Effects of acute exercise on insulin sensitivity, glucose effectiveness and disposition index in type 2 diabetic patients.
The aim of this work was to quantify the magnitude of changes in insulin sensitivity (S(I)) and glucose effectiveness (S(G)) in response to acute exercise in type 2 diabetic (T2D) patients, as previously studied in non-diabetic subjects. Seven T2D patients and seven non-diabetic controls participated in the study. Two intravenous glucose tolerance tests (0.5 g/kg) with frequent blood sampling over 180 minutes and mathematical modelling were carried out in a randomized fashion, one at rest and the other immediately following 15 minutes of exercise at 50% of the maximum theoretical heart rate (HR(max)) followed by five minutes at 85% of the HR(max). S(I) and S(G) were calculated using Bergman's minimal model. After exercise, S(I) was increased by 773% (from 0.62+/-0.16 to 5.41+/-1.59 min(-1) x 10(-4)/(microU/mL) and even reached the zone of control values at rest (5.52+/-2.28), whereas S(G) remained unchanged. The disposition index acute insulin response (AIR(G)) x S(I) and the product of fasting insulin (I(B)) x S(I) also increased after exercise. A single bout of exercise at moderate intensity in type 2 diabetics did not improve S(G), but markedly improved the low S(I) values found in these patients, indicating that the acute effects of exercise on S(I) are quantitatively important in the interpretation of training-related S(I) changes and may even be therapeutically useful on their own. Surrogates such as homoeostasis model assessment (HOMA) and quantitative insulin-sensitivity check index (QUICKI) were not sensitive enough to detect this increase in S(I) and should probably be used with caution in the follow-up of exercise protocols in diabetic patients.


Prognostic and diagnostic validity of p16/Ki-67, HPV E6/E7 mRNA, and HPV DNA in women with ASCUS: a follow-up study.
We evaluated the prognostic and diagnostic ability of p16/Ki-67 immunocytochemistry, HPV E6/E7 mRNA testing and HPV DNA assay in triaging ASCUS to find a way to manage cervical lesions more effectively. We conducted a prospective study through follow-up. The detection methods of the three factors: p16/Ki-67 immunocytochemistry conducted by using the CINtec® Plus Kit, E6/E7 mRNA testing by QuantiVirus®HPV E6/E7 mRNA assay and DNA by Hybrid Capture 2 assay. One hundred three women with ASCUS satisfied requirements and completed the entire follow-up process. All CIN2+ occurred in women who were mRNA positive at baseline, none in mRNA negative. 100% (6/6) patients with CIN2+ were HPV DNA assay positive, 100% (6/6) were HPV E6/E7 mRNA testing positive and 50.0% (3/6) were p16/Ki-67 immunocytochemistry positive. The risk ratio of E6/E7 mRNA test was 57.306 (95% CI 0.077-42,400.545). For endpoint of CIN2+, the sensitivity between HPV DNA assay and HPV E6/E7 mRNA testing is no statistical difference, but statistical difference exists between HPV E6/E7 mRNA testing vs. p16/Ki-67 immunocytochemistry (χ2 = 5.718, P = 0.023) and HPV DNA assay vs. p16/Ki-67 immunocytochemistry (χ2 = 5.718, P = 0.023). The specificity of E6/E7 mRNA testing, p16/Ki-67 and DNA assay in triaging ASCUS was 44.33, 75.26 and 11.34% respectively and is all statistical difference (χ2 = 26.277, P < 0.001(HPV DNA assay vs. HPV E6/E7 mRNA testing), χ2 = 19.297, P < 0.001(HPV E6/E7 mRNA testing vs. p16/Ki-67 immunocytochemistry), χ2 = 80.707, P < 0.001(HPV DNA assay vs. p16/Ki-67 immunocytochemistry). The expression level of 2097.09 copies/ml was the optimal cut-off value for HPV E6/E7 mRNA testing to diagnose CIN2+, the sensitivity and specificity was 61.1 and 68.2%. High expression of HPV E6/E7 mRNA could be a good candidate as a diagnostic biomarker to triage ASCUS superseding HPV DNA. p16/Ki-67 immunocytochemistry is suggested to be a good tool to triage ASCUS, but it reduced the sensitivity of diagnosis when improves the diagnostic specificity.


Effects of Gender and Estrogen Receptors on Iron-Induced Brain Edema Formation.
Our previous studies have shown that female mice have less brain edema and better recovery in neurological deficits after intracerebral hemorrhage (ICH) and that 17β-estradiol treatment in male mice markedly reduces ICH-induced brain edema. In this study, we investigated the role of gender and the estrogen receptors (ERs) in iron-induced brain edema. There were three parts in this study: (1) either male or female mice received an injection of 10 μL FeCl2 (1 mM) into the right caudate; (2) females received an intracaudate injection of FeCl2 or saline with 1 μg of ICI 182,780 (antagonists of ERs) or vehicle; and (3) males were treated with the ER regulator tamoxifen (5 mg/kg subcutaneously) or vehicle 1 h after FeCl2 injection. Mice were euthanized 24 h later for brain edema determination. FeCl2 induced lower brain edema in females than in males. Co-injection of ICI 182,780 with FeCl2 aggravated iron-induced brain edema in female mice. ICI 182,780 itself did not induce brain edema at the dose of 1 μg. Tamoxifen treatment reduced FeCl2-induced brain edema in male mice. In conclusion, iron induced less brain edema in female mice than in males. ER modification can affect iron-induced brain edema.


Sculpting the dendritic landscape: Actin, microtubules, and the art of arborization.
Dendrites are intricately designed neuronal compartments that play a vital role in the gathering and processing of sensory or synaptic inputs. Their diverse and elaborate structures are distinct features of neuronal organization and function. Central to the generation of these dendritic arbors is the neuronal cytoskeleton. In this review, we delve into the current progress toward our understanding of how dendrite arbors are generated and maintained, focusing on the role of the actin and microtubule cytoskeleton.


Interaction between CA repeat microsatellites and HIF1α regulated the transcriptional activity of porcine IGF1 promoter.
Insulin-like growth factor 1 (IGF1) is pivotal in the regulation of animal growth. Highly polymorphic CA repeat microsatellites have been identified in the IGF1 promoter region of different breeds of pigs. Previous studies showed that CA repeat microsatellites are associated with circulating IGF1 level. However, the mechanisms by which CA repeat microsatellites regulate IGF1 expression remain unclear. This study aimed to detect the association of CA repeat microsatellites with the transcriptional regulation of porcine IGF1 and the possible mechanisms. Results revealed that the number of CA repeats in porcine IGF1 promoter was 14-18, and a promoter with 14 or 15 CA repeats had a higher transcriptional activity (P < 0.01). Transcription factor hypoxia-inducible factor 1 subunit alpha (HIF1α) was confirmed to bind to the binding site upstream of CA repeat microsatellites. The microsatellites with 14 or 15 CA repeats were more sensitive to changes in the HIF1α expression level (P < 0.01). These results suggested that CA repeat microsatellites and HIF1α affected the transcriptional activity of each other in the regulation of IGF1 expression, thereby implying an interaction between them. Overall, this study provided novel evidence for elucidating the effects of CA repeat microsatellites on the transcriptional regulation of porcine IGF1.


A Call to Action: Current Challenges and Considerations for COVID-19 Vaccination in Immunocompromised Populations.
The heightened risk of infection and complexities of preventing disease in immunocompromised individuals are at the forefront of public health strategies. The COVID-19 pandemic highlighted the increased vulnerability and susceptibility to serious outcomes in this population. COVID-19 prevention efforts led to the development of vaccines, including mRNA-based options, which were initially recommended as a 2-dose primary schedule for both immunocompromised and immunocompetent individuals. However, post-rollout assessments led to updated recommendations specific to immunocompromised populations. As COVID-19 potentially transitions to become endemic disease, immunocompromised individuals will remain at high risk of severe disease; thus, the evaluation of current vaccination challenges remains crucial for guiding effective public health efforts. This article summarizes key findings from the previous articles of this supplement, highlighting current vaccination challenges for at-risk immunocompromised groups and exploring solutions to ensure protection against COVID-19 for these vulnerable populations.


Organization and transcriptional activity of brain chromatin subunits.
Digestion of brain nuclei with micrococcal nuclease produces 11.2-S chromatin subunits which comprise up to 80% of the total nuclear DNA. Hybridization studies with excess subunit DNA demonstrate that subunits are distributed throughout the repeated and nonrepeated sequences of the genome. No class of nonrepeated DNA appears to be excluded from subunits. Transcribed DNA is present in chromatin subunits since in vitro labelled poly(A+)-mRNA hybridizes to excess subunit DNA with kinetics identical to that for total DNA.


Effects of part sequences of human growth hormone on in vivo hepatic glycogen metabolism in the rat.
Acute effects of two part sequences of human growth hormone on the in vivo activity levels of hepatic glycogen synthase and glycogen phosphorylase were examined. The peptide corresponding to residues 6 to 13 of the hormone (hGH 6--13) decreased the percentage of phosphorylase in the active form without affecting synthase activity. This action was indirect and dependent upon insulin. The peptide hGH 177--191 decreased the level of the active form of synthase without affecting phosphorylase activity. This effect was also observed with analogous peptides containing the sequence hGH 178--191 (i.e., hGH 172--191 and hGH 178--191), whereas the peptide hGH 179--191 was inert. The onset of these effects was rapid, and maximum changes in activity were produced in 5 min by both peptides. The effect for hGH 177--191 was short-lived, and synthase activity had returned to normal levels by 15 min, whereas the action of hGH 6--13 was of longer duration and was still quite marked at 60 min. Both peptides showed a linear dependence of response to the log dose of peptide injected over the range 0.1--250 microgram hGH 6--13 per kg body weight and 0.05--25 microgram hGH 177--191 per kg body weight. Hepatic 3',5'-cyclicadenylic acid levels were not affected by either peptide. Incorporation of glycerol carbon into liver glycogen was increased by hGH 6--13 and decreased by hGH carbon into liver glycogen was increased by hGH 6--13 and decreased by hGH 177--191. This is discussed in terms of a futile cycle between glycogen and hexose phosphate in the liver, as the basis for a control mechanism for hepatic glycogen metabolism. The present observations are consistent with other in vivo and in vitro actions of these and related peptides.


Problems of Glioblastoma Multiforme Drug Resistance.
Glioblastoma multiforme (GBL) is the most common and aggressive brain neoplasm. A standard therapeutic approach for GBL involves combination therapy consisting of surgery, radiotherapy, and chemotherapy. The latter is based on temozolomide (TMZ). However, even by applying such a radical treatment strategy, the mean patient survival time is only 14.6 months. Here we review the molecular mechanisms underlying the resistance of GBL cells to TMZ including genetic and epigenetic mechanisms. Present data regarding a role for genes and proteins MGMT, IDH1/2, YB-1, MELK, MVP/LRP, MDR1 (ABCB1), and genes encoding other ABC transporters as well as Akt3 kinase in developing resistance of GBL to TMZ are discussed. Some epigenetic regulators of resistance to TMZ such as microRNA and EZH2 are reviewed.


The temporal stability and variability across frequency bands in neural synchrony between primary and secondary somatosensory areas following somatosensory stimulation.
To examine the temporal stability and variability of neuronal synchronization among the contralateral primary somatosensory cortex (cSI) and contralateral (cSII) and ipsilateral secondary somatosensory cortex (iSII) in response to median nerve stimulation. Both the spontaneous magnetoencephalography (MEG) signals as the pre-stimulus condition and somatosensory evoked magnetic-fields (SEF) were recorded in eleven healthy subjects. We calculated a phase-locking value (PLV) between two areas among cSI, cSII, and iSII in five frequency bands (theta: 5-7 Hz, alpha: 8-12 Hz, beta: 15-29 Hz, gamma-1: 30-59 Hz, and gamma-2: 60-90 Hz), and compared the PLV among in pre-stimulus and stimulus conditions. The PLV between cSI and cSII for the theta band activity varied within 2 s from the stimulus onset. On the other hand, the PLV between cSI and iSII for the alpha band did not vary within 2 s. The fluctuation of neuronal synchrony among sensory-related cortices in response to median nerve stimulation depends on the induced frequency band and inter-region. This study is the first to report the temporal characteristic of stimulus-driven neural synchrony following somatosensory stimulation.


A pro- and an anti-inflammatory cytokine are synthesised in distinct brain macrophage cells during innate activation.
Brain macrophages are known to exert dual and opposing functions on neuronal survival, which can be either beneficial or detrimental. The rationale of our study is that this duality could arise from an exclusive secretion of either pro- or anti-inflammatory cytokine by distinct cell subsets, cytokines that could respectively mediate neurotoxic or neurotrophic effects. Innate immune response was induced in macrophage cultures prepared from embryonic-day-16 to postnatal-day-8 mouse brains. By immunofluorescent detection of intracellular cytokines, we have assessed the occurrence of TNFalpha or IL10 synthesis at single cell level and observed distinct secretory patterns that include cells producing exclusively TNFalpha or IL10, cells producing both cytokines and non-producer cells. These secretory patterns are differentially regulated by MAP-kinase inhibitors. Altogether, these results demonstrate that synthesis of either a pro- or an anti-inflammatory cytokine can segregate distinct brain macrophages and suggests a functional cell-subset-specialisation.


Topical antibiotics in the high-risk biliary surgical patient. A prospective, randomized study.
This randomized, prospective study has evaluated the efficacy of topical antibiotics in preventing infective complications in patients undergoing high-risk biliary surgery. Sixty-nine patients who underwent bile duct exploration, choledochoenteric anastomosis, or cholecystectomy, either for acute cholecystitis or because they were older than 65 years of age, were randomized to the following three groups: Group I, topical antibiotics alone (22 patients); Group II, cefoxitin and topical antibiotics (24 patients); and Group III, penicillin, tobramycin, clindamycin, and topical antibiotics (23 patients). The incidence of infective complications was no different among the groups. There was one wound infection in each group, one episode of bacteremia in Group II, and no intraabdominal abscesses. This study has demonstrated that parenteral antibiotics administered prophylactically in the perioperative period offer no additional benefit over the use of effective topical antibiotics used intraoperatively in patients undergoing high-risk biliary surgery.


Resting-State Functional Connectivity Predicts STN DBS Clinical Response.
Deep brain stimulation of the subthalamic nucleus is a widely used adjunctive therapy for motor symptoms of Parkinson's disease, but with variable motor response. Predicting motor response remains difficult, and novel approaches may improve surgical outcomes as well as the understanding of pathophysiological mechanisms. The objective of this study was to determine whether preoperative resting-state functional connectivity MRI predicts motor response from deep brain stimulation of the subthalamic nucleus. We collected preoperative resting-state functional MRI from 70 participants undergoing subthalamic nucleus deep brain stimulation. For this cohort, we analyzed the strength of STN functional connectivity with seeds determined by stimulation-induced (ON/OFF) 15 O H2 O PET regional cerebral blood flow differences in a partially overlapping group (n = 42). We correlated STN-seed functional connectivity strength with postoperative motor outcomes and applied linear regression to predict motor outcomes. Preoperative functional connectivity between the left subthalamic nucleus and the ipsilateral internal globus pallidus correlated with postsurgical motor outcomes (r = -0.39, P = 0.0007), with stronger preoperative functional connectivity relating to greater improvement. Left pallidal-subthalamic nucleus connectivity also predicted motor response to DBS after controlling for covariates. Preoperative pallidal-subthalamic nucleus resting-state functional connectivity predicts motor benefit from deep brain stimulation, although this should be validated prospectively before clinical application. These observations suggest that integrity of pallidal-subthalamic nucleus circuits may be critical to motor benefits from deep brain stimulation. © 2020 International Parkinson and Movement Disorder Society.


Intelligent injury prediction for traumatic airway obstruction.
Airway obstruction is one of the crucial causes of death in trauma patients during the first aid. It is extremely challenging to accurately treat a great deal of casualties with airway obstruction in hospitals. The diagnosis of airway obstruction in an emergency mostly relies on the medical experience of physicians. In this paper, we propose the feature selection approach genetic algorithm-mean decrease impurity (GA-MDI) to effectively minimize the number of features as well as ensure the accuracy of prediction. Furthermore, we design a multi-modal neural network, called fully convolutional network with squeeze-and-excitation and multilayer perceptron (FCN-SE + MLP), to help physicians to predict the severity of airway obstruction. We validate the effectiveness of the proposed feature selection approach and multi-modal model on the emergency medical database from the Chinese General Hospital of the PLA. The experimental results show that GA-MDI outperforms the existing feature selection algorithms, while it is also validated that the model FCN-SE + MLP can effectively and accurately achieve the prediction of the severity of airway obstruction, which can assist clinicians in making treatment decisions for airway obstruction casualties.


Beta cell mass in diabetes: a realistic therapeutic target?
Beta cell deficiency underlies both type 1 and type 2 diabetes, and restoration or replacement of beta cell function is therefore the logical long-term solution to therapy. This review sets out to describe the defects in beta cell mass and function in both forms of diabetes, summarises current understanding of the underlying causes of beta cell death, and the methodological limitations of determining beta cell mass in vivo. Finally, the potential effects of current and future treatment regimens on beta cell mass and turnover are considered.


Development and evaluation of pH-sensitive biodegradable ternary blended hydrogel films (chitosan/guar gum/PVP) for drug delivery application.
pH responsive hydrogels have gained much attraction in biomedical fields. We have formulated ternary hydrogel films as a new carrier of drug. Polyelectrolyte complex of chitosan/guar gum/polyvinyl pyrrolidone cross-linked via sodium tripolyphosphate was developed by solution casting method. Fourier transform infrared spectroscopy, scanning electron microscopy and thermogravimetric analysis were conducted to examine the interactions between the polymeric chains, surface morphology and thermal stability, respectively. The swelling tests resulted that the swelling was reduced with the increase in the concentration of crosslinker due to the more entangled arrangement and less availability of pores in hydrogels. Ciprofloxacin hydrochloride was used as a model drug and its release in simulated gastric fluid, simulated intestinal fluid and phosphate buffer saline solution was studied. pH responsive behaviour of the hydrogels have subjected these hydrogels for drug release applications.


Sub-supercritical liquefaction of rice stalk for the production of bio-oil: Effect of solvents.
The effect of solvents (water and ethanol) on liquefaction characteristics of rice stalk (RS) was investigated in an autoclave. The highest conversion and liquid yield in water and ethanol were 84.95 wt%, 72.62 wt% and 78.93wt%, 63.84 wt%, respectively. FTIR and GC-MS of the bio-oils obtained from subcritical water (SubH2O, 300°C) and supercritical ethanol (scEtOH, 300°C) indicated that the behavior of RS liquefaction depended on solvents used. The major components of bio-oil produced in SubH2O were ketones and phenols, while esters and phenols dominated in scEtOH. ICP-OES analysis showed that the concentrations of potassium (K) and sodium (Na) in the bio-oil obtained from scEtOH were 14-15 times higher than that obtained from SubH2O. Ethanol gave rise to an improvement in the bio-oil properties including water content, density, acidity and HHV. It was concluded that the bio-oil from RS can be effectively upgraded in scEtOH.


Childhood diabetes: dietary aspects.
Insulin-dependent diabetes mellitus in children requires a delicate balance between injected insulin and food intake, taking into account physical activity and growth.


Primary leptomeningeal primitive neuroectodermal tumor.
Leptomeningeal metastases are a common complication of medulloblastomas and other primitive neuroectodermal tumors (PNETs). Much rarer are PNETs apparently arising in the leptomeninges. An 8-year-old boy presented with headache and vomiting, due to neoplastic meningitis from primary neuroectodermal tumor without an identifying mass. After craniospinal irradiation and chemotherapy (carboplatin, vincristine, cyclophosphamide and lomustine) the boy was in remission for 14 months, then suffered several relapses despite various chemotherapy regimens. After the initial presentation of 3.5 years the boy began to suffer from prolonged refractory non-convulsive status epilepticus and later expired from progression of primary leptomeningeal PNET.


Model-based assessment for human inhalation exposure risk to airborne nano/fine titanium dioxide particles.
This paper proposed a model-based approach to assess inhalation risk levels to manufacturing workers in titanium dioxide (TiO2) production factories. The risk level-based analytical schemes were present for investigations of job-related airborne nano/fine TiO2 dust exposures. A Hill model was used to reconstruct dose-response function based on data from rats exposed by chronic inhalation to poorly soluble fine and nanosized particles. A physiologically based lung model was used to predict surface area-based TiO2 burdens in alveolar surface and interstitial granuloma, respectively. The exposure effect was characterized by polymorphonuclear leukocytes (PMN) elevation effect on lung surface and lung tumor proportion on interstitium. Combining laboratory, field, and modeling results, two major findings were proposed to the current epidemiological studies: (i) the estimated median effective surface area-based TiO2 lung burden (EC50) for PMN elevation effect is 0.11 m2 g(-1) lung (95% CI: 0.04-0.2) and EC50 for lung tumor proportion is 1.15 m2 g(-1) lung (95% CI: 0.65-1.89) and (ii) the estimates of risk curves are the pivotal results for public policy. The results demonstrate that packers in US factories have approximately 85.77 fold (95% CI: 63.84-94.33) of standard PMN counts of 10(6), whereas 86.97 fold (95% CI: 66.72-94.54) for surface treatment workers in EU factories at risk of 0.5. The lung had approximately 45% (95% CI: 15%-54%) tumor proportion for packers in US factories, whereas 48.19% (95% CI: 20-53.79%) for surface treatment workers in EU factories at risk of 0.5. The findings point out that dry/wet treatment and ore handlers in US and maintenance mechanics in EU factories were unlikely to pose substantial lung cancer risks.


Synthesis of 2-hydroxy acid from 2-amino acid by Clostridium butyricum.
Cultures of Clostridium butyricum type strain in synthetic medium supplemented with various L-2-amino acids revealed the presence of the corresponding 2-hydroxy acid. This metabolite is able to produce the polyester poly(2-hydroxyalkanoic acid). The bioconversion is not stereoselective since D-2-amino acids were also converted. Chiral GC analysis demonstrated that only D-enantiomer is formed from L-leucine.


MRI-Guided Robotically Assisted Focal Laser Ablation of the Prostate Using Canine Cadavers.
a magnetic resonance imaging (MRI)-conditional needle guidance robot is developed to enhance MRI-guided focal laser ablation (FLA) therapy in patients with focal prostate cancer. inspired by the workflow of the manual FLA therapy, we developed an MRI-conditional robot with two degrees of freedom to provide the guidance for laser ablation catheter. This robot is powered by pneumatic turbine motors and encoded with the custom-designed optical encoder. The needle could be inserted manually through the designed robotic system, which keeps the patients inside MRI bore throughout the procedure. The robot hardware is integrated with the custom ablation planning and monitoring software (OncoNav) to provide an iterative treatment plan to cover the whole ablation zone. Virtual tumors were selected in three canine cadavers as targets to validate the performance of the proposed hardware and software system. phantom studies show that the average targeting error is less than 2 mm and the workflow of the entire procedure lasts for 100 minutes. Canine cadaver experiment results show that all the targets were successfully ablated in no more than three administrations. MRI-guided prostate FLA is feasible using the proposed hardware and software system, indicating potential utility in future human trials.


Voltammetric and spectroelectrochemical characterization of a water-soluble viologen polymer and its application to electron-transfer mediator for enzyme-free regeneration of NADH.
A water-soluble polyxylylviologen (PXV(2+)) was characterized with a view to making use of it as a redox electron-transfer (ET) mediator. Cyclic voltammetric and spectropotentiometric studies showed (i) that PXV(2+) gives two redox waves centering at -0.40 and -0.83 V (vs. Ag/AgCl (3.3 mol dm(-3) KCl)) and (ii) that the lifetime of its monocation radical (PXV(+.)) is two orders of magnitude greater than that of the well-utilized dimethyl viologen monocation radical. Subsequently, the reaction of the PXV(2+/+.) couple with NAD(+) was evaluated in the similar manners as above. On the basis of this evaluation and the bioluminescence assay using bacterial NADH/FMN oxidoreductase and luciferase, it was shown (i) that the PXV(2+/+.) couple functions as a useful electron-transfer mediator and (ii) that PXV(+.) reacts with NAD(+), leading to generation of the enzymatically active NADH, in the absence of any reductases.


Utilization of municipal sewage sludge as additives for the production of eco-cement.
The effects of using dried sewage sludge as additive on cement property in the process of clinker burning were investigated in this paper. The eco-cement samples were prepared by adding 0.50-15.0% of dried sewage sludge to unit raw meal, and then the mixtures were burned at 1450 °C for 2 h. The results indicated that the major components in the eco-cement clinkers were similar to those in ordinary Portland cement. Although the C(2)S phase formation increased with the increase of sewage sludge content, it was also found that the microstructure of the mixture containing 15.0% sewage sludge in raw meal was significantly different and that a larger amount of pores were distributed in the clinker. Moreover, all the eco-cement pastes had a longer initial setting time and final setting time than those of plain cement paste, which increased as the sewage sludge content in the raw meal increased. All the eco-cement pastes had lower early flexural strengths, which increased as the sewage sludge content increased, while the compressive strengths decreased slightly. However, this had no significant effect on all the strengths at later stages. Furthermore, the leaching concentrations of all the types of eco-cement clinkers met the standard of Chinese current regulatory thresholds.


Plasma levels of endothelial and B-cell-derived microparticles are restored by fingolimod treatment in multiple sclerosis patients.
No molecular marker can monitor disease progression and treatment efficacy in multiple sclerosis (MS). Circulating microparticles represent a potential snapshot of disease activity at the blood brain barrier. To profile plasma microparticles by flow cytometry in MS and determine how fingolimod could impact endothelial microparticles production. In non-treated MS patients compared to healthy and fingolimod-treated patients, endothelial microparticles were higher, while B-cell-microparticle numbers were lower. Fingolimod dramatically reduced tumour necrosis factor (TNF)-induced endothelial microparticle release in vitro. Fingolimod restored dysregulated endothelial and B-cell-microparticle numbers, which could serve as a biomarker in MS.


Structural plasticity of remote cortical brain regions is determined by connectivity to the primary lesion in subcortical stroke.
Cortical atrophy as demonstrated by measurement of cortical thickness (CT) is a hallmark of various neurodegenerative diseases. In the wake of an acute ischemic stroke, brain architecture undergoes dynamic changes that can be tracked by structural and functional magnetic resonance imaging studies as soon as 3 months after stroke. In this study, we measured changes of CT in cortical areas connected to subcortical stroke lesions in 12 patients with upper extremity paresis combining white-matter tractography and semi-automatic measurement of CT using the Freesurfer software. Three months after stroke, a significant decrease in CT of -2.6% (median, upper/lower boundary of 95% confidence interval -4.1%/-1.1%) was detected in areas connected to ischemic lesions, whereas CT in unconnected cortical areas remained largely unchanged. A cluster of significant cortical thinning was detected in the superior frontal gyrus of the stroke hemisphere using a surface-based general linear model correcting for multiple comparisons. There was no significant correlation of changes in CT with clinical outcome parameters. Our results show a specific impact of subcortical lesions on distant, yet connected cortical areas explainable by secondary neuro-axonal degeneration of distant areas.


Prevention of no-reflow/slow-flow phenomenon during rotational atherectomy--a prospective randomized study comparing intracoronary continuous infusion of verapamil and nicorandil.
The potential exists for microcirculatory impairment during rotational coronary atherectomy (RA) due to embolization of plaque debris, platelet aggregation, or vasospasm. This prospective randomized pilot study aimed to confirm favorable effects of nicorandil during RA compared with verapamil. We randomly assigned 200 patients with 219 coronary lesions planned to undergo RA with intracoronary infusion of nicorandil cocktail (100 patients, 109 lesions), which contained nicorandil 24 mg, nitroglycerin 5 mg, and heparin 10,000 U in 1000 mL saline, or verapamil cocktail (100 patients, 110 lesions), which contained verapamil 10 mg instead of nicorandil. Drug cocktails were infused through a 4F Teflon sheath of the rotablator system during RA. The primary end point was incidence of no-reflow/slow-flow phenomenon; secondary end points were those of continuous ST elevation, Q-wave myocardial infarction (MI), and non-Q-wave MI. Group baseline and coronary angiographic characteristics were similar. Rotational atherectomy was performed successfully, and no patients died or required emergency coronary artery bypass grafting. Incidence of no-reflow/slow-flow phenomenon was significantly lower in the nicorandil group (nicorandil 5/109 lesions, verapamil 13/110 lesions, P < .005). Incidences of persistent ST-segment elevation and non-Q-wave MI were significantly lower in the nicorandil group (ST-segment elevation: nicorandil 3/100 patients, verapamil 10/100 patients, P < .05; non-Q-wave MI: nicorandil 2/100, verapamil 9/100 patients, P < .05). One patient each in the 2 groups experienced Q-wave MI. Our findings suggest that continuous intracoronary infusion of nicorandil during RA prevents acute periprocedural complications. Nicorandil should be used as adjunctive treatment during RA.


Acute non-traumatic idiopathic spinal subdural hematoma: radiographic findings and surgical results with a literature review.
Intraspinal hematoma is a serious condition, and early diagnosis is necessary to permit emergency treatment. Among such hematomas, non-traumatic spinal subdural hematoma is a rare occurrence. We have experienced three patients with surgically proven subdural spinal hematoma, and here we report these cases with a review of their clinical and imaging characteristics. All three cases were idiopathic with no history of disease, no coagulopathy, and no trauma. All had acute onset that brought about paralysis of the lower limbs with severe pain. Early surgery was performed, based on a relatively early diagnosis using thoracolumbar MRI and CT. Since the epidural fat is not affected by bleeding, the normal structure remains and the boundary between hematoma and fat is a significant feature in MRI and CT. Partial Gd enhancement in MRI and ring enhancement in contrast CT were also apparent. Two of the cases had subarachnoid hematomas. Preoperative diagnosis of spinal subarachnoid hematoma is difficult because there are no specific radiological findings and confirmation can only occur intraoperatively. In particular, one case had a massive hematoma causing canal stenosis, and it was difficult to distinguish between intradural and extradural hematoma. In all cases of subarachnoid or subdural hematoma, decompression was performed within 24 h after onset, and consequently, the patients had relatively good outcomes.


Diagnosis of inherited disorders of liver metabolism.
Diagnosis of the metabolic disorder responsible for liver disease can sometimes be straightforward but it can also present a major challenge, particularly if the liver is sufficiently damaged to produce secondary biochemical abnormalities such as galactosuria, hypoglycaemia with hypoketonaemia, or excretion of 3-oxo-delta4 bile acids. It is important to consider the age of the patient, the nature of the liver disease, any extrahepatic clinical features, the imaging and the first-line laboratory tests when prioritizing diagnostic investigations. This article gives some examples of diagnoses made in our unit for patients with liver disease presenting in utero, in the neonatal period, in infancy and the preschool years, and in the school years. The differential diagnoses that should be considered for different clinical presentations are discussed.


Selection of patients for percutaneous closure in nonlacunar cryptogenic stroke associated with patent foramen ovale. Data from the NORDICTUS cooperative registry.
There is an extending use of percutaneous closure of patent foramen ovale (PFO) as therapy for PFO-associated cryptogenic strokes. The aim of our study was to investigate the clinical practice of percutaneous closure of PFO and to analyse the variables for decision-making on the selection of patients for this procedure. A prospective observational multicentric survey was conducted using all the cases of cryptogenic stroke/transient ischaemic attack associated with PFO recorded in the NORDICTUS hospital registry during the period 2018-2021. Clinical data, radiological patterns, echocardiogram data and factors related to PFO-associated stroke (thromboembolic disease and paradoxical embolism criteria) were recorded. The indication for closure was analysed according to age (≤/> 60 years) and the characteristics of the PFO. In the group ≤ 60 years (n = 488), 143 patients (29.3%) underwent PFO closure. The most influential variables for this therapy were detection of a high-risk PFO (OR 4.11; IC 2.6-6.5, P < .001), criteria for paradoxical embolism (OR 2.61; IC 1.28-5.28; P = .008) and previous use of antithrombotics (OR 2.67; IC 1.38-5.18; P = .009). In the > 60 years group (n = 124), 24 patients had PFO closure (19%). The variables related to this option were history of pulmonary thromboembolism, predisposition to thromboembolic disease, paradoxical embolism criteria, and high-risk PFO. The detection of a high-risk PFO (large shunt, shunt with associated aneurysm) is the main criterion for a percutaneous closure-based therapy. Other conditions to consider in the eligibility of patients are the history of thromboembolic disease, paradoxical embolism criteria or the previous use of antithrombotics.


Genetic polymorphisms of pharmacogenomic VIP variants in the Kyrgyz population from northwest China.
Pharmacogenomic variant information is well known for major human populations; however, this information is less commonly studied in minorities. In the present study, we genotyped 85 very important pharmacogenetic (VIP) variants (selected from the PharmGKB database) in the Kyrgyz population and compared our data with other four major human populations including Han Chinese in Beijing, China (CHB), the Japanese in Tokyo, Japan (JPT), a northern and western Europe population (CEU), and the Yoruba in Ibadan, Nigeria (YRI). There were 13, 12 and 16 of the selected VIP variant genotype frequencies in the Kyrgyz which differed from those of the CHB, JPT and CEU, respectively (p<0.005). In the YRI, there were 32 different variants, compared to the Kyrgyz (p<0.005). Genotype frequencies of ADH1B, AHR, CYP3A5, PTGS2, VDR, and VKORC1 in the Kyrgyz differed widely from those in the four populations. Haplotype analyses also showed differences among the Kyrgyz and the other four populations. Our results complement the information provided by the database of pharmacogenomics on Kyrgyz. We provide a theoretical basis for safer drug administration and individualized treatment plans for the Kyrgyz. We also provide a template for the study of pharmacogenomics in various ethnic minority groups in China.


Structure-specific recognition of quadruplex DNA by organic cations: influence of shape, substituents and charge.
Combining structure-specific recognition of nucleic acids with limited sequence reading is a promising method to reduce the size of the recognition unit required to achieve the necessary selectivity and binding affinity to control function. It has been demonstrated recently that G-quadruplex DNA structures can be targeted by organic cations in a structure-specific manner. Structural targets of quadruplexes include the planar end surfaces of the G-tetrad stacked columns and four grooves. These provide different geometries and functional groups relative to duplex DNA. We have used surface plasmon resonance and isothermal titration calorimetry to show that binding affinity and selectivity of a series of quadruplex end-stacking molecules to human telomeric DNA are sensitive to compound shape as well as substituent type and position. ITC results indicate that binding is largely enthalpy driven. Circular dichroism was also used to identify a group of structurally related compounds that selectively target quadruplex grooves.


Learning to distinguish between predators and non-predators: understanding the critical role of diet cues and predator odours in generalisation.
It is critical for prey to recognise predators and distinguish predators from non-threatening species. Yet, we have little understanding of how prey develop effective predator recognition templates. Recent studies suggest that prey may actually learn key predator features which can be used to recognise novel species with similar characteristics. However, non-predators are sometimes mislabelled as predators when generalising recognition. Here, we conduct the first comprehensive investigation of how prey integrate information on predator odours and predator diet cues in generalisation, allowing them to discriminate between predators and non-predators. We taught lemon damselfish to recognise a predator fed a fish diet, and tested them for their response to the known predator and a series of novel predators (fed fish diet) and non-predators (fed squid diet) distributed across a phylogenetic gradient. Our findings show that damselfish distinguish between predators and non-predators when generalising recognition. Additional experiments revealed that generalised recognition did not result from recognition of predator odours or diet cues, but that damselfish based recognition on what they learned during the initial conditioning. Incorporating multiple sources of information enables prey to develop highly plastic and accurate recognition templates that will increase survival in patchy environments where they have little prior knowledge.


Risk of invasive pneumococcal disease in children and adults with asthma: a systematic review.
The Advisory Committee on Immunization Practices (ACIP) recommended the inclusion of asthma as a high-risk condition that should warrant pneumococcal vaccination, but the National Advisory Committee on Immunization (NACI) in Canada has not yet done so. We aimed to determine the risk of invasive pneumococcal disease (IPD) in patients with asthma. We searched Ovid Medline, EMBASE, Classic EMBASE, PubMEd and Cochrane for articles published between January 1990 and February 2013, using the MeSH terms pneumococcal infections/or invasive pneumococcal disease and asthma. Google Scholar was used to retrieve articles citing the seminal article by Talbot et al. Articles were included if they were population-based studies that evaluated the relationship between IPD and asthma. Two authors independently assessed all titles and abstracts. All potentially relevant articles were retrieved as full text and assessed for inclusion. The combined searches yielded 376 articles, which were reviewed by title and abstract. At this stage, 330 articles were excluded; 40 articles were excluded at the full article review stage - leaving 6 articles. Two additional articles were found through Google Scholar. The evidence reviewed consistently showed a positive association between asthma and risk of IPD. However, the magnitude of this effect was heterogeneous with adjusted odds ratios ranging from 6.7 (95% CI 1.6-27.3) in adults >18 years to 1.7 (95% CI 0.99-3.0) in individuals aged 2-49 with low-risk asthma. The positive association between asthma and risk of IPD supports the addition of asthma as a high-risk condition warranting pneumococcal vaccination. Data on vaccine effectiveness in this population is needed.


The fine specificity of IgG antiguanosine antibodies in systemic lupus erythematosus.
The antigen specificity, isotype, and subclass of antinuclear antibodies may be related to their pathogenicity in systemic lupus erythematosus (SLE). Our laboratory found that IgG antibodies that bound the nucleoside, guanosine, occurred frequently in SLE patients. In contrast, sera from healthy subjects contained IgM but not IgG antiguanosine antibodies. The present studies were designed to characterized the fine specificity of IgG antiguanosine antibodies in SLE and compare them with IgM antiguanosine antibodies in normal sera. Serum antinuclear antibodies from six healthy subjects and six SLE patients were isolated by affinity binding to guanosine and measured by an enzyme-linked immunosorbent assay (ELISA). IgM in normal sera, and both IgM and IgG in SLE sera bound guanosine. IgM antiguanosine antibodies in normal sera were polyspecific and bound other nucleosides and 1-methylguanosine but not denatured DNA (ssDNA). In contrast, IgG antiguanosine antibodies from the SLE patients bound guanosine and ssDNA but not other nucleosides or 1-methylguanosine. SLE IgM antiguanosine antibodies had the same fine specificity and bound guanosine and ssDNA but not any of the other nucleosides. These results suggest that SLE IgG and IgM antiguanosine antibodies have fine specificity in contrast to the polyspecific IgM antibodies in normal sera. In addition, subclass analysis indicated that all SLE patients had either IgG1 or IgG3 subclass of antiguanosine antibodies that bind complement. Characterizing the isotype, subclass, and fine antigen specificity of antiguanosine antibodies should assist in evaluating their potential pathogenicity in SLE.


Identification of Spermatogenically Active Regions in Rat Testes by Using Narrow-band Imaging System.
To evaluate the feasibility of narrow-band imaging (NBI) system in microdissection testicular sperm extraction (micro-TESE). Firstly, we investigated angiogenic potential in human testicular specimens obtained from 48 patients who underwent micro-TESE. We then created a testicular injury model in rats with a single topical injection of cisplatin into the testes, and the testes were observed with and without NBI. To assess the relation between pathological changes and visual images, an immunofluorescence study of blood vessels in rat testes was carried out. We finally conducted an experiment that assumed micro-TESE by using a nonobstructive azoospermia (NOA) rat model induced by busulfan. The number of blood vessels in the specimens of hypospermatogenesis was significantly greater than that in the specimens of maturation arrest and Sertoli cell only. In rat testes, cisplatin caused atrophic changes, and significant differences in visual color between atrophic and normal lesions were noted using NBI. The number of seminiferous tubules with spermatozoa in atrophic regions was significantly lower than that in normal regions, and a significantly small number of blood vessels in atrophic regions was also noted compared with that in normal regions. NBI also identified patchy spermatogenesis in the busulfan-induced NOA rat model. An NBI system can distinguish spermatogenically active regions through the visualization of blood vessels in rat testes. This system may have the potential to provide useful information during micro-TESE for men with NOA.


Low-dose environmental endocrine disruptors, increase aromatase activity, estradiol biosynthesis and cell proliferation in human breast cells.
Phenolic endocrine-disrupting compounds (EDCs) have long been suspected of increasing human breast cancer risk, via aromatase up-regulation; however, the metabolic effects upon aromatase in human breast cells exposed to environmentally relevant concentrations of phenolic compounds, have not been addressed. To examine the mechanistic responses of aromatase CYP19A1 mRNA, aromatase activity, estradiol biosynthesis and cellular proliferation, in three human breast cell lines, exposed to seven phenolic compounds, at environmentally relevant concentrations. MCF-7 and ZR-75-1 breast cancer cells, and HMF3A breast fibroblasts were treated with specific concentrations of p,p'-DDT, methoxychlor, benzophenone-2, bisphenol A, bisphenol S, 4-phenylphenol and n-butylparaben, with and without the presence of aromatase inhibitors and estrogen receptor inhibitors. All test EDCs up-regulated aromatase mRNA, increased aromatase activity, significantly increased the aromatase-induced biosynthesis of the breast carcinogen 17β-estradiol, and increased ERα-positive breast cell proliferation. Inadvertent exposures to 'phenolic' EDCs, increase estradiol biosynthesis, and estrogen-sensitive breast cancer proliferation.


Is chronotype profile a risk indicator for caries in children and adolescents in sub-urban Nigeria?
To determine the association between chronotype and the prevalence of caries among in-school pupils aged 6- to 16-year-old residing in a sub-urban area in Nigeria. We hypothesize that in-school pupils who are evening chronotypes will have significantly higher prevalence of caries than those who are intermediate or morning chronotypes. This secondary analysis of a dataset collected in 2019 from 1502 children aged 6- to 16-year-old attending private and public primary and secondary schools in Ife Central Local Government Area, Nigeria. The dependent variable was caries prevalence. The explanatory variable was participants' chronotype profile (morning, intermediate, and evening). The confounding variables were caries risk factors (socio-economic status, age at last birthday, sex, use of fluoridated toothpaste, frequency of consumption of refined carbohydrates, and oral hygiene status). Poisson regression analysis was conducted. Data of 1001 (66.6%) students were retrieved. Of these, 59 (5.9%) had caries, 42 (4.2%) were evening type, 526 (52.5%) were intermediate type, and 433 (43.3%) were morning type. There was no significant association between chronotype and the prevalence of caries though children who were intermediate type (APR = 0.83; 95%CI: 0.41-1.66) and morning type (APR = 0.57; 95% CI: 0.27-1.18) were less likely to have caries than were those who were evening type. The children and adolescents' chronotype was not a significant risk indicator for caries in the study population.


Low-Dose Fluvoxamine Modulates Endocytic Trafficking of SARS-CoV-2 Spike Protein: A Potential Mechanism for Anti-COVID-19 Protection by Antidepressants.
Commonly prescribed antidepressants may be associated with protection against severe COVID-19. The mechanism of their action in this context, however, remains unknown. Here, I investigated the effect of an antidepressant drug fluvoxamine on membrane trafficking of the SARS-CoV-2 spike protein and its cell host receptor ACE2 in HEK293T cells. A sub-therapeutic concentration (80 nM) of fluvoxamine rapidly upregulated fluid-phase endocytosis, resulting in enhanced accumulation of the spike-ACE2 complex in enlarged early endosomes. Diversion of endosomal trafficking provides a simple cell biological mechanism consistent with the protective effect of antidepressants against COVID-19, highlighting their therapeutic and prophylactic potential.


Gene transfer via pollen-tube pathway for anti-fusarium wilt in watermelon.
In order to obtain transgenic fusarium wilt resistant watermelon plants, squash DNA was introduced into the ovaries of watermelon plants via the pollen-tube pathway. The introduction of foreign genes into ovaries was accomplished using co-transformation with the CaMV35S-GUS as a marker. Transformed watermelon plants contained integrated copies of the GUS activity and the seeds of transformed progeny produced a blue color when stained with 5-bromo-4-chloro-3-indolyl glucuronide, whereas seeds from untransformed control plants did not. Of 200 transformed seedlings, ten were wilt resistant. The presence of the GUS activity in the genome of stable transgenic seedlings was confirmed by Southern blot analysis. Furthermore, the generation of random amplified polymorphic DNA (RAPD) fingerprints using primers with embedded restriction sites showed amplification products unique to these transgenic plants. Primers OPA-1 and OPA-9 gave distinct band patterns of genomic DNA using the polymerase chain reaction.


A high degree of DNA strain polymorphism associated with the major heat shock gene in Caenorhabditis elegans.
We have searched for sequence variation between the Bristol and Bergerac strains of C. elegans in regions flanking three members of the 70 kilodalton (kd) heat shock peptide (hsp) gene family. No sequence variation was detected in 40 kb of DNA flanking two 70 kd hsp genes which are not stimulated by heat shock. In contrast, analysis of DNA flanking the heat shock inducible 70 kd hsp gene showed an unusually high amount of sequence variation between the two strains. Isolation and restriction map analysis of this gene from both strains revealed that the 5' and 3' flanking regions have diverged by 8.1 and 7.0% in nucleotide sequence, respectively. We have shown that these alterations are not due to large DNA rearrangements and conclude that the majority of sequence difference is the result of point mutations. Our results suggest that the heat shock inducible 70 kd hsp gene region accumulates mutations at a rate 10 to 20 fold higher than other regions of the genome. We propose that the anomalously high accumulation of mutational events is a direct consequence of the special status of the 70 kd hsp gene and its surrounding chromatin domain in the germline of C. elegans.


Cerebral metabolism in brain tumor of mice studied by in vivo 31P-NMR spectroscopy.
We now report a mouse model system of brain tumor for 31P-NMR spectroscopic study of in vivo cerebral metabolism. In vivo 31P-NMR (109 MHz) spectra were taken on the 9th day by the Faraday shield method of the brain of mice (3-week-old) transplanted intracerebrally with mKS X A tumor cells. In tumor-bearing mice, the amount of creatine phosphate decreased markedly and that of inorganic phosphate plus sugar phosphate increased accordingly. Furthermore, the broadening and splitting of individual signals were also noted with tumor-bearing mice; this is interpreted as indicating a variety of changes in chemical shift occurring in the brain of the animals due to heterogeneous distribution of pH. Binding or detaching of divalent cations to and from phosphometabolites may also be responsible for these changes.


Biosynthesis of flavonoids and effects of stress.
The accumulation of red or purple flavonoids is a hallmark of plant stress. Mounting evidence points to diverse physiological functions for these compounds in the stress response. Advances are also being made toward understanding how plants control the types and amounts of flavonoids that are produced in response to different cues.


Hydrofoam and oxygen headspace bioreactors improve cell-free therapeutic protein production yields through enhanced oxygen transport.
Protein therapeutics are powerful tools in the fight against diabetes, cancers, growth disorders, and many other debilitating diseases. However, availability is limited due to cost and complications of production from living organisms. To make life-saving protein therapeutics more available to the world, the possibility of magistral or point-of-care protein therapeutic production has gained focus. The recent invention and optimization of lyophilized "cell-free" protein synthesis reagents and its demonstrated ability to produce highly active versions of FDA-approved cancer therapeutics have increased its potential for low-cost, single-batch, magistral medicine. Here we present for the first time the concept of increased oxygen mass transfer in small-batch, cell-free protein synthesis (CFPS) reactions through air-water foams. These "hydrofoam" reactions increased CFPS yields by up to 100%. Contrary to traditional protein synthesis using living organisms, where foam bubbles cause cell-lysis and production losses, hydrofoam CFPS reactions are "cell-free" and better tolerate foaming. Simulation and experimental results suggest that oxygen transfer is limiting in even small volume batch CFPS reactors and that the hydrofoam format improved oxygen transfer. This is further supported by CFPS reactions achieving higher yields when oxygen gas replaces air in the headspace of batch reactions. Improving CFPS yields with hydrofoam reduces the overall cost of biotherapeutic production, increasing availability to the developing world. Beyond protein therapeutic production, hydrofoam CFPS could also be used to enhance other CFPS applications including biosensing, biomanufacturing, and biocatalysis.


Efficient gene transfer into human epithelial cell lines using glycosylated cationic carriers and neutral glycosylated co-lipids.
To date, no clear and constant relationship has been established between the chemical structure and the efficiency of non-viral transfection reagents. Despite the improvement of synthetic transfection systems, the capacity to transfect a target cell in a specific way is still a major challenge that gene therapy needs to overcome to be successful. Consequently, we developed a strategy aimed specifically at improving transfection of targeted human epithelial cells and to examine the possible effects of electrostatic interactions. Our attention therefore focused on the development of novel glycosylated formulations, based upon the introduction of one or two different carbohydrate ligands into (i) cationic lipid structures and (ii) synthetic neutral lipids incorporated into DNA and lipoplexes. Then, these formulations were tested in vitro on two human cell lines [HeLa and 16HBE14o(-)]. We report here that one of those formulations (CG 1/DOPE) is more efficient than DOTAP/DOPE. We determined that this non-viral transfection process is partially due to an endocytotic phenomenon mediated by targeting specific receptors directed toward specific carbohydrate elements. This was shown on 16HBE14o(-) cells where we observed a 43% and a 69% decrease in transfection when we blocked these receptors by the addition of free lactose and mannose, respectively. These results highlight the large adaptability of such monocationic glycolipids in the context of targeting and gene delivery.


Effect of dark phases and temperature on the chlorophyll a/b binding protein mRNA level oscillations in tomato seedlings.
External parameters (e.g. light/dark alterations and temperature) were tested for their ability to influence the expression pattern of the chlorophyll a/b binding protein (cab) genes and the small subunit of RuBPC/Oase (rbcS) genes. Particular interest was focused on the alterations of diurnal/circadian oscillation patterns of cab mRNA levels. Chlorophyll a/b binding protein and small subunit of RuBPC/Oase mRNA oscillations were observed in tomato seedlings grown without environmental perturbations (constant illumination and temperature), indicating that these genes are controlled by an endogenous rhythm. The rhythmic fluctuation patterns revealed a period of about 32 hours and a weekly expressed amplitude. A several-fold increase of the cab mRNA amplitude and a reduction of the period to about 24 hours (circadian) was monitored after exposure of the tomato seedlings to 3, 6 or 9 hours of darkness. The elevated amplitude disappeared at consecutive days if seedlings were not exposed to further dark phases. A circadian rhythm with clearly expressed cab mRNA amplitudes was also present after the plants had been transferred to darkness at various circadian times. However, under those circumstances the time points of maximum and minimum transcript levels were shifted by respective hours. Alteration of the growth temperature from 24 degrees C to 10 degrees C or 30 degrees C at constant illumination or in a light/dark cycle resulted in a reduction of the amplitudes or of the steady-state mRNA levels. Such extreme temperature changes do not induce or enhance the diurnal cab mRNA oscillations.


Biocontrol potential of the endophytic Epicoccum nigrum HE20 against stripe rust of wheat.
Biological control using endophytic microorganisms represents an eco-friendly and effective alternative to the health-hazardous chemical fungicides used to control devastating plant diseases such as stripe rust in wheat. In this study, the inhibitory potential of the endophytic Epicoccum nigrum HE20, isolated from a healthy wheat plant, was screened against uredospores germination in vitro. A high suppression (96%) in the germination of the uredospores was recorded. GC-MS analysis of the culture filtrate of E. nigrum HE20 showed a production of various secondary metabolites with an antifungal background such as butyric acid, α-linolenic acid, hexanoic acid, lactic acid, 10,12-Tricosadiynoic acid, and pentadecanoic acid. Results from the greenhouse experiment revealed that the application of E. nigrum HE20 suspension led to a reduction in the disease severity by 87.5%, compared with the untreated-infected plants. Real-time PCR results exhibited an overexpression in three defensive genes (JERF3, GLU, and PR1) in the infected wheat plants, in response to the application of E. nigrum HE20, recorded 8-, 15.8-, and 3.5-fold, respectively. In addition, an increment in the phenolic content, activity of POD, PPO, and CAT, and a reduction in the lipid peroxidation were recorded due to the endophyte application. Transmission electron microscopic observations indicated mitigation of the pathogen in wheat cells after the treatment with E. nigrum HE20 metabolite. Furthermore, a growth-promoting effect was also observed due to E. nigrum HE20 application, as well as an increment in the total photosynthetic pigments in wheat leaves. Based on these results, it can be concluded that E. nigrum HE20 is a probable efficient bioagent against stripe rust in wheat. However, its field evaluation is highly necessary in the future studies.


Efficient electrochemical conversion of carbon monoxide by rhodium octaethylporphyrin adsorbed on carbon black.
We have found efficient electrocatalytic removal of CO by rhodium octaethylporphyrin on carbon black at a wide potential range. Using carbon-supported rhodium octaethylporphyrin, we have separated the Rh(II) state participating reaction and the Rh(III) state participating reaction with CO. We have clearly demonstrated electrocatalytic CO oxidation by rhodium(III) porphyrin. The onset potential for CO oxidation is much lower than that for CO oxidation by conventional Pt/Ru catalysts and cobalt porphyrin.


Perspectives of stakeholders regarding the value of maternal and newborn health interventions and practices supported by UNICEF and other partners in the West Nile region of Uganda: a qualitative study.
Uganda has high maternal, neonatal, and under-five mortality rates. This study documents stakeholder perspectives on best practices in a maternal and newborn health (MNH) quality-improvement programme implemented in the West Nile region of Uganda to improve delivery and utilisation of MNH services. This exploratory cross-sectional qualitative study, conducted at the end of 2021, captured the perspectives of stakeholders representing the different levels of the healthcare system. Data were collected in four districts through: interviews with key informants working at all levels of the health system; focus group discussions with parents and caretakers and with community health workers; and interviews with individual community members whose lives had been impacted by the MNH programme. The initial content analysis was followed by a deductive synthesis pitched according to the different levels of the health system and the health-systems building blocks. The findings are summarised according to the health-systems building blocks and an account is given of three of the interventions most valued by participants: (1) data use for evidence-based decision making (with regard to human resources, essential reproductive health commodities, and financing); (2) establishment of special newborn care units and high-dependency maternity units at district hospitals and training of the health workforce (also with reference to other infrastructural improvements such as the provision of water, sanitation and hygiene facilities at health facilities); and (3) community referral of pregnant women through a commercial motorcycle voucher referral system. The MNH programme in the West Nile region adopted a holistic and system-wide approach to addressing the key bottlenecks in the planning, delivery, and monitoring of quality MNH services. There was general stakeholder appreciation across the board that the interventions had the potential to improve quality of care and newborn and maternal health outcomes. However, as the funding was largely donor-driven, questions about government ownership and sustainability in the context of limited resources remain.


Peripheral Neuropathy and Vision and Hearing Impairment in US Adults With and Without Diabetes.
We aimed to assess the associations of peripheral neuropathy (PN) with vision and hearing impairment among adults aged ≥40 years who attended the lower-extremity disease exam for the National Health and Nutrition Examination Survey (United States, 1999-2004). Overall, 11.8% (standard error (SE), 0.5) of adults had diabetes, 13.2% (SE, 0.5) had PN (26.6% (SE, 1.4) with diabetes, 11.4% (SE, 0.5) without diabetes), 1.6% (SE, 0.1) had vision impairment, and 15.4% (SE, 1.1) had hearing impairment. The prevalence of vision impairment was 3.89% (95% CI: 2.99, 5.05) among adults with PN and 1.29% (95% CI: 1.04, 1.60) among adults without PN (P < 0.001). After adjustment, PN was associated with vision impairment overall (odds ratio (OR) = 1.48, 95% confidence interval (CI): 1.03, 2.13) and among adults without diabetes (OR = 1.80, 95% CI: 1.17, 2.77) but not among adults with diabetes (P for interaction = 0.018). The prevalence of hearing impairment was 26.5% (95% CI: 20.4, 33.7) among adults with PN and 14.2% (95% CI: 12.4, 16.3) among adults without PN (P < 0.001). The association of PN with moderate/severe hearing impairment was significant overall (OR = 2.55, 95% CI: 1.40, 4.64) and among adults without diabetes (OR = 3.26, 95% CI: 1.80, 5.91). Overall, these findings suggest an association between peripheral and audiovisual sensory impairment that is unrelated to diabetes.


Burden of fungal infections in Qatar.
Few estimates of fungal disease frequency have been attempted in the Middle East. We have estimated the burden of fungal infections in Qatar. The aim of the study was to compute and determine the burden of serious fungal infections, in an attempt to estimate fungal disease frequency, which has not previously been attempted in this country. Disease statistics were collected from the Microbiology laboratory database and from 2011 WHO statistics. The data are expressed per 100,000 populations. The reported cases of candidaemia rose to 288 with an estimated rate of 15.4/100,000. A real increase in the burden of candidaemia was found over that previously reported (12.9/100,000) for the years 2004-2009. Candida peritonitis was estimated in 8.02 cases/100,000 population. Recurrent (≥4 year(-1) ) vaginal infections affect at least 32,782 women with a rate of 3506/100,000 inhabitants. Severe asthma with fungal sensitisation affected 1486 people, allergic bronchopulmonary aspergillosis 1126 people and chronic pulmonary aspergillosis 176 people. Rhinosinusitis, mucormycosis and Fusarium infection occurred at rates of 2.31, 1.23, 1.86 cases/100,000 respectively. The estimated rate of invasive aspergillosis was very low (0.6/100,000). Low rates of Cryptococcus meningitis and Pneumocystis pneumonia are attributable to low HIV infection rates. In conclusion, fungal infections are increasingly reported, especially candidaemia. Surveillance and guidelines are needed to optimise care and management of common fungal infections. In addition, a fungal registry system needs development for surveillance.


piRNA clusters as a main source of small RNAs in the animal germline.
PIWI subfamily Argonaute proteins and small RNAs bound to them (PIWI interacting RNA, piRNA) control mobilization of transposable elements (TE) in the animal germline. piRNAs are generated by distinct genomic regions termed piRNA clusters. piRNA clusters are often extensive loci enriched in damaged fragments of TEs. New TE integration into piRNA clusters causes production of TE-specific piRNAs and repression of cognate sequences. piRNAs are thought to be generated from long single-stranded precursors encoded by piRNA clusters. Special chromatin structures might be essential to distinguish these genomic loci as a source for piRNAs. In this review, we present recent findings on the structural organization of piRNA clusters and piRNA biogenesis in Drosophila and other organisms, which are important for understanding a key epigenetic mechanism that provides defense against TE expansion.


NAG-1/GDF15 protects against streptozotocin-induced type 1 diabetes by inhibiting apoptosis, preserving beta-cell function, and suppressing inflammation in pancreatic islets.
The loss of functional insulin-producing β-cells is a hallmark of type 1 diabetes mellitus (T1DM). Previously, we reported that the non-steroidal anti-inflammatory drug activated gene-1, or growth differentiation factor-15 (NAG-1/GDF15) inhibits obesity and improves insulin sensitivity in both genetic and dietary-induced obese mice. However, the regulatory role of NAG-1/GDF15 in the structure and function of β-cells and the prevention of T1DM is largely unknown. In the current study, we reported that NAG-1/GDF15 transgenic (Tg) mice are resistant to diabetogenesis induced by multiple low-dose streptozotocin (MLD-STZ) treatment. NAG-1/GDF15 overexpression significantly reduced diabetes incidence, alleviated symptoms of T1DM, and improved MLD-STZ-induced glucose intolerance and insulin resistance. Both the mass and function of pancreatic β cells were preserved in the NAG-1/GDF15 Tg mice as evidenced by significantly increased islet area and insulin production. The mechanistic study revealed that NAG-1/GDF15 significantly inhibited STZ-induced apoptosis and preserved the reduction of proliferation in the islets of the Tg mice as compared to the wild-type (WT) mice upon MLD-STZ treatment. Additionally, NAG-1/GDF15 significantly reduced both the serum and islet levels of the inflammatory cytokines (IL-1β, IL-6, and TNFα), and reduced the expression of NF-κB expression and immune cells infiltration in the islets. Collectively, these results indicate that NAG-1/GDF15 is effective in improving STZ-induced glucose intolerance, probably was mediated via suppressing inflammation, inhibiting apoptosis, and preserving β-cell mass and function.


Direct analysis in real time high-resolution mass spectrometry for authenticity assessment of lamb.
In comparison to more traditional methods of determining food authenticity, such as gas chromatography analysis, the primary advantages of DART-HRMS include its high speed and throughput of analysis. This study used a non-targeted metabolomics method based on real-time high-resolution mass spectrometry combined with chemometric analysis to distinguish lamb samples from four regions. Orthogonal least squares-discriminant analysis revealed a distinct difference between these four lamb regions. The potential markers were chosen based on the variable's importance in projection values, variance, and fold change. A total of 79 markers were identified using the matching chemistry database. These markers differed significantly between lambs in four regions according to heatmap analysis. The linear discriminatory analysis model had an initial classification rate of 100.0% and a cross-validation accuracy of 82.50% on the identified markers. The research demonstrates that DART-HRMS can perform a rapid authentication evaluation of lamb samples.


The Atoh7 remote enhancer provides transcriptional robustness during retinal ganglion cell development.
The retinal ganglion cell (RGC) competence factor ATOH7 is dynamically expressed during retinal histogenesis. ATOH7 transcription is controlled by a promoter-adjacent primary enhancer and a remote shadow enhancer (SE). Deletion of the ATOH7 human SE causes nonsyndromic congenital retinal nonattachment (NCRNA) disease, characterized by optic nerve aplasia and total blindness. We used genome editing to model NCRNA in mice. Deletion of the murine SE reduces Atoh7 messenger RNA (mRNA) fivefold but does not recapitulate optic nerve loss; however, SEdel/knockout (KO) trans heterozygotes have thin optic nerves. By analyzing Atoh7 mRNA and protein levels, RGC development and survival, and chromatin landscape effects, we show that the SE ensures robust Atoh7 transcriptional output. Combining SE deletion and KO and wild-type alleles in a genotypic series, we determined the amount of Atoh7 needed to produce a normal complement of adult RGCs, and the secondary consequences of graded reductions in Atoh7 dosage. Together, these data reveal the workings of an evolutionary fail-safe, a duplicate enhancer mechanism that is hard-wired in the machinery of vertebrate retinal ganglion cell genesis.


Generating dihydrogen by tethering an [FeFe]hydrogenase via a molecular wire to the A1A/A1B sites of photosystem I.
Photosystem I complexes from the menB deletion mutant of Synechocystis sp. PCC 6803 were previously wired to a Pt nanoparticle via a molecular wire consisting of 15-(3-methyl-1,4-naphthoquinone-2-yl)]pentadecyl sulfide. In the presence of a sacrificial electron donor and an electron transport mediator, the PS I-NQ(CH2)15S-Pt nanoconstruct generated dihydrogen at a rate of 44.3 µmol of H2 mg Chl-1 h-1 during illumination at pH 8.3. The menB deletion strain contains an interruption in the biosynthetic pathway of phylloquinone, which results in the presence of a displaceable plastoquinone-9 in the A1A/A1B sites. The synthesized quinone contains a headgroup identical to the native phylloquinone along with a 15-carbon long tail that is terminated in a thiol. The thiol on the molecular wire is used to bind the Pt nanoparticle. In this short communication, we replaced the Pt nanoparticle with an [FeFe]H2ase variant from Clostridium acetobutylicum that contains an exposed iron on the distal [4Fe-4S] cluster afforded by mutating the surface exposed Cys97 residue to Gly. The thiol on the molecular wire is then used to coordinate the corner iron atom of the iron-sulfur cluster. When all three components are combined and illuminated in the presence of a sacrificial electron donor and an electron transport mediator, the PS I-NQ(CH2)15S-[FeFe]H2ase nanoconstruct generated dihydrogen at a rate of 50.3 ± 9.96 μmol of H2 mg Chl-1 h-1 during illumination at pH 8.3. This successful in vitro experiment sets the stage for assembling a PS I-NQ(CH2)15S-[FeFe]H2ase nanoconstruct in vivo in the menB mutant of Synechocystis sp. PCC 6803.


Nitrogen and phosphorus addition exerted different influences on litter and soil carbon release in a tropical forest.
Terrestrial soils release large amount of carbon dioxide (CO2) each year, which are mainly derived from litter and soil carbon (C) decomposition. Nutrient availability, especially nitrogen (N) and phosphorus (P), plays an important role in both litter and soil C decomposition. Therefore, understanding the underlying mechanism is crucial for mitigating CO2 emission and climate changes. Here, we assessed patterns of litter and soil C decomposition after 11 yrs. in-situ N and P addition in a tropical forest where corn leaves or corn roots were added as litter C. The total CO2 efflux was quantified and partitioned using 13C isotope signatures to determine the sources (litter or soil C) every three months. In addition, Changes in C-degrading enzyme activities: β-1,4-glucosidase (BG), phenol oxidase (PHO) and peroxidase (PER), and microbial biomarkers were assessed to interpret the underlying mechanism. Total C-release was enhanced up to17% by the long-term N addition but inhibited up to 15% by P addition. Precisely, N addition only accelerated the litter decomposition and increased about 42% and 6% of the litter C release at 0-5 cm and 5-10 cm soil depths, respectively; while P addition only impeded the soil C decomposition and decreased about 9% and 11% of the soil C release at 0-5 cm and 5-10 cm, respectively. The enhanced C release under N addition might be attributed to the enhanced microbial biomass, the ratio of fungi to bacteria and C-degrading enzyme activities. However, P addition resulted in the reverse result in microbial properties and C-degrading enzyme activities, associated with a decreased C release. Our study suggests that the long-term N and P addition selectively affected the litter and soil C decomposition because of their different physiochemical properties and this tendency might be more pronounced in tropical forests exposed to increasing atmospheric N deposition in the future. The study indicates that the different patterns of litter and soil C decomposition under climate change should be taken account in the future C management strategies.


Cotton wool-like poly(lactic acid)/vaterite composite scaffolds releasing soluble silica for bone tissue engineering.
Cotton wool-like poly(L-lactic acid) and siloxane-doped vaterite (SiV) composite scaffolds were prepared with a modified electrospinning system for bone tissue engineering applications. The effects of changing the SiV content in the materials from 10 to 30 wt% on elasticity and the ability to release calcium ions and soluble silica were evaluated. The elasticity of the cotton wool-like composites was almost the same as that of the PLLA from the results of compressibility and recovery tests. The materials released calcium ions for more than 56 days and soluble silica for 28-56 days in a tris buffer solution (pH 7.4). Mouse osteoblast-like cells (MC3T3-E1 cells) were cultured on/in the cotton wool-like materials or the fibremats out of the same composite materials as that used for the cotton wool-like materials. The cells penetrated into and proliferated inside the cotton wool-like materials, although they mainly adhered on the fibremat surface.


Community voices in program development: the wisdom of individuals with incarceration experience.
This health promotion project used participatory processes to engage all stakeholders to design and pilot preventive health tools in partnership with and for individuals with incarceration experience. This article outlines the methods of engaging with this marginalized population and interventions conducted to successfully utilize participation in the planning phases of the project to develop collaborative values, mission, and project scope. Eighteen men and women with incarceration experience participated through two community organizations that were invited to work as project partners. Participatory planning was conducted through an iterative process and partnership between an academic institution and community organizations. Engagement was developed through community networks and partnership building, including articulation of shared values and formation of a Project Advisory Committee. Participatory planning was facilitated through focus groups and interviews conducted with prison leavers to narrow the scope of the project to three health priority areas. Discussion analysis was conducted using interpretive phenomenological qualitative methodology to extract themes in terms of underlying systemic barriers to health and suggestions for ways to address them. The interventions resulted in collaborative project planning and allowed for the prioritization of promoting holistic health for individuals with incarceration experience in mental health and addiction, cancer, and blood-borne infectious diseases by sharing knowledge, supporting self-advocacy, and strengthening relationships. Community engagement and participatory processes allowed the project to be more relevant to those it serves, and also meaningfully engaged prison leavers in an empowering participatory process to address health inequities.


Dynamics of directional coupling underlying spike-wave discharges.
Spike and wave discharges (SWDs), generated within cortico-thalamo-cortical networks, are the electroencephalographic biomarker of absence epilepsy. The current work aims to identify mechanisms of SWD initiation, maintenance and termination by the analyses of dynamics and directionality of mutual interactions between the neocortex and various functionally different thalamic nuclei. Local-field potential recordings of 16 male Wistar Albino Glaxo from Rijswijk (WAG/Rij) rats, equipped with electrodes targeting layer 4-6 of the somatosensory cortex, rostral and caudal reticular thalamic nuclei (rRTN and cRTN), ventro-posteromedial (VPM), anterior (ATN) and posterior (PO) thalamic nuclei, were obtained. 3s epochs prior to SWD onset, after SWD onset, prior to SWD offset and after SWD offset were analyzed with newly developed time-variant adapted nonlinear Granger causality. A gradual increase in coupling toward SWD onset between cortico-cortical pairs appears as early as 2s preictally. Next first unidirectional increase in coupling is noticed in a restricted number of cortico-thalamic and thalamo-cortical channel pairs, which turn into bidirectional coupling approaching SWD onset, and a gradual increase of intrathalamic coupling. Seizure onset is characterized by a coupling decrease for more than a second in a majority of channel pairs, only the cortex kept driving the cRTN. Intrathalamically the cRTN drives the PO, VPM and ATN. Most channel pairs no longer show differences in coupling with baseline during SWD maintenance, a major exception is the unidirectional coupling between cortex and cRTN. Toward the end of SWDs, more and more channel pairs show an increase in often bidirectional coupling, this increase suddenly vanishes at SWD offset. The initiation of SWD is due to a gradual increase in intracortical coupling, followed by a selective increase in first unidirectional and later bidirectional coupling between the cortex and thalamus and also intrathalamically. Once the network is oscillating, coupling decreases in most of the channel pairs, although the cortex keeps its influence on the cRTN. The SWD is dampened by a gradual increase in coupling strength and in the number of channel pairs that influence each other; the latter might represent an endogenous brake of SWDs.


Surgical management of symptomatic pulmonary aspergilloma.
Pulmonary aspergilloma is a potentially life-threatening disease resulting from the colonization of lung cavities by the ubiquitous fungus Aspergillus fumigatus. Complex aspergilloma, characterized by thick-walled cavities with surrounding parenchymal inflammation, is a risk factor for increased morbidity and mortality. Fifteen patients with symptomatic aspergilloma underwent major thoracic procedures at North Carolina Memorial Hospital between January 1, 1972, and December 31, 1983. Twelve of the patients had hemoptysis; in 7 it was recurrent and in 5, life threatening. Tuberculosis and sarcoidosis were the most common underlying causes of lung disease, and more than half of the patients had other coexistent serious medical illness. Eleven of the 15 patients were seen with complex aspergilloma; all of the 4 major complications and the 2 deaths occurred in these patients. Bronchopleural fistula with persistent air space was the most common serious complication, and required thoracoplasty in 3 patients. Nine patients, including 5 with complex aspergilloma, had no postoperative complications, and there were no recurrent symptoms in any of the 13 operative survivors over a mean follow-up of five years. It is concluded that aggressive pulmonary resection can provide effective long-term palliation in critically ill patients with symptomatic pulmonary aspergilloma.


Chemotherapy as monotherapy for treatment of non-metastatic bladder/prostate embryonal rhabdomyosarcoma in children: preliminary report.
This work aims at evaluation of chemotherapy as mono-therapy for treatment of non-metastatic bladder/prostate embryonal rhabdomyosarcoma in children. Between 1996 and 2002, 10 children presented with RMS of the bladder/prostate at a mean age of 6.6 years (range 1.5-18). Four patients had stage 2 disease and 6 had stage 3. The histology was embryonal in 8 and botryoid in 2. All patients received VAC chemotherapy for a mean duration of 14 months (range 12-18). CT or MRI was performed at 8 weeks, every 3 months in the first year and every 6 months thereafter. The mean follow-up duration was 48 months (range 12-96). At 8 weeks, 7 children showed more than 50% reduction in tumour size and the remaining 3 showed complete disappearance on CT or MRI. At final follow-up 8 patients are living, disease-free, with functioning bladder. The remaining 2 patients died of metastatic disease at 12 and 14 months from start of treatment. Out of the 8 survivors, 5 had complete disappearance of the tumour at last follow-up while 3 had residual tumour on CT/MRI. Those children underwent transurethral endoscopic resection and the pathology showed no evidence of malignancy in all. The 4-year disease-free survival was 100% for stage 2 and 66% for stage 3. Chemotherapy as mono-therapy is effective treatment in children with stage 2 embryonal RMS of the bladder/prostate with the advantage of bladder preservation. Within stage 3, non-survivors had statistically significant larger tumours. Adjuvant therapy or more intensive chemotherapy might be required for those with large stage 3 tumours.


Clinical and laboratory studies of the novel cyclin-dependent kinase inhibitor dinaciclib (SCH 727965) in acute leukemias.
Dinaciclib inhibits cyclin-dependent kinases 1, 2, 5, and 9 with a better therapeutic index than flavopiridol in preclinical studies. This study assessed the activity of dinaciclib in acute leukemia both in the clinic and in vitro. Adults with relapsed/refractory acute myeloid leukemia (n = 14) and acute lymphoid leukemia (n = 6) were treated with dinaciclib 50 mg/m(2) given as a 2-h infusion every 21 days. Most patients had dramatic but transient reduction in circulating blasts; however, no remissions were achieved on this schedule. The most common toxicities were gastrointestinal, fatigue, transaminitis, and clinical and laboratory manifestations of tumor lysis syndrome, including one patient who died of acute renal failure. Dinaciclib pharmacokinetics showed rapid (2 h) achievement of maximum concentration and a short elimination/distribution phase. Pharmacodynamic studies demonstrated in vivo inhibition of Mcl-1 expression and induction of PARP cleavage in patients' peripheral blood mononuclear cells 4 h after dinaciclib infusion, but the effects were lost by 24 h and did not correlate with clinical outcome. Correlative in vitro studies showed that prolonged exposures to dinaciclib, at clinically attainable concentrations, result in improved leukemia cell kill. While dinaciclib given as a 2-h bolus did not exhibit durable clinical activity, pharmacokinetic and pharmacodynamic data support the exploration of prolonged infusion schedules in future trials in patients with acute leukemias.


Reproductive water supply is prioritized during drought in tomato.
Reproductive success largely defines the fitness of plant species. Understanding how heat and drought affect plant reproduction is thus key to predicting future plant fitness under rising global temperatures. Recent work suggests reproductive tissues are highly vulnerable to water stress in perennial plants where reproductive sacrifice could preserve plant survival. However, most crop species are annuals where such a strategy would theoretically reduce fitness. We examined the reproductive strategy of tomato (Solanum lycopersicum var. Rheinlands Ruhm) to determine whether water supply to fruits is prioritized above vegetative tissues during drought. Using optical methods, we mapped xylem cavitation and tissue shrinkage in vegetative and reproductive organs during dehydration to determine the priority of water flow under acute water stress. Stems and peduncles of tomato showed significantly greater xylem cavitation resistance than leaves. This maintenance of intact water supply enabled tomato fruit to continue to expand during acute water stress, utilizing xylem water made available by tissue collapse and early cavitation of leaves. Here, tomato plants prioritize water supply to reproductive tissues, maintaining fruit development under drought conditions. These results emphasize the critical role of water transport in shaping life history and suggest a broad relevance of hydraulic prioritization in plant ecology.


A strong contender for mental health screening in Latinx immigrant youth: Psychometric properties of the Strengths and Difficulties Questionnaire.
Latinx youth seeking asylum in the U.S. experience mental health disparity due to exposure to trauma and adversity. Health systems and schools in the U.S. are unprepared to screen for psychopathology in this population, much of which is mono-lingual Spanish-speaking, due to the absence of psychometrically-vetted instruments. The Strengths and Difficulties Questionnaire (SDQ) has strong empirical support as a mental health screener in other demographics. However, there has been no psychometric research in Spanish-speaking immigrant youth and, therefore, the utility in this population remains unknown. The aims of the current study were to examine the SDQ's (a) internal structure, (b) factor structure, (c) test-retest reliability, and (d) concurrent validity. Results are based on N = 110 recently immigrated high school students (60% male, Mage = 19) who completed the SDQ in Spanish. Findings provided support for the Total Score, which displayed evidence of internal consistency, test-retest reliability, and concurrent validity with the Child Behavior Checklist. However, support for the use of the SDQ's subscale scores was limited. In sum, the SDQ Total Score holds promise as a screening instrument for recently immigrated Latinx youth in clinical, health, and educational settings, and use of the subscales requires future research and refinement.


Laparoscopic enucleation of a pancreatic insulinoma: report of a case.
We report herein the case of a 48-year-old Japanese woman in whom a pancreatic insulinoma was successfully treated by laparoscopic enucleation. The patient presented after developing episodic neurohypoglycemic symptoms, and an insulinoma in the pancreatic tail, 1.0 cm in diameter, was diagnosed by the results of biochemical and radiological examinations. A laparoscopic intraoperative ultrasonogram demonstrated a solitary hypoechogenic tumor in the pancreatic tail. After the tail and body of the pancreas with the spleen were mobilized, laparoscopic enucleation was performed without any complications. The total operative time was 225min and the estimated blood loss was 20 ml. Serial blood sugar measurements demonstrated a sharp rise in blood sugar levels at the time of enucleation. The patient's postoperative course was uneventful, and she was discharged on the seventh postoperative day. She has remained well for 33 months following surgery without any hypoglycemic symptoms.


Involution of retinochoroidal shunt vessel after radiotherapy for optic nerve sheath meningioma.
To illustrate the development and involution of retinochoroidal shunt vessel of the optic disc in a patient with primary optic nerve sheath meningioma. A 38-year-old woman presented with gradual onset of blurred vision in her right eye. Examination revealed a right relative afferent pupillary defect and mild edema of the right optic disc. Computed tomography (CT) showed changes consistent with a primary optic nerve sheath meningioma affecting the orbital portion of the right optic nerve. Patient was observed without treatment and subsequently developed a retinochoroidal shunt vessel on her right optic disc. With progression of the meningioma towards the optic chiasm, treatment with stereotactic radiosurgery was done. Following treatment, the optic disc gradually became pale and the retinochoroidal shunt vessel decreased in caliber with complete involution three years after radiotherapy.


CCAAT/enhancer-binding protein δ: multifaceted regulator in respiratory disease.
This Correspondence relates to the recently published article by Yan et al (Am J Pathol, 2012:420-430) that demonstrated that CCAAT/enhancer-binding protein δ (C/EBPδ) drives cytokine production, neutrophil accumulation, and lung vascular leakage in a murine model of lipopolysaccharide (LPS)-induced acute lung injury.


Fatigue of airway obstruction during long-term exposure to allergen aerosol.
The response to prolonged antigen exposure and the potentiation of airway resistance increase to ACH challenge, after this exposure, were studied on sixteen boxer dogs. One group of animals presented fatigue to A.E. after 3 hours of exposure. This group developed an increased response to ACH aerosol after fatigue to antigen was present. In a second group of dogs, absence of fatigue during prolonged exposure to allergen was observed. A growing tendency of Edyn (as an index of airway resistance) was observed after 5 hours of exposure. The therapeutical influence of bilateral vagus blockade was tested in these last animals. Blockade of nervus vagus released airway obstruction during prolonged allergen exposure and no bronchoconstriction was observed after ACH challenge during blockade.


[The calcium sensitizer levosimendan gives superior results to dobutamine in postoperative low cardiac output syndrome].
The use of levosimendan to treat postoperative low cardiac output syndrome (LCOS) has been studied in only small patient series and in randomized trials focusing on hemodynamic variables. The objective of the present study was to assess the effectiveness of levosimendan, compared with dobutamine, as a treatment for postoperative LCOS. Patients with LCOS were randomly assigned to receive either levosimendan (loading dose, 10 microg/kg, followed by 0.1 microg/kg per min for 24 h) or dobutamine (starting dose, 5 microg/kg per min). Hemodynamic and clinical parameters (including postoperative mortality and major complications), the need for the coadministration of another drug (such as an inotrope or a vasopressor) or for balloon counterpulsation, and length of stay in intensive care were all monitored. The study included 137 patients: 69 received levosimendan, while 68 were treated with dobutamine. Although both agents improved hemodynamic parameters, the effect of levosimendan was greater and occurred earlier than that of dobutamine. In addition, levosimendan use resulted in lower postoperative mortality (8.7% vs. 25%; P< .05), a lower incidence of major postoperative complications, and less need for an additional inotropic drug (8.7% vs. 36.8%; P< .05), a vasopressor (11.6% vs. 30.9%; P< .05), or balloon counterpulsation (2.9% vs. 14.7%; P<0.05). The length of stay in intensive care was also less (66 vs. 158 h; P< .05). In this randomized study, levosimendan proved more effective than dobutamine. Postoperative morbidity and mortality were lower, fewer patients required either an additional inotropic drug, a vasopressor or intra-aortic balloon counterpulsation, and the length of stay in intensive care was shorter.


How does the N-acylation and esterification of amphotericin B molecule affect its interactions with cellular membrane components-the Langmuir monolayer study.
This work presents the results of Langmuir monolayers study of two amphotericin B derivatives obtained by N-acylation (N-acetylamphotericin B, Ac-AmB) and esterification (amphotericin B methyl ester, AME) of the parent AmB molecule. The main objective of present investigations was to examine the strength and nature of interactions of Ac-AmB and AME with natural membrane components as compared to AmB, and verify the monolayer results with biological studies in vitro. Our experiments were based on surface pressure-area measurements of mixed monolayers formed by the investigated antibiotics and sterols/DPPC. The interactions were analyzed with the following dependencies: compression modulus-surface pressure, mean molecular area-composition, excess molecular area-composition and excess free energy-composition plots. It has been found that both Ac-AmB and AME form monolayers of a liquid expanded state and their stability is highest as compared to AmB films. The investigated compounds mix in monolayers with natural membrane components within the whole range of the antibiotic mole fraction. The quantitative analysis of the interactions of the investigated antibiotics with sterols and DPPC as well as sterols/DPPC interactions allow us to verify the monolayer results with biological results. A good correlation between both kinds of studies has been found.


Low angle light scattering studies on whole, half, and quarter molecules of T2 bacteriophage DNA.
Static light scattering measurements have been made at angles as low as 8 degrees on whole, half, and quarter molecules of native, T2 bacteriophage DNA in 0.195 M Na+. The fragments were obtained by high-speed stirring of the native DNA, and fractionated on methylated-albumin-kieselguhr columns. Accompanying measurements of sedimentation coefficients and intrinsic viscosities were made. Because linear extrapolations of light scattering data above 8 degrees for these samples were suspect, the measurements were analyzed by fitting curves calculated from the theory of wormlike coils to experimental curves at c = 0. Results showed that the excluded volume parameter, epsilon, must be used in analyzing the scattering curves; a reasonable value of epsilon was 0.08, in agreement with that found for T7 DNA (Harpst, J. A. 1980. Biophys. Chem. 11:295-302). The persistence length of all three DNAs in this paper was 50 +/- 5 nm, showed no dependence on molecular weight, but was somewhat below that reported previously for T7 DNA (60 nm). Theoretical curves calculated with the preceding parameters had a clear upward curvature in scattering envelopes below 8 degrees for quarter and half molecules, but such curvature was minimal for whole T2 DNA, so that linear extrapolations of experimental data above 8 degrees gave a molecular weight and root-mean-square radius which were nearly the same as those from theory. The molecular weight and radius for whole T2, derived from the comparison of theory and experiment, were 115 X 10(6) and 1,224 nm, respectively. The measurements on T2 DNA were clearly at the upper limit of current techniques.


A fatal case of disseminated chronic Q fever: a case report and brief review of the literature.
Chronic Q fever is a rare infection, which mainly manifests as endocarditis, infection of vascular prostheses or aortic aneurysms. We present the case of a 74-year-old immunocompromised man with a haematologically disseminated Coxiella burnetii infection, which has never been reported before. He was diagnosed with a chronic Q fever infection of an aneurysm with an endovascular prosthesis in 2015, but he died despite optimal treatment. Autopsy revealed a disseminated C. burnetii infection, confirmed by a positive PCR on samples from several organs. Retrospectively, he already had complaints and signs of inflammation since 2012, for which he had already been admitted in February 2014. At that time, Q fever diagnostics using PCR, complement fixation assay, and enzyme-linked immunosorbent assay on serum were all negative. In retrospect however, retesting available samples from February 2014 using immunofluorescence assay (IFA) already revealed serology compatible with chronic Q fever. Clinicians should be aware of this silent killer, especially in case of risk factors, and perform an appropriate diagnostic work-up for Q fever including IFA serology and PCR.