A sol-particle immunoassay for determination of anti-rubella antibodies; development and clinical validation.
A sol-particle immunoassay (SPIA) was developed for determination of anti-rubella antibodies. The test is based on antibody-coated gold sol particles, which may agglutinate in the presence of rubella haemagglutinin antigen. The agglutination which gives a decrease in optical density can be inhibited by specific antibodies present in sera incubated with the immunochemical reagents. The test is performed in microtitration plates and results can be read in a plate-reader. Clinical validation studies were performed comparing the anti-rubella SPIA with the haemagglutination inhibition test and with the latex agglutination test. The sensitivity of the SPIA was calculated to be 99%; the specificity of the test was at least 99.5%. The anti-rubella SPIA is highly suitable for large-scale screening to determine the rubella immune-status.


Electro-mechanical noise in atrial muscle fibres of the carp.
Steady membrane voltage fluctuations have been observed in atrial muscle fibres of the carp. These voltage fluctuations produce minute mechanical escillations, as revealed by an interference contrast microscope. The steady voltage fluctuations may be related to abnormal automaticity in the heart.


Liver enzyme trends in patients taking uninterrupted metformin before and after coronary surgery.
Metformin is an oral antidiabetic agent belonging to the biguanide class of antidiabetics. Possible novel applications for metformin in cardiovascular disease might exist. The aim of this study was to verify a possible association between pre-operative metformin administration and protection against ischemia-induced liver injury in diabetic patients undergoing coronary artery bypass grafting (CABG) surgery. A retrospective case-control series was conducted at a single center. Two hundred consecutive diabetic patients underwent isolated on-pump CABG during a 12-month span (July 2015 - July 2016). Metformin was uninterrupted in patients who took this drug prior to CABG; 68 patients were metformin users (34%) while 132 patients were taking other antidiabetic agents (66%). Liver enzymes and other organ markers were consecutively recorded daily for 7 days after surgery and expressed as medians with interquartile range (IQR). Both the metformin and non-metformin group of patients had similar pre-operative demographic characteristics. The median (IQR) post-operative cardiac enzyme creatinine kinase (CK) MB fraction was significantly lower in the metformin group [46.4 U/L (35.8-66.5) vs. 66.5 U/L (44-94.5), P=0.005]. Total bilirubin [0.58 (0.48-0.82) mg/dL vs. 0.67 (0.56-0.95) mg/dL, P=0.021], the transaminase aspartate aminotransferase (AST) [32.5 U/L (25.0-42.0) vs. 37.5 U/L (28.5-56), P=0.011], the transaminases alanine aminotransferase (ALT) [48.5 U/L (40.0-64.0) vs. 57.0 U/L (44.0-77.0), P=0.040] and lactate dehydrogenase (LDH) [320.0 U/L (273.5-367.2) vs. 356.5 U/L (289.5-427), P=0.014] were significantly lower in the metformin group. No differences were noted in clinical outcomes. In this limited retrospective study, the diabetic patients who took metformin before and after undergoing CABG appeared to have a reduced post-operative surge in the total bilirubin and transaminase liver enzymes. Metformin's role in mitigating oxidative stress in liver cells might explain this observation. Further experimental studies are warranted to verify this possible effect.


ATP acts as a survival signal and prevents the mineralization of aortic valve.
Calcific aortic valve disease (CAVD) is a disorder related to progressive mineralization of valvular tissue that is a leading cause of heart disease. Thus far, there is no medical treatment to prevent the mineralization of aortic valves. It is generally thought that pathologic mineralization is linked to apoptosis of vascular cells. However, the role of apoptosis during mineralization as well as the survival signals for valvular interstitial cells (VICs), the main cellular component of aortic valves, remains to be identified. Here, through several lines of evidence, we show that bioavailability of extracellular ATP is a signal which determines survival or apoptosis of VICs and, in doing so, plays a major role in the development of CAVD. Specifically, in CAVD and in VIC cultures undergoing mineralization, we found a high level of the ectonucleotidase ENPP1. In addition, a genetic polymorphism in the intron 9 of the ENPP1 gene was associated with CAVD in a case-control cohort as well as with mRNA expression levels of ENPP1 in aortic valves. A high level of ENPP1 in CAVD promoted apoptosis-mediated mineralization of VICs by depleting the extracellular pool of ATP. We then documented that release of ATP by VICs promoted cell survival via the P2Y(2) receptor and the PI3K/Akt signaling pathway. Hence, our results show that level of ENPP1 modulates extracellular concentration of ATP, which is an important survival signal for VICs. These findings may help to develop novel pharmacological treatment for CAVD.


Nasogastric tube in mechanical ventilated patients: ETCO2 and pH measuring to confirm correct placement. A pilot study.
Nasogastric tube (NGT) placement is a procedure commonly performed in mechanically ventilated (MV) patients. Chest X-Ray is the diagnostic gold-standard to confirm its correct placement, with the downsides of requiring MV patients' mobilization and of intrinsic actinic risk. Other potential methods to confirm NGT placement have shown lower accuracy compared to chest X-ray; end-tidal CO2 (ETCO2) and pH analysis have already been singularly investigated as an alternative to the gold standard. Aim of this study was to determine threshold values in ETCO2 and pH measurement at which correct NGT positioning can be confirmed with the highest accuracy. This was a prospective, multicenter, observational trial; a continuous cohort of eligible patients was allocated with site into two arms. Patients underwent general anesthesia, orotracheal intubation and MV; in the first and second group we respectively assessed the difference between tracheal and esophageal ETCO2 and between esophageal and gastric pH values. From November 2020 to March 2021, 85 consecutive patients were enrolled: 40 in the ETCO2 group and 45 in the pH group. The ETCO2 ROC analysis for predicting NGT tracheal misplacement demonstrated an optimal ETCO2 cutoff value of 25.5 mmHg, with both sensitivity and specificity reaching 1.0 (AUC 1.0, p < 0.001). The pH ROC analysis for predicting NGT correct gastric placement resulted in an optimal pH cutoff value of 4.25, with mild diagnostic accuracy (AUC 0.79, p < 0.001). In patients receiving MV, ETCO2 and pH measurements respectively identified incorrect and correct NGT placement, allowing the identification of threshold values potentially able to improve correct NGT positioning. NCT03934515 (www.clinicaltrials.gov).


Anti-Reflective Coatings Produced via Atomic Layer Deposition for Hybrid Polymer 3D Micro-Optics.
The increasing demand for optics quality requires the lowest optical power loss, which can occur from unwanted reflections. Laser direct writing (LDW) allows for the fabrication of complex structures, which is particularly advantageous in micro-optic applications. This research demonstrates the possibility of forming an anti-reflective coating on hybrid polymer micro-lenses fabricated by employing LDW without changing their geometry. Such coating deposited via atomic layer deposition (ALD) decreased the reflection from 3.3% to 0.1% at a wavelength of 633 nm for one surface of hybrid organic-inorganic SZ2080™ material. This research validates the compatibility of ALD with LDW 3D multiphoton lithography synergistically, expanding its applications on optical grade sub-100 μm scale micro-optics.


Medial hypothalamic stimulation suppresses nociceptive spinal dorsal horn neurons but not the tail-flick reflex in the rat.
This study investigated the potential analgesic effects of medial hypothalamic stimulation (HS) on a measure of nocifensive behavior (tail-flick test (TF] in awake rats, and potential inhibitory effects of identical HS on spinal dorsal horn neuronal responses to noxious skin heating in the same animals anesthetized with sodium pentobarbital. Sixty-five male Sprague-Dawley rats implanted with a bipolar stimulation electrode in histologically verified medial hypothalamic sites were tested behaviorally for TF suppression during HS (100 ms trains at 100 Hz, 3/s, 100-1100 microA) in 2-4 consecutive weekly test sessions. Thirty-three of these rats were then used in electrophysiological experiments to record responses of 36 dorsal horn units to noxious skin heating (48-54 degrees C, 10 s/2 min) of the hindfoot pad in the absence of and during HS. Behaviorally, 31/65 rats had no TF suppression at the highest HS intensity tested (1100 microA), 24/65 rats exhibited aversive behavior or motor activity which disallowed reliable TF testing, and only 10/65 rats showed TF suppression in at least one test session. In electrophysiological experiments, the heat-evoked responses of 25/36 dorsal horn units were inhibited to at least 50% of control during HS. The responses of 11 units remained at 65-100% of the control responses during HS of up to 1100 microA. In rats demonstrating TF suppression, 4/7 units were inhibited. In rats with no TF suppression, 10/15 units were inhibited, and in rats showing aversive behavior, 11/14 units were inhibited by HS. These data indicate that although HS suppresses spinal nociceptive neurons, it does not cause reliable TF suppression in unanesthetized rats and bring into question the often-held assumption that stimulation-evoked descending inhibition of spinal nociceptive neurons implies behavioral analgesia.


Validation of rapid assessment methods to determine streamflow duration classes in the Pacific Northwest, USA.
United States Supreme Court rulings have created uncertainty regarding U.S. Clean Water Act (CWA) authority over certain waters, and established new data and analytical requirements for determining CWA jurisdiction. Thus, rapid assessment methods are needed that can differentiate between ephemeral, intermittent, and perennial streams. We report on the validation of several methods. The first (Interim Method) was developed through best professional judgment (BPJ); an alternative (Revised Method) resulted from statistical analysis. We tested the Interim Method on 178 study reaches in Oregon, and constructed the Revised Method based on statistical analysis of the Oregon data. Next, we evaluated the regional applicability of the methods on 86 study reaches across a variety of hydrologic landscapes in Washington and Idaho. During the second phase, we also compared the Revised Method with a similar approach (Combined Method) based on combined field data from Oregon, Washington, and Idaho. We further compared field-based methods with a GIS-based approach (GIS Method) that used the National Hydrography Dataset and a synthetic stream network. Evaluations of all methods compared results with actual streamflow duration classes. The Revised Method correctly determined known streamflow duration 83.9% of the time, versus 62.3% accuracy of the Interim Method and 43.6% accuracy for the GIS-based approach. The Combined Method did not significantly outperform the Revised Method. Analysis showed biological indicators most accurately discriminate streamflow duration classes. While BPJ established a testable hypothesis, this study illustrates the importance of quantitative field testing of rapid assessment methods. Results support a consistent method applicable across the Pacific Northwest.


Hydroxy- and fluorapatite as sorbents in Cd(II)-Zn(II) multi-component solutions in the absence/presence of EDTA.
Apatites are suitable sorbent materials for contaminated soil and water remediation because of their low solubility and ability to bind toxic metals into their structure. Whereas in soil/water systems different complexing ligands are present, it is important to examine how these ligands affect apatite metal sorption process. The removal of cadmium (Cd) and zinc (Zn) ions from aqueous solutions by hydroxyapatite (HAP) and fluorapatite (FAP) was investigated by batch experiments with and without EDTA being present in the pH range 4-11. The surface composition of the solid phases was analyzed by X-ray photoelectron spectroscopy (XPS). The surface layer of apatites (AP), according to the (Ca+Cd+Zn):P atomic ratio, remained constant (1.4 ± 0.1) through an ion exchange. The amount of Cd(2+) and Zn(2+) removed increased with increasing pH. The removed amount of Zn(2+) was higher than Cd(2+). In the Cd-Zn binary system, competitive sorption reduced the individual removed amounts but the total maximum sorption was approximately constant. In the presence of EDTA, Cd(2+) and Zn(2+) removal was reduced because of the formation of [CdEDTA](2-) and [ZnEDTA](2-) in solution. XPS revealed an enrichment of AP surface by Cd(2+) and Zn(2+) and formation of new surface solid-solution phase with the general composition Ca8.4-xMex(HPO4)1.6(PO4)4.4(OH)0.4.


Male elderly subthreshold depression patients have smaller volume of medial part of prefrontal cortex and precentral gyrus compared with age-matched normal subjects: a voxel-based morphometry.
The brain morphological changes in subthreshold depression (sD) have not been clarified. We examined the structural difference in regional gray matter volume between community-dwelling elderly subjects with sD and age-matched nondepressed normal subjects by voxel-based morphometry (VBM) based on magnetic resonance imaging (MRI). Thirty-four community-dwelling elderly subjects with sD and 109 age-matched nondepressed normal subjects were studied by MRI. We defined subjects with sD as those who showed a Geriatric Depression Scale score of 15 or higher and a Mini Mental State Examination score of 22 or higher, and do not fulfill the criteria of major depressive disorder (MDD) in the Diagnostic and Statistical Manual for Mental Disorders IV. We collected brain magnetic resonance images of 34 subjects with sD and 109 age-matched normal subjects, and analyzed the difference in regional gray matter volume between these two groups by VBM. Male subjects with sD had significantly smaller volumes of the medial part of the bilateral frontal lobes and the right precentral gyrus than normal male subjects. We have not clarified the discrepancy in the results of gender difference. Our study revealed that even community-dwelling elderly male subjects with sD show bilateral prefrontal gray matter volume reduction, which was reported to be observed in elderly patients with MDD, although there is no significant volume reduction in the hippocampus, which was also reported to be observed in MDD. Our study may contribute to clarifying the mechanism underlying brain pathological changes in sD.


Micron-resolution Imaging of Cortical Bone under 14 T Ultrahigh Magnetic Field.
Compact, mineralized cortical bone tissues are often concealed on magnetic resonance (MR) images. Recent development of MR instruments and pulse techniques has yielded significant advances in acquiring anatomical and physiological information from cortical bone despite its poor 1 H signals. This work demonstrates the first MR research on cortical bones under an ultrahigh magnetic field of 14 T. The 1 H signals of different mammalian species exhibit multi-exponential decays of three characteristic T2 or T2 * values: 0.1-0.5 ms, 1-4 ms, and 4-8 ms. Systematic sample comparisons attribute these T2 /T2 * value ranges to collagen-bound water, pore water, and lipids, respectively. Ultrashort echo time (UTE) imaging under 14 T yielded spatial resolutions of 20-80 microns, which resolves the 3D anatomy of the Haversian canals. The T2 * relaxation characteristics further allow spatial classifications of collagen, pore water and lipids in human specimens. The study achieves a record of the spatial resolution for MR imaging in bone and shows that ultrahigh-field MR has the unique ability to differentiate the soft and organic compartments in bone tissues.


Prevention of infectious diseases by neonatal and early infantile immunization: prospects for the new millennium.
Newborns and young infants are at increased risk of severe or prolonged infections. Recent advances in our understanding of the host immune response in this age group, coupled with the development of molecular genetic tools, have paved the way for a new generation of preventive vaccines.


Elbe river flood peaks and postwar agricultural land use in East Germany.
Collectivization of farmland since the 1950s has changed the agricultural land use in former East Germany. Single fields on the collective farms became increasingly large and were cultivated with increasingly heavy farm equipment. This led to large-scale physical degradation of arable soils, enhancing the formation of surface runoff in periods with prolonged and excessive precipitation. The extent to which this development may have affected the discharge behavior of the main East German river, the Elbe, has so far not been studied. We analyzed the flood peaks of the Elbe during the past century (1900-2000). The flood discharge behavior of the Elbe has apparently changed significantly since the 1950s. Although climate changes may be involved, we conclude that the Elbe flood peaks, recorded since 1950, are related to the changes in postwar agricultural land use in former East Germany. To restore the degraded farmland soils, a change in agricultural land use may be necessary.


Exponential synchronization of stochastic delayed memristive neural networks via a novel hybrid control.
This paper investigates the exponential synchronization issue of stochastic delayed memristive neural networks (SDMNNs) via a novel hybrid control (HC), where impulsive instants are determined by the state-dependent trigger condition. The switching and quantification strategies are applied to the event-based impulsive controller to cope with the challenges induced concurrently by interval parameters, impulses, stochastic disturbance and time-varying delays. Furthermore, the control costs can be reduced and communication channels and bandwidths can be saved by using this designed controller. Then, novel Lyapunov functions and new analytical methods are constructed, which can be used to realize the exponential synchronization of SDMNNs via HC. Finally, a numerical simulation is provided to demonstrate our theoretical results.


Inhibition of lipid peroxidation by superoxide dismutase following regional intestinal ischemia and reperfusion.
In a feline model of regional intestinal ischemia, reoxygenation resulted in a rise in the concentration of oxidized glutathione, from 2.3 +/- 0.7 to 4.1 +/- 0.5% of the total glutathione. Also conjugated diene as an indirect measurement for lipid peroxidation increased after reperfusion from 2.5 +/- 0.5 mumol/g to 5.5 +/- 1.2 micrograms mol/g tissue. These results are in line with the hypothesis that ischemia results in an accumulation of hypoxanthine and a conversion of xanthine dehydrogenase into its O2-dependent form. Upon reoxygenation, hypoxanthine can be oxidized giving yield to a burst of O2-. and its interconversion products. These may initiate peroxidative tissue damage. Pretreatment of the cats with superoxide dismutase inhibited the biochemical alterations and protected the tissue from peroxidation damage.


Phase I clinical and pharmacokinetic study of orally administered N4-palmitoyl-1-beta-D-arabinofuranosylcytosine.
A phase I study of N4-palmitoyl-1-beta-D-arabinofuranosylcytosine (PLAC) was conducted in 88 patients; 36 with solid tumors and 52 with hematological malignancies, using 2 different schedules. Schedule 1 employed a single oral administration and Schedule 2, 5-day consecutive daily oral administration. In Schedule 1, the daily dose was initiated with 1 mg kg-1 which was escalated up to 24 mg kg-1 according to the modified Fibonacci's method. Side effects included nausea, vomiting and skin rashes, but myelosuppression was not seen within this dose range. In Schedule 2, the daily dose was started with 1 mg kg-1 which was escalated up to 24 mg kg-1. Major side effects were nausea, vomiting and anorexia, and mild myelosuppression was noted at 12 mg kg-1 or more. The dose-limiting toxicity was gastrointestinal toxicity, which appeared at 3.3 mg kg-1 or more and became frequent at 7 mg kg-1 or more. Pharmacokinetic study revealed that the plasma concentrations of PLAC and ara-C, obtained by the oral intake of 3.3 mg kg-1 or more of PLAC, were sufficient for these compounds to exert cytotoxic effects on various human leukemia cells in vitro. Based on these observations and plausible mechanism of action of PLAC, further clinical study should be carried out in a treatment schedule of considerably prolonged administration period with 3.3-6 mg kg-1 day-1 of PLAC.


Simultaneous occurrence of Kaposi's sarcoma and nodular lymphocyte predominant subtype of Hodgkin's lymphoma in the same lymph node.
Many cases have been established with coexisting Kaposi's sarcoma (KS) and classical Hodgkin's Lymphoma (C-HL) in the same lymph node. But composite presentation of KS and Nodular Lymphocyte Predominant subtype of Hodgkin's lymphoma (NLPHL) in the same lymph node has not been described yet. KS is related to immunodeficiency most frequently due to human immunodeficiency virus (HIV) infection or immunosupression by other reasons. Our case presented here was not related to any immunodeficiency status. Besides of being the first case of composite KS and NLPHL in the same lymph node, it was also unusual with the indolent behaviour of the NLPHL without any therapy for 8 years follow up and primary lymph node presentation of KS without cutaneous involvement.


Two different regimens of preinduction ripening of the uterine cervix with prostaglandin E2: a randomized clinical study.
A randomized clinical study was designed to test the relative efficacy of preinduction cervical ripening with 0.25 mg prostaglandin E2 (PGE2), repeated if necessary (group 1) compared to a single maturation with 0.50 mg PGE2 (group 2). In group 1 (n = 42), the ripening process was repeated every day until spontaneous onset of labor occurred or induction with oxytocin was decided (for improved Bishop score above 5, or maternal or fetal distress). In group 2 (n = 42) the patients who had not labored 12 h after the maturation procedure had labor induced with oxytocin, irrespective of their cervical status. In group 1, 28 patients experienced repeated maturations (from 2 to 9). Thirty patients had an induction of labor with oxytocin in group 2 and only 12 in group 1 (P < 0.0001). There were four failures of induction of labor in group 2 and none in group 1 (P < 0.05). Three episodes of myometrial hyperstimulation requiring an emergency cesarean section for acute fetal distress occurred in group 2 and none in group 1. There were 13 cesarean sections in group 2 and eight in group 1. The outcome of pregnancy was otherwise similar in both groups. In order to avoid failure of induction of labor, pre-induction cervical ripening with 0.25 mg PGE2, repeated daily if necessary, is therefore recommended in high risk pregnancy unless a severe maternal or a fetal distress call for a prompt delivery irrespective of the cervical status.


Hormonal pattern in women affected by rheumatoid arthritis.
Gonadal sex hormones may account for the sexual dimorphism in the immune response and for the greater incidence of autoimmune disease in females. We have previously reported the presence of progesterone (P) deficiency in female patients with thyroid and ovarian autoimmune disease. In this context, the hormonal profile in 9 women with rheumatoid arthritis (RA) and in 9 age-matched ealthy women, were evaluated to verify the presence of a steroid hormone secretion impairment in a systemic autoimmune disease, further supporting our hypothesis of P deficiency involvement. P and androgen plasma levels, in the luteal phase, were significantly lower (p < 0.05 and 0.005, respectively) in RA patients than in the control group, with a consequent decrease of the free androgen index. Moreover, despite normal cortisol values, corticosterone (B) plasma levels were significantly higher in the RA patients (p < 0.01 and 0.05 in follicular and luteal phase, respectively). Therefore, our present data confirm the androgen deficiency in patients with a systemic autoimmune disease, such as RA and support the immunomodulator effect of P. Finally, the higher B plasma levels in RA patients may suggest the presence of a slight impairment of the immune hypothalamic-pituitary-adrenal axis (HPAA), supporting its role in certain phases of RA pathogenesis. In conclusion, in addition to androgens, the immunomodulator role of P should also be taken into account in the pathogenesis of the systemic autoimmune disease.


Genomic analysis of a multidrug methicillin-resistant staphylococcus epidermidis recovered from the urine of a guinea pig (Cavia porcellus) with suspected pyelonephritis.
Staphylococcus epidermidis is an emerging pathogen causing infant pyelonephritis. There is a lack of genomic data on Staphylococcus epidermidis as the etiology of pyelonephritis and its resistant determinants. In this study, we have conducted a genomic and microbiologic investigation of an S. epidermidis recovered from the urine of a guinea pig with suspected pyelonephritis in Brazil. The genome was sequenced using the Illumina MiSeq platform and de novo assembled using SPades. Resistome, virulome, and plasmidome were in silico predicted using bioinformatics tools. Data analysis revealed that S. epidermidis USP-LZB-G06 belonged to sequence type ST332. Strikingly, a broad resistome (antibiotics, hazardous heavy metals, and biocides) was predicted, including the presence of the clinically relevant mecA, blaZ, and qacA efflux pump genes. SNP-based analysis revealed that strain USP-LZB-G06 was clustered along mecA positive S. epidermidis strains of ST332 isolated between 2008 and 2016 from humans in Australia and the United States of America. Our results indicate that the detection of this microorganism should be considered as a urinary tract infection agent in exotic pets, particularly guinea pigs. In addition, there is an urgent need to update veterinarians regarding the detection and therapeutic management of these microorganisms.


Immunoblastic sarcoma of the bladder.
We describe the first case of immunoblastic sarcoma of the bladder. Urologists should be aware of this entity arising in organs that are prone to chronic antigenic stimulation. Treatment consists of radiotherapy for localized lesions and combination chemotherapy for more advanced disease.


The ontogeny of substance P--containing nerve fibres in the developing mouse dentition.
The putative neurotransmitter, substance P, was localised in the developing teeth and periodontium of mice by indirect immunofluorescence. Substance P-containing fibres were visible in the incisor dental follicle eighteen days post-conception and entered the pulp two days after birth. The first molar pulp was innervated four days after birth and the second molar six days after birth. Innervation of the teeth by substance P fibres was delayed compared with the mucous and cutaneous innervation of adjacent areas and correlated with the stage of development of the teeth rather than the chronological age of the animal. The innervation of developing dental structures by substance P probably represents the establishment of a sensory supply prior to function of the tooth.


Regional multiparameter estimation from tomographic diffusible tracer clearance curves: modification of the double-integral method.
Measurement of regional CBF in transverse section using inert, diffusible tracers can be carried out using a double-integral form of the Kety-Schmidt equation. An implementation of this form proposed by Kanno and Lassen (the K-L estimator) is utilized by the Tomomatic 64, a dynamic single-photon computed tomography system that records washin-washout data during and following inhalation of 133Xe gas. Advantages of the algorithm include noninvasive calibration of the input function and excellent depiction of ischemia: disadvantages are sensitivity to errors in input function delay (delta), the inability to estimate the partition coefficient (lambda) (hence, only the clearance index, k, is estimated), and a noise sensitivity proportional to k. A modification of the method is proposed that not only accounts for delta variations, but also provides an estimate of relative lambda (hence, the perfusion, f, is estimated). The proposed estimator is shown to be robust in the presence of noise with error variances equal to or better than those with the K-L estimator, yet estimates of both relative f and lambda are provided by the modification. New simulation results implicate the Compton scatter fraction as a major contributor in the overestimation of white matter perfusion values using both the K-L and proposed estimators, and illustrate the need for hardware and software scatter fraction reduction and control.


Caspase-1 dependent macrophage death induced by Burkholderia pseudomallei.
Burkholderia pseudomallei is the causative agent for melioidosis, an infectious disease endemic in South-east Asia and northern Australia. Infection can result in a wide spectrum of clinical outcomes, including asymtomatic, acute or chronic conditions. The ability of the bacteria to survive intracellularly within phagocytes and non-phagocytes is postulated to help this pathogen persist in the body during latent chronic conditions. In some Gram-negative bacteria, such as Shigella and Salmonella, the ability to evade macrophage killing involves inducing rapid macrophage cell death. In several of these instances, these bacteria activate cellular caspase-1 to induce cell death, which is increasingly described to exhibit features more characteristic of oncosis than classical apoptosis. We found that B. pseudomallei is also capable of inducing caspase-1 dependent death in macrophages and this process requires a functional bsa Type III Secretion System (TTSS). Bacterial internalization and pore formation in the cell membrane is necessary for death. Furthermore, cell death is accompanied by the release of IL-1beta and IL-18. We believe that this novel description of macrophage death induced by B. pseudomallei could shed light on the pathogenesis of the bacteria in disease.


Hc-daf-2 encodes an insulin-like receptor kinase in the barber's pole worm, Haemonchus contortus, and restores partial dauer regulation.
Infective L3s (iL3s) of parasitic nematodes share common behavioural, morphological and developmental characteristics with the developmentally arrested (dauer) larvae of the free-living nematode Caenorhabditis elegans. It is proposed that similar molecular mechanisms regulate entry into or exit from the dauer stage in C. elegans, and the transition from free-living to parasitic forms of parasitic nematodes. In C. elegans, one of the key factors regulating the dauer transition is the insulin-like receptor (designated Ce-DAF-2) encoded by the gene Ce-daf-2. However, nothing is known about DAF-2 homologues in most parasitic nematodes. Here, using a PCR-based approach, we identified and characterised a gene (Hc-daf-2) and its inferred product (Hc-DAF-2) in Haemonchus contortus (a socioeconomically important parasitic nematode of ruminants). The sequence of Hc-DAF-2 displays significant sequence homology to insulin receptors (IR) in both vertebrates and invertebrates, and contains conserved structural domains. A sequence encoding an important proteolytic motif (RKRR) identified in the predicted peptide sequence of Hc-DAF-2 is consistent with that of the human IR, suggesting that it is involved in the formation of the IR complex. The Hc-daf-2 gene was transcribed in all life stages of H. contortus, with a significant up-regulation in the iL3 compared with other stages. To compare patterns of expression between Hc-daf-2 and Ce-daf-2, reporter constructs fusing the Ce-daf-2 or Hc-daf-2 promoter to sequence encoding GFP were microinjected into the N2 strain of C. elegans, and transgenic lines were established and examined. Both genes showed similar patterns of expression in amphidial (head) neurons, which relate to sensation and signal transduction. Further study by heterologous genetic complementation in a daf-2-deficient strain of C. elegans (CB1370) showed partial rescue of function by Hc-daf-2. Taken together, these findings provide a first insight into the roles of Hc-daf-2/Hc-DAF-2 in the biology and development of H. contortus, particularly in the transition to parasitism.


Visualization of spatial patterns and temporal trends for aerial surveillance of illegal oil discharges in western Canadian marine waters.
This paper examines the use of exploratory spatial analysis for identifying hotspots of shipping-based oil pollution in the Pacific Region of Canada's Exclusive Economic Zone. It makes use of data collected from fiscal years 1997/1998 to 2005/2006 by the National Aerial Surveillance Program, the primary tool for monitoring and enforcing the provisions imposed by MARPOL 73/78. First, we present oil spill data as points in a "dot map" relative to coastlines, harbors and the aerial surveillance distribution. Then, we explore the intensity of oil spill events using the Quadrat Count method, and the Kernel Density Estimation methods with both fixed and adaptive bandwidths. We found that oil spill hotspots where more clearly defined using Kernel Density Estimation with an adaptive bandwidth, probably because of the "clustered" distribution of oil spill occurrences. Finally, we discuss the importance of standardizing oil spill data by controlling for surveillance effort to provide a better understanding of the distribution of illegal oil spills, and how these results can ultimately benefit a monitoring program.


Trastuzumab potentiates doxorubicin-induced cardiotoxicity via activating the NLRP3 inflammasome in vivo and in vitro.
Trastuzumab (Tra), the first humanized monoclonal antibody that targets human epidermal growth factor receptor 2 (HER2), is commonly used alongside doxorubicin (Dox) as a combination therapy in HER2-positive breast cancer. Unfortunately, this leads to a more severe cardiotoxicity than Dox alone. NLRP3 inflammasome is known to be involved in Dox-induced cardiotoxicity and multiple cardiovascular diseases. However, whether the NLRP3 inflammasome contributes to the synergistic cardiotoxicity of Tra has not been elucidated. In this study, primary neonatal rat cardiomyocyte (PNRC), H9c2 cells and mice were treated with Dox (15 mg/kg in mice or 1 μM in cardiomyocyte) or Tra (15.75 mg/kg in mice or 1 μM in cardiomyocyte), or Dox combined Tra as cardiotoxicity models to investigate this question. Our results demonstrated that Tra significantly potentiated Dox-induced cardiomyocyte apoptosis and cardiac dysfunction. These were accompanied by the increased expressions of NLRP3 inflammasome components (NLRP3, ASC and cleaved caspase-1), the secretion of IL-β and the pronounced production of ROS. Inhibiting the activation of NLRP3 inflammasome by NLRP3 silencing significantly reduced cell apoptosis and ROS production in Dox combined Tra-treated PNRC. Compared with the wild type mice, the systolic dysfunction, myocardial hypertrophy, cardiomyocyte apoptosis and oxidative stress induced by Dox combined Tra were alleviated in NLRP3 gene knockout mice. Our data revealed that the co-activation of NLRP3 inflammasome by Tra promoted the inflammation, oxidative stress and cardiomyocytes apoptosis in Dox combined Tra-induced cardiotoxicity model both in vivo and in vitro. Our results suggest that NLRP3 inhibition is a promising cardioprotective strategy in Dox/Tra combination therapy.


Effect of Needling Parameters and Manufacturing Porosities on the Effective Thermal Conductivity of a 3D Carbon-Carbon Composite.
Needle-punching is used as an alternative to expensive and sophisticated three-dimensional (3D) weaving processes to prepare a 3D composite. In this study, a 3D needled carbon-carbon (C/C) composite structure was examined using X-ray tomography and scanning electron microscopy (SEM). The effects of manufacturing porosities, needling diameter and needling density on the thermal conductivity of the composite were determined through multiscale finite-element modelling. The degradation of thermal conductivity caused by the manufacturing porosity was higher in the longitudinal direction than in the through-thickness direction. Moreover, it was found that the through-thickness thermal conductivity of the composites increased with increasing needling diameter and density.


Characterization of gut microbiota associated with clinical parameters in intrahepatic cholestasis of pregnancy.
Intrahepatic cholestasis of pregnancy (ICP) is a liver disorder that specifically occurs in pregnancy. Elevated levels of liver transaminases aspartate aminotransferase, alanine aminotransferase and serum bilirubin levels are common biochemical characteristics in ICP. The disorder is associated with an increased risk of premature delivery and stillbirth. The characterization of the potential microbiota in ICP could go a long way in the prevention and treatment of this pregnancy disease. A total of 58 patients were recruited for our study: 27 ICP patients and 31 healthy pregnant subjects with no ICP. The V3 and V4 regions of the 16S rDNA collected from fecal samples of both diseased and control groups were amplified. 16S rRNA gene amplicon sequencing was then performed on gut microbiota. Sequencing data were analyzed and the correlation between components of microbiota and patient ICP status was found. Related metabolic pathways, relative abundance and significantly different operational taxonomic units (OTUs) between ICP and controls were also identified. Elevated levels of total bile acid, ALT, AST, Dbil and Tbil were recorded or observed in ICP subjects as compared to the control. Gut microbiota in pregnant women was dominated by four major phyla and 27 core genera. PCoA analysis results indicated that there was no significant clustering in Bray-Curtis distance matrices. Our results showed that there was a correlation between specific OTUs and measured clinical parameters of pregnant women. Comparison at the different taxonomy levels revealed high levels of abundance of Blautia and Citrobacter in ICP patients. At the family level, Enterobacteriaceae and Leuconostocaceae were higher in ICP patients. 638 KEGG Orthologs and 138 pathways significantly differed in the two groups. PLS-DA model with VIP plots indicated a total of eight genera and seven species were key taxa in ICP and control groups. Our research indicated that although there was no significant clustering by PCoA analysis, patients with ICP have increased rare bacteria at different phylogenetic levels. Our results also illustrated that all 638 KEGG Orthologs and 136 in 138 KEGG pathways were less abundant in ICP patients compared to the controls.


Base sequence selectivity in binding of aromatic hydrocarbons with synthetic polynucleotides.
The interactions between DOBP (3) and calf thymus DNA as well as four synthetic polynucleotides, poly(dA-dT), polydA:polydT, poly(dG-dC), and polydG:polydC, were investigated by spectroscopic techniques. It was found that the binding of 3 with poly(dA-dT) is favored appreciably over other synthetic polynucleotides and DNA. The results suggest that the initial association of carcinogenic BPDE (2) with DNA may take place preferentially at certain specific base sequences in DNA.


Atopic dermatitis induces anxiety- and depressive-like behaviors with concomitant neuronal adaptations in brain reward circuits in mice.
Clinically, it has been reported that atopic dermatitis (AD) has been linked with negative emotional problems such as depression and anxiety, thereby reducing the quality of life, but little is known about the molecular mechanism that underlies AD-associated emotional impairments. We sought to determine whether AD could induce anxiety- and depressive-like symptoms in mice and to identify pertinent signaling changes in brain reward circuitry. AD-like lesions were induced by the repeated intradermal application of MC903 into the cheek of the mouse. We assessed dermatitis severity with scratching behavior, histopathological changes, anxiety- and depressive-like behaviors using the elevated plus maze, open field and tail suspension tests, and serum corticosterone levels. In the nucleus accumbens (NAc), dorsal striatum (DS) and ventral tegmental area (VTA), protein levels of dopamine- and plasticity-related signaling molecules were determined by Western immunoblotting assay. Intradermal administration of MC903 into mouse cheek provoked a strong hind limb scratching behavior as well as the robust skin inflammation with epidermal thickening. MC903-treated mice also displayed markedly increased anxiety- and depressive-like behaviors, along with elevated serum corticosterone levels. Under these conditions, enhanced cAMP response element binding protein (CREB) and dopamine and cAMP-regulated phosphoprotein, 32 kDa (DARPP32) phosphorylation, significantly higher brain-derived neurotrophic factor (BDNF) and ΔFosB, but reduced tyrosine hydroxylase (TH) and dopamine D1 receptor (D1R) protein expression were found in the NAc, DS and VTA. Striatal BDNF, phospho-DARPP32 and phospho-CREB levels were significantly associated with the levels of depressive-like behavior in these mice. Taken together, these findings demonstrate that AD-like skin lesion elicits anxiety- and depressive-like phenotypes that are associated with neuroplasticity-related changes in reward circuitry, providing a better understanding of AD-associated emotional impairments.


Interplay of non-coding RNAs and approved antimetabolites such as gemcitabine and pemetrexed in mesothelioma.
Gemcitabine and pemetrexed are clinically approved antimetabolites for the therapy of mesothelioma diseases. These drugs are often applied in combination with platinum complexes and other drugs. The activity of antimetabolites depended on the expression levels of certain non-coding RNAs, in particular, of small microRNAs (miRNAs) and long non-coding RNAs (lncRNAs). The development of tumor resistance towards antimetabolites was regulated by non-coding RNAs. An overview of the interplay between gemcitabine/pemetrexed antimetabolites and non-coding RNAs in mesothelioma is provided. Further to this, various non-coding RNA-modulating agents are discussed which displayed positive effects on gemcitabine or pemetrexed treatment of mesothelioma diseases. A detailed knowledge of the connections of non-coding RNAs with antimetabolites will be constructive for the design of improved therapies in future.


Repeated ventral midbrain neurotensin injections sensitize to amphetamine-induced locomotion and ERK activation: A role for NMDA receptors.
Previous studies have shown that activation of ventral midbrain NMDA receptors is required to initiate sensitization by amphetamine. In view of the recent evidence that neurotensin modulates ventral midbrain glutamate neurotransmission, we tested the hypothesis that neurotensin is acting upstream to glutamate to initiate sensitization to the behavioral and neurochemical effects of amphetamine. During a first testing phase, adult male rats implanted with bilateral ventral midbrain cannulae were injected every second day for three days with D-[Tyr11]neurotensin (1.5 nmol/side), the preferred NMDA GluN2A/B antagonist, CPP (40 or 120 pmol/side), the selective GluN2B antagonist, Ro04-5595 (200 or 1200 pmol/side), CPP (40 or 120 pmol/side) + D-[Tyr11]neurotensin (1.5 nmol/side) or Ro04-5595 (200 or 1200 pmol/side) + D-[Tyr11]neurotensin (1.5 nmol/side) and locomotor activity was measured immediately after the injection. Five days after the last central injection, the locomotor response or the expression of phosphorylated extracellular signal-regulated kinases 1/2 (pERK1/2) in neurons of different limbic nuclei was measured following a systemic injection of amphetamine sulfate (0.75 mg/kg, i.p.). Results show that amphetamine induced significantly stronger locomotor activity and pERK1/2 expression in the nucleus accumbens shell and infralimbic cortex in neurotensin pre-exposed animals than in controls (vehicle pre-exposed). These sensitization effects initiated by neurotensin were prevented by CPP, but not Ro04-5595. These results support the hypothesis that neurotensin is stimulating glutamate neurotransmission to initiate neural changes that sub-serve amphetamine sensitization and that glutamate is acting on NMDA receptors that are mostly likely composed of GluN2A, but not GluN2B, subunits. This article is part of the Special Issue entitled 'Ionotropic glutamate receptors'.


Beyond intraocular pressure: Optimizing patient-reported outcomes in glaucoma.
Glaucoma, an irreversible blinding condition affecting 3-4% adults aged above 40 years worldwide, is set to increase with a rapidly aging global population. Raised intraocular pressure (IOP) is a major risk factor for glaucoma where the treatment paradigm is focused on managing IOP using medications, laser, or surgery regimens. However, notwithstanding IOP and other clinical parameters, patient-reported outcomes, including daily functioning, emotional well-being, symptoms, mobility, and social life, remain the foremost concerns for people being treated for glaucoma. These outcomes are measured using objective patient-centered outcome measures (PCOMs) and subjective patient-reported outcome measures (PROMs). Studies using PCOMs have shown that people with glaucoma have several mobility, navigational and coordination challenges; reading and face recognition deficits; and are slower in adapting to multiple real-world situations when compared to healthy controls. Similarly, studies have consistently demonstrated, using PROMs, that glaucoma substantially and negatively impacts on peoples' self-reported visual functioning, mobility, independence, emotional well-being, self-image, and confidence in healthcare, compared to healthy individuals, particularly in those with late-stage disease undergoing a heavy treatment regimen. The patient-centred effectiveness of current glaucoma treatment paradigms is equivocal due to a lack of well-designed randomized controlled trials; short post-treatment follow-up periods; an inappropriate selection or availability of PROMs; and/or an insensitivity of currently available PROMs to monitor changes especially in patients with newly diagnosed early-stage glaucoma. We provide a comprehensive, albeit non-systematic, critique of the psychometric properties, limitations, and recent advances of currently available glaucoma-specific PCOMs and PROMs. Finally, we propose that item banking and computerized adaptive testing methods can address the multiple limitations of paper-pencil PROMs; customize their administration; and have the potential to improve healthcare outcomes for people with glaucoma.


Fungi and mycotoxins in south african maize of the 1993 crop.
The most dominant fungi in South African maize for the 1993 crop wereFusarium moniliforme andFusarium subglutinans. The mycotoxins occurring with the most frequency were the fumonisins, deoxynivalenol and nivalenol. Levels of fungal infection and mycotoxins varied between white maize and yellow maize, and between the respective grades.


Nuclear mutation restores the reduced CO2/O2 specificity of ribulosebisphosphate carboxylase/oxygenase in a temperature-conditional chloroplast mutant of Chlamydomonas reinhardtii.
The Chlamydomonas reinhardtii temperature-sensitive mutant 68-4PP results from a mutation within the chloroplast gene that encodes the large subunit of ribulose-1,5-bisphosphate carboxylase/oxygenase. When grown at the permissive temperature (25 degrees C), the mutant has a reduced level of holoenzyme protein, and the purified enzyme has a lower CO2/O2 specificity than the wild-type enzyme. At the nonpermissive temperature (35 degrees C), the holoenzyme level is greatly reduced, and the mutant is unable to grow photosynthetically. When photosynthesis-competent revertants of 68-4PP were selected at 35 degrees C, a nuclear mutation was identified that suppresses the temperature-sensitive phenotype by enhancing both the activity and amount of the mutant enzyme. More significantly, the reduced CO2/O2 specificity of the 68-4PP enzyme is restored to the wild-type value. However, the nuclear suppressor mutation alone does not produce a phenotype different from wild type, and the CO2/O2 specificity of the suppressor strain's enzyme is normal. We have cloned and completely sequenced the two small-subunit genes from the suppressor strain, but no mutation has been found. These results suggest that some other nuclear-encoded protein is able to influence the structure of the holoenzyme, which in turn influences the CO2/O2 specificity factor.


Effects of nifedipine and Bay-K-8644 on the release of catecholamines from the dog adrenal gland in response to splanchnic nerve stimulation.
1. The effects of nifedipine and Bay-K-8644 on the release of adrenal catecholamines were examined in anaesthetized dogs. 2. Splanchnic nerve stimulation (SNS) at 1 and 3 Hz produced frequency-dependent increases in adrenaline (ADR) and noradrenaline (NA) output determined from adrenal venous blood. 3. Neither nifedipine (10 and 30 micrograms/kg, i.v.) nor Bay-K-8644 (10 and 30 micrograms/kg, i.v.) modified the SNS-induced increases in catecholamine output. Basal catecholamine output tended to be increased and decreased by nifedipine and Bay-K-8644, respectively. 4. Nifedipine produced significant decreases in arterial pressure and renal blood flow rate. Bay-K-8644 produced a significant increase in arterial pressure associated with a decrease in renal blood flow rate. 5. These results suggest that dihydropyridine-sensitive calcium channels do not play a major role in adrenal catecholamine release evoked by SNS.


New ex vivo organ model for percutaneous renal surgery using a laparoendoscopic training box: the sandwich model.
Percutaneous renal surgery (PRS) is a challenging procedure for urologic surgeons and requires a large variety of different skills. Our objective was to improve the preexisting porcine kidney-training model for percutaneous renal access and PRS. For our biologic training model, we use porcine kidneys with preserved ureter. The ureter was dissected, stones were placed into the collecting system using a 16, 5F Amplatz sheath, and a 12Ch indwelling catheter was placed in the ureter for further irrigation with blue-dyed saline. The kidney was placed between two porcine full-thickness skin lobes in an existing laparoscopy trainer (SITUS Box). The kidney was punctured with ultrasound guidance, and minimally invasive percutaneous nephrolithotomy (MIP) was then performed as previously described. The model was evaluated in MIP training courses, which are regularly held at the Hannover Medical School. All trainees were urologists with experience in endourologic surgery. Eleven participants were trained in this model. Percutaneous puncture under ultrasonographic guidance and following intrarenal surgery was successful in all 11 (100 %) cases. Therefore, all participants rated the model useful for simulating percutaneous renal surgery. Compared to recently published models, this new porcine kidney model is easy to prepare and is cost-effective by using standard material. Moreover, it provides realistic and reproducible practice for PRS in the laboratory. Unfavorably, the described organ model requires an existing laparoscopy training system. Comprehensively, the presented organ model approximates the natural retroperitoneal circumstances precisely by using the two full-thickness skin flaps with the fatty subcutaneous tissue.


Iron supplementation in HIV-infected Malawian children with anemia: a double-blind, randomized, controlled trial.
It is unknown whether iron supplementation in human immunodeficiency virus (HIV)-infected children living in regions with high infection pressure is safe or beneficial. A 2-arm, double-blind, randomized, controlled trial was conducted to examine the effects of iron supplementation on hemoglobin, HIV disease progression, and morbidity. HIV-infected Malawian children aged 6-59 months with moderate anemia (hemoglobin level, 7.0-9.9 g/dL) were randomly assigned to receive 3 mg/kg/day of elemental iron and multivitamins (vitamins A, C, and D) or multivitamins alone for 3 months. Participants were followed for 6 months. A total of 209 children were randomly assigned to treatment, and 196 (93.8%) completed 6 months of follow-up. Iron supplementation was associated with greater increases in hemoglobin concentrations (adjusted mean difference [aMD], 0.60; 95% confidence interval [CI], .06-1.13; P = .03) and reduced the risk of anemia persisting for up to 6 months follow-up (adjusted prevalence ratio, 0.59; 95% CI, .38-.92; P = .02). Children who received iron had a better CD4 percentage response at 3 months (aMD, 6.00; 95% CI, 1.84-10.16; P = .005) but an increased incidence of malaria at 6 months (incidence rate, 120.2 vs 71.7; adjusted incidence rate ratio [aIRR], 1.81 [95% CI, 1.04-3.16]; P = .04), especially during the first 3 months (incidence rate, 78.1 vs 36.0; aIRR, 2.68 [95% CI, 1.08-6.63]; P = .03). Iron supplementation in anemic HIV-infected children has beneficial effects on hemoglobin, anemia, and immunity but increases the risk of malaria. Thus, iron supplementation in HIV-infected children living in malaria-endemic areas should only be provided in combination with adequate protection from malaria. ISRCTN-62947977.


A pulp foam with highly improved physical strength, fire-resistance and antibiosis by incorporation of chitosan and CPAM.
Bio-inspired borate cross-linked pulp foam (PF) with high porosity and low density can be widely used in many fields. However, PF is flammable, and lack of mechanical strength and antibacterial activity. To solve these issues, an ultra-strong PF was prepared by incorporation of chitosan and cationic polyacrylamide (CPAM). Results showed that the obtained PF exhibited highly improved mechanical properties (the compressive strength (485 kPa at a strain of 50%) was over 6 times higher compared with the borate cross-linked PF without chitosan and CPAM, and it was even higher than most of the reported cellulose-based porous materials). Also, the prepared PF has good performance on fire-retardance (hard to light), thermal insulation, antibiosis and sound absorption, due to the synergistic actions of borate, chitosan and CPAM. Additionally, spent liquor in preparing PF could be fully recycled, and thus this sustainable approach has potential for large-scale production of high-performance PF.


GABAA agonists as targets for drug development.
1. Agents with selective actions on bicuculline-sensitive GABAA receptors have been developed by systematically restricting the conformational mobility of the GABA molecule. 2. THIP, a bicyclic isoxazole that represents GABA held in a relatively rigid and partially extended conformation, is an analgesic of potency comparable to that of morphine. THIP represents a lead compound for a novel series of analgesics acting independently of Naloxone-sensitive opiate systems. 3. ZAPA, a conformationally-restricted analogue of GABA containing an isothiouronium moiety, is a selective agonist for low affinity GABAA receptors and is a lead compound for the development of a novel series of anthelmintics. 4. (+)-TACP, a cyclopentane analogue of GABA, may activate a different subclass of GABAA receptors from THIP. 5. Pharmacological, molecular modelling and molecular biological studies provide evidence for a heterogeneity of GABAA receptors which might be exploited for drug development.


Antral and esophageal rimple: a normal variation.
The occurrence of fine antral and esophageal rimpling appears to be the result of contractions of the muscularis mucosa. The lack of persistence during distention is compatible with this conclusion. The folds have no pathologic significance.


Regional differences in rest decay and recoveries of contraction and the calcium transient in rabbit ventricular muscle.
The rates of rest decay (for rest periods of between 0.5 min and 10 min) and recovery from the rested state (following 10 min of rest) of cell shortening and the amplitude of the intracellular calcium transient were compared in epicardial and endocardial ventricular myocytes isolated from rabbit hearts. The object of these experiments was to determine whether reported transmural differences in action potential duration, myosin type expression and metabolic enzyme content are able to influence the control of contraction. Cells isolated from these two regions of the ventricular wall displayed almost identical twitch shortening and calcium transient characteristics during steady-state electrical stimulation at 0.5 Hz. Despite this, rest decay of cell shortening was faster and recovery from the rested state slower in endocardial cells than in epicardial cells. Neither of these differences could be explained in terms of changes of calcium transient amplitude or time course. We tried to mimic the effect of prolonged rest by application of caffeine to empty the sarcoplasmic reticulum of calcium. The regional differences in recovery of contraction from the rested state were not reproduced in the recovery of contraction after caffeine application, suggesting that the effect is produced by something other than refilling of the sarcoplasmic reticulum. It is suggested that changes in factors that affect myofilament calcium sensitivity produce the regional differences in rest decay and post-rest recovery of contraction.


Soluble endoglin in urine as an early-pregnancy preeclampsia marker: antenatal longitudinal feasibility study.
This study aimed to evaluate soluble endoglin (sEng) in urine as a preeclampsia predictor. Ninety-three pregnant women at risk for preeclampsia were followed. Spot urine sample ELISA analysis before 20 weeks of gestation was done to assess protein levels. Logistic regression analysis evaluated associations between preeclampsia with sEng/creatinine ratio, pg/mg, adjusted for risk factors. Preeclampsia incidence was 22.8% (20/92). Urinary sEng/creatinine (pg/mg) 0.001 (95% CI 0.001-0.136) was associated, adjusted for body mass index > 28 kg/m2 OR 6.44 (95% CI 1.11-37.47) and mean arterial pressure OR 1.20 (1.07-1.35). During the first half of gestation sEng urinary excretion was lower in pregnant women developing preeclampsia.Impact statementWhat is already known on this subject? The angiogenesis factors present in the plasma of pregnant women have shown good preclinical predictors of preeclampsia. Studies on urinary markers in pregnancy are infrequent, despite the ease of obtaining urine specimens.What do the results of this study add? Values of the sEng/creatinine ratio during the first half of pregnancy were related to a higher chance of preeclampsia occurring when it was evaluated alone or adjusted by body mass index and mean arterial pressure values.What are the implications of these findings for clinical practice and/or further research? The potential benefits of a urinary test compared to one of the blood levels include its non-invasive nature and ease of performing the test, even during prenatal care. Future research is expected to evaluate the sEng/creatinine ratio relevance to improve clinical scores of preeclampsia prediction for the identification of women at risk for this disease.


Fish can be first--advances in fish transgenesis for commercial applications.
Over the past 15 years researchers have generated stable lines of several species of transgenic fish important for aquaculture. 'All-fish' growth hormone (GH) gene constructs and antifreeze protein (AFP) genes have been successfully introduced into the fish genome resulting in a significant acceleration of growth rate and an increase in cold and freeze tolerance. However, neither gene modification is completely understood; there are still questions to be resolved. Expression rates are still low, producing variable growth enhancement rates and less than desired levels of freeze resistance. Transgene strategies are also being developed to provide improved pathogen resistance and modified metabolism for better utilization of the diet. Additional challenges are to tailor the genetically modified fish strains to prevent release of the modified genes into the environment.


Anaesthetic management of organ transplant patients.
In this paper we will describe anaesthetic management of solid organ and reconstructive transplantation (RT) patients. We will focus on similar underlying principles of reperfusion, ischaemic-reperfusion injury, preconditioning and extracorporeal donor organ preservation. Special concerns for anaesthetic management of these patients need to focus on pre-assessment, pre-operative optimisation, vascular access, fluid management, blood and products replacement, cardiovascular monitoring, use of inotropes and vasoconstrictors, maintaining electrolyte balance and regional anaesthesia. Despite the complexity and long duration of transplant procedures, fast-tracking to the surgical ward after transplantation is becoming more popular and its benefits are well recognised.


Molecular Characterization of a Catalase-Negative Staphylococcus aureus Blood Culture Isolate.
Here we report a catalase-negative methicillin-sensitive Staphylococcus aureus isolate collected from a blood culture. Sequencing through the gene encoding catalase, katA, demonstrated a 2-bp insertion. The resulting frameshift mutation generates a protein that has lost 26 amino acids (aa) at its C-terminal domain.


Genetic predisposition to hypertension is associated with preeclampsia in European and Central Asian women.
Preeclampsia is a serious complication of pregnancy, affecting both maternal and fetal health. In genome-wide association meta-analysis of European and Central Asian mothers, we identify sequence variants that associate with preeclampsia in the maternal genome at ZNF831/20q13 and FTO/16q12. These are previously established variants for blood pressure (BP) and the FTO variant has also been associated with body mass index (BMI). Further analysis of BP variants establishes that variants at MECOM/3q26, FGF5/4q21 and SH2B3/12q24 also associate with preeclampsia through the maternal genome. We further show that a polygenic risk score for hypertension associates with preeclampsia. However, comparison with gestational hypertension indicates that additional factors modify the risk of preeclampsia.


[Galactorrhea and gynecomastia as side effect of drugs].
Galactorrhoea or gynaecomastia are common and innocent phenomena, especially in certain age groups. Sometimes, however, they are secondary to serious diseases such as hormone producing tumours. Furthermore, a wide variety of drugs may in different ways induce galactorrhoea or gynaecomastia. A good knowledge of these drugs may prevent unnecessary anxiety and investigations. In spite of an abundance of often anecdotal reports scattered in the literature, little information is available on the identity of the most important drugs causing galactorrhoea or gynaecomastia in medical practice. The country-wide network of regional centres for intensified adverse drug reactions reporting of the Netherlands Pharmacovigilance Foundation LAREB can provide useful information on these and other side effects.


A national survey of disease-specific knowledge in patients with an abdominal aortic aneurysm.
Patient education is a fundamental responsibility of medical providers caring for patients with abdominal aortic aneurysms (AAA). We sought to evaluate and quantify AAA-specific knowledge in patients under AAA surveillance and in patients who have undergone AAA repair. In 2013, 1373 patients from 6 U.S. institutions were mailed an AAA-specific quality of life and knowledge survey. Of these patients, 1008 (73%) returned completed surveys for analysis. The knowledge domain of the survey consisted of nine questions. An AAA knowledge score was calculated for each patient based on the proportion of questions answered correctly. The score was then compared according to sex, race, and education level. Surveillance and repaired patients were also compared. Among 1008 survey respondents, 351 were under AAA surveillance and 657 had AAA repair (endovascular repair, 414; open, 179; unknown, 64). The majority of patients (85%) reported that their "doctor's office" was their most important source of AAA information. The "Internet" and "other written materials" were each reported as the most important source of information 5% of the time with "other patients" reported 2% of the time. The mean AAA knowledge score was 47% (range 0%-100%; standard deviation, 23%) with a broad variation in percentage correct between questions. Thirty-two percent of respondents did not know that larger AAA size increases rupture risk, and 64% did not know that AAA runs in families. Only 15% of patients answered six or more of the nine questions correctly, and 23% of patients answered two or fewer questions correctly. AAA knowledge was significantly greater in men compared with women, whites compared with nonwhites, high school graduates compared with nongraduates, and surveillance compared with repaired patients. In a national survey of AAA-specific knowledge, patients demonstrated poor understanding of their condition. This may contribute to anxiety and uninformed decision making. The need for increased focus on education by vascular providers is a substantial unmet need.


Sensorimotor maturation and alcohol responsiveness in rats prenatally exposed to alcohol during gestational day 8.
On gestational day 8, pregnant Sprague-Dawley derived rats received two intraperitoneal injections of 0.015 ml/g body weight of a 24% v/v ethanol solution representing an absolute alcohol dose of 2.82 g/kg per administration (ETOH Group). Control females were injected with similar volumes of saline (SAL Group) or did not receive any type of intraperitoneal administration of drugs (AC Group). In comparison with the control treatments, the ethanol treatment did not affect long-term maternal body weight gain during pregnancy, total length of gestation, probability of delivery, number of pups born per litter or the offsprings' preference of alcohol odor. Nevertheless, this ethanol insult was sufficient to significantly reduce body weights at birth and to retard the ontogeny of some sensorimotor patterns among offspring, as assessed through the Righting Reflex, Horizontal Screen Test and opening of the external auditory canals. The maturation of other reflexes (Cliff Aversion and Negative Geotaxis) appeared to be retarded indirectly as an outcome of the maternal injection procedure, with ETOH and SAL pups exhibiting similar developmental delays when compared with AC animals. During adulthood, rats prenatally exposed to alcohol exhibited a decreased hypothermic response to an intoxicating dose of alcohol as well as significant increases in voluntary alcohol consumption in comparison with both control conditions. Collectively, these results suggest that relatively acute alcohol exposure early in gestation may not only affect normal patterns of development but also later responsiveness to this pharmacological agent.


Obesity and cardiovascular risk.
In most industrialized countries, 40-60% of the population is now overweight or obese. Obesity has recently been recognized as a major modifiable risk factor for cardiovascular disease, second only to cigarette smoking. Excess weight and obesity markedly increase the risk for hypertension, diabetes, coronary artery disease and congestive heart failure in both men and women. Populations most severely affected include the poor, the uneducated and certain racial and ethnic groups. Obesity is currently classified based on body mass index (BMI), but measurement of waist circumference as an important determinant of cardiovascular and metabolic risk is receiving increasing acceptance. For moderate overweight and obesity, interventions include dietary modification, increasing physical activity, behavior therapy and pharmacotherapy. Surgery is currently the only viable approach to morbid obesity.


A Phase II Study of Telisotuzumab Vedotin in Patients With c-MET-positive Stage IV or Recurrent Squamous Cell Lung Cancer (LUNG-MAP Sub-study S1400K, NCT03574753).
Lung-MAP S1400K was designed to evaluate the response to telisotuzumab vedotin, an antibody-drug conjugate targeting c-MET, in patients with c-MET-positive squamous cell carcinoma (SCC). Patients with previously treated SCC with c-MET-positive tumors (H score ≥ 150, Ventana SP44 assay) were enrolled into 2 cohorts: Cohort 1 (immune checkpoint inhibitor-naive) and Cohort 2 (immune checkpoint inhibitor refractory). Telisotuzumab vedotin 2.7 mg/kg was administered intravenously every 3 weeks until disease progression or unacceptable toxicity. Response assessments were performed every 6 weeks. The primary endpoint was response by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Secondary endpoints included progression-free survival, overall survival, response within cohort, duration of response, and toxicities. Interim analysis was planned after 20 evaluable patients, with ≥ 3 responses needed to continue enrollment. Forty-nine patients (14% of screened patients) were assigned to S1400K, 28 patients enrolled (15 in Cohort 1 and 13 in Cohort 2), and 23 were eligible. S1400K closed on December 21, 2018 owing to lack of efficacy. Two responses (response rate of 9%; 95% confidence interval, 0%-20%) were reported in cohort 1 (1 complete and 1 unconfirmed partial response), whereas 10 patients had stable disease, with a disease control rate of 52%. The median overall and progression-free survival was 5.6 and 2.4 months, respectively. There were 3 grade 5 events (2 pneumonitis, in Cohort 2, and 1 bronchopulmonary hemorrhage, in Cohort 1). Telisotuzumab vedotin failed to meet the pre-specified response needed to justify continuing enrollment to S1400K. Pneumonitis was an unanticipated toxicity observed in patients with SCC.


Characterization of 46 patient-specific BCR-ABL1 fusions and detection of SNPs upstream and downstream the breakpoints in chronic myeloid leukemia using next generation sequencing.
In chronic myeloid leukemia, the identification of individual BCR-ABL1 fusions is required for the development of personalized medicine approach for minimal residual disease monitoring at the DNA level. Next generation sequencing (NGS) of amplicons larger than 1000 bp simplified and accelerated a process of characterization of patient-specific BCR-ABL1 genomic fusions. NGS of large regions upstream and downstream the individual breakpoints in BCR and ABL1 genes, respectively, also provided information about the sequence variants such are single nucleotide polymorphisms.


Model development and parameter estimation for a hybrid submerged membrane bioreactor treating Ametryn.
A lab-scale membrane bioreactor (MBR) was used to remove Ametryn from synthetic wastewater. It was found that concentrations of MLSS and extra-cellular polymeric substances (EPS) in MBR mixed liquor fluctuated (production and decay) differently for about 40 days (transition period) after the introduction of Ametryn. During the subsequent operations with higher organic loading rates, it was also found that a low net biomass yield (higher death rate) and a higher rate of fouling of membrane (a very high rate during the first 48 h) due to increased levels of bound EPS (eEPS) in MBR mixed liquor. A mathematical model was developed to estimate the kinetic parameters before and after the introduction of Ametryn. This model will be useful in simulating the performance of a MBR treating Ametryn in terms of flux, rate of fouling (in terms of transmembrane pressure and membrane resistance) as well as treatment efficiency.


Recovery from unilateral neglect.
Spontaneous recovery of function occurs in the syndrome of hemisensory neglect in monkeys. We produced this syndrome in 13 macaques by unilateral operative resection of the frontal polysensory association cortex. Using standardized behavioral measures, we documented severe acute neglect and followed the course of its improvement. Using the 2-deoxy[14C]glucose autoradiographic method, we studied animals in the acute phase of neglect and found decrements in local glucose utilization in subcortical structures, but not in cortical regions with known frontal connections. After spontaneous behavioral recovery, mild local glucose utilization decrements remained, but only in nucleus medialis dorsalis of the thalamus. The findings suggest that acute behavioral symptoms are based on widespread depression of neuronal activity in uninjured structures with synaptic relations to damaged cortex, and that return of neuronal activity in those structures is accompanied by restitution of behavioral function.


Heavy metal (Cd, Cr, Cu, Hg, Pb, Zn) concentrations in seven fish species in relation to fish size and location along the Yangtze River.
The objective of this paper is to assess the regulation of the accumulation of heavy metals in the aquatic environment and different fish species. Water and fish samples were collected from upper to lower reaches of the Yangtze River. The heavy metal (Cd, Cr, Cu, Hg, Pb, Zn) concentrations in the muscle tissue of seven fishes were measured. Additionally, the relationships between heavy metal concentrations in fish tissue and fish size (length and weight), condition factor, water layer distribution, and trophic level were investigated. Metal concentrations (milligrams per kilogram wet weight) were found to be distributed differently among different fish species. The highest concentrations of Cu (1.22 mg/kg) and Zn (7.55 mg/kg) were measured in Pelteobagrus fulvidraco, the highest concentrations of Cd (0.115 mg/kg) and Hg (0.0304 mg/kg) were measured in Silurus asotus, and the highest concentrations of Pb (0.811 mg/kg) and Cr (0.239 mg/kg) were measured in Carassius auratus and Cyprinus carpio. A positive relationship was found between fish size and metal level in most cases. The variance of the relationships may be the result of differences in habitat, swimming behavior, and metabolic activity. In this study, fishes living in the lower water layer and river bottom had higher metals concentrations than in upper and middle layers. Benthic carnivorous and euryphagous fish had higher metals concentrations than phytoplankton and herbivorous fish. Generally, fish caught from the lower reach had higher metals concentrations than those from the upper reach. Cadmium and lead concentrations in several fishes exceeded the permissible food consumption limits, this should be considered to be an important warning signal.


Dextromethorphan-associated epidural patient-controlled analgesia provides better pain- and analgesics-sparing effects than dextromethorphan-associated intravenous patient-controlled analgesia after bone-malignancy resection: a randomized, placebo-controlled, double-blinded study.
Pain after bone malignancy surgery is intense and requires large amounts of analgesics. The augmented antinociceptive effects of dextromethorphan (DM), a N-methyl-D-aspartate receptor antagonist, were demonstrated previously. We assessed the use of postoperative patient-controlled epidural analgesia (PCEA) or IV patient-controlled analgesia (PCA) in patients undergoing surgery for bone malignancy under standardized combined general and epidural anesthesia with or without DM. Patients (n = 120) were randomly allocated to receive PCEA (ropivacaine 3.2 mg plus fentanyl 8 microg/dose) or IV-PCA (morphine 2 mg/dose) postoperatively, starting at subjective visual analog scale pain intensity >or=4 of 10 for up to 96 h. Placebo or DM 90 mg orally (30 patients/group/set) was given in a double-blinded manner before surgery and for 2 days afterwards. Diclofenac 75 mg IM was available as a rescue drug. DM patients used PCA and rated their pain >50% less than their placebo counterparts in each set, especially during the first 2 postoperative days (P < 0.01). Hourly and overall maximal pain intensity among PCEA patients was approximately 50% less than in the IV-PCA set (P < 0.01). Diclofenac was used 42% less (P < 0.01) by the PCA-DM patients compared with their placebo counterparts. Seven PCEA-DM and 11 IV-PCA-DM individuals reported having side effects compared with 44 in the PCEA-placebo and the IV-PCA-placebo groups (P < 0.01). Time to first ambulation was similar with both analgesia techniques but shorter among the DM-treated patients compared with the placebo recipients (1.5 +/- 0.8 versus 2.1 +/- 1.1 days, P = 0.02). Thus, DM afforded better pain control and reduced the demand for analgesics, augmented the PCEA effect versus IV-PCA, and was associated with minimal untoward effects in each analgesia set. DM patients ambulated earlier than placebo recipients. Patients undergoing bone-malignancy surgery under combined general and epidural anesthesia received randomly patient-controlled epidural analgesia (PCEA) or IV patient-controlled analgesia (PCA) postoperatively and dextromethorphan (DM) 90 mg or placebo double-blindly for 3 days (n = 30/group/set). The DM effect was recorded with minimal untoward effects: it afforded better pain control and reduced the demand for analgesics compared with the placebo, especially when associated with PCEA. DM patients ambulated earlier than placebo recipients.


Production of Germ Cell-Less Rainbow Trout by dead end Gene Knockout and their Use as Recipients for Germ Cell Transplantation.
In germ cell transplantation experiments, the use of sterile recipients that do not produce their own gametes is an important prerequisite. Triploidization and dnd gene knockdown (KD) methods have been widely used to produce sterile fish. However, triploidization does not produce complete sterility in some fish species, and gene KD is labor and time intensive since it requires microinjection into individual fertilized eggs. To overcome these problems, in this study, we generated homozygous mutants of the dead end (dnd) gene in rainbow trout (Oncorhynchus mykiss) using the clustered regulatory interspaced short palindromic repeats/CRISPR-associated protein 9 (CRISPR/Cas9) system, analyzed their reproductive capacity, and evaluated their suitability as recipients for germ cell transplantation. By crossing F1 heterozygous mutants produced from founders subjected to genome editing, an F2 generation consisting of approximately 1/4 homozygous knockout mutants (dnd KO) was obtained. The dnd KO hatchlings retained the same number of primordial germ cells (PGCs) as the wild-type (WT) individuals, after which the number gradually decreased. At 1 year of age, germ cells were completely absent in all analyzed individuals. To evaluate the dnd KO individuals as recipients for germ cell transplantation, germ cells prepared from donor individuals were transplanted into the abdominal cavity of dnd KO hatchlings. These cells migrated to the recipient gonads, where they initiated gametogenesis. The mature recipient individuals produced only donor-derived sperm and eggs in equivalent numbers to WT rainbow trout. These results indicate that dnd KO rainbow trout are suitable recipient candidates possessing a high capacity to nurse donor-derived germ cells.


Identification of potential inhibitors of brain-specific CYP46A1 from phytoconstituents in Indian traditional medicinal plants.
Cytochrome P450 46A1 (CYP46A1) is a crucial enzyme in brain that converts cholesterol to 24 (S) hydroxy cholesterol thereby increasing its polarity to facilitate removal of excess cholesterol from the CNS. The inhibition of CYP46A1 with several synthetic molecules has been investigated extensively for treatment of Alzheimer's disease, Huntington's disease, glaucoma, and in hippocampal neurons from aged mice. However, phytochemicals have received far little attention in studies involving development of potential CYP46A1 inhibitors. Thus, in the present study phytoconstituents from Indian traditional medicinal plants; Bacopa monnieri, Piper longum, and Withania somnifera, were virtually screened for interaction with CYP46A1 using computational tools. Out of three plants, six molecules from P. longum and three molecules from W. somnifera were shortlisted to study interactions with CYP46A1 based on the physio-chemical parameters. Fargesin, piperolactam A and coumaperine from P. longum showed the higher binding affinity and the values were - 10.3, - 9.5, - 9.0 kcal/moles respectively, whereas, withaferin A from W. somnifera had a binding affinity of - 12.9 kcal/mol. These were selected as potential modulators as they exhibited suitable interactions with active site residues; Tyr109, Leu112, Trp368, Gly369, and Ala474. The selected molecules were further subjected to molecular dynamics simulation. Further, the pharmacological properties of molecules were also predicted using ADMET calculator and the data revealed that all the selected compounds had good absorption as well as solubility characteristics. In addition, sesamin, fargesin, piperolactam A, and coumaperine had minimal or no toxic effects. Thus, the study successfully identified compounds from Indian medicinal plants that may serve as potential inhibitors of CYP46A1 or base structures to design novel CYP46A1 inhibitors, which may be effective in treating neurological conditions involving perturbed cholesterol homeostasis. The online version contains supplementary material available at 10.1007/s42485-022-00098-x.


The alleviation of chronic copper toxicity in sheep by ciliate protozoa.
1. Rams, fauna-free from birth and initially of 48-65 kg live weight, were allocated to two groups of ten each and given a diet containing 14 micrograms copper/g dry matter; five additional rams were killed and their livers were analysed for Cu. 2. One group (faunated) was inoculated with a mixed population of ciliate protozoa, and contained between 60 x 10(5) and 195 x 10(5) protozoa/ml rumen fluid throughout the 184 d experiment. The other group remained fauna-free. Following blood sampling, three rams in each group were killed on day 63, two on day 125 and four on day 184. One sheep in each group died during the experiment. 3. Faunated rams showed higher weight gains and feed consumption than fauna-free rams. 4. Plasma Cu concentration (microgram/ml) increased from an initial 0.82 to a final 1.00 in faunated and 1.36 in fauna-free rams. Liver Cu concentration (micrograms/g dry matter) increased from an initial 745 to a final 962 and 1684 in faunated and in fauna-free sheep respectively, representing a 4.3-fold greater increase in the fauna-free than in the faunated group. The absorption and retention of Cu was 38-50% higher in the fauna-free than in the faunated rams. 5. It was suggested that rumen ciliate protozoa increased rumen production of sulphide (through increased breakdown of soluble proteins) which complexed part of the Cu, making it unavailable for absorption and utilization. Therefore, ciliate protozoa could determine susceptibility to chronic Cu toxicity in sheep.


Minimally invasive options for the brow and upper lid.
Eyebrow and upper eyelid aging occurs in all tissue planes, and manifests most commonly in skin quality, tissue volume loss (soft tissue and bone), and tissue descent. All these involutional changes are amenable to less-invasive (nonsurgical) interventions with natural and aesthetically pleasing results. It is critical for aesthetic facial surgeons to familiarize themselves with these procedures because they are in high demand by patients. This article outlines current concepts of nonsurgical management options for brow and upper eyelid aging. The anatomy and age-related changes in these structures are reviewed, and minimally invasive techniques to address these changes are detailed.


Alkaloids from Brugmansia arborea (L.) Lagerhein reduce morphine withdrawal in vitro.
Traditional medicine is a primary source for the study of medicinal plants. In some countries, knowledge about the therapeutic use of medicinal plants is very deep and very often 'magical' plants also are used to diagnose and treat illnesses. The study of these plants can help in the research of metabolites active on the central and peripheral nervous system. Brugmansia arborea (L.) Lagerheim (Solanaceae) is used in the northern Peruvian Andes for magic-therapeutic purposes and the present study examined the effect of three pure tropane alkaloids from Brugmansia arborea (L.) Lagerhein (Solanaceae) on morphine withdrawal in vitro. All the tropane alkaloids isolated from Brugmansia arborea (L.) (10(-7), 5 x 10(-7), 10(-6) m) significantly and in a concentration dependent manner reduced morphine withdrawal. The results of the present study suggest that these alkaloids may be a potential anti-additive agent.


Lipectomy of fat rolls.
A technique for lipectomy used on rolls of fat in the back is presented. It is proposed that multiplanar and aggressive liposuction in this region exaggerates the feminine waist and results in a lifting effect on the fat rolls. It is proposed that suction performed in a vertical way creates a new vertical collagen framework that supports skin in an antigravitational manner. Fat from fat rolls is aggressively suctioned in a multiplanar way to obtain a very thin adipose flap. The direction of suction is always perpendicular to the axis of the fat roll. The location of the incisions is cranial or caudal to the fat roll. This means they are vertical or longitudinal to the body axis. All the patients showed a marked improvement in both the clinical and photographic evaluations. The percentage of correction to the waist curvature was 26%. Only 11% of the patients showed minimal cutaneous irregularities (residual fat and depressions). Fat removal by multiplanar liposuction accomplished in a vertical way on the back rolls produces excellent results. The improvement results from the thin cutaneous flap needing to redrape over a longer concave waist curvature. On the other hand, the cutaneous flap readapts better in a vertical way because the new vertical collagen framework supports skin in an antigravitational manner. With this technique, postoperative edema is minimized. Lymph vessels have the same vertical direction from top to bottom, and thus are less injured.


Influence of litterbags on growth of fungal vegetative structures.
This study reports a test of the hypothesis that mesh litter bags restrict access of vegetative fungal structures to confined substrate. Unconfined birchwood swab sticks lost more dry weight during a field incubation than confined ones. Samples in fine mesh bags lost more weight than those in coarse mesh bags. Significantly higher numbers of mycelial strands and rhizomorphs were found on unconfined samples. The number of fungal structures was significantly correlated with weight loss of individual samples. It is suggested that the inhibitory effect is most significant in environments where higher fungi are the dominant decomposing organisms.


Review on the occurrence and profiles of polybrominated diphenyl ethers in the Philippines.
The environmental occurrence of polybrominated diphenyl ethers (PBDEs) has been a subject of concern for the past decade because they are persistent, bioaccumulative, and toxic. These compounds have been listed as persistent organic pollutants (POPs) by the Stockholm Convention and are expected to disperse in the global environment even after their use and production. While the occurrence of PBDEs has been well characterized in environmental and biological samples from North America, Europe, and some Asian countries (i.e. China, Japan, and Korea), there is a scarcity of available data in developing Asian countries, such as the Philippines. Examination of PBDE contamination in the Philippine environment is particularly important because regulations have only recently been implemented on the production and use of PBDEs in this country. Additionally, the Philippines receives e-waste from Western countries, which is becoming a major source of organic contaminants in the tropical Asian regions. Ultimately, the Philippines may be a hot spot for contributing to on-going global PBDE pollution due to long-range atmospheric transport. This paper presents a review of the available literature on PBDEs in both environmental and biological samples collected from the Philippines. It is also intended to provide an overview on the levels and congener profiles of PBDEs in samples from the Philippines and to compare these data with other Asian countries. New data are presented on PBDE occurrence and congener profiles in fish commonly consumed by Filipinos and in particulate matter samples collected in Metro Manila, the capital of the Philippines. Both studies contribute to the available knowledge of PBDEs in the Philippines. We aim to stress the importance of future studies in countries receiving e-wastes, such as the Philippines, and suggest what future directions might be taken to enhance the available data on the presence of PBDEs in the Philippine environment.


Analysis of sphingolipids in extracted human plasma using liquid chromatography electrospray ionization tandem mass spectrometry.
We have developed an analytical method used to quantify sphingolipids, including deoxysphingoid bases, in lipid extracts prepared from human plasma. In total, 39 analytes were identified and analyzed in a single chromatographic run in less than 5 min. The new method is 4-8 times faster and more sensitive than previously published methods. We also describe a simple sample preparation method that allows medium-throughput screening of human plasma samples. Mass spectrometric analyses were performed online using liquid chromatography electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) in the positive multiple reaction monitoring mode. Samples were extracted using a one-phase extraction method (methanol-dichloromethane) with appropriate internal standards. Sphingolipid analytes were linear over a wide range of concentrations, from 0.01 to 50 ng/ml, with a high correlation coefficient (r2 = 0.999). We successfully applied this method to analyze the levels of sphingolipid metabolites in healthy human plasma. The ceramide, dihydroceramide, hexosylceramide, and GM3 levels observed in females were slightly higher than those observed in males.


Effective Communication for Child Advocacy: Getting the Message out Beyond Clinic Walls.
Clinicians who want to communicate child advocacy messages, stories, and arguments can draw on their clinical and scientific experience, but effective communication to wider--and nonmedical--audiences requires careful thought. We discuss choosing and honing the message, developing writing and speaking skills that fit both the exigencies of the chosen medium and format, including op-eds, essays, social media, public testimony, and speeches. We provide guidance on proposing articles, working with editors, shaping language and diction for a general audience, and drawing on clinical experiences while respecting confidentiality. all with the goal of effective communication, spoken and written, in the service of children and child advocacy.


Effects of murine recombinant interferon-gamma on rat liver fat storing cell proliferation, cluster formation and proteoglycan synthesis.
Rat liver fat storing cells (FSC, perisinusoidal lipocytes, Ito cells) in primary culture were exposed to various concentrations of murine recombinant interferon-gamma (rIFN-gamma) in the range of 1 to 50 units/mL medium for 72 hr. FSC kept in complete medium (10% fetal calf serum) showed a dose-dependent increase of both [3H]thymidine incorporation (up to 2.3-fold) and DNA content of culture. Reverse (inhibitory) effects were obtained with cells kept under serum-reduced (0.5% fetal calf serum) conditions. The synthesis of medium proteoglycans and of total cellular protein was not affected by rIFN-gamma. By bromodeoxyuridine-staining (BrdUrd) and phase contrast microscopy it is shown that rIFN-gamma stimulates strongly the cluster growth of FSC in culture. The cluster forming cells differ in their morphology and their cytoskeleton-staining from typical FSC. They were found to be mostly desmin and alpha-actin negative or weakly positive but highly proliferative. Because no contaminating fibroblasts and other cell types were detected in any appreciable amounts in the early cultures we conclude that the clustered cells might be a rapidly proliferating subpopulation of FSC, which is promoted by rIFN-gamma.


To Have or Not to Have Sex? COVID-19 and Sexual Activity Among Chinese-Speaking Gay and Bisexual Men in Hong Kong.
The coronavirus disease 2019 (COVID-19) outbreak has fundamentally changed daily routine, including sexual activity. However, most research on sexual activity during the COVID-19 pandemic focused on heterosexual individuals. The only study so far on men who have sex with men was conducted in the United States. Our study expands the understanding of sexual activity during the COVID-19 pandemic by studying gay and bisexual men in Hong Kong. Although sexual desire and sexual activity continue to be important aspects of one's life during the COVID-19 pandemic, there are COVID-19-related barriers to having sex. This study therefore examined the association between sexual desire, COVID-19-related barriers, and whether to engage in sexual activity or not during the COVID-19 pandemic. 857 cisgender sexual minority people in Hong Kong participated in an online survey study, and for this article, only male participants were included in the analysis, yielding an analytical sample of 376 gay and bisexual men. Participants were asked to assess their sexual desire (ie, sexual drive and sexual motivation), COVID-19-related barriers (ie, perceived difficulties to have sex with another person during the pandemic and perceived risk of COVID-19 infection), and sexual activity during the COVID-19 pandemic. It was found that while sexual desire remained prevalent among the gay and bisexual men, COVID-19-related barriers were also commonly observed. Sexual drive and sexual motivation were positively associated with sexual activity. Perceived difficulties to have sex with another person during the pandemic and perceived risk of COVID-19 infection were negatively predictive of engaging in sexual activity, after controlling for general sexual desire. Understanding the ambivalence and driving and inhibiting factors for having sex during the COVID-19 pandemic can provide a new framework for understanding people's sexual activity during an unprecedented scale of the pandemic. It is likely that abstinence would not work as the respondents expressed strong sexual desire and that the pandemic is going to last for a long time. Governments, policy makers, and sexual scientists need to work together to come up with practicable, feasible, and easy-to-follow guidelines for having sex during the pandemic. This is one of the first studies to examine the impact of COVID-19 on sexual activity among gay and bisexual men. The results should be interpreted with caution because of the use of cross-sectional design and nonprobability sampling. Sexual desire and COVID-19-related barriers serve as driving and inhibiting factors in explaining whether or not people have sex during the COVID-19 pandemic. Suen YT, Chan RCH, Wong EMY. To Have or Not to Have Sex? COVID-19 and Sexual Activity Among Chinese-Speaking Gay and Bisexual Men in Hong Kong. J Sex Med 2021;18:29-34.


Novel oxidative alpha-tosyloxylation of alcohols with iodosylbenzene and p-toluenesulfonic acid and its synthetic use for direct preparation of heteroaromatics.
alpha-Tosyloxyketones and alpha-tosyloxyaldehydes were directly prepared from alcohols by treatment with iodosylbenzene and p-toluenesulfonic acid monohydrate in good yields. This method can be used for the direct preparation of thiazoles, imidazoles, and imidazo[1,2-a]pyridines from alcohols in good to moderate yields by the successive treatment with iodosylbenzene and p-toluenesulfonic acid monohydrate, followed by thioamides, benzamidine, and 2-aminopyridine, respectively.


Hepatic gluconeogenesis in chickens.
Gluconeogenesis by isolated hepatocytes resulted in glucose release but insignificant rates of glycogen synthesis. The effectiveness of precursors was similar for hepatocytes from fed and starved chickens except for impaired gluconeogenesis from pyruvate when compared to lactate in lactate starved chicken hepatocytes. The impairment was caused by limitations in cytosolic NADH production as a result of the mitochondrial location of phosphoenolpyruvate carboxykinase in chicken liver. The order of effectiveness of precursors on hepatic gluconeogenesis was generally similar to the effects of precursors on increasing the plasma glucose concentration in vivo. The exceptions were caused by interactions with other precursors in vivo. The alteration of the NADH/NAD+ ratio by ethanol and ATP/ADP ratio by adenosine could play significant roles in the control of precursor conversion to glucose. Physiological glucagon concentrations stimulated gluconeogenesis from precursors entering the pathway both above and below the level of triose phosphates, and its effect were mimicked by dibutyryl cyclic AMP. Previous results on the effects of precursor and glucagon injection on the plasma glucose concentration of chickens in vivo can largely be explained by effects at the hepatic level. Isolated chicken and rat hepatocytes share many common features. Qualitatively the ordering of gluconeogenic effectiveness was similar but quantitive differences existed as a result of differing activities and cellular locations of enzymes. Neither preparation readily synthesised glycogen and the sensitivity to glucagon was similar.