Cortical mechanisms of sensory trick in cervical dystonia.
Patients with cervical dystonia (CD) often show an improvement in dystonic posture after sensory trick (ST), though the mechanisms underlying ST remain unclear. In this study, we aimed to investigate the effects of ST on cortical activity in patients with CD and to explore the contribution of motor and sensory components to ST mechanisms. To this purpose, we studied 15 CD patients with clinically effective ST, 17 without ST, and 14 healthy controls (HCs) who mimicked the ST. We used electroencephalographic (EEG) recordings and electromyography (EMG) data from bilateral sternocleidomastoid (SCM) muscles. We compared ST-related EEG spectral changes from sensorimotor and posterior parietal areas and EMG power changes between groups. To better understand the contribution of motor and sensory components to ST, we tested EEG and EMG correlates of three different conditions mimicking ST, the first without skin touch ("no touch" condition), the second without voluntary movements ("passive" condition), and finally without arm movements ("examiner touch" condition). Results showed ST-related alpha desynchronization in the sensorimotor cortex and theta desynchronization in the sensorimotor and posterior parietal cortex. Both spectral changes were more significant during maneuver execution in CD patients with ST than in CD patients without ST and HCs who mimicked the ST. Differently, the "no touch", "passive", or "examiner touch" conditions did not show significant differences in EEG or EMG changes determined by ST execution/mimicking between CD patients with or without ST. A higher desynchronization within alpha and theta bands in the sensorimotor and posterior parietal areas correlated with a more significant activity decrease in the contralateral SCM muscle, Findings from this study suggest that ST-related changes in the activity of sensorimotor and posterior parietal areas may restore dystonic posture and that both motor and sensory components contribute to the ST effect.


Ugonin K promotes osteoblastic differentiation and mineralization by activation of p38 MAPK- and ERK-mediated expression of Runx2 and osterix.
Ugonin K is a flavonoid isolated from the roots of Helminthostachys zeylanica, a folk medicine used to strengthen bone mass and cure bone fracture. It is of interest to determine whether ugonin K has beneficial effect on osteoblast maturation. In this study, MC3T3-E1 osteoblasts were treated with ugonin K. Cell differentiation and mineralization were identified by alkaline phosphatase (ALP) activity and Alizarin red S staining, respectively. RT-PCR and Western blot were used to analyze osteoblast-associated gene expression and signaling pathways. Our results showed that ugonin K significantly induced the increase of ALP activity, expressions of bone sialoprotein (BSP) and osteocalcin (OCN), and mineralization. The mRNA expressions of the transcription factors Runx2 and osterix were also up-regulated by ugonin K. Ugonin K increased the phosphorylated level of p38 and ERK, respectively. In the presence of SB203580, ugonin K induced expressions of Runx2 and osterix, ALP activity, BSP level and bone nodule formation were all completely inhibited, but ugonin K induced OCN expression was not affected. On the other hand, ugonin K-induced ALP activity and mineralization were mildly attenuated by PD98059, but the over-expressed Runx2, osterix, BSP and OCN also were significantly repressed by PD98059. These suggested that both p38 and ERK participate in regulating ugonin K evoked osteogenesis but p38 seemed to play a more important role. Take together, the potential anabolic effect of ugonin K on bone might act through activations of p38- and ERK-mediated Runx2 and osterix expressions to induce the synthesis of osteoids and formation of bone nodule.


Postoperative complications after non-obstetric surgery among pregnant patients in the National Surgical Quality Improvement Program, 2005-2012.
To examine whether pregnant patients have higher risk of major 30-day postoperative complications compared with their non-pregnant counterparts after non-obstetric surgery. A secondary analysis of the prospective National Surgical Quality Improvement Program (NSQIP) from 2005 to 2012 of pregnant patients 18-51 years old, without surgery in the preceding 30 days, and who underwent a non-obstetrical operation. The primary outcome was composite 30-day major postoperative complications. We used modified Poisson regression. Among 354,251 assessed patients, 3655 (1%) were pregnant. The overall incidence of 30-day major postoperative complication was 6%, and did not vary by pregnancy status. Pregnant patients were not at higher risk of 30-day major postoperative complications compared to non-pregnant patients following non-obstetric surgery. This held for most procedures, except pregnant patients were at a higher risk of complications with colorectal and hernia surgeries. Secondarily, pregnant patients were at higher risk of transfusion. Pregnant patients are generally not at higher risk of major postoperative complications following non-obstetric surgery. This information can be used when counseling pregnant patients about the risks versus benefits of non-obstetric surgery.


Isolation, characterization, and localization of beta-tubulin genomic clones of three Drosophila montium subgroup species.
Genomic libraries were constructed from three Drosophila species, namely Drosophila auraria, Drosophila serrata, and Drosophila kikkawai, belonging to the Drosophila montium subgroup of the Drosophila melanogaster species group. Clones containing beta-tubulin specific sequences were isolated, characterized by restriction endonuclease digestions and Southern hybridizations, and mapped by in situ hybridization on the polytene chromosomes of the species studied. The distribution of the beta-tubulin loci was found to be similar in D. montium species and D. melanogaster.


Experimental basis of determining maximum coronary, myocardial, and collateral blood flow by pressure measurements for assessing functional stenosis severity before and after percutaneous transluminal coronary angioplasty.
Severity of coronary artery stenosis has been defined in terms of geometric dimensions, pressure gradient-flow relations, resistance to flow and coronary flow reserve, or maximum flow capacity after maximum arteriolar vasodilation. A direct relation between coronary pressure and flow, however, may only be presumed if the resistances in the coronary circulation are constant (and minimal) as theoretically is the case during maximum arteriolar vasodilation. In that case, pressure measurements theoretically can be used to predict maximum flow and assess functional stenosis severity. A theoretical model was developed for the different components of the coronary circulation, and a set of equations was derived by which the relative maximum flow or fractional flow reserve in both the stenotic epicardial artery and the myocardial vascular bed and the proportional contribution of coronary arterial and collateral flow to myocardial blood flow are calculated from measurements of arterial, distal coronary, and central venous pressures during maximum arteriolar vasodilation. To test this model, five dogs were acutely instrumented with an epicardial, coronary Doppler flow velocity transducer. Distal coronary pressures were measured by an ultrathin pressure-monitoring guide wire (0.015 in.) with minimal influence on transstenotic pressure gradient. Fractional flow reserve was calculated from the pressure measurements and compared with relative maximum coronary artery flow measured directly by the Doppler flowmeter at three different levels of arterial pressure for each of 12 different severities of stenosis at each pressure level. Relative maximum blood flow through the stenotic artery (Qs) measured directly by the Doppler flowmeter showed an excellent correlation with the pressure-derived values of Qs (r = 0.98 +/- 0.01, intercept = 0.02 +/- 0.03, slope = 0.98 +/- 0.04), of the relative maximum myocardial flow (r = 0.98 +/- 0.02, intercept = 0.26 +/- 0.07, slope = 0.73 +/- 0.08), and of the collateral blood flow (r = 0.96 +/- 0.04, intercept = 0.24 +/- 0.07, slope = -0.24 +/- 0.06). Moreover, the theoretically predicted constant relation between mean arterial pressure and coronary wedge pressure, both corrected for venous pressure, was confirmed experimentally (r = 0.97 +/- 0.03, intercept = 9.5 +/- 13.3, slope = 4.4 +/- 1.2). These results provide the experimental basis for determining relative maximum flow or fractional flow reserve of both the epicardial coronary artery and the myocardium, including collateral flow, from pressure measurements during maximum arteriolar vasodilation. With a suitable guide wire for reliably measuring distal coronary pressure clinically, this method may have potential applications during percutaneous transluminal coronary angioplasty for assessing changes in the functional severity of coronary artery stenoses and for estimating collateral flow achievable during occlusion of the coronary artery.


Barriers to, and facilitators of, the adoption of a sugar sweetened beverage tax to prevent non-communicable diseases in Namibia: a policy landscape analysis.
Background: Nutrition-related non-communicable diseases contribute to approximately half of the premature deaths in Namibia. Westernisation and urbanisation of communities have resulted in changing dietary patterns that see people eating more refined and high sugar content foods that are a risk for nutrition-related non-communicable diseases. Sugar-sweetened beverage taxation has been found to influence consumer purchasing behaviour and to raise revenue for health-promoting activity in other low- and middle-income countries.Objectives: To analyse Namibia's non-communicable diseases prevention policy landscape and assess the readiness of the Government to adopt sugar-sweetened beverage taxation policies for public health.Methods: Government policy documents relating to nutrition-related non-communicable diseases were analysed, utilising predetermined variables based on policy theory. Thirteen key informant interviews were conducted with stakeholders from Government, non-governmental organisations and academic institutions. Data sets were analysed utilising Kingdon's analytical theory for agenda setting.Results: Nutrition-related non-communicable diseases are an increasing problem that requires immediate action. Diet and lifestyle are recognised as major contributors to non-communicable diseases. The Government has adopted a multisectoral approach to the control and prevention of non-communicable diseases in Namibia. A sugar-sweetened beverage tax is envisaged in policy, but there is no progress towards its enactment. At the highest level of Government, the Ministry of Finance has ruled out immediate action towards sugar-sweetened beverage taxation. There is little publicly available information about the Namibian beverages industry, but it is closely tied to the South African drinking industry and is influenced by policy action in that country.Conclusion: The Government of Namibia has taken positive steps and the policy environment is friendly towards an SSB tax. The proximity of trade and the competitive nature of the Namibian drinks industry with South Africa suggest that a regional perspective to advocacy would be of value.


Effects of the benomyl metabolite, carbendazim, on the hypothalamic-pituitary reproductive axis in the male rat.
Carbendazim (MBC), the bioactive metabolite of the fungicide benomyl, has been reported to induce a number of testicular alterations in male rats. Since it is possible that extragonadal changes contribute to the appearance of such effects, the present study focused on the presence of concurrent endocrine changes in the hypothalamic and pituitary components of the brain-pituitary-testicular axis. Subchronic administration of MBC (50, 100, 200 or 400 mg/kg) was found to cause a dose-related elevation in serum follicle stimulating hormone (FSH) and pituitary luteinizing hormone (LH). Values for prolactin and thyroid-stimulating hormone remained unchanged. No statistical differences in gonadotropin-releasing hormone concentrations were present in mediobasal hypothalamus, although an elevation in anterior hypothalamic values was found at the low dose, followed by a dose-related decline. These findings demonstrate that previously reported gonadal differences following subchronic exposure to carbendazim are accompanied by alterations elsewhere in the reproductive system which appear to involve both changes in Sertoli cell-pituitary feedback signals and direct effects of the compound on the central nervous system.


Rate of reinfection with intestinal nematodes after treatment of children with mebendazole or albendazole in a highly endemic area.
The comparative efficacy of albendazole and mebendazole in the treatment of intestinal nematode infections were compared 3 weeks after treatment in a randomized trial among schoolchildren on Pemba Island, Tanzania. Egg counts were compared 3 weeks, 4 months and 6 months after treatment of 731 children seen on each occasion. Differences in the efficacies were apparent with some nematodes 21 d after treatment, but these were no longer apparent 4 months after treatment, and by 6 months intensities of infection were similar to pre-treatment levels. These findings suggest that treatment of schoolchildren every 4 months may be necessary in this highly endemic area in order to have an impact on the intensity of intestinal nematode infections sufficient to be likely to reduce morbidity.


Introduction of ultra-hypofractionation in breast cancer: Implications for costs and resource use.
A shift towards (ultra-)hypofractionated breast irradiation can have important implications for the practice of contemporary radiation oncology. This paper presents a systematic analysis of the impact of different fractionation schedules on multiple key performance indicators, namely resource use, costs, work times, throughput and waiting times. Time-driven activity-based costing (TD-ABC) is applied to calculate the costs and resources consumed where the perspective of the radiotherapy department in adopted. Three fractionation regimens are considered: ultra-hypofractionation (5 x 5.2 Gy, UHF), moderate hypofractionation (15 x 2.67 Gy, HF) and conventional fractionation (25 x 2 Gy, CF). Subsequently, a discrete event simulation (DES) model of the radiotherapy care pathway is developed and scenarios are compared in which the following factors are varied: distribution of fractionation regimens, patient volume and operating hours. The application of (U)HF can permit radiotherapy departments to reduce the use of scarce resources, realise work time and cost savings, increase throughput and reduce waiting times. The financial advantages of (U)HF are, however, reduced in cases of excess capacity and cost savings may therefore be limited in the short-term. Moreover, although an extension of operating hours has favourable effects on throughput and waiting times, it may also reduce cost differences between fractionation schedules by increasing the capacity of resources. By providing an in-depth analysis of the consequences associated with a shift towards (U)HF in breast cancer, the present study demonstrates how a DES model based on TD-ABC costing can assist radiotherapy professionals in making data-driven decisions.


Shining light on multi-drug resistant Candida auris: Ultraviolet-C disinfection, wavelength sensitivity, and prevention of biofilm formation of an emerging yeast pathogen.
Candida auris is an emerging fungal superbug of worldwide interest. It is associated with high mortality rates and exhibits increased resistance to antifungals. Ultraviolet subtype C (UVC) light can be used to disinfect surfaces to mitigate its spread. The objectives of this study were (1) To investigate UVC disinfection performances and wavelength sensitivity of C. auris. (2) To evaluate the UVC dose required for the prevention of biofilm formation on stainless-steel, plastic (polystyrene), and poly-cotton fabric surfaces. C. auris was grown following standard procedures. The study utilized six different UVC LED arrays with wavelengths between 252 and 280 nm. Arrays were set at similar intensities, to obtain doses of 5-40 mJ cm-2 and similar irradiation time. Disinfection performance for each array was determined using log reduction value (LRV) and percentage reduction by comparing the controls against the irradiated treatments. Evaluation of the ability of 267 nm UVC LEDs to prevent C. auris biofilm formation was investigated using stainless-steel, plastic coupons, and poly-cotton fabric. Peak sensitivity to UVC disinfection was between 267 and 270 nm. With 20 mJ cm-2 , the study obtained ≥LRV3. On stainless-steel coupons, 30 mJ cm-2 was sufficient to prevent biofilm formation, while on plastic, this required 10 mJ cm-2 . A dose of 60 mJ cm-2 reduced biofilms on poly-cotton fabric significantly (R2 = 0.9750, p = 0.0002). The study may allow for the design and implementation of disinfection systems.


Monitoring of biologically effective UV irradiance at El Arenosillo (INTA), Andalucia, in Spain.
Biological UV (ultraviolet) dosimetry was applied using the biofilm-technique (DLR patent) to determine the UV levels weighted of biologically weighted UV radiation at the INTA Sounding Station of El Arenosillo at Huelva, Spain (37 degrees 06'N, 6 degrees 44'W, 50 m a s 1=above sea level) on 2 days in 1997 [correction of 1977] (April 1, and May 5). Exposure periods were calculated for clear sky days using a radiative transfer model for erythemal doses to reach 1.3 to 1.5 MED (minimal erythemal dose). Reliability of the radiative transfer model was demonstrated by the doses registered by a Yankee-UV biometer for the same exposure periods as used for the biosensor. This work presents the methodology employed (biofilm-technique utilized [correction of utiliced], calculation of exposing periods with radiative transfer model, etc) and the results obtained with the Yankee biometer and the biofilm. At noon, the ratio of biofilm measurements (Ieff, W/m2=biological effective irradiance, in W/m2) to the UV Biometer data (in MED/h) was 3-4.


A simple procedure to determine the biological titer of recombinant retroviral vectors.
Retroviral vectors are widely used to deliver genetic material to live cells both in experimental and clinical settings. The ability of these vectors to transduce target cells is an important aspect of their clinical applicability and one of the factors determining their transduction efficiency is vector functional titer. Current methods for titrating retroviral vectors involve measuring the number of target cells in culture transduced by a given volume of vector solution. In this report, we describe a new procedure which allows one to estimate the actual number of infectious particles capable of transducing a permissive cell type. Vector biological titer is calculated from the fractional decline in transduction efficiency observed when a given volume of vector solution is sequentially added to multiple dishes containing permissive cells. Values determined this way are greater than those obtained from a single transduction experiment, with the difference being inversely proportional to the degree of cell permissiveness for vector entry. The present procedure is simple, reliable and expeditious. It will be useful to standardize vector biological titers determined in different laboratories, and help implement strategies for efficient gene delivery protocols.


Detection of multidrug-resistant Enterobacteriaceae isolated from river waters flowing to the Guanabara Bay and from clinical samples of hospitals in Rio de Janeiro, Brazil
The use of antibiotics in humans, animal husbandry and veterinary activities induces selective pressure leading to the colonization and infection by resistant strains. We evaluated water samples collected from rivers of the Guanabara Bay, which have suffered minor and major environmental degradation, and clinical samples of hospital origin to detect evidence of the presence of resistance genes to aminoglycosides, beta-lactam antibiotics and fluoroquinolones in strains of Klebsiella pneumoniae subsp. pneumoniae, K. pneumoniae subsp. ozaenae and Escherichia coli. For isolation of the water strains we employed culture media containing 32 μg/ml cephalotin and 8 μg/ml gentamicin. The strains from clinical materials were selected using culture media containing 8 μg/ml gentamicin. The strains were identified and subjected to antimicrobial susceptibility testing (AST), plasmid DNA extraction and polymerase chain reaction (PCR) to detect genes encoding enzymes modifying aminoglycosides (EMA), extended-spectrum beta-lactamases (ESBL) and plasmid mechanisms of quinolone resistance (PMQR). The AST of the isolates recovered from water samples showed multidrugresistance profiles similar to those found in isolates recovered from clinical materials. All isolates from water samples and 90% of the isolates from clinical samples showed at least one plasmid band. In the PCR assays, 7.4% of the isolates recovered from water samples and 20% of those from clinical materials showed amplification products for the three antimicrobial classes. We believe that the detection of microorganisms presenting genetic elements in environments such as water is necessary for the prevention and control of their dissemination with potential to infect humans and other animals in eventual contact with these environments.


Neurite branching pattern formation: modeling and computer simulation.
A model for nerve cell pattern formation is proposed in this paper. The model is based on some experimental results and an assumption that there is a kind of inhibitive interaction between growing neurites on the same nerve cell. In this paper, this interaction is termed lateral inhibition. A group of ordinary differential equations are used to describe the elongation of the terminal neurite segments of individual nerve cells. Computer simulation and comparison of it with in vitro studies are also made in this paper.


HIV-associated Kaposi's sarcoma: new developments in epidemiology and molecular pathology.
New epidemiological data give evidence for an unknown etiological agent of Kaposi's sarcoma (KS). Experimental support is provided by research on cultivated KS cells. These results contradict a direct involvement of HIV-1 in the pathogenesis of KS. Research on cultivated KS cells confirmed the hypothesis that KS spindle cells originate from endothelial cells and gave new insight into the pathogenesis of tumor cell growth. KS spindle cells secrete an autocrine acting growth promoting activity. Nevertheless, they seem to depend on several growth factors like PDGF and IL-6 provided by surrounding endothelial cells and macrophages, respectively. The results support the hypothesis of a tumor relying on paracrine acting factors more than on autocrine acting factors.


A study on transformation in a mutant of Candida pseudotropicalis.
This paper reports on the possible influence of various factors on the frequency of transformation in Candida pseudtropicalis. The concentration of DNA used varied between 25 mug and 100 mug/ml. The maximum percentage transformation 0-16% occured at 75 mug/ml.


The 12-month prevalence of DSM-IV anxiety disorders among Nigerian secondary school adolescents aged 13-18 years.
To estimate the 12-month prevalence of DSM-IV-specific anxiety disorders among Nigerian secondary school adolescents aged 13-18 years. A representative sample of adolescents (n=1090) from senior secondary schools in a semi-urban town in Nigeria was assessed for the 12-month prevalence of DSM-IV-specific anxiety. The 12-month prevalence for all anxiety disorders was 15.0% (females=19.6%; males=11.4%). There were significant gender differences in the prevalence for all anxiety disorders (P<0.001; OR 1.96, 95% CI 1.35-2.65) and social anxiety disorder (P=0.035; OR 1.82, 95% CI 1.03-3.19) and significant age difference in the prevalence of separation anxiety disorder (P=0.045; OR 2.43, 95% CI 0.99-5.96). The prevalence of anxiety disorders in Nigerian secondary school adolescents was comparable to the rates found in the western world. Health policies must integrate adolescents' anxiety as a disorder of public health significance. Further studies are needed to evaluate the factors associated with anxiety disorders amongst adolescents in this region.


Mechanism for 6-methylcoumarin photoallergenicity.
6-Methylcoumarin (6-MC), a synthetic fragrance material, has been reported to be photoallergenic both in man and in guinea pigs. To elucidate the possible mechanism of photoallergenicity, 6-MC in ethanolic solution was exposed to 200 joules/cm2 of long-wavelength ultraviolet (UV) ranging from 320 to 400 nm for 16 hr, and was examined for its contact allergenicity by means of a modified guinea pig maximization test. Strong allergic responses were observed, indicating that UV plays a catalytic role in forming contact allergens during irradiation. The solution was fractionated to isolate and purify contact sensitizers by gel-permeation chromatography and high-performance liquid chromatography. By employing mass spectrometry and proton and carbon-13 nuclear magnetic resonance, mono- and diethyl esters of 6-MC dimer were compounds identified which showed allergic reactions in guinea pigs sensitized with UV-irradiated 6-MC.


Reactive nitrogen and oxygen species in interleukin-1-mediated DNA damage associated with osteoarthritis.
Osteoarthritis (OA) is associated with increased levels of reactive nitrogen and oxygen species and pro-inflammatory cytokines, such as interleukin-1 (IL-1). Nitric oxide (NO) can mediate a number of the catabolic effects of IL-1 in articular cartilage. The aims of this study were to determine if OA cartilage shows evidence of DNA damage, and if IL-1 could induce DNA damage in non-OA cartilage by increasing NO or superoxide. Articular chondrocytes were isolated from porcine femoral condyles and embedded in 1.2% alginate. The effects of 24h incubation with IL-1, the nitric oxide synthase 2 (NOS2)-selective inhibitor, the free radical scavenger superoxide dismutase (SOD), the NO donor NOC18, or the combined NO and peroxynitrite donor SIN-1 on DNA damage were tested, using the "comet" assay. NO production was measured using the Griess assay. The type of oxidative damage present was assessed using a modified comet assay. OA cartilage had significantly more DNA damage than non-OA cartilage (P<0.001). IL-1 caused an increase in DNA damage (P<0.01), which was associated with increased NO production (P<0.01). Both oxidative DNA strand breaks and base modifications of purines and pyrimidines were observed. IL-1-induced DNA damage was inhibited by an NOS2 inhibitor or by SOD (P<0.01). Furthermore, NOC18 or SIN-1 caused DNA damage (P<0.001). Our work shows chondrocytes in osteoarthritic cartilage exhibit DNA damage, and that IL-1 induces DNA damage and reactive oxygen and nitrogen species in non-OA chondrocytes in alginate.


Health-related quality of life in Moroccan patients with ankylosing spondylitis.
The main objective of this study was to assess the aspects of health-related quality of life (QOL) in patients with ankylosing spondylitis (AS) and to explore the disease-related parameters influencing it. One hundred patients with AS according to New York Classification criteria were recruited in this cross-sectional study. The Medical Outcomes Study Short Form 36 Health Survey (SF-36) was used to assess health-related QOL. Assessment criteria included the evaluation of disease activity (Bath Ankylosing Spondylitis Disease Activity index [BASDAI]), global well-being (Bath Ankylosing Spondylitis Global Index [BASGI]), enthesitis (Mander enthesis index [MEI]), functional status (Bath Ankylosing Spondylitis Functional Index [BASFI]); metrology (Bath Ankylosing Spondylitis Metrology Index [BASMI]) and radiographic damage (Bath Ankylosing Spondylitis Radiologic Index [BASRI]). In this study, males comprised 67% of the subjects; mean age was 38 ± 13 years and mean disease duration was 9.5 ± 6.8 years. Among these patients, 52% had hip involvement. Our patients had a moderately active disease and severe functional disability. All domains of SF-36 were deteriorated with low scores. The SF-36 subgroups most affected were role limitation (18.8 ± 28.1), role emotional (19.4 ± 35), general health (44.9 ± 20.3) and vitality (38.0 ± 18.2). Lower scores of SF-36 had good statistically significant correlations with altered functional status (BASFI), worse general well-being (BASGI), altered metrology (BASMI); and moderate correlations with high disease activity (BASDAI), important radiological damage (BASRI); restricted chest expansion and prolonged morning stiffness (p < 0.001). This study states that health-related QOL in Moroccan patients with AS is damaged in a significant way. Mental as well as physical aspects were affected. Functional disability, patient's well-being, metrology and disease activity are the main factors associated with deteriorating domains of QOL in AS. Recognizing complicated relationships between clinical measures and QOL in patients with AS can help us to develop further management strategies to improve their QOL.


Column-in-valve designs to minimize extra-column volumes.
We report on the design and performance of in-house built column cartridges that can be directly screwed into the ports of a commercial rotor-stator valve to minimize extra-column band broadening and pressure-drop losses when pursuing ultra-fast separations such as those needed in 2D and 3D-LC separations. Two basic designs were evaluated and were compared with the results obtained with a commercial screw-in column cartridge. The system produces an extra-column band broadening as low as 0.05 to 0.1 μL2 for the employed UV-detector set-up. Despite these very low values, the obtained separation efficiency of the in-house fabricated cartridge columns was very low, corresponding to a reduced minimal plate height around h=7 at the very best, which, for the 1.7 μm particle and 26.4 mm long columns corresponds to a number of theoretical plates of N=2200 under isocratic conditions. A similar poor performance was obtained with a commercial column cartridge with similar dimensions using the same set-up. One possible explanation of the observed performance could be found in the inner diameter of the column cartridges (i.d. =0.75 mm and 1 mm) which, for the employed sub 2-μm particles, falls into a region of column diameters that, according to literature models, is most likely to suffer from inherent packing problems.


Review article: Practical considerations for fluid resuscitation in cirrhosis.
Standard clinical methods of assessing volume and providing resuscitation are not always applicable to patients with advanced or decompensated cirrhosis. Despite this being well known from a clinical perspective, there remains relatively little evidence to guide clinicians though fluid management in patients with cirrhosis and, often, multi-organ system dysfunction. This review summarises the current understanding of the circulatory dysfunction in cirrhosis, modalities for assessing volume status, and considerations for fluid selection. It additionally provides a practical approach to fluid resuscitation. We review current literature on cirrhosis pathophysiology in steady-state and shock, clinical implications of fluid resuscitation, and strategies to assess intravascular volume. Literature reviewed here was identified by the authors through PubMed search and review of selected papers' references. Clinical management of resuscitation in advanced cirrhosis remains relatively stagnant. Although several trials have attempted to establish the superior resuscitative fluid, the lack of improvement in hard clinical outcomes leaves clinicians without clear guidance. The absence of consistent evidence for fluid resuscitation in patients with cirrhosis limits our ability to produce a clearly evidence-based protocol for fluid resuscitation in cirrhosis. However, we propose a preliminary practical guide to managing fluid resuscitation in patients with decompensated cirrhosis. Further studies are needed to develop and validate volume assessment tools in the specific context of cirrhosis, while randomised clinical trials of protocolized resuscitation may improve care of this patient population.


Age at Diagnosis Impacts Molecular and Clinical Properties of Tumors.
Patient age at diagnosis influences the mutational landscape and clinical prognosis of tumors.


Synergistic effects of adipose-derived stem cells combined with decellularized myocardial matrix on the treatment of myocardial infarction in rats.
The aims of the study are to investigate whether the combination of adipose-derived stem cells (ADSCs) with decellularized extracellular matrix (dECM) of myocardium can exert synergistic therapeutic effects on acute MI and the underlying mechanism. Myocardial dECM from fresh porcine myocardium was prepared in an injectable gel, ADSCs were seeded into the myocardial dECM gels, and then the mixture was injected into the myocardium of the infarct border zone after acute MI, which was induced by ligating the left anterior descending coronary artery in male SD rats, to assess the therapeutic potential. The degree of fibrosis was detected by Masson's trichrome. The evaluation of cardiac function was performed by Electrocardiography. Myocardial dECM (2.0%) had a suitable aperture and arrangement for cell growth, and also exhibited suitable biomechanical properties. Four-weeks after treatment in vivo, the combination of ADSCs and myocardial dECM could obviously increase angiogenesis, reduce the degree of fibrosis, and decrease infarct size. Furthermore, the combination treatment exerted significant functional improvement. Compared with ADSCs or dECM group alone, the left ventricular ejection fraction (LVEF) in the combination group was 13.4% and 21.8% elevated, respectively. The combination of ADSCs and myocardial dECM has synergistic effects on cardiac repair in acute MI.


Distribution and ecological risk of polycyclic aromatic hydrocarbons in wastewater treatment plant sludge and sewer sediment from cities in Middle and Lower Yangtze River.
The objective of this study was to conduct a comparative study of the distribution and ecological risk of polycyclic aromatic hydrocarbons (PAHs) in the sewage collection and treatment system of four cities located in the middle and lower reaches of the Yangtze River. The results revealed that the mean concentration of 16 ΣPAHs was higher in the sewer sediments (1489.45 ng·g-1) than in the sewage sludge (781.78 ng·g-1). PAH monomers were detected in all cases, with higher mean Pyr, Chr, BbF and BaP concentrations. PAHs with 4-6 rings were dominant in both sewage sludge and sewer sediment monomer PAHs. With the isomer ratio method and positive definite matrix factor (PMF) method, the results showed that the major sources of PAHs in sewage sludge were petroleum sources, coal tar, and coking activities, whereas PAHs in sewer sediments were primarily from wood combustion, automobile emissions, and diesel engine emissions. Of all the PAH monomers, BaP and DahA had the highest toxic equivalents, although their levels were not the highest. Based on the assessment of ΣPAHs, it was concluded that both sewage sludge and sewer sediments had medium ecological risk. The results of this study provide reference information for the control of PAHs in the wastewater collection and treatment system of the middle and lower reaches of the Yangtze River.


Baseline and Process Factors of Anti-Retroviral Therapy That Predict Loss to Follow-up Among People Living with HIV/AIDS in China: A Retrospective Cohort Study.
We explored the predictors and predictive models of loss to follow-up (LTFU) during the first year of anti-retroviral therapy (ART). LTFU was defined as the failure to visit the clinic for antiretroviral drugs for ≥ 90 days after the last missed scheduled visit. Based on the electronic medical records of 5953 patients who were HIV positive and began ART between 2016 and 2019 in China, the LTFU rate was 7.24 (95% confidence interval 6.49-7.97) per 100 person-years during the first year of ART. ART baseline factors were associated with LTFU, but were non-optimal predictors. A model including ART process-related factors such as follow-up behaviors and physical health status had an area under the receiver operating characteristic curve of 73.4% for predicting LTFU. Therefore, the medical records of follow-up visits can be used to identify patients with a high risk of LTFU and allow interventions to be implemented proactively.


Anthropometric variables, lifestyle and sports in school-age children: comparison between the cities of Bologna and Crotone.
Weight disorders are rapidly increasing in childhood. In Italy a strong geographic North-South gradient of overweight and obesity has been reported. The purpose of this study is to examine anthropometric variables, physical activity and lifestyles in school-age children in the cities of Bologna and Crotone. The sample consists of 963 children attending primary schools, aged 6-10 years. Height, weight, triceps, and subscapular skinfolds were measured for each child; body mass index (BMI) and percentage of fat mass were calculated. Physical activity was determined through an interview with each child. Another questionnaire was submitted to parents, in order to obtain information on sleep duration, means of transport and type of physical activity. In the city of Bologna, the mean values of anthropometric variables were: height (boys - 1,335 mm, girls - 1,332 mm), BMI (boys - 17.8 kg/m(2), girls - 17.3 kg/m(2)), and the proportion of overweight and obese individuals was: boys - 20.6%, girls - 12.7%. In Crotone the mean values were: height (boys - 1,275 mm, girls - 1,265 mm), BMI (boys - 19.4 kg/m(2), girls - 19.3 kg/m(2)), and the proportion of overweight and obese individuals was: boys - 46.7%, girls - 49.0%. The results have demonstrated significant correlations of lifestyle and physical activity with children's weight status. In Crotone there is a larger variation of weight disorders with higher percentages of overweight children than in Bologna. The children in Crotone are engaged in sedentary activities for a significantly longer time than children in Bologna, who are more physically active. The data show a strong North-South gradient concerning not only distribution of weight status, but also lifestyles especially including participation in sports and sedentary behavior. Our study also provides meaningful suggestions how to define lifestyles in order to achieve an optimal health status during growth.


Simultaneous removal of Cd(II) and As(III) by graphene-like biochar-supported zero-valent iron from irrigation waters under aerobic conditions: Synergistic effects and mechanisms.
Irrigation water is commonly contaminated with cadmium and arsenic near mining regions, which significantly contributes to excessive heavy metals in rice grains. Herein, we have developed a novel graphene-like biochar (GB)-supported nanoscale zero-valent iron (nZVI) and the underlying mechanisms of synergistic effects between GB and nZVI for the simultaneous removal of Cd(II) and As(III) under aerobic conditions. The results show that GB/nZVI has a high removal capacity of 363 mg/g (nZVI) for As(III) at pH 4 and 92.8 mg/g (nZVI) for Cd(II) at pH 7. These values are significantly higher than GB and nZVI (1.7 times for Cd(II); 1.4 times for As(III)) alone, suggesting strong synergistic effects between GB and nZVI. GB promotes nZVI oxidation to form iron oxyhydroxides and causing 35 % of As(III) converting to As(V). Importantly, As(III) significantly enhance Cd(II) removal by GB/nZVI (i.e., 131.8 mg/g as nZVI). Coexisting ions such as phosphate and humic acid have a stronger inhibitory effect on the simultaneous removal of Cd(II) and As(III). Our results indicate that oxidation and surface complexation are the dominant mechanisms and electrostatic binding exists for As(III) removal, while surface complexation predominates for Cd(II) removal. These findings provide insight into developing an effective solution for removing Cd(II)/As(III) from irrigation waters.


Calculation of clinical dose distributions in proton therapy from microdosimetry.
To introduce a new algorithm-MicroCalc-for dose calculation by modeling microdosimetric energy depositions and the spectral fluence at each point of a particle beam. Proton beams are considered as a particular case of the general methodology. By comparing the results obtained against Monte Carlo computations, we aim to validate the microdosimetric formalism presented here and in previous works. In previous works, we developed a function on the energy for the average energy imparted to a microdosimetric site per event and a model to compute the energetic spectrum at each point of the patient image. The number of events in a voxel is estimated assuming a model in which the voxel is completely filled by microdosimetric sites. Then, dose at every voxel is computed by integrating the average energy imparted per event multiplied by the number of events per energy beam of the spectral distribution within the voxel. Our method is compared with the proton convolution superposition (PCS) algorithm implemented in Eclipse™ and the fast Monte Carlo code MCsquare, which is here considered the benchmark, for in-water calculations, using in both cases clinically validated beam data. Two clinical cases are considered: a brain and a prostate case. For a SOBP beam in water, the mean difference at the central axis found for MicroCalc is of 0.86% against 1.03% for PCS. Three-dimensional gamma analyses in the PTVs compared with MCsquare for criterion (3%, 3 mm) provide gamma index of 95.07% with MicroCalc vs 94.50% with PCS for the brain case and 99.90% vs 100.00%, respectively, for the prostate case. For selected organs at risk in each case (brainstem and rectum), mean and maximum difference with respect to MCsquare dose are analyzed. In the brainstem, mean differences are 0.25 Gy (MicroCalc) vs 0.56 Gy (PCS), whereas for the rectum, these values are 0.05 Gy (MicroCalc) vs 0.07 Gy (PCS). The accuracy of MicroCalc seems to be, at least, not inferior to PCS, showing similar or better agreement with MCsquare in the considered cases. Additionally, the algorithm enables simultaneous computation of other quantities of interest. These results seem to validate the microdosimetric methodology in which the algorithm is based on.


Z-Endoxifen prevents aggressive mammary cancers in mice by inhibiting cell proliferation and creating a tumor suppressive microenvironment.
Aggressive estrogen receptor (ER) positive breast cancer is frequently tamoxifen-resistant; alternative endocrine approaches exist for therapy, but not for prevention, particularly in premenopausal women. We examined the efficacy of the selective ER modulator (Z-endoxifen) as monotherapy and in combination with the selective progesterone receptor modulators (onapristone and ulipristal acetate) in the tamoxifen-insensitive C3(1)/SV40TAg mouse mammary tumorigenesis model. Unlike tamoxifen at human equivalent dose (HED) 101 mg/day, endoxifen at HED 24 mg/day significantly increased latency and reduced tumor growth relative to untreated controls. Ulipristal acetate (UPA) at HED 81 mg/day also significantly increased latency however failed to inhibit tumor growth, while onapristone (HED 98 mg/day) had no tumor prevention efficacy in this model. Addition of UPA to endoxifen did not enhance preventive efficacy over endoxifen alone. The expression of genes associated with cell cycle, cell proliferation and extracellular matrix remodeling was similarly repressed by endoxifen and UPA however only endoxifen significantly downregulated prominent genes associated with poor prognosis (Col11a1, Il17b, Pdgfa, Tnfrsf11a). Our results indicate that endoxifen can prevent breast cancers, even when tamoxifen-resistant, through its role in favorable tissue remodeling and immunomodulation.


Frameless patient registration using ultrasonic imaging: a preliminary study.
Locating the patient accurately in real time is necessary for many medical robotics applications. Current solutions are expensive or inconvenient. We show progress toward solving these problems by using ultrasound to track computed tomography (CT) reference features in realtime. We compute the locations of target features in the ultrasonic images relative to the CT reference features.


On the role of periodic structures in the lower jaw of the atlantic bottlenose dolphin (Tursiops truncatus).
This paper proposes the application of band-gap theory to hearing in the atlantic bottlenose dolphin (Tursiops truncatus). Using the transmission line modelling (TLM) technique and published computed tomography (CT) data of an atlantic bottlenose dolphin (Tursiops truncatus), a series of sound propagation experiments have been carried out. It is shown that the teeth in the lower jaw can be viewed as a periodic array of scattering elements which result in the formation of an acoustic stop band (or band gap) that is angular dependent. It is shown through simple and complex geometry simulations that performance enhancements such as improved gain and isolation between the two receive paths can be achieved. This mechanism has the potential to be exploited in direction-finding sonar.


Distribution of dystrophin gene deletions mapped by multiplex PCR in the Moravian population.
Twenty two Duchenne muscular dystrophy (DMD) patients from the province of Moravia, Czech Republic, were tested for the presence of dystrophin gene rearrangements using multiplex polymerase chain reaction (PCR). Using primer pairs for amplification of two promoter regions and 27 exons, 11 patients were found positive for deletions spanning one or more exons. In all these cases, the deletions affected the distal part of the dystrophin gene, beginning from exon 44 but not reaching exon 60.


Characterization and functional analysis of Cshsp19.0 encoding a small heat shock protein in Chilo suppressalis (Walker).
Small heat shock proteins (sHSPs) function as ATP-independent chaperones that preserve cellular proteostasis under stressful conditions. In this study, Cshsp19.0, which encodes a new small heat shock protein, was isolated and characterized from Chilo suppressalis (Walker) to better understand the contribution of sHSPs to insect development and stress tolerance. The full-length Cshsp19.0 cDNA was 697 bp and encoded a 19.0 kDa protein with an isoelectric point of 5.95. Phylogenetic analysis and amino acid alignments indicated that Cshsp19.0 is a member of the sHSP family. Cshsp19.0 was expressed at maximal levels in foreguts and showed the least amount of expression in fat bodies. Expression analysis in different developmental stages of C. suppressalis revealed that Cshsp19.0 was most highly expressed in 1st instar larvae. Furthermore, Cshsp19.0 was upregulated when insects were exposed to heat and cold stress for a 2-h period. There were significant differences in the male and female pupae in response to humidity; Cshsp19.0 expression increased in male pupae as RH increased, whereas the inverse pattern was observed in female pupae. Larvae exhibited a lower rate of survival when Cshsp19.0 was silenced by a nanomaterial-promoted RNAi method. The results confirm that Cshsp19.0 functions to increase environmental stress tolerance and regulates physiological activities in C. suppressalis.


The cost of correcting for error during sensorimotor adaptation.
Learning from error is often a slow process. In machine learning, the learning rate depends on a loss function that specifies a cost for error. Here, we hypothesized that during motor learning, error carries an implicit cost for the brain because the act of correcting for error consumes time and energy. Thus, if this implicit cost could be increased, it may robustly alter how the brain learns from error. To vary the implicit cost of error, we designed a task that combined saccade adaptation with motion discrimination: movement errors resulted in corrective saccades, but those corrections took time away from acquiring information in the discrimination task. We then modulated error cost using coherence of the discrimination task and found that when error cost was large, pupil diameter increased and the brain learned more from error. However, when error cost was small, the pupil constricted and the brain learned less from the same error. Thus, during sensorimotor adaptation, the act of correcting for error carries an implicit cost for the brain. Modulating this cost affects how much the brain learns from error.


A subchronic toxicity study, preceded by an in utero exposure phase, with refined arachidonic acid-rich oil (RAO) derived from Mortierella alpina XM027 in rats.
To evaluate the potential toxicity of refined arachidonic acid-rich oil (RAO) derived from Mortierella alpina (M. alpina) XM027, we performed a 90-day subchronic study in F1 Sprague Dawley (SD) rats. This study was preceded by a 4-week pretreatment period of parental (F0) rats and exposure of the F0 dams throughout mating, gestation, and lactation. The results indicated that RAO, at dose levels of 0.5%, 1.5%, and 5%, did not affect either reproductive performance of the parental rats, or any characteristics of the pups. In the subchronic study with the offspring (F1) rats, no treatment related abnormalities were observed. In summary, no observable adverse effect level (NOAEL) in this study was placed at 5% RAO, the highest level tested. This level corresponds to approximately 3750mg/kg in F0 females, 2850mg/kg in F0 males, 4850mg/kg in F1 females, and 4480mg/kg in F1 males.


Urate and calcium stones--picking up a drop of mercury with one's fingers?
The evidence invariably cited to support the suspicion that urinary urate is a predisposing factor in calcium oxalate (CaOx) stone formation is critically reviewed. Analysis of the relevant literature shows that speculation is based on the clinical impression that CaOx stone-formers appear to excrete more urate than do normal subjects, and that allopurinol reduces the rate of CaOx stone recurrences. On balance, this is sufficient to suggest that a high urinary excretion of urate promotes CaOx stone formation. However, in the past, evidence to disclose the mechanism by which urate could exert this effect has been largely shrouded in confusion and controversy. The evidence for two theories that have dominated thinking in this area are reviewed and new findings are reported that indicate that neither can account for the purported effect of urate. It is concluded that dissolved urate in urine, at normal physiological pH values, directly provokes CaOx crystal nucleation by the phenomenon of salting-out. The possibility that urate promotes CaOx stone formation is further strengthened by its ability to increase significantly the amount of CaOx precipitated from solution and to cause the aggregation of individual crystals into large clusters. Future avenues of investigation that should assist in the formulation of diagnostic and therapeutic guidelines are presented.


Verapamil in the treatment of maternal paroxysmal supraventricular tachycardia.
Paroxysmal supraventricular tachycardia (PSVT) is seen somewhat frequently in the emergency department but less frequently during pregnancy. Although verapamil is widely used as the drug of choice for PSVT with a narrow QRS complex in a hemodynamically stable patient, the acute IV use of verapamil during pregnancy has not been well studied. Only a limited number of case reports document its safety and efficacy in the treatment of maternal or fetal PSVT. In general, the use of medication during pregnancy requires careful assessment of both the maternal and fetal risks versus benefits and documentation of patient consent. Because it crosses the placenta, one of the major concerns with the acute use of IV verapamil centers around the drug's potential effect on fetal heart rate. The case we present describes the occurrence of PSVT on two separate occasions in a woman in the third trimester of pregnancy. In both episodes, as much as 10 mg IV verapamil was given with resulting successful conversion to normal sinus rhythm. Fetal heart monitoring during drug administration failed to show significant change in fetal heart rate.


Distributive justice, equality and the enhancement of human cognition: A commentary on fairness and 'cognitive doping'.
What implications might the use of techniques to enhance human cognition have for the kind of polities or civil societies we inhabit? What might political philosophy, if anything, have to tell us about the desirability of using drugs to increase our intellectual powers? Much of the focus in contemporary debates about human enhancement has been upon the ethical desirability of endeavouring to enhance our capacities: should we be meddling with 'human nature', as it were? Therapeutic uses of drugs are regarded as acceptable but enhancement is frowned upon in much of this literature. This rejection of enhancement is especially prevalent in the area of sport where there is a great deal of opposition to doping. Herein I take a somewhat different approach and explore enhancement as a problem in political philosophy and, more specifically, as a problem of distributive justice. Should the enhancement of human intellectual functioning be rejected on distributive grounds of equality? Alternatively, might it be plausibly be argued that distributive justice requires such enhancement? In this paper I shall outline two contemporary theories of justice-namely, the Egalitarianism and the Rawlsian Prioritarianism-and then consider what these principles might tell us about the political legitimacy (or otherwise) of 'doping for intellect'.


Contraceptive counseling and use among women with systemic lupus erythematosus: a gap in health care quality?
Disease activity and medication use can complicate pregnancies in patients with systemic lupus erythematosus (SLE). We therefore examined contraceptive counseling and use among women in the University of California, San Francisco Lupus Outcomes Study. In 2008, we queried participants regarding their pregnancy intentions, contraceptive use, and receipt of contraceptive counseling. Premenopausal women age <45 years who were sexually active with men were considered at risk of pregnancy. We compared self-reported rates of contraceptive counseling and use stratified by treatment with teratogenic medications and by history of thrombosis or antiphospholipid antibodies (aPL), using chi-square tests. We used logistic regression models to examine predictors of contraceptive counseling and use. Among 206 women, 86 were at risk for unplanned pregnancy. Most (59%) had not received contraceptive counseling in the last year, 22% reported inconsistent contraceptive use, and 53% depended solely on barrier methods. Intrauterine device contraceptives (IUDs) were used by 13%. Women using potentially teratogenic medications were no more likely to have received contraceptive counseling, to have used contraception consistently, or to have used more effective contraceptives. A history of thrombosis or aPL did not account for low rates of hormonal methods. Four women with a history of thrombosis or aPL were using estrogen-containing contraceptives. Most women at risk for unplanned pregnancy reported no contraceptive counseling in the past year, despite common use of potentially teratogenic medications. Many relied upon contraceptive methods with high failure rates; few used IUDs. Some were inappropriately using estrogen-containing contraceptives. These findings suggest the need to improve the provision of contraceptive services to women with SLE.


Effect of intravenous cocaine on uterine blood flow in the gravid baboon.
Cocaine abuse during pregnancy is associated with adverse perinatal outcome, believed to be a result of potent vasoconstrictive effects that cocaine has on the maternal cardiovascular system. The direct effect of cocaine on the pregnant, nonhuman primates' uterine vasculature in vivo has not been examined. We investigated the effects of intravenous cocaine on maternal arterial blood pressure, uterine blood flow, and uterine vascular resistance in four unanesthetized, chronically instrumented pregnant baboons. Baboons were instrumented during the latter half of pregnancy, placing an ultrasonic flow probe around one uterine artery and catheters in the maternal inferior vena cava and aorta. Bolus intravenous cocaine hydrochloride doses of 0.05 mg/kg, 0.1 mg/kg, and 0.3 mg/kg by maternal weight were infused 30 minutes apart at least 5 days after surgical instrumentation. The maternal blood pressure rose 7.3% and 12.0% after the 0.1 mg/kg and 0.3 mg/kg cocaine infusions, respectively, and the uterine blood flow fell in a dose-dependent fashion 13.1% and 22.7%. Plasma norepinephrine levels rose in response to the 0.3 mg/kg cocaine infusion. These studies show that low doses of cocaine significantly reduce uterine blood flow in the pregnant baboon in a dose-dependent manner by increasing uterine vascular resistance.


[Effect of captopril on the level of arterial pressure and functional state of the kidney in symptomatic (renal) stable and malignant arterial hypertension].
Captopril was used in 21 patients with various forms of stable and malignant hypertension. In symptomatic hypertension the drug had a good antihypertensive effect. When applied in patients with essential hypertension caused by chronic diffuse glomerulonephritis or chronic pyelonephritis captopril neither increased pathological changes in the urine, nor inhibited renal function.


Use of the Selective Cytopheretic Device in Critically Ill Children.
Critically ill children with acute kidney injury (AKI) requiring continuous kidney replacement therapy (CKRT) are at increased risk of death. The selective cytopheretic device (SCD) promotes an immunomodulatory effect when circuit ionized calcium (iCa2+) is maintained at <0.40 mmol/l with regional citrate anticoagulation (RCA). In a randomized trial of adult patients on CRRT, those treated with the SCD maintaining an iCa2+ <0.40 mmol/l had improved survival/dialysis independence. We conducted a US Food and Drug Administration (FDA)-sponsored study to evaluate safety and feasibility of the SCD in 16 critically ill children. Four pediatric intensive care units (ICUs) enrolled children with AKI and multiorgan dysfunction receiving CKRT to receive the SCD integrated post-CKRT membrane. RCA was used to achieve a circuit iCa2+ level <0.40 mmol/l. Subjects received SCD treatment for 7 days or CKRT discontinuation, whichever came first. The FDA target enrollment of 16 subjects completed the study from December 2016 to February 2020. Mean age was 12.3 ± 5.1 years, weight was 53.8 ± 28.9 kg, and median Pediatric Risk of Mortality II was 7 (range 2-19). Circuit iCa2+ levels were maintained at <0.40 mmol/l for 90.2% of the SCD therapy time. Median SCD duration was 6 days. Fifteen subjects survived SCD therapy; 12 survived to ICU discharge. All ICU survivors were dialysis independent at 60 days. No SCD-related adverse events (AEs) were reported. Our data demonstrate that SCD therapy is feasible and safe in children who require CKRT. Although we cannot make efficacy claims, the 75% survival rate and 100% renal recovery rate observed suggest a possible favorable benefit-to-risk ratio.


High-dose-rate brachytherapy combined with long-term hormonal therapy for high-risk prostate cancer: results of a retrospective analysis.
High-dose-rate (HDR) brachytherapy combined with hormonal therapy (HTx), without the addition of external beam radiation therapy (EBRT) for high-risk prostate cancer was evaluated retrospectively. Between May 1995 and April 2002, 35 patients with prostate cancer [Stage > or = T2b (UICC 1997) or tumor grading=3 or prostate-specific antigen (PSA) level > or = 20 ng/mL] were treated with HDR brachytherapy combined with HTx. Most patients (74%) had two or more of these factors. All patients received Iridium-192 HDR brachytherapy with a total dose of 54 Gy/9 fractions/5 days (48 Gy/8 fractions/5 days for the first 6 cases) in one implant session. The median neoadjuvant HTx [luteinizing hormone-releasing hormone (LH-RH) agonist and antiandrogen] period was 7 months. The median adjuvant HTx (ATH) (LH-RH agonist) period was 40 months, and median follow-up was 57 months (range, 23-117 months). The 5-year actuarial biochemical control, local control, and disease-free rates were 62%, 96%, and 76% respectively. No patients experienced local and/or regional relapse without distant progression. The 5-year actuarial cause-specific survival and overall survival rates were 89% and 87%, respectively. The acute and late toxicity were moderate and well tolerated. HDR brachytherapy plus long-term HTx is at least as effective as conventional EBRT plus long-term HTx.


Shape from sound: evidence for a shape operator in the lateral occipital cortex.
A recent view of cortical functional specialization suggests that the primary organizing principle of the cortex is based on task requirements, rather than sensory modality. Consistent with this view, recent evidence suggests that a region of the lateral occipitotemporal cortex (LO) may process object shape information regardless of the modality of sensory input. There is considerable evidence that area LO is involved in processing visual and haptic shape information. However, sound can also carry acoustic cues to an object's shape, for example, when a sound is produced by an object's impact with a surface. Thus, the current study used auditory stimuli that were created from recordings of objects impacting a hard surface to test the hypothesis that area LO is also involved in auditory shape processing. The objects were of two shapes, rods and balls, and of two materials, metal and wood. Subjects were required to categorize the impact sounds in one of three tasks, (1) by the shape of the object while ignoring material, (2) by the material of the object while ignoring shape, or (3) by using all the information available. Area LO was more strongly recruited when subjects discriminated impact sounds based on the shape of the object that made them, compared to when subjects discriminated those same sounds based on material. The current findings suggest that activation in area LO is shape selective regardless of sensory input modality, and are consistent with an emerging theory of perceptual functional specialization of the brain that is task-based rather than sensory modality-based.


Bio-Efficacy of Diatomaceous Earth, Household Soaps, and Neem Oil against Spodoptera frugiperda (Lepidoptera: Noctuidae) Larvae in Benin.
Spodoptera frugiperda was first reported in Africa in 2016 and has since become a serious threat to maize/cereal production on the continent. Current control of the pest relies on synthetic chemical insecticides, which can negatively impact the environment and promote the development of resistance when used indiscriminately. Therefore, great attention is being paid to the development of safer alternatives. In this study, several biorational products and a semi-synthetic insecticide were evaluated. Two household soaps ("Palmida" and "Koto") and a detergent ("So Klin") were first tested for their efficacy against the larvae under laboratory conditions. Then, the efficacy of the most effective soap was evaluated in field conditions, along with PlantNeem (neem oil), Dezone (diatomaceous earth), and Emacot 19 EC (emamectin benzoate), in two districts, N'Dali and Adjohoun, located, respectively, in northern and southern Benin. The soaps and the detergent were highly toxic t second-instar larvae with 24 h lethal concentrations (LC50) of 0.46%, 0.44%, and 0.37% for So Klin, Koto, and Palmida, respectively. In field conditions, the biorational insecticides produced similar or better control than Emacot 19 EC. However, the highest maize grain yields of 7387 and 5308 kg/ha were recorded, respectively, with Dezone (N'Dali) and Emacot 19 EC (Adjohoun). A cost-benefit analysis showed that, compared to an untreated control, profits increased by up to 90% with the biorational insecticides and 166% with Emacot 19 EC. Therefore, the use of Palmida soap at 0.5% concentration, neem oil at 4.5 L/ha, and Dezone at 7.5 kg/ha could provide an effective, environmentally friendly, and sustainable management of S. frugiperda in maize.


[Enlargement of the upper mediastinum in thoracic radiography?].
The authors report a case of asymptomatic sternocostoclavicular hyperostosis in a 69-year-old patient. SAPHO syndrome is described and discussed.


Pneumococcal beta-lactam resistance due to a conformational change in penicillin-binding protein 2x.
Streptococcus pneumoniae is a life-threatening human pathogen that is increasingly resistant to a wide array of drugs. Resistance to beta-lactams, the most widely used antibiotics, is correlated with tens of amino acid substitutions in their targets; that is, the penicillin-binding proteins (PBPs), resulting from multiple events of recombination. To discriminate relevant substitutions from those that are incidental to the recombination process, we report the exhaustive characterization of all the mutations in the transpeptidase domain of PBP2x from the highly resistant strain 5204. A semi-automated method combining biochemical and microbiological approaches singled out 6 mutations of 41 (15%) that are essential for high level resistance. The hitherto uncharacterized I371T, R384G, M400T, and N605T together with the previously studied T338M and M339F account for nearly all the loss of affinity of PBP2x for beta-lactams. Most interestingly, I371T and R384G cause the conformational change of a loop that borders the entrance of the active site cavity, hampering antibiotic binding. For the first time all the mutations of a PBP relevant to beta-lactam resistance have been identified, providing new mechanistic insights. Most notable is the relationship between the decreased susceptibility to beta-lactams and the dynamic behavior of a loop.


SIMBA: using Kolb's learning theory in simulation-based learning to improve participants' confidence.
Simulation via Instant Messaging- Birmingham Advance (SIMBA) delivers simulation-based learning (SBL) through WhatsApp® and Zoom® based on Kolb's experiential learning theory. This study describes how Kolb's theory was implemented in practice during SIMBA adrenal session. SIMBA adrenal session was conducted for healthcare professionals and replicated Kolb's 4-stage cycle: (a) concrete experience-online simulation of real-life clinical scenarios, (b) reflective observation-discussion and Q&A following simulation, (c) abstract conceptualisation-post-session MCQs, and (d) active experimentation-intentions to implement the acquired knowledge in future practice. Participants' self-reported confidence levels for simulated and non-simulated cases pre- and post-SIMBA were analysed using Wilcoxon Signed-Rank test. Key takeaway and feedback were assessed quantitatively and qualitatively in a thematic analysis. Thirty-three participants were included in the analysis. A Wilcoxon signed-rank test showed that the SIMBA session elicited a statistically significant change in participants' self-reported confidence in their approach to Cushing's syndrome (Z = 3.873, p = 0.0001) and adrenocortical carcinoma (Z = 3.970, p < 0.0001). 93.9% (n = 31/33) and 84.8% (n = 28/33) strongly agreed/agreed the topics were applicable to their clinical practice and accommodated their personal learning style, respectively. 81.8% (n = 27/33) reported increase in knowledge on patient management, and 75.8% (n = 25/33) anticipated implementing learning points in their practice. SIMBA effectively adopts Kolb's theory to provide best possible experience to learners, highlighting the advantages of utilising social media platforms for SBL in medical education. The ability to conduct SIMBA sessions at modest cost internationally paves way to engage more healthcare professionals worldwide.


The Secondary Harms of Parental Substance Use on Children's Educational Outcomes: A Review.
Parental substance use, that is alcohol and illicit drugs, can have a deleterious impact on child health and wellbeing. An area that can be affected by parental substance use is the educational outcomes of children. Current reviews of the literature in the field of parental substance use and children's educational outcomes have only identified a small number of studies, and most focus on children's educational attainment. To grasp the available literature, the method from Arksey and O'Malley (2005) was used to identify literature. Studies were included if they were empirical, after 1950, and focused on children's school or educational outcomes. From this, 51 empirical studies were identified which examined the relationship between parental alcohol and illicit drug use on children's educational outcomes. Five main themes emerged which included attainment, behavior and adjustment, attendance, school enjoyment and satisfaction, academic self-concept, along with other miscellaneous outcomes. This paper highlights the main findings of the studies, the gaps in the current literature, and the challenges presented. Recommendations are made for further research and interventions in the areas of parental substance use and child educational outcomes specifically, but also for broader areas of adversity and child wellbeing.


Horizontal transmission of Campylobacter jejuni amongst broiler chicks: experimental studies.
Horizontal transmission of Campylobacter jejuni was investigated in campylobacter-free broiler chicks. One hundred and twenty chicks housed individually, were provided with water containing 10(2)-10(9) c.f.u./ml C. jejuni. Colonization was rapid [47 of 73 (64%) positive cloacal cultures within 3 days and 65 of 73 (89%) within 7 days], dependent on C. jejuni strain and inoculum size but independent of chick age. Groups of 5-24 chicks in isolators were exposed to C. jejuni-contaminated water or colonized seeder chicks. Transmission occurred in 2-7 days concurrent with a gradual increase of C. jejuni in litter, water and feed. Environmental samples were culture-negative within 3 days following removal of colonized chicks. Treatment of 1-day-old chicks with adult caecal microbiota did not affect colonization. Treated and control chicks were all C. jejuni-positive within 3 days of seeder challenge.


Spruce versus Arabidopsis: different strategies of photosynthetic acclimation to light intensity change.
The acclimation of higher plants to different light intensities is associated with a reorganization of the photosynthetic apparatus. These modifications, namely, changes in the amount of peripheral antenna (LHCII) of photosystem (PS) II and changes in PSII/PSI stoichiometry, typically lead to an altered chlorophyll (Chl) a/b ratio. However, our previous studies show that in spruce, this ratio is not affected by changes in growth light intensity. The evolutionary loss of PSII antenna proteins LHCB3 and LHCB6 in the Pinaceae family is another indication that the light acclimation strategy in spruce could be different. Here we show that, unlike Arabidopsis, spruce does not modify its PSII/PSI ratio and PSII antenna size to maximize its photosynthetic performance during light acclimation. Its large PSII antenna consists of many weakly bound LHCIIs, which form effective quenching centers, even at relatively low light. This, together with sensitive photosynthetic control on the level of cytochrome b6f complex (protecting PSI), is the crucial photoprotective mechanism in spruce. High-light acclimation of spruce involves the disruption of PSII macro-organization, reduction of the amount of both PSII and PSI core complexes, synthesis of stress proteins that bind released Chls, and formation of "locked-in" quenching centers from uncoupled LHCIIs. Such response has been previously observed in the evergreen angiosperm Monstera deliciosa exposed to high light. We suggest that, in contrast to annuals, shade-tolerant evergreen land plants have their own strategy to cope with light intensity changes and the hallmark of this strategy is a stable Chl a/b ratio.


The RNA editing enzyme ADAR modulated by the rs1127317 genetic variant diminishes EGFR-TKIs efficiency in advanced lung adenocarcinoma.
The adenosine-to-inosine (A-to-I) RNA editing controlled by the editing genes are known to diversify transcripts in human. Aberrant A-to-I editing due to dysregulation of the editing genes are involved in cancer development. However, it is still largely unclear how single nucleotide polymorphisms (SNPs) in the A-to-I editing genes confer to recurrence and/or drug resistance of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) therapy in non-small-cell lung cancer (NSCLC). In this study, we systematically evaluated and validated the role of twenty-eight potential functional genetic variants in four A-to-I editing genes (ADAR, ADARB1, ADARB2 and AIMP2) in prognosis of NSCLC patients receiving EGFR-TKIs. We identified the ADAR rs1127309, rs1127317, and rs2229857 SNPs markedly contributing to prognosis of patients treated with EGFR-TKIs. Interestingly, SNP rs1127317 locating in the ADAR 3'-untranslated region regulates gene expression in an allele-specific manner via modulating binding of miR-454-5p in cells. In support of this, patients with the rs1127317 C allele correlated with elevated ADAR expression in tumors showed profoundly shorten survival after EGFR-TKIs therapy compared to the A allele carriers. Silencing of ADAR notably enhanced gefitinib sensitivities of NSCLC cells. Our findings highlight the importance of the A-to-I RNA editing in drug resistance and nominate ADAR as a potential therapeutic target for unresectable NSCLC.


Potential metabolic monitoring indicators of suicide attempts in first episode and drug naive young patients with major depressive disorder: a cross-sectional study.
Major depressive disorder is an ordinary mental disorder, and suicide is considered to be a major concern among patients with MDD. Previous studies focused on the relationship between suicide attempts and metabolism in elderly patients with MDD, while ignore the young people. The aim of this study is to find the potential relationship between suicide attempts and metabolism in young patients with MDD to find a way to prevent and ultimately reduce suicide in young patients with MDD. Cross-sectional design was employed in the study.740 patients aged between 18 and 45 years old with MDD had been consecutively recruited in this study between 2011 and 2017, 128 of whom had suicide attempts. Their serum samples used to monitor fasting blood glucose, serum lipids as well as socio-demographic characteristics were collected. Besides, some clinical scales were also employed to measure symptoms of anxiety, depression and other conditions. This study indicated that compared with non-suicide attempters, suicide attempters in young patients with MDD showed higher levels of FBG, TC, LDL-C (all p < 0.05) and lower levels of HDL-C(p < 0.001). Further logistic regression analysis suggested that suicide attempts were associated with increased FBG, decreased HDL-C, the course of disease, HAMD scores and obvious anxiety. Suicide attempts in young patients with MDD may be predicted by metabolic levels in the future. And our findings suggested that the level of FBG and HDL-C can be promising biomarkers to predict the occurrence of this event.


Infrared thermography of cutaneous melanoma metastases.
Differentiating melanoma metastasis from benign cutaneous lesions currently requires biopsy or costly imaging, such as positron emission tomography scans. Melanoma metastases have been observed to be subjectively warmer than similarly appearing benign lesions. We hypothesized that infrared (IR) thermography would be sensitive and specific in differentiating palpable melanoma metastases from benign lesions. Seventy-four patients (36 females and 38 males) had 251 palpable lesions imaged for this pilot study. Diagnosis was determined using pathologic confirmation or clinical diagnosis. Lesions were divided into size strata for analysis: 0-5, >5-15, >15-30, and >30 mm. Images were scored on a scale from -1 (colder than the surrounding tissue) to +3 (significantly hotter than the surrounding tissue). Sensitivity and specificity were calculated for each stratum. Logistical challenges were scored. IR imaging was able to determine the malignancy of small (0-5 mm) lesions with a sensitivity of 39% and specificity of 100%. For lesions >5-15 mm, sensitivity was 58% and specificity 98%. For lesions >15-30 mm, sensitivity was 95% and specificity 100%, and for lesions >30 mm, sensitivity was 78% and specificity 89%. The positive predictive value was 88%-100% across all strata, and the negative predictive value was 95% for >15-30 mm lesions and 80% for >30 mm lesions. Malignant lesions >15 mm were differentiated from benign lesions with excellent sensitivity and specificity. IR imaging was well tolerated and feasible in a clinic setting. This pilot study shows promise in the use of thermography for the diagnosis of malignant melanoma with further potential as a noninvasive tool to follow tumor responses to systemic therapies.


The Behavioral Assessment Screening Tool for Mobile Health (BASTmHealth): Development and Compliance in 2 Weeks of Daily Reporting in Chronic Traumatic Brain Injury.
To develop and evaluate the feasibility of a short form of the Behavioral Assessment Screening Tool (BASTmHealth) for high frequency in situ self-reported assessment of neurobehavioral symptoms using mobile health technology for community-dwelling adults with traumatic brain injury (TBI). Prospective, repeated-measures study of mHealth assessment of self-reported neurobehavioral symptoms in adults with and without a lifetime history of TBI over a 2-week period. Community. Community-dwelling adults with (n=52) and without (n=12) a lifetime TBI history consented to the study (N=64). Not applicable. BASTmHealth subscales (2-items each): negative affect, fatigue, executive function, substance abuse, impulsivity; feasibility measured via compliance (assessments assigned/assessments completed) and participant-reported usability. We developed the 10-item BASTmHealth as a screener for high frequency in situ self-reported assessment of neurobehavioral symptoms leveraging mHealth. Compliance for 2 weeks of BASTmHealth supports its feasibility. Fifty-six of 64 participants (87.5%) who completed baseline assessments completed the 2 weeks of daily assessments; all 8 participants who did not complete ecological momentary assessment had a history of TBI. Overall compliance was 81.4% (496 completed of 609 assigned assessments) among all 52 participants with TBI and 96.7% (494 completed of 511 assigned assessments) among the 44 who completed any daily measures, compared with 91.8% (135 completed of 147 assigned assessments) among those with no TBI history. Participants thought the daily surveys were easy to understand and complete and the number of prompts were reasonable. Conducting daily high-frequency in situ self-reported assessment of neurobehavioral symptoms using the BASTmHealth is feasible among individuals with and without a lifetime history of TBI. Developing and evaluating self-reported assessments for community-based assessment is a critical step toward expanding remote clinical monitoring systems to improve post-TBI outcomes.


Estimation of transport parameters of phenolic compounds and inorganic contaminants through composite landfill liners using one-dimensional mass transport model.
One-dimensional (1D) advection-dispersion transport modeling was conducted as a conceptual approach for the estimation of the transport parameters of fourteen different phenolic compounds (phenol, 2-CP, 2-MP, 3-MP, 4-MP, 2-NP, 4-NP, 2,4-DNP, 2,4-DCP, 2,6-DCP, 2,4,5-TCP, 2,4,6-TCP, 2,3,4,6-TeCP, PCP) and three different inorganic contaminants (Cu, Zn, Fe) migrating downward through the several liner systems. Four identical pilot-scale landfill reactors (0.25 m3) with different composite liners (R1: 0.10+0.10 m of compacted clay liner (CCL), L(e) = 0.20 m, k(e) = 1 × 10(-8) m/s, R2: 0.002-m-thick damaged high-density polyethylene (HDPE) geomembrane overlying 0.10+0.10 m of CCL, L(e) = 0.20 m, k(e) = 1 × 10(-8) m/s, R3: 0.002-m-thick damaged HDPE geomembrane overlying a 0.02-m-thick bentonite layer encapsulated between 0.10+0.10 m CCL, L(e) = 0.22 m, k(e) = 1 × 10(-8) m/s, R4: 0.002-m-thick damaged HDPE geomembrane overlying a 0.02-m-thick zeolite layer encapsulated between 0.10+0.10 m CCL, L(e) = 0.22 m, k(e) = 4.24 × 10(-7) m/s) were simultaneously run for a period of about 540 days to investigate the nature of diffusive and advective transport of the selected organic and inorganic contaminants. The results of 1D transport model showed that the highest molecular diffusion coefficients, ranging from 4.77×10(-10) to 10.67 × 10(-10)m2/s, were estimated for phenol (R4), 2-MP (R1), 2,4-DNP (R2), 2,4-DCP (R1), 2,6-DCP (R2), 2,4,5-TCP (R2) and 2,3,4,6-TeCP (R1). For all reactors, dispersion coefficients of Cu, ranging from 3.47 × 10(-6) m(2)/s to 5.37 × 10(-2) m2/s, was determined to be higher than others obtained for Zn and Fe. Average molecular diffusion coefficients of phenolic compounds were estimated to be about 5.64 × 10(-10) m2/s, 5.37 × 10(-10) m2/s, 2.69 × 10(-10) m2/s and 3.29 × 10(-10) m2/s for R1, R2, R3 and R4 systems, respectively. The findings of this study clearly indicated that about 35-50% of transport of phenolic compounds to the groundwater is believed to be prevented with the use of zeolite and bentonite materials in landfill liner systems.


Insulin resistance in non-insulin-dependent diabetes mellitus is associated with microalbuminuria independently of ambulatory blood pressure.
Microalbuminuria in both insulin-dependent (IDDM) and non-insulin-dependent diabetes mellitus (NIDDM) is a marker for insulin resistance. Microalbuminuria is also associated with hypertension, itself an insulin-resistant state. Therefore, in order to examine the independent relationships of microalbuminuria with blood pressure and insulin resistance, we measured ambulatory blood pressure (Takeda TM-2420), insulin resistance (modified Harano method), and urinary albumin excretion rate (overnight urine collection) in 36 subjects with NIDDM. Albumin excretion correlated with 24-h systolic blood pressure (r = 0.49, p = 0.003), and insulin sensitivity (r = -0.39, p = 0.007). Microalbuminuric subjects had reduced insulin sensitivity compared with normoalbuminuric subjects [Mean (SD) 2.95 (0.33) versus 4.67 (0.56) ml.kg-1.min-1; p = 0.013]. In multivariate analysis including ambulatory blood pressure and insulin resistance, urinary albumin excretion was associated primarily with insulin resistance, with smaller contributions from glycated hemoglobin and male gender. These data suggest that microalbuminuria in NIDDM, although associated with hypertension, is also independently associated with insulin resistance.


p21WAF1 mediates the IL-15-induced migration and invasion of human bladder cancer 5637 cells via the ERK1/2/NF-κB/MMP-9 pathway.
Interleukin-15 (IL-15) functions as a key regulator for the proliferation, differentiation, and activation of lymphocytes. However, the role of IL-15 in cancer biology is not yet understood. In the present study, IL-15 treatment stimulated the wound-healing migration and invasion of bladder cancer 5637 cells, without altering the proliferation of the cells. Treatment of 5637 cells with IL-15 resulted in the promotion of the MMP-9 expression and the activation of NF-κB binding, which is a functional transcription factor that activates MMP-9 expression. In addition, IL-15 induced the activation of ERK1/2. ERK inhibitor U0126 suppressed the migration, invasion, MMP-9 expression, and NF-κB binding activity in IL-15-treated 5637 cells. In addition, the cell-cycle inhibitor p21WAF1 was induced by the addition of IL-15. Finally, the siRNA-mediated knockdown of p21WAF1 attenuated the IL-15-induced stimulation of migration, invasion, ERK1/2 activation, MMP-9 expression, and NF-κB binding activation in 5637 cells. Our results suggest that p21WAF1 regulated NF-κB-mediated MMP-9 expression via the activation of ERK1/2, which resulted in the migration and invasion of 5637 cells treated with IL-15. These unexpected results suggest a potential role for IL-15 with respect to the progression of bladder cancer.


Salvage Radiosurgery for Recurrent Supratentorial Primitive Neuroectodermal Tumors: A Single Institutional Series and Review of the Literature.
Supratentorial primitive neuroectodermal tumor is a rare, aggressive intrinsic brain tumor with limited treatment options for recurrent disease. SRS as a treatment modality in the recurrent setting was investigated. A retrospective review of 8 patients treated with SRS for local or distant recurrence of supratentorial PNET from 1999 to 2014 was conducted. Thirty-six tumors were treated in 15 sessions in 8 patients. The median patient age was 22.5 (interquartile range [IQR], 14.75-43.5 years) with a median 21-month period from diagnosis until SRS (IQR, 16-23.75 months). The median prescription isodose volume was 1.85 cm3 (IQR, 1.85-7.02 cm3); median tumor margin dose was 18 Gy (IQR 14-20 Gy); and median isocenters was 2 (range 1-13). No patients experienced adverse radiation effects. All but 1 patient died, and the median overall survival was 32 months (IQR, 26.75-53.5 months) with median overall survival following SRS of 9.5 months (IQR, 5.25-30 months). Univariate analysis failed to demonstrate a statistically significant association between age, number of gamma knife treatments, interval to gamma knife, and margin radiation dose with overall survival. This series supports the use of SRS in patients with recurrent supratentorial PNET following multimodal therapy.


CT and MR appearance of cervical acrylic struts.
A patient sustained trauma to the cervical spine and underwent surgical fusion that included the use of methyl methacrylate struts. The CT and MR appearances of these acrylic struts are described.


Synthesis and drug delivery properties of Ibuprofen-Cellulose nanofibril system.
The Ibuprofen-Cellulose nanofibril (IBU-CNF) drug delivery system was prepared by esterification of Ibuprofen (IBU) and cellulose nanofibril (CNF) with isopropyl acetate as the solvent and sulfuric acid as the catalyst. The results showed that IBU was successfully grafted on to the CNF molecular chain and the crystal structure of CNF did not change. Moreover, the natural three-dimensional network structure was maintained to a large extent. The maximum drug loading of IBU-CNF was 151.38 mg/g. In vitro drug release showed that IBU-CNF was pH-responsive and could be released continuously over 24 h. The cumulative release rate was approximately 90% under alkaline conditions but was low under acidic conditions. UV-visible spectra revealed that IBU retained its chemical activity after in vitro release.


Evaluation of sex hormone profile and semen parameters in acromegalic male patients.
To investigate the changes in semen quality and bioavailable testosterone concentrations in acromegalic male patients according to their disease activity and compare them with patients with non-functional pituitary adenoma (NFA) and healthy controls (HC). Twenty-four acromegalic patients with active disease, 22 acromegalic patients in remission, 10 HCs, and 10 patients with NFA were included. Total and calculated bioavailable testosterone concentrations were lower in patients with pituitary disease. Patients with acromegaly had more severely impaired total testosterone levels and semen parameters in comparison to HCs and patients with NFA. The degree of impairment was more prominent in acromegalic patients with active disease than acromegalic patients in remission. Acromegalic patients in remission had residual impairments in both semen quality and testosterone concentrations. Patients with NFA had the lowest concentrations of calculated bioavailable testosterone, followed by acromegalic patients with active disease and acromegalic patients in remission. Increasing growth hormone (GH) levels were found to be associated with both more severely impaired semen quality and androgen concentrations. Growth hormone hypersecretion can disturb reproductive biology and thereof semen quality. The reduction in semen quality and androgen levels may not fully recover upon disease control. Clinicians should be aware of the increased risk of impaired semen parameters and reduced total/bioavailable levels in acromegalic patients, especially in the setting of active disease.


Human sperm motility in a microgravity environment.
Background and Aims: We carried out clinostat and parabolic flight experiments to examine the effects of a microgravity (µG) environment on human sperm motility. Methods: Semen samples were obtained manually from 18 healthy men (aged 27.4 ± 5.4 years) who had given their informed consent. In clinostat experiments, samples that were left stationary were used as a stationary control. Samples rotated vertically and horizontally were used as a rotation control and a clinostat rotation, respectively. In parabolic flight experiments using a jet plane, sperm motility was compared for each parameter at µG, 1G and 2G. The state of 1G during the flight was used as a control. Sperm motility was determined using an automatic motility analyzer HT-M2030 in a microgravity environment. Results: All parameters of sperm motility tended to be lower in clinostat rotation compared with rotation control at both low-speed and high-speed, but the differences were not statistically significant. In parabolic flight, sperm motility and parameters of linear movement were decreased (P < 0.05). There was no significant difference between µG and 2G, but sperm motility was significantly decreased at µG than at 1G. Conclusions: Our findings suggest that sperm motility is reduced under µG. (Reprod Med Biol 2005; 4: 161-168).


Inhibition and stimulation effects in communities of wood decay fungi: exudates from colonized wood influence growth by other species.
The effects of exudates from uncolonized and from partly decayed beech wood on the extension rates of 16 later stage decay fungi were investigated. The partly decayed wood had been colonized by the pyrenomycete Eutypa spinosa, or the basidiomycetes Fomes fomentarius, Stereum hirsutum, and Trametes versicolor, all known as common early decay agents in European beech forests. Sterilized wood pieces were placed onto 0.5% malt agar, opposite to small agar plugs containing the test fungi. The latter showed very variable and species-specific growth responses to the various wood types. The presence of uncolonized wood stimulated extension rates in many species, whereas the four previously decayed wood types had variable stimulatory or inhibitory effects. Wood decayed by S. hirsutum resulted in reduced extension rate, delayed growth, or total inhibition in the majority of species, thus it is suggested that this species uses secondary metabolites in a defensive strategy. A single species was, however, stimulated in the presence of S. hirsutum-decayed wood. In contrast, the presence of wood decayed by F. fomentarius was stimulatory to 45% of the species. The other previously decayed wood types generally resulted in more variable responses, depending upon species. The results are discussed in an ecological context and it is suggested that the exudates from the partly decayed wood that are responsible for the reported effects may function as infochemicals, structuring microbial communities in wood.


Influence of route decision-making and experience on human path integration.
Path integration refers to a process of integrating information regarding self-motion to estimate one's current position and orientation. Here we reported two experiments designed to investigate whether, and if so, how human path integration could be influenced by route decision-making and previous experience. Using head-mounted display virtual reality and hallway mazes, we asked participants to travel along several hallways and then to directly return to the starting point, namely a path completion task. We created an active condition in which the participants had the opportunity to voluntarily select the structure of outbound paths, and a passive condition in which they followed the outbound paths chosen by others. Each participant was required to take part in the study on two consecutive days, and they performed the task under different (in Experiment 1) or the same conditions (in Experiment 2) on these two days. The results of both experiments revealed a facilitation effect of route decision-making on the participants' performance on the first day. The results also revealed that both their performance and path selection strategies on the second day were subject to their experience obtained from the first day. Collectively, these findings suggest that human path integration may be improved by having the opportunity to make decisions on the structure of outbound paths and/or more experience with the task.


Fasciola hepatica saposin-like protein-2-based ELISA for the serodiagnosis of chronic human fascioliasis.
An indirect enzyme-linked immunosorbent assay (ELISA) was developed and evaluated for its diagnostic ability to detect human IgG antibodies against Fasciola hepatica saposin-like protein-2. The assay was compared with an indirect ELISA with excretory-secretory products (FhES) from adult F. hepatica. In an analysis of the sera of 37 patients infected with F. hepatica, 40 patients with other parasitic infections, and 50 healthy controls, the sensitivity of both ELISA assays was 100%. However, the FhSAP2-based ELISA was more specific (95.6%) than the FhES-ELISA (91.9%). These results demonstrated that FhSAP2 can be used in the serodiagnosis of chronic human fascioliasis with the additional advantage of being relatively cheap and easy to produce. Studies are in progress to evaluate this FhSAP2-ELISA assay in a large-scale prevalence surveys in endemic areas.


Non-traumatic emergency abdominal surgery in nonagenarian patients: a retrospective study.
The primary aim of this study was to evaluate the 30-day survival of nonagenarian patients who underwent non-traumatic emergency abdominal surgery. Other aims were: 90-day and 12-month survival rates, the postoperative complications rate, the impact of the emergency operation on postoperative functional status, the accuracy of the P-POSSUM in predicting 30-day postoperative mortality and changes in care services after surgery. This was a retrospective cohort study of nonagenarian patients who underwent non-traumatic emergency abdominal surgery between January 2010 and June 2017. Patients were divided in two groups according to the 30-day survival status to compare the distribution of patients' characteristics and postoperative outcomes. Overall survival was estimated using the Kaplan-Meier method. To assess the accuracy of P-POSSUM to predict 30-day mortality, a receiver operating characteristic curve and the Hosmer-Lemeshow goodness of fit test were used. 85 nonagenarian patients were enrolled in this study; of these, 27 (31.8%) died within 30 days. The Kaplan-Meier curve showed a rapid decline in survival over the first 30 postoperative days, followed by a more gradual reduction during the rest of the first year. The majority of patients (92.6%) who died within 30 days experienced a medical complication, with a preponderance of respiratory failure (48.2%) and multiple organ failure (33.3%). In the surviving patients, the postoperative functional status had worsened, and 64.2% of patients did not return to their original housing situation or were institutionalized. The accuracy of P-POSSUM in predicting 30-day mortality in nonagenarian patients was poor. This study may help doctors convey the postoperative risks of morbidity and mortality, and also to adequately inform relatives about the possible adverse discharge destination of surviving nonagenarian patients with a consequent increase in care needs.


Axonal neuropathy associated with interferon-alpha treatment for hepatitis C: HLA-DR immunoreactivity in Schwann cells.
A 44-year-old man developed a peripheral neuropathy during treatment with interferon-alpha for chronic hepatitis C. The onset was insidious, beginning symmetrically in the hands with paresthesia. Neurophysiological investigation revealed a predominantly sensory axonal neuropathy. A sural nerve biopsy confirmed primary axonal damage. Immunofluorescence studies showed increased expression of HLA-DR molecules prevalently on Schwann cells of non-myelin-forming type.


Prenatal diagnosis of hypoplastic left heart syndrome.
Over a 21-month period 200 fetal echocardiographic studies were performed on pregnancies at high risk for congenital heart disease referred to the NSW Fetal Echocardiography Service. Four cases of hypoplastic left heart syndrome were diagnosed in-utero during this period. These cases demonstrated the heterogeneity of this lesion, its known association with other defects and chromosomal anomalies, and evidence of in-utero evolution. Hypoplastic left heart syndrome is reliably diagnosed by fetal echocardiography. This lesion is heterogenous and may evolve beyond the first trimester. Careful attention to ventricular function, endocardial echoes and Doppler flow may assist with diagnosis.