Charge-transfer excitations in uranyl tetrachloride ([UO2Cl4]2-): how reliable are electronic spectra from relativistic time-dependent density functional theory?
Four-component relativistic time-dependent density functional theory (TD-DFT) is used to study charge-transfer (CT) excitation energies of the uranyl molecule as well as the uranyl tetrachloride complex. Adiabatic excitation energies and vibrational frequencies of the excited states are calculated for the lower energy range of the spectrum. The results for TD-DFT with the CAM-B3LYP exchange-correlation functional for the [UO(2)Cl(4)](2-) system are in good agreement with the experimentally observed spectrum of this species and agree also rather well with other theoretical data. Use of the global hybrid B3LYP gives qualitatively correct results, while use of the BLYP functional yields results that are qualitatively wrong due to the too low CT states calculated with this functional. The applicability of the overlap diagnostic of Peach et al. (J. Chem. Phys.2008, 128, 044118) to identify such CT excitations is investigated for a wide range of vertical transitions using results obtained with three different approximate exchange-correlation functionals: BLYP, B3LYP, and CAM-B3LYP.


Myofibrillar Myopathies: New Perspectives from Animal Models to Potential Therapeutic Approaches.
Myofibrillar myopathies (MFMs) are muscular disorders involving proteins that play a role in the structure, maintenance processes and protein quality control mechanisms closely related to the Z-disc in the muscular fibers. MFMs share common histological characteristics including progressive disorganization of the interfibrillar network and protein aggregation. Currently no treatment is available. In this review, we describe first clinical symptoms associated with mutations of the six genes (DES, CRYAB, MYOT, ZASP, FLNC and BAG3) primary involved in MFM and defining the origin of this pathology. As mechanisms determining the aetiology of the disease remain unclear yet, several research teams have developed animal models from invertebrates to mammalians species. Thus we describe here these different models that often recapitulate human clinical symptoms. Therefore they are very useful for deeper studies to understand early molecular and progressive mechanisms determining the pathology. Finally in the last part, we emphasize on the potential therapeutic approaches for MFM that could be conducted in the future. In conclusion, this review offers a link from patients to future therapy through the use of MFMs animal models.


PPARG gene C161T CT/TT associated with lower blood lipid levels and ischemic stroke from large-artery atherosclerosis in a Han population in Guangdong.
Peroxisome proliferator-activated receptor gamma (PPARG) is a transcription factor involved in atherosclerosis and related diseases. In this study, we aimed to investigate whether PPARG C161T was associated with lipid levels and large-artery atherosclerosis (LAA) ischemic stroke in a Han Chinese population in Guangdong province. The genotype PPARG C161T in 149 LAA ischemic stroke patients and 125 healthy controls was examined by polymerase chain reaction-restriction fragment length polymorphism (RFLP) assay. Associations with LAA ischemic stroke were analyzed for PPARG C161T genotype, total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C), and a logistic regression analysis was performed to identify risk factors for LAA ischemic stroke. The frequency of CC was higher than that of CT + TT and was significantly associated with LAA ischemic stroke. In both the LAA and control groups, TC and LDL-C levels were significantly higher in the CC type than the CT + TT, but TG and HDL-C levels were comparable. The only verified independent risk factors for LAA ischemic stroke were ischemic heart disease (OR: 2.784, 95% CI: 1.377-5.632; p = 0.004) and systolic blood pressure (OR: 1.014, 95% CI: 1.001-1.026; p = 0.029); the PPARG C161T allele was not independently associated with an increased risk of LAA ischemic stroke (OR = 0.697, 95% CI: 0.372-1.305; p = 0.260). In this Han population, PPARG C161T CT/TT was associated with LAA ischemic stroke and lower levels of blood TC and LDL-C, but was not an independent risk factor for LAA ischemic stroke.


Creatine is an ergogen for anaerobic exercise.
Throughout history, athletes have searched for performance-enhancing agents. Recently, creatine (N-[aminoiminomethyl]-N-methyl glycine) has been marketed as an ergogenic dietary supplement. There appears to be scientific merit to the claim that creatine is ergogenic when taken in large amounts. However, several issues regarding its use need to be addressed.


Hydrodynamic effects on the disorder-to-order transitions of diblock copolymer melts.
Dynamic self-consistent field theory and Navier-Stokes equation are coupled to study hydrodynamic effects on the disorder-to-order transition of diblock copolymer melts. Simulations are performed for different values of the viscosity and the results are compared with those without the hydrodynamic effects. The lower the viscosity is, the faster the free energy density decays. Starting from uniformly mixed initial states, body-centered-cubic spheres, hexagonally packed cylinders, and lamellar structures are obtained in the presence of the hydrodynamic effects. On the contrary, the bicontinuous double gyroid structure cannot be obtained even with the hydrodynamic effects. The scattering intensities of the domain structures are calculated to confirm these properties of the ordering of the structures.


Simple neural substrate predicts complex rhythmic structure in duetting birds.
Horneros (Furnarius Rufus) are South American birds well known for their oven-looking nests and their ability to sing in couples. Previous work has analyzed the rhythmic organization of the duets, unveiling a mathematical structure behind the songs. In this work we analyze in detail an extended database of duets. The rhythms of the songs are compatible with the dynamics presented by a wide class of dynamical systems: forced excitable systems. Compatible with this nonlinear rule, we build a biologically inspired model for how the neural and the anatomical elements may interact to produce the observed rhythmic patterns. This model allows us to synthesize songs presenting the acoustic and rhythmic features observed in real songs. We also make testable predictions in order to support our hypothesis.


An Integrated Building Block for Cascade Diels-Alder and Hetero-Diels-Alder Reactions.
The Diels-Alder (DA) reaction and hetero-Diels-Alder (HDA) reaction are among the most powerful methods for the construction of carbocycles and heterocycles. Herein, an integrated building block of DA and HDA reactions is described. The triazenyl dienes could undergo a DA reaction, while the newly released alkene moiety and the triazene were able to engage in a HDA reaction. In these processes, the triazene group could facilitate the electron-demand DA reaction and also act as a fragment of diazadiene.


Potent anti-cancer effects of less polar Curcumin analogues on gastric adenocarcinoma and esophageal squamous cell carcinoma cells.
Curcumin and its chalcone derivatives inhibit the growth of human cancer cells. It is reported that replacement of two OH groups in curcumin with less polar groups like methoxy increases its anti-proliferative activity. In this study, we explored benzylidine cyclohexanone derivatives with non-polar groups, to see if they possess increased anti-cancer activity. Novel 2,6-bis benzylidine cyclohexanone analogues of curcumin were synthesized, and their inhibitory effects on gastric adenocarcinoma (AGS) and esophageal squamous cell carcinoma (KYSE30) cancer cells were studied using an MTT assay. Cell apoptosis was detected by EB/AO staining, and cell cycle was analyzed by flow cytometry. Real-time PCR was performed for gene expression analysis. All synthesized analogues were cytotoxic toward gastric and esophageal cancer cells and showed lower IC50 values than curcumin. Treatment with 2,6-Bis-(3-methoxy-4-propoxy-benzylidene)-cyclohexanone (BM2) was 17 times more toxic than curcumin after 48 h incubation. All novel compounds were more effective than curcumin in apoptosis induction and cell cycle arrest at G1 phase. These results suggest that less polar analogues of curcumin have potent cytotoxicity in vitro. However, they need to be investigated further, especially with animal tumor models, to confirm their chemotherapeutic activity in vivo.


Tumor ablation with photodynamic therapy: introduction to mechanism and clinical applications.
Photodynamic therapy (PDT) has been used to treat cancer for more than 25 years. Although the focus has been primarily on surface or superficial lesions, there has been a rapid growth in its application to the treatment of deeper parenchymal malignancies. The photochemical reaction consists of a photosensitizer, which, when irradiated by light at a specific wavelength, generates a cytotoxic oxygen singlet. The end result is an efficient induction of cell death, primarily through apoptosis, microvascular damage, and an antitumor immune response. PDT is currently being used in the treatment of many cancers including lung cancer, head and neck cancers, liver metastases, cholangiocarcinoma, and prostate cancer. The growing body of evidence concerning its efficacy, the increasing use of imaging to guide PDT, and the innate minimally invasive characteristics of PDT suggest that it should become an important addition to the growing array of techniques in interventional oncology.


Assessment of Psychological and Psycho-physiological Problems Among Visually Impaired Adolescents.
Visual impairment tends to evoke more discomfiture than any other disability. Primarily, the biggest issue may be that blindness is visible. Furthermore, visual impairment develops serious medical, psychological, social and economic problems. The focus of the current study was to investigate the psychological and psycho physiological problems of visually impaired adolescent students. Purposive sampling was adopted to select 150 visually impaired students (71 males and 72 females) from five schools in Coimbatore city of the Tamil Nadu state, India. Anxiety, frustration, aggression and social and personal adjustment levels of the visually impaired students were measured in this study using Taylor's manifest anxiety scale, frustration test, aggression scale and the adolescent adjustment inventory, respectively. Anxiety (χ(2) = 185.66, P = 0 at P < 0.01), frustration (χ(2) = 167.23, P = 0 at P < 0.01) and aggression (χ(2) = 57.66, P = 0 at P < 0.01) were significantly related to adjustment among visually impaired students. The adjustment score had a significant positive correlation with anxiety (r = 0.919, P = 0 at P < 0.01), frustration (r = 0.887, P = 0 at P < 0.01) and aggression levels (r = 0.664, P = 0 at P < 0.01), anxiety was significantly correlated with frustration (r = 0. 961, P = 0 at P < 0.01) and aggression levels (r = 0.727, P < 0.01) and frustration was significantly correlated with aggression level (r = 0. 637, P = 0 at P < 0.01) of visually impaired adolescents. There was a positive relationship between psycho-physiological disorders and anxiety frustration, aggression and adjustment among visually impaired students. Visually impaired students exhibited significant levels of psychological and psycho-physiological problems.


Protective effects of Spirulina maxima on hyperlipidemia and oxidative-stress induced by lead acetate in the liver and kidney.
Oxidative damage has been proposed as a possible mechanism involved in lead toxicity, specially affecting the liver and kidney. Previous studies have shown the antioxidant effect of Spirulina maxima in several experimental models of oxidative stress. The current study was carried out to evaluate the antioxidant activity of Spirulina maxima against lead acetate-induced hyperlipidemia and oxidative damage in the liver and kidney of male rats. Control animals were fed on a standard diet and did not receive lead acetate (Control group). Experimental animals were fed on a standard laboratory diet with or without Spirulina maxima 5% in the standard laboratory diet and treated with three doses of lead acetate (25 mg each/weekly, intraperitoneal injection) (lead acetate with Spirulina, and lead acetate without Spirulina groups). The results showed that Spirulina maxima prevented the lead acetate-induced significant changes on plasma and liver lipid levels and on the antioxidant status of the liver and kidney. On the other hand, Spirulina maxima succeeded to improve the biochemical parameters of the liver and kidney towards the normal values of the Control group. It was concluded that Spirulina maxima has protective effects on lead acetate-induced damage, and that the effects are associated with the antioxidant effect of Spirulina.


Glaucomatous outflow pathway and oxidative stress.
Oxidative free radicals and reactive oxygen species (ROS) are able to affect the cellularity of the human trabecular meshwork (HTM). These findings suggest that intraocular pressure increase, which characterises most glaucomas, is related to oxidative degenerative processes affecting the HTM and specifically its endothelial cells. Much evidence indicates that in this region ROS play a fundamental pathogenic role by reducing local antioxidant activities, inducing outflow resistance and exacerbating the activities of superoxide dismutase and glutathione peroxidase in glaucomatous eyes. Furthermore, hydrogen peroxide induces rearrangement of HTM cells and compromises their integrity. Glaucomatous subjects might have a genetic predisposition rendering them more susceptible to ROS-induced damage. A fairly significant correlation between oxidative DNA damage in the HTM and intraocular pressure increase and visual field defects in glaucomatous patients has been demonstrated. Thus, oxidative stress may play a significant role during glaucoma course initially damaging HTM cells, then contributing to the alteration of the homeostasis between NO and endothelins, and finally through its possible involvement in ganglional cell death. On the whole, these findings support the hypothesis that oxidative damage is an important step in the pathogenesis of primary open-angle glaucoma, and might be a relevant target for both prevention and therapy.


Depressive effect of amiodarone on hepatic drug metabolism in the rat.
The effect of pretreatment of rats with three daily i.p. doses of 25, 50 and 100 mg/kg of the antiarrhythmic agent, amiodarone, on the activity of some hepatic drug metabolizing enzymes, on the levels of cytochromes P-450 and b5 as well as on lipid peroxidation is reported. Amiodarone at doses of 50 and 100 mg/kg significantly reduced the hydroxylation of aniline, the 0- and N-demethylations of p-nitroanisole and aminopyrine respectively and the level of cytochromes P-450. No inhibition in enzymic activity was observed with the 25 mg/kg dose. Testosterone hydroxylation was only depressed with the 100 mg/kg dose; in this case, all four hydroxylation reactions were reduced. Cytochrome b5 content and lipid peroxidation were significantly decreased with doses of 25 and 50 mg/kg. Addition of 1 mM of amiodarone to incubation mixtures containing either aminopyrine or p-nitroanisole or aniline only decreased aniline hydroxylation indicating that at high doses amiodarone acts as a competitive inhibitor of aniline hydroxylase but that the depressive effect observed on the 0- and N-demethylations of p-nitroanisole and aminopyrine is mediated via an indirect mechanism. The inhibitory effect of amiodarone was also shown in vivo by an increase in the elimination half-life and a decrease in the clearance of antipyrine. The results reported herein may explain, in part at least, the drug interactions recently reported in man with amiodarone.


Comprehensive review on sexual dimorphism to improve scalp acupuncture in nervous system disease.
With the development of modern medicine, the Traditional Chinese Medicine (TCM) combined with western medicine began to be produced and applied. Scalp acupuncture (SA) as a Chinese medicine based on neurological theory, has a great advantage compared with TCM in the treatment of nervous system diseases. In this paper, we analyze the physiological and pathological manifestations of sexual dimorphism (SD) to illustrate the necessity of SD treatment. In addition, we review the factors that can affect SD and analyze in physiological structure, function, and pathological neurons. Diseases (pathological basis, pathological manifestations, and incidence) and factors leading to gender differences, which to analyze the possibility of gender differences in SA. Furthermore, we creatively a new insight of SD-SA and provide the complete SD treatment cases on the basis of the existing SA in different kinds of diseases including stroke, migraine, attention deficit hyperactivity disorder (ADHD), and depression. In summary, we believe that it is feasible to improve the clinical effectiveness of SA, which is able to promote the development of SA, and then provides an actionable evidence for the promotion of precision medicine in the future.


Synthesis and biological action of two glucocorticoid alkylating agents.
Two alkylating glucocorticoids have been synthesized in order to test the possibility of alkylating glucocorticoid receptors. The title compounds are 9alpha-fluoro-11beta,16alpha,17alpha,21-tetrahydroxypregna-1,4-diene-3,20-dione 21-[bis(2-chloroethyl)carbamate] 16,17-acetonide (I) and 11beta,17alpha,21-trihydroxypregn-4-ene-3,20-dione 21-[bis(2-chloroethyl)carbamate] (II), prepared from triamcinolone acetonide and cortisol, respectively, through the reaction of the C-21 hydroxyl group with phosgene and di-2-chloroethylamine in the presence of triethylamine. Both compounds are biologically active as inhibitors of the growth of cultured mouse fibroblasts and are able to compete for the specific binding of radiolabeled triamcinolone acetonide to the L929 cell receptor. The bis(2-chloroethyl)carbamate moiety is capable of reacting with nucleophilic groups as evidenced by the colorimetric reaction with 4-(p-nitrobenzyl)pyridine. Both the interaction with the receptor and inhibition of cell growth by these two glucocorticoids are reversible.


[Effect of High-Concentration Uric Acid on Nitric Oxide].
Uric acid (UA) is the final product of purine metabolism in human body,and its metabolic disorder will induce hyperuricemia (HUA).The occurrence and development of HUA are associated with a variety of pathological mechanisms such as oxidative stress injury,activation of inflammatory cytokines,and activation of renin-angiotensin-aldosterone system.These mechanisms directly or indirectly affect the bioavailability of endogenous nitric oxide (NO).The decrease in NO bioavailability is common in the diseases with high concentration of UA as an independent risk factor.In this review,we summarize the mechanisms by which high concentrations of UA affect the endogenous NO bioavailability,with a focus on the mechanisms of high-concentration UA in decreasing the synthesis and/or increasing the consumption of NO.This review aims to provide references for alleviating the multisystem symptoms and improving the prognosis of HUA,and lay a theoretical foundation for in-depth study of the correlations between HUA and other metabolic diseases.


Spin exchange monitoring of the strong positive homotropic allosteric binding of a tetraradical by a synthetic receptor in water.
The flexible tetranitroxide 4T has been prepared and was shown to exhibit a nine line EPR spectrum in water, characteristic of significant through space spin exchange (J(ij)) between four electron spins interacting with four nitrogen nuclei (J(ij) ≫ a(N)). Addition of CB[8] to 4T decreases dramatically all the Jij couplings, and the nine line spectrum is replaced by the characteristic three line spectrum of a mononitroxide. The supramolecular association between 4T and CB[8] involves a highly cooperative asymmetric complexation by two CB[8] (K1 = 4027 M(-1); K2 = 202,800 M(-1); α = 201) leading to a rigid complex with remote nitroxide moieties. The remarkable enhancement for the affinity of the second CB[8] corresponds to an allosteric interaction energy of ≈13 kJ mol(-1), which is comparable to that of the binding of oxygen by hemoglobin. These results are confirmed by competition and reduction experiments, DFT and molecular dynamics calculations, mass spectrometry, and liquid state NMR of the corresponding reduced complex bearing hydroxylamine moieties. This study shows that suitably designed molecules can generate allosteric complexation with CB[8]. The molecule must (i) carry several recognizable groups for CB[8] and (ii) be folded so that the first binding event reorganizes the molecule (unfold) for a better subsequent recognition. The presence of accessible protonable amines and H-bond donors to fit with the second point are also further stabilizing groups of CB[8] complexation. In these conditions, the spin exchange coupling between four radicals has been efficiently and finely tuned and the resulting allosteric complexation induced a dramatic stabilization enhancement of the included paramagnetic moieties in highly reducing conditions through the formation of the supramolecular 4T@CB[8]2 complex.


Occupational Therapist-Led Mindfulness Training Program for Older Adults Living with Early Cognitive Decline in Primary Care: A Pilot Randomized Controlled Trial.
Community-dwelling older adults with early cognitive deficits experience less efficiency in performing everyday life tasks, resulting in decreased satisfaction and other adverse psychological outcomes. Mindfulness training has been linked to cognitive and psychological improvements and, most recently, has been identified as a potential intervention supporting performance of everyday life activities. This study aimed to evaluate whether mindfulness practice can improve perceived performance and satisfaction with everyday life activity and secondary psychological outcomes. This study is a pilot randomized controlled trial (RCT) in an interprofessional primary care team practice in Toronto, Ontario, Canada. The participants were 27 older adults aged 60 years of age or older living with early cognitive deficits. Participants were randomized into an 8-Week mindfulness training program (n = 14) group or a Wait-List Control (WLC; n = 13) group compared at baseline, post-intervention and 4-weeks follow-up. MANOVAs with post-hoc independent t-tests were used to compare between groups at different time points. There was a significant improvement in anxiety for the intervention group compared to the WLC group at post-intervention; Time-2 (mean difference = 3.90; CI = 0.04-7.75; p = 0.04) with large effect size (d = 0.80). Mindfulness training significantly improved anxiety scores for patients with early cognitive deficits post-intervention. Further work is required to test the sustainability of reduced anxiety over time, but this study demonstrated that MBSR is a promising primary care intervention for those living with early cognitive deficits. This study warrants the pursuit of a future study in exploring how long the reduced anxiety effects would be sustained.


[Indoor air quality in an Italian military submarine].
In recent years there has been increasing interest on studies concerning indoor air quality and focusing on risk factors for exposed subjects. Particularly, airborne chemicals, whose adverse effects are well known, have been identified and determined in means of transport as in other indoor places. As concerns chemical air concentrations in submarines, only a limited number of studies have been published. This paper reports measured concentration data for organic compounds (total volatile organic compounds, substances with a chemical bond S-O, nitrogen compounds, carbon monoxide, carbon dioxide, and different organic solvents) in the air sampled during an 8-h period in an Italian Military submarine, under routine operations. We observed that a periodicalfresh-air intake operation (snorkel) might cause temporary increase of contaminants levels in indoor air. Moreover, we could find that pollutants sometimes reach notable peak concentrations being potentially able to induce adverse health effects in crewmembers. Our data highlight the need to promote further investigations.


Comparative transcriptomic profiling of peripheral efferent and afferent nerve fibres at different developmental stages in mice.
Peripheral nerve injury impairs motor and sensory function in humans, and its functional recovery largely depends on the axonal outgrowth required for the accurate reinnervation of appropriate targets. To better understand how motor and sensory nerve fibres select their terminal pathways, an unbiased cDNA microarray analysis was conducted to examine differential gene expression patterns in peripheral efferent and afferent fibres at different developmental stages in mice. Gene ontology (GO) and Kyoto Enrichment of Genes and Genomes (KEGG) analyses revealed common and distinct features of enrichment for differentially expressed genes during motor and sensory nerve fibre development. Ingenuity Pathway Analysis (IPA) further indicated that the key differentially expressed genes were associated with trans-synaptic neurexin-neuroligin signalling components and a variety of gamma-aminobutyric acid (GABA) receptors. The aim of this study was to generate a framework of gene networks regulated during motor and sensory neuron differentiation/maturation. These data may provide new clues regarding the underlying cellular and molecular mechanisms that determine the intrinsic capacity of neurons to regenerate after peripheral nerve injury. Our findings may thus facilitate further development of a potential intervention to manipulate the therapeutic efficiency of peripheral nerve repair in the clinic.


HIV-1 Env DNA vaccine plus protein boost delivered by EP expands B- and T-cell responses and neutralizing phenotype in vivo.
An effective HIV vaccine will most likely require the induction of strong T-cell responses, broadly neutralizing antibodies (bNAbs), and the elicitation of antibody-dependent cellular cytotoxicity (ADCC). Previously, we demonstrated the induction of strong HIV/SIV cellular immune responses in macaques and humans using synthetic consensus DNA immunogens delivered via adaptive electroporation (EP). However, the ability of this improved DNA approach to prime for relevant antibody responses has not been previously studied. Here, we investigate the immunogenicity of consensus DNA constructs encoding gp140 sequences from HIV-1 subtypes A, B, C and D in a DNA prime-protein boost vaccine regimen. Mice and guinea pigs were primed with single- and multi-clade DNA via EP and boosted with recombinant gp120 protein. Sera were analyzed for gp120 binding and induction of neutralizing antibody activity. Immunization with recombinant Env protein alone induced low-titer binding antibodies with limited neutralization breath. In contrast, the synthetic DNA prime-protein boost protocol induced significantly higher antibody binding titers. Furthermore, sera from DNA prime-protein boost groups were able to neutralize a broader range of viruses in a panel of tier 1 clade B viruses as well as multiple tier 1 clade A and clade C viruses. Further investigation of synthetic DNA prime plus adaptive EP plus protein boost appears warranted.


One-Pot Synthesis of Polysubstituted Spirofluorene-Indene via Ru(II)-Catalyzed [3 + 2] Annulation and Intramolecular Friedel-Crafts Cyclization.
Ru(II)-catalyzed one-pot synthesis of polysubstituted spirofluorene-indenes via [3 + 2] annulation and then intramolecular Friedel-Crafts alkylation has been achieved. The simple method provides a broad scope of aryl ketones and internal alkynes, achieving PAHs skeletons in moderate to good yields.


Major malformations of the urinary tract. Anatomic and genetic aspects.
This paper outlines the problem of major malformations of the urinary tract, their frequency and their etiology. It is based on data analysis of 900 neonatal autopsies performed in our center from 1978 to 1987. These major malformations are often lethal and they can essentially be separated into disorders of the kidney and malformations of the lower urinary tract. Single-gene disorders are often seen in the former whereas the second group is more likely to be multifactorially controlled. We do insist on the importance of a strict collaboration between pathologists and geneticists.


Design of Pore Size and Functionality in Pillar-Layered Zn-Triazolate-Dicarboxylate Frameworks and Their High CO2/CH4 and C2 Hydrocarbons/CH4 Selectivity.
In the design of new materials, those with rare and exceptional compositional and structural features are often highly valued and sought after. On the other hand, materials with common and more accessible modes can often provide richer and unsurpassed compositional and structural variety that makes them a more suitable platform for systematically probing the composition-structure-property correlation. We focus here on one such class of materials, pillar-layered metal-organic frameworks (MOFs), because different pore size and shape as well as functionality can be controlled and adjusted by using pillars with different geometrical and chemical features. Our approach takes advantage of the readily accessible layered Zn-1,2,4-triazolate motif and diverse dicarboxylate ligands with variable length and functional groups, to prepare seven Zn-triazolate-dicarboxylate pillar-layered MOFs. Six different gases (N2, H2, CO2, C2H2, C2H4, and CH4) were used to systematically examine the dependency of gas sorption properties on chemical and geometrical properties of those MOFs as well as their potential applications in gas storage and separation. All of these pillar-layered MOFs show not only remarkable CO2 uptake capacity, but also high CO2 over CH4 and C2 hydrocarbons over CH4 selectivity. An interesting observation is that the BDC ligand (BDC = benzenedicarboxylate) led to a material with the CO2 uptake outperforming all other metal-triazolate-dicarboxylate MOFs, even though most of them are decorated with amino groups, generally believed to be a key factor for high CO2 uptake. Overall, the data show that the exploration of the synergistic effect resulting from combined tuning of functional groups and pore size may be a promising strategy to develop materials with the optimum integration of geometrical and chemical factors for the highest possible gas adsorption capacity and separation performance.


Exogenous N addition enhances the responses of gross primary productivity to individual precipitation events in a temperate grassland.
Predicted future shifts in the magnitude and frequency (larger but fewer) of precipitation events and enhanced nitrogen (N) deposition may interact to affect grassland productivity, but the effects of N enrichment on the productivity response to individual precipitation events remain unclear. In this study, we quantified the effects of N addition on the response patterns of gross primary productivity (GPP) to individual precipitation events of different sizes (Psize) in a temperate grassland in China. The results showed that N enrichment significantly increased the time-integrated amount of GPP in response to an individual precipitation event (GPPtotal), and the N-induced stimulation of GPP increased with increasing Psize. N enrichment rarely affected the duration of the GPP response, but it significantly stimulated the maximum absolute GPP response. Higher foliar N content might play an important role in the N-induced stimulation of GPP. GPPtotal in both the N-addition and control treatments increased linearly with Psize with similar Psize intercepts (approximately 5 mm, indicating a similar lower Psize threshold to stimulate the GPP response) but had a steeper slope under N addition. Our work indicates that the projected larger precipitation events will stimulate grassland productivity, and this stimulation might be amplified by increasing N deposition.


Spatially Resolved Polarization Manipulation of Ferroelectricity in Twisted hBN.
Robust room-temperature interfacial ferroelectricity has been formed in the 2D limit by simply twisting two atomic layers of non-ferroelectric hexagonal boron nitride (hBN). A thorough understanding of this newly discovered ferroelectric system is required. Here, twisted hBN is used as a tunneling junction and it is studied at the nanometer scale using conductive atomic force microscopy. Three properties unique to this system are discovered. First, the polarization dependence of the tunneling resistance contrasts with the conventional theory. Second, the ferroelectric domains can be controlled using mechanical stress, highlighting the original meaning of the emergent "slidetronics". Third, ferroelectric hysteresis is highly spatially dependent. The hysteresis is symmetric at the domain walls. A few nanometers away, the hysteresis shifts completely to the positive or negative side, depending on the original polarization. These findings reveal the unconventional ferroelectricity in this 2D system.


[Sinonasal extranodal natural killer/T-cell lymphoma: a case report and review of recent developments in the management].
Nasal extranodal natural killer/T-cell lymphoma, which is a highly aggressive disease, is more frequently seen in Asia than in Western countries. No consensus has been reached on the management of the disease and the survival depends on the stage of the disease. Localized NK/T-cell lymphoma often responds to radiotherapy well. However, patients with advanced disease or recurrence after chemoradiotherapy, similar to our patient, have a very poor prognosis. In this article, we present a 52-year-old male patient with early recurrence and who was refractory to chemotherapy. The management of the disease was reviewed in the light of the recent literature data.


Effects of age, sex and arm on the precision of arm position sense-left-arm superiority in healthy right-handers.
Position sense is an important proprioceptive ability. Disorders of arm position sense (APS) often occur after unilateral stroke, and are associated with a negative functional outcome. In the present study we assessed horizontal APS by measuring angular deviations from a visually defined target separately for each arm in a large group of healthy subjects. We analyzed the accuracy and instability of horizontal APS as a function of age, sex and arm. Subjects were required to specify verbally the position of their unseen arm on a 0-90° circuit by comparing the current position with the target position indicated by a LED lamp, while the arm was passively moved by the examiner. Eighty-seven healthy subjects participated in the study, ranging from 20 to 77 years, subdivided into three age groups. The results revealed that APS was not a function of age or sex, but was significantly better in the non-dominant (left) arm in absolute errors (AE) but not in constant errors (CE) across all age groups of right-handed healthy subjects. This indicates a right-hemisphere superiority for left APS in right-handers and neatly fits to the more frequent and more severe left-sided body-related deficits in patients with unilateral stroke (i.e. impaired APS in left spatial neglect, somatoparaphrenia) or in individuals with abnormalities of the right cerebral hemisphere. These clinical issues will be discussed.


Adapting the Interpersonal Quality in Family Planning care scale to assess patient perspectives on abortion care.
Women value receiving quality interpersonal care during abortion services, yet no measure exists to assess this outcome from patients' perspectives. We sought to adapt the Interpersonal Quality in Family Planning care scale (Dehlendorf et al., American Journal of Obstetrics Gynaecology 10.1016/j.ajog.2016.01.173, 2016) for use in abortion care. We adapted items from the original scale for the abortion context, and conducted cognitive interviews to explore the acceptability, understandability, and importance of the adapted items. Adults who spoke English and/or Spanish, had an abortion in the past year, and lived in the US were eligible to participate. Interview memos were analyzed concurrently with data collection to refine the measure in stages. We interviewed 26 participants. Items were tested over seven stages and led to four main changes. First, we revised three items to reflect concepts perceived as important to the specific decision-making context of abortion. Second, we removed two items that emerged as potentially inappropriate for this context. Third, we modified language in four items to improve their appropriateness for this context (e.g., 'telling me' to 'explaining'; 'letting me say' to 'listening to'). Fourth, we modified language in three items to improve their clarity. Three items remained unchanged, as there was consistent agreement on their importance, understandability, and relevance. The resulting 10-item measure, the Interpersonal Quality in Abortion Care scale, was perceived to be highly important, understandable, and feasible to complete. Future psychometric evaluation can prepare it for use in clinical practice to ensure women feel adequately informed and supported during abortion care.


The Association Between Migraine, Metabolic Syndrome, Insulin Resistance, and Obesity in Women: A Case-Control Study.
The aim of this study was to examine the relationship between migraines and obesity, insulin resistance (IR), and metabolic syndrome in female migraineurs. A total of 141 female patients who experience migraines and a control group of 141 sex- and age-matched individuals who do not were enrolled in this case-control study. The migraine group was composed of patients from the Gebze Fatih Community Hospital (Kocaeli, Turkey) neurology outpatient service and the control group included hospital staff and friends who volunteered to participate. Descriptive statistics and multivariate logistic regression analyses were performed. Migraine was designated as a dependent variable. Family history of migraine, stroke, metabolic syndrome, cardiac disease, hypertension, hyperlipidemia, and diabetes mellitus; cigarette use; alcohol consumption; and the presence of hypertension, IR, hypertriglyceridemia, low level of high-density lipoprotein (HDL), central obesity, metabolic syndrome; as well as homeostasis model assessment and quantitative insulin sensitivity check index results were selected as independent variables. The mean waist circumference, mean height, mean weight, and central obesity were greater in the control group (p=0.009, 0.004, 0.036, and 0.015, respectively). A multivariate logistic regression model of migraine presence showed that a family history of migraine (odds ratio [OR]: 1.542, 95% confidence interval [CI]: 2.451-8.905; p<0.0001), family history of stroke (OR: 1.043, 95% CI: 1.214-6.633; p=0.016), and no central obesity (OR: -0.705, 95% CI: -0.290-0.843; p=0.010) were statistically significant variables in our study. The results of our study indicated that IR and metabolic syndrome were not associated with migraine in women. There was an inverse relationship between central obesity and migraine. Additional research with larger participant groups should be performed to further explore the complex relationship between migraine, obesity, IR, and metabolic syndrome.


Lithium suppresses seizure susceptibility in pentylenetetrazol-kindled rats.
With regard to the still debatable effect of lithium in epilepsy the effect of chronic lithium treatment on the development of pentylenetetrazol(PTZ)-kindling and the anti-convulsive potency of acute lithium administration on PTZ-induced seizure behaviour in PTZ-kindled and non-kindled rats was examined. Lithium significantly suppressed the development of PTZ-kindling. In kindled rats the acute application of lithium reduced seizure susceptibility in a dose-dependent manner. In contrast to kindled rats, in non-kindled animals lithium had very weak anticonvulsive potency. The results suggest that lithium may be of potential interest in the treatment of special forms of epilepsy and epileptic brain disorders.


Spatiotemporal evolution of habitat quality and its response to landscape patterns in karst mountainous cities: a case study of Guiyang City in China.
Habitat quality heterogeneity is one of the concrete manifestations of landscape pattern changes caused by human activities, which is of great significance to improve habitat quality by optimizing landscape pattern, thus scientifically protecting biodiversity and promoting ecological civilization construction. The coupling of rapid urbanization and ecological restoration measures has had a significant influence on the habitat quality of fragile and fragmented karst mountainous cities in recent years. In this study, spatiotemporal dynamics and heterogeneity of habitat quality and the impact of landscape patterns on habitat quality are analyzed in Guiyang, a typical karst mountain city in southwest China, mainly using the key methodologies such as the Integrated Valuation of Ecosystem Services and Tradeoffs (InVEST) model, Exploratory Spatial Data Analysis (ESDA), and hierarchical partitioning (HP). We found that the habitat quality index of Guiyang City improved from 0.6643 to 0.6988 during 2000-2019; the distribution of habitat quality has significant spatiotemporal heterogeneity and spatial aggregation effect with the low values or the decreased areas concentrated in and around the built-up areas or urbanization expansion areas. Landscape composition had greater contribution than landscape configuration to habitat quality. The increased areas of natural habitat have had a positive effect on habitat quality. Moreover, each landscape configuration had a significant positive or negative correlation with the habitat quality. Therefore, implementing ecological protection and restoration measures in karst mountainous cities might be an effective strategy to improve habitat quality during rapid urbanization. Furthermore, optimizing habitat patterns, reducing the habitats loss, and protecting the natural habitat integrity are crucial to improving and maintaining biodiversity in the study area.


Lead awareness: North Philly Style.
Lead poisoning in children has been associated with reduced intelligence, shortened memory, slowed reaction times, poor hand-eye coordination, and antisocial behavior. The cost to society includes not only medical treatment and special education but also higher high-school drop-out rates, which are associated with crime and low earning potential.


Destabilizing Alzheimer's Abeta(42) protofibrils with morin: mechanistic insights from molecular dynamics simulations.
Alzheimer's disease is a progressive, neurodegenerative disorder that is the leading cause of senile dementia, afflicting millions of individuals worldwide. Since the identification of the amyloid beta-peptide (Abeta) as the principal toxic entity in the progression of Alzheimer's disease, numerous attempts have been made to reduce endogenous Abeta production and deposition, including designing inhibitors of the proteases that generate the peptide, generating antibodies against Abeta aggregates, utilizing metal chelators, and identifying small molecules that target the peptide during the aggregation pathway. The last approach is particularly attractive, as Abeta is normally present in vivo, but aggregation is a purely pathological event. Studies conducted in vitro and in vivo have suggested that administration of flavonoids, compounds naturally present in many foods, including wine and tea, can prevent and reverse Abeta aggregation, but mechanistic details are lacking. In this work, we employ atomistic, explicit-solvent molecular dynamics (MD) simulations to identify the mechanism of Abeta fibril destabilization by morin, one of the most effective anti-aggregation flavonoids, using a model of the mature Abeta fibril. Through the course of 24 simulations totaling 4.3 mus, we find that morin can bind to the ends of the fibrils to block the attachment of an incoming peptide and can penetrate into the hydrophobic core to disrupt the Asp23-Lys28 salt bridges and interfere with backbone hydrogen bonding. The combination of hydrophobicity, aromaticity, and hydrogen bonding capacity of morin imparts the observed behavior.


Inhalation of progesterone inhibits chronic airway inflammation of mice exposed to ozone.
Chronic ozone exposure leads to a model of mice with lung inflammation, emphysema and oxidative stress. Progesterone plays an important role in attenuating the neuroinflammation. We assume that progesterone will reduce the chronic airway inflammation exposed to ozone and evaluate whether combination of progesterone with glucocorticoids results in synergistic effects. C57/BL6 mice were exposed to ozone (2.5ppm, 3h) 12 times over 6 weeks, and were administered with progesterone (0.03 or 0.3mg/L; inhaled) alone or combined with budesonide (BUD) (0.2g/L) after each exposure until the tenth week. Mice were studied 24h after final exposure, cells and inflammatory mediators were assessed in bronchoalveolar lavage fluid (BALF) and lungs used for evaluation of glucocorticoids receptors (GR), p38 mitogen-activated protein kinase (MAPK) phosphorylation and nuclear transcription factor κB (NF-κB) activation. Exposure to ozone resulted in a marked lung neutrophilia. Moreover, in ozone-exposed group, the levels of oxidative stress-related interleukin (IL)-1β, IL-6, IL-8, IL-17A, activated NF-κB and p38MAPK, airway inflammatory cells infiltration density, mean linear intercept (Lm) were greatly increased, FEV25 and glucocorticoids receptors (GR) were markedly decreased. Comparable to BUD, progesterone treatment dose-dependently led to a significant reduction of IL-1β, IL-6, IL-8, IL-17A, activated NF-κB and p38MAPK, and an increase of FEV25 and GR. Progesterone combined with BUD resulted in dramatic changes, compared to monotherapy of BUD or progesterone. Therefore, these results demonstrate that chronic ozone exposure has profound airway inflammatory effects counteracted by progesterone and progesterone acts synergistically with glucocorticoids in attenuating the airway inflammation dose-dependently.


Emergent carotid stenting and intra-arterial abciximab in acute ischemic stroke due to tandem occlusion.
Acute occlusions of the extracranial internal carotid artery (ICA) and a major intracranial artery respond poorly to intravenous tissue plasminogen activator (tPA) and present an endovascular challenge. The aim of our study was to retrospectively delineate the feasibility of the combined use of emergent carotid stenting and intra-arterial (IA) Abciximab with intracranial revascularization in the setting of acute ischemic stroke and carotid occlusions at our institution. Eleven patients with complete cervical carotid occlusion with or without concomitant intracranial ICA and/or MCA occlusion were identified from a single center, retrospective review of patients admitted to the Stroke unit. We evaluated all cases for complications of emergent cervical ICA recanalization employing carotid stenting and IA Abciximab. All patients had complete cervical carotid occlusion with (n = 8) or without (n = 3) concomitant intracranial ICA and/or MCA occlusion. Successful emergent cervical ICA recanalization was achieved in all cases. All patients were administered IA Abciximab (dose range 6-17 mg, average 11.4 mg) immediately following the cervical carotid stenting. There was complete recanalization in all patients with no procedural morbidity or mortality. A single case (1/11, 9%) developed asymptomatic hemorrhagic transformation. Upon discharge, 9 patients (9/11, 82%) had a mRS of 0-2 and 2 patients (2/11, 18%) had a mRS of 3. In acute ICA-MCA/distal ICA occlusions, extracranial stenting followed by intracranial IA Abciximab and thrombectomy appears feasible, effective, and safe. Further evaluation of this treatment strategy is warranted.


With a little help from my assistant: buffering the negative effects of emotional dissonance on dentist performance.
In this study, we hypothesized that dentist' interpersonal resources (good cooperation with one's assistant) together with their personal resources (optimism) buffer the negative effects of emotional dissonance (a demand that occurs when there is a difference between felt and displayed emotions) on job performance (in-role and extra-role performance) over time. We carried out Hierarchical Regression Modeling on a sample of 1954 Finnish dentists who participated in a two-wave 4-year longitudinal study. Results showed that good cooperation with dental assistants buffered the negative effects of emotional dissonance on both in-role and extra-role performance among the dentists in the long term. However, unexpectedly, dentists' high optimism did not buffer their in-role nor extra-role performance over time under conditions of experiencing high emotional dissonance. We conclude that interpersonal job resources such as good cooperation with one's colleagues may buffer the negative effect of emotional dissonance on dentists' job performance even in the long term, whereas the role of personal resources (e.g., optimism) may be less important for maintaining high job performance under conditions of emotional dissonance. The study novelties include the test of the negative effects of emotional dissonance on long-term performance in dentistry and the identification of the job rather than personal resources as the buffers against the negative effects of emotional dissonance on long-term performance.


Heterogeneity of skin surface oxygen level of wrist in relation to acupuncture point.
The distribution of partial oxygen pressure (pO(2)) is analyzed for the anterior aspect of the left wrist with an amperometric oxygen microsensor composed of a small planar Pt disk-sensing area (diameter = 25 μm). The pO(2) levels vary depending on the measurement location over the wrist skin, and they are systematically monitored in the analysis for both one-dimensional single line (along the wrist transverse crease) and two-dimensional square area of the wrist region. Relatively higher pO(2) values are observed at certain area in close proximity to the position of acupuncture points with statistical significance, indicating strong relationship between oxygen and acupuncture point. The used oxygen microsensor is sensitive enough to detect the pO(2) variation depending on the location. This study may provide information helpful to understand possible physiological roles of the acupuncture points.


Novel compounds that enhance Agrobacterium-mediated plant transformation by mitigating oxidative stress.
Agrobacterium tumefaciens caused tissue browning leading to subsequent cell death in plant transformation and novel anti-oxidative compounds enhanced Agrobacterium -mediated plant transformation by mitigating oxidative stress. Browning and death of cells transformed with Agrobacterium tumefaciens is a long-standing and high impact problem in plant transformation and the agricultural biotechnology industry, severely limiting the production of transgenic plants. Using our tomato cv. MicroTom transformation system, we demonstrated that Agrobacterium caused tissue browning (TB) leading to subsequent cell death by our correlation study. Without an antioxidant (lipoic acid, LA) TB was severe and associated with high levels of GUS transient expression and low stable transformation frequency (STF). LA addition shifted the curve in that most TB was intermediate and associated with the highest levels of GUS transient expression and STF. We evaluated 18 novel anti-oxidative compounds for their potential to enhance Agrobacterium-mediated transformation, by screening for TB reduction and monitoring GUS transient expression. Promising compounds were further evaluated for their effect on MicroTom and soybean STF. Among twelve non-antioxidant compounds, seven and five significantly (P < 0.05) reduced TB and increased STF, respectively. Among six antioxidants four of them significantly reduced TB and five of them significantly increased STF. The most efficient compound found to increase STF was melatonin (MEL, an antioxidant). Optimal concentrations and stages to use MEL in transformation were determined, and Southern blot analysis showed that T-DNA integration was not affected by MEL. The ability of diverse compounds with different anti-oxidative mechanisms can reduce Agrobacterium-mediated TB and increase STF, strongly supporting that oxidative stress is an important limiting factor in Agrobacterium-mediated transformation and the limiting factor can be controlled by these compounds at different levels.


Phylogeny of the fungus Spilocaea oleagina, the causal agent of peacock leaf spot in olive.
The fungus Spilocaea oleagina causes peacock leaf spot in olive. Virtually nothing is known about S. oleagina despite the loss of crop yield caused by this fungus. In order to get insight, an in vitro culture of the fungus has been established and its identity confirmed by amplified fragment length polymorphism analysis. Using this in vitro culture, we have cloned and analysed the DNA sequences of the 18S and 28S ribosomal RNA genes (rDNA) as well as the internal transcribed spacers (ITS) and 5.8S rDNA region of S. oleagina. Sequence analysis and comparison to other fungi determined that this fungus belongs to the Dothideomycetes class. We have also determined that S. oleagina is an anamorphic phase of a yet unidentified Venturia species based on phylogenetic analysis using the 28S rDNA and ITS sequences.


Hepatic stellate cells contribute to progenitor cells and liver regeneration.
Retinoid-storing hepatic stellate cells (HSCs) have recently been described as a liver-resident mesenchymal stem cell (MSC) population; however, it is not clear whether these cells contribute to liver regeneration or serve as a progenitor cell population with hepatobiliary characteristics. Here, we purified HSCs with retinoid-dependent fluorescence-activated cell sorting from eGFP-expressing rats and transplanted these GFP(+) HSCs into wild-type (WT) rats that had undergone partial hepatectomy in the presence of 2-acetylaminofluorene (2AAF) or retrorsine, both of which are injury models that favor stem cell-based liver repair. Transplanted HSCs contributed to liver regeneration in host animals by forming mesenchymal tissue, progenitor cells, hepatocytes, and cholangiocytes and elevated direct bilirubin levels in blood sera of GUNN rats, indicating recovery from the hepatic bilirubin-handling defect in these animals. Transplanted HSCs engrafted within the bone marrow (BM) of host animals, and HSC-derived cells were isolated from BM and successfully retransplanted into new hosts with injured liver. Cultured HSCs transiently adopted an expression profile similar to that of progenitor cells during differentiation into bile acid-synthesizing and -transporting hepatocytes, suggesting that stellate cells represent a source of liver progenitor cells. This concept connects seemingly contradictory studies that favor either progenitor cells or MSCs as important players in stem cell-based liver regeneration.


Drug-induced psoriasis: clinical perspectives.
Exposure to certain drugs can elicit an induction or exacerbation of psoriasis. Although well-conducted systematic studies on drug-related psoriasis are mostly lacking, traditionally strong associations have been documented for beta-blockers, lithium, antimalarial drugs such as (hydroxy)chloroquine, interferons, imiquimod, and terbinafine. More recently, new associations have been reported for monoclonal antibody- and small-molecule-based targeted therapies used for oncological and immunological indications, such as tumor necrosis factor-alpha antagonists and anti-programmed cell death protein 1 immune checkpoint inhibitors. Recognizing potential drug-related psoriasis is of clinical relevance to allow an optimal management of psoriasis. However, in clinical practice, identifying medication-related exacerbations and induction of psoriasis can be challenging. The clinical and histopathological features of drug-provoked psoriasis may differ little from that of "classical" nondrug-related forms of psoriasis. In addition, the latency period between start of the medication and onset of psoriasis can be significantly long for some drugs. Assessment of the Naranjo adverse drug reaction probability scale could be used as a practical tool to better differentiate drug-related psoriasis. The first step in the management of drug-related psoriasis is cessation and replacement of the offending drug when deemed clinically possible. However, the induced psoriasis skin lesions may persist after treatment withdrawal. Additional skin-directed treatment options for drug-related psoriasis follows the conventional psoriasis treatment guidelines and includes topical steroids and vitamin D analogs, ultraviolet phototherapy, systemic treatments, such as acitretin, methotrexate, and fumaric acid esters, and biological treatments.


The beta 1 subunit mRNA of the rat brain Na+ channel is expressed in glial cells.
Although the molecular characteristics of glial Na+ channels are not well understood, recent studies have shown the presence of mRNA for rat brain Na+ channel alpha subunits in astrocytes and Schwann cells. In this study, we asked whether the mRNA for the rat brain Na+ channel beta 1 subunit is expressed in glial cells. We performed in situ hybridization using a complementary RNA probe for the coding regions of the rat brain Na+ channel beta 1 subunit mRNA and detected beta 1 subunit mRNA in cultured rat optic nerve astrocytes and sciatic nerve Schwann cells. The beta 1 subunit was amplified by reverse transcription-polymerase chain reaction in rat optic and sciatic nerves, which lack neuronal somata but contain astrocytes and Schwann cells, respectively. Doublet bands of the beta 1 subunit mRNA were amplified from both optic and sciatic nerves. Through the cloning and sequencing of these bands, we confirmed the amplification of a mRNA highly homologous to the previously cloned rat brain Na+ channel beta 1 subunit (beta 1.1) and a novel form of the beta 1 subunit mRNA (beta 1.2), which is closely homologous to beta 1.1 but contains an additional 86-nucleotide insert in 3' noncoding regions. Two beta 1 subunit mRNAs were also amplified from rat brain and skeletal muscle, but not from rat liver or kidney. These results indicate that rat brain Na+ channel beta 1 subunit mRNAs are expressed in glial cells as well as in neurons.


[Multiple sclerosis: beyong first line therapies].
We are currently experiencing a key period in the management of patients with relapsing remitting multiple sclerosis. The application of new criteria allows early diagnosis, thus at a stage when the available immune treatments are the most likely to show a good efficacy. The therapeutic offer is expanding but its complexity too. It is thus important, for a given patient, to assess as precisely as possible the degree of severity of his/her disease, in order to give the drug with the optimal risk/benefit ratio.


Ageing and chronic disease-related changes in the morphometric characteristics of ovarian follicles in cynomolgus monkeys (Macaca fascicularis).
How is the localisation of ovarian follicles affected by ageing and chronic diseases? Ovarian follicles shift deeper towards the medulla, due to thickening of the tunica albuginea (TA), with ageing and some major common chronic diseases. The ovary undergoes morphological and functional changes with ageing. The follicular pool follows these changes with alterations in the amount and distribution of residual follicles. Diseases causing a chronic inflammatory process are associated with morphological changes and impaired ovarian function. We conducted a cross-sectional study, examining 90 ovaries from 90 female monkeys. The samples were collected from April 2018 to March 2019 at Tsukuba Primate Research Center in National Institutes of Biomedical Innovation, Health and Nutrition, Japan. Ovarian samples were obtained from cynomolgus monkeys that died from natural causes or were euthanised. Ovarian sections were stained with haematoxylin and eosin (H&E) for histological analyses. In ovarian sections from 64 female macaques aged 0-25 years, a total of 13 743 follicles at different developmental stages (primordial, intermediary, primary, early secondary and late secondary) were assessed to determine the depth of each follicle from the outer surface of the ovarian cortex to the far end of the follicle, by using a digital imaging software. TA thickness was measured as sum of basal membrane and tunica collagen layer for each ovary under H&E staining. To explore the possibility of age-related trends in ovarian morphometric characteristics, samples were divided into four different age groups (0-3 years (pre-menarche), 4-9 years, 10-14 years and 15-20 years). To evaluate the effect of common chronic diseases on ovarian morphometric characteristics, macaques with diabetes mellitus (DM) (n = 10), endometriosis (n = 8) or inflammatory bowel disease (IBD) (n = 8) were compared to age-matched controls without chronic diseases. Ovarian morphometric analysis revealed that the relative location of follicles became deeper in all age groups according to development of follicles (P < 0.05). Total follicle distance from the ovarian surface was increased with ageing (P < 0.05). In a sub-analysis according to developmental stage, only primordial and intermediary follicles were localised deeper with increasing age (P < 0.05). TA thickness was also increased with ageing (P < 0.05). The localisation of the total number of follicles became deeper in ovaries from monkeys with DM, endometriosis or IBD as compared to the control group (P < 0.05). With DM, analysis of follicles distance at almost each developmental stage was significantly deeper compared to controls (P < 0.05) with the exception of early secondary follicles. With endometriosis, follicles at primary and early and late secondary stages were significantly deeper compared to controls (P < 0.05). Also with IBD, follicles at primary and early and late secondary follicles were significantly deeper compared to controls (P < 0.001). The TA was thicker with DM and endometriosis compared to controls (P < 0.05), but not with IBD (P = 0.16). NA. Two-dimensional histology was used to assess follicle localisation. The possibility of minimal variations between the measured distance to the actual distance in a spherical structure cannot be excluded. Additionally, the severity of disease was not assessed. This study is the first step towards enhancing our understanding of how ageing and chronic diseases affect the relative localisation of dormant and developing follicles. These observations, combined with possible future human studies, may have managerial implications in the field of fertility preservation and other conditions involving ovarian tissue cryopreservation. The present work was supported by the Grant-in-Aid for Scientific Research B (19H03801) (to K.K.), Challenging Exploratory Research (18K19624), Japan Agency for Medical Research and Development, Mochida Memorial Foundation for Medical and Pharmaceutical Research, Takeda Science Foundation and Naito Foundation (to K.K.). All authors have no conflicts of interest directly relevant to the content of this article.


PARP-1 determines specificity in a retinoid signaling pathway via direct modulation of mediator.
We show that PARP-1 is indispensable to retinoic acid receptor (RAR)-mediated transcription from the RARbeta2 promoter in a highly purified, reconstituted transcription system and that RA-inducible expression of all RARbeta isoforms is abrogated in PARP-1(-/-) cells in vivo. Importantly, PARP-1 activity was independent of its catalytic domain. PARP-1 directly interacts with RAR and Mediator. Chromatin immunoprecipitation experiments confirmed the presence of PARP-1 and Mediator on RAR-responsive promoters in vivo. Importantly, Mediator was inactive (Cdk8+) under basal conditions but was activated (Cdk8-) upon induction. However, in PARP-1(-/-) cells, Mediator was retained in its inactive state (Cdk8+) upon induction consistent with the absence of gene expression. PARP-1 became dispensable for ligand-dependent transcription in a chromatin reconstituted transcription assay when Mediator was devoid of the Cdk8 module (CRSP). PARP-1 appears to function as a specificity factor regulating the RA-induced switch of Mediator from the inactive (Cdk8+) to the active (Cdk8-) state in RAR-dependent transcription.


Mechanism of T cell immunosuppression by infectious bursal disease virus of chickens.
Spleen cells of chickens infected with IBDV responded poorly to in vitro stimulation with Con A. The mitogenic hyporesponsiveness was due to the presence of suppressor cells that could be removed by pretreatment of IS cells with carbonyl iron or cytodex-3 microcarrier beads. Addition of suppressor cells to normal spleen cells prevented the normal cells from responding to mitogen. Cell-to-cell contact between responder and suppressor cells was not necessary for suppression to occur; the effect was mediated by soluble product(s) released by the suppressor cells. IS cells were also deficient in producing mitogen-induced IL-2 and addition of exogenous IL-2 did not restore mitogenic response of IS.


Percutaneous trigeminal ganglion compression for trigeminal neuralgia. Experience in 22 patients and review of the literature.
Between 1983 and 1988, a percutaneous trigeminal ganglion compression (PTGC) procedure for trigeminal neuralgia was performed on 22 patients. All patients were initially relieved of their pain. There were three recurrences (14%); two of these patients underwent a second PTGC procedure and one a partial trigeminal nerve root section. Follow-up examination 3 to 53 months after the procedure showed that all patients were free of pain. Morbidity included persistent minor hypesthesia in five patients, persistent minor dysesthesias in three, persistent minor weakness in three, aseptic meningitis in one, transient sixth nerve palsy in one, and transient otalgia in three. None of the patients had either anesthesia dolorosa or an absent corneal reflex.


Ossification and Bone Regeneration in a Canine GBR Model, Part 1: Thick vs Thin Glycated Cross-Linked Collagen Devices.
Purpose: To compare glycated multilayered membranes (OV) to a commercially available thin-layer membrane (OP) in a lateral ridge augmentation model in dogs. Materials and Methods: This was designed as a three-arm study, where one negative control (empty defect) was compared to two test arms: alveolar bone defects grafted with a mixture of 90% deproteinized bovine bone mineral and 10% porcine collagen, then covered with either a thick- (OV) or thin-layered (OP) membrane. Animals were randomly divided into three groups corresponding to the final sacrifice times of 4 weeks, 12 weeks, and 24 weeks. Sections underwent microCT, histology, histopathology, and histomorphometry. Results: No statistical differences were observed for OV compared to OP regarding the percentage of mineral volume and mean mineral density, amount of bone maturation, percentage of bone graft and membrane remaining in the grafted area, alveolar ridge width measurements, membrane mineralization, or ossification. Test groups presented significantly higher values compared to the empty control for all the endpoints. Conclusions: Within its limitations, this in vivo study highlighted that multilayered thick glycated membranes can serve as effective occlusive barriers for up to 6 months.


The dry eye: an introduction.
Understanding the dry eye would be a great deal easier if we thoroughly understood normal tear function. To date, many aspects of tear function remain poorly understood. Only when normal tear characteristics and function are fully illuminated will the treatment of tear abnormalities and ocular surface disease be remedied. This instructional article aims to provide the reader with basic information regarding tear production, abnormalities, and current therapies in order to permit ophthalmic health care providers to intervene and teach patients who suffer from the frustrating and often chronic maladies associated with a dry eye.


When a Seemingly Harmless Prescription Turns into Toxicity.
Valacyclovir neurotoxicity is commonly seen in the elderly and those with impaired renal function. Differential diagnosis can be challenging as a myriad of medical conditions, including herpes zoster virus associated encephalitis, may present in a similar fashion. We present a case of a 71-year-old male who presented with altered mental status in the setting of recent herpes zoster eruption. His condition was attributed to valacyclovir neurotoxicity, and initiation of appropriate supportive therapy was met with complete resolution of symptoms and normalization of cognitive function.


Introduction-First Billion Years: Habitability.
The physical processes active during the first billion years (FBY) of Earth's history, such as accretion, differentiation, and impact cratering, provide constraints on the initial conditions that were conducive to the formation and establishment of life on Earth. This motivated the Lunar and Planetary Institute's FBY topical initiative, which was a four-part conference series intended to look at each of these physical processes to study the basic structure and composition of our Solar System that was set during the FBY. The FBY Habitability conference, held in September 2019, was the last in this series and was intended to synthesize the initiative; specifically, to further our understanding of the origins of life, planetary and environmental habitability, and the search for life beyond Earth. The conference included discussions of planetary habitability and the potential emergence of life on bodies within our Solar System, as well as extrasolar systems by applying our knowledge of the Solar System's FBY, and in particular Earth's early history. To introduce this Special Collection, which resulted from work discussed at the conference, we provide a review of the main themes and a synopsis of the FBY Habitability conference.


Determinants of the irrelevant speech effect: Changes in spectrum and envelope.
The irrelevant sound effect (ISE) denotes the fact that short-term memory is disrupted while being exposed to sound. The ISE is largest for speech. The presented study investigated the underlying acoustic properties that cause the ISE. Stimuli contained changes in either the spectral content only, the envelope only, or both. For this purpose two experiments were conducted and two vocoding strategies were developed to degrade the spectral content of speech and the envelope independently. The first strategy employed a noise vocoder that was based on perceptual dimensions, analyzing the original utterance into 1, 2, 4, 8, or 24 channels (critical bands) and independently manipulating loudness. The second strategy involved a temporal segmentation of the signal, freezing either spectrum or level for durations ranging from 50 ms to 14 s. In both experiments, changes in envelope alone did not have measurable effects on performance, but the ISE was significantly increased when both the spectral content and the envelope varied. Furthermore, when the envelope changes were uncorrelated with the spectral changes, the effect size was the same as with a constant-loudness envelope. This suggests that the ISE is primarily caused by spectral changes, but concurrent changes in level tend to amplify it.


Asthmatics without rhinitis have more fixed airway obstruction than those with concurrent rhinitis.
Rhinitis and asthma usually occur together. There are increasing evidences that allergic rhinitis (AR) may influence the clinical course of asthma. The aim of this study is to evaluate clinical parameters and therapeutic response in patients with between asthma and asthma with AR. Four-hundred eighty-five patients with asthma and 428 asthmatics with AR, who had lesser than 50 years old and smoked less than 10 pack-years were recruited. We compared FEV1 and FEV1/FVC following bronchodilator, atopy, IgE, emphysema on HRCT, and aspirin intolerance between two groups. Also we compared physiologic fixed airway obstruction defined using FEV1/FVC and FEV1 less than 75% following anti-asthmatic drug for 1 year. 46.8% (428/913) asthmatics suffered from AR. There were no differences of total IgE, body mass index, PC20, sputum eosinophils and emphysema on HRCT between two groups. The age in asthmatics was higher than that in those with AR. FEV1/FVC was lower in asthmatics than in those with AR. The prevalence of atopy was higher in asthmatics with AR than in asthmatics. Aspirin intolerance was higher in asthmatics with AR than in asthmatics (42/218 vs 13/109, P=0.001). Fixed airway obstruction were more observed in asthmatics than in those with AR (39/319 vs 28/355, P=0.001) after anti-asthmatic drug for 1 year. Asthmatics with AR had more atopy and aspirin intolerance than asthmatics, and asthmatics had poor response to anti-inflammatory drugs than those with concurrent rhinitis, indicating that asthmatics have more fixed airway obstruction than those with concurrent rhinitis.


Endovascular Therapy for Spontaneous Ilio-Iliac Arteriovenous Fistula Due To Iliac Artery Aneurysm Rupture With Multi-Organ Dysfunction.
Iliac artery aneurysms can rarely present with rupture into adjacent iliac vein resulting in arteriovenous fistula leading to acute cardiac failure or multi-organ failure. End-organ damage can be reversed with timely diagnosis and intervention. Endovascular therapy is an attractive option to treat this pathology besides allowing for a quick recovery and mitigating the risk of mortality associated with open surgical treatment options. We report treatment of this pathology with Endovascular repair with preservation of ipsilateral hypogastric artery flow using an iliac branch graft device. The postoperative course was complicated by type 3 endoleak due to the separation of components between iliac branch graft and aortic stent graft with resultant recurrence of the fistula. Additional endovascular techniques, including placement of a venous stent and stent grafts to bridge the components, was used to treat the endoleak. We present this report due to the unique nature of the recurrent arteriovenous fistula, technical complexity, and resultant multi-organ dysfunction.


Identification of the calmodulin-binding domain of neuron-specific protein kinase C substrate protein CAP-22/NAP-22. Direct involvement of protein myristoylation in calmodulin-target protein interaction.
Various proteins in the signal transduction pathways as well as those of viral origin have been shown to be myristoylated. Although the modification is often essential for the proper functioning of the modified protein, the mechanism by which the modification exerts its effects is still largely unknown. Brain-specific protein kinase C substrate, CAP-23/NAP-22, which is involved in the synaptogenesis and neuronal plasticity, binds calmodulin, but the protein lacks any canonical calmodulin-binding domain. In the present report, we show that CAP-23/NAP-22 isolated from rat brain is myristoylated and that the modification is directly involved in its interaction with calmodulin. Myristoylated and non-myristoylated recombinant proteins were produced in Escherichia coli, and their calmodulin-binding properties were examined. Only the former bound to calmodulin. Synthetic peptides based on the N-terminal sequence showed similar binding properties to calmodulin, only when they were myristoylated. The calmodulin-binding site narrowed down to the myristoyl moiety together with a nine-amino acid N-terminal basic domain. Phosphorylation of a single serine residue in the N-terminal domain (Ser5) by protein kinase C abolished the binding. Furthermore, phosphorylation of CAP-23/NAP-22 by protein kinase C was also found myristoylation-dependent, suggesting the importance of myristoylation in protein-protein interactions.


C-terminal cleavage of DeltaNp63alpha is associated with TSA-induced apoptosis in immortalized corneal epithelial cells.
In the central human corneal epithelium, loss of DeltaNp63 occurs in all surface epithelial cells preparing to undergo desquamation, suggesting a potential role for DeltaNp63 isoforms in mediating surface cell apoptotic shedding. In this study, the authors investigated a role for DeltaNp63 isoforms in caspase-mediated apoptosis in a telomerase-immortalized corneal epithelial cell line. For in vitro studies, hTCEpi cells were cultured in KGM-2 serum-free culture media containing 0.15 mM calcium. To assess dynamic protein interactions among individual DeltaNp63 isoforms, DeltaNp63-EGFP expression plasmids were transiently expressed in hTCEpi cells and evaluated by FRAP. Trichostatin-A (TSA; 3.31 muM) was used to induce cell death as measured by caspase activity. Cleavage and loss of endogenous DeltaNp63alpha, DeltaNp63-EGFP expression plasmids, and p53 were assessed after treatment with TSA and siRNA. Transient expression of DeltaNp63-EGFP alpha and beta isoforms resulted in the formation of a smaller isoform similar in size to DeltaNp63gamma-EGFP. FRAP demonstrated that DeltaNp63alpha-EGFP has greater immobile fraction than beta or gamma. TSA induced caspase-mediated apoptotic pathways; caspase induction was accompanied by a decrease in endogenous DeltaNp63alpha and p53. TSA upregulated DeltaNp63-EGFP plasmid expression; this was accompanied by a selective increase in cleavage of DeltaNp63alpha-EGFP. siRNA knockdown of DeltaNp63alpha correlated with a reduction in p53 independently of TSA. DeltaNp63alpha is the dominant active isoform in corneal epithelial cell nuclei. Loss of DeltaNp63alpha occurs during apoptotic signaling by cleavage at the C terminus. The corresponding loss of p53 suggests that a significant relationship appears to exist between these two regulatory proteins.


Nuclear Reprogramming by Defined Factors: Quantity Versus Quality.
The generation of induced pluripotent stem cells (iPSCs) and directly converted cells holds great promise in regenerative medicine. However, after in-depth studies of the murine system, we know that the current methodologies to produce these cells are not ideal and mostly yield cells of poor quality that might hold a risk in therapeutic applications. In this review we address the duality found in the literature regarding the use of 'quality' as a criterion for the clinic. We discuss the elements that influence reprogramming quality, and provide evidence that safety and functionality are directly linked to cell quality. Finally, because most of the available data come from murine systems, we speculate about what aspects can be applied to human cells.


Battling bacteria in wound care.
A critical aspect of effective and cost-efficient wound management is infection prevention and actions taken to minimize bacterial levels in the wound. This article describes effective wound cleansing and debridement, appropriate use of advanced dressings, procedures for dressing changes, and the appropriate use and understanding of topical antimicrobial agents.


The PROCESS experiment: exposure of amino acids in the EXPOSE-E experiment on the international space station and in laboratory simulations.
To understand the chemical behavior of organic molecules in the space environment, amino acids and a dipeptide in pure form and embedded in meteorite powder were exposed in the PROCESS experiment in the EXPOSE-E facility mounted on the European Technology Exposure Facility (EuTEF) platform on board the International Space Station (ISS). After exposure to space conditions for 18 months, the samples were returned to Earth and analyzed in the laboratory for reactions caused by solar UV and cosmic radiation. Chemical degradation and possible racemization and oligomerization, the main reactions caused by photochemistry in the vacuum ultraviolet domain (VUV, wavelength range 100-200 nm for photon energy from 6.2 to 12.4 eV) were examined in particular. The molecules were extracted and derivatized by silylation and analyzed by gas chromatograph coupled to a mass spectrometer (GC-MS) to quantify the rate of the degradation of the compounds. Laboratory exposure in several wavelength ranges from UV to VUV was carried out in parallel in the Cologne Deutsches Zentrum für Luft- und Raumfahrt (DLR) Center and Centre de biophysique moléculaire (CBM) laboratories. The results show that resistance to irradiation is a function of the chemical nature of the exposed molecules and the wavelengths of the UV light. The most altered compounds were the dipeptide, aspartic acid, and aminobutyric acid. The most resistant were alanine, valine, glycine, and aminoisobutyric acid. Our results also demonstrate the protective effect of meteorite powder, which reemphasizes the importance of exogenic contribution to the inventory of prebiotic organics on early Earth.


[Use of an external minifixator in severe open injuries of the hand].
Since January 1979 we have treated 14 patients at the 1st University Clinic of Traumatology in Vienna with the MFE described by Jaquet. The MFE was used mainly in severe open fractures of fingers and metacarpal bones. All 14 patients were examined for follow-up after a mean interval of 20 months. This method of treatment warrants minimal strain on the soft tissues while it ensures stability and optimal care of the wounds. Osseous consolidation was achieved in 13 of 14 patients; although one patient developed pseudarthrosis, he was, like 12 other patients, perfectly satisfied with the result of surgery. Only one patient was less satisfied by the result, as there was a rotational and axial deviation of 30 degrees between the fragments. However she refused operative correction, as the deviation does not interfere with her profession.


Aloe vera-derived graphene-coupled phenosafranin photocatalyst for generation and regeneration of ammonia and NADH by mimicking natural photosynthetic route.
Aloe vera-derived graphene (ADG) coupled system photocatalyst, mimicking natural photosynthesis, is one of the most promising ways for converting solar energy into ammonia (NH3 ) and nicotinamide adenine dinucleotide (NADH) that have been widely used to make the numerous chemicals such as fertilizer and fuel. In this study, we report the synthesis of the aloe vera-derived graphene-coupled phenosafranin (ADGCP) acting as a highly efficient photocatalyst for the generation of NH3 and regeneration of NADH from nitrogen (N2 ) and oxidized form of nicotinamide adenine dinucleotide (NAD+ ). The results show a benchmark instance for mimicking natural photosynthesis activity as well as the practical applications for the solar-driven selective formation of NH3 and the regeneration of NADH by using the newly designed photocatalyst.


Early repeat resection for residual glioblastoma: decision-making among an international cohort of neurosurgeons.
The importance of extent of resection (EOR) in glioblastoma (GBM) has been thoroughly demonstrated. However, few studies have explored the practices and benefits of early repeat resection (ERR) when residual tumor deemed resectable is unintentionally left after an initial resection, and the survival benefit of ERR is still unknown. Herein, the authors aimed to internationally survey current practices regarding ERR and to analyze differences based on geographic location and practice setting. The authors distributed a survey to the American Association of Neurological Surgeons and Congress of Neurological Surgeons Tumor Section, Society of British Neurological Surgeons, European Association of Neurosurgical Society, and Latin American Federation of Neurosurgical Societies. Neurosurgeons responded to questions about their training, practice setting, and current ERR practices. They also reported the EOR threshold below which they would pursue ERR and their likelihood of performing ERR using a Likert scale of 1-5 (5 being the most likely) in two sets of 5 cases, the first set for a patient's initial hospitalization and the second for a referred patient who had undergone resection elsewhere. The resection likelihood index for each respondent was calculated as the mean Likert score across all cases. Overall, 180 neurosurgeons from 25 countries responded to the survey. Neurosurgeons performed ERRs very rarely in their practices (< 1% of all GBM cases), with an EOR threshold of 80.2% (75%-95%). When presented with 10 cases, the case context (initial hospitalization vs referred patient) did not significantly change the surgeon ERR likelihood, although ERR likelihood did vary significantly on the basis of tumor location (p < 0.0001). Latin American neurosurgeons were more likely to pursue ERR in the provided cases. Neurosurgeons were more likely to pursue ERR when the tumor was MGMT methylated versus unmethylated, with a resection likelihood index of 3.78 and 3.21, respectively (p = 0.004); however, there was no significant difference between IDH mutant and IDH wild-type tumors. Results of this survey reveal current practices regarding ERR, but they also demonstrate the variability in how neurosurgeons approach ERR. Standardized guidelines based on future studies incorporating tumor molecular characteristics are needed to guide neurosurgeons in their decision-making on this complicated issue.


Cranial surgery in ancient Peru.
Trephination is the oldest known surgical technique. Peru has been recognized as a major source of ancient trephined skulls, many of which date back 2300 years. This presentation reviews from a neurosurgical perspective many of the archaeological studies performed on these skulls. Comparative osteology has shown that almost 70% of patients survived the procedure. The various instruments, hemostatic agents, anesthetics, surgical techniques, and cranioplasties used are reconstructed from the anthropological literature. The possible reasons for the use of trephination are discussed. Analysis of the data leads to the conclusion that, despite their rudimentary knowledge of disease, the ancient Incas must have had some knowledge of anatomy and proper surgical procedure.


Aldo van Eyck's Playgrounds: Aesthetics, Affordances, and Creativity.
After World War II, the Dutch architect Aldo van Eyck developed hundreds of playgrounds in the city of Amsterdam. These public playgrounds were located in parks, squares, and derelict sites, and consisted of minimalistic aesthetic play equipment that was supposed to stimulate the creativity of children. Over the last decades, these playgrounds have been studied by sociologists, theorists of art and architecture, and psychologists. Adopting an ecological approach to the human environment, it is argued that the abstract forms of van Eyck's play sculptures indeed stimulate the creativity of the child. Whereas a slide or a swing almost dictates what a child is supposed to do, van Eyck's play equipment invites the child to actively explore the numerous affordances (action possibilities) it provided. However, it is argued that the standardization (e.g., equal distances between blocks or bars) that tends to characterize van Eyck' play equipment has negative effects on the playability. This standardization, which was arguably the result of the aesthetic motives of the designer, might be appealing to children when simply looking at the equipment, but it is not of overriding importance to them when playing in it. Indeed, a recent study indicates that the affordances provided by messy structures appear to have a greater appeal to playing children.


Systematic tracking of altered modules identifies the key biomarkers involved in chronic lymphocytic leukemia.
Key genes in chronic lymphocytic leukemia (CLL) were investigated through systematically tracking the dysregulated modules from protein-protein interaction (PPI) networks. Microarray data of normal subjects and CLL patients recruited from ArrayExpress database were applied to extract differentially expressed genes (DEGs). Additionally, we re-weighted the PPI network of normal and CLL conditions by means of Pearsons correlation coefficient (PCC). Furthermore, clique-merging method was applied to extract the modules and then the altered modules were screened out. The intersection genes were selected from miss and add genes in the altered modules. The common genes were screened from the intersection genes and DEGs in CLL. A total of 734 DEGs were screened by statistical analysis. In this investigation, there were 1,805 and 703 modules in normal as well as disease PPI network. In addition, 875 altered modules were obtained which included 145 miss genes, 353 add genes and 85 intersection genes. Finally, in-depth analysis revealed 9 mutual genes between the intersection genes and DEGs in CLL. Our analysis revealed several key genes associated with CLL by systematically tracking the dysregulated modules, which might be candidate targets for diagnosis and management of CLL.


Subjective Quality of Vision in Evaporative Dry Eye Patients After Intense Pulsed Light.
Background and objective: Intense pulsed light (IPL) improves visual and clinical symptoms of dry eye disease and helps improve meibomian gland (MG) function thereby positively contributing to the tear lipid layer, a major component for a normal tear film physiology. The objective of this study was to assess the effectiveness of IPL in moderate to severe evaporative dry eye (DE) owing to meibomian gland dysfunction (MGD) on the subjective quality of vision (QOV). Methods: This is a prospective, open-label study; patients with moderate to severe evaporative DE owing to MGD were consecutively enrolled and underwent two IPL treatment sessions at 3-week intervals. Clinical assessments included: Ocular Surface Disease Index (OSDI) and QOV questionnaires, noninvasive tear breakup time (NITBUT), interferometric fringe pattern as determined by tear film lipid layer (TFLL) quality, lid margin abnormalities, corneal fluorescein staining (CFS), conjunctival hyperemia (CH) redness score, MG (evaluated with a slit-lamp microscope), best-corrected visual acuity, endothelial cell count, and intraocular pressure were conducted at pretreatment, days 21 and 42 after IPL treatment. Results: A total of 128 eyes of 64 patients (39 women, 25 men; mean age 36.09 ± 11.13 years) with moderate to severe DE owing to MGD consecutively received IPL treatment at days 1 and 21. OSDI (p < 0.05), QOV (p < 0.05), NITBUT (p < 0.05), TFLL score (p < 0.05), and MG quality and expressibility (p < 0.05) improved significantly at day 42, whereas CFS and CH showed minor not significant improvements (p > 0.05) at day 42 of assessment. Conclusions: IPL treatment reduced the severity of DE symptoms and improved the overall tear film stability in patients with moderate to severe evaporative DE owing to MGD. In addition, visual complaints experienced by DE patients secondary to MGD significantly decreased.


Cross-reactivity of anti-yellowtail thymic lymphocyte monoclonal antibody (YeT-2) with lymphocytes from other fish species.
The monoclonal antibody YeT-2, generated in mice hyper-immunized with thymic lymphocytes of the yellowtail, Seriola quinqueradiata, reacts with the major population of peripheral blood lymphocytes, which might be putative T cells. In this study, we examined the cross-reactivity of YeT-2 with lymphocytes from various fish species. Flow cytometric analysis showed that YeT-2 reacts with 69.8% lymphocytes in the thymus, 89.7% in the peripheral blood, 87.5% in the spleen, and 59.7% in the head-kidney. Among the six fish species examined, only the red sea bream, Pagrus major, which is included in the same suborder Percoidei with the yellowtail, showed the presence of YeT-2 positive cells. Electron microscopic studies revealed that YeT-2 positive cells in the peripheral blood of the red sea bream were lymphocytes or unidentified leucocytes. Thymic lymphocytes of the red sea bream were also immunocytochemically stained with YeT-2. The molecular weight of the YeT-2 cross-reacting antigen on blood cells from the red sea bream was identical with that from the yellowtail, which was identified at approximately 115 kDa. These results suggest that the monoclonal antibody YeT-2 recognizes a conserved antigen on lymphocytes common to the red sea bream and yellowtail.


HMGA2 regulation by miRNAs in cancer: Affecting cancer hallmarks and therapy response.
High mobility group A 2 (HMGA2) is a protein that modulates the structure of chromatin in the nucleus. Importantly, aberrant expression of HMGA2 occurs during carcinogenesis, and this protein is an upstream mediator of cancer hallmarks including evasion of apoptosis, proliferation, invasion, metastasis, and therapy resistance. HMGA2 targets critical signaling pathways such as Wnt/β-catenin and mTOR in cancer cells. Therefore, suppression of HMGA2 function notably decreases cancer progression and improves outcome in patients. As HMGA2 is mainly oncogenic, targeting expression by non-coding RNAs (ncRNAs) is crucial to take into consideration since it affects HMGA2 function. MicroRNAs (miRNAs) belong to ncRNAs and are master regulators of vital cell processes, which affect all aspects of cancer hallmarks. Long ncRNAs (lncRNAs) and circular RNAs (circRNAs), other members of ncRNAs, are upstream mediators of miRNAs. The current review intends to discuss the importance of the miRNA/HMGA2 axis in modulation of various types of cancer, and mentions lncRNAs and circRNAs, which regulate this axis as upstream mediators. Finally, we discuss the effect of miRNAs and HMGA2 interactions on the response of cancer cells to therapy. Regarding the critical role of HMGA2 in regulation of critical signaling pathways in cancer cells, and considering the confirmed interaction between HMGA2 and one of the master regulators of cancer, miRNAs, targeting miRNA/HMGA2 axis in cancer therapy is promising and this could be the subject of future clinical trial experiments.


Entrapment neuropathies. A guide to avoiding misdiagnoses.
Nerve entrapment has many possible causes and can mimic a broad range of disorders. A carefully taken history and thorough neurologic examination are the most important parts of evaluation, and plain radiography, electromyography, and nerve conduction velocity studies are useful adjuncts. Treatment options include correction of underlying causes; reduction in activity; exercise programs; wearing of splints, arch supports, or foot braces; local injections of corticosteroids and/or anesthetics; use of nonsteroidal anti-inflammatory drugs; and surgical decompression. Early, appropriate therapy ensures a good outcome.


Retinol-binding protein 4 in human obesity.
Studies in mice suggest that adipocytes serve as glucose sensors and regulate systemic glucose metabolism through release of serum retinol-binding protein 4 (RBP4). This model has not been validated in humans. RBP4 was highly expressed in isolated mature human adipocytes and secreted by differentiating human adipocytes. In contrast to the animal data, RBP4 mRNA was downregulated in subcutaneous adipose tissue of obese women, and circulating RBP4 concentrations were similar in normal weight, overweight, and obese women (n = 74). RBP4 was positively correlated with GLUT4 expression in adipose tissue, independent of any obesity-associated variable. Five percent weight loss slightly decreased adipose RBP4 expression but did not influence circulating RBP4. In another set of experiments, we stratified patients (n = 14) by low or high basal fasting interstitial glucose concentrations, as determined by the microdialysis technique. Venous glucose concentrations were similar throughout oral glucose tolerance testing, and basal RBP4 expression in adipose tissue and serum RBP4 concentrations were similar in the groups with higher and lower interstitial glucose levels. Our findings point to profound differences between rodents and humans in the regulation of adipose or circulating RBP4 and challenge the notion that glucose uptake by adipocytes has a dominant role in the regulation of RBP4.


The effect of hypertonic salt on interferon and interferon mRNA synthesis in human MG63 cells.
After infection with Sendai virus or Newcastle disease virus (NDV) strain F, human osteosarcoma MG63 cells produced large amounts of interferon-beta. Both interferon production and overall protein synthesis were strongly inhibited by hypertonic salt. Interferon mRNA synthesis, however, was little affected by hypertonic salt up to twice normal salt concentrations, although cellular RNA synthesis was inhibited under these conditions. The results are compared to those obtained with polyriboinosinic acid: polyribocytidylic acid copolymer [poly(rI) . poly(rC)] inductions of MG63 cells.


[Fluorescent angiography of the papillary region in glaucoma].
The results of fluorescent angiography show that the main blood supply to the papilla comes from the ciliary circulation in the region of the lamina cribrosa, generally from the posterior ciliary arteries and less frequently from Zinn's corona, in the prelaminar region, to a considerable extent from the peripapillary choroid membrane and in the retrolaminar part also from the recurrent branches of the peripapillary choroid membrane. It also emerges that the vascular supply of the papilla in this region is arranged by segments, which explains, for example, the formation of nerve-fibre bundle defects in glaucoma. Papillary irrigation and the peripapillary choroid membrane are extremely sensitive to an increase in intra-ocular pressure. All these results provide a good basis for the assumption that, in glaucoma, the main factor producing restriction of the field of vision and excavations of the papilla is defective irrigation of the papillary vessels, originating in the choroid membrane, with chronic ischemia of the papilla. Our own studies lead us to suspect that disturbances of irrigation can precede functional disorders. For several reasons, fluorescence angiography is ill-suited to routine diagnosis. In general, however, this method does underline the significance of disturbances of papillary irrigation in the origin of glaucoma damage.