[Gene expression in obese patients with non-alcoholic steatohepatitis].
Although the molecular basis for the pathophysiology of non-alcoholic steatohepatitis (NASH) is poorly understood, we evaluate the hepatic gene expression of cytokines, chemokines, cell receptors, growth factors, intracellular transducers and extracellular communication proteins in liver tissue of obese patients (with and without NASH), and we determine the specific intrahepatic gene expression profiles associated with histological severe NASH.Thirty-eight obese patients with BMI > 35 were analyzed, who underwent bariatric surgery. Biopsy specimen samples were snap-frozen in liquid nitrogen. Hepatic gene expression was determined in liver biopsy specimens from 3 groups: a) obese patients without NASH (n = 12); b) patients with NASH without fibrosis (n = 13); and c) patients with NASH and fibrosis (n = 13). Genes were considered to be expressed differentially in NASH only if there was a greater than 2-fold difference in abundance of mRNA when compared with each of the control group. These results were confirmed by real-time PCR. Fourteen genes were differentially expressed (10 overexpressed and 4 underexpressed) in patients with NASH. Genes that were significantly overexpressed included prohibitin, TNF, TNF RI (p55), MCSF, R2-TRAIL, b1-CTGF, FGF, VEGF, and BIGH3OBR. Insulin growth factor-1, insulin growth factor-2, interleukin-2 and tyrosine-receptor were underexpressed in NASH patients. 1. The obese patients with NASH without fibrosis show an overexpression of proinflammatory and proapoptotic genes. Also, the NASH patients with fibrosis show an overexpression of fibrogenic genes, including the leptin receptor Ob-Rb.2. The up-regulated gene expression of prohibitin suggests mitochondrial dysfunction in NASH patients.


Fertility in patients with Hirschsprung's disease: population-based cohort study.
The aim of this study was to assess fertility in patients treated for Hirschsprung's disease. This was a nationwide, population-based cohort study, including all patients with Hirschsprung's disease registered in the Swedish National Patient Register between 1964 and 2004. Five age- and sex-matched controls per patient were randomly selected by Statistics Sweden. Outcome data were retrieved from the Multi-Generation Register, and the Swedish National Patient Register. Study exposure was Hirschsprung's disease and the primary outcome was fertility, defined as having one or more children. Individuals with chromosomal anomalies were excluded. The study cohort comprised 597 patients with Hirschsprung's disease (143 female) and 2969 controls (714 female). The mean(s.d.) age at follow-up was 29.6(10.0) years for patients and 29.8(10.1) years for the controls. A total of 191 (32.0 per cent) patients compared with 1072 (36.1 per cent) controls had one or more children (P = 0.061). The analysis showed that fewer female patients with Hirschsprung's disease had a child (29.4 versus 38.7 per cent, P = 0.037), they were older when they gave birth to their first child (28.1 versus 26.4 years, P = 0.033), and they had fewer children. Of the female patients with Hirschsprung's disease, 19 (45.2 per cent) had only one child, compared with 79 (28.6 per cent) of the female control group (P = 0.047). No difference was noted in the male group in this regard. Female patients with Hirschsprung's disease were less likely to have a child, had fewer children, and were older when they gave birth to their first child compared with the controls, indicating impaired fertility. There was no significant difference between male patients with Hirschsprung's disease and controls.


Gender differences in the risk for chronic renal allograft failure.
Despite the known differences in immunological reactivity between males and females, no differences in graft survival have been described among renal transplant recipients with regard to gender. To address this paradox, we analyzed data from 73,477 primary renal transplants collected in the US Renal Data System database. Logistic regression and Cox proportional hazard models were used to investigate the primary study end points, graft loss secondary to acute rejection (AR) or chronic allograft failure (CAF). CAF was defined as graft loss beyond 6 months, not attributable to death, recurrent disease, acute rejection, thrombosis, infection, noncompliance, or technical problems. The models adjusted for 15 covariates including immunosuppressive regimen, and donor and recipient characteristics. The overall 8-year graft and patient survivals were significantly better in female renal transplant recipients compared with male recipients. However graft survival censored for death was not significantly different by gender. By multivariate analysis, females had a 10% increased odds of AR (OR=1.10, CI 1.02-1.12), but conversely a 10% lower risk of graft loss secondary to CAF (RR=0.9, CI 0.85-0.96). The risk for CAF increased significantly with increasing age for both males and females, but this effect was greater for males than for females (P<0.001). Although female renal transplant recipients have a similar death censored graft survival compared with males, there are important differences in immunological behavior. Females have a higher risk of AR while having a decreased risk of graft loss secondary to CAF.


Adhesion of a polymer-grafted nanoparticle to cells explored using generalized Langevin dynamics.
We model a polymer-grafted stealth nanoparticle (SNP) as a composite system consisting of a spherical core coated with a porous polymeric brush with end-ligands. Adjacent to target cells, the near-wall hydrodynamics, thermal fluctuations, and thermodynamic adhesive interactions simultaneously impact the transient motion of the SNP. Employing both the Langevin framework for the effective hard sphere dynamics and the coupled generalized Langevin framework for the nanoparticle-polymer dynamics, we comprehensively investigate the velocity and position temporal relaxations of the SNP in the absence and presence of end-to-end distance fluctuations for the tethered polymer. We demonstrate that polymer structural relaxations substantially impact the SNP adhesive dynamics, especially when the grafted polymer is more flexible. Moreover, a long-time tail with t-3/2 scaling due to polymer chain-length fluctuations is observed in the velocity autocorrelation for a bound SNP. Finally, the thermodynamic effects of membrane morphology on SNP adhesion are explored by modifying the membrane-mediated binding potential of mean force.


Healthcare institutions' recommendation regarding the use of FFP-2 masks and SARS-CoV-2 seropositivity among healthcare workers: a multicenter longitudinal cohort study.
Health care workers (HCW) are heavily exposed to SARS-CoV-2 from the beginning of the pandemic. We aimed to analyze risk factors for SARS-CoV-2 seroconversion among HCW with a special emphasis on the respective healthcare institutions' recommendation regarding the use of FFP-2 masks. We recruited HCW from 13 health care institutions (HCI) with different mask policies (type IIR surgical face masks vs. FFP-2 masks) in Southeastern Switzerland (canton of Grisons). Sera of participants were analyzed for the presence of SARS-CoV-2 antibodies 6 months apart, after the first and during the second pandemic wave using an electro-chemiluminescence immunoassay (ECLIA, Roche Diagnostics). We captured risk factors for SARS-CoV-2 infection by using an online questionnaire at both time points. The effects of individual COVID-19 exposure, regional incidence and FFP-2 mask policy on the probability of seroconversion were evaluated with univariable and multivariable logistic regression. SARS-CoV-2 antibodies were detected in 99 of 2794 (3.5%) HCW at baseline and in 376 of 2315 (16.2%) participants 6 months later. In multivariable analyses the strongest association for seroconversion was exposure to a household member with known COVID-19 (aOR: 19.82, 95% CI 8.11-48.43, p < 0.001 at baseline and aOR: 8.68, 95% CI 6.13-12.29, p < 0.001 at follow-up). Significant occupational risk factors at baseline included exposure to COVID-19 patients (aOR: 2.79, 95% CI 1.28-6.09, p = 0.010) and to SARS-CoV-2 infected co-workers (aOR: 2.50, 95% CI 1.52-4.12, p < 0.001). At follow up 6 months later, non-occupational exposure to SARS-CoV-2 infected individuals (aOR: 2.54, 95% CI 1.66-3.89 p < 0.001) and the local COVID-19 incidence of the corresponding HCI (aOR: 1.98, 95% CI 1.30-3.02, p = 0.001) were associated with seroconversion. The healthcare institutions' mask policy (surgical masks during usual exposure vs. general use of FFP-2 masks) did not affect seroconversion rates of HCW during the first and the second pandemic wave. Contact with SARS-CoV-2 infected household members was the most important risk factor for seroconversion among HCW. The strongest occupational risk factor was exposure to COVID-19 patients. During this pandemic, with heavy non-occupational exposure to SARS-CoV-2, the mask policy of HCIs did not affect the seroconversion rate of HCWs.


Midline cutaneous and spinal defects. Midline cutaneous abnormalities associated with occult spinal disorders.
Failure of separation of the neuroectoderm from the epithellal ectoderm to proceed in an orderly and complete fashion results in a wide variety of defects involving the skin, spinal cord, and cauda equina, as well as the surrounding structures of mesodermal origin. Congenital dermal sinuses occur most commonly in the lumbosacral region, are usually associated with a spina bifida, and may connect the skin directly to the spinal canal. Epidermoid or dermoid cysts may form at any point along a dermal sinus. Four types of cutaneous or subcutaneous abnormalities commonly seen associated with occult spinal disorders are abnormal hair, angioma, lipoma, and dimple. It is essential that these lesions are investigated at an early age, since surgical excision may prevent future neurologic deficits.


Degranulating mast cells secrete an endoglycosidase that degrades heparan sulfate in subendothelial extracellular matrix.
Mast cells are widely distributed in perivascular connective tissues, especially in areas of active tumor growth and vascular reactivity. Incubation of metabolically [35S]O4 = -labeled subendothelial extracellular matrix (ECM) with lysates of bone marrow-derived mouse mast cells (BMMC) resulted in extensive degradation of heparan sulfate (HS) into fragments 5 to 6 times smaller than intact HS side chains. A much lower activity (seven- to eightfold) was expressed by intact BMMC incubated in contact with the ECM. These fragments were not produced in the presence of heparin, were sensitive to deamination with nitrous acid, and resistant to further degradation with papain or chondroitinase ABC. These results indicate that an endoglycosidase (heparanase) is involved in BMMC-mediated degradation of HS in the subendothelial ECM. Heparanase activity was not detected in medium conditioned by cultured BMMC, or in lysates of Ableson transformed BMMC and rat basophilic leukemic (RBL) cells. Both heparanase and beta-hexosaminidase, a mast cell granule enzyme, were released on degranulation of BMMC induced by the calcium ionophore A23187, or by exposure to IgE-Ag, suggesting that heparanase is localized in the cell granules. Under these conditions, less than 5% of the cellular content of lactate dehydrogenase were released. Degradation of the ECM-HS by the mast cell heparanase and the associated release of HS-bound endothelial cell growth factors that are stored in ECM (Vlodavsky et al, Proc Natl Acad Sci USA 84:2292, 1987; Bashkin et al, Biochemistry 28:1737, 1989) may play a role in the proposed mast cell-mediated stimulation of neovascularization.


Differential distribution of calpain small subunit 1 and 2 in rat brain.
Calpains, the Ca(2+)-dependent thiol proteases, are abundant in the nervous tissue. The ubiquitous enzyme forms in mammals are heterodimers consisting of a specific, micro or m, large (catalytic) subunit and, apparently, a common small (regulatory) subunit (CSS1). Recently, however, we described a second form of small subunit (CSS2), which is of restricted occurrence [Schád, E., Farkas, A., Jékely, G., Tompa, P. & Friedrich, P. (2002) Biochem. J., 362, 383-388]. Here we analysed the distribution of immunoreactivity in various parts of rat brain against two anti-CSS1 and two anti-CSS2 antibodies by correlated light and electron microscopy. Remarkably, the antibodies showed differential distribution in various parts of rat cortex: anti-CSS1 reacted mainly with perikarya and dendrites, whereas anti-CSS2 was more prominent in axons. In serial sections CSS2 and synaptophysin gave very similar patterns, i.e. these epitopes seem to colocalize. Electron microscopy confirmed that CSS1 was mainly localized postsynaptically in dendrites and somata, whereas CSS2 was found presynaptically. The hypothesis is advanced that these distinct distributions of calpain subunits may be related to the transport of these enzymes in nerve cells.


Spectral imaging using single-axis spectrally dispersed illumination.
Spectral imaging is a powerful tool for a wide variety of applications; however, low imaging rates and signal-to-noise ratios (SNRs) often limit its use for many biomedical applications. Here, we present a technique for spectral imaging using a unique two-dimensional illumination pattern having spectral dispersion in one axis. The method, which is called spectrally dispersed illumination spectral imaging (SDISI), allows high-speed, high-resolution acquisition of spectral data from specimens that often cannot tolerate high illumination intensities or require fast imaging for avoiding motion artifacts. The technique is demonstrated by capturing spectral data cubes of the finger of a human volunteer using short exposure durations and a high (33.5 dB) SNR.


Hypomethylation and activation of syncytin-1 gene in endometriotic tissue.
Syncytin-1 plays a critical role in the maintenance of normal pregnancy by mediating the formation of syncytiotrophoblasts through a fosugenic action. Encoded by the human endogenous retrovirus envelope gene HERV-W, syncytin-1 trophoblast-specific expression is controlled by epigenetic mechanisms. In non-placental tissues, the syncytin-1 gene is suppressed by hypermethylation in the LTR promoter region. Hypomethylated and activated syncytin-1 gene is found in placental trophoblast lineages and malignant cells. We here demonstrate that while syncytin-1 gene remains silenced in the eutopic endometrium from endometriotic patients, syncytin-1 mRNA and protein are detected in ectopic, endometriotic lesions; particularly the endometrioid glandular endothelial cells. LINE-1 COBRA assay and immunohistochemistry using the 5-MC-specific antibody did not detect any changes in global DNA methylation in the endometriotic tissues. However, results from COBRA and bisulfite sequencing indicated that the LTR region of the syncytin-1 promoter is hypomethylated in endometriotic tissues, highlighting the significance of DNA demethylation in syncytin-1 gene activation. Analysis of DNA methyltransferase 3B (DNMT3B) mRNA levels revealed that DNMT3B3, an isoform carrying methyltransferase activity, is downregulated; whereas DNMT3B7, the isoform without enzymatic activity, is upregulated in the endometriotic tissues, pointing to positive and negative regulatory functions, respectively, of these isoforms on syncytin-1 methylation. These results have provided the first evidence supporting the involvement of epigenetic mechanisms for syncytin-1 upregulation in endometriotic tissues. Considering recent findings on the nonfusogenic activity of syncytin-1, its expression in endometriotic tissues suggests that this multifunctional protein may be implicated in the pathogenesis and/or progression of endometriosis.


Benign asbestos pleurisy in the rabbit. A model for the study of pathogenesis.
Benign asbestos pleurisy is a manifestation of asbestos-induced disease that is not uncommon but often ignored. We developed an animal model to study the pathogenesis of this syndrome. Crocidolite asbestos injected into the rabbit pleural space resulted in the appearance of chemotactic activity in an exudative effusion, characterized by a polymorphonuclear leukocyte (PMN) response that peaked 4 h after the injection. The chemotactic activity and the PMN responses occurred equally in normal animals and in animals that had been depleted of complement with cobra venom. Neutropenia, induced with vinblastine, did not alter the appearance of chemotactic activity but abrogated the PMN response. Treatment with colchicine failed to block the release of chemotactic activity into the pleural fluid, but decreased the PMN response without affecting the ability of peripheral blood PMN to respond to pleural fluid chemotactic activity. When pleural fluid containing chemotactic activity was injected into the pleural space of another rabbit, a PMN response was observed. These studies suggest that the acute exudative response seen in the rabbit model of benign asbestos pleurisy results from the release of chemotactic activity from sources other than complement. The response probably depends on interaction between the asbestos and the pleural tissue. Asbestos-PMN interaction may release chemotactic factors that amplify the response secondarily. Colchicine blocked the acute response to intrapleural asbestos by a mechanism yet to be understood.


First results of frontal sinus obliteration with a synthetic, resorbable and osteoconductive bone graft of ß-tricalcium phosphate.
Despite advances in endoscopic sinus surgery, frontal sinus obliteration is still indicated in some cases. Current options for obliteration include autologous and synthetic materials. The use of ß-tricalcium phosphate as a resorbable bone graft substitute is a good alternative for frontal sinus obliteration. This study aimed to report our experience with this material. A retrospective chart review of patients who underwent frontal sinus obliteration at our clinic between 2008 and 2013 was performed. Demographic data, indications, previous surgery, and immediate and late complications were examined. Information on persisting symptoms and patient outcomes was collected using a telephone questionnaire in February 2016. None of the patients underwent further surgery for frontal sinus disease. All of them reported a good cosmetic result and symptom improvement. ß-tricalcium phosphate is a good, safe and cost-effective material for frontal sinus obliteration.


Dead or alive: Deoxyribonuclease I sensitive bacteria and implications for the sinus microbiome.
Recently, there has been tremendous interest in the sinus microbiome and how it relates to disease. However, a lack of a standardized sample collection and DNA extraction methods makes comparison of results across studies nearly impossible. Furthermore, current techniques fail to identify which components of the microbiome are actually alive within the host at the time of sampling. To develop and optimize a method to differentiate which bacterial species in the human sinus microbiome are live versus dead. Duplicate samples from the middle meatus of patients with healthy sinus tissue and those patients with chronic rhinosinusitis were collected by using brushes (n = 12), swabs (n = 27), and tissue biopsy (n = 8) methods. One sample from each pair was either deoxyribonuclease I- or control-treated before DNA extraction. The relative bacterial versus human composition of each sample was determined. A 16S ribosomal RNA gene analysis was performed on a six-paired sample from patients with healthy sinus tissue. We found that swabs and brushes collected a higher percentage of bacterial DNA than did tissue biopsy. We also determined that as much as 50% of the bacteria collected in these samples was already dead at the time of collection. The 16S ribosomal RNA gene analysis found significant changes in the relative abundance of taxa identified in the live versus dead bacterial communities of healthy human sinuses. Our findings indicated that swabs provided the best quality microbiome samples and that a large portion of the bacteria identified in the sinus were deoxyribonuclease I sensitive. These results highlighted the need for improved techniques such as those presented here, which can differentiate between living and dead bacteria in a sample, a potentially critical distinction when examining changes in sinus innate immune function because both components play important, but distinct, functions. Further studies will determine how these living and dead bacterial populations shift in different disease states and after clinical intervention.


Deficiencies and Missed Opportunities to Formulate Clinical Guidelines in Australia for Withholding or Withdrawing Life-Sustaining Treatment in Severely Disabled and Impaired Infants.
This paper examines the few, but important legal and coronial cases concerning withdrawing or withholding life-sustaining treatment from severely disabled or critically impaired infants in Australia. Although sparse in number, the judgements should influence common clinical practices based on assessment of "best interests" but these have not yet been adopted. In particular, although courts have discounted assessment of "quality of life" as a legitimate component of determination of "best interests," this remains a prominent component of clinical guidelines. In addition, this paper highlights the lack of uniform clinical guidelines available to medical professionals and parents in Australia when making end-of-life decisions for severely ill infants. Thus, it is argued here that there is a need for an overarching prescriptive uniform framework or set of guidelines in end-of-life decision-making for impaired infants. This would encourage greater transparency, consistency, and some degree of objectivity in an area that often appears subjective.


Case Series: Mixed Infectious Keratitis by Pythium insidiosum and Fungal Species.
This case series will be the first to illustrates mixed infection from Pythium sp. and fungal species in corneal ulcer. This case series is aimed to alert all towards the possibility of both Pythium sp. and fungal species infection in case of non-responding corneal ulcer treated with either antifungals or anti-pythium drugs alone. Increased suspicion of mixed infection in case of non-responding fungal/pythium keratitis may facilitate early and prompt management. Six patients presented with signs of either fungal or pythium keratitis. They underwent ophthalmological examinations, smear examinations, cultures, and polymerase chain reaction (PCR). Therapeutic penetrating keratoplasty (TPK) was performed in cases where symptoms worsened after treatment with either antifungal or anti-pythium drugs. The half corneal button (HCB) was shared for histopathological and microbiological examinations. In the first case, smear examination from corneal scraping (CS) revealed Pythium-like filaments, which were confirmed with PCR; however, Aspergillus nidulans grew in culture. In the second case, iodine-potassium iodide (IKI) staining was positive for Pythium; however, PCR was positive for both Pythium and fungus, which was further confirmed by DNA sequencing. In the third case, IKI staining and HCB were positive for Pythium; however, PCR was positive for fungus, which was identified as Candida saitoana with DNA sequencing. In the fourth case, Pythium grew in the CS culture; however, Candida sp. grew in the HCB culture. In the fifth case, Cladosporium sp. grew in culture from CS; however, Pythiuminsidiosum grew from the anterior chamber exudate after TPK. In the sixth case, smear examination revealed septate fungal filaments, and Cladosporium sp. grew in culture; however, HCB on histopathological examination showed features of Pythium keratitis. In unresponsive cases of Pythium or fungal keratitis, diagnostic modalities such as IKI and PCR should be implemented as a routine practice, in addition to smears and cultures.


Primate auditory prototype in the evolution of the arcuate fasciculus.
The human arcuate fasciculus pathway is crucial for language, interconnecting posterior temporal and inferior frontal areas. Whether a monkey homolog exists is controversial and the nature of human-specific specialization unclear. Using monkey, ape and human auditory functional fields and diffusion-weighted MRI, we identified homologous pathways originating from the auditory cortex. This discovery establishes a primate auditory prototype for the arcuate fasciculus, reveals an earlier phylogenetic origin and illuminates its remarkable transformation.


Illicit tobacco trade is 'booming': UK newspaper coverage of data funded by transnational tobacco companies.
Transnational tobacco companies (TTCs) have heavily publicised their argument that standardised tobacco packaging will increase the illicit tobacco trade. Leaked Philip Morris International (PMI) documents suggest that the company may have intended to use third parties to promulgate this argument in the UK. We examined articles in UK newspapers (1 April 2013 to 31 March 2015) from LexisNexis for presence and nature of tobacco industry data. We also examined documents released by Freedom of Information requests made to Scottish Councils for evidence of how PMI operationalised its third-party strategy. Two-thirds of newspaper articles (63%, 99/157) mentioned a PMI consultant; 36% of which did not disclose this industry funding. Most articles mentioned counterfeit tobacco, illicit whites or both (72%, 113/157), while few (4%, 7/157) specifically mentioned tobacco industry illicit tobacco and none explained that the latter can include tobacco-company involvement. Freedom of Information documents revealed that the PMI consultant sought to build relationships with Trading Standards officers, conducted undercover test purchases (UTPs) in illicit tobacco 'hotspots' and may have promoted unrepresentative findings in the media. While the data set featured PMI data predominantly, other TTCs also engaged in third-party techniques to promulgate messages on illicit tobacco. PMI engaged a third party, seemingly with the aim of securing media coverage on illicit tobacco positing that standardised packaging would worsen the problem. The predominant focus of articles which featured industry-funded data and information was on counterfeit tobacco despite official data showing tobacco-industry illicit tobacco as the most prevalent. Other jurisdictions considering the policy should anticipate that third parties will promote the illicit-trade argument.


Development of visual pattern discrimination in the fly depends on light experience.
Pattern discrimination by dewinged walking flies (Boettcherisca peregrina) was tested in behavioral experiments. After emergence, the flies were deprived of light or visual patterns. Deprivation impaired the normal development of visual pattern discrimination without impairing phototaxis. Flies kept in a lighted, white, unpatterned environment could not discriminate visual patterns, nor could flies kept in continuous darkness. These results indicate that there is considerable plasticity in the structure of the visual system of these flies.


Expression of the Epstein-Barr virus BamHI A fragment in nasopharyngeal carcinoma: evidence for a viral protein expressed in vivo.
A family of mRNAs that are transcribed rightward through the BamHI A fragment have been detected in C15, a nasopharyngeal carcinoma (NPC) which has been passaged in nude mice. Northern (RNA) blot hybridizations indicate that these RNAs are also expressed in three other NPCs which have been established in nude mice and in an NPC obtained at biopsy. Moreover, hybridization in situ detected transcription from BamHI A in 12 NPCs and 1 Epstein-Barr virus (EBV)-containing carcinoma of the parotid gland. In each case, transcription was detected in all of the malignant epithelial cells. Transcription was not detected in two cases of EBV-positive lymphoma biopsies by in situ hybridization nor in latently infected EBV-positive lymphoblastoid cell lines by Northern blot hybridization. The consistent transcription of these sequences in latently infected epithelial malignancy but not in lymphoid cells suggests that this viral function is associated with latent EBV infection of epithelial cells. Sequence analysis of a cDNA synthesized from the C15 tumor, representing the 3' end of BamHI A messenger RNA, revealed an open reading frame (ORF). Translation of this ORF in vitro produced several peptides that were immunoprecipitated with antisera from patients with NPC. The detection of antibodies to the protein encoded by the ORF present in the BamHI A cDNA indicates that BamHI A encodes a protein which is expressed in vivo and is antigenic.


Generation of Stimulus Triggering from Intracortical Spike Activity for Brain-Machine-Body Interfaces (BMBIs).
Brain-machine-body interfaces (BMBIs) aim to create an artificial connection in the nervous system by converting neural activity recorded from one cortical region to electrical stimuli delivered to another cortical region, spinal cord, or muscles in real-time. In particular, conditioning-mode BMBIs utilize such activity-dependent stimulation strategies to induce functional re-organization in the nervous system and promote functional recovery after injury by exploiting mechanisms underlying neuroplasticity. This paper reports on reconfigurable, field-programmable gate array (FPGA)-based implementation of a translation algorithm to extract multichannel stimulus trigger signals from intracortical neural spike activity. The approach features digital spike discrimination based on user-set thresholding and time-amplitude windowing, decision making to support different triggering patterns for various stimulation scenarios, as well as trigger-pattern-dependent blanking schemes for robust operation in the presence of stimulus artifacts. Readily lending itself to low-power, low-area implementation for future integration, the algorithm has been synthesized on a Cyclone II FPGA using Altera's Quartus II design software and validated experimentally with prerecorded intracortical neural spike activity from an anesthetized laboratory rat.


Examining the relationship between cue-induced craving and actual smoking.
Smoking cue-reactivity studies have consistently demonstrated heightened self-report craving, as well as moderate autonomic reactivity, among smokers exposed to salient drug-related cues. However, significantly fewer studies have examined whether exposure to smoking cues affects smokers' actual smoking, or examined the predictive relationship between cue-induced craving and smoking behavior. Using our well-tested pictorial cues in a cue-reactivity paradigm, we investigated the impact of smoking-related cues relative to neutral cues on subjective craving and smoking behavior (assessed via CReSS; Plowshare Technologies, Baltimore, MD) measures of latency to smoke, puff volume, and number of puffs). Further, we examined the predictive value of cue-induced craving on subsequent smoking behavior. Sixty nondeprived daily smokers completed 2 experimental sessions involving exposure to either smoking-related or neutral pictorial cues. Following initial exposure to cues, smokers rated their craving and were then allowed to smoke freely if they chose to during a subsequent 6-min cue exposure period. Result showed that exposure to smoking cues relative to neutral predicted significantly greater craving and increases in smoking behavior. Likewise, the magnitude of the difference in cue-induced craving when exposed to smoking cues relative to neutral cues (i.e., the cue-reactivity effect) was highly predictive of shorter latency to smoke, as well as increased number of puffs and puff volume.


A case of autoimmune pulmonary alveolar proteinosis with fluctuating lung shadows in parallel with cigarette smoke burden.
The association between the development of pulmonary alveolar proteinosis (PAP) and dust inhalation has been established; however, the link between PAP and smoking is less clear. A 46-year-old man with mild bronchial asthma and a 52-pack-year smoking history was diagnosed with autoimmune PAP (APAP) based on computed tomography (CT) shadows, pathologic findings of the lung, and a high serum level of anti-granulocyte macrophage colony-stimulating factor (GM-CSF) IgG autoantibody. Smoking was stopped and he was treated three times with unilateral whole lung lavage (WLL). However, his respiratory failure did not improve because of incomplete WLL due to bronchospasm and decreased compliance of the ventilated lung during WLL. A fourth WLL was planned, but was cancelled because his respiratory status and lung shadows on CT scan unexpectedly improved immediately before WLL. During the follow-up period without smoking, the lung shadows resolved almost completely. However, the abnormalities relapsed after he resumed smoking and then modestly improved after changing to cigarettes containing less tar. Serum levels of anti-GM-CSF IgG were not compatible with the lung shadows. These observations in this patient suggested a link between smoking and APAP. Since variable smoking rates in patients with APAP have been reported in epidemiologic studies, a definite conclusion requires precise case-control studies in the future. (Sarcoidosis Vasc Diffuse Lung Dis 2017; 34: 257-259).


Hyperperfusion and hypermetabolism in brain radiation necrosis with epileptic activity.
We report a case of high uptake of 11C-methionine (MET), 18F-FDG (FDG) and 201Tl-Cl (Tl) in brain radiation necrosis. Twenty-one years previously, the patient had undergone surgery and radiation therapy consisting of 60-Gy for ependymoma in the anterior horn of the right lateral ventricle. The clinical features consisting of frequent seizures of the left face and arm suddenly appeared 2 wk before admission. MRI depicted a Tl and T2-prolonged lesion in the right frontal lobe. Abnormally high uptake in this area demonstrated by MET-PET, FDG-PET, Tl-SPECT or HMPAO-SPECT suggested the presence of a recurrent tumor. A craniotomy was then performed and an intraoperative electrocorticogram showed continuous epileptic spikes in the lesion. The epileptic foci were resected and the histological features of the lesion were consistent with radiation necrosis. After surgery, the seizures disappeared and the postoperative examinations with MET-PET, FDG-PET, Tl-SPECT and HM-PAO-SPECT no longer showed abnormally high uptake. Hypermetabolism and hyperperfusion related to epileptic fits are therefore thought to result in high uptake of MET, FDG and Tl in radiation necrosis.


Surgical aspects of patellar tendonitis: technique and results.
Patellar tendonitis is a difficult clinical problem, and surgical treatment remains unclear in its indications, technique, and functional outcome. This article reviews 17 patients (18 knees) with either primary or secondary patellar tendonitis who required operative treatment. Twelve men and 5 women aged 19-50 years comprised the study population. The right knee was involved in 10 patients, and the left knee was involved in 8. Average time from injury to surgery was 24 months, and average postoperative follow-up was 12 months (range: 6-24 months). Criteria were developed for subjective, objective, functional, and overall evaluation. All knees that were operated on were rated as "very abnormal" preoperatively. Postoperatively, 16 (89%) knees were rated as normal or nearly normal, whereas 2 (11%) knees were rated as abnormal. A surgical technique is described, with emphasis on the rationale and technique, and reasons for initial surgical failure and poor functional outcomes are discussed.


Non-conventional therapeutics for oral infections.
As our knowledge of host-microbial interactions within the oral cavity increases, future treatments are likely to be more targeted. For example, efforts to target a single species or key virulence factors that they produce, while maintaining the natural balance of the resident oral microbiota that acts to modulate the host immune response would be an advantage. Targeted approaches may be directed at the black-pigmented anaerobes, Porphyromonas gingivalis and Prevotella intermedia, associated with periodontitis. Such pigments provide an opportunity for targeted phototherapy with high-intensity monochromatic light. Functional inhibition approaches, including the use of enzyme inhibitors, are also being explored to control periodontitis. More general disruption of dental plaque through the use of enzymes and detergents, alone and in combination, shows much promise. The use of probiotics and prebiotics to improve gastrointestinal health has now led to an interest in using these approaches to control oral disease. More recently the potential of antimicrobial peptides and nanotechnology, through the application of nanoparticles with biocidal, anti-adhesive and delivery capabilities, has been explored. The aim of this review is to consider the current status as regards non-conventional treatment approaches for oral infections with particular emphasis on the plaque-related diseases.


Uric acid level and erectile dysfunction in patients with coronary artery disease.
Erectile dysfunction (ED) is a frequent complaint of elderly subjects and is closely associated with endothelial dysfunction and cardiovascular disease (CVD). Uric acid is also associated with endothelial dysfunction, oxidative stress, and CVD, raising the hypothesis that an increased serum uric acid might predict ED in patients who are at risk for coronary artery disease (CAD). This study aims to evaluate the association of serum uric acid levels with presence and severity of ED in patients presenting with chest pain of presumed cardiac origin. This is a cross-sectional study of 312 adult male patients with suspected CAD who underwent exercise stress test (EST) for workup of chest pain and completed a sexual health inventory for men survey form to determine the presence and severity of ED. Routine serum biochemistry (and uric acid levels) were measured. Logistic regression analysis was used to assess risk factors for ED. The short version of the International Index of Erectile Function questionnaire diagnosed ED (cutoff score ≤ 21). Serum uric acid levels were determined. Patients with chest pain of suspected cardiac origin underwent an EST. One hundred forty-nine of 312 (47.7%) male subjects had ED by survey criteria. Patients with ED were older and had more frequent CAD, hypertension, diabetes and impaired renal function, and also had significantly higher levels of uric acid, fibrinogen, glucose, C-reactive protein, triglycerides compared with patients without ED. Uric acid levels were associated with ED by univariate analysis (odds ratio = 1.36, P = 0.002); however, this association was not observed in multivariate analysis adjusted for estimated glomerular filtration rate. Subjects presenting with chest pain of presumed cardiac origin are more likely to have ED if they have elevated uric acid levels.


A network of coupled chaotic maps for adaptive multi-scale image segmentation.
In this paper, a network of coupled chaotic maps for multi-scale image segmentation is proposed. Time evolutions of chaotic maps that correspond to a pixel cluster are synchronized with one another, while this synchronized evolution is desynchronized with respect to time evolution of chaotic maps corresponding to other pixel clusters in the same image. The number of pixel clusters is previously unknown and the adaptive pixel moving technique introduced in the model makes it robust enough to classify ambiguous pixels.


Reactivation Kinetics of HIV-1 and Susceptibility of Reactivated Latently Infected CD4+ T Cells to HIV-1-Specific CD8+ T Cells.
The "shock and kill" model of human immunodeficiency virus type 1 (HIV-1) eradication involves the induction of transcription of HIV-1 genes in latently infected CD4(+) T cells, followed by the elimination of these infected CD4(+) T cells by CD8(+) T cells or other effector cells. CD8(+) T cells may also be needed to control the spread of new infection if residual infected cells are present at the time combination antiretroviral therapy (cART) is discontinued. In order to determine the time frame needed for CD8(+) T cells to effectively prevent the spread of HIV-1 infection, we examined the kinetics of HIV transcription and virus release in latently infected cells reactivated ex vivo. Isolated resting, primary CD4(+) T cells from HIV-positive (HIV+) subjects on suppressive regimens were found to upregulate cell-associated HIV-1 mRNA within 1 h of stimulation and produce extracellular virus as early as 6 h poststimulation. In spite of the rapid kinetics of virus production, we show that CD8(+) T cells from 2 out of 4 viremic controllers were capable of effectively eliminating reactivated autologous CD4(+) cells that upregulate cell-associated HIV-1 mRNA. The results have implications for devising strategies to prevent rebound viremia due to reactivation of rare latently infected cells that persist after potentially curative therapy. A prominent HIV-1 cure strategy termed "shock and kill" involves the induction of HIV-1 transcription in latently infected CD4(+) T cells with the goal of elimination of these cells by either the cytotoxic T lymphocyte response or other immune cell subsets. However, the cytotoxic T cell response may also be required after curative treatment if residual latently infected cells remain. The kinetics of HIV-1 reactivation indicate rapid upregulation of cell-associated HIV-1 mRNA and a 5-h window between transcription and virus release. Thus, HIV-specific CD8(+) T cell responses likely have a very short time frame to eliminate residual latently infected CD4(+) T cells that become reactivated after discontinuation of antiretroviral therapy following potentially curative treatment strategies.


Effects of gender and preference for information and control on anxiety early after myocardial infarction.
Men and women differ in anxiety, which is one of the most stressful outcomes of an acute myocardial infarction (AMI). This anxiety may be moderated by coping styles of preference for information and control. This study aimed to examine the relation of gender and preference for information and control to anxiety during the critical care period after AMI. As part of a larger study on complications after AMI, a descriptive cross-sectional multicenter one-group investigation designed with a convenience sample of AMI patients admitted to acute care units was conducted. Within the first 48 hours after the patients were admitted to the hospital, anxiety was assessed using the State Anxiety Inventory, and preference for information and control was measured using the Krantz Health Opinion Survey. The sample of AMI patients (N = 410) was 68% male, 87% White, 68% married. The women were significantly older than the men (p <.05) and significantly more anxious (p <.05). Multiple stepwise regression analysis with a control for age demonstrated that neither preference for information nor preference for control moderated the relation of gender and anxiety. The women expressed greater anxiety than the men. However, the men and women were similar at all levels of anxiety in their preference for information and control. The search for other factors related to the stress of AMI will help healthcare providers design effective interventions to reduce anxiety among men and women.


Cx26 deafness: mutation analysis and clinical variability.
Mutations in the gap junction protein connexin 26 (Cx26) gene (GJB2) seem to account for many cases of congenital sensorineural hearing impairment, the reported prevalence being 34-50% in autosomal recessive cases and 10-37% in sporadic cases. The hearing impairment in these patients has been described as severe or profound. We have studied 53 unrelated subjects with congenital non-syndromic sensorineural hearing impairment in order to evaluate the prevalence and type of Cx26 mutations and establish better genotype-phenotype correlation. Mutations in the Cx26 gene were found in 53% of the subjects tested, 35.3% of the autosomal recessive and 60% of the sporadic cases in our series. Three new mutations were identified. The hearing deficit varied from mild to profound even in 35delG homozygotes within the same family. No evidence of progression of the impairment was found. Alterations of the Cx26 gene account for a large proportion of cases of congenital non-syndromic sensorineural deafness, so it seems appropriate to extend the molecular analysis even to subjects with mild or moderate prelingual hearing impairment of unknown cause.


On the use of logarithmic scales for analysis of diffraction data.
Predictions of the possible model parameterization and of the values of model characteristics such as R factors are important for macromolecular refinement and validation protocols. One of the key parameters defining these and other values is the resolution of the experimentally measured diffraction data. The higher the resolution, the larger the number of diffraction data N(ref), the larger its ratio to the number N(at) of non-H atoms, the more parameters per atom can be used for modelling and the more precise and detailed a model can be obtained. The ratio N(ref)/N(at) was calculated for models deposited in the Protein Data Bank as a function of the resolution at which the structures were reported. The most frequent values for this distribution depend essentially linearly on resolution when the latter is expressed on a uniform logarithmic scale. This defines simple analytic formulae for the typical Matthews coefficient and for the typically allowed number of parameters per atom for crystals diffracting to a given resolution. This simple dependence makes it possible in many cases to estimate the expected resolution of the experimental data for a crystal with a given Matthews coefficient. When expressed using the same logarithmic scale, the most frequent values for R and R(free) factors and for their difference are also essentially linear across a large resolution range. The minimal R-factor values are practically constant at resolutions better than 3 A, below which they begin to grow sharply. This simple dependence on the resolution allows the prediction of expected R-factor values for unknown structures and may be used to guide model refinement and validation.


The social and clinical characteristics of patients on antiretroviral therapy who are 'lost to follow-up' in KwaZulu-Natal, South Africa: a prospective study.
A significant proportion of those initiating antiretroviral treatment (ART) for HIV infection are lost to follow-up. Causes (including HIV symptoms, quality of life, depression, herbal treatment and alcohol use) for discontinuing ART follow-up in predominantly rural resource-limited settings are not well understood. This is a prospective study of the treatment-naïve patients recruited from three (one urban, one-semi-urban and one rural) public hospitals in Uthukela health district in KwaZulu-Natal from October 2007 to February 2008. The aim of this study was to investigate predictors of loss to follow-up or all caused attrition from an ART programme within a cohort followed up for over 12 months. A total of 735 patients (217 men and 518 women) prior to initiating ART completed a baseline questionnaire and 6- and 12-months' follow-up. At 12-months follow-up 557 (75.9%) individuals continued active ART, 177 (24.1%) were all cause attrition, there were 82 deaths (13.8%), 58 (7.9%) transfers, 7 (1.0%) refused participation, 8 (1.1%) were not yet on ART and 22 (3.0%) could not be traced. Death by 12-months of follow-up was associated with lower CD4 cell counts (risk ratio, RR=2.05, confidence intervals, CI=1.20-3.49) and higher depression levels (RR=1.05, CI=1.01-1.09) at baseline assessment. The high early mortality rates indicate that patients are enrolling into ART programmes with far too advanced immunodeficiency; median CD4 cell counts 119 (IQR=59-163). Causes of late access to the ART programme, such as delays in health care access (delayed health care seeking), health system delays, or inappropriate treatment criteria, need to be addressed. Differences in health status (lower CD4 cell counts and higher depression scores) should be taken into account when initiating patients on ART. Treating depression at ART initiation is recommended to improve treatment outcome.


Iron Homeostasis Disruption and Oxidative Stress in Preterm Newborns.
Iron is an essential micronutrient for early development, being involved in several cellular processes and playing a significant role in neurodevelopment. Prematurity may impact on iron homeostasis in different ways. On the one hand, more than half of preterm infants develop iron deficiency (ID)/ID anemia (IDA), due to the shorter duration of pregnancy, early postnatal growth, insufficient erythropoiesis, and phlebotomy losses. On the other hand, the sickest patients are exposed to erythrocytes transfusions, increasing the risk of iron overload under conditions of impaired antioxidant capacity. Prevention of iron shortage through placental transfusion, blood-sparing practices for laboratory assessments, and iron supplementation is the first frontier in the management of anemia in preterm infants. The American Academy of Pediatrics recommends the administration of 2 mg/kg/day of oral elemental iron to human milk-fed preterm infants from one month of age to prevent ID. To date, there is no consensus on the type of iron preparations, dosages, or starting time of administration to meet optimal cost-efficacy and safety measures. We will identify the main determinants of iron homeostasis in premature infants, elaborate on iron-mediated redox unbalance, and highlight areas for further research to tailor the management of iron metabolism.


Bioderived Pickering Emulsion Based on Chitosan/Trialkyl Phosphine Oxides Applied to Selective Recovery of Rare Earth Elements.
A novel biobased pickering emulsion (PE) material was prepared by the encapsulation of Cyanex 923 (Cy923) into chitosan (CS) to selectively recover rare earth elements (REEs) from the aqueous phase. The preparation of PE was optimized through sequentially applying a 23 full factorial design, followed by a 33 Box-Behnken design varying the Cy923 content, CS concentration, and pH of CS. The material was characterized by Fourier transform infrared (FTIR) spectroscopy, scanning electron microscopy (SEM), optical microscopy, rheological, compositional, and stability measurements. The resultant material was evaluated in the removal of yttrium by pH influence, nitrate concentration, kinetics, equilibrium isotherms, reusability, and a comparison with liquid-liquid (L-L) extraction and tested in a real scenario to extract Y from a fluorescent lamp powder waste. In addition, the selectivity of PE for REE was investigated with Y/Ca, Gd/Ca, and La/Ni systems. PE extracts REE at 1 ≤ pH ≤ 5 at nitrate concentrations up to 2 mol/L. The kinetics and equilibrium studies showed reaction times <5 min and a maximum sorption capacity of 89.98 mg/g. Compared with L-L extraction, PE consumed 48% less Cy923 without using organic diluents. PE showed a remarkable selectivity for REE in the systems evaluated, showing separation factors of 22.62, 9.35, and 504.64 for the blends Y/Ca, Gd/Ca/Mg, and La/Ni, respectively. PE showed excellent selectivity extracting Y from a real aqueous liquor from the fluorescent lamp powder. PE demonstrates to be an effective and sustainable alternative for REE recovering due to its excellent efficiency in harsh conditions, favorable green chemistry metrics, and use of a biopolymer material in its composition avoiding the use of organic solvents used in L-L extraction.


Secondary cardiac tumor in children.
We describe our clinical experience of eight cases of secondary cardiac tumor. The pathology of the tumors were lymphoma (three), Wilms' tumor (two), malignant teratoma (one), neuroblastoma (one), and pleuropulmonary blastoma (one). Metastatic sites were the right atrium in Wilms' tumor and neuroblastoma, the left atrium in pleuropulmonary blastoma and malignant teratoma, and multiple sites in lymphoma. Primary masses in the mediastinum extended directly to the heart (three lymphoma, malignant teratoma, pleuropulmonary blastoma). Wilms' tumor and neuroblastoma showed cardiac metastases through the inferior vena cava. Many cases revealed vague abnormal cardiovascular findings (symptoms in six; physical signs in five). In five cases surgery was performed to relieve the possible obstruction to flow and to identify the pathology (lymphoma in three, Wilms' tumor in one, and malignant teratoma in one). Chemotherapy prior to operation resulted in the disappearance of the intracardiac masses in each case of Wilms' tumor and pleuropulmonary blastoma. All three patients with lymphoma died immediately after operation. Four died of multiple metastases or Pneumocystis pneumonia several months after operation. This study indicates that suspicion of a secondary cardiac tumor is crucial to early diagnosis. Because of the poor postoperative outcome, surgery for secondary cardiac tumors should be done cautiously only in cases with definite hemodynamic decompensation.


Drinking and acquisition of unrecorded alcohol across educational groups in Sweden.
It is estimated that 18.5% of total alcohol consumption in Sweden in 2018 was unrecorded. However, little is known about the socio-economic profile of consumers of unrecorded alcohol. The aim of this study was to elucidate this issue by analysing data from a unique Swedish national repeated cross-sectional alcohol use survey. Individual-level information on alcohol consumption and socio-economic status (SES) for the years 2013-2018 was retrieved from the Monitoring Project; a nationally representative monthly alcohol use survey. The analytical sample comprised 64 375 respondents aged 25-74 years. SES was measured by educational level. We used three educational groups: (i) low (<10 years); (ii) intermediate (10-12 years); and (iii) high (13+ years). We included indicators of the following sources of unrecorded alcohol consumption: travellers' import, smuggled alcohol, home production, internet and illicit home-distilling. We estimated adjusted SES-specific means of the various forms of unrecorded consumption. The means were adjusted for the effects of age, sex and region. There were no significant educational differences in the total of unrecorded alcohol consumption; the same holds true for home-production and internet. However, with respect to smuggled and home-distilling, a statistically significant educational gradient was observed with the lowest educational group scoring approximately four times higher than the highest. Our findings suggest that there are no differences across educational groups in the consumption of unrecorded alcohol as a whole. However, consumption of smuggled alcohol and illicitly distilled spirits is elevated in the low educational group.


Mutation at tyrosine in AMLRY (GILRY like) motif of yeast eRF1 on nonsense codons suppression and binding affinity to eRF3.
Termination translation in Saccharomyces cerevisiae is controlled by two interacting polypeptide chain release factors, eRF1 and eRF3. Two regions in human eRF1, position at 281-305 and position at 411-415, were proposed to be involved on the interaction to eRF3. In this study we have constructed and characterized yeast eRF1 mutant at position 410 (correspond to 415 human eRF1) from tyrosine to serine residue resulting eRF1(Y410S). The mutations did not affect the viability and temperature sensitivity of the cell. The stop codons suppression of the mutant was analyzed in vivo using PGK-stop codon-LACZ gene fusion and showed that the suppression of the mutant was significantly increased in all of codon terminations. The suppression on UAG codon was the highest increased among the stop codons by comparing the suppression of the wild type respectively. In vitro interaction between eRF1 (mutant and wild type) to eRF3 were carried out using eRF1-(His)6 and eRF1(Y410S)-(His)6 expressed in Escherichia coli and indigenous Saccharomyces cerevisiae eRF3. The results showed that the binding affinity of eRF1(Y410S) to eRF3 was decreased up to 20% of the wild type binding affinity. Computer modeling analysis using Swiss-Prot and Amber version 9.0 programs revealed that the overall structure of eRF1(Y410S) has no significant different with the wild type. However, substitution of tyrosine to serine triggered the structural change on the other motif of C-terminal domain of eRF1. The data suggested that increasing stop codon suppression and decreasing of the binding affinity of eRF1(Y410S) were probably due to the slight modification on the structure of the C-terminal domain.


Hyaluronan Nanoparticles Selectively Target Plaque-Associated Macrophages and Improve Plaque Stability in Atherosclerosis.
Hyaluronan is a biologically active polymer, which can be formulated into nanoparticles. In our study, we aimed to probe atherosclerosis-associated inflammation by using hyaluronan nanoparticles and to determine whether they can ameliorate atherosclerosis. Hyaluronan nanoparticles (HA-NPs) were prepared by reacting amine-functionalized oligomeric hyaluronan (HA) with cholanic ester and labeled with a fluorescent or radioactive label. HA-NPs were characterized in vitro by several advanced microscopy methods. The targeting properties and biodistribution of HA-NPs were studied in apoe-/- mice, which received either fluorescent or radiolabeled HA-NPs and were examined ex vivo by flow cytometry or nuclear techniques. Furthermore, three atherosclerotic rabbits received 89Zr-HA-NPs and were imaged by PET/MRI. The therapeutic effects of HA-NPs were studied in apoe-/- mice, which received weekly doses of 50 mg/kg HA-NPs during a 12-week high-fat diet feeding period. Hydrated HA-NPs were ca. 90 nm in diameter and displayed very stable morphology under hydrolysis conditions. Flow cytometry revealed a 6- to 40-fold higher uptake of Cy7-HA-NPs by aortic macrophages compared to normal tissue macrophages. Interestingly, both local and systemic HA-NP-immune cell interactions significantly decreased over the disease progression. 89Zr-HA-NPs-induced radioactivity in atherosclerotic aortas was 30% higher than in wild-type controls. PET imaging of rabbits revealed 6-fold higher standardized uptake values compared to the muscle. The plaques of HA-NP-treated mice contained 30% fewer macrophages compared to control and free HA-treated group. In conclusion, we show favorable targeting properties of HA-NPs, which can be exploited for PET imaging of atherosclerosis-associated inflammation. Furthermore, we demonstrate the anti-inflammatory effects of HA-NPs in atherosclerosis.


Time-resolved seismic tomography detects magma intrusions at Mount Etna.
The continuous volcanic and seismic activity at Mount Etna makes this volcano an important laboratory for seismological and geophysical studies. We used repeated three-dimensional tomography to detect variations in elastic parameters during different volcanic cycles, before and during the October 2002-January 2003 flank eruption. Well-defined anomalous low P- to S-wave velocity ratio volumes were revealed. Absent during the pre-eruptive period, the anomalies trace the intrusion of volatile-rich (>/=4 weight percent) basaltic magma, most of which rose up only a few months before the onset of eruption. The observed time changes of velocity anomalies suggest that four-dimensional tomography provides a basis for more efficient volcano monitoring and short- and midterm eruption forecasting of explosive activity.


'I'm not doing this for me': mothers' accounts of creating smoke-free homes.
This article explores mothers' narratives of changing home smoking behaviours after participating in an intervention (Reducing Families' Exposure to Smoking in the Home [REFRESH]) aimed at reducing families' exposure to secondhand smoke (SHS) in homes in Scotland. An analysis of qualitative findings illuminates quantitative changes in levels of SHS exposure. Prospective quantitative and qualitative data were drawn from 21 smoking mothers with at least one child under 6 years. Quantitative change was measured by home air quality, i.e. fine particulate matter <2.5μg (PM(2.5)). These measurements guided the organization of mothers into categories of change (smoke-free home at baseline [SFB], smoke-free home at final, some change and no change [NC]). Qualitative data from 17 mothers with non-SFB were analysed thematically within and across these categories. Three comparative case studies illustrate the varying changes made, barriers to change and how mothers valued such changes. The outcomes varied post-intervention, with homes smoke-free, partially smoke-free or making NC. The changes in home smoking behaviour were incremental, yet beneficial to reducing SHS exposure, and related to the nature of the restrictions and personal circumstances in the home pre-intervention. Across all change categories, mothers valued the changes they had made and expressed an intention to increase the changes.


A Pipeline for the Generation of Realistic 3D Synthetic Echocardiographic Sequences: Methodology and Open-Access Database.
Quantification of cardiac deformation and strain with 3D ultrasound takes considerable research efforts. Nevertheless, a widespread use of these techniques in clinical practice is still held back due to the lack of a solid verification process to quantify and compare performance. In this context, the use of fully synthetic sequences has become an established tool for initial in silico evaluation. Nevertheless, the realism of existing simulation techniques is still too limited to represent reliable benchmarking data. Moreover, the fact that different centers typically make use of in-house developed simulation pipelines makes a fair comparison difficult. In this context, this paper introduces a novel pipeline for the generation of synthetic 3D cardiac ultrasound image sequences. State-of-the art solutions in the fields of electromechanical modeling and ultrasound simulation are combined within an original framework that exploits a real ultrasound recording to learn and simulate realistic speckle textures. The simulated images show typical artifacts that make motion tracking in ultrasound challenging. The ground-truth displacement field is available voxelwise and is fully controlled by the electromechanical model. By progressively modifying mechanical and ultrasound parameters, the sensitivity of 3D strain algorithms to pathology and image properties can be evaluated. The proposed pipeline is used to generate an initial library of 8 sequences including healthy and pathological cases, which is made freely accessible to the research community via our project web-page.


Discovery and functional analysis of a retinitis pigmentosa gene, C2ORF71.
Retinitis pigmentosa is a genetically heterogeneous group of inherited ocular disorders characterized by progressive photoreceptor cell loss, night blindness, constriction of the visual field, and progressive visual disability. Homozygosity mapping and gene expression studies identified a 2 exon gene, C2ORF71. The encoded protein has no homologs and is highly expressed in the eye, where it is specifically expressed in photoreceptor cells. Two mutations were found in C2ORF71 in human RP patients: A nonsense mutation (p.W253X) in the first exon is likely to be a null allele; the second, a missense mutation (p.I201F) within a highly conserved region of the protein, leads to proteosomal degradation. Bioinformatic and functional studies identified and validated sites of lipid modification within the first three amino acids of the C2ORF71 protein. Using morpholino oligonucleotides to knockdown c2orf71 expression in zebrafish results in visual defects, confirming that C2ORF71 plays an important role in the development of normal vision. Finally, localization of C2ORF71 to primary cilia in cultured cells suggests that the protein is likely to localize to the connecting cilium or outer segment of photoreceptor cells.


Functional monosomy of 6q27-qter and functional disomy of Xpter-p22.11 due to X;6 translocation with an atypical X-inactivation pattern.
Pattern of X chromosome inactivation (XCI) is typically random in females. However, chromosomal rearrangements affecting the X chromosome can result in XCI skewing due to cell growth disadvantage. In case of an X;autosome translocation, this usually leads to an XCI pattern of 100:0 with the derivative X being the active one in the majority of females. A de novo balanced X;6 translocation [46,X,t(X;6)(p22.1;q27)] and a completely skewed XCI pattern (100:0) were detected in a female patient with microcephaly, cerebellar vermis hypoplasia, heart defect, and severe developmental delay. We mapped the breakpoint regions using fluorescence in situ hybridization and found the X-linked gene POLA1 to be disrupted. POLA1 codes for the catalytic subunit of the polymerase α-primase complex which is responsible for initiation of the DNA replication process; absence of POLA1 is probably incompatible with life. Consequently, by RBA banding we determined which of the X chromosomes was the active one in the patient. In all examined lymphocytes the wild-type X chromosome was active. We propose that completely skewed XCI favoring the normal X chromosome resulted from death of cells with an active derivative X that was caused by a non-functional POLA1 gene. In summary, we conclude that functional monosomy of 6q27-qter and functional disomy of Xpter-p22.11 are responsible for the clinical phenotype of the patient. This case demonstrates the importance of determining which one of the X chromosomes underwent inactivation to correlate clinical features of a female with an X;autosome translocation with the nature of the genetic alteration.


Mineralization of palm oil mill effluent by advanced oxidation processes: A review on current trends and the way forward.
Palm oil mill effluent (POME) is regarded as deleterious to the environment, primarily owing to the substantial volume of waste it produces during palm oil extraction. In terms of contaminant composition, POME surpasses the pollutant content typically found in standard municipal sewage, therefore releasing it without treatment into water bodies would do irreparable damage to the environment. Main palm oil mills are normally located in the proximity of natural rivers in order to take advantage of the cheap and abundant water source. The same rivers are also used as a water source for many villages situated along the river banks. As such, it is imperative to degrade POME before its disposal into the water bodies for obvious reasons. The treatment methods used so far include the biological processes such as open ponding/land application, which consist of aerobic as well as anaerobic ponds, physicochemical treatment including membrane technology, adsorption and coagulation are successful for the mitigation of contaminants. As the above methods require large working area and it takes more time for contaminant degradation, and in consideration of the strict environmental policies as well as palm oil being the most sort of vegetable oil in several countries, numerous researchers have concentrated on the emerging technologies such as advanced oxidation processes (AOPs) to remediate POME. Methods such as the photocatalysis, Fenton process, sonocatalysis, sonophotocatalysis, ozonation have attained special importance for the degradation of POME because of their efficiency in complete mineralization of organic pollutants in situ. This review outlines the AOP technologies currently available for the mineralization of POME with importance given to sonophotocatalysis and ozonation as these treatment process removes the need to transfer the pollutant while possibly degrading the organic matter sufficiently to be used in other industry like fertilizer manufacturing.


Web-based social media for professional medical education: Perspectives of senior stakeholders in the nursing home sector.
Participatory web-based platforms, including social media, have been recognised as valuable learning tools in healthcare education for over a decade. Use of these platforms is now widespread in tertiary education. It is less widely accepted as a tool for continuing professional education and development at the industry level. This study explores perspectives of senior stakeholders in the nursing home sector to explore perceived benefits, barriers and risks for use in professional education. Qualitative data were collected through semi-structured interviews of 'high level' clinical and executive staff from a cross section of nursing home stakeholder organisations. Established printed educational material (PEM) was used as a case study for adaptation to web-based social applications. Questions were designed to gather information about the interviewee's views on the potential to apply PEM to programs such as blogs, Twitter and YouTube to deliver education and aid communication in the sector. Twelve participants from eleven stakeholder organisations took part in the study. Most participants were cautious about the use of social media programs in continuing professional education. Participants described the benefits (contemporary information, delivered rapidly, varying formats) and barriers (credibility of information, potential misinterpretation, sector demographics, time constraints) to uptake of these programs. The majority of participants preferred formal e-learning programs to web-based social media applications. Reservations expressed about the use of social media, such as accuracy, legal and privacy risks to the organisation reflected those previously expressed by the broader medical community.


Assessment of antimicrobial activity of nanosized Ag doped TiO(2) colloids.
In the present research, the antimicrobial effects of nanosized silver (Ag) doped TiO(2) colloidal solutions prepared using a sol-gel technique were investigated. In order to determine the solution characteristics, the turbidity, viscosity and pH of the colloidal solutions were measured. Differential thermal analysis-thermogravimetry equipment was used to determine the chemical structures and reaction types of the films formed from these solutions. The morphology of Ag doped TiO(2) nanoparticles was evaluated by atomic force microscopy. The disc diffusion method was employed to explore antimicrobial activity, and the Broth Microdilution method was used to obtain MIC values of nanosized Ag doped TiO(2) colloidal solutions against the test microorganisms Escherichia coli, Staphylococcus aureus, Candida albicans, Bacillus subtilis, and Salmonella typhimurium. It was found that the silver doped TiO(2) nanoparticles inhibited the growth and multiplication of the test microorganisms, including the fungus C. albicans. Antimicrobial activity was observed against all tested microorganisms at a very low concentration of 1.125-2.81 μg/ml of nano silver in 1-25 % Ag-TiO(2) solutions.


Binding of benzo(a)pyrene and dibenz(a,h)anthracene to the Ah receptor in mouse and rat hepatic cytosols.
Binding of the polycyclic aromatic hydrocarbon (PAH) carcinogens [3H]benzo(a)pyrene (BP) and [3H]dibenz(a,h)anthracene [DB(a,h)A] to components in rodent hepatic cytosols was characterized by sucrose density gradient centrifugation and by gel permeation chromatography on Sephacryl S-300. In hepatic cytosols from Sprague-Dawley rats, [3H]BP and [3H]DB(a,h)A bound to a component which sedimented at 8 to 9S under low-ionic-strength conditions, and had a Stokes' radius of 4.7 nm. The 8 to 9S component also bound [3H]-2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and [3H]-3-methylcholanthrene (MC), two compounds previously established as Ah receptor ligands. In hepatic cytosols from C57BL/6J mice [a strain genetically "responsive" for induction of aryl hydrocarbon hydroxylase (AHH, cytochrome P1-450) by PAHs], [3H]DB(a,h)A bound to a component sedimenting at 8 to 9S which had a Stokes' radius of approximately 6 nm. The 8 to 9S component also bound [3H]TCDD and [3H]MC, but no direct binding of [3H]BP could be detected at 8 to 9S in hepatic cytosol from C57BL/6J mice, nor could specific [3H]BP binding to the 6 nm component be detected in C57BL/6J cytosol by Sephacryl S-300 chromatography. The 8 to 9S component was not detectable in hepatic cytosol from DBA/2J mice (genetically "nonresponsive" to AHH induction by PAHs) with [3H]BP or [3H]DB(a,h)A, nor with the previously established Ah receptor ligands [3H]TCDD or [3H]MC. In addition to binding to the 8 to 9S-6 nm component in C57BL/6J cytosols, [3H]BP, [3H]DB(a,h)A, and [3H]MC also bound extensively to a cytosolic component sedimenting at 4 to 5S with a Stokes' radius of approximately 3 nm. The 4 to 5S-3 nm component was present in hepatic cytosols from genetically nonresponsive DBA/2J mice, as well as in genetically responsive C57BL/6J mice. Binding of [3H]BP, [3H]DB(a,h)A, and [3H]MC to the 8 to 9S component in rodent hepatic cytosols was eliminated by incubation in the presence of a 100-fold molar excess of nonradioactive TCDD, whereas TCDD had no effect on binding of [3H]BP, [3H]DB(a,h)A, or [3H]MC to the 4 to 5S-3 nm component. The 8 to 9S component segregates with the Ahb allele in genetic crosses with mice, but the 4 to 5S component is not associated with the Ahb allele which governs AHH responsiveness. Specificity of chemicals that bind to the 8 to 9S component and segregation of the 8 to 9S component with the Ahb allele identify it as the Ah receptor which functions to regulate AHH induction in animals treated with PAHs.(ABSTRACT TRUNCATED AT 400 WORDS)


Motor trajectories from birth to 5 years of children born at less than 30 weeks' gestation: early predictors and functional implications. Protocol for a prospective cohort study.
Motor impairments are one of the most frequently reported adverse neurodevelopmental consequences in children born < 30 weeks' gestation. Up to 15% of children born at < 30 weeks have cerebral palsy and an additional 50% have mild to severe motor impairment at school age. The first 5 years of life are critical for the development of fundamental motor skills. These skills form the basis for more complex skills that are required to competently and confidently participate in schooling, sporting and recreational activities. In children born at < 30 weeks' gestation, the trajectory of motor development from birth to 5 years is not fully understood. The neural alterations that underpin motor impairments in these children are also unclear. It is essential to determine if early clinical evaluations and neuroimaging biomarkers can predict later motor impairment and associated functional problems at 5 years of age. This will help to identify children who will benefit the most from early intervention and improve functional outcomes at school age. The primary aim of this study is to compare the prevalence of motor impairment from birth to 5 years of age between children born at < 30 weeks and term-born controls, and to determine whether persistent abnormal motor assessments in the newborn period in those born at < 30 weeks predict abnormal motor functioning at 5 years of age. Secondary aims for children born at < 30 weeks and term-born children are: 1) to determine whether novel early magnetic resonance imaging-based structural or functional biomarkers that can predict motor impairments at 5 years are detectable in the neonatal period; 2) to investigate the association between motor impairments and concurrent deficits in body structure and function at 5 years of age; and 3) to explore how motor impairments at 5 years (including abnormalities of gait, postural control and strength) are associated with concurrent functional outcomes, including physical activity, cognitive ability, learning ability, and behavioural and emotional problems. Prospective longitudinal cohort study. 150 preterm children (born at < 30 weeks' gestation) and 151 term-born children (born at > 36 completed weeks' gestation and weighing > 2499g) admitted to the Royal Women's Hospital, Melbourne, were recruited at birth and will be invited to participate in a 5-year follow-up study. This study will examine previously collected data (from birth to 2 years) that comprise detailed motor assessments, and structural and functional brain MRI images. At 5 years, preterm and term, children will be examined using comprehensive motor assessments, including: the Movement Assessment Battery for Children (2nd edition) and measures of gait function through spatiotemporal (assessed with the GAITRite® Walkway) and dynamic postural control (assessed with Microsoft Kinect) variables; and hand grip strength (assessed with a dynamometer); and measures of physical activity (assessed using accelerometry), cognitive development (assessed with Wechsler Preschool and Primary Scale of Intelligence), and emotional and behavioural status (assessed with the Strengths and Difficulties Questionnaire and the Developmental and Wellbeing Assessment). At the 5-year assessment, parents/caregivers will be asked to complete questionnaires on demographics, physical activity, activities of daily living, behaviour, additional therapy (eg, physiotherapy and occupational therapy), and motor function (assessed with Pediatric Evaluation of Disability Inventory, Pediatric Quality of Life Questionnaire, the Little Developmental Co-ordination Questionnaire and an activity diary). For the primary aim, the prevalence of motor impairment from birth to 5 years will be compared between children born at < 30 weeks and at term, using the proportion of children classified as abnormal at each of the time points (term age, 1, 2 and 5 years). Persistent motor impairments during the neonatal period will be assessed as a predictor of severity of motor impairment at 5 years of age in children born < 30 weeks using linear regression. Models will be fitted using generalised estimating equations to allow for the clustering of multiple births. Analysis will be repeated with adjustment for predictors of motor outcome, including additional therapy, sex, brain injury and chronic lung disease. Understanding the developmental precursors of motor impairment in children born before 30 weeks is essential for limiting disruption to skill development, and potential secondary impacts on physical activity, participation, academic achievement, self-esteem and associated outcomes (such as obesity, poor physical fitness and social isolation). An improved understanding of motor skill development will enable targeting of interventions and streamlining of services to children at highest risk of motor impairments.


[Risk factors and the course of myocardial infarction in elderly women].
to elucidate risk factors and special features of myocardial infarction (MI) in elderly women. We included into the study 217 women aged 34 to 89 years who had Q-wave or non Q-wave MI and were admitted for treatment in the cardiology department. These patients were divided into two age groups - younger than 60 years (n=79, mean age 51.6+/-5.9 years) and more or equal 60 years (n=138, mean age 71.7+/-6.9 years). The following risk factors were more frequent among older women: hypertension (95.7 vs 89.9%), diabetes mellitus (32.2 vs 24%). Women aged <60 years more often had obesity (43.0 vs 26.8%), dyslipidemia (63.3 vs 42.8%), smoking (18.9 vs 0.7%), and premature menopause (12.8% vs 5.0%). Women aged <60 years had combinations of 3 or 4 risk factors. Coronary angiography was carried out in 34.2% of women aged <60 years and in 18.8% of older women. Women aged <60 years compared with older women more often had single vessel coronary artery stenosis (55.6 and 23.3%, respectively), whereas in women aged more or equal 60 years prevailed multivessel coronary artery involvement (22.2 and 42.3%, respectively). MI in elderly women was more often complicated by Killip class III-IV acute heart failure, arrhythmias, recurrent MI, and hemotamponade, while younger women (aged <60 years) more often had early postinfarction angina and Dressler syndrome.


Lipomatous myofibroblastoma of the breast: case report with diagnostic and histogenetic considerations.
We report rare case of myofibroblastoma (MFB) of the breast comprised predominantly of a mature fatty component, representing approximately 70% of the entire tumour area. This tumour, designated "lipomatous MFB", should be interpreted as the morphological result of an unbalanced bidirectional differentiation of the precursor mammary stromal cell, with the adipocytic component overwhelming the fibroblastic/myofibroblastic one. Lipomatous MFB is a rare variant of mammary MFB, which can mimic malignancy because of the close juxtaposition of fibroblasts/myofibroblasts with mature adipocytes, resulting in a finger-like infiltrative growth pattern of the former towards the latter. Histogenetic considerations and differential diagnostic problems with other bland-looking spindle cell tumours containing infiltrating fat are provided.


Expression of laminin 5, fibronectin, and epithelium-associated integrins in recurrent aphthous ulcers.
Recurrent aphthous ulceration (RAU) is characterized by an ulcerated lesion that persists longer than traumatic ulcers of similar size. This delayed healing phase of the lesion was investigated for extracellular matrix components and matrix receptors (integrins). The hypothesis tested was that aphthous ulcers may lack key extracellular matrix components, or their receptors, that are necessary for the migration of marginal keratinocytes from the ulcer edge. We immunocytochemically stained biopsy specimens of RAUs and non-involved mucosal specimens from HIV+ and non-infected individuals to investigate the presence and distribution of molecules reported to be associated with reepithelialization of mucosal and cutaneous wounds. Fibronectin, laminin type 5 (kalinin), and integrin subunits beta 1, beta 4, alpha 6, and alpha v were consistently found at the margins of RAU, as they are in traumatic ulcers. The alpha 5 and beta 6 subunits were not always present. We also found alpha v in the intact stratified squamous epithelium adjacent to ulcers. Immunohistochemical stains showed distruption in the deposition of laminin 5 and an apparent lack of fibronectin at the edges of some ulcers. Although these tissue results do not determine which integrin subunits are paired with each other, they do show some alterations in their expression in RAU. Absence of one or more of these molecules at the migrating front may contribute to delayed epithelial regeneration. It is likely that the absence or inappropriate expression of keratinocyte integrins or their extracellular matrix receptors occurs after the causative factors (currently unknown) of the lesion are gone. The reason for the altered expression of these molecules may be related to the secretory products (including lymphokines and proteinases) of the lymphocytic infiltrate.


Blood pressure characteristics of hypertensive patients in Austria as determined by self-monitoring (SCREEN-II).
This is the first large-scale, countrywide study evaluating blood pressure levels in treated hypertensive patients based on home blood pressure monitoring. The study was conducted all over Austria by 166 physicians enrolling a total of 1303 patients each taking at least 30 home blood pressure readings (a total of 39,000 readings). Stratification of patients into groups with normotension, mild hypertension or severe hypertension followed the recommendations of the Austrian Hypertension League (normotension defined as no more than seven readings higher than 135/85 mmHg, according to a blood pressure load of no more than 25%). The data collected show that these patients are inadequately treated, with only 17% being normotensive. Treatment results are no better than in patients with blood pressure measured in an office setting: the number of those achieving normotension is 17% vs 16%, although the self-measuring patients obviously receive better treatment with more patients being prescribed combination therapy.


[Diagnosis and treatment of the toxic syndrome in diffuse peritonitis].
Based on an analysis of clinico-laboratory manifestations of intoxication in 202 patients with widespread forms of peritonitis the authors give a classification of severity of the intoxication syndrome. The role of proteases and middle size peptides in pathogenesis of endogenous intoxication in peritonitis is shown. The irrigation of the abdominal cavity with Kontrical is recommended in the postoperative period for decreasing the intoxication. Hemosorption was also used in patients with the growing syndrome of endogenous III degree intoxication. The methods used lowered lethality from 29.9% to 17.8%.


Non-lethal growth inhibition by arresting the starch utilization system of clinically relevant human isolates of Bacteroides dorei.
We describe the inhibition of the starch utilization system (Sus) belonging to various strains of Bacteroides dorei in a non-lethal manner using the small molecule probe, acarbose. Concentrations of acarbose as low as 5 μM significantly impede the growth of B. dorei and increase the doubling time of cultures. The successful inhibition of this species of Bacteroides is relevant to several disease states including type I diabetes mellitus. This method continues to explore a new, potential route to intervene in illnesses associated with aberrant changes in the composition of the human gut microbiota through the strategic manipulation of its constituents.


[Musculoskeletal complications in diabetes mellitus].
Musculoskeletal abnormalities are common and multiple in diabetic patients. They often result from pathologic changes in the microvasculature (microangiopathy), connective tissue, and peripheral nerves related to chronic hyperglycaemia. Their prevalence in patients with diabetes vary depending upon the diagnostic criteria, the study population and is generally correlated with poor glycaemic control and the occurrence of other complications of diabetes. These entities are important to recognize because they often respond to treatment, preventing pain and disability and improving quality of life.


Rosmarinic Acid, the Main Effective Constituent of Orthosiphon stamineus, Inhibits Intestinal Epithelial Apoptosis Via Regulation of the Nrf2 Pathway in Mice.
Many studies have shown that Orthosiphon stamineus extract (OE) has antioxidant activity, and we previously reported that OE protects the intestine against injury from a high-fat diet. However, the molecular mechanism underlying this protective effect of OE was unclear. Here, OE was separated according to polarity and molecular weight, and the antioxidant activity of each component was compared. The components with the highest antioxidant activity were analyzed by HPLC, which confirmed that rosmarinic acid (RA) was the main effective constituent in OE. OE and RA were then tested in a mouse high-fat diet-induced intestinal injury model. The antioxidant indices and morphological characteristics of the mouse jejunum were measured, and activation of the nuclear factor E2-related factor 2 (Nrf2) pathway and apoptosis of jejunal epithelial cells were analyzed. Of all the constituents in OE, RA contributed the most. Both RA and OE activated the Nrf2 pathway and increased downstream antioxidant enzyme activity. RA and OE protected the mouse intestine against high-fat diet-induced oxidative stress by preventing intestinal epithelial cell apoptosis via both extracellular and intracellular pathways. Thus, RA, the main effective constituent in OE, inhibits intestinal epithelial apoptosis by regulating the Nrf2 pathway in mice.


Otitis Media with Effusion: Our National Practice.
Otitis media with effusion (OME) is the focus of an updated multidisciplinary clinical practice guideline published by the American Academy of Otolaryngology-Head and Neck Surgery Foundation (AAO-HNSF) and the American Academy of Pediatrics (AAP). Based on data from clinical trials, the guideline recommends against using antihistamines, antibiotics, oral steroids, and intranasal steroids for OME. To understand practice patterns related to these guidelines, we assessed nationally representative data. Despite controlling for age, sex, race/ethnicity, and other potential confounders individualized for each medication class, an increased risk of antihistamine (odds ratio [OR], 3.53), antibiotic (OR, 4.31), and intranasal steroid administration (OR, 3.58) was seen when OME was diagnosed. These analyses have demonstrated opportunities for quality improvement in the care of patients with OME, quantifying gaps in practice relevant to proposed quality measures. Education targeted according to practice setting may facilitate appropriate therapy and/or referral for definitive intervention in children with OME.


ANGPTL3 (Angiopoietin-Like 3) Preferentially Resides on High-Density Lipoprotein in the Human Circulation, Affecting Its Activity.
Background ANGPTL3 (angiopoietin-like protein 3) is an acknowledged crucial regulator of lipid metabolism by virtue of its inhibitory effect on lipoprotein lipase and endothelial lipase. It is currently unknown whether and to which lipoproteins ANGPTL3 is bound and whether the ability of ANGPTL3 to inhibit lipase activity is affected by binding to lipoproteins. Methods and Results Incubation of ultracentrifugation-isolated low-density lipoprotein (LDL) and high-density lipoprotein (HDL) fractions from healthy volunteers with recombinant ANGPTL3 revealed that ANGPTL3 associates with both HDL and LDL particles ex vivo. Plasma from healthy volunteers and a patient deficient in HDL was fractionated by fast protein liquid chromatography, and ANGPTL3 distribution among lipoprotein fractions was measured. In healthy volunteers, ≈75% of lipoprotein-associated ANGPTL3 resides in HDL fractions, whereas ANGPTL3 was largely bound to LDL in the patient deficient in HDL. ANGPTL3 activity was studied by measuring lipolysis and uptake of 3H-trioleate by brown adipocyte T37i cells. Unbound ANGPTL3 did not suppress lipase activity, but when given with HDL or LDL, ANGPTL3 suppressed lipase activity by 21.4±16.4% (P=0.03) and 25.4±8.2% (P=0.006), respectively. Finally, in a subset of the EPIC (European Prospective Investigation into Cancer) Norfolk study, plasma HDL cholesterol and amount of large HDL particles were both positively associated with plasma ANGPTL3 concentrations. Moreover, plasma ANGPTL3 concentrations showed a positive association with incident coronary artery disease (odds ratio, 1.25 [95% CI, 1.01-1.55], P=0.04). Conclusions Although ANGPTL3 preferentially resides on HDL, its activity was highest once bound to LDL particles.


Sporadic desmoid tumor. An exceptional cause of cystic pancreatic lesion.
Desmoid tumors are rare, benign soft tissue tumors, characterized by the proliferation of fibroblasts in an abundant collagen extra-cellular matrix. Intra-abdominal forms involve the mesentery and retroperitoneum and usually occur associated with familial adenomatous polyposis or Gardner's syndrome. Sporadic cases are more uncommon. Although desmoid tumors do not metastasize, their evolution can be life-threatening due to aggressive local invasion, such as mesentery involvement. We herein report a very rare location of sporadic desmoid tumors involving the pancreatic tail, presenting as a cystic lesion. A 51-year-old woman presented with recurrent abdominal pain and weight loss. The diagnosis of mucinous cystadenocarcinoma was suspected preoperatively and the patient underwent a splenopancreatectomy with en-bloc resection of the left colonic flexure, duodenojejunal junction and part of the posterior gastric wall. Pathological analysis revealed fibroblastic proliferation arising in musculoaponeurotic structures consistent with a desmoid tumor. The diagnosis was confirmed by immunocytochemical analysis and the assessment of the beta-catenin gene mutation. Perioperative examination reported gastric and small-bowel invasion. No treatment was given postoperatively to prevent desmoid tumor recurrence. After a 1-year follow-up, no recurrence was observed. Desmoid tumors are very rare in the pancreas and their diagnosis can be difficult, such as in our case where it presented as a cystic lesion. In contrast to intra-abdominal forms, sporadic pancreatic desmoid tumors are more frequent than those associated with familial adenomatous polyposis.


Annual Report on surveillance for avian influenza in poultry and wild birds in Member States of the European Union in 2020.
In 2020, Council Directive 2005/94/EC required EU Member States (MSs) to carry out surveillance for avian influenza (AI) in poultry and wild birds and notify the results to the responsible authority. Based on this, MSs, Iceland, Norway, Switzerland and the United Kingdom implemented ongoing surveillance programmes to monitor incursions of AI viruses in poultry and wild birds. EFSA received a mandate from the European Commission to collate, validate, analyse and summarise the data resulting from the avian influenza surveillance programmes in an annual report. This is the second such report produced using data directly submitted to EFSA by MSs. This report summarises the results of the surveillance activities carried out in poultry and wild birds in 2020. Overall, 24,768 poultry establishments (PEs) were sampled, of which 46 were seropositive for H5 virus strains and seven for H7 strains. Seropositive PEs were found in nine MSs (Belgium, Denmark, Finland, France, Italy, the Netherlands, Poland, Spain and Sweden) and the United Kingdom. As per previous years, the highest percentages of seropositive PEs were found in establishments raising waterfowl game birds and breeding geese. Out of the 53 PEs with positive serological tests for H5/H7, seven tested positive in polymerase chain reaction (PCR) or virology for H5/H7 virus strains: six for Low Pathogenic Avian Influenza (LPAI) and one for Highly Pathogenic Avian Influenza (HPAI). In addition, 13 countries also reported PCR results from 748 PEs which did not correspond to the follow-up testing of a positive serology event (e.g. in some PEs, PCR tests were used for screening). Twenty-five of these PEs were found positive for AI viral RNA. These positive PEs were located in Bulgaria, Estonia, Germany, Romania and Slovakia. A total of 18,968 wild birds were sampled, with 878 birds testing positive to HPAI virus. Fourteen countries reported HPAI-positive wild birds, with all HPAI strains identified as H5. Most positive birds were infected with H5N8, with a smaller number of N1, N3, N5 and unidentified NA subtypes. In addition, there were 317 birds testing positive for LPAI H5 or H7 virus and 429 birds testing positive for non-H5/H7 AI virus, reported by 31 countries. The surveillance findings for poultry and wild birds for 2020 are discussed in relation to the current knowledge of the epidemiology of AI in Europe, in particular the H5N8 epidemic which has been identified late 2020.


A glance at black cumin (Nigella sativa) and its active constituent, thymoquinone, in ischemia: a review.
Black cumin (Nigella sativa) belonging to Ranunculaceae family has a long history of medicinal use in various folk and traditional systems of medicine, including Iranian traditional medicine (ITM). These valuable medicinal seeds have been used traditionally against a variety of diseases such as dyspepsia, diabetes, headache, influenza and asthma. In addition, several scientific investigations have reported the therapeutic properties of N. sativa and thymoquinone (TQ), one of the most important constituent of black cumin, for treatment of a large number of diseases, including ischemia. As there is no comprehensive review study about the anti-ischemic activity of black cumin and its mechanism of action, in the current study, we aimed to review the anti-ischemic activities of N. sativa and TQ in different organ-related disorders. We searched the words N. sativa or black cumin and ischemia in the combination of related organs through available databases including Scopus, Web of Science, and Google Scholar. Several studies were found reporting the anti-ischemic activity of black cumin and its active constituent on different organs including brain, kidneys, heart, and liver. Black cumin exert its beneficial effects as an antioxidant, anti-inflammatory, anti-apoptosis, and anti-necrosis agent through inhibition of growth factors, biochemical and oxidative stress markers and regulating gene expression. Thus, N. sativa could be a potential candidate for treatment of ischemia related disorders in key organs such as brain, liver, digestive system, kidney, and heart. To figure out the exact mechanism of action, further investigations are proposed in this regard.