Projection decomposition algorithm for dual-energy computed tomography via deep neural network.
Dual-energy computed tomography (DECT) has been widely used to improve identification of substances from different spectral information. Decomposition of the mixed test samples into two materials relies on a well-calibrated material decomposition function. This work aims to establish and validate a data-driven algorithm for estimation of the decomposition function. A deep neural network (DNN) consisting of two sub-nets is proposed to solve the projection decomposition problem. The compressing sub-net, substantially a stack auto-encoder (SAE), learns a compact representation of energy spectrum. The decomposing sub-net with a two-layer structure fits the nonlinear transform between energy projection and basic material thickness. The proposed DNN not only delivers image with lower standard deviation and higher quality in both simulated and real data, and also yields the best performance in cases mixed with photon noise. Moreover, DNN costs only 0.4 s to generate a decomposition solution of 360 × 512 size scale, which is about 200 times faster than the competing algorithms. The DNN model is applicable to the decomposition tasks with different dual energies. Experimental results demonstrated the strong function fitting ability of DNN. Thus, the Deep learning paradigm provides a promising approach to solve the nonlinear problem in DECT.


[Scaphocephaly: mathematical and geometrical principles. Surgical incidences].
Authors have reported the mathematical and geometrical principles of cranioplasty used for the surgical treatment of patients with scaphocephaly. After a review of classical mathematical procedures utilized to modify the surface of spherical or hemispherical structures, and after some considerations about relevant properties of bone, the authors illustrate the possibility of a clinical application. The technique described and used in a series of 40 patients, is a simple adaptation of the principles used by engineers to build complex structure such as ships hulls, domes and airfoils. The very satisfactory results obtained, encouraged us to extend the application of the method reports to the reshaping of the skull in other cranio-facial malformations characterized by abnormal skull morphology.


Chi-miR-4110 promotes granulosa cell apoptosis by targeting Sma- and Mad-related protein 2 (Smad2) in the caprine ovary.
Follicular atresia mainly results from the apoptosis of granulosa cells (GCs). Whilst our previous investigations examined the role of chi-miR-4110 in regulating ovarian function, the present study detected the role of chi-miR-4110 in GC development. We transfected caprine GCs cultured in vitro with chi-miR-4110 mimics. Results revealed that chi-miR-4110 decreased mRNA and protein levels of Smad2 by targeting its 3'-untranslated region (3'UTR). FoxC1 and Sp1 mRNA and protein levels markedly increased, whereas those of bHLHe22 significantly decreased (P<0.01 or 0.05) in GCs transfected with the chi-miR-4110 mimics. Further studies revealed a significantly higher number of apoptotic cells in GCs transfected with the chi-miR-4110 mimics (P< 0.05) than in GCs transfected with mimics negative control. GCs transfected with the chi-miR-4110 mimics exhibited significantly increased mRNA and protein levels of the pro-apoptotic gene Bax (P<0.01) and significantly decreased expression levels of the anti-apoptotic gene BCL-2 (P<0.01). Smad2 interference (Si-1282) results were consistent with those of the chi-miR-4110 mimics. Previous reports and our results showed that chi-miR-4110 increases Sp1 expression by repressing Smad2. The increase in Sp1 induces p53-upregulated modulator of apoptosis, which increases the relative abundance of Bax and causes caprine GC apoptosis. Our findings may provide relevant data for the investigation of miRNA-mediated regulation of ovarian functions.


Magnetic resonance evaluation of hydronephrosis in the dog.
The ability of magnetic resonance (MR) imaging to detect and distinguish various stages of obstruction in the canine kidney was investigated. MR images were obtained at acute, subacute, and chronic stages of experimentally produced hydronephrosis. The renal cortex was distinguished from the renal medulla in the normal dog and in the acute and subacute stages of hydronephrosis. T1 relaxation times of the renal cortex and medulla were measured in vitro in 14 normal and nine experimental animals. These values were used to compute the amount of tissue contrast between the cortex and medulla and were compared with the degree of corticomedullary differentiation seen in the image. A relationship was noted between increasing T1 values and increasing water content. Corticomedullary contrast decreased with obstruction. The variation in corticomedullary image contrast may be useful for assessing the duration of hydronephrosis.


Exploring yawning with neuroimaging.
The neural mechanisms responsible for spontaneous yawning as well as contagious yawning are not well characterized. Neuroimaging is an essential tool for helping to identify the seminal neural structures and their inter-related functions to carry out this complex stereotyped motor program. Studies to date have explored the structural neural correlates of yawning through a series of lesion-based case reports and identified participatory structures at various levels of the central nervous system. Functional neuroimaging methods like fMRI have also shed led on the genesis of contagious yawning, though cohesive models explaining the neural mechanisms of contagious motor programs such as yawning remain limited.


[Comparative proteomic analysis of human large cell lung cancer cell line with high and low metastasis potentials].
A comparative proteomic analysis on two human large cell lung cancer strains with high metastasis potential (L9981) and low metastasis potential (NL9980) were conducted. The total proteins of the two cell lines were separated by immobilized pH gradient (IPG )-based two-dimensional gel electrophoresis. The differential expression proteins of the two cell lines were analyzed using image analysis software. Thirteen differential expressed proteins were further identified using in-gel digestion with trypsin, of which peptide extracts were prepared for MALDI-TOF MS/MS analysis by Daltonics AutoFlex TOF-TOF LIFT Mass Spectrometer (Bruker). Protein identifications were searched in the NCBInr protein database using the Mascot search engine. Protein image analysis indicated that 8 protein spots were observed only in L9981, not in NL9980; 8 protein spots were observed only in NL9980, not in L9981; 19 protein spots were detected in both L9981 and NL9980, of which 9 showed significantly higher volumes in L9981 than in NL9980 and 10 showed significantly higher volumes in NL9980 than in L9981. MS and biological informatics study found that the expressions of heat shock 70 kD protein 9B precursor, MTHSP75 and glutathione synthetas incerased in L9981 cells. However, a variant of P47 protein, immunoglobulin heavy chain variable region, enolasel, heat shock protein and eukaryotic translation initiation fact 3 were down-regulated in L9981 cells. Pyruvate kinase (PK) was only expressed in L9981 cells while WD-40 repeat protein was only expressed in NL9980 cells. The metastatic lung cancer cell lines display different protein profiles compared to the non metastatic lung cancer cell lines. The identified proteins are likely to be associated with tumor metastasis, 4hich could serve as a basis for searching potential prognosis markers of lung cancer and elucidating the mechanisms of the metastasis of lung cancer.


Induction of pyrimidine nucleoside metabolizing enzymes in E. coli B.
Induction studies on pyrimidine metabolizing enzymes in E. coli B have shown that the enzymes fall into three distinct groups according to their induction pattern. a) Cytidine deaminase and uridine phosphorylase, are induced by cytidine, CMP and adenosine; no induction was observed with uridine and AMP; b) thymidine phosphorylase is induced by cytidine, adenosine, all deoxyribonucleosides, CMP, deoxyribonucleotides, deoxyribose and deoxyribose-1-phosphate; c) uridine-cytidine kinase, uracil phosphoribosyltransferase, 5'-nucleotidase, thymidine kinase, are uninducible enzymes. Simultaneous addition of cytidine and glucose partially overcomes the cytidine deaminase and uridine phosphorylase induction. Cytidine deaminase reaches its maximum activity levels, in E. coli growing cells in presence of cytidine, two hours before the uridine phosphorylase activity. Maximum glucose repression of cytidine deaminase and uridine phosphorylase was obtained in correspondence of maximum cytidine induction.


Adenosine monophosphate-activated protein kinase suppresses vascular smooth muscle cell proliferation through the inhibition of cell cycle progression.
Vascular smooth muscle cell (VSMC) proliferation is a critical event in the development and progression of vascular diseases, including atherosclerosis. We investigated whether the activation of adenosine monophosphate-activated protein kinase (AMPK) could suppress VSMC proliferation and inhibit cell cycle progression. Treatment of human aortic smooth muscle cells (HASMCs) or isolated rabbit aortas with the AMPK activator 5-Aminoimidazole-4-carboxamide ribonucleoside (AICAR) induced phosphorylation of AMPK and acetyl Co-A carboxylase. AICAR significantly inhibited HASMC proliferation induced by both platelet-derived growth factor-BB (PDGF-BB) and fetal calf serum (FCS). Treatment with AICAR inhibited the phosphorylation of retinoblastoma gene product (Rb) induced by PDGF-BB or FCS, and increased the expression of cyclin-dependent kinase inhibitor p21(CIP) but not that of p27(KIP). Pharmacological inhibition of AMPK or overexpression of dominant negative-AMPK inhibited both the suppressive effect of AICAR on cell proliferation and the phosphorylation of Rb, suggesting that the effect of AICAR is mediated through the activation of AMPK. Cell cycle analysis in HASMCs showed that AICAR significantly increased cell population in G0/G1-phase and reduced that in S- and G2/M-phase, suggesting AICAR induced cell cycle arrest. AICAR increased both p53 protein and Ser-15 phosphorylated p53 in HASMCs, which were blocked by inhibition of AMPK. In isolated rabbit aortas, AICAR also increased Ser-15 phosphorylation and protein expression of p53 and inhibited Rb phosphorylation induced by FCS. These data suggest for the first time that AMPK suppresses VSMC proliferation via cell cycle regulation by p53 upregulation. Therefore, AMPK activation in VSMCs may be a therapoietic target for the prevention of vascular diseases.


Anti-Toxoplasma gondii antibodies in hemodialysis patients receiving long-term hemodialysis therapy in Turkey.
Toxoplasma is a globally distributed pathogen for humans and animals. In situations of immunodeficiency, Toxoplasma gondii (T. gondii) emerges as a life-threatening infection. Toxoplasma gondii is transmitted parenterally, flourish in state immunosuppression and, most toxoplasma infections are asymptomatic. In the present study, we aimed to investigate the prevalence of anti-T. gondii antibodies in hemodialysis patients with chronic renal failure. We undertook a prospective study of our maintenance hemodialysis patients to determine whether these sources posed a risk for transmission of T. gondii. This study was carried out on patients undergoing regular hemodialysis in the dialysis units (Hemodialysis Center of Antakya State Hospital, Emir Hemodialysis Center and Antakya Hemodialysis Center, Hatay, Turkey) between January 2004 and June 2004. Two hundred and fifty-five hemodialysis patients and 50 healthy controls were studied for the prevalence of anti-T. gondii antibodies by enzyme-linked immunosorbent assay. Anti-immunoglobulin G (IgG) and immunoglobulin M (IgM) T. gondii antibodies positivity were found to be 195 (76.5%) of the 255 hemodialysis patients and 24 (48%) of the 50 control subjects. The difference between them was statistically significant (p<0.05). In addition, an increase of the seropositivity rate was detected with increasing length of time on hemodialysis treatment, indicating a statistically significant difference between these 2 parameters (p<0.05). These findings confirm a high prevalence of toxoplasma infection in hemodialysis patients. These patients are a risk group for toxoplasma infection. Moreover, it is recommended that hemodialysis patients who are susceptible to toxoplasma infections should be identified by T. gondii IgG and IgM specific serological tests. Therefore, patients undergoing hemodialysis should be screened for toxoplasma before dialysis to prevent the dissemination of this infection through the hemodialysis procedure.


[Features of cerebral venous hemodynamic in patients with hypertensive encephalopathy].
To study the characteristics of main clinical and diagnostic indicators of cerebral venous circulation and their dynamics in patients with hypertensive encephalopathy of various stages treated with cytoflavin. Clinical and instrumental data of the examination of 105 patients with the established diagnosis of hypertensive encephalopathy of various stages were analyzed. Cerebral hemodynamics was investigated using transcranial duplex scanning of the veins and sinuses of the brain. Patients (n=85) with diagnostic signs of cerebral venous dysfunction were stratified into two groups by treatment regimen: main group (n=39) received standard antihypertensive therapy with cytoflavin (2 tablets 2 times a day from 1 to 30 days), the control group (n=46) received standard treatment. Control studies of cerebral hemodynamics were performed in both groups on the 30th and 60th day from the start of therapy. Conclusion. The patients who received cytoflavin in the treatment regimen showed a slight improvement on the 30th day and a significant improvement in venous cerebral circulation indicators on the 60th day (p<0,05), which made it possible to conclude that the drug is effective for improving cerebral venous hemodynamics, and to recommend it in the complex therapy of patients with hypertensive encephalopathy of various stages with existing venous cerebral disorders.


Rapid Acquisition of X-Ray Scattering Data from Droplet-Encapsulated Protein Systems.
Encapsulating reacting biological or chemical samples in microfluidic droplets has the great advantage over single-phase flows of providing separate reaction compartments. These compartments can be filled in a combinatoric way and prevent the sample from adsorbing to the channel walls. In recent years, small-angle X-ray scattering (SAXS) in combination with microfluidics has evolved as a nanoscale method of such systems. Here, we approach two major challenges associated with combining droplet microfluidics and SAXS. First, we present a simple, versatile, and reliable device, which is both suitable for stable droplet formation and compatible with in situ X-ray measurements. Second, we solve the problem of "diluting" the sample signal by the signal from the oil separating the emulsion droplets by multiple fast acquisitions per droplet and data thresholding. We show that using our method, even the weakly scattering protein vimentin provides high signal-to-noise ratio data.


The role of α₂ adrenoceptor in mediating noradrenaline action in the ventrolateral orbital cortex on allodynia following spared nerve injury.
The present study examined the role of α₂ adrenoceptor in mediating noradrenaline action in the ventrolateral orbital cortex (VLO) on allodynia induced by spared nerve injury (SNI) in the rat. The mechanical paw withdrawal threshold (PWT) was measured using von-Frey filaments. Microinjection of noradrenaline (1, 2, 4 μg in 0.5 μl) into the VLO, contralateral to the site of nerve injury, reduced allodynia; PWT increased in a dose-dependent manner. Similar to noradrenaline, microinjection of selective α₂ adrenoceptor agonist clonidine into the same VLO site also reduced allodynia, and was blocked by selective α₂ adrenoceptor antagonist yohimbine. Furthermore, administration of γ-aminobutyric acid A (GABAA) receptor antagonist bicuculline or picrotoxin to the VLO significantly enhanced clonidine-induced inhibition of allodynia, while GABAA receptor agonist muscimol or THIP (2,5,6,7-retrahydroisoxazolo(5,4-c)pyridine-3-ol hydrochloride) attenuated clonidine-induced inhibition. These results suggest that noradrenaline acting in the VLO can potentially reduce allodynia induced by SNI, and this effect is mediated by α₂ adrenoceptor. Moreover, GABAergic disinhibition may participate in α₂ receptor mediating effects in neuropathic pain in the central nervous system.


University Students and Their Ability to Perform Self-Regulated Online Learning Under the COVID-19 Pandemic.
The COVID-19 pandemic has affected all aspects of the educational system, including students' learning styles, which are heavily dependent on self-regulated studying strategies and motivation. The purpose of this study was to discover whether Central European students, in this case the Slovak and Czech students, were able to perform self-regulated learning during online learning under the COVID-19 pandemic to achieve their learning goals and improve academic performance, as well as to propose a few practical recommendations how to develop and maintain students' self-regulation learning in this new online environment. The methodology was based on a questionnaire survey conducted among 268 students at two Central European universities in February and March 2021. The findings indicate that Central European students seemed to be able to perform their online self-study, especially in regard to personal competencies, meaningfulness and motivation. They reported higher awareness of their strengths and weaknesses in learning, time management, and/or the usefulness of making an effort to study. However, the findings reveal an urgent need for more work to be done in the area of metacognitive strategies, such as reflective and critical thinking, analyzing and evaluating. In this respect, the teacher's role is replaceable since s/he serves as a facilitator and promotes these metacognitive strategies by providing students with constructive feedback, monitoring their learning, reviewing their progress, and/or providing opportunities to reflect on their learning. There were not any striking differences between the Czech and Slovak students. Nevertheless, Slovak students (females in particular) seemed to be more self-disciplined and goal-oriented in their learning.


The NADPH Oxidase Inhibitor Apocynin Suppresses Preneoplastic Liver Foci of Rats.
Reactive oxygen species (ROS) have been revealed to be important factors for carcinogenesis and tumor progression. Therefore, we focused on an ROS-generating protein, nicotinamide adenine dinucleotide phosphate oxidase, and evaluated whether its inhibitor, apocynin, could suppress hepatocarcinogenesis in a medium-term rat liver bioassay. The number and size of glutathione S-transferase placental form (GST-P)-positive foci were significantly reduced by apocynin in a dose-dependent manner. The reduction of ROS generation by apocynin was confirmed by dihydroethidium staining. Apocynin treatment also significantly reduced Ki-67 positivity, downregulated cyclooxygenase 2, and suppressed the activation of the c-Myc pathway. Meanwhile, ROS generation was not different between GST-P-positive foci and surrounding GST-P-negative areas of the liver. In conclusion, the present data suggest that apocynin possesses a potential antihepatocarcinogenic property.


Illicit drugs in Emergency Department patients injured in road traffic accidents.
Urine and blood samples from 1730 drivers involved in road accidents (July 2012 - December 2015) were analyzed for the evaluation of driving under influence of drug of abuse according to the Lombardia Region guideline. The 22.5% (95% CI 20.5 to 24.5) of urine screenings tested positive for at least one class of drugs. 10.6% (95% CI 9.2 to 12.1) of the 1730 drivers were under the influence of drug, being blood concentration above the cut-off limit for at least one active substance; the proportion of illicit drugs in blood was cocaine 5.7 % (95% CI 4.7 to 6.9), cannabinoids 3.7 % (95% CI 2.9 to 4.7), opiates 1.4% (95% CI 0.9 to 2.1), methadone 1.4% (95% CI 0.9 to 2.1), amphetamines 0.2% (95% CI 0.04 to 0.5). Trend in proportion showed similar percentage (about 5%) of cocaine and cannabinoids consumption in the last two years. Poly-drug of abuse consumption emerged in the 10.4% (95% CI 6.4 to 15.7) of the positive blood and alcohol was above the legal limit in 47% (95% CI 39.6 to 54.5) of the subjects driving under the influence of drugs.


Oestrogen and progesterone receptors in acoustic neuroma.
Tissue samples from fourteen consecutive (8 male: 6 female) acoustic neuromas were assayed for hormone receptors using either a monoclonal antibody (MA), dextran coated charcoal (DCC) or isoelectric focusing (IEF) technique. In this series there were no unequivocally positive results, a finding at variance with previously published results.


An Improved Imaging Algorithm for High-Resolution Spotlight SAR with Continuous PRI Variation Based on Modified Sinc Interpolation.
This paper focuses on an improved imaging algorithm for spotlight synthetic aperture radar (SAR) with continuous Pulse Repetition Interval (PRI) variation in extremely high-resolution. Conventional SAR systems are limited in that a wide swath cannot be achieved with a high azimuth resolution in the meantime. This limitation can be overcome by Pulse Repetition Frequency (PRF) variation in a SAR system. However, there are problems such as the ambiguities of point targets or extended targets caused by nonuniform sampling. A reconstructive method, Nonuniform Discrete Fourier Transform (NUDFT) has been presented in the current literature, but it is rather computationally expensive. In this paper, a modified sinc interpolation based on NUDFT is proposed, which is used to reconstruct the uniformly sampled echo in time domain. Since the interpolation kernel length is relatively short, it is more computationally efficient. Then, the two-step processing approach combined with the modified sinc interpolation is further presented, which has much better accuracy than that combined with the conventional sinc interpolation. Both the simulated data and the extracted GF-3 data experiment demonstrate the validity and accuracy of the proposed approach.


CoCoA-diff: counterfactual inference for single-cell gene expression analysis.
Finding a causal gene is a fundamental problem in genomic medicine. We present a causal inference framework, CoCoA-diff, that prioritizes disease genes by adjusting confounders without prior knowledge of control variables in single-cell RNA-seq data. We demonstrate that our method substantially improves statistical power in simulations and real-world data analysis of 70k brain cells collected for dissecting Alzheimer's disease. We identify 215 differentially regulated causal genes in various cell types, including highly relevant genes with a proper cell type context. Genes found in different types enrich distinctive pathways, implicating the importance of cell types in understanding multifaceted disease mechanisms.


24-h blood pressure monitoring in normal tension glaucoma: night-time blood pressure variability.
Systemic arterial hypotension, hypertension and altered ocular blood flow are known risk factors in glaucoma. In this study, 24-h ambulatory blood pressure monitoring was performed in patients with normal tension glaucoma (NTG) and controls to evaluate blood pressure variability. In all, 51 patients with NTG and 28 age-matched controls were included in this prospective study. A 24-h ambulatory blood pressure monitoring (SpaceLabs Medical Inc., Redmond, USA) was performed and systolic, diastolic and mean arterial blood pressures were measured every 30 min during daytime (0800-2000) and night time (0000-0600). To evaluate blood pressure variability a variability index was defined as the s.d. of blood pressure measurements. Night-time blood pressure depression ('dip') was calculated (in percent of the daytime blood pressures). Patients with NTG exhibited higher night-time diastolic (P = 0.01) and mean arterial blood pressure values (P = 0.02) compared to controls, whereas systolic blood pressure data were not significantly different. The variability indices of night-time systolic, diastolic and mean arterial blood pressure measurements were significantly increased in patients with NTG compared to controls (P < 0.05). The night-time blood pressure depression of systolic (P = 0.47), diastolic (P = 0.11) and mean arterial blood pressures (P = 0.28) was not significantly different between patients with NTG and controls. In conclusion, patients with NTG showed increased variability of night-time blood pressure measurements compared to controls. Increased fluctuation of blood pressure may lead to ocular perfusion pressure fluctuation and may cause ischaemic episodes at the optic nerve head.


Antihistamines modulate the integrin signaling pathway in h9c2 rat cardiomyocytes: Possible association with cardiotoxicity.
The identification of biomarkers for toxicity prediction is crucial for drug development and safety evaluation. The selective and specific biomarkers for antihistamines-induced cardiotoxicity is not well identified yet. In order to evaluate the mechanism of the life-threatening effects caused by antihistamines, we used DNA microarrays to analyze genomic profiles in H9C2 rat cardiomyocytes that were treated with antihistamines. The gene expression profiles from drug-treated cells revealed changes in the integrin signaling pathway, suggesting that cardiac arrhythmias induced by antihistamine treatment may be mediated by changes in integrin-mediated signaling. It has been reported that integrin plays a role in QT prolongation that may induce cardiac arrhythmia. These results indicate that the integrin-mediated signaling pathway induced by antihistamines is involved in various biological mechanisms that lead to cardiac QT prolongation. Therefore, we suggest that genomic profiling of antihistamine-treated cardiomyocytes has the potential to reveal the mechanism of adverse drug reactions, and this signal pathway is applicable to prediction of in vitro cardiotoxicity induced by antihistamines as a biomarker candidate.


Global MicroRNAs Expression Profile Analysis Reveals Possible Regulatory Mechanisms of Brain Injury Induced by Toxoplasma gondii Infection.
Toxoplasma gondii (T. gondii) is an obligate intracellular parasitic protozoan that can cause toxoplasmosis in humans and other endotherms. T. gondii can manipulate the host gene expression profile by interfering with miRNA expression, which is closely associated with the molecular mechanisms of T. gondii-induced brain injury. However, it is unclear how T. gondii manipulates the gene expression of central nervous system (CNS) cells through modulation of miRNA expression in vivo during acute and chronic infection. Therefore, high-throughput sequencing was used to investigate expression profiles of brain miRNAs at 10, 25, and 50 days post-infection (DPI) in pigs infected with the Chinese I genotype T. gondii strain in this study. Compared with the control group 87, 68, and 135 differentially expressed miRNAs (DEMs) were identified in the infected porcine brains at 10, 25, and 50 DPI, respectively. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis showed that a large number significantly enriched GO terms and KEGG pathways were found, and were mostly associated with stimulus or immune response, signal transduction, cell death or apoptosis, metabolic processes, immune system or diseases, and cancers. miRNA-gene network analysis revealed that the crucial connecting nodes, including DEMs and their target genes, might have key roles in the interactions between porcine brain and T. gondii. These results suggest that the regulatory strategies of T. gondii are involved in the modulation of a variety of host cell signaling pathways and cellular processes, containing unfolded protein response (UPR), oxidative stress (OS), autophagy, apoptosis, tumorigenesis, and inflammatory responses, by interfering with the global miRNA expression profile of CNS cells, allowing parasites to persist in the host CNS cells and contribute to pathological damage of porcine brain. To our knowledge, this is the first report on miRNA expression profile in porcine brains during acute and chronic T. gondii infection in vivo. Our results provide new insights into the mechanisms underlying T. gondii-induced brain injury during different infection stages and novel targets for developing therapeutic agents against T. gondii.


Pulmonary artery hypertension and sleep-disordered breathing: ACCP evidence-based clinical practice guidelines.
The objective of this article is to review the available data on the relationship between sleep-disordered breathing (SDB) and pulmonary arterial hypertension (PAH), with a focus on the prevalence of SDB in patients with idiopathic PAH (IPAH); the prevalence of PAH in patients with SDB; and the effects of SDB treatment on PAH. The evidence to date suggests that PAH may occur in the setting of SDB, although the prevalence is low. However, pulmonary hypertension (PH) in SDB is most strongly associated with other risk factors, such as left-sided heart disease, parenchymal lung disease, nocturnal desaturation, and obesity. The limited data available also suggest that SDB is uncommon in patients with IPAH. Treatment of SDB with continuous positive airway pressure may lower pulmonary artery pressures when the degree of PH is mild.


Pseudomonas fitomaticsae sp. nov., isolated at Marimurtra Botanical Garden in Blanes, Catalonia, Spain.
In the framework of the research project called fitomatics, we have isolated and characterized a bacterial plant-endophyte from the rhizomes of Iris germanica, hereafter referred to as strain FIT81T. The bacterium is Gram negative, rod-shaped with lophotrichous flagella, and catalase- and oxidase-positive. The optimal growth temperature of strain FIT81T is 28 °C, although it can grow within a temperature range of 4-32 °C. The pH growth tolerance ranges between pH 5 and 10, and it tolerates 4% (w/v) NaCl. A 16S rRNA phylogenetic analysis positioned strain FIT81T within the genus Pseudomonas, and multilocus sequence analysis revealed that Pseudomonas gozinkensis IzPS32dT, Pseudomonas glycinae MS586T, Pseudomonas allokribbensis IzPS23T, 'Pseudomonas kribbensis' 46-2 and Pseudomonas koreensis PS9-14T are the top five most closely related species, which were selected for further genome-to-genome comparisons, as well as for physiological and chemotaxonomic characterization. The genome size of strain FIT81T is 6 492 796 base-pairs long, with 60.6 mol% of G+C content. Average nucleotide identity and digital DNA-DNA hybridization analyses yielded values of 93.6 and 56.1%, respectively, when the FIT81T genome was compared to that of the closest type strain P. gozinkensis IzPS32dT. Taken together, the obtained genomic, physiologic and chemotaxonomic data indicate that strain FIT81T is different from its closest relative species, which lead us to suggest that it is a novel species to be included in the list of type strains with the name Pseudomonas fitomaticsae sp. nov. (FIT81T=CECT 30374T=DSM 112699T).


The relative importance of water temperature and residence time in predicting cyanobacteria abundance in regulated rivers.
Despite a growing awareness of the problems associated with cyanobacterial blooms in rivers, and particularly in regulated rivers, the drivers of bloom formation and abundance in rivers are not well understood. We developed a Bayesian hierarchical model to assess the relative importance of predictors of summer cyanobacteria abundance, and to test whether the relative importance of each predictor varies by site, using monitoring data from 16 sites in the four major rivers of South Korea. The results suggested that temperature and residence time, but not nutrient levels, are important predictors of summer cyanobacteria abundance in rivers. Although the two predictors were of similar significance across the sites, the residence time was marginally better in accounting for the variation in cyanobacteria abundance. The model with spatial hierarchy demonstrated that temperature played a consistently significant role at all sites, and showed no effect from site-specific factors. In contrast, the importance of residence time varied significantly from site to site. This variation was shown to depend on the trophic state, indicated by the chlorophyll-a and total phosphorus levels. Our results also suggested that the magnitude of weir inflow is a key factor determining the cyanobacteria abundance under baseline conditions.


HIV- positive anal cancer: an update for the clinician.
Anal cancer used to be a rare cancer traditionally associated with elderly women. There are approximately 5260 cases per year in the U.S. (1). The onslaught of the Human Immunodeficiency Virus (HIV) virus has led to a change in anal cancer demographics. Anal cancer is on the rise in the U.S and the number of anal cases documented has quadrupled in the past 20 yrs correlating with the rise of the HIV epidemic. The incidence of anal cancer is 40 to 80 fold higher in the HIV positive (HIV+) population when compared to the general population (2). With the advent of highly active antiretroviral therapy (HAART), HIV+ patients are living longer as less are progressing to AIDS. As a consequence non AIDS defining cancers such as anal cancer are on the rise. Factors implicated in the etiology of anal cancer in HIV+ patients include (Human papillomavirus) HPV virus status, sexual habits, and a history of smoking. HPV 16 and receptive anal intercourse (RAI) increase the risk of anal cancer by 33% over the general population. In the general population, the rate of anal cancer is approximately 0.9 cases per 100,000. In patients with a history of RAI, the rate approaches 35 cases per 100,000 which is equivalent to the prevalence of cervical cancer (3). Smokers are eight times more likely to develop anal cancer. There has been much discussion about tailoring treatment decisions in HIV+ patients with anal cancer. This review focuses on squamous cell carcinomas of the anal canal which comprise 80 to 90% of all anal cancers diagnosed and highlight key issues in the management of HIV+ anal cancer patients including recent clinical trials.


Progress of bis(heteroaryl)piperazines (BHAPs) as non-nucleoside reverse transcriptase inhibitors (NNRTIs) against human immunodeficiency virus type 1 (HIV-1).
Since the first case of acquired immunodeficiency syndrome (AIDS) was reported in 1981, AIDS, as the global disease affecting 33.2 million people in 2007, has always been an unsolved problem worldwide. Reverse transcriptase (RT) is a crucial enzyme in the life cycle of human immunodeficiency virus type 1 (HIV-1), and thereby has been the prime drugs target for antiretroviral (ARV) therapy against AIDS. To date, two classes of RT inhibitors (RTIs), e.g., nucleoside reverse transcriptase inhibitors (NRTIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs), and a lot of compounds tested as RTIs have been described. To our knowledge, bis(heteroaryl)piperazines (BHAPs) have been considered as one class of promising NNRTIs, such as structurally and chemically related NNRTI delavirdine, which was approved by the U. S. Food and Drug Administration (FDA) for the treatment of HIV-1 infection in 1997. In this mini-review, we make attempts to report the progress of synthesis and structure-activity relationship (SAR) of BHAPs, in the meantime, the synergistic inhibition of HIV-1 replication by combining delavirdine with other HIV-1 inhibitors is also discussed. It will pave the way for the design and development of BHAPs as anti-HIV-1 agents in AIDS chemotherapy in the future.


Large-area alignment of tungsten oxide nanowires over flat and patterned substrates for room-temperature gas sensing.
Alignment of nanowires over a large area of flat and patterned substrates is a prerequisite to use their collective properties in devices such as gas sensors. In this work, uniform single-crystalline ultrathin W18 O49 nanowires with diameters less than 2 nm and aspect ratios larger than 100 have been synthesized, and, despite their flexibility, assembled into thin films with high orientational order over a macroscopic area by the Langmuir-Blodgett technique. Alignment of the tungsten oxide nanowires was also possible on top of sensor substrates equipped with electrodes. Such sensor devices were found to exhibit outstanding sensitivity to H2 at room temperature.


DSM265 for Plasmodium falciparum chemoprophylaxis: a randomised, double blinded, phase 1 trial with controlled human malaria infection.
A drug for causal (ie, pre-erythrocytic) prophylaxis of Plasmodium falciparum malaria with prolonged activity would substantially advance malaria control. DSM265 is an experimental antimalarial that selectively inhibits the parasite dihydroorotate dehydrogenase. DSM265 shows in vitro activity against liver and blood stages of P falciparum. We assessed the prophylactic activity of DSM265 against controlled human malaria infection (CHMI). At the Institute of Tropical Medicine, Eberhard Karls University (Tübingen, Germany), healthy, malaria-naive adults were allocated to receive 400 mg DSM265 or placebo either 1 day (cohort 1A) or 7 days (cohort 2) before CHMI by direct venous inoculation (DVI) of 3200 aseptic, purified, cryopreserved P falciparum sporozoites (PfSPZ Challenge; Sanaria Inc, Rockville, MD, USA). An additional group received daily atovaquone-proguanil (250-100 mg) for 9 days, starting 1 day before CHMI (cohort 1B). Allocation to DSM265, atovaquone-proguanil, or placebo was randomised by an interactive web response system. Allocation to cohort 1A and 1B was open-label, within cohorts 1A and 2, allocation to DSM265 and placebo was double-blinded. All treatments were given orally. Volunteers were treated with an antimalarial on day 28, or when parasitaemic, as detected by thick blood smear (TBS) microscopy. The primary efficacy endpoint was time-to-parasitaemia, assessed by TBS. All participants receiving at least one dose of chemoprophylaxis or placebo were considered for safety, those receiving PfSPZ Challenge for efficacy analyses. Log-rank test was used to compare time-to-parasitemia between interventions. The trial was registered with ClinicalTrials.gov, number NCT02450578. 22 participants were enrolled between Oct 23, 2015, and Jan 18, 2016. Five participants received 400 mg DSM265 and two participants received placebo 1 day before CHMI (cohort 1A), six participants received daily atovaquone-proguanil 1 day before CHMI (cohort 1B), and six participants received 400 mg DSM265 and two participants received placebo 7 days before CHMI (cohort 2). Five of five participants receiving DSM265 1 day before CHMI and six of six in the atovaquone-proguanil cohort were protected, whereas placebo recipients (two of two) developed malaria on days 11 and 14. When given 7 days before CHMI, three of six volunteers receiving DSM265 became TBS positive on days 11, 13, and 24. The remaining three DSM265-treated, TBS-negative participants of cohort 2 developed transient submicroscopic parasitaemia. Both participants receiving placebo 7 days before CHMI became TBS positive on day 11. The only possible DSM265-related adverse event was a moderate transient elevation in serum bilirubin in one participant. A single dose of 400 mg DSM265 was well tolerated and had causal prophylactic activity when given 1 day before CHMI. Future trials are needed to investigate further the use of DSM265 for the prophylaxis of malaria. Global Health Innovative Technology Fund, Wellcome Trust, Bill & Melinda Gates Foundation through Medicines for Malaria Venture, and the German Center for Infection Research.


Cheminformatics and systems pharmacology approaches to unveil the potential plant bioactives to combat COVID-19.
COVID-19 was a global pandemic in the year 2020. Several treatment options failed to cure the disease. Thus, plant-based medicines are becoming a trend nowadays due to their less side effects. Bioactive chemicals from natural sources have been utilised for centuries as treatment options for a variety of ailments. To find out the potent bioactive compounds to counteract COVID-19, we use systems pharmacology and cheminformatics. They use the definitive data and predict the possible outcomes. In this study, we collected a total of 72 phytocompounds from the medicinally important plants such as Garcinia mangostana and Cinnamomum verum, of which 13 potential phytocompounds were identified to be active against the COVID-19 infection based on Swiss Target Prediction and compound target network analysis. These phytocompounds were annotated to identify the specific human receptor that targets COVID-19-specific genes such as MAPK8, MAPK14, ACE, CYP3A4, TLR4 and TYK2. Among these, compounds such as smeathxanthone A, demethylcalabaxanthone, mangostanol, trapezifolixanthone from Garcinia mangostana and camphene from C. verum were putatively target various COVID-19-related genes. Molecular docking results showed that smeathxanthone A and demethylcalabaxanthone exhibit increased binding efficiency towards the COVID-19-related receptor proteins. These compounds also showed efficient putative pharmacoactive properties than the commercial drugs ((R)-remdesivir, favipiravir and hydroxychloroquine) used to cure COVID-19. In conclusion, our study highlights the use of cheminformatics approach to unravel the potent and novel phytocompounds against COVID-19. These phytocompounds may be safer to use, more efficient and less harmful. This study highlights the value of natural products in the search for new drugs and identifies candidates with great promise.


Pulp Changes Secondary to Orthodontic Forces: A Review of Literature.
This review article encompasses the literature pertaining to changes in the dental pulp subsequent to forces exerted secondary to orthodontic treatment. The review was conducted at the College of Dentistry, Qassim University, Saudi Arabia, from October 2022 to February 2023. A literature search was conducted on PubMed, Embase, The Cochrane Library and Google Scholar for articles from 2000 to 2023. Keywords and MeSH terms used were 'orthodontic forces', 'pulp changes', 'dental pulpal changes', and 'pulp volume'. Two reviewers went through the titles. After removing irrelevant and duplicate articles, abstracts were assessed for relevant articles. Finally, the reviewers analyzed full-text articles, and a total of five articles including four randomized controlled trials and one retrospective study were selected. It was concluded that managing and minimizing injury to the pulp or supporting tissues is important when using orthodontic mechanics. In order to do so, clinicians must thoroughly understand any change in the pulpal tissue following the orthodontic treatment. Orthodontic tooth movements cause inflammatory changes in the tooth pulp and periodontal ligament which are directly related to the amount, direction, and time duration of force used. Long-term pulp blood flow analysis shows that even though there is a transient uptrend in the flow of blood after the removal of the orthodontic force, it reverts to normal levels three months later. However, pulp volume has been reported to decrease, more prominently in anterior teeth, as orthodontic forces stimulate the pulp to produce tertiary dentin.


Limb Body Wall Complex Associated with Placenta Accreta: A Mere Coincidence or a Sign of an Etiopathogenic Link?
A case was reported of a fetus with the anomaly of limb body wall complex associated with placenta accreta. To date, only one account of this condition has been published in the world literature. Due to the low frequency of both complications, the hypothesis has been raised that this association may have happened not by mere coincidence, but rather by a possible common etiopathogenic mechanism. For the first time, a study proposes the existence of a possible etiopathogenic connection between the anomaly of limb body wall complex and hypoxic disorders caused by inadequate placentation in previous uterine scarring.


Reduced neural selectivity for mental states in deaf children with delayed exposure to sign language.
Language provides a rich source of information about other people's thoughts and feelings. Consequently, delayed access to language may influence conceptual development in Theory of Mind (ToM). We use functional magnetic resonance imaging and behavioral tasks to study ToM development in child (n = 33, 4-12 years old) and adult (n = 36) fluent signers of American Sign Language (ASL), and characterize neural ToM responses during ASL and movie-viewing tasks. Participants include deaf children whose first exposure to ASL was delayed up to 7 years (n = 12). Neural responses to ToM stories (specifically, selectivity of the right temporo-parietal junction) in these children resembles responses previously observed in young children, who have similar linguistic experience, rather than those in age-matched native-signing children, who have similar biological maturation. Early linguistic experience may facilitate ToM development, via the development of a selective brain region for ToM.


Segmental aplasia of the caudal vena cava in a dog.
Ultrasonography, angiography, magnetic resonance imaging, and exploratory laparotomy of a 2-year-old wheaten terrier with lethargy, exercise intolerance, and ascites revealed segmental aplasia of the caudal vena cava with azygos continuation, complicated by thrombus formation. Surgeries were performed on the blind-ended vessel to remove thrombi, enhancing shunting of blood through the azygos vein.


Effect of pretransplant hepatitis C virus RNA status on posttransplant outcome.
Undetectable hepatitis C virus (HCV) RNA [RNA(-)] before liver transplantation (OLT) has been shown to decrease the rates of disease recurrence. We sought to determine whether RNA(-) subjects differ in post-OLT recurrence (virological/VR, histological/HR), graft failure (GF), or patient survival from RNA(+) patients using a retrospective review. From 1995 to 2004, a total of 49 patients were RNA(-) at OLT as a result of interferon-based therapy: 22 SVR and 27 with end-of-treatment response (ETR) transplanted when RNA(-) within 6 months of ET. Forty-eight RNA(+) patients were analyzed as controls. Virological recurrence (VR) was seen in 55% of RNA(-) subjects with no difference in HR between RNA(-) vs (+) groups, namely 36.7% versus 56.3% (P = .068), respectively. The RNA(+) subjects showed a lower time to HR (5.6 vs 11 months; P = .027). The SVR subjects displayed lower VR (36.4%) and histological recurrence (HR) (13.6%) compared to ETR (VR 70.4%, P = .023; HR 55.6%, P = .003) or RNA(+) (HR 56%, P = .0008). The SVR subjects, who were identified with a sensitive assay (SVR(S), lower limit <600 IU/mL) showed no VR, HR, or GF. The 1- and 5-year survivals were 87.8%/75.6% and 89.6%/77.8% for RNA(-) and (+) groups, respectively (P = .77). In conclusion, RNA(-)-transplanted patients displayed lower VR and longer time to HR. The SVR patients showed lower VR and HR compared to ETR and RNA(+) patients.


C^C* Platinum(II) Complexes with Electron-Withdrawing Groups and Beneficial Auxiliary Ligands: Efficient Blue Phosphorescent Emission.
The combination of strong electron-withdrawing groups in cyclometalated N-heterocyclic carbene ligands (C^C*) with known beneficial auxiliary ligands in phosphorescent platinum(II) complexes leads to efficient light-to-deep-blue emission with quantum yields of up to 92%. All compounds were characterized and investigated regarding their photophysical, electrochemical, and thermal properties, and three complexes could additionally be characterized by solid-state structures. Density functional theory calculations (PBE0/6-311G* with dispersion correction) are reported.


Determination of the structure of the organized phase of the block copolymer PEO-PPO-PEO in aqueous solutions under flow by small-angle neutron scattering.
The organization of Tetronic 908 (T908), a star copolymer of poly(ethylene oxide) (PEO) and poly(propylene oxide) (PPO) blocks, has been examined. Above critical conditions of temperature and concentration, the micelles formed by the aggregation of PPO units self-organize into particular structures. While small-angle neutron scattering (SANS) characterizations performed with static conditions demonstrate the organization of the medium, the experimental results do not allow us to make a distinction between simple cubic and body-centered-cubic structures. However, SANS measurements realized under shear produce characteristic diffraction diagrams. In this paper, an accurate methodology is proposed to identify, without ambiguity, the exact nature of the organized phase. Applied to our system, indexing of the diffraction pattern spots reveals that the organization of T908 is of bcc type oriented with the [111] direction parallel to the direction of flow, but the crystals can present any orientation about this direction. The lattice size has been estimated and compared to previous published results.


Obscure gastrointestinal bleeding.
I want to convey the notion that enteroscopy has opened many doors, and continues to open up more doors, in understanding and diagnosing diseases of the small intestine. The true nature of small-bowel angiodysplasia is still unanswered. It seems unlikely that the lesions in the small bowel are similar to the lesions that Scott Boley talks about in the right colon. I doubt that the intermittent obstruction to venous outflow, theorized in the colon, is the pathophysiologic change in the small intestine. Those studies, trying to look for the changes that Boley described, need to be done. We are trying to better characterize angiodysplasia of the small intestine, understanding where they occur, with how many lesions, and whether they are associated with any other illnesses. We are looking at the association of small-bowel vascular lesions with lesions in the stomach and colon. Enteroscopy will in the future, we hope, answer these questions. Enteroscopy, especially push enteroscopy, can help us with the treatment of angiodysplasias. We are now evaluating new instruments that reach not just two feet beyond the ligament of Treitz, but the entire jejunum, reaching 6 feet beyond the ligament of Treitz (16). Enteroscopy facilitates clinical research, can be used in patient care, and guides treatment.


Effect of Different Irrigation Systems on Sealer Penetration into Dentinal Tubules.
Different irrigation systems have been developed to improve the efficacy and distribution of the irrigants. The aim of this study was to compare the effect of conventional endodontic needle irrigation with other irrigant delivery and/or agitation systems on sealer penetration into dentinal tubules. Fifty single-rooted teeth with round-shaped root canals were distributed in 5 homogeneous groups characterized by the different cleansing system used: conventional endodontic needle irrigation, EndoActivator, Irrisafe, Self-Adjusting File, and EndoVac. After instrumentation, all teeth were filled by Thermafil obturators and rhodamine B dye labeled TopSeal sealer. Teeth were transversally sectioned at 2-, 5-, and 7-mm levels from the apex and observed under confocal laser scanning microscope. Maximum, mean, and percentage of sealer penetration inside tubules around the root canal were measured. Moreover, the integrity of the sealer layer perimeter was evaluated. No significant differences both in mean (p > .05) and in maximum penetration depth (p > .05) were observed among groups, whereas both parameters showed an increased trend within each group from the 2- to the 7-mm level from apex. Similarly, the percentage of penetration around the root canal wall did not differ among groups (p > .05) and showed an increasing trend within each group from the apical to the coronal portion of the canal. Sealer penetration into dentinal tubules is not affected by the irrigant delivery and/or agitation systems studied. Thermafil with TopSeal technique achieves complete sealer perimeter integrity in all groups.


Successful pregnancy following partial pancreatectomy after complications from a laparoscopic adjustable gastric banding.
Each year, increasing numbers of bariatric surgeries are being performed to reduce health risks related to obesity. The improvement in health for these patients has promoted an increase in the possibility of pregnancy for some woman. Because there are lifelong adjustments and the possibility of unique complications from bariatric surgery, pregnancy presents special nursing concerns. Very few cases have been identified in nursing literature discussing pregnancy after complications following a bariatric surgery. This article presents a successful pregnancy after a partial pancreatectomy was performed secondary to acute pancreatitis and ischemic enterocolitis as a complication of laparoscopic gastric banding.


Comparison of canal transportation and centering ability of rotary protaper, one shape system and wave one system using cone beam computed tomography: An in vitro study.
The aim of the present study was to compare the canal transportation and centering ability of Rotary ProTaper, One Shape and Wave One systems using cone beam computed tomography (CBCT) in curved root canals to find better instrumentation technique for maintaining root canal geometry. Total 30 freshly extracted premolars having curved root canals with at least 10 degrees of curvature were divided into three groups of 10 teeth each. All teeth were scanned by CBCT to determine the root canal shape before instrumentation. In Group 1, the canals were prepared with Rotary ProTaper files, in Group 2 the canals were prepared with One Shape files and in Group 3 canals were prepared with Wave One files. After preparation, post-instrumentation scan was performed. Pre-instrumentation and post-instrumentation images were obtained at three levels, 3 mm apical, 3 mm coronal and 8 mm apical above the apical foramen were compared using CBCT software. Amount of transportation and centering ability were assessed. The three groups were statistically compared with analysis of variance and Tukey honestly significant. All instruments maintained the original canal curvature with significant differences between the different files. Data suggested that Wave One files presented the best outcomes for both the variables evaluated. Wave One files caused lesser transportation and remained better centered in the canal than One Shape and Rotary ProTaper files. The canal preparation with Wave One files showed lesser transportation and better centering ability than One Shape and ProTaper.


Relationship of Hypertension and Systolic Blood Pressure With the Risk of Stroke or Bleeding in Patients With Atrial Fibrillation: The Fushimi AF Registry.
Hypertension is considered a major risk factor of stroke and systemic embolism (SE) as well as bleeding in patients with atrial fibrillation (AF). The purpose of this study was to investigate the relationship of hypertension and systolic blood pressure (SBP) with the risk of stroke/SE or bleeding in AF patients. The Fushimi AF Registry, a community-based prospective survey, was designed to enroll all of the AF patients in Fushimi-ku, Kyoto. Fushimi-ku is densely populated with a total population of 283,000. Follow-up data were available for 3,713 patients (follow-up rate 90.0%) as of August 2015, and the median follow-up period was 1,035 days. We compared the clinical backgrounds at baseline, and follow-up outcomes of AF patients between those with hypertension (HTN; n = 2,304, 62.1% of total) and those without (non-HTN; n = 1,409). History of hypertension was neither associated with the incidence of stroke/SE, ischemic stroke, hemorrhagic stroke nor major bleeding. However, when we divided the HTN group by baseline SBP ≥150 mm Hg (HTN-high blood pressure [HBP]: n = 305, 13.3% of HTN group) or <150 mm Hg (HTN-low blood pressure [LBP]: n = 1,983), HTN-HBP group was significantly associated with a higher incidence of both stroke/SE (hazard ratio [HR]: 1.74, 95% confidence interval [CI]: 1.08-2.72) and major bleeding (HR: 2.01, 95% CI: 1.21-3.23) compared with the non-HTN group. In contrast, HTN-LBP group was not associated with the risk of stroke/SE or major bleeding, compared with the non-HTN group. The incidences of stroke/SE and bleeding were higher in AF and hypertension patients with elevated SBP. UMIN Clinical Trials Registry: UMIN000005834.


Body Image and Self-Esteem in Patients with Rheumatoid Arthritis.
The study was conducted in order to investigate the effect of disease-related variables such as socio-demographic characteristics, disease complaints and use of necrosis factor (anti-TNF) on the body image and self-esteem in patients with rheumatoid arthritis. The data was collected by an Introductory Information Form, Body Image Scale (PfP) BIS and the Coopersmith Self-Esteem Inventory (SEI) in 120 patients with rheumatoid arthritis and in 120 healthy controls. One-way analysis of variance, Tukey HDS analysis, t-test, Kruskal-Wallis test, the Mann-Whitney U test, and Pearson's and Spearman's correlation coefficients were used to compare the data. 60% of the control group were in the 20-44 year-age group, 75% were women and 30.8% had a bachelor's degree or above, while 60% of patient group were in the 20-44 year-age group, 71.7% were women and 36.7% had a bachelor's degree or higher education level. We observed that the body satisfaction and self-esteem levels were higher in the 20-44 age group, in those with a bachelor's degree or higher education and in the patients who had no additional disease and who did not use anti-TNF. The body satisfaction and self-esteem levels were lower in those who had been receiving treatment for longer than 5 years, who had changes in hands and body, who had gait disturbance and who had changes in family and working life. The assessment of the psychosocial needs with a holistic approach and training programs for body image and self-esteem would be advisable for patients with rheumatoid arthritis who are aged 45-59 years, who have low self-esteem, who have additional diseases, who use anti-TNF, who have changes in hands and body and who have primary-school education.


The association between gastroesophageal flap valve function and gastroesophageal reflux symptoms.
Upper gastrointestinal endoscopic examination is usually the first step in the evaluation of patients with suspected gastroesopageal reflux disease. The primary aim of this study was to investigate the association between gastroesophageal flap valve function (GEFV) and gastroesophapgeal reflux symptoms in patients undergoing routine upper endoscopy. Patients and methods: 1507 patients were included into the study and the GEFV graded I to IV as follows: Hill I-II: normal GEFV, and Hill III-IV: abnormal GEFV. Patients in abnormal GEFV group had a higher incidence of reflux symptoms compared to normal GEFV group (53.4% vs 47.4% for heartburn p=0.03 and 53.2% vs 42.4% for regurgitation, p<0.01). In abnormal GEFV patients, esophagitis was more common compared to those with normal GEFV (32.6% vs 11.1%, p<0.01). Presence of heartburn and regurgitation (n =556) correlated with Hill III-IV grades (n = 184/556), (sensitivity: 33%, p = 0.003). In contrast, 24.6% (157/638) of patients without reflux symptoms were in abnormal GEFV group. In patients undergoing endoscopy because of reflux symptoms, Grade III-IV valve was detected more commonly in patients with reflux symptoms compared to patients without reflux symptoms (p = 0.01). Patients with abnormal valves (Hill grades III and IV) but without reflux symptoms, esophagitis and hiatal hernia should be evaluated individually by means of the presence of gastroesophageal reflux disease which means that GEFV is not a good indicator of reflux disease.


Terminal illness and suicide.
Case vignette: Henry, age 19, has been under medical care struggling for 5 months with a non-Hodgkin's lymphoma that has been resistant to treatment. Proven chemotherapy protocols have failed to sustain a remission, and it is evident that his condition is terminal, although not immediately so. When not in temporary remissions he is in extreme pain. The quantity of analgesic medication needed to control the pain also leaves him feeling, in his own words, "too snowed out to do anything." During his last hospital admission, a week ago, he had talked obliquely about ending his life when signs of another painful relapse become evident. Today he appeared in the outpatient clinic, although he had no appointment scheduled. He sought out several of the people who had cared for him over the past few months to thank them and to "say good-bye." He gave some prized personal possessions to one or two of the staff with whom he felt especially close. As this was happening, some of the staff members realized that Henry had a sufficient stock of narcotics at home to end his life. Our commentators are Sanford Leikin, MD, and Richard A. McCormick, SJ.


Neonatal Acute Paronychia.
Paronychia is defined as infection afflicting the eponychial nail folds of the hand or foot. Such infections are rarely reported in the perinatal age group, and not previously described in a neonate younger than 2 weeks. Trauma resulting in inoculation of the nail fold is the most common predisposing factor to paronychia. Oral trauma in the pediatric population from finger sucking predisposes this population to a different set of bacterial pathogens than adults. Contamination can progress to infection and abscess formation within the nail fold with the most prevalent vector in adult infections being Staphylococcus aureus. Comparatively, mixed anaerobic and aerobic infections tend to afflict children with oral soothing habits. This is a case report will present the rare occurrence of a paronychia in a neonate caused by methicillin-resistant Staphylococcus aureus. The management and treatment strategies for paronychia in this atypical neonatal patient consisted of incision and drainage and antibiotic therapy. Neonates with oral self-soothing behaviors may be more at risk for developing paronychia of mixed anaerobic and aerobic infections. Initial therapy with broad-spectrum antibiotics amoxicillin/clavulanate or clindamycin is suggested. Incision and drainage in the perinatal setting coupled with antibiotics is curative.


[Development and cell differentiation of the vestibulocochlear nuclei in cattle].
Based upon light- and electron microscopic examinations (50 embryos ranging from 1 to 53 cm crown-rump-length, CRL) the origin of the nuclei of the cranial nerve VIII is described with special regard to neurogenesis. The ventricular matrix lateral to the sulcus limitans represents the alar plate with its sensory areas. Up to 2.7 cm CRL migrating neurons from the vestibular nuclei can be detected, the bigger neuronal elements of which are the early formed lateral vestibular nucleus. From 6.7 cm CRL onward all nuclear groups of the vestibular nerve can be identified. At 1 cm CRL the recess plate represents the primordium of the cochlear nuclear complex. Identification of the definitive nuclei is possible at 3.8 cm CRL. Subsequently from 7.6 cm CRL onward the process of lamination can be observed in the dorsal cochlear nucleus. Due to the proceeding maturation the nuclei of the cranial nerve VIII correspond at 53 cm CRL topographically and cytologically to the characteristics of adult animals. Electron microscopic examinations are documenting characteristic features of cytogenesis of sensory neurons (vestibular nucleus) during early embryonic stages (2.5 cm and 3.6 cm CRL). At 2.5 cm CRL the elements exhibiting features of migrating neurons are predominating, whereas at 3.6 cm CRL an increased differentiation is typical for neurons localized in their ultimate position. At this stage synapses can be identified for the first time.


Association of circulating tumour cells with early relapse and 18F-fluorodeoxyglucose positron emission tomography uptake in resected non-small-cell lung cancers.
More than 20% of lung cancer patients develop a recurrence, even after curative resection. We hypothesized that relapse may arise from the dissemination of circulating tumour cells (CTCs). This study evaluates the significance of CTC detection as regards the recurrence of non-small-cell lung cancer (NSCLC) in surgically resected patients. Secondly, we investigated the association between CTCs and the uptake of 18 F-fluorodeoxyglucose (FDG) by the primary tumour on a positron emission tomographic (PET) scan. In this single-centre prospective study, blood samples for analysis of CTCs were obtained from 102 patients with Stage I-IIIA NSCLC both before (CTC1) and 1 month after (CTC2) radical resection. CTCs were isolated using immunomagnetic techniques. The presence of CTCs was correlated with the maximum standardized uptake value (SUVmax) measured on preoperative FDG PET/computed tomographic scans. Recurrence free survival (RFS) analysis was performed. CTCs were detected in 39.2% of patients before and in 27.5% 1 month after the operation. The presence of CTCs after the operation was significantly correlated with SUVmax on PET scans, pathological stage and surgical approach. Only SUVmax was an independent predictor for the presence of CTC2 on multivariate analysis. Postoperative CTCs were significantly correlated with a shorter RFS ( P = 0.005). In multivariate analysis, the presence of CTC2 was associated with RFS, independent of disease staging. Detection of CTCs 1 month after radical resection might be a useful marker to predict early recurrence in Stage I-III NSCLC. The SUVmax value of the primary tumour on preoperative PET scans was associated with the presence of CTC 1 month after the operation.


A prone technique for treatment of the breast, supraclavicular and axillary nodes.
Radiation therapy to women with large pendulous breasts presents dosimetric challenges when the whole breast (WB) and supraclavicular and axillary (SCF + AX) nodes need to be encompassed. The aim of this case study was to demonstrate the feasibility of planning and treating a pendulous breasted patient in the prone position. Computerised tomography (CT) images were acquired of the patient in both the prone and supine positions. A Perspex plate was added to the CDR Systems Inc. (Calgary, Canada) prone breastboard to minimize SCF + AX contour variations. Dosimetry was performed on both CT scans and the resultant treatment plans were evaluated for conformity, homogeneity, dose to the lung and maximum doses to the spinal cord (SC) and irradiated volume. The daily set-up in the prone position was monitored for stability and reproducibility. The patient completed her treatment course in the prone position. Minimal daily interventions were required to ensure the position was reproduced. Grade 3 skin toxicity was recorded in the SCF + AX region where the Perspex plate was added to the prone positioning device. There was minimal difference in dosimetry between prone and supine plans in the SCF + AX region. The prone WB plan showed improved homogeneity (prone 0.15; supine 0.22) and conformity (prone 0.90; supine 0.77). A simple addition to the breastboard has enabled a pendulous breasted woman with SC + AX involvement to be treated in the prone position. Set-up of this technique is achievable on a daily basis with minimal impact on workflow. It is a feasible alternative to supine treatment for this patient group.


Comparison of the Effectiveness and Safety of d-Penicillamine and Zinc Salt Treatment for Symptomatic Wilson Disease: A Systematic Review and Meta-Analysis.
Background: Pharmacological therapy is currently the main treatment method for patients with Wilson disease (WD). We aimed to evaluate the efficacy and safety of the common treatment regimens in these patients. Methods: We conducted a systemic review and meta-analysis by searching multiple databases for studies from inception to October 2021. Outcomes of interest were the improved rate and safety of d-penicillamine and zinc salts treatment in WD patients. Two independent reviewers performed the study selection and data extraction. Results: Sixteen studies were included in this meta-analysis. The pooled improved rate for all included symptomatic WD patients was 78.0% (95% CI: 70.8%-85.2%). In symptomatic hepatic WD patients, there is no difference in the treatment efficiency of d-penicillamine and zinc salts (RR: 0.98, 95% CI: 0.86%-1.12%; p = 0.765). In neurological WD patients, the pooled improved rate of those who received d-penicillamine and zinc salts was 56.3% (95% CI: 37.5%-75.1%) and 80.2% (95% CI: 67.2%-93.2%), respectively. The incidence of adverse effects (RR: 2.42, 95% CI: 1.20%-4.88%; p = 0.014) and neurological deterioration (RR: 1.96, 95% CI: 1.31%-2.93%; p = 0.001) in all symptomatic WD patients treated with d-penicillamine was both higher than that of patients treated with zinc salts. Conclusion: Our analysis suggests that symptomatic WD patients treated with d-penicillamine have higher incidence of adverse effects and neurological deterioration than that of zinc salts. The therapeutic effectiveness of these two regimens does not seem to be significantly different, and these results must be interpreted with caution. Systematic Review Registration: PROSPERO registration, identifier CRD 42021287126.


Somatostatin receptor expression and clinical outcome of multilineage pituitary tumours expressing PIT1 and SF1.
The application of transcription factor immunohistochemistry to pituitary neuroendocrine tumour (PitNET) assessment has allowed identification of tumours that do not conform to a single lineage. Multilineage pituitary transcription factor 1 (PIT1) and steroidogenic factor 1 (SF1) PitNETs are a rare and relatively newly described tumour subtype. These tumours express both transcription factors and may also express combinations of hormones corresponding to both lineages. Histological and clinical characteristics can vary, and overall clinical behaviour and prognosis is not known. We describe the clinical outcomes and somatostatin receptor status (SSTR) of a series of nine cases identified from our cohort of pituitary tumours at Westmead Hospital. Eight PitNETs (88.9%) expressed growth hormone and caused acromegaly at presentation. Of the seven macrotumours that caused acromegaly, one had cavernous sinus invasion. The Ki-67 labeling index score ranged from 0.6% to 3.6%. About 88% of tumours that secreted excess growth hormone exhibited strong immunostaining for SSTR 2 and all tumours displayed weak immunoreactivity for SSTR5. In 62.5% of patients with acromegaly, cure was achieved after surgical resection. Somatostatin receptor ligands resulted in clinical remission in cases where medical treatment was initiated. There was no new tumour recurrence or regrowth over an overall mean follow-up period of 62.5 months.


Taming the great: enhanced syphilis screening in HIV-positive men who have sex with men in a hospital clinic setting.
Syphilis incidence in HIV-positive men who have sex with men (MSM) continues to increase, with strategies based on early detection and treatment urgently required to control rising infections. There are barriers to enhanced testing in certain settings. At our tertiary referral HIV centre, testing rates before and after a period of enhanced syphilis testing in HIV-positive MSM were assessed. When compared with the control period (pre-enhanced screening), the enhanced syphilis testing was associated with a significant increase in syphilis testing of HIV-positive patients undergoing routine viral load testing (136 out of 574, 23% vs 317 out of 574, 55%; P<0.0001) and a three-fold increase in new syphilis diagnoses (4 out of 574 vs 18 out of 574, P=0.004).


Efficient in vitro digestion of lipids and proteins in bovine milk fat globule membrane ingredient (MFGMi) and whey-casein infant formula with added MFGMi.
The relative immaturity of the infant digestive system has the potential to affect the bioavailability of dietary lipids, proteins, and their digested products. We performed a lipidomic analysis of a commercial bovine milk fat globule membrane ingredient (MFGMi) and determined the profile of lipids and proteins in the bioaccessible fraction after in vitro digestion of both the ingredient and whey-casein-based infant formula without and with MFGMi. Test materials were digested using a static 2-phase in vitro model, with conditions simulating those in the infant gut. The extent of digestion and the bioaccessibility of various classes of neutral and polar lipids were monitored by measuring a wide targeted lipid profile using direct infusion-mass spectrometry. Digestion of abundant proteins in the ingredient and whey-casein infant formula containing the ingredient was determined by denaturing PAGE with imaging of Coomassie Brilliant Blue stained bands. Cholesterol esters, diacylglycerides, triacylglycerides, phosphatidylcholines, and phosphatidylethanolamines in MFGMi were hydrolyzed readily during in vitro digestion, which resulted in marked increases in the amounts of free fatty acids and lyso-phospholipids in the bioaccessible fraction. In contrast, sphingomyelins, ceramides, and gangliosides were largely resistant to simulated digestion. Proteins in MFGMi and the infant formulas also were hydrolyzed efficiently. The results suggest that neutral lipids, cholesterol esters, phospholipids, and proteins in MFGMi are digested efficiently during conditions that simulate the prandial lumen of the stomach and small intestine of infants. Also, supplementation of whey-casein-based infant formula with MFGMi did not appear to alter the profiles of lipids and proteins in the bioaccessible fraction after digestion.


Multimodality imaging in carcinoid heart disease.
Neuroendocrine neoplasms arise from the gastrointestinal tract and can lead to carcinoid syndrome. Carcinoid heart disease affects more than half of these patients and is the initial presentation of carcinoid syndrome in up to 20 % of patients. Carcinoid heart disease typically leads to valve dysfunction, but in rare instances, carcinoid tumours can also metastasise to the endocardium and myocardium. Cardiovascular imaging plays an integral role in the diagnosis and prognosis of carcinoid heart disease. The use of multimodality imaging techniques including echocardiography, cardiac MRI, cardiovascular CT and positron emission tomography have allowed for a more comprehensive assessment of carcinoid heart disease. In this review, we discuss the features of carcinoid heart disease observed on multimodality imaging, indications for obtaining imaging studies and their role in carcinoid heart disease management.


Tracing Filaments in Simulated 3D Cryo-Electron Tomography Maps Using a Fast Dynamic Programming Algorithm.
We propose a fast, dynamic programming-based framework for tracing actin filaments in 3D maps of subcellular components in cryo-electron tomography. The approach can identify high-density filament segments in various orientations, but it takes advantage of the arrangement of actin filaments within cells into more or less tightly aligned bundles. Assuming that the tomogram can be rotated such that the filaments can be oriented to be directed in a dominant direction (i.e., the X, Y, or Z axis), the proposed framework first identifies local seed points that form the origin of candidate filament segments (CFSs), which are then grown from the seeds using a fast dynamic programming algorithm. The CFS length l can be tuned to the nominal resolution of the tomogram or the separation of desired features, or it can be used to restrict the curvature of filaments that deviate from the overall bundle direction. In subsequent steps, the CFSs are filtered based on backward tracing and path density analysis. Finally, neighboring CFSs are fused based on a collinearity criterion to bridge any noise artifacts in the 3D map that would otherwise fractionalize the tracing. We validate our proposed framework on simulated tomograms that closely mimic the features and appearance of experimental maps.


Actin-mediated gene expression in neurons: the MRTF-SRF connection.
The traditional view of cellular actin is a rather autarkic cytoskeletal framework function confined to the cytoplasm. However, there is now evidence that alterations in actin dynamics are sensed by the nucleus and subsequently modulate gene expression. In communicating with the nucleus, cytoplasmic, and most likely also nucleus-resident actin, provides a further (gene) regulatory loop to cell motility. A transcription module composed of MRTF (myocardin-related transcription factor) and SRF (serum response factor) emerges as prime target of such actin signaling. Here, I focus on the nervous system, where the actin-MRTF-SRF entity governs multiple aspects of neuronal motility.


Cleavage of trypanosome surface glycoproteins by alkaline trypsin-like enzyme(s) in the midgut of Glossina morsitans.
EP and GPEET procyclin, the major surface glycoproteins of procyclic forms of Trypanosoma brucei, are truncated by proteases in the midgut of the tsetse fly Glossina morsitans morsitans. We show that soluble extracts from the midguts of teneral flies contain trypsin-like enzymes that cleave the N-terminal domains from living culture-derived parasites. The same extract shows little activity against a variant surface glycoprotein on living bloodstream form T. brucei (MITat 1.2) and none against glutamic acid/alanine-rich protein, a major surface glycoprotein of Trypanosoma congolense insect forms although both these proteins contain potential trypsin cleavage sites. Gel filtration of tsetse midgut extract revealed three peaks of tryptic activity against procyclins. Trypsin alone would be sufficient to account for the cleavage of GPEET at a single arginine residue in the fly. In contrast, the processing of EP at multiple sites would require additional enzymes that might only be induced or activated during feeding or infection. Unexpectedly, the pH optima for both the procyclin cleavage reaction and digestion of the trypsin-specific synthetic substrate Chromozym-TRY were extremely alkaline (pH 10). Direct measurements were made of the pH within different compartments of the tsetse digestive tract. We conclude that the gut pH of teneral flies, from the proventriculus to the hindgut, is alkaline, in contradiction to previous measurements indicating that it was mildly acidic. When tsetse flies were analysed 48 h after their first bloodmeal, a pH gradient from the proventriculus (pH 10.6+/-0.6) to the posterior midgut (pH 7.9+/-0.4) was observed.


Effect of labetalol on cerebral blood flow and middle cerebral arterial flow velocity in healthy volunteers.
The effect of labetalol, a combined alpha- and beta-adrenoceptor antagonist, on the cerebral circulation was investigated in 7 normotensive subjects. Cerebral blood flow (CBF) was measured with the intravenous 133Xe method and mean flow velocity (Vmean) in the middle cerebral artery was determined using transcranial Doppler (TCD) ultrasound. Examination was performed before and then 15, 60 and 120 min after 0.75 mg/kg i.v. labetalol. Reactivity to inhalation of 5% CO2 in air was studied before, and again 90 min after labetalol administration. Neither CBF nor Vmean changed following labetalol administration, whereas a marked increase occurred during inhalation of CO2. The median CO2 reactivity was 3.2%/mmHg (range: 1.8-4.0) for CBF and 4.4%/mmHg (1.5-5.6) for Vmean. These results indicate that labetalol, given in moderate but clinically relevant doses, does not affect the cerebral circulation in normotensive subjects. Neither does it affect CO2 reactivity. The uniform results obtained with the two methods suggest TCD as a usable alternative to conventional CBF technique in the assessment of cerebral vasoactivity of various drugs in subjects with a normal cerebral circulation.


Quantification of myocardial ischemic injury.
Quantitative assessment of infarct size is becoming increasingly important, particularly since this parameter appears to be a major determinant of prognosis. Morphologic, radioisotopic and electrophysiological techniques for assessing the extent of irreversible ischemic injury entail certain unavoidable limitations. Experimental and preliminary clinical findings suggest that estimation of the extent of infarction from biochemical markers in serum is practical and useful. Furthermore, prediction of infarct size during its early evolution may improve selection of patients for interventions designed to protect ischemic myocardium and may contribute to objective assessment of their efficacy.


Primary and secondary relaxation process in plastically crystalline cyanocyclohexane studied by 2H nuclear magnetic resonance. II. Quantitative analysis.
We analyze the results of our previously reported 2H nuclear magnetic resonance (NMR) experiments in the plastically crystalline (PC) phase of cyanocyclohexane (Part I of this work) to study the fast secondary relaxation (or β-process) in detail. Both, the occurrence of an additional minimum in the spin-lattice relaxation T1 and the pronounced effects arising in the solid-echo spectrum above the glass transition temperature T(g) = 134 K, allow for a direct determination of the restricting geometry of the β-process in terms of the "wobbling-in-a-cone" model. Whereas at temperatures below T(g) the reorientation is confined to rather small solid angles (below 10°), the spatial restriction decreases strongly with temperature above T(g), i.e., the distribution of cone angles shifts continuously towards higher values. The β-process in the PC phase of cyanocyclohexane proceeds via the same mechanism as found in structural glass formers. This is substantiated by demonstrating the very similar behavior (for T < T(g)) of spin-lattice relaxation, stimulated echo decays, and spectral parameters when plotted as a function of <log τ(β)> (taken from dielectric spectroscopy). We do, however, not observe a clear-cut relation between the relaxation strength of the β-process observed by NMR (calculated within the wobbling-in-a-cone model) and dielectric spectroscopy.


The melanin biosynthesis genes of Alternaria alternata can restore pathogenicity of the melanin-deficient mutants of Magnaporthe grisea.
The phytopathogenic fungi Magnaporthe grisea and Alternaria alternata produce melanin via the polyketide biosynthesis, and both fungi form melanized colonies. However, the site of melanin deposition and the role of melanin in pathogenicity differ between these two fungi. M. grisea accumulates melanin in appressoria, and their melanization is essential for host penetration. On the other hand, A. alternata produces colorless appressoria, and melanin is not relevant to host penetration. We examined whether the melanin biosynthesis genes of A. alternata could complement the melanin-deficient mutations of M. grisea. Melanin-deficient, nonpathogenic mutants of M. grisea, albino (Alb-), rosy (Rsy-), and buff (Buf-), were successfully transformed with a cosmid clone pMRB1 that carries melanin biosynthesis genes ALM, BRM1, and BRM2 of A. alternata. This transformation restored the melanin synthesis of the Alb- and Buf- mutants, but not that of the Rsy- mutant. The melanin-restored transformants regained mycelial melanization, appressorium melanization, and pathogenicity to rice. Further, transformation of Alb- and Buf- mutants with subcloned ALM and BRM2 genes, respectively, also produced melanin-restored transformants. These results indicate that the Alternaria genes ALM and BRM2 can restore pathogenicity to the mutants Alb- and Buf-, respectively, due to their function during appressorium development in M. grisea.


Aniquinazolines A-D, four new quinazolinone alkaloids from marine-derived endophytic fungus Aspergillus nidulans.
Four new quinazolinone alkaloids, namely, aniquinazolines A-D (1-4), were isolated and identified from the culture of Aspergillus nidulans MA-143, an endophytic fungus obtained from the leaves of marine mangrove plant Rhizophora stylosa. The structures of the new compounds were elucidated by spectroscopic analysis, and their absolute configurations were determined on the basis of chiral HPLC analysis of the acidic hydrolysates. The structure for 1 was confirmed by single-crystal X-ray diffraction analysis. All these compounds were examined for antibacterial and cytotoxic activity as well as brine shrimp (Artemia salina) lethality.


Controlled drug delivery for alopecia: A review.
Alopecia or hair loss is a benign treatable disorder which, over time, becomes chronic, affecting a significant fraction of the population that affects the patient's self-esteem and quality of life. The existing treatment regimen for alopecia is inadequate for drug delivery directly to hair follicles to result in continuous hair growth. The challenges are due to multiple-dose regimes and patient non-adherence, where it requires motivated clinical attention. Developing a prolonged drug delivery system by exploration of specific pathways to advance the delivery system into nanomedicine would be beneficial for clinical advancement. In this review, factors affecting the progress of the current therapeutic regimen towards controlled release nanomedicine (CRNM's) are analysed for existing clinical unmet needs, current treatment strategy, and research efforts taken in this direction. Correspondingly, changes in anatomy and pathophysiology of hair growth being analyzed in detail to focus the exact scenario of hair growth cycle and supplementation of medication. Besides, the current treatment regimen with various classes of drugs, their different pathways, and dosing limitations are analyzed. Possibilities of research effort for prolonged drug delivery are discussed in detail, including marketed products, clinical trials as well as various patents filed in the direction. Repurposing of multiple therapeutics using the nanotechnology platform, subsequently, results in a strategy to develop nanomedicine to treat alopecia, which could develop into several technologies (CRNM's), fore coming years from now.


Development of cell density gradients in the retinal ganglion cell layer of marsupials.
An area centralis and visual streak, specializations of high cell density in the mammalian retinal ganglion cell layer, develop from a more uniform cell distribution. In the wallaby and kangaroo, this transition is first seen 60 days postnatally. Total live cell numbers in this layer fall by approximately one-third as these specializations start to appear and dying cells are seen. However, dying cells have already become concentrated at the retinal rim prior to the emergence of live cell density gradients. Our results suggest that cell death may partially sculpt patterns of live cells, particularly by lowering densities around the entire far periphery. Studies of cell division demonstrate that ganglion cells are generated and enter the ganglion cell layer before the area centralis and visual streak are formed. However, cell addition to the inner and outer nuclear layers continues as cell density gradients become apparent in the ganglion cell layer. Furthermore, this late cell generation ceases first in areas adjacent to the presumptive area centralis. The differential distribution of such prolonged cell addition to the inner and outer nuclear layers may result in an asymmetric expansion of the retina. This process would partially explain the changing topography of cells in the ganglion cell layer. Mathematical analysis of patterns of overall retinal growth support this interpretation.


Atrial Repolarization Waves (Ta) Mimicking Inferior Wall ST Segment Elevation Myocardial Infarction in a Patient with Ectopic Atrial Rhythm.
We present a case of atrial repolarization waves from an ectopic atrial rhythm mimicking inferior ST segment elevation myocardial infarction in a 78-year-old male patient who presented with left sided chest wall and shoulder pain. His ischemic workup was negative, and the ST elevations completely resolved upon the resumption of sinus rhythm before discharge.


Sustained Remission After Maintenance Irinotecan in Patient With Multiply Relapsed Hepatoblastoma.
Children with recurrent hepatoblastoma have a poor prognosis and limited treatment options. The authors describe a child with metastatic hepatoblastoma who had multiple relapses. He was treated with surgical resection and adjuvant chemotherapy at first relapse. At second relapse, he had progressive disease postresection. He was treated with ifosfamide/carboplatin/etoposide chemotherapy followed by maintenance irinotecan and achieved long-term disease-free survival. Irinotecan as maintenance should be explored in recurrent hepatoblastoma.


A Novel Approach to Investigate the Superheating Grain Refinement Process of Aluminum-Bearing Magnesium Alloys Using Rapid Solidification Process.
The superheating process is a unique grain refining method found only in aluminum-containing magnesium alloys. It is a relatively simple method of controlling the temperature of the melt without adding a nucleating agent or refining agent for grain refinement. Although previous studies have been conducted on this process, the precise mechanism underlying this phenomenon has yet to be elucidated. In this study, a new approach was used to investigate the grain refinement mechanism of aluminum-containing magnesium alloys by the melting superheating process. AZ91 alloy, a representative Mg-Al alloy, was used in the study, and a rapid solidification process was designed to enable precise temperature control. Temperature control was successfully conducted in a unique way by measuring the temperature of the ceramic tube during the rapid solidification process. The presence of Al8Mn5 and Al10Mn3 particles in non-superheated and superheated AZ91 ribbon samples, respectively, manufactured by the rapid solidification process, was revealed. The role of these Al-Mn particles as nucleants in non-superheated and superheated samples was examined by employing STEM equipment. The crystallographic coherence between Al8Mn5 particles and magnesium was very poor, while Al10Mn3 particles showed better coherence than Al8Mn5. We speculated that Al10Mn3 particles generated by the superheating process may act as nucleants for α-Mg grains; this was the main cause of the superheating grain refinement of the AZ91 alloy.


1-(Benzenesulfonyl)-1,5-dihydro-4,1-benzoxazepine as a new scaffold for the design of antitumor compounds.
Bozepinib is a potent and selective anticancer compound which chemical structure is made up of a benzofused seven-membered ring and a purine moiety. We previously demonstrated that the purine fragment does not exert antiproliferative effect per se. A series of 1-(benzenesulfonyl)-4,1-benzoxazepine derivatives were synthesized in order to study the influence of the benzofused seven-membered ring in the biological activity of bozepinib by means of antiproliferative, cell cycle and apoptosis studies. Our results show that the methyleneoxy enamine sulfonyl function is essential in the antitumor activity of the structures and thus, it is a scaffold suitable for further modification with a view to obtain more potent antitumor compounds.


Genetic and environmental factors associated with laboratory rearing affect survival and assortative mating but not overall mating success in Anopheles gambiae sensu stricto.
Anopheles gambiae sensu stricto, the main vector of malaria in Africa, is characterized by its vast geographical range and complex population structure. Assortative mating amongst the reproductively isolated cryptic forms that co-occur in many areas poses unique challenges for programs aiming to decrease malaria incidence via the release of sterile or genetically-modified mosquitoes. Importantly, whether laboratory-rearing affects the ability of An. gambiae individuals of a given cryptic taxa to successfully mate with individuals of their own form in field conditions is still unknown and yet crucial for mosquito-releases. Here, the independent effects of genetic and environmental factors associated with laboratory rearing on male and female survival, mating success and assortative mating were evaluated in the Mopti form of An. gambiae over 2010 and 2011. In semi-field enclosures experiments and despite strong variation between years, the overall survival and mating success of male and female progeny from a laboratory strain was not found to be significantly lower than those of the progeny of field females from the same population. Adult progeny from field-caught females reared at the larval stage in the laboratory and from laboratory females reared outdoors exhibited a significant decrease in survival but not in mating success. Importantly, laboratory individuals reared as larvae indoors were unable to mate assortatively as adults, whilst field progeny reared either outdoors or in the laboratory, as well as laboratory progeny reared outdoors all mated significantly assortatively. These results highlight the importance of genetic and environment interactions for the development of An. gambiae's full mating behavioral repertoire and the challenges this creates for mosquito rearing and release-based control strategies.


[The place of mineral water in the metaphylaxis of urolithiasis].
Urinary stone disease is a metabolic disorder tending to recur and having a growing proportion of younger patients. Current methods of surgical treatment do not guarantee the disease non-recurrence without effective subsequent metaphylaxis. At present, the principles of general and special (medical) metaphylaxis of urolithiasis have been developed and widely applied according to underlying metabolic disorders, the type of stone formation and risk factors for recurrence. Oversaturation of the urine with stone forming substances is a major factor in stone formation. Recommendations for using mineral water should not be given without a clear understanding of the expected effect of particular water. Its selection for treating urolithiasis depends on the chemical composition of the stones, underlying metabolic disorders, urine pH, the functional state of the gastrointestinal tract, concomitant diseases, etc.


Bi-parametric magnetic resonance imaging applied to obstetrics.
Foetal magnetic resonance imaging (MRI) plays an increasingly important role in the diagnosis of foetal abnormalities. Over the years, we have successfully applied bi-parametric MRI (bp-MRI) to the following obstetric conditions: (1) neurologic vascular diseases; (2) assessment of lung parenchyma maturation; (3) renal pathologies, such as polycystic kidney, suspected renal infarction, unilateral or bilateral renal agenesis; (4) placental pathologies, as twin-twin transfusion syndrome or placenta accreta; (5) benignant and malignant congenital tumours or cysts of the liver, such as haemangioendothelioma, hepatoblastoma or metastatic neuroblastoma, of the kidney (e.g. mesoblastic nephroma) and of the retroperitoneum, such as teratoma. The information derived from bp-MRI, and concerned with water motions in different tissues, improved the morphologic details provided by conventional foetal MRI. It has the potential to increase the value of MRI in the assessment of a wide range of foetal pathologies, particularly in renal diseases, allowing an adequate management decision and therapy.


A comparison of four electrical stimulation types on Staphylococcus aureus growth in vitro.
We evaluated the efficacy of common electrical stimulation (ES) types on bacterial growth in vitro using clinically relevant conditions. Four types of ES--continuous microamperage direct current (microADC), high-voltage pulsed current (HVPC), low-voltage monophasic milliamperage pulsed current (LVMmAPC), and low-voltage biphasic milliamperage pulsed current (LVBmAPC)--were each applied to a separate set of culture plates containing Staphylococcus aureus for 1 h at 37 degrees C on 3 consecutive days. After ES treatment, the zone of inhibition surrounding each electrode was measured. Zone of inhibition measurements showed a significant inhibitory effect for continuous microADC and HVPC (p < 0.05), but not for LVMmAPC and LVBmAPC. Differences in bacterial growth inhibition were not found for polarity and time. These data suggest that for infected wounds, HVPC and continuous microADC treatments may have an initial bacterial inhibitory effect, which does not significantly change with subsequent treatments.


Virulence evolution at the front line of spreading epidemics.
Understanding and predicting the spatial spread of emerging pathogens is a major challenge for the public health management of infectious diseases. Theoretical epidemiology shows that the speed of an epidemic is governed by the life-history characteristics of the pathogen and its ability to disperse. Rapid evolution of these traits during the invasion may thus affect the speed of epidemics. Here we study the influence of virulence evolution on the spatial spread of an epidemic. At the edge of the invasion front, we show that more virulent and transmissible genotypes are expected to win the competition with other pathogens. Behind the front line, however, more prudent exploitation strategies outcompete virulent pathogens. Crucially, even when the presence of the virulent mutant is limited to the edge of the front, the invasion speed can be dramatically altered by pathogen evolution. We support our analysis with individual-based simulations and we discuss the additional effects of demographic stochasticity taking place at the front line on virulence evolution. We confirm that an increase of virulence can occur at the front, but only if the carrying capacity of the invading pathogen is large enough. These results are discussed in the light of recent empirical studies examining virulence evolution at the edge of spreading epidemics.