A new look at energy conversion in ectothermic and endothermic animals.
In this review I offer a solution to the problem why endotherm populations appear to be so inefficient in converting food energy into body substance despite the fact that individual endotherms are just as 'efficient' in this respect as individual ectotherms. Calculated for individuals of half the adult mass both ectotherms and endotherms convert about the same proportion of food energy into somatic growth although for a given body mass the latter expend about 10 times more aerobic power than the former. On the other hand, early in life, during the period of maximum growth, ectotherms channel a 2-3 times greater percentage of metabolic energy into growth than endotherms. Even greater becomes the difference between these two groups if we consider the relative cost of reproduction. It can be shown that, weight by weight, nematodes, fish, birds and mammals require almost the same amount of energy for the production of offspring-, roughly 250 kJ per day and kg of eggs, hatchlings or litter. However, whereas the cost of producing offspring represents only 2%-6% of the total metabolizable energy of an endotherm, a fish has to spend 35%, a nematode nearly everything it has for this purpose. This may explain the finding by Humphreys (1979) and others that in nature the production, 'efficiencies' of endotherm populations appear to be at least one order of magnitude lower than those of ectotherm populations. However, rather than calling endotherms less 'efficient' energy converters, I suggest that by increasing total metabolic power more than ten-fold but keeping the energy cost of reproduction constant, this group of animals achieved emancipation from the burden of reproduction. Conversely, ectotherms have to channel a much greater proportion of metabolic power into reproduction because only in this way are they able to fit their low-rate life cycle schedules into the ecological schedules of the environment.


Global gene expression profiling of blast lung injury of goats exposed to shock wave.
Blast lung injury (BLI) is the most common damage resulted from explosion-derived shock wave in military, terrorism and industrial accidents. However, the molecular mechanisms underlying BLI induced by shock wave are still unclear. In this study, a goat BLI model was established by a fuel air explosive power. The key genes involved in were identified. The goats of the experimental group were fixed on the edge of the explosion cloud, while the goats of the control group were 3 km far away from the explosive environment. After successful modeling for 24 h, all the goats were sacrificed and the lung tissue was harvested for histopathological observation and RNA sequencing. Gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) analysis were performed to identify the main enriched biological functions of differentially expressed genes (DEGs). Quantitative real-time polymerase chain reaction (qRT-PCR) was used to verify the consistency of gene expression. Of the sampled goat lungs, 895 genes were identified to be significantly differentially expressed, and they were involved in 52 significantly enriched GO categories. KEGG analysis revealed that DEGs were highly enriched in 26 pathways, such as cytokine-cytokine receptor interaction, antifolate resistance, arachidonic acid metabolism, amoebiasis and bile secretion, JAK-STAT, and IL-17 signaling pathway. Furthermore, 15 key DEGs involved in the biological processes of BLI were confirmed by qRT-PCR, and the results were consistent with RNA sequencing. Gene expression profiling provide a better understanding of the molecular mechanisms of BLI, which will help to set strategy for treating lung injury and preventing secondary lung injury induced by shock wave.


[Auditory and vestibular findings in Fabry disease: a study of 25 patients].
Fabry disease (FD, OMIM 301500) is an X-linked lysosomal storage disorder due to deficient activity of the enzyme alpha-galactosidase A. Males and females exhibit severe organ involvement. The high incidence of otological symptoms was recently reported. Monocentric and retrospective study of twenty-five patients with FD (13 families; seven males and 18 females). The patients underwent audiological assessment before initiation and during enzyme replacement therapy. We also analysed neurologic heart and kidney status. Twenty patients (80%; 13 females and seven males) complained of otologic symptoms. Audiological evaluation showed a sensorineural hearing loss in 17 patients, bilateral in 16 out of them. Vestibular examination showed a functional impairment in two patients (one female, one male). Correlations were found between hearing loss and either kidney disease (73,3%), neurological complications (100%) and cardiomyopathy (80%). Fourteen patients (56%; seven females, seven males) received enzyme replacement therapy. Improvement or stabilization of the audiological evaluation was reported in seven patients, whereas worsening was observed in three patients. This study confirms the high frequency of audiological involvements in females and males with FD. Our analysis suggests that the frequency of hearing loss is increased in the presence of renal or neurologic involvement or cardiomyopathy. There is no clinically significant efficacy of enzyme replacement therapy on hearing function. Although the pathophysiology remains unknown, a vascular mechanism responsible of the inner ear involvement seems to be privileged.


Late intravenous immunoglobulin treatment in patients with Kawasaki disease.
To evaluate the effectiveness of intravenous immunoglobulin (IVIG) treatment of Kawasaki disease ≥10 days after illness onset. We selected patients initially treated with IVIG on days 11 to 20 in the database of the 20th nationwide survey in Japan. We then selected pair-matched control subjects of the same gender and age, who were initially treated with IVIG on days 4 to 8 with the same dose at the same institutions. We compared the proportions of additional treatments and coronary artery lesions (CALs) between the groups. We also compared fractional changes in various laboratory data before and after IVIG. Fractional change was defined as follows: (Y - X)/X, in which X represents the data before treatment and Y the data after treatment. One hundred fifty patients (75 pairs) were studied. The proportion of patients who received additional treatments among those given initial IVIG after days 10 was slightly lower than those treated earlier (12% vs 16%). The fractional changes in the white blood cell count, % neutrophils, and C-reactive protein were similar. Among all patients, the proportions of CALs during the convalescent phase were significantly higher in the late than in the early group (27% vs 1%). Among patients who had not developed CALs before initial treatment, the proportions with CALs during the acute phase were similar (8% vs 8%). IVIG treatment ≥10 days after illness onset achieves resolution of inflammation but was found to be insufficient for preventing CALs.


Understanding the effect of the membrane-mimetic micelles on the interplay between α-synuclein and Cu(II)/Cu(I) cations.
α-Synuclein (αS) is a presynaptic protein whose aggregates are considered as a hallmark of Parkinson's disease (PD). Although its physiological function is still under debate, it is widely accepted that its functions are always mediated by its interaction with membranes. The association of αS with phospholipid membranes occurs concomitant to its folding from its monomeric, unfolded state towards an antiparallel amphipathic α-helix. Besides this, copper ions can also bind αS and modify its aggregation propensity. The effect of Cu(II) and Cu(I) on the lipid-αS affinity and on the structure of the membrane-bound αS have not yet been studied. This knowledge is relevant to understand the molecular pathogenesis of PD. Therefore, we have here studied the affinities between Cu(II) and Cu(I) and the micelle-bound αS, as well as the effect of these cations on the structure of micelle-bound αS. Cu(II) or Cu(I) did not affect the α-helical structure of the micelle-bound αS. However, while Cu(I) binds at the same sites of αS in the presence or in the absence of micelles, the micelle-bound αS displays different Cu(II) binding sites than unbound αS. In any case, sodium docecyl sulphate -micelles reduce the stability of the αS complexes with both Cu(II) and Cu(I). Finally, we have observed that the micelle-bound αS is still able to prevent the Cu(II)-catalysed oxidation of neuronal metabolites (e.g. ascorbic acid) and the formation of reactive oxygen species, thus this binding does not impair its biological function as part of the antioxidant machinery.


Antidromic activation of rat dorsomedial hypothalamic neurons from locus coeruleus and median eminence.
In rats anesthetized with urethane, single unit activity was recorded in the hypothalamic dorsomedial nucleus (DMH) to obtain antidromic response to stimulation of locus coeruleus (LC) and median eminence (ME). Ninety-two cells were activated antidromically from LC and/or ME. Antidromic latencies to LC stimulation ranged from 7 to 39 msec and those to ME stimulation ranged from 5 to 20 msec. Approximately 13% of the neurons recorded revealed antidromic responses simultaneously from LC and ME, and they were found to bifurcate near the soma. The majority of DMH neurons projecting to LC alone were not spontaneously active, while those projecting to ME tended to discharge spontaneously.


Acutely Trapped Ventricle: Clinical Significance and Benefit from Surgical Decompression.
Focal ventricular obstruction--trapped ventricle--results in cerebrospinal fluid accumulation, mass effect and possible clinical deterioration. There are no systematic studies on the benefit of surgical decompression in adults. We reviewed patients admitted with acutely trapped ventricle on brain imaging to assess their prognosis and the effect of surgical intervention on 30-day mortality. Of the 392 patients with trapped ventricle, the most common causes were brain tumor (45%), intracerebral hemorrhage (ICH) (20%), and subdural hematoma (SDH) (14%). Lateral ventricle trapping accounted for 97% of cases. Two hundred and twenty-one patients (56%) received a surgical intervention for trapped ventricle or its causes; 126 (83%) were treated with craniotomy, 26 (17%) with craniectomy, 30 (14%) with external ventricular drain (EVD) alone, 23 (10%) with ventriculoperitoneal shunt alone, and 16 (7%) with endoscopic fenestration of the septum pellucidum. Surgical intervention was associated with mortality reduction from 95% (n = 54) to 48% (n = 11) in the ICH group, from 47% (n = 27) to 12% (n = 15) in the tumor group and from 90% (n = 18) to 20% (n = 7) in the SDH group (p < 0.001 for all comparisons). Univariate logistic analysis showed that surgical intervention and tumor etiology were associated with decreased mortality while age, ICH etiology, intraventricular hemorrhage, midline shift, and anticoagulation were associated with increased mortality. On multivariate logistic regression, surgical intervention remained associated with decreased mortality (p < 0.0001; OR 0.20, 95% CI 0.09-0.42). On subgroup analysis of the ICH cohort, surgical intervention was also associated with decreased mortality (p = 0.028). Neurosurgical intervention for decompression in patients with trapped ventricle can have a measurable beneficial effect on early mortality.


[Evaluation of processing suitability of bread cereals in official responsibility].
In the annual national survey ('Besondere Ernteermittlung') the quality of German cereals was analysed. The samples for this approach were collected from statistically selected fields. One of the analysed parameters was the content of mycotoxins. Thus, it was possible to get an area-wide survey of the content of mycotoxins under natural growing conditions. In 2003 a total number of 974 samples were analysed consisting of wheat, rye and barley samples. A special mode of choosing the wheat samples ensured also a statistically validated result for the federal states of Germany. In the year 2003 the content of the mycotoxins DON and ZEA in wheat and rye samples was lower than in 2002 referred to the median. On the other hand the frequency of detection of DON was not reduced. In barley, which was analysed for the first time in this kind of study, the level of DON was in between the levels of wheat and rye.


Brain-specific proteins in the occipital cortex of rats housed in enriched and impoverished environments.
The occipital cortex was dissected from the brain of rats housed in either enriched or impoverished environment for four weeks. In environmentally enriched rats the weight of occipital cortex was found to be increased 5.7%, compared to environmentally impoverished rats, and the amount of protein was increased 6.0%. The amount of six nervous system-specific proteins was measured by crossed immunoelectrophoresis. Synaptin increased 4.7%, D3 increased 8.3%, and D1 increased 9.6%, whereas D2 was not significantly increased. Compared to D2, D3 and D1 were still increased significantly, although all were present in synaptosomal membrane fractions. The protein S-100 was increased 3.4% and the neuronal protein 14-3-2 was increased 12.2% for the cathodal component whereas the anodal component was not increased. The results were interpreted as representing delayed development of environment-dependent neurons in the environmentally impoverished rats.


Prediction of fluid flow in porous media by sparse observations and physics-informed PointNet.
We predict steady-state Stokes flow of fluids within porous media at pore scales using sparse point observations and a novel class of physics-informed neural networks, called "physics-informed PointNet" (PIPN). Taking the advantages of PIPN into account, three new features become available compared to physics-informed convolutional neural networks for porous medium applications. First, the input of PIPN is exclusively the pore spaces of porous media (rather than both the pore and grain spaces). This feature diminishes required computer memory. Second, PIPN represents the boundary of pore spaces smoothly and realistically (rather than pixel-wise representations). Third, spatial resolution can vary over the physical domain (rather than equally spaced resolutions). This feature enables users to reach an optimal resolution with a minimum computational cost. The performance of our framework is evaluated by the study of the influence of noisy sensor data, pressure observations, and spatial correlation length.


FASTory assembly line power consumption data.
Machine learning (ML) techniques are widely adopted in manufacturing systems for discovering valuable patterns in shopfloor data. In this regard, machine learning models learn patterns in data to optimize process parameters, forecast equipment deterioration, and plan maintenance strategies among other uses. Thus, this article presents the dataset collected from an assembly line known as the FASTory assembly line. This data contains more than 4,000 data samples of conveyor belt motor driver's power consumption. The FASTory assembly line is equipped with web-based industrial controllers and smart 3-phase energy monitoring modules as an expansion to these controllers. For data collection, an application was developed in a timely manner. The application receives a new data sample as JavaScript Object Notation (JSON) every second. Afterwards, the application extracts the energy data for the relevant phase and persists it in a MySQL database for the purpose of processing at a later stage. This data is collected for two separate cases: static case and dynamic case. In the static case, the power consumption data is collected under different loads and belt tension values. This data is used by a prognostic model (Artificial Neural Network (ANN)) to learn the conveyor belt motor driver's power consumption pattern under different belt tension values and load conditions. The data collected during the dynamic case is used to investigate how the belt tension affects the movement of the pallet between conveyor zones. The knowledge obtained from the power consumption data of the conveyor belt motor driver is used to forecast the gradual behavioural deterioration of the conveyor belts used for the transportation of pallets between processing workstations of discrete manufacturing systems.


[The revolution in the relationship between caregiver and patient].
The caregiver-patient relationship has progressively evolved to focus on the development of the patient's autonomy. The mobilization of the patient's resources is fundamental to their participation in the co-construction of the care protocol. Identifying these resources is an essential component of caregiving know-how. Differents tools are available to help patients develop their own abilities and skills. These strategies have a positive impact on their quality of life and the satisfaction they experience, through a renewed sense of efficacy over their lives.


Azithromycin suppresses proliferation, interleukin production and mitogen-activated protein kinases in human peripheral-blood mononuclear cells stimulated with bacterial superantigen.
Macrolide antibiotics are used for the treatment of immunological disorders such as psoriasis. However, few studies have investigated the immunoregulatory efficacy of macrolides in bacterial superantigen-stimulated immune cells. The suppressive efficacies of azithromycin, clarithromycin, roxithromycin and prednisolone were evaluated in vitro against the concanavalin A- or toxic shock syndrome toxin 1 (TSST-1)-induced proliferation of peripheral-blood mononuclear cells (PBMCs) obtained from nine healthy subjects. The concentrations of six cytokines in a PBMC-culture medium were measured using bead-array procedures followed by flow cytometry. Cellular c-jun N-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK) activity were measured using cell-based ELISA procedures. Azithromycin, clarithromycin and roxithromycin inhibited the proliferation of both the concanavalin A- and superantigen-stimulated PBMCs dose-dependently. The effect of azithromycin was the strongest, with IC50 values of less than 5 µg/ml. Furthermore, the suppressive efficacy of prednisolone against concanavalin A- or TSST-1-stimulated PBMCs was significantly promoted in combination with 5 µg/ml azithromycin (P < 0.002). The concentrations of TNF-α, interleukin (IL)-2, -4, -5 and -10 in the supernatant of concanavalin A- or TSST-1-stimulated PBMCs cultured for 72 h decreased by 65-98% in the presence of 5 µg/ml azithromycin. The stimulation of PBMCs with concanavalin A or TSST-1 increased cellular JNK and ERK activity, and 5 µg/ml azithromycin significantly attenuated the increased activity of JNK in the TSST-1-stimulated cells and ERK in the concanavalin A- and TSST-1-stimulated PBMCs, respectively (P < 0.05). Azithromycin suppresses mitogen- or superantigen-induced proliferation of PBMCs by possibly inhibiting both cellular JNK and ERK activity.


Specific in vitro transcription of the insertion sequence IS2.
The insertion sequence IS2 is a small transposable element of Escherichia coli that lacks any known genetic markers. Insertion of this element in one orientation (I) within bacterial operons blocks expression of downstream genes. In the other orientation (II), IS2 has been associated with the constitutive expression of genes distal to its insertion, suggesting that IS2 might contain promoters directing transcription of IS2(II) into other genes. To test the transcription potential of IS2, we have transcribed in vitro DNA templates from gal3, a Gal- allele in which an IS2(I) is inserted between the gal promoter and the gal genes. We have detected two IS2-specific RNAs which initiate from promoters within IS2 and are transcribed in orientation II (away from the galETK genes). Though the presence and orientation of these promoters suggests that they could be responsible for the constitutive expression of genes adjacent to an IS2(II) element, an alternative role could be for transcription of IS2-encoded genes. Although IS2(I) insertions normally block expression of adjacent genes, certain altered (e.g. mutant) IS2(I) sequences lead to the constitutive expression of downstream genes. We have transcribed DNA templates from galwc5 and galc331, which are Galc alleles that contain altered IS2(I) insertions within the gal operon. For each allele, we have detected two gal-directed transcripts initiating within the IS2 sequence. These RNAs are not detected upon transcription of the unaltered IS2(I) DNA and the promoters arise as a direct consequence of the IS2(I) alterations. This result suggests that these promoters detected in vitro are responsible for the Galc phenotype of these alleles.


Human oviductal fluid proteins. VI. Correlation between alpha-fetoprotein and serum levels of ovarian hormones.
To determine the relationship, if any, between the ovarian hormonal status of women and levels of alpha-fetoprotein (AFP) in their oviductal fluid. The threshold questions were the following: (1) does the presence of AFP in human oviductal fluid (hOF) represent a generalized phenomenon and (2) if so, is there any relationship between AFP in hOF and the ovarian hormones, estradiol (E2) and progesterone (P)? Eleven women who elected minilaparotomy tubal ligations volunteered to donate hOF and serum samples for this study. AFP, E2, and P were determined be radioimmunoassay. Procedures were performed in an academic research environment. This study encompasses only those patients who elected minilaparotomy tubal ligation and volunteered to donate hOF and sera. Clinical features of these patients are described. Patients undergoing tubal ligations had Foley catheters inserted into the fimbriated ends of each oviduct, and hOF was collected for 24 hours. Concomitantly, blood was drawn for analyses of serum. The Investigational Review Board of the Erie County Medical Center approved this study requiring the collection of oviductal fluid from human subjects. Levels of AFP in hOF did not correlate with the serum concentrations of E2 and P per se. However, there was a highly significant correlation between levels of AFP in hOF and serum E2:P ratio. The concentration of AFP in hOF progressively increased with respect to the ratio of serum E2:P. Although AFP was present in all samples of hOF, it was undetectable in corresponding sera. Based on these data, it is concluded that AFP is generally present in hOF. Furthermore, it is suggested that AFP in hOF may be under the control of ovarian steroids.


The ladybird Thalassa saginata, an obligatory myrmecophile of Dolichoderus bidens ant colonies.
The larvae and pupae of the ladybird Thalassa saginata develop inside colonies of the dolichoderine ant Dolichoderus bidens. This association is the first specific and obligatory relationship recorded between ants and ladybirds. The ants provide shelter and protection to the larvae but the diet of the latter remains unclear. The integration of T. saginata larvae into the ant colonies is achieved by mimicking the cuticular patterns of the ants' brood. Moreover, the larvae secrete substances from their hairs and anal gland that are likely to enhance their attractiveness.


Self-Driven Multicolor Electrochromic Energy Storage Windows Powered by a "Perpetual" Rechargeable Battery.
Electrochromic windows (ECWs) become an appealing concept for green buildings. However, conventional ECWs need external biases to operate causing energy consumption and are usually restricted by monotonous color. Recently, electrochromic energy storage windows (EESWs) integrating the functions of electrochromism and energy storage in one device have attracted particular attention in various fields, such as self-powered addressable displays, human-readable batteries, and most importantly energy-efficient smart windows. Herein, a color-tunable (nonemissive-red-yellow-green) self-powered EESW is initially presented utilizing Prussian blue (PB) as a controller of the fluorescent component of CdSe quantum dots. The key design feature is that without any external stimuli, the EESW can be powered by a rechargeable "perpetual" battery, which is composed of two half-cell couples of Fe/PB and Prussian white (PW)/Pt. This technique allows to achieve only by switching the connection status of the two half-cells, the fast discharging and self-charging process of the EESWs with high and sustainable charge-storage capacity. Remarkably, the fabricated self-powered EESWs exhibit quick response ("off" 7 s, "on" 50 s), large transmittance spectra contrast, and high fluorescent contrast modulation (60-86%) over a wide optical range, and great reproducibility (only 3% of the modulation ratio decreased after 30 cycles), which is comparable to ECWs powered by an electrochemical potentiostat.


A bifunctional fluorescent probe based on PET & ICT for simultaneously recognizing Cys and H2S in living cells.
Most reported probes that respond to Cysteine (Cys) and Hydrogen sulfide (H2S) can only identify one analyte, or they were interfered with homocysteine (Hcy) and glutathione (GSH) when recognizing Cys and H2S. In addition, nitrobenzoxadiazole (NBD) ether, as one of thiols recognition sites, inevitably encounters the situation that Cys, GSH and H2S cannot be distinguished on the same channel at the cellular level. In this work, by introducing NBD ether and NBD amine, we constructed a bifunctional fluorescent probe NJB for dual-site response to Cys and H2S via PET & ICT processes. NJB has wonderful selectivity for identifying Cys and HS-, with limits of detection as low as 58.4 nM and 81.1 nM, respectively. Interestingly, NJB has been successfully applied to detect Cys and HS- in MCF-7 cells. Therefore, the probe that serves as a great tool for inquiring the physiological and pathological functions of Cys and H2S in living cells is promising.


Improving stability of vitamin B12 (Cyanocobalamin) using microencapsulation by spray chilling technique.
Vitamin-B12 or cyanocobalamin is an essential micronutrient, so it must be supplied by diet. However, vitamin-B12 is found just in foods derived from animals and it is sensitive of many factors. Due to the unrelenting increase of people with deficiency in vitamin-B12 and easy degradation of this vitamin when subjected to adverse conditions, the aim of this research was to produce solid lipid microparticles (SLM) loaded with vitamin-B12 using the spray chilling technique. It was produced 6 SLM (with 0.1 and 1% vitamin and 0, 2.5 and 5% of lecithin) that were analyzed for optical and scanning electron microscopy, size and particles size distribution, water activity, instrumental color, X-ray diffraction, yield and encapsulation efficiency, release profile, besides free and encapsulated vitamin stability for 120 days. It was reported that the SLM presented a spherical shape and smooth surfaces, medium size values varying from 13.28 to 26.99 μm. The yield and encapsulation efficiency values within the range of 80.7 to 99.7% and from 76.7 to 101.1%, respectively. The encapsulation promoted better protection of vitamin-B12 (>91.1% for all formulations after 120 days of storage) when compared to the free one (75.2%). In addition, it was observed a good effect of the presence of soya lecithin in formulations; it promoted a more controlled release of vitamin-B12 in fluids and also shown better stability results. The spray chilling encapsulation technique proved to be a promising alternative, since it protected vitamin-B12 without the necessity of using high temperatures or organic solvents to encapsulate it, besides having a low cost.


Mechanism for ganglioside-mediated modulation of a calmodulin-dependent enzyme. Modulation of calmodulin-dependent cyclic nucleotide phosphodiesterase activity through binding of gangliosides to calmodulin and the enzyme.
Gangliosides were recently shown to bind to calmodulin (Higashi, H., Omori, A., and Yamagata, T. (1992) J. Biol. Chem. 267, 9831-9838). This prompted us to investigate the effects of gangliosides on the calmodulin-dependent enzyme, cyclic nucleotide phosphodiesterase. Several species of gangliosides competitively inhibited calmodulin-stimulated phosphodiesterase activity, with GD1b, GT1b, and GD1a being noted to do so particularly (group 1). GM1, GQ1b, and GM2 (group 2) were less inhibitory, and GM3, GM3(NeuGc), GalCer, sulfatide, GgOse4Cer, and oligosaccharide portions of inhibitory gangliosides showed no inhibition in accordance with the binding specificity of calmodulin to gangliosides. Trypsin-activated phosphodiesterase was inhibited by gangliosides with similar specificity, indicating interactions of gangliosides with the enzyme. Inhibition, however, was less than that of calmodulin-dependent activity by these compounds and, in both cases, was eliminated by excess calmodulin. In the absence of calmodulin, group 1 gangliosides at lower concentrations activated the intact enzyme but inhibited it over a certain range of increase in concentration. Ganglioside-dependent modulation of calmodulin-dependent phosphodiesterase activity is thus shown to be due to interactions of gangliosides with both calmodulin and the enzyme, and consequently, ganglioside-calmodulin binding is likely the mechanism for regulation of the enzyme.


Conserving total synaptic weight ensures one-trial sequence learning of place fields in the hippocampus.
The hippocampus plays a critical role in the rapid acquisition of information from a novel experience. Recent theoretical studies on the rat hippocampus have shown the possibility of behavioral sequence learning in a single traversal experience by theta phase coding. Specifically, previous work using computer simulations demonstrated that the extent of overlap among individual events of sequence and rat running velocity should be quantitatively incorporated into the learning rule to ensure one-trial sequence learning. These extents of overlap- and running velocity-dependent properties in the learning rule are called the input-dependent regulation of the learning rule. However, the biological meaning of such learning properties remains poorly understood. In this study, we quantitatively derive these learning properties with mathematical analyses. We further find that the input-dependent regulation of the learning rule allows maintenance of total synaptic weight over a given neuron during one-trial learning. Our results predict that a homeostatic plasticity mechanism should exist for conserving total synaptic weight on a rapid timescale.


Distribution of the mammalian-wide interspersed repeats (MIRs) in the isochores of the human genome.
The distribution of MIRs (mammalian-wide interspersed repeats) was investigated in 164 human sequences (> or = 100 kb), which were assigned, according to their GC level, to isochore families L, H1, H2 and H3. MIR elements, whose total number in the genome was estimated to be about 3.3 x 10(5), were found to be unevenly distributed in human isochores. The majority of MIRs (55%) were found in the L isochore family. In contrast, MIR density was highest in H2, closely followed by H1, whereas densities in L and H3 were 2- and 3-fold lower than in H2, respectively. For this reason, the assessment of MIR distribution by inter-repeat PCR led to an overestimation of MIR numbers in H2 isochore and an underestimation in L isochores.


An overview of the electrocardiographic monitoring devices in sports cardiology: Between present and future.
Athletes represent a mainly healthy population, which however could be considered at risk of major arrhythmic events, especially in case of undiagnosed cardiomyopathies. For this reason, the periodical sports medicine examination and the electrocardiography are essential tools in the cardiovascular screening, even though they do not always succeed in identifying rhythm disturbances, particularly when asymptomatic or rarely symptomatic. Prolonged cardiac monitoring often enables clinicians to stratify the arrhythmic risk and reach the diagnosis. The technological progress of the last decades has produced an always-increasing number of heart rhythm monitoring devices, starting from the 24-hour electrocardiogram Holter monitoring and ending with the wide world of wearable devices. In the literature, the extreme utility of this equipment in the patients affected by cardiovascular diseases and in the general population is well established. On the contrary, athletes-based randomized trials or large-scale epidemiological studies targeting the frequency of cardiac symptoms and the use of cardiac monitoring are missing, while an ever-growing number of case series and small observational studies are flourishing in recent years. The present review showcases the available electrocardiographic monitoring options, principally in the medical setting, listing their characteristics, their indications, their supporting evidence, and their general pros and cons. The ultimate goal of this review is guiding physicians through the wide variety of heart rhythm monitoring options in the specific subfield of sports cardiology, when an arrhythmia is suspected in an athlete, to tailor the diagnostic process and favor the best diagnostic accuracy.


Docosahexaenoic acid- and eicosapentaenoic acid-enriched cardiolipin in the Manila clam Ruditapes philippinarum.
The FA composition of cardiolipin (CL) from the Manila clam Ruditapes philippinarum was investigated in whole body and individual organs. CL was isolated by HPLC and its chemical structure characterized using NMR spectroscopy. Two prominent FA, EPA and DHA, were found in approximately equal proportions, contributing together up to 73 mol% of the total FA. The FA composition of CL is presumed to reflect a specific synthesis pathway independent of diet and of total glycerophospholipid FA composition. To the best of our knowledge, this is the first time that a CL dominated by the two PUFA 22:6n-3 and 20:5n-3 has been characterized and described. This EPA + DHA specificity of the CL in the Manila clam is thought to reflect a functional and structural modification of mitochondrial membranes of this bivalve species compared with scallops, oysters, and mussels that possess a CL dominated by DHA. The FA composition and levels of CL differed little between separated organs, and the large pool of DHA and EPA was found fairly equally distributed in gills, mantle, foot, siphon, and muscle. However, whereas DHA and PUFA levels were most stable between organs, EPA and arachidonic acid were significantly more variable and seemed to be interrelated.


A review of recent developments in the application of machine learning in solar thermal collector modelling.
Over the past few decades, the popularity of solar thermal collectors has increased dramatically because of many significant advantages like being a free, natural, environmentally friendly and permanent energy source. Today, developing and optimising different solar thermal energy systems are more important than before. Thus, there are various methods for investigating the performance of these systems, such as experimental, numerical and mathematical methods. One of the cutting-edge methods is artificial intelligence, which can predict key and effective parameters in solar collector efficiency. This review identified recent machine learning modelling, including multilayer perceptron artificial neural network (MLP-ANN), group method of data handling (GMDH), radial basis function (RBF), artificial neuro-fuzzy inference system (ANFIS), support vector machine (SVM) and studies regarding different types of solar thermal collectors, namely non-concentration and concentration. Furthermore, it investigated the effect of various essential factors on the accuracy, potential issues and challenges facing the application of artificial intelligence in these systems. Finally, it will also be recommended opportunities for future research.


Epidermal and hair follicle transglutaminases and crosslinking in skin.
Epidermal and hair follicle transglutaminases crosslink structural proteins in the skin by epsilon-(gamma-glutamyl)-lysine bonds. This crosslinking produces protein polymers that are extremely insoluble and, until recently, difficult to characterize. Epidermal transglutaminase is localized to the granular layer of the epidermis. It catalyzes the crosslinking of a soluble cytoplasmic precursor to form the cornified envelope that lines the inner membrane of the mature keratinocyte in the stratum corneum. Hair follicle transglutaminase is localized to the inner root sheath and medulla of the hair follicle. It crosslinks a poorly characterized citrulline-rich protein. The enzymes and their substrates have been shown to be important markers of normal differentiation. Regulation of these processes is currently under investigation.


Influence of midazolam-related genetic polymorphism on conscious sedation during upper gastrointestinal endoscopy in a Korean population.
Genetic polymorphism can result in abnormal pharmacodynamics that subsequently leads to the individual variance in sedative effects and adverse reactions. The aim of this study was to elucidate the association between midazolam-related genetic polymorphism and sedative effects, including adverse reactions, under conscious sedation during upper gastrointestinal endoscopy. We prospectively enrolled 100 eligible patients undergoing upper gastrointestinal endoscopy. The efficacy of the sedation, adverse reactions, plasma concentration of midazolam and 1-hydroxymidazolam were investigated as well as the genetic polymorphism of MDR1 and CYP3A5. The correlation between genetic polymorphism and sedative effects was assessed. Regarding MDR1 gene, the plasma concentration of midazolam was greater in patients with CGC haplotype (P = 0.012), while it was lower in patients with CAC haplotype (P = 0.005) than in those with other haplotypes. However, genetic polymorphism of neither MDR1 nor CYP3A5 correlated with the plasma concentration of 1-hydroxymidazolam. CGT haplotype of MDR1 was significantly correlated with sedation grade after midazolam administration (P = 0.042). In contrast, genetic polymorphism of CYP3A5 was not correlated with sedation grade. There was no association between genetic polymorphism of MDR1 or CYP3A5 and selected adverse reactions related to midazolam. Genetic polymorphism of MDR1 influences the concentration of midazolam and the sedation grade. However, it is not associated with adverse reactions such as paradoxical response and retrograde amnesia.


Clinical study on the factors affecting the post-partum recovery of patients with hypertensive pregnancy disorders at a Chinese hospital.
The aim of this study was to investigate the post-partum recovery of blood pressure (BP) in women with hypertensive disorders of pregnancy (HDP) and to evaluate HDP risk factors. A total of 124 patients with gestational hypertension (n = 63) or pre-eclampsia (n = 61) who gave birth at Peking University People's Hospital between January and December 2013 were included in this study. The recorded clinical and laboratory parameters included the patients' general information, maternal pre-pregnancy body mass index, gestational weight gain, gestational age at onset and delivery, delivery mode and time taken for BP to return to normal level. Logistic regression analysis was performed to evaluate the influence of various risk factors on post-partum BP recovery. The mean interval for BP normalization was 24.1 ± 22.8 days (median, 7 days). Forty-six percent of the patients recovered from hypertension within three days, and 75% recovered within six weeks of delivery. About 90% of the patients required 60 days for BP to normalize after delivery. After adjusting for confounding factors, post-partum recovery from hypertension was found to be influenced by hypertension severity, maternal serum albumin level, a family history of hypertension and gestational week at delivery. The BP of the majority of the patients with gestational hypertension or pre-eclampsia returned to normal within 60 days of delivery. Hypertension severity, maternal serum albumin level, a family history of family hypertension and gestational week at delivery influenced the time required for BP normalization.


Impact of peak respiratory exchange ratio on the prognostic power of symptoms-limited exercise testing using Bruce protocol in patients with Fontan physiology.
We evaluated the impact of peak respiratory exchange ratio on the prognostic values of cardiopulmonary exercise variables during symptoms-limited incremental exercise tests in patients with Fontan physiology. Retrospective single-centre chart review study of Fontan patients who underwent exercise testing using the Bruce protocol between 2014 and 2018 and follow-up. A total of 34 patients (age > 18 years) had a Borg score of ≥7 on the Borg 10-point scale, but only 50% of patients achieved a peak respiratory exchange ratio of ≥ 1.10 (maximal test). Peak oxygen consumption, percent-predicted peak oxygen consumption, and peak oxygen consumption at the ventilatory threshold was reduced significantly in patients with a peak respiratory exchange ratio of < 1.10. Peak oxygen consumption and percent-predicted peak oxygen consumption was positively correlated with peak respiratory exchange ratio values (r = 0.356, p = 0.039). After a median follow-up of 21 months, cardiac-related events occurred in 16 (47%) patients, with no proportional differences in patients due to their respiratory exchange ratio (odds ratio, 0.62; 95% CI: 0.18-2.58; p = 0.492). Multivariate Cox proportional hazard analysis showed percent-predicted peak oxygen consumption, peak heart rate, and the oxygen uptake efficient slope were highly related to the occurrence of events in patients only with a peak respiratory exchange ratio of ≥ 1.10. The value of peak cardiopulmonary exercise variables is limited for the determination of prognosis and assessment of interventions in Fontan patients with sub-maximal effort. Our findings deserve further research and clinical application.


[Hematopoietic study of rats in experiments with exchange blood replacement by an emulsion of perfluorotributylamine].
In experiments on nonanesthetized rats blood was substituted with perfluorotributyl emulsion (PFTBA). The mean volume of transfused PFTBA was 10 ml/100 g of body weight. During the period of blood replacement and the following 5 days the rats were kept in an atmosphere with increased oxygen content, and then they were placed under normal atmospheric conditions. The influence of PFTBA solution on hemopoiesis was studied in these experiments. A marked erythropoiesis activation in the bone marrow combined with expressed peripheral blood reticulocytosis was observed 6 days after the exchange blood substitution. Hemoglobin content decreased to 8.2 g% mature and immature white cell count rose; immature erythropoiesis cells were found: polychromatophilic erythro- and normoblasts (4.2% on the average). By the 13th day there was complete normalization of hemopoiesis which lasted 12 months without any significant deviations. Basing upon the results obtained it may be concluded that the PFTBA emulsion under study produces no negative effect on the animal hemopoiesis, and does not disturb the normal regulation process under conditions of the experiment conducted.


Definitive radiotherapy of prostate cancer: the possible role of staging lymphadenectomy.
To evaluate the postradiotherapy 5-year cancer-specific (CSS), clinical progression-free (cPFS), and overall (OS) survival rates in patients with pN0 M0 prostate cancer (PC). Between 1989 and 1996, 203 consecutive pN0 M0 PC patients (T1-2, 66; T3-4, 137) received conformal prostatic four-field radiotherapy (median target dose 66 Gy). Any hormone manipulation was delayed until clinical progression (growth of the primary tumor or development of distant metastases). After a median observation time of 87 months (range 11-156), 99 patients had relapsed clinically and 70 patients were dead, 37 of them as a result of prostate cancer. Five-year CSS, cPFS, and OS rates were, respectively, 90% (95% CI 86-94%), 64% (95% CI 57-71%), and 82% (95% CI 77-87%), with no difference of OS compared with age-matched males from the general population. Gleason score (< or =7A vs. > or =7B) and the T category predicted cPFS, whereas CSS was associated with Gleason score only. Preradiotherapy PSA failed to predict survival. Patients with T1-2 Gleason score < or =7A had a 97% 5-year CCS, as compared with 89% for all other patients. A median of eight lymph nodes (range 0-29) were described in the specimens from pelvic lymphadenectomy (LA). Despite still preliminary observations, our 5-year results challenge the use of combined hormone radiotherapy in patients who are proven to be pN0 by preradiotherapy LA; in particular, in patients with T1-2/Gleason score < or =7A, whereas the survival in all other patients with pN0 M0 prostate cancer may be improved by adjuvant androgen deprivation.


Hydrochemical composition and potentially toxic elements in the Kyrgyzstan portion of the transboundary Chu-Talas river basin, Central Asia.
Water chemistry and the assessment of health risks of potentially toxic elements have important research significance for water resource utilization and human health. However, not enough attention has been paid to the study of surface water environments in many parts of Central Asia. Sixty water samples were collected from the transboundary river basin of Chu-Talas during periods of high and low river flow, and the hydrochemical composition, including major ions and potentially toxic elements (Zn, Pb, Cu, Cr, and As), was used to determine the status of irrigation suitability and risks to human health. The results suggest that major ions in river water throughout the entire basin are mainly affected by water-rock interactions, resulting in the dissolution and weathering of carbonate and silicate rocks. The concentrations of major ions change to some extent with different hydrological periods; however, the hydrochemical type of calcium carbonate remains unchanged. Based on the water-quality assessment, river water in the basin is classified as excellent/good for irrigation. The relationship between potentially toxic elements (Zn, Pb, Cu, Cr, and As) and major ions is basically the same between periods of high and low river flow. There are significant differences between the sources of potentially toxic elements (Zn, Pb, Cu, and As) and major ions; however, Cr may share the same rock source as major ions. The risk assessment revealed low non-carcinogenic and carcinogenic risks for human health; however, the maximum carcinogenic risk for As exceeded the allowable value, which requires further consideration. These results provide a scientific basis for the management of agricultural irrigation uses and also infill existing gaps regarding the hydrochemical composition in the Chu-Talas river basin, Central Asia.


The combination therapy of transarterial chemoembolisation and sorafenib is the preferred palliative treatment for advanced hepatocellular carcinoma patients: a meta-analysis.
To compare the efficacy of three types of palliative therapy for advanced hepatocellular carcinoma (HCC), including transarterial chemoembolisation (TACE) monotherapy, sorafenib alone and their combination. The databases of PubMed, Embase and Cochrane Library were retrieved. The odds ratio (OR) with its 95% confidence interval (CI) was used to investigate the binary variables, and the standardised mean difference (SMD) with its 95% CI was employed to evaluate the continuous variables. All statistical tests were performed by using Stata/SE, version 12.0. Thirty-one clinical studies, containing 5125 unique cases of patients with advanced HCC, were included. There were significant improvements in overall survival (OS) (pooled SMD = 2.54; 95% CI 1.74-3.34) and time to progression (TTP) (pooled SMD = 2.49; 95% CI 0.87-4.12) of the patients after receiving the combination therapy of TACE and sorafenib, compared to TACE monotherapy, and the OS in the combined treatment cohort was also longer than that in the sorafenib-alone cohort (pooled SMD = 2.92; 95% CI 1.72-4.13). The combination therapy group in comparison to the TACE group benefited a significantly increased overall response rate (ORR) (pooled OR = 2.61; 95% CI 1.43-4.77), 1-year (pooled OR = 2.96; 95% CI 1.71-5.14) and 2-year (pooled OR = 1.64; 95% CI 1.18-2.28) survival rates and reduced disease progression rate (DPR) (pooled OR = 0.47; 95% CI 0.33-0.68); in parallel, the ORR in the group was also significantly higher than that in the sorafenib-alone group (pooled OR = 3.62; 95% CI 1.28-10.22), although without a difference in the DPR (pooled OR = 0.28; 95% CI 0.05-1.48). In addition, we discovered that the 1-year (pooled OR = 1.39; 95% CI 0.84-2.29) and 2-year (pooled OR = 1.70; 95% CI 0.69-4.18) survival rates in the TACE monotherapy cohort were not significantly different to those in the sorafenib-alone cohort. The combination therapy is more effective than monotherapy in improving the prognostic outcomes of patients with advanced HCC. Therefore, we recommend it as the preferred treatment intervention for those patients.


Prevalence of sufficient physical activity among parents attending a university.
The benefits of regular physical activity are well documented. However, approximately half of all university students are insufficiently active, and no research to date exists on the activity behavior of university students who are also parents. Using an adapted version of the Godin Leisure Time Exercise Questionnaire (ie, the Physical Activity Prevalence Questionnaire), the authors examined the prevalence of sufficient physical activity among 245 parent students from 6 faculties and 12 programs. Half (49.5%) of the students who were not parents (n = 90) were sufficiently physically active, compared with 16% of students who were parents (n = 3, p < .002). The authors found that 33.3% of parents and 13% of nonparents limited their activity level as a result of illness or injury (p < .05). Most parent students in this study were insufficiently active and at potential risk for the negative health consequences of inactivity. This is a grossly understudied population, and researchers must conduct further studies to understand what can be done to facilitate physical activity among this potentially vulnerable group of students.


Reporting and case management of occupational exposures to blood-borne pathogens among healthcare workers in three healthcare facilities in Tanzania.
In sub-Saharan Africa, blood-borne pathogens exposure (BPE) is a serious risk to healthcare workers (HCW). We conducted a cross-sectional study assessing BPE among HCW at three public hospitals in Tanzania. From August to November 2012, HCW were surveyed using Audio-Computer Assisted Self-Interview. All HCW at risk for BPE were invited to participate. Factors associated with reporting BPE were identified using logistic regression. Of the 1102 eligible HCW, 973 (88%) completed the survey. Of these, 690 (71%) were women and 499 (52%) were nurses and nurse assistants. Of the 357 HCW who had a BPE (32%) in the previous 6 months, 120 (34%) reported it. Among these 120 reported exposures, 93 (78%) HCWs reported within 2 h of exposure, 98 (82%) received pre- and post-HIV test counselling, and 70 (58%) were offered post-exposure prophylaxis (PEP). Independent factors associated with reporting BPE were being female (adjusted odds ratio [AOR], 2.0; 95% confidence interval [CI], 1.2-3.5), having ever-received BPE training (AOR, 2.0; 95% CI, 1.2-3.5), knowledge that HCW receive PEP at another facility (AOR, 2.6; 95% CI, 1.5-4.4), low/no perceived risk related to BPE (AOR, 4.2; 95% CI, 1.9-9.4) and HIV testing within the past year (AOR, 2.3; 95% CI, 1.2-4.4). These results highlight the importance of appropriate training on the prevention and reporting of occupational exposure to increase acceptance of HIV testing and improve access to PEP after BPE.


An intuitive framework for Bayesian posterior simulation methods.
Bayesian inference has become popular. It offers several pragmatic approaches to account for uncertainty in inference decision-making. Various estimation methods have been introduced to implement Bayesian methods. Although these algorithms are powerful, they are not always easy to grasp for non-statisticians. This paper aims to provide an intuitive framework of four essential Bayesian computational methods for epidemiologists and other health researchers. We do not cover an extensive mathematical discussion of these approaches, but instead offer a non-quantitative description of these algorithms and provide some illuminating examples. Bayesian computational methods, namely importance sampling, rejection sampling, Markov chain Monte Carlo, and data augmentation are presented. The substantial amount of research published on Bayesian inference has highlighted its popularity among researchers, while the basic concepts are not always straightforward for interested learners. We show that alternative approaches such as a weighted prior approach, which are intuitively appealing and easy-to-understand, work well in the case of low-dimensional problems and appropriate prior information. Otherwise, MCMC is a trouble-free tool in those cases.


A comparative study on the efficacy of rofecoxib in monoarticular arthritis induced by latex of Calotropis procera and Freund's complete adjuvant.
The role of prostaglandins in Calotropis procera latex induced inflammation and hyperalgesia has been well established. The acute inflammation induced by the dried latex (DL) of this plant could be effectively ameliorated by standard anti-inflammatory drugs. In present study we have evaluated the efficacy of rofecoxib, a COX-2 inhibitor in monoarthritis induced by intra-articular injection of DL and compared it with that against Freund's Complete Adjuvant (FCA). DL and FCA were injected into the right ankle joint of the rat and the joint diameter was measured by a micrometer screw gauge on day 0, 4, 8, 12, 20 and 28. Concomitantly the hyperalgesic response was also evaluated by motility test, stair climbing ability test, dorsal flexion pain test and compression test. The effect of rofecoxib was evaluated on these parameters in both the models. Both DL and FCA produced peak inflammation on day 4 that was associated with decreased pain threshold and functional impairment. Although rofecoxib was more effective in improving motility in the DL model, its effect on joint inflammation, hyperalgesia and stair climbing ability was comparable in both the models. Thus, our study indicates that DL induced monoarthritis could be used as a model for the screening and evaluation of anti-inflammatory and anti-arthritic drugs.


Antibody variable-region sequencing as a method for hybridoma cell-line authentication.
Cross-contamination and misidentification of various cell lines is a widespread problem that can lead to spurious scientific conclusions. DNA fingerprinting is a powerful identification technique, which can be effectively used for the authentication of human cell lines. In contrast to human cancer cell lines, little attention has so far been given to establishing authentication practices for hybridoma cell lines. Since the majority of hybridomas stem from inbred animals, they have high genetic uniformity, which reduces the applicability of DNA fingerprinting. In the present study, we propose antibody variable-region sequencing as a method of choice for hybridoma cell-line authentication. This method focuses on the most diverse characteristic of hybridoma cell lines and thereby achieves a very high discriminatory power. The sequencing of light-chain variable regions has proven to be especially suitable for routine use because of its high success rate. Two other possible authentication methods, random amplified polymorphic DNA analysis and two-dimensional gel electrophoresis, were also examined. Compared to these and other methods that can be used for discrimination between hybridoma cell lines, variable-region sequencing has many advantages, most notably those of a very high discriminatory power, insensitivity to changes in experimental conditions, simple data analysis, and accessibility to most laboratories.


Detergents as tools for the purification and classification of lipid rafts.
The relative insolubility of lipid rafts in cold non-ionic detergents is the most widely used method to purify these fascinating membrane domains from intact cells or membranes. Most of what we know about lipid raft function has been derived from experiments utilising detergent insolubility as the basis for raft purification. Recently, a wider range of detergents have been used to purify 'rafts', and rafts have been subclassified based on their differential solubility in different detergents. This minireview critically examines the use of detergents as tools for raft isolation and for the subclassification of rafts.


Apo alpha-lactalbumin and lysozyme are colocalized in their subsequently formed spherical supramolecular assembly.
We have reported previously that the calcium-depleted form of bovine alpha-lactalbumin (apo alpha-LA) interacts with hen egg-white lysozyme (LYS) to form spherical supramolecular structures. These supramolecular structures contain an equimolar ratio of the two proteins. We further explore here the organization of these structures. The spherical morphology and size of the assembled LYS/apo alpha-LA supramolecular structures were demonstrated using confocal scanning laser microscopy and scanning electron microscopy. From confocal scanning laser microscopy experiments with labelled proteins, it was found that LYS and apo alpha-LA were perfectly colocalized and homogeneously distributed throughout the entire three-dimensional structure of the microspheres formed. The spatial colocalization of the two proteins was also confirmed by the occurrence of a fluorescence resonance energy transfer phenomenon between labelled apo alpha-LA and labelled LYS. Polarized light microscopy analysis revealed that the microspheres formed differ from spherulites, a higher order semicrystalline structure. As the molecular mechanism initiating the formation of these microspheres is still unknown, we discuss the potential involvement of a LYS/apo alpha-LA heterodimer as a starting block for such a supramolecular assembly.


Heterogeneous treatment effect analysis based on machine-learning methodology.
Heterogeneous treatment effect (HTE) analysis focuses on examining varying treatment effects for individuals or subgroups in a population. For example, an HTE-informed understanding can critically guide physicians to individualize the medical treatment for a certain disease. However, HTE analysis has not been widely recognized and used, even given the explosive increase of data availability attributed to the arrival of the Big Data era. Part of the reason behind its underuse is that data are often of high dimension and high complexity, which pose significant challenges for applying conventional HTE analysis methods. To meet these challenges, a newly developed causal forest HTE method has been derived from the random forest machine-learning algorithm. We conducted a systematic performance evaluation for the causal forest method against the conventional two-step method by simulating scenarios with different levels of complexity for the analysis. Our results show that causal forest outperforms the conventional HTE method in assessing treatment effect, especially when data are complex (e.g., nonlinear) and high dimensional, suggesting that causal forest is a promising tool for real-world applications of HTE analysis.


Androgenic anabolic steroid-induced liver injury: two case reports assessed for causality by the updated Roussel Uclaf Causality Assessment Method (RUCAM) score and a comprehensive review of the literature.
Anabolic androgenic steroids (AAS) usage is widespread and increasing. AAS drug-induced liver injury (DILI) is recognised but its clinical course and management is poorly described. We report 2 cases of AAS DILI with associated renal dysfunction, managed successfully with oral corticosteroids. A comprehensive review identified 50 further cases to characterise the clinical and biochemical course. Causality grading was calculated using the updated Roussel Uclaf Causality Assessment Method (RUCAM) score. Data are presented as median values. The most common AAS taken was methyldrostanolone. Patients commonly present with jaundice and pruritus but may exhibit other constitutional symptoms. Patients presented 56 days after starting, and bilirubin peaked 28 days after stopping, AAS. Causality assessment was 'unlikely' in 1 (2%), 'possible' in 31 (60%) and 'probable' in 20 (38%). Peak values were: bilirubin 705 μmol/L, alanine transaminase 125 U/L, aspartate transaminase 71 U/L, alkaline phosphatase 262 U/L, gamma-glutamyl transferase 52 U/L, international normalised ratio 1.1. Liver biopsies showed 'bland' canalicular cholestasis. 43% of patients developed kidney injury (peak creatinine 225 μmol/L). Therapies included antipruritics, ursodeoxycholic acid and corticosteroids. No patients died or required liver transplantation. Physicians are likely to encounter AAS DILI. Causality assessment using the updated RUCAM should be performed but defining indications and proving efficacy for therapies remains challenging.


Energy metabolism of isolated rat thymus cells.
The energy metabolism of rat thymus cells has been investigated using preparations of isolated cells obtained by mechanical treatment of whole organs. The addition of glycolytic substrates such as glucose, pyruvate and lactate stimulates the endogenous respiration of these cells by 50%. On the other hand, succinate, glutamate and malate do not produce any effect. Oligomycin (10 mug/ml) inhibits both endogenous and glucose stimulated respiration by about 40%; 2, 4-DNP (50 muM) increases by 100% glucose induced respiration. The results obtained by using mitochondrial and glycolytic inhibitors as well as aminoxyacetic acid (AOA) and following pyridine nucleotides redox changes, support the idea that in thymus cells glucose is able to induce a great enhancement of O2 consumption both by raising the level of endogenous pyruvate and feeding the mitochondrial respiratory chain with cytosolic reducing equivalents, through an active malate-aspartate shuttle. Thymus cells exhibit a high Pasteur effect (74%). Both AOA and 2,4 DNP are able to stimulate aerobic lactate accumulation by 200% and 100% respectively, indicating that either the redox or phosphate potential do influence the rate of aerobic glycolysis in isolated thymus cells. Similar experiments are also reported on other cells with well known biochemical characteristics.


Impact of ankle osteoarthritis on the energetics and mechanics of gait: the case of hemophilic arthropathy.
Osteoarthritis may affect joints in any part of the body, including the ankle. The purpose of this study was to assess the impact of ankle osteoarthritis on the energetics and mechanics of gait, while taking into account the effect of slower speed generally adopted by patients with osteoarthritis. Using a motion analysis system, synchronous kinematic, kinetics, spatiotemporal, mechanics and metabolic gait parameters were measured in 10 patients diagnosed with ankle osteoarthritis consecutive to hemophilia. The subjects walked at a self-selected speed and their performance was compared to speed-matched normal values obtained in healthy control subjects. Speed-normalization using a Z-score transformation showed a significant increase in metabolic cost (Z=1.78; P=0.006) and decrease in mechanical work (Z=-0.97; P=0.009). As a consequence, muscular efficiency also decreased (Z=-0.97; P=0.001). These changes were associated with a surprising efficacy of the pendular mechanism, i.e., an improved recovery index (Z=0.97; P=0.004). Our findings suggest that patients with ankle osteoarthritis adopt a walking strategy which improves recovery through the pendular mechanism. This may be a compensatory mechanism in order to economize energy which would counterbalance the energy waste due to low muscle efficiency. These modifications are proportional to the impaired ankle function. Our data provides a quantitative baseline to better understand the dynamics of ankle osteoarthritis and determine the individual role that lower limb joints play in the multiple chronic joint affections.


25-Hydroxyvitamin D levels in acute monosymptomatic optic neuritis: relation to clinical severity, paraclinical findings and risk of multiple sclerosis.
Optic neuritis (ON) is a common first symptom of MS and only few studies have thus far investigated vitamin D at this early stage of MS. The objectives of the study were to examine total 25-hydroxyvitamin D levels (25HVITDL) in patients in acute (A) ON and to determine whether 25HVITD levels in AON (1) predict risk of RRMS and (2) are associated with visual tests of ON severity. A cross-sectional study was conducted of mean 25HVITDL differences between ON (n = 164) and MS (n = 948) patients and of prevalence of 25HVITDL deficiency (<50 nmol/L) in ON and MS (two-sample t test, χ (2) test). Associations between 25HVITDL and (1) clinical ON severity, (2) paraclinical findings suggestive of MS [logistic regression (LRA), Spearman correlation] and (3) hazard of MS development [Cox (C) RA] in ON patients were assessed. 25HVITDL were deseasonalized before analysis. The mean levels were 47.6 (ON) and 63.9 (MS) nmol/L (p < 0.0001), and a significantly higher prevalence of 25HVITD deficiency in ON (56 %; 35 %) (p < 0.0001), most pronounced in females, was shown. Associations were found between 25HVITDL and both CSF leukocyte count (ρ = -0.177, p = 0.028) and IgG index elevation (OR 0.980, p = 0.031). Forty-one ON patients developed MS during the study. Multivariate CRA showed no effect on hazard of MS (HR: 0.991, p 0.284). No association was found between 25HVITDL and visual tests (acuity, contrast vision) or OCT RNFL or GCL thickness. The study indicates a high prevalence of 25HVITD deficiency in AON. 25HVITDL was significantly associated with CSF leukocyte count, but not ON severity. The study indicates a possible role of vitamin D in the early stages of MS, but does not support the use of 25HVITDL as a predictor of MS development in acute ON.


Nicotine modulation of the lateral habenula/ventral tegmental area circuit dynamics: An electrophysiological study in rats.
Nicotine, the addictive component of tobacco, has bivalent rewarding and aversive properties. Recently, the lateral habenula (LHb), a structure that controls ventral tegmental area (VTA) dopamine (DA) function, has attracted attention as it is potentially involved in the aversive properties of drugs of abuse. Hitherto, the LHb-modulation of nicotine-induced VTA neuronal activity in vivo is unknown. Using standard single-extracellular recording in anesthetized rats, we observed that intravenous administration of nicotine hydrogen tartrate (25-800 μg/kg i.v.) caused a dose-dependent increase in the basal firing rate of the LHb neurons of nicotine-naïve rats. This effect underwent complete desensitization in chronic nicotine (6 mg/kg/day for 14 days)-treated animals. As previously reported, acute nicotine induced an increase in the VTA DA neuronal firing rate. Interestingly, only neurons located medially (mVTA) but not laterally (latVTA) within the VTA were responsive to acute nicotine. This pattern of activation was reversed by chronic nicotine exposure which produced the selective increase of latVTA neuronal activity. Acute lesion of the LHb, similarly to chronic nicotine treatment, reversed the pattern of DA cell activation induced by acute nicotine increasing latVTA but not mVTA neuronal activity. Our evidence indicates that LHb plays an important role in mediating the effects of acute and chronic nicotine within the VTA by activating distinct subregional responses of DA neurons. The LHb/VTA modulation might be part of the neural substrate of nicotine aversive properties. By silencing the LHb chronic nicotine could shift the balance of motivational states toward the reward.


Epigenome and DNA methylation in oral squamous cell carcinoma.
Epigenetics studies and defines inherited changes in gene expression that are not encoded in the DNA sequence. The most studied epigenetic change in mammalian DNA is cytosine methylation in CpG dinucleotide areas. The other main group in epigenetic changes includes the posttranslational modifications of histones, mainly phosphorylation, deacetylation changes, and in the ubiquitinylation status. Oral squamous cell carcinoma is the most common malignancy of the oral cavity, and epigenetic changes are very common, as described in this chapter. Alterations in the DNA methylation status resulting from exposure to environmental stress agents have been documented even before birth. Although many epigenetic markers are potentially reversible, the mechanism still remains unclear and many epigenetic changes persist across cell lines and the life of the organism.


Which species, Alexandrium catenella (Group I) or A. pacificum (Group IV), is really responsible for past paralytic shellfish poisoning outbreaks in Jinhae-Masan Bay, Korea?
Paralytic shellfish poisoning (PSP) caused the deaths of four people in coastal area of Korea, mainly Jinhae-Masan Bay and adjacent areas, in April 1986 and in 1996. The PSP outbreaks were caused by the consumption of mussels, Mytilus edulis. The organism that caused PSP was identified, from morphological data only, as Alexandrium tamarense which is recently renamed as A. catenella, however recent studies have shown that the morphological diagnostic characteristics used to identify Alexandrium species have uncertainties and molecular tools and other criteria should be considered as well. The organism that caused past PSP outbreaks and incidents in Korea therefore need to be carefully reconsidered. The aim of this study was to re-evaluate the species really responsible for past outbreaks of PSP in Jinhae-Masan Bay, Korea. The temporal production and fluxes of the resting cysts of Alexandrium species were investigated for one year (from March 2011 to February 2012) using a sediment trap, and the morphology and phylogeny of vegetative cells germinated from the resting cysts were analysed. The production of Alexandrium species peaked in August and November, when temporal discrepancies were found in the water temperature (22.4 and 22.7°C in August, 19.1 and 19.6°C in November) and salinity (29.5 and 26.1 psu in August, 30.5 and 31.8 psu in November). The morphological data revealed that Alexandrium species germinated from resting cysts collected in August have a ventral pore on the 1' plate, whereas the 1' plate in Alexandrium species germinated from resting cysts collected in November lacks a ventral pore. Molecular phylogenetic data for the vegetative cells from the germination experiments allowed the August and November peaks to be assigned to Alexandrium catenella (Group I) and A. pacificum (Group IV), respectively. This indicates that the production of resting cysts of A. catenella can be enhanced by relatively high water temperature. This result is not consistent with those of previous studies that A. catenella responsible for PSP outbreaks was found at relatively low water temperature. In addition, large subunit ribosomal sequences data revealed that A. pacificum isolates from Korea were closely related to those from Australia, Japan and New Zealand where the PSP toxicity of shellfish and blooms occurred in the 1990s, indicating that the introduction of toxic dinoflagellates were related to ballast water from bulk-cargo shipping. Based on these results, we concluded that past PSP outbreaks in Jinhae-Masan Bay of Korea could have been caused by A. pacificum rather than by A. catenella.


Multivariate and behavior genetic analysis of avoidance of complex visual stimuli and activity in recombinant inbred strains of mice.
Sixty-six mice of 11 genetic stocks (the Bailey recombinant inbred strains CXBD, CXBE, CXBG, CXBH, CXBI, CXBJ, CXBK; their progenitor strains, BALB/cBy and C57BL/6By: and the reciprocal hybrids, B6CF and CB6F) were tested in a two-compartment apparatus and in a shuttlebox, with five measures taken relating to activity and to approaches to novel and complex stimuli. A factor analysis of these measures revealed two factors, the first involving behavior relating to novel stimuli and the second relating to locomotor activity. In a second experiment, 132 mice of the same strains were tested on four of the measures used previously. On the two measures which had high loadings on the first factor and very low loadings on the second, it was possible to determine a strain distribution pattern (SDP), with the same SDP being found for both measures. When confirmed by testing mice from two congenic histocompatibility strains H(w54) and H(w80), we were able to determine that avoidance of novel/complex stimuli (neophobia) is controlled by a gene or genes at chromosomal segments H-24c and H-1b. It was also found that a polygenic model is consistent with behavior measured by the second (activity) factor.


Albumosomes formed by cytoplasmic pre-folding albumin maintain mitochondrial homeostasis and inhibit nonalcoholic fatty liver disease.
Hepatic mitochondrial dysfunction contributes to the progression of nonalcoholic fatty liver disease (NAFLD). However, the factors that maintain mitochondrial homeostasis, especially in hepatocytes, are largely unknown. Hepatocytes synthesize various high-level plasma proteins, among which albumin is most abundant. In this study, we found that pre-folding albumin in the cytoplasm is completely different from folded albumin in the serum. Mechanistically, endogenous pre-folding albumin undergoes phase transition in the cytoplasm to form a shell-like spherical structure, which we call the "albumosome". Albumosomes interact with and trap pre-folding carnitine palmitoyltransferase 2 (CPT2) in the cytoplasm. Albumosomes control the excessive sorting of CPT2 to the mitochondria under high-fat-diet-induced stress conditions; in this way, albumosomes maintain mitochondrial homeostasis from exhaustion. Physiologically, albumosomes accumulate in hepatocytes during murine aging and protect the livers of aged mice from mitochondrial damage and fat deposition. Morphologically, mature albumosomes have a mean diameter of 4μm and are surrounded by heat shock protein Hsp90 and Hsp70 family proteins, forming a larger shell. The Hsp90 inhibitor 17-AAG promotes hepatic albumosomal accumulation in vitro and in vivo, through which suppressing the progression of NAFLD in mice.


Possible visual pathways to the cat vestibular nuclei involving the nucleus prepositus hypoglossi.
Non-cerebellar afferents from visual relays to the vestibular nuclei (VN) of the cat have been re-evaluated with the use of the horseradish peroxidase technique. From our data it can be concluded that: (1) A monosynaptic projection from the nucleus reticularis tegmenti pontis to the VN can be excluded. (2) Monosynaptic projections from the superior colliculus and some of the pretectal nuclei (nucleus of the optic tract, olivary pretectal nucleus) to the nucleus prepositus hypoglossi may constitute polysynaptic visual afferents to the VN, which would account for the residual visual sensitivity of the VN neurons after cerebellar or inferior olivary lesions.


Mechanical Thrombectomy for Stroke After Cardiac Surgery.
Stroke after cardiac surgery remains a devastating complication and its treatment options are limited. Systemic fibrinolysis is a relative contraindication, because it raises the risk of systemic hemorrhage. Endovascular therapy, mechanical thrombectomy, and intra-arterial fibrinolysis have emerged as safer options. We present three patients who developed strokes following cardiac surgery who underwent successful mechanical thrombectomy and review the literature on this subject. doi: 10.1111/jocs.12776 (J Card Surg 2016;31:517-520).


Effect of age and overweight on the QT interval and the prevalence of long QT syndrome in children.
The change in QT interval with age during childhood of normal children and children with long QT syndrome (LQTS) and the effects of body mass index on the QT interval have not been studied in detail. The prevalence of LQTS in children is not well known. We measured 3 consecutive QT and RR intervals in 4,655 children. Their electrocardiograms along with their height and weight were recorded when they were in the first grade in 1994 and again when they were in the seventh grade in 2000. The QT interval was corrected by Bazett's formula. The longer corrected QT intervals in female subjects than male subjects start at elementary school age, earlier than previously reported. Overweight did not have an impact on the uncorrected or corrected QT interval. None of the 4 children diagnosed with LQTS in the seventh grade had characteristic electrocardiographic findings of LQTS in the first grade. All 4 are nonfamilial cases. The prevalence of LQTS in children was found to be 1 of 1,164. These data suggest that abnormal electrocardiographic phenotypes in children with nonfamilial LQTS may appear during the elementary school year. The longer QT intervals in female subjects than male subjects start at the same period. No correlation was found between obesity and length of the QT interval. Finally, the prevalence of LQTS in children is greater than previously suspected.


Effects of copper on the acute cortisol response and associated physiology in rainbow trout.
The aim of this study was to determine the effects of chronic waterborne copper (Cu) exposure on the acute stress-induced cortisol response and associated physiological consequences in rainbow trout (Oncorhynchus mykiss). Trout were exposed to 30 μg Cu/L in moderately hard water (120 mg/L as CaCO(3)) for 40 days, following which time the acute cortisol response was examined with a series of stressors. At 40 days, a 65% increase in Cu was observed in the gill, but no accumulation was observed in the liver, brain or head kidney. Stressors such as air exposure or confinement did not elicit an increase in circulating cortisol levels for Cu-exposed fish, in contrast to controls. However, this inhibitory effect on the acute cortisol response appeared to have few implications on the ability of Cu-exposed fish to maintain ion and carbohydrate homeostasis. For example, plasma Na(+), Ca(2+) and glucose levels as well as hepatic glycogen levels were the same post-stress in control and Cu-exposed fish. Trout were also challenged with exposure to 50% seawater for 48 h, where Cu-exposed trout maintained plasma Na(+), glucose and hepatic glycogen levels. However, Cu-exposed fish experienced decreased plasma K(+) levels throughout the Cu exposure and stress tests. In conclusion, chronic Cu exposure resulted in the abolition of an acute cortisol response post-stress. There was no Cu accumulation in the hypothalamus-pituitary-interrenal axis (HPI axis) suggesting this was not a direct toxic effect of Cu on the cortisol regulatory pathway. However, the lack of an acute cortisol response in Cu-exposed fish did not impair the ability of the fish to maintain ion and carbohydrate homeostasis. This effect on cortisol may be a strategy to reduce costs during the chronic stress of Cu exposure, and not endocrine disruption as a result of toxic injury.


Clustering psychopathology in male anabolic-androgenic steroid users and nonusing weightlifters.
Prior research has demonstrated that personality disorders and clinical psychiatric syndromes are common among users of anabolic-androgenic steroids (AAS). However, the prevalence, expression, and severity of psychopathology differ among AAS users and remain poorly understood. In this study, we examine the existence of potential clinically coherent psychopathology subgroups, using cluster procedures. A sample of 118 male AAS users and 97 weightlifting nonusers was assessed using the Millon Clinical Multiaxial Inventory-III (MCMI-III), measuring personality disorders and clinical syndromes. Group differences in MCMI-III scales were assessed using Wilcoxon-Mann-Whitney tests and Fisher's exact test. Agglomerative hierarchical clustering was used to identify clusters based on MCMI-III scale scores from the whole sample. AAS users displayed significantly higher scores on all personality disorder (except narcissistic) and clinical syndrome scales compared to nonusing weightlifters. The clustering analysis found four separate clusters with different levels and patterns of psychopathology. The "no psychopathology" cluster was most common among nonusing weightlifters, while the three other clusters were more common among AAS users: "severe multipathology," "low multipathology," and "mild externalizing." The "severe multipathology" cluster was found almost exclusively among AAS users. AAS users also displayed the highest scores on drug and alcohol dependence syndromes. AAS users in our sample demonstrated greater psychopathology than the nonusing weightlifters, with many exhibiting multipathology. This may pose a significant challenge to clinical care for AAS users, particularly as there appears to be significant variation in psychopathology in this population. Individual psychiatric profiles should be taken into consideration when providing treatment to this group. As a group, AAS users displayed markedly greater psychopathology than nonusing weightlifters. Multipathology was common among AAS users. Four different subgroups of personality profiles were identified with distinct patterns of pathology and severity. The cross-sectional nature of the study precludes inferences about causality. The study is limited by possible selection bias, as participants choosing to be involved in research may not be entirely representative for the group as a whole. The study is vulnerable to information bias, as the results are based on self-report measures and interviews.


Glucose deprivation mediates interaction between CTDK-I and Snf1 in Saccharomyces cerevisiae.
Ctk1 is a kinase involved in transcriptional control. We show in the two-hybrid system that Ctk1 interacts with Snf1, a kinase regulating glucose-dependent genes. Co-purification experiments confirmed the two-hybrid interaction but only when cells were grown at low glucose concentrations. Deletion of Ctk1 or its associated partners, Ctk2 and Ctk3, conferred synthetic lethality with null mutants of Snf1 or Snf1-associated proteins. Northern blot analysis suggested that Ctk1 and Snf1 act together in vivo to regulate GSY2. These findings support the view that Ctk1 interacts with Snf1 in a functional module involved in the cellular response to glucose limitation.


First in-human intrathecal delivery of bevacizumab for leptomeningeal spread from recurrent glioblastoma: rationale for a dose escalation trial.
To outline the dose rationale for the first in-human intrathecal delivery of bevacizumab for LMS of GBM. A 19-year-old female patient presented to Lenox Hill Hospital following thalamic GBM recurrence. She subsequently underwent two infusions of intra-arterial BEV (NCT01269853) and experienced a period of relative disease stability until progression in 2022. One month later, MRI disclosed diffuse enhancement representative of LMS of GBM. The patient subsequently underwent five cycles of IT BEV in mid-2022 (IND 162119). Doses of 25 mg, 37.5 mg, 50 mg, 50 mg, and 37.8 mg were delivered at two-week intervals between doses 1-4. The final 37.8 mg dose was given one day following her fourth dose, given that the patient was to be discharged, traveled several hours to our center, and was tolerating therapy well. Dosage was decreased due to the short interval between the final two treatments. Shortly after IT BEV completion, she received a third dose of IA BEV. Our patient did not show any signs of serious adverse effects or dose limiting toxicities following any of the treatments. It is difficult to determine PFS due to the rapid progression associated with LMS of GBM and rapid timeframe of treatment. LMS continues to be a devastating progression in many types of cancer, including GBM, and novel ways to deliver therapeutics may offer patients symptomatic and therapeutic benefits.


The greater sensitivity of elderly APOE ε4 carriers to anticholinergic medications is independent of cerebrovascular disease risk.
Recent studies found use of anticholinergic medications to be associated with greater performance decrements in older persons who carry an ε4 allele of the apolipoprotein E (APOE) gene than in those carrying only ε2 or ε3 alleles. The present study examined whether the apparently greater behavioral toxicity of anticholinergic drugs in ε4 carriers may result from an increased risk of cerebrovascular disease, which is more common in ε4 carriers. Cross-sectional data were available from 240 elderly community volunteers who had participated in 2 different studies of the cognitive and motor effects of normal aging. As part of these studies, information was gathered on subjects' use of anticholinergic medications (based on an inventory of medications taken within 24 hours of testing), risk of cerebrovascular disease (Framingham Stroke Risk Profile), and APOE genotype. Performance data were also available from measures of general cognitive status (Mini-Mental State Examination), executive function (Trail Making Test), mood (Geriatric Depression Scale), sleep (Pittsburgh Sleep Quality Index), and walking speed. Logistic and linear regression models were used to examine how outcomes differed between genotypes and drug use, independent of the risk of cerebrovascular disease. In persons with a non-ε4 genotype, anticholinergic medication use did not significantly affect any of the behavioral measures. By contrast, among ε4 carriers, those taking anticholinergic drugs performed significantly worse than did those not taking such drugs on tests of general cognitive status, executive function, mood, and sleep. Adjusting for participants' stroke risk had a minimal effect on these results. Anticholinergic medication use was associated with poorer performance on measures of cognition, sleep, and mood only in older persons who carried 1 or more ε4 alleles of the APOE gene; this effect did not appear to be the result of an increased risk of cerebrovascular disease.


Fungal diversity and natural occurrence of fusaproliferin, beauvericin, deoxynivalenol and nivalenol in wheat cultivated in Santa Fe Province, Argentina.
The Fusarium diversity and the mycobiota associated with moldy wheat kernels from Santa Fe province, Argentine, was assessed. The wheat cultivated area in Santa Fe province is divided according to agrometeorological conditions into two zones: Zone I (north-central) and Zone II (south). The natural occurrence of Fusarium toxins BEA, FUP, DON and NIV was also determined. Cladosporium was the most abundant of the 19 genera identified, followed by Fusarium, Phoma and Alternaria. Zone II shows a predominance of F. graminearum and F. culmorum. In Zone I, DON was present in 13/32 samples (range 0.43-3.60 mg kg(-1)) and NIV in 6/32 samples (range 0.11-0.40 mg kg(-1)). In zone II, DON was found in 11/21 samples (range 0.57-9.50 mg kg(-1)) and NIV in 4/21 samples (range 0.10-0.60 mg kg(-1)). BEA and FP were not detected in both zones.


Calf thymus ds-DNA intercalation with pendimethalin herbicide at the surface of ZIF-8/Co/rGO/C3N4/ds-DNA/SPCE; A bio-sensing approach for pendimethalin quantification confirmed by molecular docking study.
Pendimethalin (PND) is a herbicide that is regarded to be possibly carcinogenic to humans and toxic to the environment. Herein, we fabricated a highly sensitive DNA biosensor based on ZIF-8/Co/rGO/C3N4 nanohybrid modification of a screen-printed carbon electrode (SPCE) to monitor PND in real samples. The layer-by-layer fabrication pathway was conducted to construct ZIF-8/Co/rGO/C3N4/ds-DNA/SPCE biosensor. The physicochemical characterization techniques confirmed the successful synthesis of ZIF-8/Co/rGO/C3N4 hybrid nanocomposite, as well as the appropriate modification of the SPCE surface. The utilization of ZIF-8/Co/rGO/C3N4 nanohybrid as a modifier was analyzed using. The electrochemical impedance spectroscopy results showed that the modified SPCE exhibited significantly lowered charge transfer resistance due to the enhancement of its electrical conductivity and facilitation of the transfer of charged particles. The proposed biosensor successfully quantified PND in a wide concentration range of 0.01-35 μM, with a limit of detection (LOD) value of 8.0 nM. The PND monitoring capability of the fabricated biosensor in real samples including rice, wheat, tap, and river water samples was verified with a recovery range of 98.2-105.6%. Moreover, to predict the interaction sites of PND herbicide with DNA, the molecular docking study was performed between the PND molecule and two sequence DNA fragments and confirmed the experimental findings. This research sets the stage for developing highly sensitive DNA biosensors that will be used to monitor and quantify toxic herbicides in real samples by fusing the advantages of nanohybrid structures with crucial knowledge from a molecular docking investigation.


PET imaging to assess the impact of P-glycoprotein on pulmonary drug delivery in rats.
Several drugs approved for inhalation for the treatment of pulmonary diseases are substrates of the adenosine triphosphate-binding cassette (ABC) transporter P-glycoprotein (P-gp). P-gp is expressed in the apical membrane of pulmonary epithelial cells and could play a role in modulating the pulmonary absorption and distribution of inhaled drugs, thereby potentially contributing to variability in therapeutic response and/or systemic side effects. We developed a new in vivo experimental approach to assess the functional impact of P-gp on the pulmonary delivery of inhaled drugs in rats. By using positron emission tomography (PET) imaging, we measured the intrapulmonary pharmacokinetics of the model P-gp substrates (R)-[11C]verapamil ([11C]VPM) and [11C]-N-desmethyl-loperamide ([11C]dLOP) administered by intratracheal aerosolization in three rat groups: wild-type, Abcb1a/b(-/-) and wild-type treated with the P-gp inhibitor tariquidar. Lung exposure (AUClung_right) to [11C]VPM was 64% and 50% lower (p < 0.05) in tariquidar-treated and in Abcb1a/b(-/-) rats, respectively, compared to untreated wild-type rats. For [11C]dLOP, AUClung_right was 59% and 34% lower (p < 0.05) in tariquidar-treated and in Abcb1a/b(-/-) rats, respectively. Our results show that P-gp can affect the pulmonary disposition of inhaled P-gp substrates, whereby a decrease in P-gp activity may lead to lower lung exposure and potentially to a decrease in therapeutic efficacy. Our study highlights the potential of PET imaging with intratracheally aerosolized radiotracers to assess the impact of membrane transporters on pulmonary drug delivery, in rodents and potentially also in humans.


Ultra-Short Course of Neo-Adjuvant Denosumab for Nerve-Sparing Surgery for Giant Cell Tumor of Bone in Sacrum.
This was a retrospective study about sacral giant cell tumor of bone (GCTB). This study aimed to investigate whether ultra-short course of neo-adjuvant denosumab treatment for sacral GCTB could (1) induce radiological and histological response? (2) Facilitate nerve-sparing surgery? (3) Achieve satisfactory oncological and functional outcomes? Previous reports on long course of neo-adjuvant denosumab treatment for GCTB showed significant tumor response and a relatively high recurrent rate after curettage. Sixty-six patients with sacral GCTB treated with neoadjuvant denosumab and nerve-sparing surgery were categorized into ultra-short course group (≤3 doses and operation within D21 since 1st dose, 41 patients) or conventional group (>3 doses or operation after D21 since 1st dose, 25 patients). The radiological and histological response, operative data, oncological and functional outcomes were compared. The ultra-short course group demonstrated fewer doses of neo-adjuvant denosumab (mean: 2.1 vs. 4.8, P < 0.001) and shorter time to surgery (12.2 days vs. 72.3 days, P < 0.001). Similar patterns of radiological and histological response were observed in the two groups with less fibrosis and ossification in the ultra-short course group. The operative duration (199.9 min vs. 187.8 min, P = 0.364) and estimated blood loss (1552.4 mL vs. 1474.0 mL, P = 0.740) were comparable. Most (94.8%) of the patients received adjuvant denosumab. After a mean follow-up of 29.4 months, three cases (8.8%) and five cases (20.8%) showed local recurrence in each group (P = 0.255). The estimated recurrence-free survival (56.2 vs. 51.2 months, P = 0.210) and the functional status [Motor-Urination-Defecation scores: 25.9 vs. 25.7, P = 0.762] did not differ between the two groups. Ultra-short course of neo-adjuvant denosumab for sacral GCTB could elicit radiological and histological responses as conventional course did. The less degree of fibrosis and ossification might facilitate nerve-sparing surgery and help to achieve satisfactory local control and functional status.Level of Evidence: 4.


Partially saturated fluid attenuated inversion recovery (FLAIR) sequences in multiple sclerosis: comparison with fully relaxed FLAIR and conventional spin-echo.
Fluid attenuated inversion recovery (FLAIR) sequences produce selective cerebrospinal fluid (CSF) suppression by employing a very long inversion time (TI). We used the FLAIR sequence to study patients with multiple sclerosis (MS) at 0.6 T. So far, a very long TR (and long acquisition time) has been used in a fully relaxed (FR-FLAIR) system. To speed up the FLAIR sequences, we used a shorter TR, and demonstrated that complete CSF suppression can be maintained with partial saturation (PS-FLAIR) by reducing TI at the same time. The introduction of partial saturation, however, reduced the contrast between lesions and normal appearing white matter (NAWM). Suboptimal CSF suppression therefore had to be accepted to maintain sufficient lesion to NAWM contrast. Using a TE of 60 ms, the PS-FLAIR and FR-FLAIR performed equally well in the detection of MS-lesions, although the former provided poorer CSF suppression. Both FLAIR sequences, however, provided poorer constrast between lesions and NAWM compared to conventional spin-echo sequences. Although the long acquisition time of the FLAIR sequence can be reduced by using partial saturation, complete CSF suppression and good lesion to NAWM contrast are incompatible at short TRs. Using a TE of 60 ms, conventional spin-echo sequences detect more lesions and provide better contrast between lesions and NAWM than FLAIR sequences in MS patients.


Treatment of facial venous malformations with combined radiofrequency current and 900 nm diode laser.
Laser treatment of venous malformations is a major challenge because of the large variations in skin pigmentation, anatomic location, and vessel size and depth. To determine the safety and effectiveness of electro-optical synergy, a new technology that combines the 900 nm diode laser with radiofrequency current for the treatment of facial venous malformation. Fourteen patients with Fitzpatrick skin types II to IV were treated for facial venous malformations with simultaneous radiofrequency energy (60-80 J/cm3) and optical diode laser energy (fluence 80-100 J/cm2) in one to three sessions. All lesions measured less than 100 cm2. Lesion clearance was evaluated by three specialists on the basis of digital photographs taken before the first treatment and 1 and 2 months after the last treatment. Thirteen patients showed a complete response and one patient a partial response. The results were rated excellent in the 13 patients and good in one patient. Transient swelling, erythema, and pain were present in all patients, with permanent scarring in only one patient. The combination of laser light and radiofrequency energy is effective and safe for the treatment of facial venous malformations. It provides additional heating of the vessels without increasing laser intensity. The side effects are minimal.


Factors Affecting Predation by Cyclidium sp. and Euplotes sp. on PAH-Degrading and Nondegrading Bacteria.
Abstract If predators select for or against contaminant-degrading bacteria, it will affect bacterial survival and has important implications for bioremediation. Protozoa are important predators of bacteria. In order to determine whether protozoa preyed differentially on bacteria with different degradation abilities, two ciliates (Euplotes sp. and Cyclidium sp.) and three strains of PAH-degrading bacteria (Vibrio spp., degrading naphthalene, anthracene, or phenanthrene) were isolated from sediment from New York/New Jersey Harbor. By manipulating growth conditions, bacterial strains with different PAH-degradation abilities and different cell properties were produced. Stepwise regression models were used to analyze how clearance rates on suspended bacteria and grazing rates on bacteria attached to particles were affected by bacterial size, hydrophobicity, C:N ratio, protein content, and PAH-degradation ability. Clearance rates ranged from 0 to 49 nl ciliate-1 h-1 for Euplotes sp. and from 0 to 1.7 nl ciliate-1 h-1 for Cyclidium sp. Clearance rates of both ciliates were positively correlated with bacterial size, hydrophobicity, and protein content, and negatively correlated with C:N ratio. PAH degradation ability had no (for Euplotes sp.) or small (for Cyclidium sp.) effects on clearance rates. The models accounted for 63-75% of the variation in clearance rates on different bacteria. Only Euplotes sp. grazed on attached bacteria, at rates from 3 to 176 bacteria ciliate-1 h-1. A regression model with only C:N ratio and protein content explained 45% of the variation in grazing rates. These models indicate that multiple properties of bacteria affect their susceptibility to predation by ciliates, but PAH-degradation ability per se has little effect.