The rate of preterm birth in the United States is affected by the method of gestational age assignment.
The objective of the study was to examine the rate of preterm birth in the United States using 2 different methods of gestational age assignment and determine which method more closely correlates with the known morbidities associated with preterm birth. Using National Center for Health Statistics data from 2012 United States birth certificates, we computed the rate of preterm birth defined as a birth at 36 or fewer completed weeks with gestational age assigned using the obstetric estimate as specified in the revised birth certificate. This rate was then compared with the rate when gestational age is calculated using the last menstrual period alone. The rates of neonatal morbidities associated with preterm birth were examined for each method of assigning gestational age. The rate of preterm birth was 9.7% when the obstetric estimate is used to calculate gestational age, which is significantly different from the rate of 11.5% when gestational age is calculated using the last menstrual period alone. In addition, the neonates identified as preterm by obstetric estimate were more likely to qualify as low birthweight (54% vs 42%; P < .001) and suffer morbidities such as need for assisted ventilation and surfactant use than those identified with the last menstrual period alone. That is to say obstetric estimate is more sensitive and specific for preterm birth by all available markers of prematurity. The preterm birth rate is 9.7% vs 11.5% and more closely correlates with adverse neonatal outcomes associated with preterm birth when gestational age is assigned using the obstetric estimate. This method of gestational age assignment is currently used by most industrialized nations and should be considered for future reporting of US outcomes.


In situ prepared algae-supported iron sulfide to remove hexavalent chromium.
The effects of algae on the removal of contaminant by iron sulfide (FeS) are still unknown. Chlorella vulgaris (CV), a remarkable algal specie, was used to prepare the CV-supported FeS (CV-FeS) and to investigate the role that CV plays in the removal of a heavy metal (i.e., hexavalent chromium (Cr(VI)) by FeS. The stabilized effect from algal extracellular polymeric substance (EPS) enhanced the reactivity of FeS due to the decrease of FeS aggregation, thus increasing Cr(VI) removal rate from 0.21 min-1 to 0.79 min-1. Furthermore, the strong buffering induced by the algal functional groups could effectively prevent the solution pH from increasing, which improved Cr(VI) removal because acidic solution facilitated Cr(VI) reduction by FeS. However, the complexing capacity from algal EPS made Fe(II) unavailable for Cr(VI) reduction, which led to 35% decrease of Cr(VI) removal. The Fe(II) was oxidized to α-FeOOH by Cr(VI) in the absence of CV, while the unreacted Fe(II) was detected as in the form of Fe(OH)2 in CV-FeS. Cr(VI) was reduced to Cr(III) and S(-II) was oxidized to elemental sulfur (S8) regardless of the CV. This work showed the different roles of algae in the removal of Cr(VI) by FeS and provided value information for the application of FeS in the polluted algae-containing water system.


Role of wrist arthroscopy in scapholunate dissociation.
Scapholunate ligament tear is most frequently encountered in the aftermath of trauma in supination and extension of the wrist. It generates chronic instability, leading to osteoarthritis. It may be associated with fracture of the distal epiphysis of the radius or of the scaphoid. These lesions are often difficult to diagnose, especially in early stages. Treatment of chronic scapholunate ligament lesions before onset of osteoarthritis is a challenge for the surgeon. To date, recommendations are for open reconstruction or repair, which can improve pain and grip strength, but very often at the cost of wrist stiffness. The advent of arthroscopy has completely changed the understanding and treatment of these lesions. The present review focuses on recent contributions to the anatomy of the scapholunate complex and the anatomopathology of these dissociations, and explores classical treatments and the emerging role of arthroscopy. We shall seek to answer five questions: (1) What are the anatomical bases of the scapholunate complex, (2) What is the initial clinical and paraclinical work-up for scapholunate dissociations, and how are they to be classified, (3) What are the classical treatments for scapholunate dissociation, (4) What are the technical principles and results of arthroscopic treatment, (5) What are the limits and perspectives of arthroscopic treatment?


MRI in occipital lobe infarcts: classification by involvement of the striate cortex.
We reviewed the MRI studies of 25 patients with occipital lobe infarcts to clarify the distribution of infarcts in the posterior cerebral arterial territory, focussing on their relationship to the striate cortex. Visual field defects and MRI findings were also correlated in 16 patients. On coronal and/or sagittal images, the distribution of the infarct and its relationship to the striate cortex were classified. Involvement of the cortex of both upper and lower lips of the calcarine fissure was observed in 10 patients, and involvement of the lower lip alone in 15. The upper cortical lesions were always accompanied by lower cortical lesions. The visual field defects were complete hemianopia in nine patients, superior quadrantanopia in six and hemianopia with a preserved temporal crescent in one. All patients with superior quadrantanopia had involvement of the lower cortex alone; there were no cases of inferior quadrantanopia. The characteristic vascular anatomy, and poor development of the collateral circulation in the lower cortical area, may explain the vulnerability of this area to infarcts.


Early myointimal hyperplasia after balloon catheter embolectomy: effect of shear forces and multiple withdrawals.
Arterial stenosis occurring after balloon catheter embolectomy may be caused by myointimal hyperplasia (MIH). This study investigated the effects of shear force and repeated catheter withdrawals on the development of MIH after embolectomy. The procedures were performed in the common carotid and common femoral arteries of 18 anesthetized dogs. During catheter withdrawal, the balloons were filled gradually to produce shear forces rising smoothly from 50 to 200 gm. Four weeks after embolectomy, the vessels were perfusion-fixed in situ with 2% glutaraldehyde and were excised. The thickness and circumferential extent of MIH were measured in cross sections from segments of the vessels exposed to shear forces of 50, 100, and 200 gm. Sixty-nine of 72 arteries remained patent. Low shear force (50 gm) consistently elicited less MIH than did higher shear forces (p less than 0.05). At each level of shear force, repeated withdrawals resulted in greater circumferential extent of MIH than did single withdrawals (p less than 0.005). Although clinically it usually is necessary to perform multiple passes during balloon embolectomy, these data suggest that, in humans, attempts should be made to perform a minimal number of catheter withdrawals at low shear force to minimize the subsequent development of MIH.


Pre-TCR signaling regulates IL-7 receptor alpha expression promoting thymocyte survival at the transition from the double-negative to double-positive stage.
The pre-T cell receptor (pre-TCR) and IL-7 receptor (IL-7R) are critical mediators of survival, proliferation and differentiation in immature thymocytes. Here we show that pre-TCR signaling directly maintains IL-7Ralpha expression as developing thymocytes undergo beta-selection. Inhibition of IL-7/IL-7R signaling in (CD44-CD25-) DN4 cells results in decreased generation of double-positive thymocytes due to increased death of rapidly proliferating beta-selected cells. Thus, we identify a mechanism by which pre-TCR signaling controls the selective survival of TCRbeta+ thymocytes, and define a further stage of T cell differentiation in which signaling from a TCR regulates the ability of that cell to respond to cytokine.


Insomnia on dialysis nights: the beneficial effects of cool dialysate.
Hemodialysis (HD) induces physiological changes that may affect the ability to dissipate heat and adversely affect sleep on the nights following treatment. We studied the effects of altering dialysate temperature on polysomnographic measures of nocturnal sleep and the time course of proximal skin temperature. The sample included seven stable HD patients. The three-phase randomized trial was conducted in a research facility. After one acclimatization night, subjects were readmitted in the evening on two additional occasions for 42 hours and received HD the next morning in the warm condition (dialysate--37 degrees C) and cool condition (dialysate--35 degrees C) in random order. Continuous proximal skin temperature (axillary, Tax) and polysomnographic measures of sleep were recorded the nights before and after HD was administered. Highly significant findings included that the course of Tax was markedly affected by the interaction of time and condition. In addition, there was a greater drop of Tax in the early morning following the warm condition than during the baseline nights or in the cool condition. Logistic regression indicated that the odds for the occurrence of sleep and its deeper stages were strongly and positively associated with Tax. Time of sleep onset was earlier in the cool condition (p = 0.032) with trends toward longer total sleep times (p = 0.090) and shorter REM latencies (p = 0.088). These observations suggest that the use of cool dialysate during HD may improve nocturnal sleep the night following treatment by decreasing sympathetic activation and sustaining the normally elevated nocturnal skin temperature until later into the morning hours.


Characterization of Trypanosoma cruzi MutY DNA glycosylase ortholog and its role in oxidative stress response.
Trypanosoma cruzi is a protozoan parasite and the causative agent of Chagas disease. Like most living organisms, it is susceptible to oxidative stress, and must adapt to distinct environments. Hence, DNA repair is essential for its survival and the persistence of infection. Therefore, we studied whether T. cruzi has a homolog counterpart of the MutY enzyme (TcMYH), important in the DNA Base Excision Repair (BER) mechanism. Analysis of T. cruzi genome database showed that this parasite has a putative MutY DNA glycosylase sequence. We performed heterologous complementation assays using this genomic sequence. TcMYH complemented the Escherichia coli MutY- strain, reducing the mutation rate to a level similar to wild type. In in vitro assays, TcMYH was able to remove an adenine that was opposite to 8-oxoguanine. We have also constructed a T. cruzi lineage that overexpresses MYH. Although in standard conditions this lineage has similar growth to control cells, the overexpressor is more sensitive to hydrogen peroxide and glucose oxidase than the control, probably due to accumulation of AP sites in its DNA. Localization experiments with GFP-fused TcMYH showed this enzyme is present in both nucleus and mitochondrion. QPCR and MtOX results reinforce the presence and function of TcMYH in these two organelles. Our data suggest T. cruzi has a functional MYH DNA glycosylase, which participates in nuclear and mitochondrial DNA Base Excision Repair.


Changes of arterial oxygen saturation (SpO2) following push-back operation.
This study showed the influence of the push-back operation on the occurrence of sleep-related apnea in cleft-palate patients with an analysis of arterial oxygen saturation (SpO2) during sleep, polygraphic analysis of nasal air flow, and chest wall movements. The postoperative SpO2 was lower than that of the presurgical period in all cases, requiring from five to nine days to recover to presurgical levels. According to polygraphic analysis this depression of SpO2 was caused by peripheral obstructive apnea, while, in spite of the cessation of nasal airflow, chest wall movement continued.


Lack of posteromedial tibiofemoral congruence at full flexion as a causative factor in isolated medial meniscal tears.
The aim of the current study was to investigate posteromedial tibiofemoral congruence at full flexion of the knee in control knee joints and those affected by an isolated medial meniscal tear, to examine whether lack of such congruence was a causative factor in isolated medial meniscal tears. In this study, 1677 knee joints in 875 subjects were evaluated. The joints were classified as a control group (1345 joints), an isolated medial meniscal tear group (224 joints), and a contralateral isolated medial meniscal tear group (108 joints). Posteromedial tibiofemoral congruence was examined on a lateral radiograph of the knee joint at full flexion. The tangent touching the anterior and posterior parts of the articular surface of the medial tibial condyle was assumed to be the X-axis. To evaluate posteromedial tibiofemoral congruence, we measured the angle formed by the tangent that maximized the gradient of the tangent on the articular surface of the medial femoral condyle, and the tangent that maximized the gradient of the tangent on the articular surface of the medial tibial condyle. The mean angle differed significantly between the control and the isolated medial meniscal tear groups, regardless of sex. Isolated medial meniscal tears were found to be strongly related to an abnormally decreased angle, and, therefore, incongruence of the posteromedial tibiofemoral articulation at full flexion was considered to be one of the causes of isolated medial meniscal tears.


Hydrothorax in association with Scopulariopsis brumptii in an AIDS patient in Chennai, India.
Over the past decade, an increasing number of opportunistic fungal infections have been reported in immunocompromised subjects. Microascus spp. and their anamorphs Scopulariopsis spp. have been recovered from a wide geographical range. We report a case of Scopulariopsis brumptii in a 27-year-old man with AIDS presenting with breathlessness, pericardial effusion and hydrothorax in Chennai, southern India, in February 2007. Because of respiratory arrest, the patient was intubated. However, the patient developed obstructive shock and died due to cardiac dysfunctions. This report underlines the need for a direct, intensive approach to investigations in immunocompromised patients, especially those with AIDS.


Rapid detection of BRCA1 mutations by the protein truncation test.
More than 75% of the reported mutations in the hereditary breast and ovarian cancer gene, BRCA1, result in truncated proteins. We have used the protein truncation test (PTT) to screen for mutations in exon 11, which encodes 61% of BRCA1. In 45 patients from breast and/or ovarian cancer families we found six novel mutations: two single nucleotide insertions, three small deletions (1-5 bp) and a nonsense mutation identified two unrelated families. Furthermore, we were able to amplify the remaining coding region by RT-PCR using lymphocyte RNA. Combined with PTT, we detected aberrantly spliced products affecting exons 5 and 6 in one of two BRCA1-linked families examined. The protein truncation test promises to become a valuable technique in detecting BRCA1 mutations.


Usefulness of microalbuminuria in patients with the metabolic syndrome to predict subclinical atherosclerosis and cardiovascular disease outcomes.
The clinical implications of microalbuminuria (MA) in nondiabetic persons with the metabolic syndrome (MS) are largely unknown. The present post hoc analysis of the Multiethnic Study of Atherosclerosis (MESA) included 5,809 nondiabetic persons with no history of cardiovascular disease aged 45 to 84 years. The study population was divided according to the presence or absence of MS and MA into 4 study groups: no MS and no MA, MA only, MS only, and MS plus MA. The measurements included markers of systemic inflammation, subclinical atherosclerosis, left ventricular mass index, composite and individual cardiovascular end points, and all-cause mortality. Prospective and cross-sectional analyses were performed to ascertain the association of study groups with these covariates. The MS plus MA group showed a consistently stronger association with the markers of systemic inflammation, subclinical atherosclerosis, and most clinical end points compared to the other study groups. In conclusion, stratification by MA can help identify a high-risk subset of nondiabetic patients with the MS.


Dexamethasone depresses the expression of L-selectin but not the in vivo migration of bovine neutrophils into the uterus.
There are several indications that periparturient depression of functional properties of polymorphonuclear neutrophilic granulocytes (PMN) may be of great importance for the pathogenesis of genital infections after calving. As the periparturient period is characterized by high plasma levels of corticosteroids, the hypothesis to be tested was that high concentrations of glucocorticoids during the periparturient period suppress uterine PMN in number and functionality. An in vivo endometritis model was applied to examine uterine PMN. Recombinant human interleukin-8 (rhIL-8) was infused into the uterus of estrous cows and heifers 24 h after pretreatment with dexamethasone (0.07 mg/kg i.m.). Six hours after rhIL-8 infusion high numbers of uterine PMN were isolated and characterized as to their immunophenotype and function. Animals treated with dexamethasone animals showed leucocytosis due to neutrophilia in peripheral blood. Despite a downregulation of expressed L-selectin, cattle treated with dexamethasone showed more uterine PMN than those treated with placebo. Dexamethasone decreased plasma concentrations of the immunomodulatory steroidal hormones cortisol and estrogen. Dexamethasone directly reduced the generation of reactive oxygen species (ROS) by uterine PMN. This may be a useful mechanism since it would protect the endometrium from tissue damage by excessive extracellular ROS. However, it is not known if the net effect is in fact a reduction in ROS, as the number of uterine cells increases. Our study shows that glucocorticoids may not be considered immunosuppressive in all cases and may play an important role in the regulation of post partum uterine defense mechanisms.


Assessment of clinical efficacy of traditional Chinese medicine for the management of primary dysmenorrhea in the UK: A protocol of systematic review.
This study aims to appraise the clinical efficacy of traditional Chinese medicine (TCM) for the management of patients with primary dysmenorrhea (PD) in the UK. We will comprehensively search electronic databases (Cochrane Library, PUBMED/MEDLINE, EMBASE, PsycINFO, AMED, Web of Science, and CNKI) and additional resources for original articles on randomized controlled trials published in English, Chinese, German, Spanish, Korean and Japanese. Outcomes will be the pain intensity, pain duration, menstrual cramps, amount of bleeding, and severity of dysmenorrhea symptoms, quality of life, and adverse events. Two authors will independently check all citations, extract data, and assess study quality. All potential conflicts will be solved through discussion by consulting another experienced author. A narrative synthesis will summarize the characteristics and findings of eligible trials. If it is possible, we will also pool the data and carry out meta-analysis. The available evidence of the clinical efficacy of TCM for the treatment of PD in UK will be assessed through outcome measurements. The findings of this study will determine whether or not TCM is effective and safe for the treatment of PD in UK. OSF REGISTRATION NUMBER:: osf.io/jyc95.


A conflict between nutritionally adequate diets and meeting the 2010 dietary guidelines for sodium.
Compliance with dietary guidelines means incorporating multiple foods and nutrients into everyday diets, to be consumed in smaller or larger amounts. Feasibility studies can help determine whether one nutrient guideline comes into conflict with another. For one half of the U.S. population, the 2010 dietary guidelines for sodium were set at 1500 mg/d. To test the compatibility of the 1500 mg/day sodium goal with nutrient-adequate diets. Analyses, conducted in 2010, used U.S. federal nutrient composition and dietary intake databases to create modeled food patterns for six gender-age groups using linear programming techniques. The food patterns were designed to meet nutritional standards for 27 nutrients as the mean sodium content was progressively reduced from levels observed in the 2001-2002 National Health and Nutrition Examination Survey (NHANES) down to 1500 mg/day. For adults aged <50 years, the 2300 mg/day sodium goal was consistent with nutrient-adequate diets but required large deviations from current eating patterns. The 1500 mg/day goal was not feasible and no mathematical solution was obtained. The lowest-sodium food patterns that were nutrient-adequate and theoretically achievable were very high in fruit juices, nuts, and seeds but were low in grains and meats. Compliance with the 2010 sodium guidelines will require large deviations from current eating behaviors and/or a profound modification of the U.S. food supply.


Affective cognition in eating disorders: a systematic review and meta-analysis of the performance on the "Reading the Mind in the Eyes" Test.
The Reading the Mind in the Eyes Test (RMET) is listed in the National Institute of Mental Health's Research Domain Criteria as a tool apt to measure the understanding of others' mental states. People diagnosed with anorexia nervosa (AN) showed poorer performances on the RMET than healthy controls. Less data are available concerning other eating disorders. Systematic review of four major databases from inception to July 15, 2021 following the PRISMA guidelines. Meta-analysis of cross-sectional observational studies comparing the scores of the RMET between patients with eating disorders and age- and-gender matched control groups. Out of 21 studies, we retrieved 29 independent samples of patients diagnosed with an eating disorder. Patients with active AN (n = 580) showed worse performances on the RMET than controls (n = 1019). Year of publication accounted for 61% of the (substantial: I2 = 81%) heterogeneity in the meta-analysis. Earlier studies were more likely to find worse performances on the RMET of patients with active AN than later studies. Patients with bulimia nervosa (n = 185) performed poorly as compared to controls (n = 249), but the results were not statistically significant on the random-effect model. Obese patients with binge-eating disorder (n = 54) did not differ on the RMET from obese controls (n = 52). Patients with eating disorder not otherwise specified (n = 57) showed minimal differences compared to controls (n = 96). Study quality was good in six studies only. Patients with eating disorders do not suffer from an impaired understanding of others' mental states, except for a still-to-be-identified subgroup of patients with active AN. I, systematic review and meta-analysis.


Pholeter anterouterus Fischthal & Nasir, 1974 (Digenea: Opisthorchiidae) redescribed, together with remarks on the genera Pholeter Odhner, 1914 and Phocitrema Goto & Ozaki, 1930 and their relationship to the centrocestine heterophyids.
Photoleter anterouterus Fischthal & Nasir, 1974, from Pelecanus occidentalis Linnaeus and Pelecanus erythrorhynchos Gmelin from Florida, USA and the ventro-genital complexes of Photeleter gastrophilus (Kossack, 1910) from Delphinus delphis Linnaeus from Queensland, Australia and of Phocitrema fusiforme Goto & Ozaki, 1930 from Alopex lagopus (Linnaeus) and Phoca vitulina Linnaeus from Alaska are redescribed. The genus Photoleter Odhner, 1914 is emended and compared with Phocitrema Goto & Ozaki, 1930 and both genera are compared with members of, and as a result transferred from the family Opisthorchiidae Looss, 1899 to, the subfamily Centrocestinae Looss, 1899, family Heterophyidae Odhner, 1914.


Visualization of Protonation/Deprotonation of Active Pharmaceutical Ingredient in Solid State by Vapor Phase Amine-Selective Alkyne Tagging and Raman Imaging.
Here, we report a simple and direct method to visualize the protonation/deprotonation of an amine active pharmaceutical ingredient (API) in the solid state using a solid-vapor reaction with propargyl bromide and Raman imaging for the assessment of the API during the manufacturing process of solid formulations. An alkyne tagging occurred on the free form of solid haloperidol by the vapor phase reaction, and a distinct Raman signal of alkyne was detected. Alkyne signal monitoring by Raman imaging enabled us to visualize the distribution of the free-form haloperidol in a solid formulation. On the other hand, haloperidol hydrochloride did not react with propargyl bromide in the solid-vapor reaction, and the alkyne signal was not observed. Using the difference in reactivity, the protonation/deprotonation of the amine API in the solid state could be visualized. As an example of application, we tried to visually assess the protonation/deprotonation state when the free-form haloperidol was ground with acids using the solid-vapor reaction and Raman imaging and found that haloperidol was partially protonated when ground with 2 equivalents of hydrogen chloride. Furthermore, we demonstrated the relationship between the degree of protonation and the amount of water added as a medium for grinding haloperidol with succinic acid.


Molecular characterization and antimicrobial resistance profile of pathogenic Escherichia coli from goats with respiratory disease in eastern China.
Pathogenic Escherichia coli (E. coli) can cause a variety of intestinal and extra-intestinal infections in humans and animals. Similar with the intestinal disease, respiratory disease is also a major threat to the breeding industry of goats. But the reports on respiratory disease associated E. coli are very limited. In this study, E. coli and other pathogens were examined for the 77 submitted respiratory cases. The serotypes, virulence genes, phylogenetic group and antimicrobial resistance characteristics of the E. coli isolates were identified. The results showed that 34 cases (44.16%) were associated with E. coli and 22 cases showed mixed infections of E. coli with Mycoplasma ovipneumoniae, Mannheimia haemolytica or Pasteurella . Among the 49 E. coli isolates, O8 (32.65%), O9 (20.41%) and O89 (10.20%) were the predominant serotypes (31/49, 63.27%). 22 virulence genes were detected and the most prevalent genes were fimH (100%), yijp (100%), mat (97.96%), ompA (95.92%) ibeB (91.84%) and fyuA (77.55%). In addition, ibeA was detected in 6.12% (3/49) of the strains. Markers of extra-intestinal pathogenic E. coli (ExPEC) were also identified and 14 strains were classified as ExPECs. 14 (28.57%), 25 (51.02%), 3 (6.12%) and 7 (14.29%) strains belonged to phylogenetic group A, B1, B2 and D, respectively, and group A and B1 were the predominant ones. The E. coli strains showed high resistant (48.98%-100%) to the 14 selected antimicrobials and all of them were defined as multiple drug resistant (MDR) strains. This is the first systemically study on E. coli of goats respiratory diseases origin in eastern China. The results suggest that E. coli infection may play an important role in goat respiratory diseases and that goats are reservoir hosts of ExPECs, which needs continuous monitoring in the future.


Genetic variants of VWF gene in type 2 von Willebrand disease.
von Willebrand disease (VWD) is the most common inherited bleeding disorder. Few studies have explored the molecular basis of type 2 VWD. This study aimed to identify variants associated with type 2 VWD. We collected clinical and laboratory data, as well as response to desmopressin and bleeding assessment tool (BAT) score in patients diagnosed with type 2 VWD. We sequenced exons 17, 18, 20 and 28 of the VWF gene. We identified 19 different variants in 40 unrelated patients (47.5%). Most of the variants (84.2%) were found in exon 28. A total of 10/19 variants (52.6%) were identified as "likely causative" in 17/40 patients (42.5%), according to the ISTH-SSC and EAHAD VWF gene mutations databases. Nine variants were initially identified as potentially benign. However, through analyses in silico, four of these variants were reclassified as "likely pathogenic" (Ile1380Val, Asn1435Ser, Ser1486Leu and Tyr1584Cys). Response to desmopressin was associated with three variants: Met740Ile, Arg1597Gln and Tyr1584Cys. Major bleeding was associated with variants related to VWD subtypes 2B and 2M. In conclusion, we identified 19 variants, of which 14 are "likely pathogenic" and therefore associated with VWD. We suggest a possible association of pathogenic variants with major bleeding, response to desmopressin and BAT score ≥10, although this requires further confirmation.


Water potential of standing-dead shoots of an intertidal grass.
Dead stems and leaves of smooth cordgrass (Spartina alterniflora Loisel.) undergo substantial fungal decay in the standing position. We conducted a series of experiments to determine the probable range of water availabilities that cordgrass-fungal decomposers experience; we determined the effects of duration of wetting and drying, site on shoots, leaching of osmotica, and stage of decomposition on water potential (ψ) of cordgrass shoots. Dried pieces of cordgrass shoots took up water rapidly when submerged, rising from values which were probably less than -150 megapascals (MPa) water potential to about -3.5 (soaked in seawater) or -1.5 (soaked in tapwater) within 5 min. Air-drying resulted in a return to low ψ (<-7.5 MPa) within an hour. Literature reports show that most litter and wood-decomposing fungi which have been tested cannot grow at ψ more negative than -6 MPa. The more lignified stems showed a more negative matric ψ than leaves at water contents greater than 25% fresh weight. As leaves decomposed in the marsh, their ψ increased (from -1.7 to -0.5 MPa, under standard conditions of 30 min freshwater soaking and 30 min air-drying), similar to what other investigators have found for wheat and forest litter. The water content at which cordgrass leaves reached -6 MPa was about 23% fresh weight, within the range (15-32%) found for wheat straw and forest litter.


Positional distribution of exogenous and endogenous fatty acids in triacylglycerols formed by rat adipocytes in vitro.
Rat adipocytes were used in vitro to compare the positional distributions of fatty acids of intra- and extra-cellular origin in triacyl-sn-glycerols. Fatty acids of extracellular origin were esterified to each position in similar, but not identical, proportions to the natural distributions. A high proportion of the oleic acid synthesised in the tissue by desaturation of exogenous stearic acid was found in position sn-3. When palmitic acid was the only fatty acid added, tripalmitoylglycerol was synthesised by the adipocytes. The rate and pattern of fatty acids synthesised de novo from acetate was dependent on the age of the donor rat and the concentration of acetate and presence or absence of long-chain fatty acids in the medium. The newly synthesised fatty acids were esterified in very different proportions from the natural distributions and thus from those of extracellular fatty acids. The results are discussed in terms of esterification of the fatty acids from the two sources in different compartments of the cell.


Long-term mortality following complications after elective surgery: a secondary analysis of pooled data from two prospective cohort studies.
Complications after surgery affect survival and quality of life. We aimed to confirm the relationship between postoperative complications and death within 1 yr after surgery. We conducted a secondary analysis of pooled data from two prospective cohort studies of patients undergoing surgery in five high-income countries between 2012 and 2014. Exposure was any complication within 30 days after surgery. Primary outcome was death within 1 yr after surgery, ascertained by direct follow-up or linkage to national registers. We adjusted for clinically important covariates using a mixed-effect multivariable Cox proportional hazards regression model. We conducted a planned subgroup analysis by type of complication. Data are presented as mean with standard deviation (sd), n (%), and adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs). The pooled cohort included 10 132 patients. After excluding 399 (3.9%) patients with missing data or incomplete follow-up, 9733 patients were analysed. The mean age was 59 [sd 16.8] yr, and 5362 (55.1%) were female. Of 9733 patients, 1841 (18.9%) had complications within 30 days after surgery, and 319 (3.3%) died within 1 yr after surgery. Of 1841 patients with complications, 138 (7.5%) died within 1 yr after surgery compared with 181 (2.3%) of 7892 patients without complications (aHR 1.94 [95% CI: 1.53-2.46]). Respiratory failure was associated with the highest risk of death, resulting in six deaths amongst 28 patients (21.4%). Postoperative complications are associated with increased mortality at 1 yr. Further research is needed to identify patients at risk of complications and to reduce mortality.


Ecotoxicological effects of silver nanoparticles in marine mussels.
As the production of silver nanoparticles (AgNPs) is becoming more prevalent, it is becoming increasingly necessary to understand the toxicological effects they can have on different ecosystems. In the marine bioindicator species M. galloprovincialis Lam we predicted toxicity and bioaccumulation of 5 nm alkane-coated and 50 nm uncoated silver nanoparticles (AgNPs) along with silver nitrate as a function of the actual dose level. We generated a time persistence model of silver in seawater and used the Area Under the Curve (AUC) as independent variable in the hazard assessment. This approach allowed us to evaluate unbiased ecotoxicological endpoints for acute (survival) and chronic toxicity (byssal adhesion). Logistic regression analysis rendered an overall LC5096h values of 0.81 ± 0.07 mg h L-1 irrespectively of the silver form. By contrast, for byssal adhesion regression analysis revealed a much higher toxicological potential of silver nitrate vs AgNPs with EC5024h values respectively of 0.0024 ± 0.0009 vs 0.053 ± 0.016 and 0.063 (no computable error for 50 nm AgNP) mg h L-1, undoubtedly confirming a prevalence of ionic silver effects over AgNPs. Bioaccumulation was more efficient for silver nitrate >5 nm AgNP >50 nm AgNP reflecting a parallel with the preferential uptake route / target organ. Finally, we derived Risk Quotient (RQs) for acute and chronic effects of nanosilver in shellfish and showed that the RQs are far from the Level of Concern (LoC) at current estimated environmental concentrations (EECs). This information can ultimately help researchers, policy makers, and industry professionals decide how to safely regulate and/or dispose of AgNPs.


[Magnetic resonance imaging of the female pelvis].
The use of magnetic resonance (MR) imaging of the female pelvis has expanded considerably over the past decade. We here review important indications, including congenital anomalies, benign and malignant diseases and special emphasis is given to the diagnostic value and possible limitations of MR. MR also plays an increasing role in minimal access surgery.


[Severe malaria in children in Togo].
The definition of severe malaria is no longer limited to cerebral malaria, but is as well extended to other clinical forms of the disease. This work analyses epidemiological, clinical and evolutive aspects of severe malaria in Togo. This study included 549 children, aged from 0 to 15 years, hospitalized in 1994-5 in the pediatric department of the Lome-Tokoin University Teaching Hospital for severe malaria as defined by World Health Organization (WHO) criteria. The hospitalization frequency was 7.44%; the maximum frequency was from 1 to 5 years of age, but 6.56% of patients were more than 10 years old. The most frequent clinical form was that of severe anemia, followed by cerebral complications, as seen in many African countries. The death rate was 18.94% and the proportional mortality was 8.21%; 2.73% of the patients had neurological sequelae (behaviour disturbances in five cases, aphasia in four, hemiplegia in three, mumbling in one, oculomotor paralysis in one, and cerebellar ataxia in one). Hypoglycemia was fairly frequent (11.6%) and was associated with a poor prognosis. It is possible to improve severe malaria prognosis in Africa by insisting not only on better equipment in intensive care wards, but also on improved and early management of hypoglycemia.


The potential cardioprotective effects of amifostine in irradiated rats.
The aim of this study is to determine the cardioprotective efficacy of amifostine. The study consists of researching the relationship between plasma brain natriuretic peptide levels and the electrical and morphologic changes in irradiated rats with or without amifostine. Sixty Wistar albino rats were divided into 4 groups, and their hearts were given 15 Gy/fraction with (60)Co. In Groups I and II, the rats were killed after 24 hours to detect early effects; in Groups III and IV, the rats were killed 100 days after irradiation to detect late effects. Before irradiation, Groups I and III received 0.9% saline solution, whereas Groups II and IV received amifostine (200 mg/kg). Twenty rats were used as a control group. On the 100th day, mild myocardial degeneration was detected in 5 rats (33%) from Group III (no amifostine). This percentage was statistically different from that of Group IV (treated with amifostine) and the controls (p = 0.042). There was no statistically significant difference between the mean plasma brain natriuretic peptide values of the groups (p > 0.05). There was no significant difference in electrocardiographies between the groups. There was no correlation between continuous variables. In the amifostine group (IV) on the 100th day, there was no myocardial degeneration, suggesting that amifostine has a cardioprotective effect.


Two classes of spontaneous miniature excitatory junction potentials and one synaptic vesicle class are present in the ray electrocyte.
Cross sections (1-2 mm thick) of the ray (Raja) tail were secured to a dish and immersed in elasmobranch saline. Spontaneous miniature excitatory junction potentials (MEJPs) were recorded by advancing a 50 k omega, KCl filled electrode into the electric organ (20 microV peak-to-peak baseline noise). Data were filmed, and/or recorded on magnetic tape for computer analyses. Intracellularly recorded MEJP amplitude histograms showed a peak at 60 microV and had a right-hand skew with MEJPs up to 0.5 mV. The small peak amplitude and the skewed amplitude distribution of intracellularly recorded MEJPs result from the relatively low input resistance and the short space constant of the electrocyte coupled with the dispersed synapses on the electrocyte. At 23 degrees C the intracellularly recorded MEJP frequency ranged from 1-10 MEJPs/s. The MEJPs became larger and became focally recorded as the electrode was advanced against the intracellular surface of the innervated membrane of the electrocyte. Focal extracellular MEJPs (reversed polarity) were also recorded with the electrode positioned against the outside surface of the innervated side of the electrocyte. The frequency of focally recorded intracellular MEJPs was increased (up to 40/s) when the electrode was pushed against the membrane. Focal MEJP frequencies decreased to a few/min within 5-10 min but the mean amplitude of 3-5 mV remained constant. Decreases in amplitude and frequency in focally recorded intracellular MEJPs are attributed to changes in electrode pressure against the membrane. Amplitude histograms were constructed from focally recorded intracellular or extracellular MEJPs which showed the same time characteristics. The focal MEJP amplitude histograms have two distinct classes, each forming a bell-shaped distribution. It is concluded that both classes are generated at the electrode tip. The smaller class of MEJPs has a mean 1/10th that of the larger class and composes about 2% of the MEJPs. The small class is analogous to the sub-MEPP class found in the frog sartorius (Kriebel and Gross 1974) and mouse diaphragm (Kriebel et al. 1976, 1982). Distributions of synaptic vesicle diameters are slightly log normal (right hand skew) such that the mean diameter (57 nm) is slightly larger than the modal value (52 nm). Vesicles touching the membrane were of the same size and diameter distribution as the entire vesicle population. The profiles of the distributions are smooth and suggest only 1 class of synaptic vesicle based on diameter.


Autonomy Maps: Building a Shared Mental Model for Progressive Resident Operative Autonomy on the Road to Entrustable Professional Activities (EPAs).
Our residents expressed dissatisfaction with operative autonomy and faculty feedback regarding technical skills. They reported variability among faculty regarding allowed operative autonomy. Our goals were to establish a shared mental model among residents and faculty regarding intraoperative performance expectations. We asked faculty to assign a level of expected autonomy (Zwisch scale) for various steps of common procedures according to the resident post-graduate year. Through an iterative process, the maps were standardized across service lines. The resulting "Autonomy Maps" were distributed to the faculty and residents. We held educational sessions and set expectations for use. Selected benchmarks were incorporated into resident end-of-rotation assessment forms. Initial operative case mapping identified variability in faculty expectations for a given post-graduate year and procedure. Residents reported improved satisfaction with understanding expectations regarding operative performance. Establishing autonomy benchmarks facilitated more specific feedback regarding residents' technical skills. Faculty expectations for resident operative autonomy are variable. Autonomy Maps provide structure for a shared mental model between faculty and residents for progressive operative autonomy and serve as a framework for expectations that improve resident satisfaction. Case-specific technical benchmarks are useful tools for assessing residents' technical milestones.


Upregulation of interferon-alpha gene in bovine embryos produced in vitro in response to experimental infection with noncytophatic bovine-viral-diarrhea virus.
In-vitro fertilization is a routine livestock-breeding technique widely used around the world. Several studies have reported the interaction of bovine viral-diarrhea virus (BVDV) with gametes and in-vitro-produced (IVP) bovine embryos. Since, gene expression in BVDV-infected IVP bovine embryos is scarcely addressed. The aim of this work was to evaluate the differential expression of genes involved in immune and inflammatory response. Groups of 20-25 embryos on Day 6 (morula stage) were exposed (infected) or not (control) to an NCP-BVDV strain in SOF medium. After 24 h, embryos that reached expanded blastocyst stage were washed. Total RNA of each embryo group was extracted to determine the transcription levels of 9 specific transcripts related with antiviral and inflammatory response by SYBR Green real time quantitative (RT-qPCR). Culture media and an aliquot of the last embryos wash on Day 7 were analyzed by titration and virus isolation, respectively. A conventional PCR confirmed BVDV presence in IVP embryos. A significantly higher expression of interferon-α was observed in blastocysts exposed to NCP-BVDV compared to the controls (p < 0.05). In this study, the upregulation of INFα and TLR7 genes involved in inflammatory and immune response in BVDV-infected IVP bovine embryos is a new finding in this field. This differential expression suggest that embryonic cells could function in a manner like immune cells by recognizing and responding early to interaction with viral pathogens. These results provide new insights into the action of BVDV on the complex molecular pathways controlling bovine early embryonic development.


The elephant man. Part III.
This is the third paper in a series of three articles on Joseph Merrick, The Elephant Man. Three matters are discussed about which there is uncertainty: the disease which affected his left femoral head, the cause of his deformity and the cause of his death.


The 3'-untranslated region of apolipoprotein II mRNA contains two independent domains that bind distinct cytosolic factors.
The 3'-untranslated region of apolipoprotein II (apoII) mRNA contains target sites for mRNA breakdown (Binder, R., Hwang, S.-P. L., Ratnasabapathy, R., and Williams, D. L. (1989) J. Biol. Chem. 264, 16910-16918). Degradation occurs via endonucleolytic cleavage at 5'-AAU-3'/5'-UAA-3' elements in single-stranded loop domains of the 3'-untranslated region. Degradation target sites occur in two clusters that are localized within two larger domains of secondary structure. In this study, gel shift and label transfer assays were used to identify liver cytosolic factors that recognize the 3'-untranslated region of apoII mRNA. The results show preferential binding of cytosolic factors to the 3'-untranslated region as compared to the coding region. UV cross-linking experiments confirmed that cytosolic factors labeled by the 3'-untranslated region are a subset of proteins labeled by the entire mRNA. Two distinct binding domains were identified within the 3'-untranslated region. The upstream domain encompassing nucleotides 400-547 extends from the translation stop codon through the complex stem-loop D structure described previously. This domain labeled primarily a 34-kDa protein in UV cross-linking experiments. The downstream binding domain encompassing nucleotides 568-643 includes another region of secondary structure and terminates within the universal polyadenylation signal. The downstream domain labeled primarily a 60-kDa protein in UV cross-linking experiments. The upstream and downstream binding domains did not compete with each other in gel shift or cross-linking experiments. These results indicate that the 3'-untranslated region can form two independent messenger ribonucleoprotein complexes localized to domains that include target sites for apoII mRNA degradation. We speculate that these messenger ribonucleoprotein complexes may play a role in the degradation of apoII mRNA or in the regulation of this process.


Enhanced hydrophobic paper-sheet derived from Miscanthus × giganteus cellulose fibers coated with esterified lignin and cellulose acetate blend.
Biobased packaging materials derived from carbon-neutral feedstocks are sustainable alternatives to conventional fossil-based polymers. In this study, a method was developed to prepare paper-sheets derived from Miscanthus × giganteus cellulose fibers for potential food contact applications. The papers were hydrophobized with modified lignin from Miscanthus × giganteus biomass and commercial Kraft alkali lignin through hydroxyethylation with ethylene carbonate, followed by esterification with propionic acid. The esterified lignin (10 % w/w) and cellulose acetate (5 % w/w, based on lignin content) were dissolved in acetone and applied as a coating on the miscanthus paper sheets. The esterified lignins were characterized using FTIR, NMR, DSC, TGA, and elemental analyses. The uncoated and coated paper-sheets had contact angle values 52.4° and >130°, respectively, indicating an increased surface hydrophobicity of the coated paper samples. The water vapor transmission rate decreased significantly from 213.7 (uncoated paper-sheet) to 63.3 g/m2.d (coated paper-sheet). The tensile strength of the coated paper (64.6 MPa) was higher than the uncoated counterpart (57.1 MPa). Results from this study suggest that the esterified lignin coated miscanthus paper is a promising hydrophobic food packaging material alternative to conventional fossil-based thermoplastics.


Development of human monoclonal antibodies: A review.
This article describes the current status in the development of human monoclonal antibodies. Over the last ten years a lot of information about the human immune system has emerged. Combining these with the many new (bio-)technologies it is plausible that the long awaited breakthrough of this technology is close. This paper focuses on the "classical" cell-biological methods of achieving stable, antibody-producing human cell lines via cell fusion methods or virus derived transformations of human B-lymphocytes, as well as genetic engineering methods e.g. DNA libraries or phage display technology. The available in vitro immunization methods are critically reviewed and their impact on this topic is discussed. Therapeutic applications for cancer treatment or passive immunization against infectious diseases with antibodies derived by both ways are also reviewed.


The organizational model of the interregional transplant agency Organizzazione Centro-Sud Trapianti.
In Italy, all donation and transplant activities were officially disciplined in 1999 by the law 91 of April 1, 1999. This law enacted a coordinator-based model of transplantation, instituted the National Center for Transplantation (Centro Nazionale Trapianti-CNT), and endorsed the existing interregional transplant agencies (ITA), such as the Nord Italia Transplant program (NITp), the Associazione InterRegionale Trapianti (AIRT), and the Organizzazione Centro-Sud Trapianti (OCST). Within its borders each ITA has adopted its own organizational model; there is no overt centralized control exerted by the CNT according to the law 91/1999. The aim of the current work is to report on the organizational model adopted by OCST, the ITA gathering the Italian regions of Abruzzo, Basilicata, Calabria, Campania, Latium, Molise, Sardinia, Sicily, and Umbria.


Neonatal intensive care unit sound levels before and after structural reconstruction.
This study compared sound levels before and after structural reconstruction within an NICU. Using a descriptive design, sound level recordings (in decibels, A-weighted scale) of the Leq, L10, and Lmax were measured continuously for 8 hours (0600-1400) before and after reconstruction in an NICU located in north central Florida. Levels before reconstruction were Leq M = 60.44 dB, L10 M = 59.26 dB, and Lmax M = 78.39 dB. The average overall sound levels after reconstruction were Leq M = 56.4 dB, L10 M = 60.6 dB, and LmaxM = 90.6 dB. Although an approximate 4-decibel decrease in the Leq sound level after reconstruction was noted, a similar decrease in the L10 and Lmax did not occur. Furthermore, sound levels after reconstruction in the NICU still exceeded recommended levels (Leq < 50 dB, L10 < 55 dB, and Lmax < 70 dB). Findings from this study demonstrated the positive impact that reconstruction can have on sound levels (4 dB Leq decrease); however, additional interventions may be needed to meet the current standards for noise reduction in an NICU.


Comparison of preparative HPLC/MS and preparative SFC techniques for the high-throughput purification of compound libraries.
A diverse set of 16 high-throughput organic synthesis libraries, consisting of 48 samples per library, has been purified by both preparative supercritical fluid chromatography (SFC) and preparative high-performance liquid chromatography (HPLC). This paper details the relative effectiveness of these two purification techniques in terms of success, yield, and purity of final product.


Isolation and characterization of jack bean beta-galactosidase.
A simple procedure has been devised to isolate beta-galactosidase from jack bean meal. The final preparation gives one major protein banc in disc gel electrophoresis. The substrate specificity of this enzyme toward some natural oligosaccharides, glycoproteins, and sphingoglycolipids has been examined in detail. Among three isomers of N-acetyllactosamine, Galbeta1leads to4GlcNAc; while Galbeta1leads to3GlcNAc was hydrolyzed very slowly. This property can be used to distinguish the galactose linkage in asialo-GM1 (Galbeta1leads to3GalNAcbeta1leads to4Galbeta1leads to4Glcleads toCer) and that in lacto-N-neotetraosylceramide (Galbeta1leads to4GlcNAcbeta1leads to 3Galbeta1leads to4Glcleads toCer). For hydrolyzing glycolipids, the effect of sodium taurodeoxycholate and sodium taurochenodeoxycholate on the rate of hydrolysis was carefully examined. This enzyme hydrolyzes lactosylceramide and asialo-GM1 faster than GM1. These results suggest that in addition to the type and linkage of the penultimate sugar unit, the sugar unit at the distal position of the saccharide chain also affects the hydrolysis rate. It also readily liberates 80% D-galactosyl units from asialo alpha1-acid glycoprotein. Escherichia coli beta-galactosidase on the other hand cannot hydrolyze asialo-alpha1-acid glycoprotein, lactosylceramide, GM1, asialo-GM1, and lacto-N-neotetraosylceramide. The molecular weight of this enzyme is about 75,000 and the isoelectric point is pH 8.0. With p-nitrophenyl beta-D-galactopyranoside as substrate, optimal activity occurs at pH 2.8 with glycine-HCl buffer and at pH 3.5 with citrate-phosphate buffer. With lactose as substrate, the pH optimum in these two buffers are 2.8 and 4.0, respectively. Km values for p-nitrophenyl beta-D-galactopyranoside, o-nitrophenyl beta-D-galactopyranoside and lactose are 0.51 mM, 0.63 mM, and 12.23 mM, respectively. Many inhibitors for this enzyme including inorganic ions, monosaccharides, and glycosides are investigated. In contrast to E. coli beta-galactosidase, jack bean beta-galactosidase is not inhibited by p-aminophenyl thio-beta-D-galactopyranoside.


Retinal dystrophins and the retinopathy of Duchenne muscular dystrophy.
Duchenne muscular dystrophy (DMD) is caused by X-linked inherited or de novo DMD gene mutations predominantly affecting males who develop early-onset muscle degeneration, severely affecting their quality of life and leading to reduced life expectancy. DMD patients may also develop proliferative retinopathy, cataract, ERG abnormalities, altered contrast sensitivity, color vision losses, and elevated flash detection thresholds during dark adaptation. Depending on the position of the genetic alteration in the large DMD gene, it is associated with a lack of the full-length dystrophin protein possibly with an additional loss of one or several other dystrophins, which are normally transcribed from internal promoters in retina and crystalline lens. During the last decades, the properties of the dystrophins have been characterized in patients with different genetic alterations and in genetic mouse models of DMD. The complex expression pattern of the dystrophins in photoreceptors, Müller glial cells and astrocytes, likely influences synaptic transmission, ionic balance and vascular integrity of the retina. However, the specific function of each retinal dystrophin remains largely unknown. This review describes the current knowledge on dystrophin expression, the putative molecular, structural, and physiological properties of retinal dystrophins, and the main clinical implications associated with the loss of dystrophins in DMD patients and mouse models. Current data and working hypotheses warrant future research on retinal dystrophins to increase our understanding of dystrophin function in the central nervous system in general and to unveil new retinal mechanisms and therapeutic avenues for retinal diseases.


New halogenated tris-(phenylalkyl)amines as h5-HT2B receptor ligands.
A series of compounds in which various halogen substituents were incorporated into a phenyl ring of a tris-(phenylalkyl)amine scaffold, was synthesized and evaluated for affinity to h5-HT2 receptors. In general, all compounds were found to have good affinity for the 5-HT2B receptor and were selective over 5-HT2A and 5-HT2C receptors. Compound 9i was the most selective compound in this study and is the highest affinity 5-HT2B receptor ligand bearing a tris-(phenylalkyl)amine scaffold to date.


Bromocriptine in pregnancy: safety aspects.
Since Bromocriptine is used to restore fertility in hyperprolactinemic women, its safety in pregnancy and the offspring was investigated in a stepwise approach: (i) the first survey in pregnancy was based on spontaneous reporting, (ii) the second investigation was conducted at 33 clinics as an intensive monitoring project and, (iii) the third study consisted in a full examination of children up to the age of 9 years who had been exposed to Bromocriptine in utero. The data collated in this program includes information on 2587 pregnancies in 2437 women treated with Bromocriptine during some stage of gestation, and follow-up examinations for 988 infants. The results show that the use of Bromocriptine in the treatment of infertility in women is not associated with an increased risk of spontaneous abortion, multiple pregnancy or the occurrence of congenital malformation in their progeny. Moreover, exposure to this drug in utero has no adverse influence on the postnatal development.


Sex-based differences in cardiac resynchronization therapy upgrade and outcome for patients with pacemaker and new-onset heart failure.
Patients with chronic right ventricular (RV) pacing are at an increased risk of heart failure. Previous studies have indicated that cardiac resynchronization therapy (CRT) is underused in this setting, and that there may be sex-based differences in both CRT use and clinical outcome. To evaluate sex-based differences in CRT use and clinical outcome for patients with new-onset heart failure post RV pacing. Data from the Swedish pacemaker registry was matched with data from the national death and disease registries. Patients with de novo pacemaker implant due to AV block during the period 2005-2020 were included. New-onset heart-failure within two years post-implant was evaluated, primary outcome was all-cause mortality. In all, 30183 patients (37% female) were included. Women were on average 3 years older, but had less comorbidities than men. Median follow-up time was 4.5 [2.0-8.0] years. Women had better age- and comorbidity-adjusted survival (HR 0.78 [0.73-0.84], p < .001). For the 3560 patients (12.4% men and 10.7% women, p < .001) who were diagnosed with new-onset heart failure, 5-year mortality was similar for men and women (50% vs. 48%, p = .29). However, women were less likely to receive CRT-upgrade (3.8% vs. 9.1%, p < .001), and those who did were almost ten years younger than the men. Women with pacemaker due to AV block are older but have less comorbidities than men. They are less likely to develop new-onset heart failure, but also less likely to receive a CRT upgrade if they do develop heart failure. Increased awareness of the positive effects of CRT upgrade and potential sex- and age-based discrimination is warranted.


Topographic distribution of the 40 Hz auditory evoked-related potential in normal and aged subjects.
Galambos, Makeig and Talmachoff (1981) described what they called the 40 Hz event-related potential (ERP). This steady-state response is an EEG following response to repetitive auditory stimulation which becomes sinusoidal in form and maximal in amplitude at rates between 35 and 45 Hz. The present study was designed to examine the scalp topography of the 40 Hz ERP in order to complement previous magnetoencephalographic studies which implicate auditory cortex in the generation of the response. In addition, this study was designed to collect normative data on an aged sample in order to assess the effects of aging on the response. 40 Hz ERP's were recorded from a group of seven audiometrically and neurologically normal elderly subjects (mean age = 69.6 years) and a younger group of five normal adults (mean age = 38.0 years), using 1000 Hz tones presented binaurally at 40 per second. A 21 channel recording system was used to obtain a comprehensive picture of the scalp distribution of the response. Recorded ERP's were Fourier transformed to enhance the signal-to-noise ratio. No significant differences were found in phase or amplitude of the 40 Hz ERP between the two age groups, indicating that the normal aging process does not have an effect on this response. Topographic maps of the 40 Hz ERP showed reversals of electrode potential in temporal regions, supporting an interpretation of bilateral sources in temporal cortex. The data presented in this study complement previous studies of the 40 Hz event-related magnetic field and support the position that temporal cortex is involved in the generation of the response.


Novel data-mining methodologies for adverse drug event discovery and analysis.
An important goal of the health system is to identify new adverse drug events (ADEs) in the postapproval period. Datamining methods that can transform data into meaningful knowledge to inform patient safety have proven essential for this purpose. New opportunities have emerged to harness data sources that have not been used within the traditional framework. This article provides an overview of recent methodological innovations and data sources used to support ADE discovery and analysis.


[Growth and development in the practice of health services. Historical review of the concept of child].
Conditions for the emergence and development of health and social policy programs for children are discussed. The concepts of the child, health and health services prevalent in certain historical periods are expounded, as are the relationships of these proposals to the political and economic interest dominant in each social context, in the light of the social aspect of knowledge.


Construction and validation of prognostic models in critically Ill patients with sepsis-associated acute kidney injury: interpretable machine learning approach.
Acute kidney injury (AKI) is a common complication in critically ill patients with sepsis and is often associated with a poor prognosis. We aimed to construct and validate an interpretable prognostic prediction model for patients with sepsis-associated AKI (S-AKI) using machine learning (ML) methods. Data on the training cohort were collected from the Medical Information Mart for Intensive Care IV database version 2.2 to build the model, and data of patients were extracted from Hangzhou First People's Hospital Affiliated to Zhejiang University School of Medicine for external validation of model. Predictors of mortality were identified using Recursive Feature Elimination (RFE). Then, random forest, extreme gradient boosting (XGBoost), multilayer perceptron classifier, support vector classifier, and logistic regression were used to establish a prognosis prediction model for 7, 14, and 28 days after intensive care unit (ICU) admission, respectively. Prediction performance was assessed using the receiver operating characteristic (ROC) curve and decision curve analysis (DCA). SHapley Additive exPlanations (SHAP) were used to interpret the ML models. In total, 2599 patients with S-AKI were included in the analysis. Forty variables were selected for the model development. According to the areas under the ROC curve (AUC) and DCA results for the training cohort, XGBoost model exhibited excellent performance with F1 Score of 0.847, 0.715, 0.765 and AUC (95% CI) of 0.91 (0.90, 0.92), 0.78 (0.76, 0.80), and 0.83 (0.81, 0.85) in 7 days, 14 days and 28 days group, respectively. It also demonstrated excellent discrimination in the external validation cohort. Its AUC (95% CI) was 0.81 (0.79, 0.83), 0.75 (0.73, 0.77), 0.79 (0.77, 0.81) in 7 days, 14 days and 28 days group, respectively. SHAP-based summary plot and force plot were used to interpret the XGBoost model globally and locally. ML is a reliable tool for predicting the prognosis of patients with S-AKI. SHAP methods were used to explain intrinsic information of the XGBoost model, which may prove clinically useful and help clinicians tailor precise management.


Effects of endocrine disruptors on the formation of prostaglandin and arachidonoyl-CoA formed from arachidonic acid in rabbit kidney medulla microsomes.
Under physiological conditions, small amounts of free arachidonic acid (AA) are released from membrane phospholipids, and cyclooxygenase (COX) and acyl-CoA synthetase (ACS) competitively act on this fatty acid to form prostaglandins (PGs) and arachidonoyl-CoA (AA-CoA). To explore the possible actions of endocrine disruptors on the metabolic fate of free AA into these two pathways, we investigated the effects of nonylphenol (NP), bisphenol A (BPA), di-n-butyl phthalate (DBP), benzyl-n-butyl phthalate (BBP) and di-2-ethylhexyl phthalate (DEHP) on the formation of PG and AA-CoA from 5 microM AA (close to the physiological concentration of the substrate) in rabbit kidney medulla microsomes. The kidney medulla microsomes were incubated with 5 microM [(14)C]-AA in 0.1 M Tris/HCl buffer (pH 8.0) containing cofactors of COX (reduced glutathione and hydroquinone) and cofactors of ACS (ATP, MgCl(2) and CoA). After incubation, PG (as total PGs) and AA-CoA were separated by selective extraction using petroleum ether and ethyl acetate. NP (1-200 microM) strongly enhanced the AA-CoA formation with a coincident decrease in the PG formation. BPA, DBP, BBP and DEHP failed to show any effect on the PG and AA-CoA formation up to 200 microM. Experiments utilizing 60 microM AA as the substrate concentration indicated that, under a low concentration of AA, NP decreases PG formation by inhibiting the COX activity, and reduces the AA flow into the COX pathway through inhibition on the COX activity, increasing availability of the substrate for the ACS and leading to enhanced AA-CoA formation. These results firstly show that NP has the potential to disturb the balance of PG and AA-CoA formations under normal physiological conditions.


Modulation of cardiometabolic pathways in skin and serum from patients with psoriasis.
Moderate-to-severe psoriasis is associated with an increased risk of atherosclerotic cardiovascular disease (ASCVD); however, the link is poorly understood. Skin and serum from patients with psoriasis were evaluated to understand if there was evidence of dysregulation in a targeted group of inflammatory and lipid genes related to ASCVD. Microarray analyses of expression of targeted ASCVD genes from skin in 89 patients with moderate-to-severe psoriasis from the ACCEPT trial were compared with non-diseased skin from healthy controls (n = 25). Serum (n = 149) was tested at baseline for monocyte chemoattractant protein-1 (MCP-1), macrophage-derived chemokine (MDC), and apolipoprotein-A1 (Apo-A1) comparing to healthy controls (n=162). An increase in skin gene expression for MCP-1 (7.98-fold) and MDC (6.66-fold) (p < 0.001 each) was observed in lesional versus healthy skin. Significant decreases in liver X receptor-alpha (LXR-α) (-5.94-fold), a protective lipoprotein metabolism gene, and in peroxisome proliferator-activated receptor-alpha (PPAR-α) (-7.58-fold), a protective anti-inflammatory and lipid modulating gene, were observed in lesional versus healthy skin (p < 0.001 each). Serum analyses revealed that MCP-1 (502 vs. 141 pg/mL) and MDC (1240 vs. 409 pg/mL) levels were significantly elevated in psoriasis compared with healthy controls (p < 0.001 each). Dysregulated lipid metabolism was also evident in the serum, as Apo-A1, a protein product related to PPAR-α activation, was significantly decreased in patients with psoriasis compared with healthy controls (25.2 vs. 38.9 mg/dL; p < 0.001). Analyses of targeted genes and their products known to be associated with ASCVD revealed dysregulation of inflammatory (MCP-1 and MDC) and lipid metabolism (LXR-α, PPAR-α) genes in psoriasis. These findings provide evidence of a potential shared pathophysiology linking psoriasis to cardiometabolic diseases.


Persistence of PCR-positive tissue in benznidazole-treated mice with negative blood parasitological and serological tests in dual infections with Trypanosoma cruzi stocks from different genotypes.
To assess different methodologies to better define an early post-therapeutic cure criterion after benznidazole treatment in BALB/c mice following mixed infection with dual Trypanosoma cruzi genotypes. According to the classical cure criteria, animals were classified as treated not cured (TNC = 76.4%), treated cured (TC = 12.5%) and dissociated (DIS = 11.1%) using parasitological [fresh blood examination (FBE), blood culture (BC) and blood PCR] and serological methods [conventional serology (CS-ELISA) and non-conventional serology (NCS-FC-ALTA)]. Tissues were also evaluated by PCR. FBE was able to detect patent parasitaemia in only 18.1% of TNC and therapeutic failure was detected in 79.1% and 97.2% of TNC by BC and blood PCR, respectively. CS-ELISA should not be used before 3 months after treatment since it may lead to false-negative results. At 3 months after treatment with benznidazole, NCS-FC-ALTA was more efficient for categorizing the groups of treated mice. In the TNC group, although a decreased frequency of PCR-positive tissue was observed in several host tissues, increased positivity was also observed, despite the T. cruzi genotype combination. All TC animals presented at least two positive tissue-PCR results. Our results confirm that NSC-FC-ALTA and blood PCR are the most suitable methods to early detect therapeutic failure in acute murine T. cruzi infection. Additionally, our data show that BC positivity is highly dependent upon the T. cruzi genotype combination. Moreover, our findings demonstrated that PCR tests performed on tissues from animals considered cured after benznidazole treatment still detected T. cruzi DNA, most probably indicating residual infection.


Effects of Impulsive Pile-Driving Exposure on Fishes.
Six species of fishes were tested under aquatic far-field, plane-wave acoustic conditions to answer several key questions regarding the effects of exposure to impulsive pile driving. The issues addressed included which sound levels lead to the onset of barotrauma injuries, how these levels differ between fishes with different types of swim bladders, the recovery from barotrauma injuries, and the potential effects exposure might have on the auditory system. The results demonstrate that the current interim criteria for pile-driving sound exposures are 20 dB or more below the actual sound levels that result in the onset of physiological effects on fishes.


Amyloid-independent functional neural correlates of episodic memory in amnestic mild cognitive impairment.
Although amnestic mild cognitive impairment (aMCI) could have various biological characteristics, little attention has been given to the nature of episodic memory decline in aMCI with pathophysiologies other than Alzheimer's disease (AD), i.e., aMCI with low beta-amyloid (Aβ) burden. This study aimed to identify the functional neural basis of episodic memory impairment in aMCI with Aβ burden negative (aMCI-Aβ-) and to compare these results with aMCI with Aβ burden positive (aMCI-Aβ+). Individuals with aMCI (n = 498) were selected from the Alzheimer's Disease Neuroimaging Initiative database. Based on the mean florbetapir standard uptake value ratio, participants were classified as aMCI-Aβ- or aMCI-Aβ+. Correlations between memory scores and regional cerebral glucose metabolism (rCMglc) were analyzed separately for the two subgroups using a multiple regression model. For aMCI-Aβ-, significant positive correlations between memory and rCMglc were found in the bilateral claustrum, right thalamus, left anterior cingulate cortex, left insula, and right posterior cingulate. For aMCI-Aβ+, significant positive correlations between memory and rCMglc were found in the temporoparietal areas. These correlation patterns remained unchanged when clinical severity was added as a covariate Our findings indicate that memory impairment in aMCI-Aβ- is related to multimodal integrative processing and the attentional control system, whereas memory impairment in aMCI-Aβ+ is related to the typical brain memory systems and AD signature. These results suggest that although the two subgroups are clinically in the same category as aMCI, the memory impairment process depends on completely different functional brain regions according to their Aβ burden level.


Synthesis and antitumor activity of leinamycin derivatives: modifications of C-8 hydroxy and C-9 keto groups.
A series of leinamycin derivatives were synthesized and evaluated for antitumor activity. Modifications at C-8 and C-9 positions revealed a broad structure-activity relationship in vitro and some derivatives showed potent antiproliferative activity against HeLa S3 cells.


Avalanche Fatalities in the United States: A Change in Demographics.
To describe demographic patterns in avalanche fatalities in the United States during the past 6 decades according to geographic location and preavalanche activity. The Colorado Avalanche Information Center currently manages the National Avalanche Accident Dataset. This dataset describes deidentified avalanche fatalities beginning in 1951. Covariates included age, sex, month, state of occurrence, and preavalanche activity. Both absolute and proportional avalanche fatalities were calculated by year and by each covariate. A linear regression model was used to trend the proportion of avalanche fatalities stratified by covariate. There were 925 recorded avalanche fatalities in the United States between 1951 and 2013. There were an average of 15 ± 11 fatalities/y (mean ± SD; range, 0 to 40 fatalities/y). The mean (+/- SD) age was 29 ± 6.6 years (range, 6-67 years), and 86% were men. Total avalanche fatalities have increased linearly (R(2) = 0.68). Despite the highest number of total deaths in Colorado (n = 253), the proportion of avalanche fatalities in Colorado decreased (-5% deaths/decade; P = .01). Snowmobilers are now the largest group among fatalities and accounted for 23% of deaths (n = 213). The proportion of snowmobile fatalities has increased (+7% deaths/decade; P < .01), as has the proportion of snowboarder fatalities (+2% deaths/decade; P < .01). Avalanche fatalities have increased. This is most likely related to an overall rise in backcountry utilization. Fatalities have increased among snowmobilers and snowboarders. Despite a rise in backcountry utilization, avalanche fatalities in Colorado are decreasing. A strategy of focused training and education aimed toward at-risk groups could result in lower avalanche fatalities.


Keep circularity meaningful, inclusive and practical: A view into the plastics value chain.
New policies to promote the circular economy have created an urgent need for businesses and public authorities to quantify and monitor the level of circularity of materials, components and products. However, flows of materials, components and products through society are inherently complex, involving intricate value chains, many stakeholders, and interests. We argue that current actions may be overly focused on superficial effects, and losing sight of true circular economy goals. Using plastic packaging as an example, the present contribution deliberates the questions, "does measuring circularity address its goals?", "does it cover new technologies and regional specificities?", and "can its goals be addressed with simple assessment approaches?". In answering these questions, we argue that there is an impending risk of cementing policy and infrastructures that may not contribute to true sustainability. Furthermore, future technologies and developing regions are hardly included in the current circularity strategies. To further spark a discussion on the challenge of simplicity, we present a scorecard which can help incumbents to approximate the level of sustainable circularity of their products.


Proposal of an innovative benchmark for accuracy evaluation of dental crown manufacturing.
An innovative benchmark representing a dental arch with classic features corresponding to different kinds of prepared teeth is proposed. Dental anatomy and general rules for tooth preparation are taken into account. This benchmark includes tooth orientation and provides oblique surfaces similar to those of real prepared teeth. The benchmark is produced by additive manufacturing (AM) and subjected to digitization by a dental three-dimensional scanner. The evaluation procedure proves that the scan data can be used as reference model for crown restorations design. Therefore this benchmark is at the basis for comparative studies about different CAD/CAM and AM techniques for dental crowns.


The disposition of carboplatin in the beagle dog.
Carboplatin was administered i.v. to four groups of three male beagle dogs at doses of 3, 6, 12, and 24 mg/kg (60-580 mg/m2). Plasma samples were obtained at appropriate times and protein-free plasma ultrafiltrates (PU) were generated with Amicon Centrifree micropartition systems. Urine was collected at 24-h intervals for 96 h. PU and urine samples were analyzed for carboplatin by HPLC and for total platinum by atomic absorption spectrophotometry. Carboplatin accounted for about 90% of the free platinum in plasma. The Cmax and AUCinf values for carboplatin and for free platinum increased linearly with dose. The terminal elimination half-life and mean residence times for carboplatin and free platinum were each about 1 h. Total-body clearances for carboplatin (5.6 l/h per m2) and free platinum (5.1 l/h per m2) were constant over the dose range studied, as were the respective volumes of distribution (5.7 and 5.0 l/m2). A mean of 46% of the dose was excreted as carboplatin in 24-h urine; and by 72 h, 70% of the platinum administered was excreted in the urine. Free platinum was cleared by both renal and non-renal processes. These results show that a dose of carboplatin is rapidly excreted in the urine and that carboplatin and plasma-free platinum exhibit linear pharmacokinetics in the beagle dog.


Developing in a warming intertidal, negative carry over effects of heatwave conditions in development to the pentameral starfish in Parvulastra exigua.
Ocean warming and increasing incidence of marine heat waves (MHW) are having far-reaching impacts on coastal ecosystems. The small intertidal asterinid starfish, Parvulastra exigua, in south-eastern Australia, occurs in a global warming hotspot. Development occurs in the intertidal as this species lays eggs and has benthic larvae. The impact of temperature on development to the juvenile was determined over a broad temperature range (12-28 °C) encompassing temperatures experienced during the breeding season (16-20 °C) and cool (- 4 °C) and warm (+10 °C) extremes with the higher temperatures (24-28 °C) simulating a MHW. As the larva to juvenile transition involves major body reorganisation, we determined the impact of temperature on metamorphosis and formation of the normal five-armed juvenile. Development was faster at the higher temperatures 24-28 °C, but survival decreased from 1 to 5 days post fertilisation (dpf). Mortality was evident from day 15 at 22 °C and no larvae survived to 20 dpf at 28 °C. Thermal tolerance decreased over developmental time and the thermal optimum for 95% survival to the 20 day old juvenile spanned from 12 to 20.0 °C with the lethal temperature for 50% survival being 23.5 °C (5.5 °C above ambient). Juveniles reared in 26 °C were smaller, suggesting application of the temperature size rule. Increased temperature (22-26 °C) perturbed pentamery with three, four, six and no-armed juveniles present, contrasting with the low level of non-pentamerous individuals (<3%) in the cooler cultures and in nature (five populations surveyed). Despite the high thermal tolerance in premetamorphic stages, negative carry over effects were evident in the juveniles. This shows the importance of considering the whole of development in climate warming studies. As sea surface temperatures increase and heatwaves become more prevalent, habitat warming will be detrimental to P. exigua populations.


Effect of septal extension graft on nasal tip support: A finite element analysis.
Septal extension graft (SEG) is an effective method to control the projection, rotation, and shape of the nasal tip. However, the structural mechanics of SEG have not yet been adequately determined. The purpose of this study was to examine the effect of SEG parameters on nasal tip support using finite element analysis. A multicomponent nasal model was constructed from a computed tomographic scan. A control model without graft and a total of 15 models with different SEGs were created, regarding the direction, length, width, and piece of SEG. The nasal tip compression was simulated to analyze the von Mises stress, reaction force, and strain energy of the tip structure. The SEG increased the max stress, reaction force, and strain energy of the nasal tip compared to the normal control. The SEG perpendicular to the nasal dorsum resulted in the highest maximum stress, reaction force, and strain energy for the same size of SEG. With the length increasing from 15 × 8 × 1 mm to 25 × 8 × 1 mm, the reaction force remained relatively stable, but the stress on the graft reduced significantly. Adding the width and pieces of the SEG increased the reaction force and strain energy of the tip. The placement of SEG can strengthen the nasal tip support. The direction, length, width, and piece of SEG have an impact on the mechanics. Diagnostic, III.


Occupational dermatitis in a 10-year material.
This study included 1,752 patients considered to have occupational dermatoses. The most common diagnosis was contact dermatitis. The dermatitis was of an allergic type in three-quarters of men and in half of women. One-fifth of the women with irritant contact dermatitis had an atopic history. Contact dermatitis was localized on the hands in 94% of women and in 84% of men. The most common allergens in men were chromium, rubber and plastic, and in women nickel, rubber and chromium. Chromium allergy occurred in four-fifths of the men in the building, metal and tanning industries. In one-fifth of the women, nickel allergy developed in cleaning work. Rubber allergy developed in the rubber industry in one-fifth of the cases. Half of the women with contact dermatitis were engaged in either nursing or cleaning work. A follow-up 2-3 years after treatment of 555 patients with contact dermatitis was completed by means of questionnaires. The eczema was healed in one-quarter of the patients, one-half had periodic symptoms, and one-quarter had permanent symptoms. The prognosis was the same for those who changed their work or stopped working as it was for those who continued their eczema-inducing work.


Sarcoma botryoides of the uterine cervix in young women: a clinicopathological study of 13 cases.
Although the clinical and pathological features of sarcoma botryoides of the vagina in infancy are well documented in the literature, only occasional cases of a histologically similar tumor of the uterine cervix have been described, mostly as individual case reports. We have reviewed 13 cases of sarcoma botryoides of the cervix. The patients range in age from 12 to 26 years, with a mean of 18 years. All presented with vaginal bleeding, "something" protruding from the introitus, or both. On gross examination the tumors were polypoid, smooth, glistening, and focally hemorrhagic. Microscopic examination revealed the presence of a cambium layer and cells showing the features of rhabdomyoblasts in all the cases. Six of the 13 tumors (45%) contained foci of mature cartilage. All the patients were alive and well 1 to 8 years (average 3.5 years) postoperatively except for one who died of the tumor after 1 year. Although most of the patients had a radical operation, sometimes followed by chemotherapy, three had excellent results after polypectomy or cervicectomy. The findings indicate that, unlike its counterpart in the vagina, which has a poor prognosis, sarcoma botryoides of the cervix in young women has a favorable outlook.


Topological spintronics and magnetoelectronics.
Topological electronic materials, such as topological insulators, are distinct from trivial materials in the topology of their electronic band structures that lead to robust, unconventional topological states, which could bring revolutionary developments in electronics. This Perspective summarizes developments of topological insulators in various electronic applications including spintronics and magnetoelectronics. We group and analyse several important phenomena in spintronics using topological insulators, including spin-orbit torque, the magnetic proximity effect, interplay between antiferromagnetism and topology, and the formation of topological spin textures. We also outline recent developments in magnetoelectronics such as the axion insulator and the topological magnetoelectric effect observed using different topological insulators.


The role of the GABAergic and dopaminergic systems in the brain response to an intragastric load of alcohol in conscious rats.
The brain's response to ethanol intake has been extensively investigated using electrophysiological recordings, brain lesion techniques, and c-Fos immunoreactivity. However, few studies have investigated this phenomenon using functional magnetic resonance imaging (fMRI). In the present study, we used fMRI to investigate the blood oxygenation level-dependent (BOLD) signal response to an intragastric (IG) load of ethanol in conscious, ethanol-naive rats. An intragastrically infused 10% ethanol solution induced a significant decrease in the intensity of the BOLD signal in several regions of the brain, including the bilateral amygdala (AMG), nucleus accumbens (NAc), hippocampus, ventral pallidum, insular cortex, and cingulate cortex, and an increase in the BOLD signal in the ventral tegmental area (VTA) and hypothalamic regions. Treatment with bicuculline, which is an antagonist of the gamma-aminobutyric acid A (GABA(A)) receptor, increased the BOLD signal intensity in the regions that had shown decreases in the BOLD signal after the IG infusion of 10% ethanol solution, but it did not affect the BOLD signal increase in the hypothalamus. Treatment with SCH39166, which is an antagonist of D1-like receptors, eliminated the increase in the BOLD signal intensity in the hypothalamic areas but did not affect the BOLD signal decrease following the 10% ethanol infusion. These results indicate that an IG load of ethanol caused both a GABA(A) receptor-mediated BOLD decrease in the limbic system and the cortex and a D1-like receptor-mediated BOLD increase in the hypothalamic regions in ethanol-naive rats.


Determination of erythrocyte protoporphyrin by magnetic circular dichroism.
A method for the determination of erythrocyte protoporphyrin by magnetic circular dichroism is reported. The method was sufficiently sensitive to distinguish normal from elevated levels of erythrocyte protoporphyrin and may be useful for diagnostic screening purposes. Erythrocyte protoporphyrin levels determined by magnetic circular dichroism correlated well with levels determined by the fluorimetric method of Piomelli, viz. a plot of MCD versus fluorimetry yielded a straight line relationship with a slope of 0.98 +/- 0.01, y-intercept of 0.05 +/- 0.35 and correlation coefficient of 0.99.


Phytosphingosine-induced cell apoptosis via a mitochondrially mediated pathway.
Cyanobacterial blooms, usually dominated by Microcystis aeruginosa, pose a serious threat to global freshwater ecosystems owing to their production and release of various harmful secondary metabolites. Detection of the chemicals in M. aeruginosa exudates using metabolomics technology revealed that phytosphingosine (PHS) was one of the most abundant compounds. However, its specific toxicological mechanism remained unclear. CNE-2 cells were selected to illustrate the cytotoxic mechanism of PHS, and it was determined to cause excessive production of reactive oxygen species and subsequently damage the mitochondrial structure. Mitochondrial membrane rupture led to matrix mitochondrial membrane potential disintegration, which induced Ca2+ overload and interrupted ATP synthesis. Furthermore, rupture of the mitochondrial membrane induced the opening of the permeability transition pore, which caused the release of proapoptotic factors into the cytoplasm and the expression of apoptosis-related proteins Bax, Bcl-2, cytochrome-c and cleaved caspase-3 in CNE-2 cells. These events, in turn, activated the mitochondrially mediated intrinsic apoptotic pathway. A mitochondrial repair mechanism, namely, PINK1/Parkin-mediated mitophagy, was then blocked, which further promoted apoptosis. Our findings suggest that more attention should be paid to the ecotoxicity of PHS, which is already listed as a contaminant of emerging concern.


Sonochemical synthesis of ZnS nanolayers on the surface of microbial cells and their application in the removal of heavy metals.
In order to improve the adsorption performance of microorganisms, we synthesized a novel material - phanerochaete chrysosporium cells covered with a layer of ZnS nanoparticles (ZnS-cells). The preparation of the ZnS-cells is based on the Sonochemical method to synthesize the ZnS nanoparticle layer on the surface of the microbial cells. The ZnS-cells were characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), energy dispersive X-ray spectroscopy (EDS) and Fourier transform infrared spectroscopy (FTIR). Characterization results showed that wurtzite ZnS was coated on the cell surface in the form of nanoclusters by sonochemical reaction, and the formation of ZnS was related to the carboxyl group on the cell surface. Batch experiments showed that the ZnS-cells exhibited high adsorption efficiency for Pb2+and Cd2+, the removal rate of Pb2+ and Cd2+ by ZnS-cells was 140 % and 160 % higher than that of pure P. chrysosporium, respectively. Studies on the adsorption mechanism showed that the removal of heavy metals by ZnS-cells mainly depended on the complexation of surface functional groups on the surface of the cells and the ion exchange of ZnS nanofilms.


Age-dependent endothelial dysfunction is associated with failure to increase plasma nitrite in response to exercise.
Age-dependent alterations of the vessel wall may predispose older individuals to increased cardiovascular pathology. Aging is associated with an impaired bioactivity of nitric oxide (NO). Plasma nitrite reflects NO-synthase activity under fasting conditions and is an important storage pool of NO. To test the hypothesis that aging is associated with an impaired capacity of the vasculature to increase plasma nitrite during exercise, 29 young and 28 old healthy individuals (25 +/- 1 years and 58 +/- 2 years; P < 0.001) without major cardiovascular risk factors were enrolled. Exercise stress was similar in both groups. Baseline nitrite did not differ (107 +/- 8 vs. 82 +/- 10 nmol/l, young vs. old; n.s.) although a trend toward higher nitrite levels in young individuals was seen. In young subjects, exercise increased plasma nitrite by 38 +/- 7% (P < 0.001) compared to only 13 +/- 8% (P = n.s.) in older subjects. L-NMMA blocked increases of nitrite. Endothelial function, as defined by flow-mediated-dilation (FMD) of the brachial artery via ultrasound, was impaired in older subjects (5.4 +/- 0.4% vs. 6.7 +/- 0.3%; P < 0.01). Multivariate analysis showed that age (P = 0.007), BMI (P = 0.010), and LDL (P = 0.021) were independent predictors of nitrite increase. The fact that aging is associated with an impaired capacity of the vasculature to adequately increase nitrite to physiological stimuli may contribute to attenuated maintenance and further deterioration of vascular homeostasis with aging.


Direct measurement of the capillary condensation time of a water nanobridge.
Water menisci wet all sorts of cavities, produce among the most intense forces at the nanoscale and play a role in many physical and chemical processes. The physical properties of these menisci are therefore relevant to understand a multitude of phenomena at the nanoscale where these are involved. Here, using a force feedback microscope, we directly measured the capillary condensation time of a water meniscus, by approaching two surfaces at different speeds and monitoring the relative position of the surfaces at the instant the meniscus is formed.


Dissociation of human follicle-stimulating hormone. Comparison with luteinizing hormone.
Rat testis tissue receptor assays were utilized to study the kinetics of dissociation of human follicle-stimulating hormone (hFSH) and luteinizing hormone (hLH) under varying conditions of urea concentration and pH. In these competitive protein binding assays, 125I-hFSH and 125I-hLH were the radioligands and hormone dissociation was followed by a decrease in the ability of the dissociating hormone to inhibit uptake of the radioligand by tissue receptors. Rate data for dissociation of the gonadotropins were analyzed for quality of fit to first or second order integrated rate equations by nonlinear regression analysis. Treatment of hFSH with 4 M urea at pH 8 and 25 degrees for 22 hours did not result in significant dissociation, whereas in 8 M urea, over 90% dissociation was observed. The rate of dissociation of hFSH in 8 M urea was increased approximately 4-fold by raising the temperature from 25 to 37 degrees. Similar results were obtained when dissociation of hFSH was followed through use of an accepted whole animal bioassay for FSH, thus confirming the reliability of the tissue receptor assay for such dissociation studies. Kinetic studies showed that hFSH was undissociated by incubation in 6 M urea of pH 8 after 4 hours at 25 degrees. In contrast, hLH was 90% dissociated under similar conditions. This differential rate of inactivation of hLH allowed preparation of hFSH having significant reduced levels of contaminating LH activity, as determined by tissue receptor assays and by whole animal bioassays. Marked differences were noted in the rate of dissociation of hFSH and hLH under acid conditions. hFSH completely dissociated after approximately 2 min of incubation of pH 2 (25 degrees), and over 90% dissociated after 15 min of incubation at pH 3. In contrast, hLH was dissociated 60% after 20 min of incubation at pH 2 (25 degrees) and 40% dissociated after 60 min at pH 3. Neither hormone was significantly dissociated at pH 4.4 after 60 min, but hFSH showed a slightly greater rate of dissociation than did LH in the period between 1 and 23 hours of incubation at that pH. hFSH and hLH were relatively resistant to dissociation after incubation at pH 12 for 1 hour, bu;t dissociated significantly after incubation for 22 hours at that pH. The time course for dissociation of hFSH or hLH under the various conditions described above did not conform clearly to either first or second order kinetics, indicating that the over-all dissociation process represents a mixed order reaction. It appears that urea or acid-induced denaturation of one or both subunits of hLH and hFSH may occur prior to their dissociation. The very rapid rate of dissociation at acid pH values, particularly of hFSH, indicate that ionic interactions contribute importantly to the subunit association phenomenon.


A hydrazone covalent organic polymer based micro-solid phase extraction for online analysis of trace Sudan dyes in food samples.
Covalent organic polymers (COPs) connected by covalent bonds are a new class of porous network materials with large surface area and potential superiority in sample pretreatment. In this study, a new hydrazone linked covalent organic polymer (HL-COP) adsorbent was well-designed and synthesized based on a simple Schiff-base reaction. The condensation of 1,4-phthalaldehyde and 1,3,5-benzenetricarbohydrazide as organic building blocks led to the synthesis of HL-COP with uniform particle size and good adsorption performance. This HL-COP adsorbent with high hydrophobic property and rich stacking π electrons contained abundant phenyl rings and imine (CN) groups throughout the entire molecular framework. The adsorption mechanism was explored and discussed based on π-π affinity, hydrophobic effect, hydrogen bonding and electron-donor-acceptor (EDA) interaction, which contributed to its strong recognition affinity to target compounds. Enrichment factors were 305-757 for six Sudan dyes by HL-COP micro-solid phase extraction (μ-SPE), indicating its remarkable preconcentration ability. Furthermore, the adsorption amounts by HL-COP μ-SPE were 1.0-11.0 folds as those by three commonly used commercial adsorbents. Then, HL-COP was applied as adsorbent of online μ-SPE coupled with high performance liquid chromatography (HPLC) for enrichment and analysis of trace Sudan dyes in food samples with detection limit of 0.03-0.15μg/L. The method was successfully applied for online analysis of chilli powder and sausage samples. Sudan II and Sudan III in one positive chilli powder sample were actually found and determined with concentrations of 8.3 and 6.8μg/kg, respectively. The recoveries of chilli powder and sausage samples were in range of 75.8-108.2% and 73.8-112.6% with relative standard deviations of 1.2-8.5% and 1.9-9.4% (n=5), respectively. The proposed method was accurate, reliable and convenient for the online simultaneous analysis of trace Sudan dyes in food samples.