An internally-standardized assay for amphotericin B in tissues and plasma.
A high-performance liquid chromatographic (HPLC) method with p-nitrophenol as internal standard is described for the rapid analysis of amphotericin B recovered by methanolic extraction from tissues and plasma. Programmed, gradient elution of the ODS column was used with detection by tungsten light at 388 nm. Standard curves were derived based on the peak height ratios. The lowest reproducible limit of the assay was 0.04 micrograms/ml with plasma. The extraction and chromatographic procedures recovered 53-71% of the amphotericin B from each of these sources. The coefficient of variation of the recovery ratios was less than 18% from plasma over a range of concentrations of amphotericin B from 0.08 to 10.0 micrograms/ml. Recovery from tissues, studied over a narrower concentration range, showed a similar degree of precision. Variations in precolumns apparently resulting in selective binding of the amphotericin B were found to have a systematic but important influence on recovery efficiency. No substances were detected which interfered with the assay procedures as described. By incorporating an internal standard we have enhanced the reliability and flexibility of the HPLC assay for amphotericin B especially for assay of tissues.


The lower the better: target values after LDL-Apheresis and semi-selective LDL-elimination therapies.
Prior to 1980 the drug therapy of hereditary hypercholesterolaemia was, as compared to nowadays standards, rather limited. There was virtually no effective therapy for homozygous patients, though plasma exchange introduced in France and Britain, demonstrated the use-fullness of the introduction of apheresis techniques. Parallel to the improvement of cholesterol lowering drug therapy for heterozygous patients, apheresis was developed as therapeutic affinity chromatography since 1980 at the university of Cologne for both homozygous and therapy refractory heterozygous patients. This development was named LDL-Apheresis based on the specificity for the removal of Apoprotein B bound cholesterol, the capacity due to the development of a repetitive cycling technique and the economy determined from the reuse of affinity chromatography columns for each single patient. The capacity of the system allowed for the introduction of new standards of post-treatment values such as 100mg/dl total cholesterol or alternatively 50mg/dl LDL-cholesterol and if cholesterol lowering drugs can also applied for a limited extent the rebound can be also slowed down. After 33 years of experience with seven homozygotes and 32 heterozygotes without treatment alternative, we found that in addition to the improvement of the quality of live the extension of live expectancy are the real proof of a therapeutic success as compared to other diagnostic procedures. The average live expectancy of our seven homozygous patients is 45.6 years; our oldest heterozygous patient is 81 years. There are no comparable long term data at present available neither from studies using drugs nor from subsequently developed apheresis techniques which also removed LDL-cholesterol together with plasma constituents not participating in the development of atherosclerosis. Also two homozygous patients giving birth to four children without complication support our concept of aggressive cholesterol lowering therapy being without major side effects (3-4% minor undesired reactions).


Some Advice for Physicians and Other Clinicians Treating Minorities, Women, and Other Patients at Risk of Receiving Health Care Disparities.
Studies of inequalities in health care have documented 13 groups of patients who receive disparate care. Disparities are partly due to socioeconomic factors, but nonsocioeconomic factors also play a large contributory role. This article reviews nonsocioeconomic factors, including unconscious bias, stereotyping, racism, gender bias, and limited English proficiency. The authors discuss the clinician's role in addressing these factors and reducing their impact on the quality of health care. They indicate the significance of cultural humility on the part of caregivers as a means of amelioration. Based on a review of the clinician's role as well as background considerations in the health care environment, the authors put forward a set of 18 recommendations in the form of a checklist. They posit that implementing these recommendations as part of the patient clinician interaction will maximize the delivery of equitable care, even in the absence of desirable in-depth cross-cultural and psychosocial literacy on the part of the clinician. Trust, mutual respect, and understanding on the part of the caregiver and patient are crucial to optimizing therapeutic outcomes. The guidelines incorporated here are tools to furthering this goal.


Heterologous expression of peptide hormone precursors in the yeast Saccharomyces cerevisiae. Evidence for a novel prohormone endoprotease with specificity for monobasic amino acids.
The peptide somatostatin (SRIF) exists as two different molecular species. In addition to the most common form, which is a 14-residue peptide, there is also a 14-amino acid amino-terminally extended form of the tetradecapeptide, SRIF-28. Both peptides are synthesized as larger precursors containing paired basic and monobasic amino acids at their processing sites, which, upon cleavage, generate either SRIF-14 or -28, respectively. In mammals a single prepro-SRIF molecule undergoes tissue-specific processing to generate the mature hormone whereas in some species of fish separate genes encode two distinct but homologous precursors prepro-SRIF-I and -II that give rise to SRIF-14 and -28, respectively. To investigate the molecular basis for differential processing of the prohormones we introduce their cDNAs into yeast cells (Saccharomyces cerevisiae). The signal peptides of both precursors were poorly recognized by the yeast endoplasmic reticulum translocation apparatus, consequently only low levels of SRIF peptides were synthesized. To circumvent this problem a chimeric precursor consisting of the alpha-factor signal peptide plus 30 residues of the proregion was fused to pro-SRIF-II. This fusion protein was efficiently transported through the yeast secretory pathway and processed to SRIF-28 exclusively, which is identical to the processing of the native precursor in pancreatic islet D-cells. Most significantly, cleavage of the precursor to SRIF-28 was independent of the Kex 2 endoprotease since processing occurred efficiently in a kex 2 mutant strain. We conclude that in addition to the Kex 2 protease, yeast possess a distinct prohormone converting enzyme with specificity toward monobasic processing sites.


A 13C magnetic resonance study of embryonic chick aorta.
13C nmr spectra of defatted aorta, obtained from chick embryos, ranging in age from 13 to 20 days, showed that linewidths were independent of the age of the embryo, this, in spite of the fact that crosslinking increases with age. As expected the dipolar decoupled spectrum of defatted aorta had a larger C-H signal intensity than the scalar decoupled spectrum, since collagen in the sample contributes signal intensity only in the former case. Significantly, the dipolar decoupled spectrum of autoclaved aorta also had a larger C-H signal intensity. This result indicates that ca. 30% of the carbons in the tissue, swollen by 0.15 M NaCl, has restricted motion at 37 degrees. Preliminary data indicate that tissue culture techniques can be used to enrich specific amino acids in chick aorta with 13C, thereby affording a means to study possible differences in molecular structure of the chemically distinct regions in elastin.


Prehospital Helicopter Air Ambulances Part 2: Utilization Criteria and Training.
The decision to request a helicopter air ambulance (HAA) is critical and complex. Emergency medical service (EMS) professionals must know how to appropriately and safely use HAA resources. We sought to describe important criteria for using HAA and the prevalence of HAA-related training among EMS professionals. Then, we identified characteristics associated with receiving training. We sent an electronic questionnaire to all nationally certified EMS professionals. We performed descriptive analyses and multivariable logistic regression modeling. We received 15,366 responses. Nearly all respondents reported that time to nearest trauma center and mechanism of injury were important in their last decision to use a HAA. About two thirds received HAA safety training (66.7%), whereas 69.0% received HAA utilization training within the past 24 months. Nearly three fourths (74.2%) received training in at least 1 HAA-related topic. Providers working at advanced life support levels, fire-based services, agencies providing 911 response, or in rural communities had greater odds of having received HAA training, whereas women, members of minority ethic/racial groups, and those with higher weekly call volumes had decreased odds. Although their decision-making criteria appear to include the major factors recommended within current evidence-based guidelines, many nationally certified EMS professionals had not received recent HAA training.


Metformin action on lipid metabolism in lesions of experimental aortic atherosclerosis of rabbits.
The aim of the present study was to investigate whether metformin was capable of altering aortic lipid metabolism during the progression and regression of cholesterol-induced atherosclerosis in rabbits. Three hours after intravenous injection of a 200-microCi tracer dose of [2-14C]acetate, metformin (120 mg/kg per os) strongly diminished the radioactivity in all lipid fractions of the aorta of the normal rabbit. The incorporation of acetate into lipids was greater in the fatty streaks of rabbits fed cholesterol for 2 months than in normal aorta, independent of the plasma radioactivity level. There was increased acetate incorporation into all major lipid groups in the fatty streak, with the greatest relative increase in the cholesteryl ester fraction. No change was observed in the acetate incorporation into lipids in atheromatous deposits after pretreatment of cholesterol-fed rabbits for 8 days with metformin. Concomitant treatment for 2 months with metformin in rabbits fed a cholesterol-enriched diet strongly reduced the radioactivity of total aortic lipids 3 h after intravenous injection of labelled acetate. The inhibition of acetate incorporation into arterial lipids was observed in all lipid fractions (i.e. free cholesterol, free fatty acids, triglycerides and especially esterified cholesterol and phospholipids). In rabbits fed a cholesterol-enriched diet for a period of two months, followed by a normal diet during 12 months, long-term treatment with metformin significantly reduced total lipid radioactivity in the aorta, 3 h after intravenous injection of the 200-microCi tracer dose of [2-14C]acetate. The incorporation of labelled precursor was markedly reduced in the various lipid fractions. These properties, added to others previously described, can to a large extent explain the protective effect of metformin on experimental atherosclerosis.


Chronic CXCL10 alters the level of activated ERK1/2 and transcriptional factors CREB and NF-kappaB in hippocampal neuronal cell culture.
Signal transduction pathways may be important targets of chemokines during neuroinflammation. In the current study, Western blot analyses show that in rat hippocampal neuronal/glial cell cultures chronic CXCL10 increases the level of protein for ERK1/2 as well as for the transcriptional factors CREB and NF-kappaB. Bcl-2, an anti-apoptotic protein whose expression can be regulated by a pathway involving ERK1/2, CREB and NF-kappaB, was also increased in the CXCL10 treated cultures. These results implicate a role for ERK1/2, CREB and NF-kappaB in effects of CXCL10 on hippocampal cells and suggest that chronic CXCL10 may have a protective role during certain neuroinflammatory conditions.


Possible origin of the bluetongue epidemic in Cyprus, August 1977.
Possible origins of an epidemic of bluetongue in Cyprus in August 1977 have been analysed. First outbreaks occurred simultaneously in the south-east of the Famagusta district and on the north coast of the Kyrenia district respectively. Although the epidemic was due to type 4, which had been responsible for the previous outbreak in 1969, no evidence of persistance of virus could be found. Imports of domestic animals in the past year were not implicated since the imported cattle were introduced only to the southern part and not to the northern part of the island. Easterly, north-easterly and northerly winds during the period 11-14 August could have brought infected midges at a height of 0.5--1.5 km from Syria and Turkey, and such a movement would fit well the dates of the first outbreaks (20-25 August). Temperatures at a height of 1.5 km were 20-25 degrees C and at 0.5 km 30 35 degrees C, and with wind speeds 10-20 km h-1 the distance from Turkey and Syria would have been covered in 5-20 h. It follows that, in addition to surface winds, winds at all levels warm enough for flight should be taken into account when the possibility of disease spread by windborne midges is being assessed.


Perinatal malnutrition programs sympathoadrenal and hypothalamic-pituitary-adrenal axis responsiveness to restraint stress in adult male rats.
In humans, an altered control of cortisol secretion was reported in adult men born with a low birth weight making the hypothalamic-pituitary-adrenal (HPA) axis a possible primary target of early life programming. In rats, we have recently shown that maternal food restriction during late pregnancy induces both an intrauterine growth retardation and an overexposure of fetuses to maternal corticosterone, which disturb the development of the HPA axis in offspring. The first aim of this work was to investigate, in adult male rats, whether perinatal malnutrition has long-lasting effects on the HPA axis activity during both basal and stressful conditions. Moreover, as the HPA axis and sympathetic nervous system are both activated by stress, the second aim of this work was to investigate, in these rats, the adrenomedullary catecholaminergic system under basal and stressful conditions. This study was conducted on 4-month-old male rats malnourished during their perinatal life and on age-matched control animals. Under basal conditions, perinatal malnutrition reduced body weight and plasma corticosteroid-binding globulin (CBG) level but increased mineralocorticoid receptor (MR) gene expression in CA1 hippocampal area. After 30 min of restraint, perinatally malnourished (PM) rats showed increased plasma noradrenaline, adrenocorticotropin hormone (ACTH) and corticosterone concentrations similarly as controls, but calculated plasma-free corticosterone concentration was significantly higher and adrenaline level lower than controls. During the phase of recovery, PM rats showed a rapid return of plasma ACTH and corticosterone concentrations to baseline levels in comparison with controls. These data suggest that in PM rats, an elevation of basal concentrations of corticosterone, in face of reduced CBG and probably increased hippocampal MR lead to a much larger impact of corticosterone on target cells that mediate the negative-feedback mechanism on the activities of both the HPA axis and sympathoadrenal one.


Split notochord syndrome presenting with meningomyelocoele and dorsal enteric fistula.
Split notochord syndrome is a rare congenital anomaly. We present the history of a 16-day-old male infant who presented to us with a lumbosacral meningomyelocoele and a dorsal enteric fistula along with the cleft of lower vertebrae. Review of the literature, has revealed eight such cases with very few survivals. We successfully treated the patient.


Measurement of cerebral glucose utilization from brain uptake of [14C]2-deoxyglucose and [3H]3-O-methylglucose in the mouse.
Glucose utilization (GU) in the mouse brain in vivo was measured by the simultaneous use of [14C]2-deoxyglucose (2DG), the glucose analogue that can be phosphorylated in the brain, and [3H]3-O-methylglucose (3MG), the nonmetabolizable glucose analogue. Originally, this method was developed by Gjedde et al. (1985) in the rat and in humans. The present study examined the validity of this method in the mouse brain. The effects of urethane and pentobarbital (PB) on GU were also studied. Whereas the distribution volume of 3MG reached a constant value under each condition after 10 min of the tracer circulation, the apparent volume of distribution of 2DG, which increased with time in the awake mice, did not increase so greatly in the anesthetized and hypothermic mice, indicating that the net rate of 2DG phosphorylation is lowered under these conditions. These data were fitted for the conventional three-compartmental model and the values of rate constants of influx (K1), efflux (k2), phosphorylation, and dephosphorylation for 2DG, and K1 and k2 for 3MG were computed by nonlinear least square regression method. No significant difference in the value of K1/k2, the distribution volume of the precursor pool, was observed between 2DG and 3MG, indicating that 3MG can be used to estimate the distribution volume of unmetabolized 2DG in the brain. The values of GU calculated from the values of estimated parameters were not significantly different from those calculated from blood and tissue radioactivities obtained during 10 min after the injection of the tracers in both awake and PB-anesthetized mice. These findings indicate that the double tracer technique is useful for measuring GU in a short duration experiment.


Investigation of the multi-targeted protection potential of tannic acid against doxorubicin-induced kidney damage in rats.
Doxorubicin (DOX) is an antitumor drug that is powerful but can cause worse outcomes, including nephrotoxicity, and therefore has limited clinical use. Therefore, it is necessary to identify safer agents that can minimize the damage caused by the drug without shifting the treatment performance, in addition to clarifying the underlying mechanisms of DOX-induced aberrant in vivo renal activation. In this study, we tested the prophylactic capacity and mechanisms of action of tannic acid (TA) against DOX-mediated kidney damage in rats and evaluated the nephrotoxic activity of DOX when used with TA. Rats were treated during the two weeks with cumulative (18 mg/kg with six different injections) DOX, daily TA (50 mg/kg), and the DOX + TA combination. Changes in major metabolites and components involved in antioxidant metabolism were evaluated in the kidney tissues of all animals. Further, the gene expression levels of regulatory factors that have critical importance in cell metabolism, inflammation, and apoptosis were investigated. Both biochemical and molecular examinations showed that TA improved DOX-induced dysregulations at both protein and gene levels in the kidneys. Increased lipid peroxidation and decreased glutathione levels were reversed. Consistent with oxidative stress marker metabolites, suppressed antioxidant enzyme activities and transcript levels of antioxidant system members were restored. Of note, combination treatment with TA could overcome doxorubicin-induced gene expressions markedly altered by DOX, suggesting that nephroprotection conferred by TA involved the remodeling of stress resistance, cell metabolism, inflammation, and apoptosis. Collectively, the present in vivo study suggests that TA could be used as a multitarget and effective agent for the mitigation of doxorubicin-induced nephrotoxicity without changing the therapeutic efficacy of the drug.


Structural and mechanistic insights into the DNA glycosylase AAG-mediated base excision in nucleosome.
The engagement of a DNA glycosylase with a damaged DNA base marks the initiation of base excision repair. Nucleosome-based packaging of eukaryotic genome obstructs DNA accessibility, and how DNA glycosylases locate the substrate site on nucleosomes is currently unclear. Here, we report cryo-electron microscopy structures of nucleosomes bearing a deoxyinosine (DI) in various geometric positions and structures of them in complex with the DNA glycosylase AAG. The apo nucleosome structures show that the presence of a DI alone perturbs nucleosomal DNA globally, leading to a general weakening of the interface between DNA and the histone core and greater flexibility for the exit/entry of the nucleosomal DNA. AAG makes use of this nucleosomal plasticity and imposes further local deformation of the DNA through formation of the stable enzyme-substrate complex. Mechanistically, local distortion augmentation, translation/rotational register shift and partial opening of the nucleosome are employed by AAG to cope with substrate sites in fully exposed, occluded and completely buried positions, respectively. Our findings reveal the molecular basis for the DI-induced modification on the structural dynamics of the nucleosome and elucidate how the DNA glycosylase AAG accesses damaged sites on the nucleosome with different solution accessibility.


Longitudinal Associations between Gender and Ethnic-Racial Identity Felt Pressure from Family and Peers and Self-Esteem among African American and Latino/a Youth.
Gender identity felt pressure is negatively associated with adjustment indices, including self-esteem, among children and early adolescents, and both gender and ethnic-racial identity felt pressure are negatively associated with self-esteem among young adults. This study explored the longitudinal associations between gender identity and ethnic-racial identity felt pressure from family and peers to behave in either gender or race/ethnic-accordant ways, and self-esteem among a sample of 750 (49.2% female) African American (n = 194) and Latino/a youth (n = 556) (M = 12.10 years, SD = .97 years). For African Americans, the results revealed significant negative longitudinal associations between (a) ethnic-racial identity felt pressure from family at Time 1 and self-esteem at Time 2 and (b) ethnic-racial identity felt pressure from peers at Time 1 and self-esteem at Time 2, controlling for self-esteem at Time 1. These associations were not found among Latinos/as, nor were associations found between gender identity felt pressure from peers or family and self-esteem. The findings are discussed by drawing on the gender identity and ethnic-racial identity literatures.


Borna disease virus - fact and fantasy.
The occasion of Brian Mahy's retirement as editor of Virus Research provides an opportunity to reflect on the work that led one of the authors (Lipkin) to meet him shortly after the molecular discovery and characterization of Borna disease virus in the late 1980s, and work with authors Briese and Hornig to investigate mechanisms of pathogenesis and its potential role in human disease. This article reviews the history, molecular biology, epidemiology, and pathobiology of bornaviruses.


Attractive Interaction between Fully Charged Lipid Bilayers in a Strongly Confined Geometry.
We investigate the interaction between highly charged lipid bilayers in the presence of monovalent counterions. Neutron and X-ray reflectivity experiments show that the water layer between like-charged bilayers is thinner than for zwitterionic lipids, demonstrating the existence of counterintuitive electrostatic attractive interaction between them. Such attraction can be explained by taking into account the correlations between counterions within the Strong Coupling limit, which falls beyond the classical Poisson-Boltzmann theory of electrostatics. Our results show the limit of the Strong Coupling continuous theory in a highly confined geometry and are in agreement with a decrease in the water dielectric constant due to a surface charge-induced orientation of water molecules.


Long-Term Outcomes of Selected Patients with IIIA-N2 Non-small Cell Lung Cancer Receiving Upfront Surgical Resection.
Stage IIIA non-small cell lung cancer (NSCLC) is a diverse group that requires multimodality treatment. The aim of this study was to report the long-term outcomes for patients with IIIA-N2 disease. We conducted a retrospective review of cases with IIIA-N2 (T1-2N2) NSCLC who underwent upfront surgery. Kaplan-Meier curves and Cox proportional hazard analyses were used to assess the impact of various variables on survival. A total of 475 patients were ultimately included. With a median follow-up time of 108 months, the 5- and 10-year overall survival (OS) rates were 42.2% and 27.7%, respectively. R0 resection was found to be associated with improved progression-free survival (PFS) and OS compared with R1/R2 resection (p = 0.041 for PFS; p = 0.015 for OS). Patients with single-station N2 disease demonstrated significantly better PFS and OS than those with multiple-station N2 disease (p < 0.001 for PFS; p = 0.002 for OS). Following surgical resection, adjuvant therapy was significantly correlated with prolonged PFS and OS compared with those patients without any treatment. However, there was no significant difference in PFS and OS between chemotherapy and radiochemotherapy (p = 0.915 for PFS; p = 0.287 for OS). Patients with EGFR exon 19 deletion had significantly improved OS compared with those with L858R (p = 0.040). Our study shows promising long-term outcomes for selected patients with stage IIIA-N2 NSCLC treated with upfront surgery followed by adjuvant therapy, especially those with R0 resection and single-station N2. This study sheds light on the potential management and treatment options for this challenging population.


Intraspinal devices for pain management.
Intraspinal drug delivery is one of several important pain management therapies. Numerous delivery methods and drugs are available for administration into the epidural or intrathecal space. The choice of systems and drugs is based on the nature and duration of the patient's pain, his or her other medical problems, and patient resources. Patients must be carefully selected to ensure optimal results. Nurses can assist in this screening and perform preoperative teaching, postoperative care, and long-term follow-up. Essential knowledge includes general pain management principles as well as principles of intraspinal drug delivery.


New insights into the causes and therapy of cerebral vasospasm following subarachnoid hemorrhage.
Cerebral vasospasm lingers as the leading preventable cause of death and disability in patients who experience aneurysmal subarachnoid hemorrhage. Despite the potentially devastating consequences of cerebral vasospasm, the mechanisms behind it are incompletely understood. Nitric oxide, endothelin-1, bilirubin oxidation products and inflammation appear to figure prominently in its pathogenesis. Therapies directed at many of these mechanisms are currently under investigation and hold significant promise for an ultimate solution to this substantial problem.


Factors associated with leisure-time physical activity among patients undergoing hemodialysis.
End-stage renal disease patients are characterized by low levels of physical activity, especially during leisure time. However, the recognition of variables associated with patterns of physical activity in this population has been little explored. Thus, the objective was to assess factors associated with levels of physical activity during leisure time among patients on haemodialysis. Ninety-eight patients (51.6 ± 15.7 years, 57 M/41 F) from two dialysis centres in São Paulo, Brazil participated in this cross-sectional study. Participants were divided into those who never exercised during leisure-time (inactive) and those who exercised at least once a week (active). The independent factors assessed were: socio-demographic data, comorbidities, personal barriers to exercise and physical activity records from childhood to adulthood (tracking of physical activity). Only 27 % of patients were engaged in PA during their leisure time at least once a week. Patients who engaged in regular physical activity during adulthood before the initiation of the hemodialysis treatment (adjusted OR: 7.24 95 % IC: 1.99; 26.50), those who developed the renal disease through diseases other than diabetes or hypertension (adjusted OR: 4.82; 95 % IC: 1.48; 15.68), and those who had no cardiovascular diseases (adjusted OR: 11.33; 95 % IC: 1.23; 103.8) where more likely to be active during their leisure-time. Comorbidities such as cardiovascular disease, hypertension and diabetes mellitus as well as the level of physical activity prior to end-stage renal disease could predict leisure-time physical activity among patients receiving hemodialysis therapy.


The imbalance between N2O production and reduction by multi-microbial communities determines sedimentary N2O emission potential in the Pearl River Estuary.
Denitrification is the dominant process of nitrogen removal and nitrous oxide (N2O) emissions in estuarine ecosystems. However, little is known regarding the microbial mechanism of the production and reduction of N2O in estuaries. We investigated in situ dissolved N2O as well as potential N2O production rate (NPR), reduction rate (NRR), and emission rate (NER), and key functional genes related to N2O transformation of denitrification in the Pearl River Estuary. Higher N2O emission potential was found in the upstream and midstream regions with higher NPR and lower NRR values. In contrast, higher NRR values were detected in downstream. Notably, nirS and nirK type N2O producers dominated the upstream zone, whereas abundant N2O reducers, especially nosZ II type N2O reducers, were observed in downstream. Most importantly, the gene abundance ratio (Rnir/nosZ) was significantly correlated with the N2O emission potential (Re). Niche differentiation between N2O producers and N2O reducers from upstream to downstream affected N2O emission potential. This study highlights the N2O emission potential in estuarine sediments is determined by an imbalance between N2O production and the reduction of multi-bacterial communities.


Laser diode wavelength-modulation spectroscopy for simultaneous measurement of temperature, pressure, and velocity in shock-heated oxygen flows.
Wavelength modulation at 10 MHz of an AlGaAs laser diode, superposed on repetitive linear scans of wavelength, is applied to measure second-harmonic absorption line shapes of oxygen in the A band. Theoretical expressions of the harmonic line shapes, including the effect of laser amplitude modulation and varying modulation depth, are presented. A least-squares fit of the experimental line shapes to theoretical second-harmonic line shapes permits simultaneous determination of the temperature and the pressure. The use of high-repetition-rate (10-kHz) linear scans of the studied wavelength region permits application of the technique to high-speed unidimensional transient flows generated in a shock tube; velocity is derived from the Doppler shift of the absorption profiles.


Trichorhinophalangeal syndrome type 1 (TRPS1) expression in male breast carcinoma.
Currently, there is a paucity of highly specific and sensitive markers to identify breast carcinoma in male patients. Immunohistochemical stains commonly used for unmasking primary breast carcinomas include estrogen receptor (ER) and GATA3. However, these markers are commonly expressed in carcinomas originating from other organ systems and can be reduced in breast carcinomas with higher histologic grades. Androgen receptor (AR) may be used to highlight primary male breast cancer, but this marker can also be expressed in other carcinomas. We evaluated TRPS1, a highly sensitive and specific marker for female breast carcinoma, in cases of male breast carcinoma. Through an institutional database search, we identified 72 cases of primary invasive breast carcinoma in male patients. Among ER/progesterone receptor (PR)-positive cancers, 97% showed intermediate or high positivity for both TRPS1 and GATA3. Among HER2-positive cancers, 100% showed intermediate or high positivity for TRPS1 and GATA3. One case of triple-negative breast cancer was collected, showing high positivity for TRPS1 and negativity for GATA3. AR staining was non-specific and heterogeneous: 76% showed high positivity, but the remaining 24% showed low or intermediate positivity. Additionally, among 29 cases of metastatic carcinoma to male breast tissue, 93% were negative for TRPS1, and the remaining 2 cases (7%), which were carcinomas from salivary gland primary tumors, were intermediate positive. TRPS1 is a sensitive and specific marker in the unmasking of male primary invasive breast carcinoma across different subtypes. Additionally, TRPS1 is not expressed in metastatic carcinomas of multiple primaries, with the exception of salivary gland primaries.


Synergistic treatment of carbon dioxide and nitrogen-containing wastewater by electrochemical C-N coupling.
Electrocatalytic CO2 reduction technology has been considered a promising approach to alleviate the severe environmental and energy issues caused by the anthropogenic over-emission of CO2. Coupling CO2 reduction with nitrogen (N)-pollutants reduction from wastewater to produce higher valued products (e.g., urea, amide, amine, etc.) could significantly extend the application scenarios and product categories of CO2 reduction technologies. This paper investigates the available CO2 and N-pollutants sources and summarizes the recent progress of electrocatalytic C-N coupling reactions. Based on the fundamental research, technical concerns for scale-up applications of C-N coupling electrocatalysis are thoroughly discussed. Finally, we prospect the opportunities and challenges with an in-depth understanding of the underlying dominant factors in applying C-N coupling electrocatalysis. Further development in recycling CO2 and N pollutants via the electrocatalytic C-N coupling process is also discussed.


Role of parenteral nutrition in preventing malnutrition and decreasing bacterial translocation to liver in obstructive jaundice.
Surgery in patients with obstructive jaundice is associated with significant infectious complications probably due to impaired immune function and malnutrition. Total parenteral nutrition (TPN) may alleviate malnutrition but may also promote bacterial translocation (BT) from the gut. To elucidate if TPN can prevent malnutrition without promotion of BT in obstructive jaundice, 40 dogs underwent laparotomy for tissue sampling and placement of a central venous line and were allocated into one of four groups: I (PO-control) received dog chow and water ad libitum; II (PO-CBDL) underwent ligation of common bile duct (CBDL) and was fed dog chow; III (TPN-control) received TPN; and IV (TPN-CBDL) underwent CBDL and received TPN. Body weight, blood samples for liver function tests and bacterial culture, and tissues from liver and mesenteric lymph nodes (MLN) for quantitative bacterial culture and for histology were obtained prior to and 2 weeks after the experiment. The incidence of BT to MLN was 40% in the PO-CBDL and TPN-CBDL animals, which was significantly different from the other two groups (0%; p < 0.05). The incidence of BT to liver was 70% (7/10) in the PO-CBDL animals, which was significantly higher than that in groups I, III, and IV (0%, 20%, 20%, respectively) (p < 0.05). The PO-CBDL animals showed a significant decrease in body weight and prealbumin compatible with malnutrition, whereas the TPN-CBDL animals showed a significant increase in alkaline phosphatase and a consistent cholestasis on histology. The data suggest that TPN can prevent jaundice-associated malnutrition and decrease BT to liver but should be administered cautiously because it may precipitate cholestasis.


CV Benefits of Statins Outweigh Muscle Pain Risk.
According to this study: Statin therapy causes a small increase in reports of muscle pain, largely during the first year of treatment.The cardiovascular benefits of statins outweigh the risk of muscle pain.


Defining the role of thoracic spinal anaesthesia in the 21st century: a narrative review.
Since the performance of the first thoracic spinal anaesthetic in early 1908 many anaesthetists have gained interest in this unorthodox neuraxial anaesthetic technique. The main rationale justifying its use is to prevent complications related to general anaesthesia in high-risk patient populations. There is, however, significant debate regarding this practice around the world. The main concerns are fear of iatrogenic injury to the spinal cord, cephalad spread of local anaesthetic causing a complete spinal block, and haemodynamic instability owing to blockade of cardioaccelerator sympathetic fibres. The purpose of this narrative review is to appraise the literature critically regarding thoracic spinal anaesthesia, to synthesise the available information, and to provide a summary of evidence justifying its use in modern anaesthesia.


Hospitalizations in adult patients with congenital heart disease: an emerging challenge.
The vast majority of patients with congenital heart disease (CHD) survive into adulthood, but many face lifelong complications, which often result in a hospital admission. The increasing number of hospitalizations in adults with CHD (ACHD) poses a significant challenge for healthcare systems globally, especially as heart failure (HF) is becoming increasingly common in this population and is the leading cause of morbidity and mortality. Besides HF, other major contributors to this increase in admission volume are hospitalizations related to mild lesions, comorbidities and pregnancies. Ιn-hospital mortality ranges between 0.8 and 6.1%, while hospitalizations related to HF predict medium-term mortality in ACHD population. Understanding the predictors of hospitalization and in-hospital mortality is, therefore, important for ACHD healthcare providers, who should identify patients at risk that require escalation of treatment and/or close monitoring. This article reviews the available literature on hospitalization patterns in ACHD patients, with a focus on HF-related hospital admissions and specific diagnostic subgroups.


Harnessing cell reprogramming for cardiac biological pacing.
Electrical impulses from cardiac pacemaker cardiomyocytes initiate cardiac contraction and blood pumping and maintain life. Abnormal electrical impulses bring patients with low heart rates to cardiac arrest. The current therapy is to implant electronic devices to generate backup electricity. However, complications inherent to electronic devices remain unbearable suffering. Therefore, cardiac biological pacing has been developed as a hardware-free alternative. The approaches to generating biological pacing have evolved recently using cell reprogramming technology to generate pacemaker cardiomyocytes in-vivo or in-vitro. Different from conventional methods by electrical re-engineering, reprogramming-based biological pacing recapitulates various phenotypes of de novo pacemaker cardiomyocytes and is more physiological, efficient, and easy for clinical implementation. This article reviews the present state of the art in reprogramming-based biological pacing. We begin with the rationale for this new approach and review its advances in creating a biological pacemaker to treat bradyarrhythmia.


Synthesis, characterization and biological studies of some novel 3-fluorosalicylaldehyde based amine derivatives.
A series of biologically important substituted 3-fluorosalicylaldehyde derivatives (1a-h) with various primary amines were synthesized by using ionic liquid (1-Butyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide) as an efficient catalyst. A new series of Schiff base derivatives (1a-h) were synthesized and characterized by IR, NMR ((1)H, (13)C, (1)H-(1)H COSY and HSQC), mass spectra and elemental analysis. Further crystal structure of compound 1a was evaluated by single crystal X-ray diffraction techniques. All the synthesized compounds were screened for in vitro antimicrobial activity against a panel of selected bacterial and fungal strains using Streptomycin and Amphotericin B as standards. Most of the synthesized compounds demonstrated moderate effects on both antibacterial and antifungal activities at minimum inhibitory concentrations (MIC's).


Bioavailability of pollutants sets risk of exposure to biota and human population in reservoirs from Iguaçu River (Southern Brazil).
The Iguaçu River, located at the Southern part of Brazil, has a great socioeconomic and environmental importance due to its high endemic fish fauna and its potential to generate hydroelectric power. However, Iguaçu River suffers intense discharge of pollutants in the origin of the river. In a previous report, the local environmental agency described water quality to improve along the river course. However, no study with integrated evaluation of chemical analysis and biological responses has been reported so far for the Iguaçu River. In the current study, three different Brazilian fish species (Astyanax bifasciatus, Chrenicicla iguassuensis, and Geophagus brasiliensis) were captured in the five cascading reservoirs of Iguaçu River for a multi-biomarker study. Chemical analysis in water, sediment, and muscle indicated high levels of bioavailable metals in all reservoirs. Polycyclic aromatic hydrocarbons (PAHs) were detected in the bile of the three fish species. Integration of the data through a FA/PCA analysis demonstrated the poorest environmental quality of the reservoir farthest from river's source, which is the opposite of what has been reported by the environmental agency. The presence of hazardous chemicals in the five reservoirs of Iguaçu River, their bioaccumulation in the muscle of fish, and the biological responses showed the impacts of human activities to this area and did not confirm a gradient of pollution between the five reservoirs, from the source toward Iguaçu River's mouth. Therefore, diffuse source of pollutants present along the river course are increasing the risk of exposure to biota and human populations.


In vitro antioxidant, anticancer, anti-inflammatory, anti-diabetic and anti-Alzheimer potentials of innovative macroalgae bio-capped silver nanoparticles.
The antagonistic side effects of chemical medications led to the search for safe strategies such as biogenic agents. Correspondingly, this study aims to create biogenic, appropriate, auspicious and innovative therapeutic agents like Galaxaura elongata {GE}, Turbinaria ornata {TO} and Enteromorpha flexuosa {EF} macroalgae-based silver nanoparticles (Ag-NPs). The Ag+ reduction and the creation of Ag[GE]-NPs, Ag[TO]-NPs and Ag[EF]-NPs have been validated using UV-visible spectroscopy, Fourier transform infrared spectroscopy (FTIR), scanning electron microscope (SEM) and zeta potential analysis, and the chemical composition of macroalgae crude extracts was estimated through gas chromatography-mass spectrometry (GC-MS). Further, macroalgae-based Ag-NPs were tested for their free radical scavenging activity DPPH, ABTS, anticancer activity in human liver carcinoma (HepG2) cell line, distinctive inflammation forms and elevated α-amylase. Results showed that the biosynthesized Ag-NPs have unique mechanical and physicochemical characters attributed to their high relative surface area, nanosized dimensions and spherical shape. At dose of 200 µg/mL, the DPPH radical scavenging capacity was maximized with Ag[TO]-NPs (67.26%); however, Ag[EF]-NPs was the most potent as ABTs scavenger (97.74%). Additionally, Ag[GE]-NPs had the maximum proteinase inhibitory action with 59.78%. The 1000 µg/mL of Ag[GE]-NPs, Ag[TO]-NPs and Ag[EF]-NPs revealed significant inhibitions of cell growth of HepG2 resulting in cell viabilities 5.92%, 4.44% and 11.33%, respectively. These findings suggest that macroalgae bio-capped Ag-NPs have magnificent biological potentials for safe biomedical applications.


The polypeptide of immunoglobulin G influences its galactosylation in vivo.
To examine the nature of the factors influencing the galactosylation pattern of the heavy chain of murine immunoglobulin G (IgG), cell fusion was performed between a myeloma (P3x63Ag8) and a hybridoma (Sp2HL/Bu) cell line which secrete different IgGs possessing structurally distinct CH2-linked oligosaccharide moieties. The glycosylation patterns of the IgGs of the parental and fused cells were studied. Pronase digestion of the purified heavy chains and subsequent end labeling with fluorescein isothiocyanate produced fluoresceinated glycopeptides which were detected and purified by polyacrylamide gel electrophoresis. Structural information was obtained by enzymatic digestion, lectin affinity chromatography, and methylation analysis. IgGs from both parental lines possessed oligosaccharide units displaying microheterogeneity based upon a common symmetrical biantennary structure terminating in beta-GlcNAc. The structures of both IgGs, however, differed in the pattern of the mono- and digalactosylated components. Clones, selected following the fusion of the parental cells, were expanded; and the individual IgGs were purified. All clones produced homodimeric IgG1 and IgG2b as well as heterodimeric IgG possessing both the gamma 1 and gamma 2b heavy chains. Analysis of the carbohydrate moieties of the gamma 1 chain from the homodimeric and heterodimeric IgGs and of the gamma 2b chain from the heterodimeric molecule demonstrates that the polypeptide structure of the heavy chain influences the terminal galactosylation of the glycan unit at the conserved site of glycosylation of IgGs.


Synthesis of muscothiazoles A and B: Critical role of methyl group substitution in RCM-based syntheses of macrocycles.
[reaction: see text] Muscothiazoles A (2b) and B (2c) have been prepared by two approaches that differ in the order of assembly of the rings. Comparative studies show that substitution of the carbon chains in substrate 5 or 12 (respective precursors to 13-membered and 14-membered rings by RCM), even by a single methyl group, can have a profound effect on increasing the efficiency of the macrocyclization.


Obesity as a risk factor for severe influenza-like illness.
Obesity was recognized as in independent risk factor for influenza during the 2009 H1N1 influenza pandemic. We evaluated the association between body mass index (BMI) and influenza-like illness (ILI) during two non-pandemic influenza seasons (2003-2004 and 2004-2005) and during the spring and fall waves of the 2009 H1N1 pandemic. Adults with severe (inpatient) and mild (outpatient) ILI were compared to those without ILI using a case-cohort design. The study was nested among those insured by a single health insurance company, receiving care from a large multispecialty practice. Data were collected from insurance claims and the electronic health record. The primary exposure was obesity (BMI ≥ 30·0 kg/m(2) ). Across three seasons, the crude and adjusted ORs for obesity and severe ILI were 1·65 (95% CI 1·31, 2·08) and 1·23 (95% CI 0·97, 1·57), respectively. An association was observed for those aged 20-59 years (adjusted OR 1·92, 95% CI 1·26, 2·90), but not for those 60 and older (adjusted OR 1·08, 95% CI 0·80, 1·46). The adjusted ORs for obesity and severe ILI in 2003-2004, 2004-2005, and during H1N1 were 1·14 (95% CI 0·80, 1·64), 1·24 (95% CI 0·86, 1·79), and 1·76 (95% CI 0·91, 3·42), respectively. Among those with a Charlson Comorbidity Index score of zero, the adjusted ORs for 2003-2004, 2004-2005, and H1N1 were 1·60 (95% CI 0·93, 2·76), 1·43 (95% CI 0·80, 2·56), and 1·90 (95% CI 0·68, 5·27), respectively. Our results suggest a small to moderate association between obesity and hospitalized ILI among adults.


Repeated witness social stress causes cardiomyocyte contractile impairment and intracellular Ca2+ derangement in female rats.
The impact of psychosocial stressors on cardiovascular health in women is of growing interest in both the popular and scientific literature. Rodent models are useful for providing direct experimental evidence of the adverse cardiovascular consequences of psychosocial stressors, yet studies in females are scarce. Here, we investigated the effects of repeated exposure to witness social defeat stress (WS) on cardiomyocyte contractile function and intracellular Ca2+ homeostasis in young adult wild-type Groningen female rats. Female rats bore witness to an aggressive social defeat episode between two males for nine consecutive days or were exposed to a control procedure. Stress-related behaviors were assessed during the first and last WS/control exposure. Twenty-four hours after the last exposure, plasma corticosterone levels were measured, and cardiomyocytes were isolated for analyses of contractile properties and Ca2+ transients, and expression levels of proteins involved in intracellular Ca2+dynamics. The results show an impairment of the intrinsic cardiac mechanical properties and prolonged intracellular Ca2+decay in WS female rats showing social stress-related behavioral (larger amounts of burying behavior) and neuroendocrine (elevated plasma corticosterone levels) phenotypes. Further, the results implicate alterations in the sarcoplasmic reticulum Ca2+-ATPase/phospholamban complex in the contractile defects described in cardiomyocytes of WS female rats. In conclusion, this study highlights the utility of the WS model as an ethologically relevant social stressor for investigating pathophysiological processes that occur in the heart of female subjects and may increase vulnerability to social stress-related cardiovascular risk.


13C-NMR reveals glycerol as an unexpected major metabolite of the protozoan parasite Trichomonas vaginalis.
13C-NMR has been used to study the kinetics of the formation of metabolites from [1-13C]glucose in intact cells of Trichomonas vaginalis during anaerobic incubation. As well as the expected metabolites lactate and acetate, this technique revealed glycerol as an additional major product, present in amounts equimolar with acetate. The formation of glycerol is readily explained in terms of the need to maintain redox balance. This protozoan now joins the small group of organisms which are known to produce glycerol as a result of normal metabolic activities.


In vitro studies on the infection and replication of porcine circovirus type 2 in cells of the porcine immune system.
Porcine circovirus type 2 (PCV2) nucleic acid and/or antigens are consistently observed in cells of monocytic morphology in lesions of pigs affected by post-weaning multisystemic wasting syndrome (PMWS). In this study, PCV2 antigen was detected in the cytoplasm of monocytes, pulmonary macrophages (PMs) and monocyte-derived macrophages exposed to the virus in vitro, by immunofluorescence analysis (IFA) and the phenotype of these cells confirmed by detection of monocytic cell surface markers using flow cytometry. Viral antigen was not observed in lymphocytic cells. Replication of the virus in PMs was investigated further by comparison to that observed in the continuous pig kidney cell line (PK15A) using quantitative virus titration, quantitative PCR and by the detection of double stranded DNA intermediates of viral replication by Southern blotting analyses. Although increases in viral DNA and levels of infectious virus progeny and the presence of replicative intermediates, indicative of viral replication, were observed in PK15A cells, no such changes were observed in PMs in spite of the fact that infectious virus, viral antigen and viral DNA persisted in the cells for at least the duration of the experiment. These results suggest that in vivo, monocytic cells may not represent the primary target for PCV2 replication.


Vitamin d deficiency is associated with ulcerative colitis disease activity.
Previous studies on experimental mouse models have suggested a role of vitamin D in immune system regulation and IBD disease severity. In this study, we examine the relationship between vitamin D levels and clinical disease activity in human subjects with ulcerative colitis (UC). We hypothesized that patients with vitamin D deficiency will display increased UC disease activity as compared to patients with normal vitamin D levels. A cross-sectional study was performed by querying the outpatient electronic medical record of our health system for patients seen in the gastroenterology clinic from January 2007 to October 2009 who carried both a diagnosis of UC and a documented 25-OH vitamin D level within 30 days of their clinic visit. Demographic and clinical variables were collected. Clinical disease activity was calculated using the six-point partial Mayo index. Active disease was defined as a six-point index score of ≥ 1. Vitamin D deficiency was defined as a 25-OH D level below 30 ng/ml. Data were analyzed using the chi-square distribution test. Thirty-four patients met inclusion criteria (53 % female, mean age 45.7 ± 24.7 years). Fifteen patients had normal vitamin D levels and 19 patients were vitamin D deficient. Twelve patients had vitamin D levels <20 ng/ml. Vitamin D deficient patients were statistically more likely to have increased disease activity than patients with normal vitamin D levels (p = 0.04), with 68 % of deficient patients displaying active disease compared with 33 % in the sufficient group. There was also a statistically significant association between vitamin D status and need for treatment with steroids, with a higher percentage of vitamin D deficient patients (47 %) requiring such treatment compared with 7 % in the sufficient group (p = 0.02). There was no association between season of visit and disease activity. Vitamin D deficiency is common among patients with active UC, particularly those requiring corticosteroids. Further investigation is needed to determine the clinical utility of vitamin D monitoring in patients with UC and whether there is a role for vitamin D as a treatment for UC.


Linguistic Differences by Gender in Letters of Recommendation for Maternal-Fetal Medicine Fellowship Applicants.
As in many realms of academia and medicine, in obstetrics and gynecology, women experience gender bias in residency evaluations and academic promotions. More specifically, women in Maternal-Fetal Medicine (MFM) are underrepresented within departmental leadership positions. As a means of identifying spaces where bias may exist, multiple investigators have previously reported on gender bias in letters of recommendation (LORs) for residency and subspecialty training programs. We aimed to determine if linguistic differences exist in LORs for self-identified male and female applicants to MFM fellowship at an academic institution. This was a retrospective single-site cohort study from 2019 to 2021. Data collected included applicant's age, self-reported race/ethnicity and gender, geographic region of residency, step 1 and 2 scores, scholarly and volunteer activities, and number of LORs. The Linguistic Inquiry and Word Count (LIWC) software, a validated text analysis program, was used to characterize LOR linguistic content. Multivariable analysis was used to compare letter characteristics to applicant demographics. A total of 212 applications were reviewed, including 808 LORs. Women comprised 76.9% of applicants, and men 23.1%. Most applicants identified as non-Hispanic White (52.8%). Men were more likely to be international medical graduates (20 vs. 6%, p ≤ 0.01), and women reported more volunteer activities (7.1 ± 5.1 vs. 5.5 ± 4.3, p = 0.04). There were no differences in step scores, number of research projects, or number of LORs. Multivariable analysis controlling for applicant race, step 1 score, and gender of letter writer revealed that letters written for males contained significantly more references to the word category cognitive processes (7.4 ± 0.2 vs. 7.1 ± 0.1, p = 0.046), specifically in reference to the subcategories of certainty and differentiation. We identified linguistic differences in LORs written for MFM applicants, suggesting potential bias in the style of writing for male and female physicians applying to this field. · Gender bias exists in the evaluation and promotion of women in medicine.. · We sought to determine whether it also exists in letters of recommendation for MFM fellowship.. · Previous studies have examined gender bias in letters of recommendation for other specialties.. · Linguistic bias was detected in letters of recommendation for MFM fellowship from 2019 through 2021.. · We found evidence of linguistic differences based on gender of applicant and letter writers..


Peroxiredoxin 3 is a key molecule regulating adipocyte oxidative stress, mitochondrial biogenesis, and adipokine expression.
Increased oxidative stress and mitochondrial dysfunction in obese adipocytes contribute to adipokine dysregulation, inflammation, and insulin resistance. Through an advanced proteomic analysis, we found that peroxiredoxin 3 (Prx3), a thioredoxin-dependent mitochondrial peroxidase, is highly expressed in 3T3-L1 adipocytes compared to preadipocytes. Interestingly, in obese db/db mice and human subjects, adipose Prx3 levels were significantly decreased, indicating its association with obesity. We therefore employed Prx3 knockout (KO) mice and transfected 3T3-L1 cells to examine the role of endogenous Prx3 in adipocyte metabolism. Prx3 KO mice had increased fat mass compared to wild-type due to adipocyte hypertrophy. Increased adipogenic transcription factors and lipogenic gene expression during differentiation of adipose tissue-derived stem cells from Prx3-deficient mice confirmed that these adipocytes are likely to accumulate fat. Mitochondrial protein carbonylation in Prx3 KO adipose tissue and mitochondrial superoxide level in Prx3 knockdown 3T3-L1 cells were increased showing aberrant regulation of oxidative stress. Proteomic analysis and gene expression analysis of Prx3 KO mice adipocytes also showed defect in mitochondria biogenesis along with enzymes involved in glucose/lipid metabolism and oxidative phosphorylation. In addition, expression level of adiponectin was downregulated and plasminogen activator inhibitor-1 was upregulated in Prx3 KO adipocytes. Impaired glucose tolerance and insulin resistance further implied metabolic dysregulation in Prx3 KO mice. These data suggest that endogenous Prx3 may play an essential role in maintaining normal characteristics of adipocytes and that defect in Prx3 alters mitochondrial redox state and function, and adipokine expression in adipocytes leading to metabolic alteration.


Single institution experience of cloacal malformation.
The aim of this study is to report on the outcomes of patients born with cloacal malformation, managed at a single institution more than the last 28 years. The focus of this study is the long term renal and colorectal outcomes. Patients were identified from the departmental database from 1994 to 2021. The medical records and operative notes were retrospectively reviewed. Twenty-one patients fulfilled the inclusion criteria. Eleven long common channel (LCC) and ten short common channel (SCC) cloacae patients were identified. Median age at the time of primary reconstruction was 11 months in both groups. In the LCC group, seven (63.6%) patients underwent a Total Urogenital Mobilisation (TUM), and 4 (36.4%) required a vaginal replacement. 6/11 (54.5%) of patients required drainage of a hydrocolpos. In the SCC group, four patients required a TUM, two patients underwent mobilisation of the rectum and vagina alone, and three underwent rectal mobilisation alone. Two patients have required renal transplant for congenital renal dysplasia, and two have developed chronic renal failure associated with the sequalae of vesicoureteric reflux. Eleven (52.3%) of the patients manage their bowels with an antegrade continent enema (ACE), and two of the LCC cloaca are defunctioned with a colostomy. Clean intermittent catheterisation is performed by 12 (57%) of the patients, either per urethra or via a Mitrofanoff channel. The urinary and faecal continence are the main challenges in the management of cloaca patients. Many require surgical intervention to achieve social continence. Level IV.


Nanoscale zerovalent iron-mediated degradation of DDT in soil.
Nanoscale zerovalent iron (nZVI)-mediated degradation of 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane (DDT) was investigated in a spiked soil under different conditions (iron sources, iron dosage, soil moisture, temperature, and soil types) and DDT-contaminated field. The degradation efficiency of p,p'-DDT by nZVI and nZVI coated with sodium oleate (SO-nZVI) was much higher than that by nZVI coated with polyimide (PI-nZVI). The rapid degradation of p,p'-DDT by nZVI only occurred in flooded soil. The degradation half-life of p,p'-DDT decreased significantly from 58.3 to 27.6 h with nZVI dosage from 0.5 to 2.0% and from 46.5 to 32.0 h with temperature from 15 to 35 °C. The degradation efficiency of p,p'-DDT by nZVI differed in Jinhua (JH), Jiaxing (JX), Xiaoshan (XS), Huajiachi (HJC), and Heilongjiang (HLJ) soils. A good correlation was found between the degradation half-life of p,p'-DDT and multiple soil properties. The probable nZVI-mediated degradation pathway of p,p'-DDT in soil was proposed as DDT → DDD/DDE → DDNS → DDOH based on the metabolites identified by GC-MS. The in situ degradation efficiency of residual DDTs in a contaminated field was profoundly enhanced by the addition of nZVI as compared to the control. It is concluded that nZVI might be an efficient agent for the remediation of DDT-contaminated soil under anaerobic environment.


Distinct clinical and biological characteristics of acute myeloid leukemia with higher expression of long noncoding RNA KIAA0125.
Expression of long non-coding RNA KIAA0125 has been incorporated in various gene expression signatures for prognostic prediction in acute myeloid leukemia (AML) patients, yet its functions and clinical significance remain unclear. This study aimed to investigate the clinical and biological characteristics of AML bearing different levels of KIAA0125. We profiled KIAA0125 expression levels in bone marrow cells from 347 de novo AML patients and found higher KIAA0125 expression was closely associated with RUNX1 mutation, but inversely correlated with t(8;21) and t(15;17) karyotypes. Among the 227 patients who received standard chemotherapy, those with higher KIAA0125 expression had a lower complete remission rate, shorter overall survival (OS) and disease-free survival (DFS) than those with lower expression. The prognostic significance was validated in both TCGA and GSE12417 cohorts. Subgroup analyses showed that higher KIAA0125 expression also predicted shorter DFS and OS in patients with normal karyotype or non-M3 AML. In multivariable analysis, higher KIAA0125 expression remained an adverse risk factor independent of age, WBC counts, karyotypes, and mutation patterns. Bioinformatics analyses revealed that higher KIAA0125 expression was associated with hematopoietic and leukemic stem cell signatures and ATP-binding cassette transporters, two predisposing factors for chemoresistance.


Impact of Hematologic Malignancies on Outcome of Cardiac Surgery.
Previous studies suggest that patients with prior or current hematologic malignancy are at increased risk of intraoperative and postoperative complications when undergoing cardiac surgery. The aim of this review was to compare clinical outcomes of patients with a history of hematologic malignancy to those of similar patients with no known blood dyscrasia. From January 1993 to June 2017, 37,839 patients underwent elective cardiac surgery at Mayo Clinic. We matched 612 patients (1.6%) with a history of hematologic malignancy to 612 controls, and compared operative details, early postoperative complications, and late survival. The median age of matched patients with hematologic malignancy was 71 years (interquartile range [IQR], 62 to 77) and 71 years (IQR, 62 to 77) for patients without cancer. Patients with prior diagnosis of malignancy had lower hemoglobin levels, 12.8 (IQR, 11.5 to 13.8) vs 13.5 (IQR, 12.2 to 14.6; P < .001), but similar platelet counts, 195 (IQR, 147 to 263) vs 203 (IQR, 170 to 245; P = .533). Patients with malignancy were at greater risk of receiving postoperative blood transfusions (47.4% vs 35.6%, P < .001). However, reoperations for postoperative bleeding (4.7% vs 3.3%, P = .253) and stroke (1.3% vs 1.3%, P > .999) were similar. Thirty-day mortality was 3.3% among patients with hematologic malignancy and 1.5% among matched controls (P = .061). Overall survival among patients with cancer was reduced (P < .0001). Although late survival is reduced in patients with hematologic malignancies, early outcomes are generally similar to those of matched controls. Therefore, surgery should not be withheld from patients with a diagnosis of hematologic malignancy who would benefit from cardiac procedures.


The method matters. A comparative study of biologging and camera traps as data sources with which to describe wildlife habitat selection.
Habitat use is a virtually universal activity among animals and is highly relevant as regards designing wildlife management and conservation actions. This has led to the development of a great variety of methods to study it, of which resource selection functions combined with biologging-derived data (RSF) is the most widely used for this purpose. However this approach has some constraints, such as its invasiveness and high costs. Analytical approaches taking into consideration imperfect detection coupled with camera trap data (IDM) have, therefore, emerged as a non-invasive cost-effective alternative. However, despite the fact that both approaches (RSF and IDM) have been used in habitat selection studies, they should also be comparatively assessed. The objective of this work is consequently to assess them from two perspectives: explanatory and predictive. This has been done by analyzing data obtained from camera traps (60 sampling sites) and biologging (17 animals monitored: 7 red deer Cervus elaphus, 6 fallow deer Dama dama and 4 wild boar Sus scrofa) in the same periods using IDM and RSF, respectively, in Doñana National Park (southern Spain) in order to explain and predict habitat use patterns for three studied species. Our results showed discrepancies between the two approaches, as they identified different predictors as being the most relevant to determine species intensity of use, and they predicted spatial patterns of habitat use with a contrasted level of concordance, depending on species and scale. Given these results and the characteristics of each approach, we suggested that although partly comparable interpretations can be obtained with both approaches, they are not equivalent but rather complementary. The combination of data from biologging and camera traps would, therefore, appear to be suitable for the development of an analytical framework with which to describe and characterise the habitat use processes of wildlife.


The feasibility of 18F-FDG PET/CT for predicting pathologic risk status in early-stage uterine cervical squamous cancer.
Postoperative pathologic risk factors (PRFs) could increase the recurrence rate in early-stage uterine cervical squamous cancer (ECSC). Our study intended to explore the efficiency of 18F-FDG PET/CT for assessing the pathologic risk status (PRS) in ECSC patients. This retrospective study was performed in 240 ECSC patients with stage IA2-IIA2 (FIGO 2009), who underwent preoperative PET/CT scans and subsequent radical surgery between January 2010 and July 2015. Intermediate-risk (tumour diameter ≥ 4 cm, stromal invasion depth ≥ 1/2, lymphovascular space invasion (LVSI)), and high-risk factors (parametria involvement, positive surgery margin, pelvic lymph node metastasis) were confirmed by postoperative pathology. Patients with none of these PRFs were at a low risk for relapse. One of these PRFs was defined as positive risk. The relationship between each PRF and 18F-FDG uptake was analysed by t-test. Chi-square tests and logistic regression analyses were used to determine the efficiency of PET/CT parameters for assessing the PRS. The area under the curve (AUC) was used as an indicator for predictive efficiency. Patients with higher SUVmax (p < 0.001), MTV (p < 0.001) and TLG (p < 0.001) had larger tumour sizes and deeper stromal invasion. Further multivariate analyses showed SUVmax and TLG were independent predictors for positive- and intermediate-risk status. In high-risk group, MTV and TLG were associated with pelvic lymph node metastasis and parametria involvement. However, only MTV was a significant indicator. Preoperative 18F-FDG PET/CT had an independent predictive value for PRS in ECSC.


Protein crystals make it big at electrode surfaces.
Enhanced and rapid growth of lysozyme crystals at the surface of a platinum electrode, using an applied current and a simplified crystallizing solution, is demonstrated.


Endomyocardial upregulation of beta1 adrenoreceptor gene expression and myocardial contractile reserve following cardiac resynchronization therapy.
Congestive heart failure (CHF) is associated with a blunted force-frequency relation (FFR) and myocardial contractile reserve (MCR) partially from a downregulation of beta1-adrenoreceptors (beta1-AR). We investigated whether acute and chronic cardiac resynchronization therapy (CRT) was capable of reversing the blunted FFR and MCR and if this was associated with upregulation of beta1-AR. Left ventricle dP/dtmax was invasively measured in 10 CHF patients (New York Heart Association class > or =3; ejection fraction <25%) during incremental dual chamber (DDD)-CRT pacing at 70, 90, 110, and 130 beats/min, with and without continuous infusion of intravenous dobutamine, immediately after CRT implantation (BL) and 4 months later (FU). In a subgroup of 5 patients, serial left ventricle beta1 and beta2-AR gene expression was measured using reverse transcriptase-polymerase chain reaction. Four months after the initiation of resynchronization therapy, DDD-CRT pacing results in a significant upward shift of the heart rate versus LV dP/dtmax relationship (P < .01) with force frequency amplification as evidenced by the steeper slope of the force frequency response (P = .04). Infusion of dobutamine recruits myocardial contractile reserve and increases the heart rate versus LV dP/dtmax relationship at BL and at FU (both P < .05). However, only at follow-up was an additional force frequency amplification noticed (P < .05) during dobutamine infusion. This observation was paralleled by a significant upregulation of beta1-AR gene expression (P = .02). Chronic CRT is associated with a partial restoration of the FFR and with a recruitment in myocardial contractile reserve, which is paralleled by upregulation of beta1-AR.


Transradial and transulnar access for iliac artery interventions using sheathless guiding systems: A feasibility study.
Our aim was to evaluate the acute success and complication rates of the transradial and transulnar access for iliac artery stenting using sheathless guiding systems. Clinical and angiographic data from 156 consecutive patients with symptomatic iliac artery stenosis who were treated with transradial or transulnar access were evaluated. All patients underwent Duplex ultrasound before and after the intervention. The primary endpoints were the procedural success rate, major adverse events, and access site complication rates. The secondary endpoints were the angiographic result of the iliac artery intervention, fluoroscopy time, X-ray dose, procedure length, crossover rate to another puncture site and hospitalization duration. The impact of the learning curve was also investigated, along with right or left radial access. The indication for the intervention was intermittent claudication in 109 patients (69.9%), critical limb ischemia in 44 (28.2%) subjects and acute limb ischemia in three individuals (1.9%). Technical success was achieved in 155 patients (99.4%), with a crossover rate of 3.8%. Radial and ulnar artery access was used in 151 (96.8%) and 7 (4.5%) patients, respectively. The Ankle-brachial index increased from 0.69 [0.65-0.72] to 0.91 [0.88-0.95] as a result of the procedures (P < 0.001). The cumulative incidence of major adverse events was 3.8% at the 2-month follow-up (0% in patients with intermittent claudication and 13.8% in patients with critical limb ischemia). Radial artery access site complications were encountered in eight patients (5.1%). We documented decreased X-ray doses (1742.0 [783.9-2701] vs. 1435 [991.1-1879] vs. 692.8 [275.3-1110] Gy cm-2 P < 0.05) over time; however, the fluoroscopy time, procedure time, and contrast consumption were not significantly different. Left hand access was not associated with significantly better results than right radial artery access. Iliac artery stenting can be safely and effectively performed using radial or ulnar artery access and sheathless guiding catheters, with acceptable complication rates and high levels of technical success. The physician learning curve plays an important role in decreasing the X-ray dose. © 2016 The Authors. Catheterization and Cardiovascular Interventions Published by Wiley Periodicals, Inc.


Middle East Respiratory Syndrome Coronavirus Seropositivity in Camel Handlers and Their Families, Pakistan.
A high percentage of camel handlers in Saudi Arabia are seropositive for Middle East respiratory syndrome coronavirus. We found that 12/100 camel handlers and their family members in Pakistan, a country with extensive camel MERS-CoV infection, were seropositive, indicating that MERS-CoV infection of these populations extends beyond the Arabian Peninsula.


Conversations between self and self as Sigmund Freud--A virtual body ownership paradigm for self counselling.
When people see a life-sized virtual body (VB) from first person perspective in virtual reality they are likely to have the perceptual illusion that it is their body. Additionally such virtual embodiment can lead to changes in perception, implicit attitudes and behaviour based on attributes of the VB. To date the changes that have been studied are as a result of being embodied in a body representative of particular social groups (e.g., children and other race). In our experiment participants alternately switched between a VB closely resembling themselves where they described a personal problem, and a VB representing Dr Sigmund Freud, from which they offered themselves counselling. Here we show that when the counsellor resembles Freud participants improve their mood, compared to the counsellor being a self-representation. The improvement was greater when the Freud VB moved synchronously with the participant, compared to asynchronously. Synchronous VB movement was associated with a much stronger illusion of ownership over the Freud body. This suggests that this form of embodied perspective taking can lead to sufficient detachment from habitual ways of thinking about personal problems, so as to improve the outcome, and demonstrates the power of virtual body ownership to effect cognitive changes.


Characteristics and mechanism of phosphate removal by lanthanum modified bentonite in the presence of dissolved organic matter.
Lanthanum modified bentonite (LMB) is a widely used adsorbent for removing inorganic phosphorus from polluted water to prevent eutrophication. However, its efficiency can be affected by various environmental factors, including dissolved organic matter (DOM), which is still unclear. In this study, we systematically explored the influence of model DOMs, including HA, bovine serum albumin (BSA), and sodium alginate (SA), on phosphate adsorption by LMB, as well as to elucidate the underlying adsorption mechanisms. Our results showed that only HA had a significant effect on phosphate adsorption by LMB, causing inhibition. When three DOMs were mixed with phosphate in different proportions and DOM was mainly HA, the performance of phosphate adsorption on LMB became worse, while BSA can slightly offset this impact. The kinetics of HA and phosphate adsorption on LMB followed the pseudo-second-order kinetic model, and isotherms fitted the Langmuir model, with a maximum adsorption capacity of 5.7 mg g-1 for P and 12 mg g-1 for HA. However, when HA and phosphate were mixed based on their Qm, a C/P molar ratio of 5.35, LMB preferentially adsorbed phosphate. HA invasion was also disadvantageous for phosphate removal by LMB, in which P adsorption was less efficient at low-concentrations. However, during co-adsorption the adsorption capacity for HA was higher. With a secondary addition of higher levels of P, both pollutants were adsorbed more effectively. In the natural water experiment, phosphate concentration decreased with increasing shaking time, while the UV254 value showed a downward trend, indicating that LMB also adsorbed HA. Characterization results showed that La and phosphate formed LaPO4 precipitation, forming La-O-P inner-sphere complexes as the main mechanism of phosphate removal by LMB. La and HA formed La-HA complexes, with O-CO bonds from HA competing for lanthanum with phosphate. Despite HA obstructing pores from adsorbent, LMB still maintained a good binding ability with phosphate. It may form La-P-HA ternary complexes during adsorption to keep HA adsorption amount.


A hierarchical CoTe2-MnTe2 hybrid nanowire array enables high activity for oxygen evolution reactions.
In this communication, we demonstrate the development of hierarchical CoTe2-MnTe2 hybrid nanowires grown on Ti mesh (CoTe2-MnTe2/TM) as an electrocatalyst for the oxygen evolution reaction. The catalyst exhibits excellent conductivity and exposes sufficient active sites derived from its favorable composition and structure, which only needs an overpotential of 310 mV to drive a current density of 50 mA cm-2 in 1.0 M KOH.


A novel pyroptosis risk model composed of NLRP6 effectively predicts the prognosis of hepatocellular carcinoma patients.
Pyroptosis is a unique inflammatory-related cell death process, and inflammation is considered to be a key factor in hepatocellular carcinoma (HCC). However, the pyroptosis landscape in HCC has not been thoroughly studied. Clinical data and RNA sequencing data of HCC patients were collected from The Cancer Genome Atlas database, and differentially expressed genes (DEGs) associated with pyroptosis were discovered. The relationship between DEGs and prognosis was studied. Using The Cancer Genome Atlas cohort, a least absolute shrinkage and selection operator regression model was built on the basis of pyroptosis-related DEGs, which was then verified by the Gene Expression Omnibus (GEO) cohort. Functional enrichment analysis and immunological states were also studied between distinct risk subgroups. Finally, the potential tumor suppressive function of NLRP6 in HCC was analyzed. In total, 26 pyroptosis-related DEGs were identified. Consensus clustering results showed patients with high levels of pyroptosis were associated with higher tumor stage, grade, and poor prognosis. The least absolute shrinkage and selection operator risk model was built using six genes linked with prognosis (GSDMC, GSDME, NOD2, NLRP6, CASP8, and SCAF11). Risk score was an independent risk factor that suggested shortened overall survival in both the training cohort (HR: 3.52, 95% CI: 1.351-9.193) and validation cohort (HR: 3.31, 95% CI: 1.435-7.617). Meanwhile, the low-risk population had higher immunological activity. We also found a novel potential tumor suppressor gene NLRP6, which may negatively regulate the E2F and MYC pathways and be associated with higher immune cell infiltration levels, which lead to better prognosis. This study revealed the pyroptosis landscape of HCC and provided a promising clinical prognosis evaluation model. Additionally, some new targets related to prognosis such as NLRP6 are proposed for further study.


Chemopreventive effect of methanolic extract of Azadirachta indica on experimental Trypanosoma brucei induced oxidative stress in dogs.
The medicinal properties of Azadirachta indica have been harnessed for many years in the treatment of many diseases in both humans and animals. Twenty-five apparently healthy dogs weighing between 3 and 8 kg were randomly divided into five groups with five dogs in each group. Ameliorative effect of A. indica on erythrocyte antioxidant status and markers of oxidative stress were assessed. Liver and kidney function tests were also performed. Pre-treatment with methanolic extract of Azadirachta indica (MEAI) at different doses did not significantly alter the values of alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase activity in Trypanosoma brucei infection. Although, serum creatinine significantly (P < 0.05) decreased with pre-treatment with 50 mg/kg A. indica, after 2 weeks of T. brucei infection. However, the reduced glutathione (GSH) content of the erythrocyte increased significantly in animals pre-treated with 50 mg/kg and 200 mg/kg of A. indica respectively. Markers of oxidative stress such as malondialdehyde and hydrogen peroxide generated were higher in animals infected with T. brucei with no significant (P >0.05) difference compared to the values obtained in pre-treated animals. Pre-treatment with 100 mg/kg and 200 mg/kg of A. indica significantly (P < 0.05) decreased serum myeloperoxidase activity at 2 weeks post-infection with T. brucei. From this study, MEAI showed significant ability to attenuate oxidative stress and inflammation during experimental T. brucei infection.


Early impairment of long-term depression in the perirhinal cortex of a mouse model of Alzheimer's disease.
Visual recognition memory is early impaired in Alzheimer's disease. Long-term depression of synaptic transmission in the perirhinal cortex is critically involved in this form of memory. We found that synaptic transmission was impaired in perirhinal cortex slices obtained from 3-month-old Tg2576 mice, and that 3,000 pulses at 5 Hz induced long-term depression in perirhinal cortex slices from age-matched control mice, but not in those from Tg2576 mice. To our knowledge, these data provide the first evidence of synaptic transmission and long-term depression impairment in the perirhinal cortex in an animal model of Alzheimer's disease, and the earliest synaptic deficit in Tg2576 mice.


Atorvastatin ameliorates tissue damage of obstructed ureter in rats.
To investigate the effects of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor on the tissue damage and fibrosis of obstructed ureters, 80 rats were studied. Atorvastatin, a HMG-CoA reductase inhibitor, was administered to 40 rats at the dose of 20 mg/kg per day 1day before unilateral ligation of ureters and every day thereafter. The other rats served as controls. Eight rats from each group were sacrificed for examination on days 7, 14, 21, 28 and 42 after ligation, respectively. The expressions of transforming growth factor-β1 (TGF-β1), Interleukine-1β (IL-1β), Interleukine-6 (IL-6), tumor necrosis factor-alpha (TNF-α), proliferation cell nuclear antigen (PCNA), and the apoptotic cells in the ureteric smooth muscle were examined. Hydroureter and fibrosis of the muscle layer became progressively aggravated in the ligated ureters of the atorvastatin-treated group and control group. The severities of hydroureter and muscle layer fibrosis in the ligated ureters of the treated group were significantly less than in the control group. The atorvastatin administration also decreased the expression of TGF-β1, IL-1β, IL-6, TNF-α, PCNA and the labeling index of apoptotic cells in the smooth muscle layer of ligated ureters in the treated group. We concluded that atorvastatin might ameliorate the tissue damage of obstructed ureters, at least partially, via the inhibition on TGF-β1) expression and by diminishing the effects of pro-inflammatory cytokines.


Speech perception and auditory P300 potentials after section of the posterior half of the truncus of the corpus callosum.
A 47 year old woman who underwent surgical section of the posterior half of the corpus callosum because of meningioma in the right lateral ventricle was studied from the aspects of speech perception and auditory evoked potentials. The pure tone audiometry showed normal hearing levels for both ears. The monosyllable perception test disclosed that the left ear had lower correct percent than the right ear. The dichotic listening test demonstrated remarkable extinction in response to verbal stimuli in the left ear. Auditory brainstem, middle latency and slow vertex responses were normal for both ears, without right and left difference. P300 event related potentials were recorded by three different pairs of stimuli: pure tone (1 KHz vs. 2 KHz), words (Aka vs. Kuro), and monosyllable (PA vs. BA). Both P300 for pure tone and word stimuli to each ear showed large positive potentials within 200-500 msec but P300 for monosyllable stimuli to each ear did not show obvious potentials within 200-500 msec. These results suggest that the posterior half of the truncus of the corpus callosum can be related to transfer of speech information between right and left hemispheres.


1H-Imidazol-3-ium-4-carboxyl-ate.
In the title compound, C(4)H(4)N(2)O(2), both imidazole N atoms are protonated and carboxyl-ate group is deprotonated, resulting in a zwitterion. The mol-ecule is essentially planar, with an r.m.s. deviation of 0.012 (1) Å. In the crystal, N-H⋯O hydrogen bonds and π-π stacking inter-actions [centroid-centroid distance = 3.674 (2) Å] between the imidazole rings link the mol-ecules into a three-dimensional supra-molecular network.


Critical interval of somal calcium transient after neurite transection determines B 104 cell survival.
Nerve cells may survive or die after axonal or dendritic transection. After neurite transection near (<50 mum) the cell body of Fura-2-loaded B 104 neuroblastoma (rat brain-derived) cells, the somal calcium concentration (SCC) undergoes a three-phase transient change: a rapid (0-0.15-min post-transection [PT]) rise phase, followed by an early (0.15--1.5-min PT) rapid decay phase, and succeeded by a late (1.5-60-min PT) slower decay phase that restores SCC to preinjury levels. The SCC in a critical interval (1.5-12.5 min PT) of the third transient phase correlates with cell fate, i.e., most transected cells that exclude dye (restore a barrier) and die have a significantly higher (P<0.005) SCC in this critical interval than do transected cells that exclude dye and survive at 24-hr PT. Loading BAPTA (chelation of somal Ca(2+)) before, but not after, the critical interval increases the percentage of cells that survive compared to that of cells transected without BAPTA loading. Furthermore, most transected cells that die despite successful barrier restoration exhibit characteristics consistent with apoptosis initiated during the critical interval of the SCC, including caspase activation and plasmalemmal phosphatidylserine translocation. These data suggest that decreased cell survival for injuries near the soma is due to Ca(2+)-initiated apoptosis during the critical interval of the third phase of the SCC transient. (c) 2005 Wiley-Liss, Inc.


Diaphragmatic vasodilation elicited by pulmonary C-fiber stimulation.
This study was performed to assess the effect of pulmonary C-fiber stimulation with capsaicin on vascular resistance in the diaphragm. Nine dogs were anesthetized with pentobarbital sodium and were instrumented with right and left ventricular catheters. The left phrenic artery was isolated and perfused from an extracorporeal reservoir. Right ventricular capsaicin injections (5-20 micrograms/kg) caused significant decreases in phrenic perfusion pressure (-16%), systemic arterial pressure (-32%), and heart rate (-19%). Injection of identical doses of capsaicin into the left ventricle led to no significant changes in phrenic arterial perfusion pressure or systemic arterial pressure but a 10% decrease in heart rate. Bilateral cervical vagotomy eliminated the response to both right and left ventricular injection of capsaicin, as did administration of the autonomic ganglion blocker hexamethonium bromide. The results indicate that pulmonary C-fiber stimulation reflexly vasodilates vessels in the diaphragm.


Proteolytic processing of the ovine prion protein in cell cultures.
The cellular compartment and purpose of the proteolytic processing of the prion protein (PrP) are still under debate. We have studied ovine PrP constructs expressed in four cell lines; murine neuroblastoma cells (N2a), human neuroblastoma cells (SH-SY5Y), dog kidney epithelial cells (MDCK), and human furin-deficient colon cancer cells (LoVo). Cleavage of PrP in LoVo cells indicates that the processing is furin independent. Neither is it reduced by some inhibitors of lysosomal proteinases, proteasomes or zinc-metalloproteinases, but incubation with bafilomycin A1, an inhibitor of vacuolar H+/ATPases, increases the amount of uncleaved PrP in the apical medium of MDCK cells. Mutations affecting the putative cleavage site near amino acid 113 reveal that the cleavage is independent of primary structure at this site. Absence of glycosylphosphatidylinositol anchor and glycan modifications does not influence the proteolytic processing of PrP. Our data indicate that PrP is cleaved during transit to the cell membrane.


Serological reactivity of some monoclonal antibodies to varicella-zoster virus.
Monoclonal antibodies to varicella-zoster virus, free from host cell reactivity, were produced by cell fusion technics. Antibodies from four different clones showed diverse activities in neutralization immunofluorescence and complement fixation assays. The antibodies provide useful reagents for viral diagnosis and viral antigenic characterization.


Development and validation of an HPLC assay for fentanyl, alfentanil, and sufentanil in swab samples.
A high performance liquid chromatography (HPLC) method for the assay of fentanyl citrate, alfentanil hydrochloride, and sufentanil citrate swab samples was developed and validated in order to control a cleaning procedure. The swabbing procedure involved Super POLX 1200 wipers moistened with water. The assay employed extraction of swabs with water and analysis by isocratic, reversed-phase, HPLC with varying ultraviolet (UV) detection for desired sensitivity, depending on the analyte. The method was shown to be selective and linear from the limits of quantitation (0.10, 0.20, and 0.15 microg/swab for fentanyl citrate, alfentanil, and sufentanil, respectively) to over three times these concentrations. The assay limits (detection levels) per swab area were set at least at 0.2% of the concentrations of the actives in the drug products (0.02, 0.10, and 0.10 microg/swab or approximately 0.03, 0.02, and 0.2% for fentanyl citrate, alfentanil, and sufentanil, respectively). It should be noted that all active concentrations listed in this work were calculated based on the salt form concentration for fentanyl (citrate salt) and the free base forms for alfentanil and sufentanil. No reference standard was available for alfentanil hydrochloride and sufentanil citrate. Drug product was used instead throughout this study.


Targeting endothelial dysfunction in hypertensive subjects.
The endothelium is a favourite early target of cardiovascular risk factors and cardiovascular diseases like hypertension. This key role of the endothelium results from its capacity to respond to numerous autocrine and paracrine stimuli and to mechanical factors like shear stress but also from the pathophysiological consequences of endothelial dysfunction on vasomotor tone, arterial stiffness, arterial remodelling, and inflammation, all of which are factors that play a critical role in atherosclerosis and target-organ damage. In hypertension, endothelial dysfunction has been shown at the level of both resistance and conduit arteries and mainly results from an increase in nitric oxide (NO) degradation by interaction between NO and superoxide anions, while in experimental models of hypertension a decrease in NO production can also be observed. The fact that forearm endothelial dysfunction is a marker of future cardiovascular events in patients with hypertension stresses the importance of the clinical evaluation of endothelial function and of the evaluation of the effects of the different antihypertensive drug classes on this parameter. In this context, many studies have demonstrated that angiotensin-converting enzyme inhibitors, the perindopril-indapamide combination, and angiotensin II type I receptor (AT1) blockers improve endothelium-dependent vasodilatation partly independently of arterial pressure. Both their antioxidant effects and the stimulation of the release of NO are involved in their beneficial effects. For calcium antagonists, only the recent drugs have been shown to improve endothelial function with a simultaneous improvement in several markers of oxidative stress. Finally, beta-blockers classically do not affect endothelial function. Only nebivolol, a beta-blocker with NO donor properties, has been shown to improve endothelial function, but this effect results from the increase in NO and not from the beta-blocking properties of the drug.


Postoperative elevation of CA15-3 due to pernicious anemia in a patient without evidence of breast cancer recurrence.
Cancer antigen 15-3 (CA15-3) is considered as a marker for breast cancer recurrence. However, we encountered a case where the patient showed postoperative elevation of the CA15-3 level due to pernicious anemia without evidence of breast cancer recurrence. The patient was a 60-year-old postmenopausal woman. She had undergone partial mastectomy and sentinel lymph node biopsy (SLNB) for her T1 left breast cancer. SLNB had indicated no lymph node metastases. The tumor was positive for hormone receptors and negative for human epidermal growth factor receptor 2. Therefore, an aromatase inhibitor and external beam irradiation had been administered as adjuvant therapy. However, the CA15-3 level was found to be elevated at 6 months postoperatively. Although imaging studies did not indicate breast cancer recurrence, CA15-3 levels continued to increase. Based on the findings of blood tests and gastroendoscopy, a diagnosis of pernicious anemia due to vitamin B12 deficiency was finally confirmed at 2 years and 6 months postoperatively. The CA15-3 level returned to normal after vitamin B12 administration. The possibility of pernicious anemia should be considered in cases of postoperative elevated CA15-3 levels with no evidence of recurrence in patients with early breast cancer.


T cell lines responding to Mycoplasma arthritidis and chondrocytes in the Mycoplasma arthritidis infection of rats.
CD 4+ T cell lines responding specifically to Mycoplasma (M.) arthritidis were established from spleen and lymph nodes of a Lewis rat infected with M. arthritidis. The T cell response to M. arthritidis was MHC class II-restricted. M. arthritidis-reactive T cell lines also responded to syngeneic chondrocytes suggesting that M. arthritidis and chondrocytes may share a common antigenic structure. The T cell lines reacting with chondrocytes may play an important role in the chronic stage of the M. arthritidis-induced arthritis of rats by maintaining immune reactions initiated by M. arthritidis antigens and originally established to eliminate the mycoplasmas. These autoimmune reactions could perpetuate after disappearance of the mycoplasmas and possibly last for the entire lifetime.


A new route to fabricate biocompatible hydrogels with controlled drug delivery behavior.
Hydrogels for drug delivery have attracted extensive interests since they can be used for biomaterials such as contact lenses. Here, we report that biocompatible hydrogels for contact lenses with controlled drug delivery behavior can be fabricated using copolymer hydrogels and Layer-by-Layer (LbL) surface modification technique. Methyl acrylic anhydride (MAA) modified β-cyclodextrin (β-CD) (MA-β-CD) was synthesized and copolymerized with hydroxyethyl methacrylate (HEMA) to form copolymer hydrogel. The introduction of second monomer of MA-β-CD would accelerate the polymerization of hydrogel, leading to increase of residual CC groups. The structure of copolymers was characterized by differential scanning calorimetry (DSC). Transparence, equilibrium swelling ratio and contact angle of copolymer hydrogel were also detailed discussed in the work. In vitro drug release results showed that copolymer hydrogel with higher MA-β-CD content exhibited a better drug loading capacity and drug release behaviors could be tuned by MA-β-CD/monomer ratio. Finally, alkynyl functional hyaluronic acid (HA-BP) and nitrine functional chitosan (CS-N3) were synthesized and covalently cross-linked to copolymer hydrogel surface using LbL technique through click chemistry. The successful LbL multilayers were confirmed by X-ray Photoelectron Spectroscopy (XPS). Resultsofcytotoxicityexperiment revealed that the hydrogels were biocompatible since they could support the growth of cells.


Catecholamines and convulsions.
Severe depletion of brain noradrenaline and separately of brain dopamine was induced in rats by intracerebral injection of the selective neurotoxin 6-hydroxydopamine, and the susceptibility of the treated animals to various seizure-inducing manipulations was examined. A significant potentiation of the seizures induced both by Metrazol and by electroconvulsive shock was found in animals depleted of brain noradrenaline, but no alteration was seen after depletion of brain dopamine on either measure. The catecholaminergic drug cocaine also induced seizures, but these were found not to depend on either brain noradrenaline or dopamine as they continued to occur in the virtual absence of either catecholamine. It is concluded that cocaine induces seizures by a non-specific toxic mechanism and that noradrenaline, but not dopamine, is involved in reducing the suceptibility of the central nervous system to the several distinct forms of seizure induction examined.


Failure of intertrochanteric fracture fixation with a dynamic hip screw in relation to pre-operative fracture stability and osteoporosis.
We have reviewed 178 intertrochanteric fractures treated by dynamic hip screw (DHS) fixation between March 1995 and December 1999 and followed for a minimum of 1 year. We used Singh's classification of the trabecular bone structure in the proximal femur as a measure of osteoporosis and also classified the fractures according to three different systems (Boyd-Griffin, Evans, AO). The postoperative radiographs were examined for loss of reduction, i.e. varus angulation >100, perforation of the femoral head, more than 20-mm extrusion of a lag screw or metal failure. We found 49 cases which showed radiographic failures. Two were stable fractures and 47 unstable fractures (Evans' classification). Unstable fractures with osteoporosis had a failure rate of more than 50%. In such cases DHS should not be the first choice for treatment.