in the analyses. Diabetes and insulin use were assessed by self-report. The mean crude hearing thresholds in diabetics were significantly higher than in non-diabetics at each of the four frequencies. However, after adjustment for age, gender, and socioeconomic status, diabetics had a significantly higher mean threshold than non-diabetics only at 500 Hz (mean difference +/- SE: 2.8 +/- 1.2, p = 0.04). Diabetics who were not using insulin had significantly higher thresholds than those who were using insulin at 2000 (mean difference +/- SE: 5.6 +/- 2.6, p = 0.03) and 4000 Hz (7.7 +/- 3.3, p = 0.02). Also, at 4000 Hz, insulin users had a significantly lower mean threshold than non-diabetics (mean difference +/- SE: -4.9 +/- 1.6, p = 0.02). Our data suggest that associations between diabetes and decreased hearing acuity in the higher frequencies are present only amongst diabetic Mexican-Americans who do not use insulin.


Combined segregation and linkage analysis of fibrinogen variability in Israeli families: evidence for two quantitative-trait loci, one of which is linked to a functional variant (-58G > A) in the promoter of the alpha-fibrinogen gene.
The association of alpha- and beta-fibrinogen polymorphisms with plasma fibrinogen levels was examined in a sample of 452 family members from 80 Israeli kindreds. The measured genotype analysis indicated that the beta-fibrinogen -455G > A polymorphism was not associated with fibrinogen levels, while the alpha-fibrinogen -58G > A locus showed a significant association with fibrinogen levels (chi2= 17.7; df = 3; p < 0.001), with the -58A allele being associated with higher levels. Segregation analysis in this sample suggested a recessive quantitative-trait locus (QTL) with a major effect that controlled the sex- and age-adjusted fibrinogen levels. Results from a combined segregation/linkage analysis indicated that a single QTL influencing plasma fibrinogen is in gametic equilibrium with the beta-fibrinogen -455G > A and alpha-fibrinogen -58G > A polymorphisms. An extended analysis with a two-QTL model significantly improved the fit of the model (p < or = 0.001), and gave support for linkage between the fibrinogen QTL and the alpha-fibrinogen polymorphism. In vitro analysis with a DNA fragment containing this variant, linked to a reporter gene, showed 2-fold higher expression of the A allele compared to the G allele in the liver cell line HepG2, both under basal conditions and after stimulation with interleukin 6. These results demonstrate that two QTLs are jointly involved in determining plasma fibrinogen levels in this sample of families, one of which is located close to a functional variant in the alpha-fibrinogen locus.


Molecular staging using qualitative RT-PCR analysis detecting thyreoglobulin mRNA in the peripheral blood of patients with differentiated thyroid cancer after therapy.
The prognostic significance of molecular staging using thyroglobulin (Tg)-based RT-PCR analysis in the peripheral blood of patients with differentiated thyroid cancer (DTC) was investigated. Herein, the specificity of molecular staging in DTC patients after thyroidectomy and 131I ablation therapy was analysed, using different specific cDNA primers in qualitative nested and classical RT-PCR protocols. Ninty-five patients receiving TSH suppressive therapy were included, of whom 51 were disease-free and 44 presented residual/recurrent or metastatic disease as evidenced by biochemical and/or 131I whole-body scan. Our analysis detected RT-PCR products suggestive of the presence of Tg mRNA in all the blood samples tested, including healthy controls. A splice variant (350 bp) of Tg transcript (missing exon 3) was detected by nested RT-PCR in 34% of blood samples, however, without correlation to disease status. Qualitative Tg-based molecular staging in the peripheral blood of patients with DTC shows poor specificity in assessing DTC disease status.


Hypotensive effect of the methanolic extract of Mimusops elengi in normotensive rats.
The methanolic extract of Mimusops elengi caused hypotensive activity in anaesthetized rats. On intravenous administration (i.v.) at a dose range of 2-16 mg/kg, it produced about a 7-38% fall in mean arterial blood pressure, in a dose-dependent manner. The effect was independent of adrenergic, muscarinic and histaminergic receptors. The hypotension was also unchanged after autonomic ganglion or angiotensin-converting-enzyme blockade. Administration of calcium channel blockers, however, including nifedipine (0.9 mg/kg) and verapamil (3.9 mg/kg), caused corresponding reductions of 81 and 64% in extract-induced hypotension. These data imply M. elengi might possess calcium-blocking activity which would explain its hypotensive effect.


Renal cortex neuronal nitric oxide synthase in response to rapamycin in kidney transplantation.
Decreased renal neuronal nitric oxide synthase (nNOS) is present in various chronic kidney diseases although there is relative little known in chronic allograft nephropathy (CAN). Female sex increases the risk of acute rejection and calcineurin-inhibitor toxicity but decreases the risk of CAN. Rapamycin (RAPA) is an alternative immunosuppress although there is no information whether it is effective in females. We therefore investigated the efficacy of RAPA in both sexes and the impact of RAPA on renal cortex structure and nNOS expression. Male (M) and female (F) F344 kidneys were transplanted into same sex Lewis (ALLO) or F344 (ISO) recipients and treated with 1.6 mg/kg/day of RAPA for 10 days. Grafts were removed for renal histology and endothelial (e)NOS and neuronal (n)NOS protein measurements at 22 weeks. All ALLO rats survived without acute rejection. ALLO F survived with mild proteinuria and CAN at 22 weeks similar to ALLO M, while ISO F had better outcome than ISO M. Cortical nNOSalpha was undetectable in all RAPA groups; however, nNOSbeta transcript and protein were compensatory increased. Both ALLO and ISO F showed higher medullary nNOSalpha but lower cortical eNOS abundance than M groups. In male ALLO RAPA decreased renal cortical nNOSalpha but increased nNOSbeta expression. This may represent compensatory upregulation of nNOSbeta when nNOSalpha-derived NO is deficient.


Adsorptive amputation of hazardous azo dye Congo red from wastewater: a critical review.
Increasing amount of dyes in an ecosystem has propelled the search of various methods for dye removal. Amongst all the methods, adsorption occupies a prominent place in dye removal. Keeping this in mind, many adsorbents used for the removal of hazardous anionic azo dye Congo red (CR) from aqueous medium were reviewed by the authors. The main objectives behind this review article are to assemble the information on scattered adsorbents and enlighten the wide range of potentially effective adsorbents for CR removal. Thus, CR sorption by various adsorbents such as activated carbon, non-conventional low-cost materials, nanomaterials, composites and nanocomposites are surveyed and critically reviewed as well as their sorption capacities are also compared. This review also explores the grey areas of the adsorption performance of various adsorbents with reference to the effects of pH, contact time, initial dye concentration and adsorbent dosage. The equilibrium adsorption isotherm, kinetic and thermodynamic data of different adsorbents used for CR removal were also analysed. It is evident from a literature survey of more than 290 published papers that nanoparticle and nanocomposite adsorbents have demonstrated outstanding adsorption capabilities for CR. Graphical abstract .