A parallel algorithm for the enumeration of benzenoid hydrocarbons

We present an improved parallel algorithm for the enumeration of fixed benzenoids B_h containing h hexagonal cells. We can thus extend the enumeration of B_h from the previous best h=35 up to h=50. Analysis of the associated generating function confirms to a very high degree of certainty that $B_h \sim A \kappa^h /h$ and we estimate that the growth constant $\kappa = 5.161930154(8)$ and the amplitude $A=0.2808499(1)$.Comment: 14 pages, 6 figure

Sildenafil Reduces Expression and Release of IL-6 and IL-8 Induced by Reactive Oxygen Species in Systemic Sclerosis Fibroblasts

Oxidative stress linked to vascular damage plays an important role in the pathogenesis of systemic sclerosis (SSc). Indeed, vascular damage at nailfold capillaroscopy in patients with Raynaud’s Phenomenon (RP) is a major risk factor for the development of SSc together with the presence of specific autoantiobodies. Here, we investigated the effects of the phosphodiesterase type 5 inhibitor (PDE5i) sildenafil, currently used in the management of RP, in modulating the proinflammatory response of dermal fibroblasts to oxidative stress in vitro. Human fibroblasts isolated from SSc patients and healthy controls were exposed to exogenous reactive oxygen species (ROS) (100 µM H2O2), in the presence or absence of sildenafil (1 µM). Treatment with sildenafil significantly reduced dermal fibroblast gene expression and cellular release of IL-6, known to play a central role in the pathogenesis of tissue damage in SSc and IL-8, directly induced by ROS. This reduction was associated with suppression of STAT3-, ERK-, NF-κB-, and PKB/AKT-dependent pathways. Our findings support the notion that the employment of PDE5i in the management of RP may be explored for its efficacy in modulating the oxidative stress-induced proinflammatory activation of dermal fibroblasts in vivo and may ultimately aid in the prevention of tissue damage caused by SSc

Estrogen-receptor-positive breast cancer in postmenopausal women: The role of body composition and physical exercise

Breast cancer (BC) is the most commonly diagnosed cancer among women worldwide and the most common cause of cancer-related death. To date, it is still a challenge to estimate the magnitude of the clinical impact of physical activity (PA) on those parameters producing significative changes in future BC risk and disease progression. However, studies conducted in recent years highlight the role of PA not only as a protective factor for the development of ER+ breast cancer but, more generally, as a useful tool in the management of BC treatment as an adjuvant to traditional therapies. In this review, we focused our attention on data obtained from human studies analyzing, at each level of disease prevention (i.e., primary, secondary, tertiary and quaternary), the positive impact of PA/exercise in ER+ BC, a subtype representing approximately 70% of all BC diagnoses. Moreover, given the importance of estrogen receptors and body composition (i.e., adipose tissue) in this subtype of BC, an overview of their role will also be made throughout this review

Pattern electroretinogram detects localized glaucoma defects

Purpose: We evaluated the clinical ability of pattern electroretinogram (PERG) to detect functional losses in the affected hemifield of open-angle glaucoma patients with localized perimetric defects. Methods: Hemifield (horizontally-defined) steady-state PERGs (h-PERGs) were recorded in response to 1.7 c/deg alternating gratings from 32 eyes of 29 glaucomatous patients with a perimetric, focal one-hemifield defect, 10 eyes of 10 glaucomatous patients with a diffuse perimetric defect, and 18 eyes of 18 age-matched normal subjects. Standard automated perimetry (SAP) and spectral-domain optical coherence tomography (SD-OCT) for retinal nerve fiber layer (RNFL) thickness also were performed. h-PERG amplitudes and ratios, calculated corresponding hemifield perimetric deviations, as well as hemiretina RNFL thicknesses were analyzed. Results: h-PERG amplitudes, perimetric deviations, and RNFL thicknesses showed losses (P < 0.001) when comparing affected with unaffected hemifields of localized glaucomatous eyes. No differences were found in h-PERG amplitudes between hemifields of normal or diffuse glaucomatous eyes. h-PERG amplitude ratios (affected/ unaffected hemifield) in localized glaucoma were lower (P < 0.001) than the ratios from normal or diffuse glaucomatous eyes. The areas under the receiver operating characteristic curves for h-PERG amplitude ratios, comparing localized-defect glaucomatous eyes with normal or diffuse glaucomatous eyes, were 0.93 and 0.91, respectively. Conclusions: h-PERG assessment showed good diagnostic accuracy to confirm localized glaucomatous defects detected perimetrically. This test may be particularly useful in cognitively impaired patients or young/nonverbal patients unable to provide reliable visual fields. Translational Relevance: h-PERG provides a sensitive objective measure to confirm

Sildenafil Counteracts the In Vitro Activation of CXCL-9, CXCL-10 and CXCL-11/CXCR3 Axis Induced by Reactive Oxygen Species in Scleroderma Fibroblasts

Oxidative stress plays a key role in systemic sclerosis (SSc) pathogenesis, and an altered redox homeostasis might be responsible for abnormal inflammatory status, fibrosis and tissue damage extension. In this study, we explored the effect of the phosphodiesterase type 5 inhibitor sildenafil in modulating the activation of the CXCL-9, -10, -11/CXCR3 axis, which is fundamental in the perpetuation of inflammation in different autoimmune diseases, in the cell culture of SSc human dermal fibroblasts exposed to a pro-oxidant environment. We observed that sildenafil significantly reduced gene expression and release of CXCL-9, -10 and -11, inhibited the CXCR3 action and suppressed the activation of STAT1-, JNK- and p38MAPK pathways. This in vitro study on dermal fibroblasts supports clinical studies to consider the efficacy of sildenafil in preventing tissue damage and fibrosis in SSc by targeting central biomarkers of disease progression, vascular injuries and fibrosis and reducing the pro-inflammatory activation induced by oxidative stress

Sam68 splicing regulation contributes to motor unit establishment in the postnatal skeletal muscle

RNA-binding proteins orchestrate the composite life of RNA molecules and impact most physiological processes, thus underlying complex phenotypes. The RNA-binding protein Sam68 regulates differentiation processes by modulating splicing, polyadenylation, and stability of select transcripts. Herein, we found that Sam68-/- mice display altered regulation of alternative splicing in the spinal cord of key target genes involved in synaptic functions. Analysis of the motor units revealed that Sam68 ablation impairs the establishment of neuromuscular junctions and causes progressive loss of motor neurons in the spinal cord. Importantly, alterations of neuromuscular junction morphology and properties in Sam68-/- mice correlate with defects in muscle and motor unit integrity. Sam68-/- muscles display defects in postnatal development, with manifest signs of atrophy. Furthermore, fast-twitch muscles in Sam68-/- mice show structural features typical of slow-twitch muscles, suggesting alterations in the metabolic and functional properties of myofibers. Collectively, our data identify a key role for Sam68 in muscle development and suggest that proper establishment of motor units requires timely expression of synaptic splice variants

Macular impairment in fabry disease: A morpho-functional assessment by swept-source OCT angiography and focal electroretinography

PURPOSE. Fabry disease (FD) is a multiorgan X-linked condition characterized by a deficiency of the lysosomal enzyme alpha-galactosidase A, resulting in a progressive intralysosomal deposit of globotriaosylceramide. The aim of this study was to evaluate the macular ultrastructure of the vascular network using optical coherence tomography angiography (OCTA) and to evaluate macular function using focal electroretinography (fERG) in Fabry patients (FPs). METHODS. A total of 20 FPs (38 eyes, mean age 57 \ub1 2.12 SD, range of 27\u201380 years) and 17 healthy controls (27 eyes, mean age 45 years \ub1 20.50 SD, range of 24\u201365 years) were enrolled in the study. Color fundus photography, swept-source optical coherence tomography (SS-OCT), OCTA and fERG were performed in all subjects. The OCTA foveal avascular zone (FAZ), vasculature structure, superficial and deep retinal plexus densities (images of 4.5 X 4.5 mm) and fERG amplitudes were measured. Group differences were statistically assessed by Student\u2019s t-test and ANOVA. RESULTS. In the FP group, the FAZ areas of the superficial and deep plexuses were enlarged (P = 0.036, t = 2.138; P < 0.001, t = 3.889, respectively), the vessel density was increased in the superficial plexus, and the fERG amplitude was reduced (P < 0.001, t = 10.647) compared with those in healthy controls. No significant correlations were found between the structural and functional data. CONCLUSIONS. OCTA vascular abnormalities and reduced fERG amplitudes indicate subclinical signs of microangiopathy with early retinal dysfunction in FPs. This study highlights the relevance of OCTA imaging analysis in the identification of abnormal macular vasculature as an ocular hallmark of FD

Analyse automatique des données scripturales prétraitées par des outils de visualization

RÉSUMÉ: Plusieurs méthodes pour analyser le processus d'écriture ont été utilisés afin de comprendre les stratégies des scripteurs. L'outil principal pour analyser le processus d'écriture est le fichier log, qui contient de façon exhaustive et détaillée l'ensemble des opérations effectuées par le scripteur lors de la rédaction d'un texte. Les données qui y sont emmagasinées sont de quantité considérable et lorsqu'elles ne sont pas préalablement traitées, elles sont hostiles à être analysées par l'humain. Parmi les outils d'analyse utilisés, les représentations du processus d'écriture permettent l'agrégation des données grâce à un pré-traitement. Les structures sous-jacentes des données ainsi représentées sont généralement plus propices à l'analyse que les données brutes. Cet article vise à démontrer différentes méthodes d'analyse automatique pouvant être appliquées à ces structures afin de trouver ou confirmer des structures et tendances à travers les données. ABSTRACT: Several methods to analyze the writing process were used in order to understand the strategies of the writers. The main tool to analyze the writing process is the log file which contains all the operations performed by the writer when writing a text, in a comprehensive and detailed way. The data stored in it is of considerable amount and when not previously treated, it is not made to be analyzed by humans. Among the analytical tools used, the representations of the writing process allow aggregation of data through a pre-treatment. The underlying data structures as shown by these tools are generally conducive to analyzing the raw data afterwards. This article aims to demonstrate various automatic analysis methods that can be applied to these structures to find or confirm the structures and trends through data

Acute tubulointerstitial nephritis complicating Legionnaires' disease: a case report

<p>Abstract</p> <p>Introduction</p> <p>Legionnaires' disease is recognized as a multi-systemic illness. Afflicted patients may have pulmonary, renal, gastrointestinal tract and central nervous system complications. However, renal insufficiency is uncommon. The spectrum of renal involvement may range from a mild and transient elevation of serum creatinine levels to anuric renal failure requiring dialysis and may be linked to several causes. In our present case report, we would like to draw attention to the importance of the pathological documentation of acute renal failure by reporting a case of a patient with acute tubulointerstitial nephritis complicating Legionnaires' disease.</p> <p>Case presentation</p> <p>A 55-year-old Caucasian man was admitted to our hospital for community-acquired pneumonia complicated by acute renal failure. <it>Legionella pneumophila </it>serogroup type 1 was diagnosed. Although the patient's respiratory illness responded to intravenous erythromycin and ofloxacin therapy, his renal failure worsened, he became anuric, and hemodialysis was started. A renal biopsy was performed, which revealed severe tubulointerstitial nephritis. After initiation of steroid therapy, his renal function improved dramatically.</p> <p>Conclusions</p> <p>This case highlights the importance of kidney biopsies in cases where acute renal failure is a complicating factor in Legionnaires' disease. If the presence of acute tubulointerstitial nephritis can be confirmed, it will likely respond favorably to steroidal treatment and thus irreversible renal damage and chronic renal failure will be avoided.</p