Biocompatibility of Intensified Decellularized Equine Carotid Arteries in a Rat Subcutaneous Implantation Model and in a Human In Vitro Model.
Limited biocompatibility of decellularized scaffolds is an ongoing challenge in tissue engineering. We recently demonstrated that intensified detergent-based decellularization of equine carotid artery (dEACintens) removed residual cellular molecules from the scaffold more efficiently than a conventional decellularization (dEACcon), although this approach did not eliminate its immunogenicity entirely. CCN1 has been shown to improve biocompatibility of dEACcon in a sheep model. In this study, we tested the biocompatibility of dEACintens and dEACcon with or without CCN1 coating after subcutaneous implantation in rats for up to 12 weeks. Explants were assessed by conventional histopathology and immunostaining for infiltrating M2 macrophages. Moreover, human macrophages derived from monocytes (MDM) or THP-1 cells (THP-derived macrophages [TDM]) were seeded onto dEACcon and dEACintens, and activation was assessed either by cytokine expression or matrix metalloprotease 2 and 7 staining. dEACintens showed a significantly reduced inflammatory infiltration (52%; p < 0.0001), as well as an earlier and denser neovascularization (1.4-fold, p < 0.0001) independent of CCN1 coating, which, however, reduced fibrosis exclusively with dEACintens (26-53%; p < 0.05). Human MDM seeded for 48 h onto dEACintens showed higher transcript levels for anti-inflammatory IL-10 (2.3-fold), proinflammatory TNFα (2.2-fold), and macrophage/monocyte recruiting MIP1α (3.5-fold; all p < 0.05) and MCP (2.7-fold; p < 0.01), whereas 1.92-fold more TDM on dEACintens showed staining for MMP2 (p > 0.001). Thus, although being advantageous in regard to fibrosis, CCN1 coating of dEACintens does not appear to be necessary for further improving dEACintens excellent biocompatibility in rats. In humans, the unspecific cellular immune response toward dEACintens seemed to be more complex, but generally comparable to the mild acute inflammatory tissue reaction with high remodeling activity as observed after rat subcutaneous implantation.


Predation and searching efficiency of a ladybird beetle, Coccinella septempunctata Linnaeus in laboratory environment.
The predation and searching efficiency of fourth instar of predatory C. septempunctata at various densities of mustard aphid, Lipaphis erysimi (Kaltenbach) and predator was investigated under laboratory conditions. The feeding rate of predatory stage decreased at increased prey- and predator densities. Highest percent (92.80%) prey consumption was observed at initial prey density and lowest percent (40.86%) prey consumption at highest prey density by the fourth instar, though the total prey consumption increased with increase in either prey- or predator densities. Similarly, the individual prey consumption was also highest at initial predator density and lowest at highest predator density owing to the mutual interference between the predators at higher densities. The area of discovery (searching efficiency) also decreased with increase in prey- and predator densities. Handling time of predator was highest at lower prey densities, which decreased with increased prey densities. The highest percentage of prey consumption at the prey density of 50 revealed that 1:50 predator-prey ratio was the best to reduce the pest population.


Insulin and leptin combine additively to reduce food intake and body weight in rats.
Leptin and insulin are distinct adiposity signals that regulate food intake and body weight. Because recent evidence suggests that the central catabolic action of each is mediated by the hypothalamic melanocortin system, we tested the hypothesis that leptin and insulin interact within the brain, either additively or synergistically, to suppress food intake and reduce body weight. Using a within-subjects design, we co-administered leptin and insulin into the 3rd cerebral ventricle (i.c.v.) over a wide range of doses, and compared the combined effects to what occurred following the administration of each peptide alone. The data suggest that leptin and insulin interact sub-additively to regulate food intake and body weight over the first few hours. That is, the ability of combinations of leptin and insulin to reduce food intake and body weight was less than what would be predicted by the sum of their independent actions. Over 24 hours, however, the combined doses fit a strictly additive model. These data therefore imply a redundancy in the functional intracellular pathways or neuronal circuits that leptin and insulin utilize in the acute regulation of food intake and body weight, and they further imply that over time, the redundancy dissipates.


Removal of antibiotics in sponge membrane bioreactors treating hospital wastewater: Comparison between hollow fiber and flat sheet membrane systems.
Hollow fiber (HF) and flat sheet (FS) Sponge MBRs were operated at 10-20 LMH flux treating hospital wastewater. Simultaneous nitrification denitrification (SND) occurred considerably with TN removal rate of 0.011-0.020mg TN mgVSS-1d-1. Furthermore, there was a remarkable removal of antibiotics in both Sponge MBRs, namely Norfloxacin (93-99% (FS); 62-86% (HF)), Ofloxacin (73-93% (FS); 68-93% (HF)), Ciprofloxacin (76-93% (FS); 54-70% (HF)), Tetracycline (approximately 100% for both FS and HF) and Trimethoprim (60-97% (FS); 47-93% (HF). Whereas there was a quite high removal efficiency of Erythromycin in Sponge MBRs, with 67-78% (FS) and 22-48% (HF). Moreover, a slightly higher removal of antibiotics in FS than in HF achieved, with the removal rate being of 0.67-32.40 and 0.44-30.42µgmgVSS-1d-1, respectively. In addition, a significant reduction of membrane fouling of 2-50 times was achieved in HF-Sponge MBR for the flux range.


Modeling alternative binding registers of a minimal immunogenic peptide on two class II major histocompatibility complex (MHC II) molecules predicts polarized T-cell receptor (TCR) contact positions.
Several major histocompatibility complex class II (MHC II) complexes with known minimal immunogenic peptides have now been solved by X-ray crystallography. Specificity pockets within the MHC II binding groove provide distinct peptide contacts that influence peptide conformation and define the binding register within different allelic MHC II molecules. Altering peptide ligands with respect to the residues that contact the T-cell receptor (TCR) can drastically change the nature of the ensuing immune response. Here, we provide an example of how MHC II (I-A) molecules may indirectly effect TCR contacts with a peptide and drive functionally distinct immune responses. We modeled the same immunogenic 12-amino acid peptide into the binding grooves of two allelic MHC II molecules linked to distinct cytokine responses against the peptide. Surprisingly, the favored conformation of the peptide in each molecule was distinct with respect to the exposure of the N- or C-terminus of the peptide above the MHC II binding groove. T-cell clones derived from each allelic MHC II genotype were found to be allele-restricted with respect to the recognition of these N- vs. C-terminal residues on the bound peptide. Taken together, these data suggest that MHC II alleles may influence T-cell functions by restricting TCR access to specific residues of the I-A-bound peptide. Thus, these data are of significance to diseases that display genetic linkage to specific MHC II alleles, e.g. type 1 diabetes and rheumatoid arthritis.


Prognostic value of copeptin in patients with acute myocardial infarction treated with percutaneous coronary intervention: a prospective cohort study.
Ischemic myocardial injury leads to neurohormonal system activation and increased release of copeptin. Although diagnostic value of copeptin has been widely described, data on its prognostic performance in patients with myocardial infarction is inconclusive. The aim of this study was to asses if elevated copeptin concentration provides prognostic information for long-term adverse cardiac events in a cohort of first acute myocardial infarction patients treated with percutaneous coronary intervention. Copeptin concentration was assessed in a cohort of 100 consecutive patients (39% women; mean age 63±7 years) presenting with first acute myocardial infarction and subjected to percutaneous coronary intervention. Samples were collected at the time of admission and on the 4th/5th day of hospitalisation. All patients were followed-up prospectively for 12 months for the occurrence of major adverse cardiovascular events defined as reinfarction, unscheduled coronary revascularisation and all-cause death. Elevated copeptin concentration on the 4th/5th day of hospitalisation was identified as a predictor of major adverse cardiovascular events (P=0.0445). The increase between copeptin level on admission and on day 4th/5th was associated with the requirement for unscheduled coronary revascularisation in receiver operating characteristics (ROC) analysis (AUC =0.639; 95% CI: 0.504-0.773; P=0.0430). In a multivariate analysis, copeptin concentration on the 4th/5th day of hospitalisation and left ventricular ejection fraction assessed by transthoracic echocardiography, were the only predictors for major adverse cardiac events during follow-up (P=0.024 and P=0.001, respectively). Copeptin seems to be a prognostic marker in patients with first myocardial infarction treated with percutaneous coronary intervention.


Bidirectionally positioned flap surgery: a case report with 3-year follow-up.
A new technique to cover recessions to take advantage of connective tissue grafts and coronally advanced flaps is proposed. A 34-year-old woman presented with a 2-mm Class I recession on the buccal aspect of her maxillary right canine. A full-thickness flap was placed coronally to cover the exposed root, and a partial thickness flap was positioned apically. Complete root coverage was obtained, and the width of keratinized tissue had increased from 2 to 4 mm at the 6-month postoperative visit. These clinical outcomes were maintained for 3 years. This single surgical approach benefits from obtaining not only complete root coverage but also increasing width of keratinized tissue, without requiring a second surgical site.


Local osteo-articular tuberculosis complicating closed fractures: report of two cases.
The localisation of acute haematogenous pyogenic osteomyelitis following a local injury is well known. Whilst there is often a history of trauma in patients developing bone and joint tuberculosis, its role is obscure. Two patients are reported who developed histologically proven tuberculosis in the vicinity of closed fractures during the healing process. These two patients make a total of four so far reported.


Immunostaining of visceral leishmaniasis caused by Leishmania infantum using monoclonal antibody (19-11) to the Leishmania homologue of receptors for activated C-kinase.
It sometimes is difficult to diagnose leishmaniasis in tissue sections or in smears, particularly in unusual sites or if few parasites are present in the lesion. Leishmania species must be differentiated morphologically from a variety of other microorganisms, including Toxoplasma gondii, Histoplasma capsulatum, Trypanosoma cruzi, and Penicillium marneffei. We tested the value of monoclonal antibody p19-11 raised against the Leishmania homologue of receptors for activated C-kinase (LACK) as an immunohistochemical marker for amastigotes of Leishmania infantum. We evaluated a total of 117 paraffin-embedded lesions due to L infantum (92 cases), T gondii (15 cases), H capsulatum (5 cases), T cruzi (3 cases), and P marneffei (2 cases). Amastigotes of Leishmania species were detected in 92 (100%) of the leishmaniasis lesions. There were no false-positive LACK immunoreactions in any of the toxoplasmosis, histoplasmosis, trypanosomiasis, or penicilliosis specimens (0/25). We found the anti-LACK antibody p19-11 to be a highly specific and sensitive paraffin-reactive immunohistochemical marker for the confirmation or identification of Leishmania species in tissue sections.


An untargeted serum and urine lipidomics research based on UPLC-MS revealed the lipid alterations on adjuvant-induced arthritis rats.
Rheumatoid arthritis (RA) is a systemic autoimmune disease dominated by chronic inflammatory lesions of peripheral synovial joints. Growing evidence suggests that abnormal lipid metabolism levels contribute to the progression of RA. Although several metabolomics studies have shown abnormality in the RA lipidome, the relationship between the overall lipid metabolites and RA has not been systematically evaluated. In this study, an untargeted lipidomics method based on ultra performance liquid chromatography-mass spectrometry (UPLC-MS) was used to analyze the serum and urine lipidomes of adjuvant-induced arthritis rats to study the characteristics of lipid metabolism changes in the rats and search lipid markers for diagnosing RA. By combining with orthogonal partial least squares discriminant analysis, a total of 52 potential lipid markers were identified, mainly involved in sphingolipid metabolism, glycerophospholipid metabolism, sterol lipid metabolism, glycerolipid metabolism and fatty acid metabolism, which provided crucial insight into lipid metabolism disturbances in RA. Further receiver operating characteristic analysis revealed that the areas under the curve of PC(22:4/16:0), PI(18:1/16:0) and LacCer(d18:1/12:0) from serum and 25-hydroxycholesterol from urine were 0.94, 1.00, 1.00 and 1.00, respectively, indicating the high predictive ability of this method for RA. In this study, our results indicated that a combination of serum and urine analysis can provide a more comprehensive and reliable assessment of RA, and a UPLC-MS-based lipidomics strategy is a powerful tool to search for potential lipid markers associated with RA and explore the pathogenesis of RA.


Expression of Sonic hedgehog pathway genes is altered in colonic neoplasia.
The Hedgehog (Hh) signalling pathway is crucial for normal development and patterning of numerous human organs including the gut. Hh proteins are also expressed during gastric gland development and gastric epithelial differentiation in adults. Recently, dysregulation of these developmentally important genes has been implicated in cancer, leading to the present study of the expression of Hh signalling proteins in colon cancer. In this study, normal colon and colonic lesions (hyperplastic polyp, adenoma, and colonic adenocarcinoma) were examined by immunohistochemistry using antibodies against Hh signalling molecules: the secreted protein Sonic hedgehog (SHH), its receptor Patched (PTCH), and the PTCH-associated transmembrane protein Smoothened (SMOH). The study shows that Hh signalling pathway members are expressed in normal colonic epithelium. SHH was expressed at the top of the crypts and in a few basally located cells, while PTCH was detected in the neuroendocrine cells and SMOH at the brush border of superficial epithelium. RT-PCR analysis of laser-microdissected crypts from normal human colon confirmed that mRNAs encoding these proteins were expressed in colonic epithelium. Expression of SHH, PTCH, and SMOH was up-regulated in hyperplastic polyps, adenomas, and adenocarcinomas of the colon, and SHH expression correlated with increased expression of the proliferation marker Ki-67 in all lesions examined. To address whether the Hh signalling pathway is functional in the gut, the effect of Shh on epithelial cells in vitro was explored by treating primary murine colonocytes with either Shh peptide or neutralizing anti-Shh antibody. The proportion of cells in the S-phase was assessed by bromodeoxyuridine (BrdU) incorporation. It was found that exogenous Shh promotes cell proliferation in colonocytes, while anti-Shh inhibits proliferation, suggesting that Shh is required during proliferation of epithelial cells in vitro. It is suggested that SHH is required during epithelial proliferation in the colon and that there is a possible role for Hh signalling in epithelial colon tumour progression in vivo.


Double Copies of Fermions as Matter that Interacts Only Gravitationally.
Inspired by the recent progress in the field of scattering amplitudes, we discuss hypothetical particles which can be characterized as the double copies of fermions-in the same way gravitons can be viewed as double copies of gauge bosons. As the gravitons, these hypothetical particles interact only through gravitational interactions. We present two equivalent methods for the computation of the relevant scattering amplitudes. The hypothetical particles can be massive and nonrelativistic.


Contextual Translation Embedding for Visual Relationship Detection and Scene Graph Generation.
Relations amongst entities play a central role in image understanding. Due to the complexity of modeling (subject, predicate, object) relation triplets, it is crucial to develop a method that can not only recognize seen relations, but also generalize to unseen cases. Inspired by a previously proposed visual translation embedding model, or VTransE [1] , we propose a context-augmented translation embedding model that can capture both common and rare relations. The previous VTransE model maps entities and predicates into a low-dimensional embedding vector space where the predicate is interpreted as a translation vector between the embedded features of the bounding box regions of the subject and the object. Our model additionally incorporates the contextual information captured by the bounding box of the union of the subject and the object, and learns the embeddings guided by the constraint predicate ≈ union (subject, object) - subject - object. In a comprehensive evaluation on multiple challenging benchmarks, our approach outperforms previous translation-based models and comes close to or exceeds the state of the art across a range of settings, from small-scale to large-scale datasets, from common to previously unseen relations. It also achieves promising results for the recently introduced task of scene graph generation.


A new species in the water mite subgenus Majumderatax Vidrine, 1993 from Sri Lanka (Acari: Hydrachnidia).
Majumderatax was originally established by Vidrine (1993) as a subgenus of Unionicola Haldeman, 1842 with U. hankoi Szalay, 1927 as type species. It is probably a monophyletic clade (Gerecke et al. 2016), characterized by the following features: (i) I-L-5 with a characteristic, blade-like distoventral seta, and (ii) P-5 short and stocky, with a strong, bifurcated claw.


The role of symmetry in neural networks and their Laplacian spectra.
Human and animal nervous systems constitute complexly wired networks that form the infrastructure for neural processing and integration of information. The organization of these neural networks can be analyzed using the so-called Laplacian spectrum, providing a mathematical tool to produce systems-level network fingerprints. In this article, we examine a characteristic central peak in the spectrum of neural networks, including anatomical brain network maps of the mouse, cat and macaque, as well as anatomical and functional network maps of human brain connectivity. We link the occurrence of this central peak to the level of symmetry in neural networks, an intriguing aspect of network organization resulting from network elements that exhibit similar wiring patterns. Specifically, we propose a measure to capture the global level of symmetry of a network and show that, for both empirical networks and network models, the height of the main peak in the Laplacian spectrum is strongly related to node symmetry in the underlying network. Moreover, examination of spectra of duplication-based model networks shows that neural spectra are best approximated using a trade-off between duplication and diversification. Taken together, our results facilitate a better understanding of neural network spectra and the importance of symmetry in neural networks.


Three-dimensional human placenta-like bud synthesized from induced pluripotent stem cells.
Placental dysfunction is related to the pathogenesis of preeclampsia and fetal growth restriction, but there is no effective treatment for it. Recently, various functional three-dimensional organs have been generated from human induced-pluripotent cells (iPSCs), and the transplantation of these iPSCs-derived organs has alleviated liver failure or diabetes mellitus in mouse models. Here we successfully generated a three-dimensional placental organ bud from human iPSCs. The iPSCs differentiated into various lineages of trophoblasts such as cytotrophoblast-like, syncytiotrophoblast-like, and extravillous trophoblast-like cells, forming organized layers in the bud. Placental buds were transplanted to the murine uterus, where 22% of the buds were successfully engrafted. These iPSC-derived placental organ buds could serve as a new model for the study of placental function and pathology.


[New antiepileptic drugs: new therapeutic options].
Introduction of new generation antiepileptic drugs on the French market has considerably diversified our conventional therapeutic schemes for epilepsy. New arrivals, topiramate, tiagabine and oxcarbazepine, will further amplify these changes. Compared with conventional drugs, these new products present more favorable pharmacokinetic properties, with no or very weak interactions and better tolerability, especially concerning cognition. These new agents should be used in accordance with their spectrum of activity, which depends on their mechanism of action. In add-on trials in partial epilepsy patients, all these new products have shown efficacy in partial and secondarily generalized seizures. Seizure frequency is reduced by at least 50% in 30 to 50% of the patients. Some of these drugs have a broader spectrum, also exhibiting efficacy for the different seizure types of generalized, symptomatic or idiopathic epilepsy. Gabamimetic agents may have worsening effects in some patients with generalized epilepsy, especially with absence or myoclonic seizures. The most obvious benefits, some patients become seizure-free, are obtained in patients with intermediate severity given a two-drug regimen including one of these new agents. For children progress has been less rapid but prognosis, including cognitive outcome, has been considerably improved, for example in infantile spasms with vigabatrin and in Lennox-Gastaut syndrome with lamotrigine and felbamate, the latter drug being highly toxic. For the moment in France, authorities have limited the use of all these new antiepileptic drugs to adjunctive therapy for epilepsy resistant to conventional drugs. Recent monotherapy data have however demonstrated similar efficacy and better tolerability. Once the pivotal, controlled studies have enabled regulatory approval, all these compounds will have to undergo large-scale evaluation in order to better define dosages, long-term tolerability, indications and possible contra-indications in the various epileptic syndromes, including childhood epilepsy.


Neuronal regulation of astrocyte morphology in vitro is mediated by GABAergic signaling.
The addition of isolated neurons to monolayers of cultured astrocytes induced a morphological change in the astrocytes that came into contact with the added neuronal cell bodies or neurites. The change, which included an increase in the complexity of cell shape, took at least 3 days to become detectable and was enhanced in proportion to the number of attached neurons. Astrocytes that did not make contact with any neurons had a less complex contour, comparable to those in control cultures with no neurons added. Treatment of neuron-astrocyte cocultures with a sodium channel blocker, tetrodotoxin, suppressed the neuron-induced morphological changes in astrocytes. A GABAA-receptor antagonist, bicuculline, mimicked the inhibitory effect of tetrodotoxin. In cultures without added neurons, morphological alteration of astrocytes was also observed when cultures were incubated for 1 or more days with exogenous GABA together with a GABA-uptake inhibitor, 4,5,6,7-tetrahydroisoxazolo[4,5-c]pyridin-3-ol. The effect of exogenous GABA was mimicked by treatment with a GABAA-receptor agonist, muscimol, and blocked by bicuculline treatment. These results suggest that GABA released from neurons with their activity serves as a signal from neurons to astrocytes that triggers the morphological change in astrocytes through the activation of GABAA receptors.


Thyroid hormone excess increases insulin-like growth factor I transcripts in bone marrow cell cultures: divergent effects on vertebral and femoral cell cultures.
Thyroid hormones (T3 and T4) regulate bone development, growth, and turnover. Studies have suggested that different skeletal sites respond differently to thyroid hormones. Therefore, we examined the in vitro T3 responsiveness of cells committed to the osteoblast lineage as a function of skeletal location. Bone marrow cells derived from female rat femurs and vertebrae were cultured using conditions that induce osteogenic differentiation. Cells from both sites formed mineralized bone nodules in primary and secondary culture. In femoral cultures, collagen type I (coll I) and osteocalcin (OC) messenger RNA (mRNA) levels increased from the earliest time point examined (day 3) to a maximum on day 12 and thereafter declined to undetectable levels. T3 increased both OC and coll I mRNA, resulting in a continuous expression throughout the culture period. Insulin-like growth factor I (IGF-I) gene expression was detected at very low levels by Northern analysis of femoral total RNA, and T3 only marginally enhanced IGF-I mRNA levels. In vertebral cultures, OC and coll I mRNA levels also increased with time in culture, but remained expressed throughout the culture period. OC and coll I mRNA levels were not markedly altered in response to T3. In contrast to femoral cells, IGF-I gene expression was easily visualized in Northern blots from untreated vertebral cultures and was markedly increased by the addition of T3. The continuous presence of T3 (10(-7) M) in the medium for 18 days caused a marked decrease in the number of alkaline phosphatase-positive colonies formed in femoral secondary cultures, but only a slight decrease in the number in vertebral cultures. In addition, short term (6 days) exposure to T3 (10(-7) M) at the beginning of the culture period decreased alkaline phosphatase activity in femoral cultures, but not in vertebral cultures. These findings indicate that there are skeletal site-dependent differences in the in vitro responses of cells of the osteoblastic lineage to thyroid hormone.


Discrimination between leukaemia and non-leukaemia-related chromosomal abnormalities in the patient's lymphocytes.
The inability to measure precancer-related genetic damage accurately in blood cells of patients with leukemia or lymphoma has prevented the use in such patients of available biodosimetric methods to determine prior exposure to clastogenic agents. This is because a substantial amount of disease-related genetic damage appears in the blood cells of these patients, thus masking genetic damage that may have been caused prior to the disease. We describe a new approach that may be used to measure precancer-related chromosomal aberrations in such patients by totally separating the affected T lymphocytes from the malignant B lymphocytes. The approach employs stable chromosome translocations and will detect prior exposures above the detection limit of approximately 0.05-0.1 Gy. The utility of this approach is illustrated by using blood lymphocytes from a nuclear dockyard worker who claims his B cell leukaemia was induced by work-related radiation exposures. Blood lymphocytes were obtained after diagnosis of the disease, but prior to therapy, and measurements were made of the frequency of chromosomal abnormalities in PHA-stimulated lymphocytes without prior separation of T and B cells and in T lymphocytes after complete separation from B cells using a rosetting technique. Results show that the separation of T cells prior to PHA stimulation eliminates the cancer-related chromosomal damage and thus appears to facilitate biodosimetry of pre-cancer exposures in such patients.


Chromatin binding and silencing: Two roles of the same protein Lem2.
Transcriptionally repressed chromatin localizes to specific areas within the eukaryotic nucleus and is often found at the nuclear periphery, which is thought to provide a specialized compartment for gene silencing. However, the molecular mechanisms that establish this spatial chromatin organization are still poorly understood. In our recent work (Barrales et al. 2016), we identified the nuclear envelope protein Lem2, a homolog of metazoan lamin-associated proteins (LAPs), as a relevant factor for heterochromatin silencing and perinuclear localization in the fission yeast Schizosaccharomyces pombe. Several other LAPs have previously been reported to associate with heterochromatin, and it has been proposed that this interaction might directly contribute to gene repression, perhaps through tethering via chromatin-binding domains like the LEM domain. We demonstrated that the LEM domain of Lem2 is indeed essential for centromere binding and perinuclear tethering. However, we made the surprising finding that tethering via the LEM domain is functionally independent of Lem2's role in silencing, which instead is mediated by a different part of the protein, the MSC domain. Our study demonstrates that tethering and silencing, although mediated by the same molecule, Lem2, can be mechanistically separated. This further unveils a complex function of this protein at the interface between the nuclear periphery and silent chromatin, which might be preserved among the other members of this conserved family of LEM proteins.


Integrative Frequency Power of EEG Correlates with Progression of Mild Cognitive Impairment to Dementia in Parkinson's Disease.
Clinically, predicting the progression of mild cognitive impairment (MCI) and diagnosing dementia in Parkinson's disease (PD) are difficult. This study aims to explore an integrative electroencephalography (EEG) frequency power that could be used to predict the progression of MCI in PD patients. Twenty-six PD patients, in this study, were divided into the mild cognitive impairment group (PDMCI, 17 patients) and dementia group (PDD, 9 patients) according to cognitive performance. Beta peak frequency, alpha relative power, and alpha/theta power were recorded and analyzed for the prediction. Mini Mental State Examination (MMSE) scores at initiation, in the first year, and in the second year were examined. The sensitivity, specificity, positive predictive value, Matthew correlation coefficient, and positive likelihood ratio were calculated in both the integrative EEG biomarkers and single best biomarker. Of the 17 patients with MCI for 2 years, 6 progressed to dementia. Integrative EEG biomarkers, mainly associated with beta peak frequency, can predict conversion from MCI to dementia. These biomarkers had sensitivity of 82% and specificity of 78%, compared with sensitivity of 61% and specificity of 58% of the beta peak frequency. In conclusion, the integrative EEG frequency powers were more sensitive and specific to MCI progression in PD patients.


Quality assurance in radiation therapy: clinical and physical aspects. Quality assurance: past and present in Canada.
Quality assurance in any clinical field must involve the three components of clinical care: (a) diagnosis and evaluation of patients; (b) medical decision making and treatment; and (c) outcome analysis. Nationally, there have been five annual reviews of outcome from all cancer centers following radiation therapy for cancer at various sites. These reviews are voluntary and organized through the Canadian Association of Radiologists. The objective is to determine if there are any major differences in outcome across the country, and if so, can such differences be related to the population treated or technique used. So far no major differences have been noted, although the reviews have led to improved communication between centers and constructive discussions of dose and technique. There is a National Tumour Reference Centre funded by the National Cancer Institute of Canada (NCIC) to provide assistance in establishing diagnostic criteria in pathology. Ontario has been active through the Ontario Cancer Treatment & Research Foundation and the Ontario Cancer Institute in establishing UICC TNM staging and reporting, together with an evaluative program for this staging system. All other quality assurance programs take place at the level of local centers.


Inactivation of the Lactobacillus leichmannii ribonucleoside triphosphate reductase by 2'-chloro-2'-deoxyuridine 5'-triphosphate: stoichiometry of inactivation, site of inactivation, and mechanism of the protein chromophore formation.
The ribonucleoside triphosphate reductase (RTPR) of Lactobacillus leichmannii is inactivated by the substrate analogue 2'-chloro-2'-deoxyuridine 5'-triphosphate (ClUTP). Inactivation is due to alkylation by 2-methylene-3(2H)-furanone, a decomposition product of the enzymic product 3'-keto-2'-deoxyuridine triphosphate. The former has been unambiguously identified as 2-[(ethylthio)methyl]-3(2H)-furanone, an ethanethiol trapped adduct, which is identical by 1H NMR spectroscopy with material synthesized chemically. Subsequent to rapid inactivation, a slow process occurs that results in formation of a new protein-associated chromophore absorbing maximally near 320 nm. The terminal stages of the inactivation have now been investigated in detail. The alkylation and inactivation stoichiometries were studied as a function of the ratio of ClUTP to enzyme. At high enzyme concentrations (0.1 mM), 1 equiv of [5'-3H]ClUTP resulted in 0.9 equiv of 3H bound to protein and 83% inactivation. The amount of labeling of RTPR increased with increasing ClUTP concentration up to the maximum of approximately 4 labels/RTPR, yet the degree of inactivation did not increase proportionally. This suggests that (1) RTPR may be inactivated by alkylation of a single site and (2) decomposition of 3'-keto-dUTP is not necessarily enzyme catalyzed. The formation of the new protein chromophore was also monitored during inactivation and found to reach its full extent upon the first alkylation. Thus, out of four alkylation sites, only one appears capable of undergoing the subsequent reaction to form the new chromophore. While chromophore formation was prevented by NaBH4 treatment, the chromophore itself is resistant to reduction.(ABSTRACT TRUNCATED AT 250 WORDS)


The chemokine system: a possible therapeutic target in acute graft versus host disease.
Allogeneic hematopoetic stem cell transplantation often presents the only chance for cure in a number of malignant and nonmalignant hematologic diseases. However, its beneficial effects are counterweighed by the development of potentially lethal complications, most importantly the development of acute and chronic graft-vs.-host disease (GVHD). Alloantigen-reactive immune responses mediate injury and destruction of GVHD target organs, including the gastrointestinal tract, the liver, the skin, and the lung. Donor leukocyte infiltration into the respective tissues is orchestrated by interactions between chemokines and chemokine receptors, which will be reviewed using a basic science - clinical comparative approach.


Effect of treatment with interferon alpha-2b and ribavirin in patients infected with genotype 2 hepatitis C virus.
Nearly 20% of chronic hepatitis C (CHC) patients with genotype 2 hepatitis C virus (HCV) infection are not curable, even by interferon (IFN)-ribavirin combination therapy. The aim of this study is to investigate the factors that determine the efficacy of combination therapy in patients with genotype 2 HCV infection. Fifty patients with CHC who underwent a treatment of 6 MU IFN alpha-2b with ribavirin for 24 weeks were retrospectively analyzed. All the patients showed no serum HCV-RNA within 12 weeks after starting the therapy. Forty-one of the 50 patients (82%) achieved a sustained virological response (SVR). The age, sex, genotype (2a vs. 2b) and grade/stage of the liver by histopathology and pretreatment viral load werenot different between the sustained responders and relapsers. Univariate analysis showed that an earlier viral clearance from blood and a larger number of amino acid substitutions in the interferon sensitivity determining region (ISDR) were predictors of SVR. Multivariate analysis showed that a large number of amino acid substitutions in the ISDR was a predictor of SVR. The characterization of the amino acid sequences of ISDR may be helpful for predicting a relapse after combination therapy in patients with genotype 2 HCV infection.


Extending insulin action in vivo by conjugation to carboxymethyl dextran.
The biochemical and pharmacological properties of bioactive peptides and proteins can be altered by conjugation with polymers. This report describes site-specific attachment of insulin to activated carboxyl groups of carboxymethyl dextran (CMD, MW=51000) through the GlyA1 insulin amino group. On average, three or four insulin molecules were grafted to a CMD linear chain. Coupled insulin molecules were properly folded, and the bioactivity of conjugated insulin in the blood glucose depression assay was 9.6 IU/mg, which was only 2.6 times less than that for native insulin. The cell growth study indicated that the CMD-insulin conjugate was as mitogenic as insulin on vascular smooth muscle cells, whereas the starting CMD polymer was not. The insulin receptor binding constant of the conjugate (3.6 x 10[9] M[-1]) compared well with that of native insulin (7.6 x 10[9] M[-1]), indicating that the CMD chain does not present any major constraints to binding. Plasma clearance of CMD-insulin obeyed a two-compartment pharmacokinetic (PK) model with a CMD-insulin conjugate plasma elimination half-life of 114.1 min, which was significantly longer than that of soluble Zn-insulin (12.4 min). In contrast, pharmacodynamic (PD) profiles (blood glucose lowering effects) after intravenous (iv) administration of the conjugate or insulin in rats were not different. Subcutaneous (sc) administration of the conjugate resulted in a significantly prolonged plasma profile with a noncompartmental PK parameter mean residence time (MRT) of 103.5 min which was significantly longer than that of soluble Zn-insulin (40.5 min). This was reflected in the protracted PD effect of sc administered conjugate with time needed to reach minimum glucose concentration Tnadir of 95.7 min, which was significantly longer than that of insulin (62 min). We conclude that the conjugation of insulin to CMD leads to a bioactive conjugate with a delayed sc PD profile showing prolonged response, resembling intermediate acting insulin preparations.


Use of MAG1 recombinant antigen for diagnosis of Toxoplasma gondii infection in humans.
This paper describes the cloning, purification, and serological applications of matrix antigen MAG1 of Toxoplasma gondii. The expression system used allows the production of a large amount of T. gondii recombinant protein, which was assessed for its potential use in an enzyme-linked immunosorbent assay (ELISA) for detection of T. gondii infection in humans. Serum samples from 117 patients with different stages of infection, along with 10 serum samples from seronegative patients obtained for routine diagnostic tests, were used. The results were compared with those of an ELISA that uses a native T. gondii antigen extract. The MAG1 antigen detected antibodies more frequently from the acute stage (97.3%) than from the chronic stage (7.5%) of toxoplasmosis. Hence, this antigen may be used as a tool for detection of T. gondii immunoglobulin G antibodies in persons with acute toxoplasmosis.


Adenine crosses the biomarker bridge: from 'omics to treatment in diabetic kidney disease.
Enabling the early detection and prevention of diabetic kidney damage has potential to substantially reduce the global burden of kidney failure. There is a critical need for identification of mechanistic biomarkers that can predict progression and serve as therapeutic targets. In this issue of the JCI, Sharma and colleagues used an integrated multiomics approach to identify the metabolite adenine as a noninvasive biomarker of progression in early diabetic kidney disease (DKD). The highest tertile of urine adenine/creatinine ratio (UAdCR) was associated with higher risk for end-stage kidney disease and mortality across independent cohorts, including participants with early DKD without macroalbuminuria. Spatial metabolomics, single-cell transcriptomics, and experimental studies localized adenine to regions of tubular pathology and implicated the mTOR pathway in adenine-mediated tissue fibrosis. Inhibition of endogenous adenine production was protective in a diabetic model. These findings exemplify the potential for multiomics to uncover mechanistic biomarkers and targeted therapies in DKD.


The lollipop with strawberry aroma may be promising in reduction of infusion-related nausea and vomiting during the infusion of cryopreserved peripheral blood stem cells.
Nausea and vomiting during the infusion of cryopreserved peripheral blood stem cells (PBSC) are common. The aim of this study was to explore the effect of lollipop with strawberry aroma on the infusion-related nausea and vomiting of cryopreserved autologous PBSCs. We compared 2 groups of adult patients receiving lollipop with strawberry aroma during cryopreserved PBSC infusions or not to assess the incidences of nausea and vomiting occurring during infusions. All patients received granisetron 3 mg i.v. twice a day, and lorazepam 1 mg every 4 hours orally for prophylaxis of the nausea and vomiting during conditioning phase and infusion day. Before infusion, all patients were premedicated with pheniramine maleate 45.5 mg i.v. and paracetamol 500 mg orally. The patients had no evidence of nausea or vomiting prior to cryopreserved PBSC infusions. The patients with ongoing nausea or vomiting owing to conditioning regimens and/or receiving additional antiemetics were excluded from the study. One hundred fifty-eight patients who consecutively underwent autologous stem cell transplantation for malignancy were included in the study. The first 110 patients (median age: 42.5, range: 17-75) were observed for the infusion related adverse effects only. The consecutive 48 patients (median age: 48, range: 18-80) were given a lollipop with strawberry aroma during cryopreserved PBSC infusions and observed for the infusion-related adverse effects. The 2 groups were comparable with respect to age, sex, diagnosis, stem cell collection methods, conditioning regimens administered, total mononuclear cell dose infused, number of total nucleated cells (TNCs) infused, number of CD34+ cells infused, number of bags infused, total volume infused, amount of dimethylsulfoxide (DMSO), and infusion rate. Patients who received a lollipop with a strawberry aroma during infusions had significantly less nausea (6.3%, n = 3 versus 21.8%, n = 24, P = .02) and vomiting (2%, n = 1 versus 13.6%, n = 15, P = .04) than the ones who did not (observation only group). Other infusion-related adverse events were as follows; hypoxia, cough, dyspnea, abdominal cramping, tachycardia, hiccup, fever, chills, chest pain, hypotension, hypertension, agitation, sore throat, and arrhythmia. Incidences of each of these adverse events were <5% in both groups and were comparable. The use of a lollipop with a strawberry aroma during infusion of cryopreserved autologous PBSCs may be promising in reduction of infusion-related nausea and vomiting, with an easy administration at a very cheap cost.


Glycolysis and Flux Control.
Central metabolism of carbohydrates uses the Embden-Meyerhof-Parnas (EMP), pentose phosphate (PP), and Entner-Doudoroff (ED) pathways. This review reviews the biological roles of the enzymes and genes of these three pathways of E. coli. Glucose, pentoses, and gluconate are primarily discussed as the initial substrates of the three pathways, respectively. The genetic and allosteric regulatory mechanisms of glycolysis and the factors that affect metabolic flux through the pathways are considered here. Despite the fact that a lot of information on each of the reaction steps has been accumulated over the years for E. coli, surprisingly little quantitative information has been integrated to analyze glycolysis as a system. Therefore, the review presents a detailed description of each of the catalytic steps by a systemic approach. It considers both structural and kinetic aspects. Models that include kinetic information of the reaction steps will always contain the reaction stoichiometry and therefore follow the structural constraints, but in addition to these also kinetic rate laws must be fulfilled. The kinetic information obtained on isolated enzymes can be integrated using computer models to simulate behavior of the reaction network formed by these enzymes. Successful examples of such approaches are the modeling of glycolysis in S. cerevisiae, the parasite Trypanosoma brucei, and the red blood cell. With the rapid developments in the field of Systems Biology many new methods have been and will be developed, for experimental and theoretical approaches, and the authors expect that these will be applied to E. coli glycolysis in the near future.


Memantine prevents memory consolidation failure induced by soluble beta amyloid in rats.
It has been well documented that β-amyloid (Aβ) peptide accumulation and aggregation in the brain plays a crucial role in the pathophysiology of Alzheimer's disease (AD). However, a new orientation of the amyloid cascade hypothesis has evidenced that soluble forms of the peptide (sAβ) are involved in Aβ-induced cognitive impairment and cause rapid disruption of the synaptic mechanisms underlying memory. The primary aim of this study was to elucidate the effects of sAβ, acutely injected intracerebrally (i.c.v., 4 μM), on the short term and long term memory of young adult male rats, by using the novel object recognition task. Glutamatergic receptors have been proposed as mediating the effect of Aβ on synaptic plasticity and memory. Thus, we also investigated the effects of sAβ on prefrontal cortex (PFC) glutamate release and the specific contribution of N-methyl-D-aspartate (NMDA) receptor modulation to the effects of sAβ administration on the cognitive parameters evaluated. We found that a single i.c.v. injection of sAβ 2 h before testing did not alter the ability of rats to differentiate between a familiar and a novel object, in a short term memory test, while it was able to negatively affect consolidation/retrieval of long term memory. Moreover, a significant increase of glutamate levels was found in PFC of rats treated with the peptide 2 h earlier. Interestingly, memory deficit induced by sAβ was reversed by a NMDA-receptor antagonist, memantine (5 mg/kg i.p), administered immediately after the familiarization trial (T1). On the contrary, memantine administered 30 min before T1 trial, was not able to rescue long term memory impairment. Taken together, our results suggest that an acute i.c.v. injection of sAβ peptide interferes with the consolidation/retrieval of long term memory. Moreover, such sAβ-induced effect indicates the involvement of glutamatergic system, proposing that NMDA receptor inhibition might prevent or lead to the recovery of early cognitive impairment.


Genetic analysis of the forkhead transcriptional factor 2 gene in three Chinese families with blepharophimosis syndrome.
Clinically, blepharophimosis syndrome (BPES) has been divided into two subsets according to the association of ocular malformation with (type I) or without (type II) premature ovarian failure (POF). BPES is ascribed to mutations in the forkhead transcriptional factor 2 (FOXL2) gene. This study aimed at identifying clinical features and mutations within the FOXL2 gene in three Chinese families with BPES. A clinical and molecular genetic investigation was performed in affected and unaffected members from three Chinese families with BPES. Genomic DNA was prepared from leucocytes of peripheral venous blood, the entire coding region of FOXL2 were amplified with PCR, and direct DNA sequencing of the PCR products was performed for mutations in FOXL2. Three mutations in FOXL2 were found in three families, including c.672_701dup30, c.663_692dup30, and c.475dupC. Of the three, the c.475dupC (p.His159fs) was novel in family C and resulted in a frameshift mutation to generate a truncated protein owing to a premature stop codon at codon 238. The new duplication mutation was associated with BPES type II. The c.672_701dup30 (p.Ala224_Ala234dup10) and the c.663_692dup30 (p.Ala221_Ala231dup10) were detected in family A and family B, respectively, leading to expansions of the polyalanine (poly-Ala) tract that is frequently the hot spot of mutations within FOXL2. Our results expand the spectrum of FOXL2 mutations, and further indicate the association of a novel duplication mutation leading to a truncated protein with BPES type II. The other two known mutations may support the previous hypothesis regarding expansions of the polyalanine tract associated with BPES type II as a mutational hot spot in FOXL2.


Correction: Giant vesicles from rehydrated crude mixtures containing unexpected mixtures of amphiphiles formed under plausibly prebiotic conditions.
Correction for 'Giant vesicles from rehydrated crude mixtures containing unexpected mixtures of amphiphiles formed under plausibly prebiotic conditions' by Michele Fiore et al., Org. Biomol. Chem., 2017, 15, 4231-4240.


Pressure ulcers in older persons: a preventive approach.
Strategies for the prevention of pressure ulcers are presented on the basis of the Agency for Health Care Policy and Research guidelines. A broad, holistic approach to care of the elderly, focusing on rehabilitative and restorative measures is introduced. Topics include the effects of bed rest and deconditioning, nutrition, and mobility issues. A broad approach to care, involving the expertise of multiple disciplines, is advocated.


Leveraging linkage evidence to identify low-frequency and rare variants on 16p13 associated with blood pressure using TOPMed whole genome sequencing data.
In this study, we investigated low-frequency and rare variants associated with blood pressure (BP) by focusing on a linkage region on chromosome 16p13. We used whole genome sequencing (WGS) data obtained through the NHLBI Trans-Omics for Precision Medicine (TOPMed) program on 395 Cleveland Family Study (CFS) European Americans (CFS-EA). By analyzing functional coding variants and non-coding rare variants with CADD score > 10 residing within the chromosomal region in families with linkage evidence, we observed 25 genes with nominal statistical evidence (burden or SKAT p < 0.05). One of the genes is RBFOX1, an evolutionarily conserved RNA-binding protein that regulates tissue-specific alternative splicing that we previously reported to be associated with BP using exome array data in CFS. After follow-up analysis of the 25 genes in ten independent TOPMed studies with individuals of European, African, and East Asian ancestry, and Hispanics (N = 29,988), we identified variants in SLX4 (p = 2.19 × 10-4) to be significantly associated with BP traits when accounting for multiple testing. We also replicated the associations previously reported for RBFOX1 (p = 0.007). Follow-up analysis with GTEx eQTL data shows SLX4 variants are associated with gene expression in coronary artery, multiple brain tissues, and right atrial appendage of the heart. Our study demonstrates that linkage analysis of family data can provide an efficient approach for detecting rare variants associated with complex traits in WGS data.


Sensor-Augmented Insulin Pumps and Hypoglycemia Prevention in Type 1 Diabetes.
Hypoglycemia can lead to seizures, unconsciousness, or death. Insulin pump treatment reduces the frequency of severe hypoglycemia compared with multiple daily injections treatment. The addition of a continuous glucose monitor, so-called sensor-augmented pump (SAP) treatment, has the potential to further limit the duration and severity of hypoglycemia as the system can detect and in some systems act on impending and prevailing low blood glucose levels. In this narrative review we summarize the available knowledge on SAPs with and without automated insulin suspension, in relation to hypoglycemia prevention. We present evidence from randomized trials, observational studies, and meta-analyses including nonpregnant individuals with type 1 diabetes mellitus. We also outline concerns regarding SAPs with and without automated insulin suspension. There is evidence that SAP treatment reduces episodes of moderate and severe hypoglycemia compared with multiple daily injections plus self-monitoring of blood glucose. There is some evidence that SAPs both with and without automated suspension reduces the frequency of severe hypoglycemic events compared with insulin pumps without continuous glucose monitoring.


[Research of anti-proliferation of curcumin on A549 human lung cancer cells and its mechanism].
To investigate the mechanism of anti-tumor effects of curcumin on human lung cancer cell (A549). MTT colorimetry method, fluoroscope, FCM combine PI and Annexin V-FITC double pigmentation method and Western blot method were used. Under the effect of the curcumin, cell grew against the wall and suspended in the culture liquid, the A549 cell nucleolus were found fragmentated into different size of apoptosis body under fluoroscopy. The cell proliferation were obvious suppressed after treated with different concentration curcumin for 72 hours. The IC50 were 18 micromol/L by using linear regression. The apoptosis induced by curcumin of A549 cell is concentration dependent. With curcumin increased from 5 micromol/L to 30 micromol/L, Annexin-FITC single positive cell (early apoptosis cell) increased from 3.4% to 59.1%. When curcumin concentration reached 40 micromol/L, PI and Annexin V-FITC double positive cell (secondary apoptosis necrosis cell) became major part of cells, and the cell showed G2 phase block. Observed with western blot method, with the increase of curcumin concentration to 10 micromol/L, the expression of PARP increased simultaneously. Curcumin can interfere cell growth cycle of A549 cell and suppress cell growth. The suppression effect is concentration dependent. The effect depends not only from the nonspecific cytotoxic but also from induced cell apoptosis.


Dose to radiation therapists from activation at high-energy accelerators used for conventional and intensity-modulated radiation therapy.
The increased beam-on times which characterize intensity-modulated radiation therapy (IMRT) could lead to an increase in the dose received by radiation therapists due to induced activity. To examine this, gamma ray spectrometry was used to identify the major isotopes responsible for activation at a representative location in the treatment room of an 18 MV accelerator (Varian Clinac 21EX). These were found to be 28Al, 56Mn, and 24Na. The decay of the dose rate measured at this location following irradiation was analyzed in terms of the known half-lives to yield saturation dose rates of 9.6, 12.4, and 6.2 microSv/h, respectively. A formalism was developed to estimate activation dose (microSv/week) due to successive patient irradiation cycles, characterized by the number of 18 MV fractions per week, F, the number of MU per fraction, M, the in-room time between fractions, td (min), and the treatment delivery time t'r (min). The results are represented by the sum of two formulas, one for the dose from 28Al 1.8 x 10(-3) F M (1-e(-03t'(r))/t'r and one for the dose from the other isotopes approximately 1.1 x 10(-6) F(1.7) Mt(d). For conventional therapy doses are about 60 microSv/week for an 18 MV workload of 60,000 MU/week. Irradiation for QA purposes can significantly increase the dose. For IMRT as currently practiced, lengthy treatment delivery times limit the number of fractions that can be delivered per week and hence limit the dose to values similar to those in conventional therapy. However for an IMRT regime designed to maximize patient throughput, doses up to 330 microSv/week could be expected. To reduce dose it is recommended that IMRT treatments should be delivered at energies lower than 18 MV, that in multienergy IMRT, high-energy treatments should be scheduled in the latter part of the day, and that equipment manufacturers should strive to minimize activation in the design of high-energy accelerators.


Pentachloro-1,3,6-tris(diethylphenylphosphino)dirhenium(II,III).
The title complex [systematic name: pentachloro-1kappa(3)Cl,2kappa(2)Cl-tris(diethylphenylphosphino)-1kappaP,2kappa(2)P-dirhenium(II,III)(Re-Re)], 1,3,6-Re(2)Cl(5)(PEt(2)Ph)(3) or [Re(2)Cl(5)(C(10)H(15)P)(3)], consists of dirhenium molecules with eclipsed structures similar to those of previously characterized 1,3,6-Re(2)Cl(5)(PR(3))(3) compounds. The Re-Re bond distance is 2.2262 (3) A and the metal-metal bond order is 3.5.


[Chronic obstructive pulmonary disease. Admission, course and prognosis].
The aim of this study was to describe the prognosis after hospitalization after exacerbation of chronic obstructive pulmonary disease (COPD). A retrospective study of 300 consecutively admitted patients with exacerbation of COPD in three departments of internal medicine with special interest in respiratory medicine. Data were collected from patient charts. The mean age was 71.3 years. 59.7% were women and 60.9% had cor pulmonale. In 44% of the patients hypoxia was documented at the time of admission. Twentysix(9%) patients died during hospitalization. After three and 12 months mortality was 19% and 36%, respectively. Age, cor pulmonale and hypoxia at the time of admission were associated with increased mortality, whereas impaired lung function, long term oxygen treatment, and a record of hospitalization with the same diagnosis in the previous 30 days were associated with increased mortality in univariate analysis, but not when adjusted for age, gender, and hypoxia at admission. The risk of readmission was increased in cor pulmonale, while cessation of smoking during hospitalization reduced this risk. Patients who have been hospitalized with exacerbation of COPD has a high mortality and a high risk of readmission.


Widely-tunable, passively Q-switched erbium-doped fiber laser with few-layer MoS2 saturable absorber.
We propose and demonstrate a MoS2-based passively Q-switched Er-doped fiber laser with a wide tuning range of 1519.6-1567.7 nm. The few-layer MoS2 nano-platelets are prepared by the liquid-phase exfoliation method, and are then made into polymer-composite film to construct the fiber-compatible MoS2 saturable absorber (SA). It is measured at 1560 nm wavelength, that such MoS2 SA has the modulation depth of ∼ 2% and the saturable optical intensity of ∼ 10 MW/cm(2). By further inserting the filmy MoS2-SA into an Er-doped fiber laser, stable Q-switching operation with a 48.1 nm continuous tuning from S- to C-waveband is successfully achieved. The shortest pulse duration and the maximum pulse energy are 3.3 μs and 160 nJ, respectively. The repetition rate and the pulse duration under different operation conditions have been also characterized. To the best of our knowledge, it is the first demonstration of MoS2 Q-switched, widely-tunable fiber laser.


[Dermatological manifestations in the antiphospholipid syndrome].
Antiphospholipid syndrome is regarded as a systemic disease. A total of 41% of the patients are presented with one form of the diverse skin findings at diagnosis. Due to the high prevalence of skin affliction it was recently suggested to include this syndrome in the diagnostic criteria of APS. The importance of these findings also entails the fact that in 25% of the patients the skin manifestations precede thromboembolic phenomena. The findings entail livedo reticularis, anetoderma, skin necrosis and others. This article discusses their prevalence and their relationships to other clinical manifestations in APS and how to approach them therapeutically.


Regulation of endothelial barrier function by reactive oxygen and nitrogen species.
Excessive generation of reactive oxygen species (ROS) and reactive nitrogen species (RNS), by activated neutrophils and endothelial cells, has been implicated in the pathophysiology of endothelial barrier dysfunction. Disruption of the integrity of this barrier markedly increases permeability to fluids, solutes and inflammatory cells and is the hallmark of many disorders such as acute lung injury (ALI) and sepsis. There has been considerable progress in our understanding of the sequence of molecular and structural events that mediate the response of endothelial cells to oxidants and nitrosants. In addition, substantial experimental evidence demonstrates improvement of endothelial barrier dysfunction with antioxidant strategies. However, no significant benefits have been observed, so far, in clinical trials of antioxidants for the treatment of endothelial barrier dysfunction. This article will review the available evidence implicating ROS and RNS in endothelial barrier dysfunction, explore potential underlying mechanisms, and identify areas of further research.


[Treatment of infected tibial fractures and pseudarthrosis using an external fixator].
The clinical course and the results of our treatment of 18 patients with External Fixator after infection or pseudarthrosis are demonstrated. On an average of 6.1 months the patients wore the external fixator, the time of consolidation of the fracture was 17.2 months from the accident. At the date of examination - 16 months to 10 years after removal the external fixator all fractures and pseudarthroses were united. Two patients still had a fistula three years after removal of the external fixator. Three patients had slight pain in the area of the former fracture or the complication-wound; disturbance of sensibility in the area of the scar and the meshgrafts were found at 11 patients. The mobility of the knee joint was nearly free in all patients, the mobility of the ankle joint was impaired in most of them.


Epidermal growth factor (EGF) in human preovulatory follicles.
Concentrations of epidermal growth factor (EGF), progesterone (P4) and oestradiol (E2) were determined in follicular fluid (FF) aspirated from 69 preovulatory follicles in 15 women undergoing ovarian hyperstimulation and ovulation induction as part of IVF-ET treatment for infertility. Sixty-nine oocytes were obtained from these FF aspirates and 35 (51%) fertilized and cleaved in vitro. Pregnancy was achieved in five (33%) of the women. Concentrations of EGF in FF ranged between 0.60 and 2.42 ng/ml, corresponding to approximately 50% of the level in serum at the time of follicle aspiration. A significant linear correlation between levels of EGF in FF and in serum was demonstrated. By contrast, no significant relationships were found between intrafollicular levels of EGF and those of P4 and E2, or between EGF in FF and oocyte cleavage rate in vitro and the achievement of pregnancy after ET. It is concluded that EGF in FF of the human preovulatory follicles reflects a passive diffusion into the follicle from the circulation. Moreover, that intrafollicular EGF is not involved in the local regulation of human preovulatory follicle and oocyte maturation. These results, however, do not preclude an auto- and/or paracrine role of intrafollicular EGF in smaller human follicles.


Beta-haemolytic group A, B, C and G streptococcal septicaemia: a clinical study.
87 beta-haemolytic streptococcal septicaemias in adult patients during 1979-86 in a university hospital were reviewed. 25% were caused by group A streptococcus, 17% by group B, 14% by group C and 44% by group G streptococcus. 67% of the septicaemias due to group B streptococcus were nosocomial, whereas the group A, C or G septicaemias were in most cases community-acquired. Alcoholism was the most common underlying disease in group A (32%) and malignancy in group G streptococcal septicaemias (45%). The most common origin and focus of infection in group A, C and G streptococcal septicaemias was the skin. The total mortality in beta-haemolytic streptococcal septicaemias was 20%, higher in septicaemias caused by group A (32%) and group B (33%) than by group C (17%) and group G (8%) streptococci. Nevertheless, there were more patients in group G streptococcal septicaemias with severe underlying diseases than in other groups of beta-haemolytic streptococci. The present data seem to indicate that a septicaemia due to group G is a more benign disease than a septicaemia due to group A streptococcus.


Effect of Xianling Gubao capsules on bone mineral density in osteoporosis patients.
This paper aimed to analyze the clinical effects of Xianling Gubao capsules on the bone mineral density (BMD) of 94 patients with osteoporosis. After reviewing and analyzing the clinical information in our hospital from January 2015 to January 2016, the patients were divided into a control group and a treatment group with 47 cases in each group. Patients in the control group were treated with routine Western medicine, while the treatment group received Xianling Gubao capsules. Both groups were treated continuously for 3 courses (30 days each course) and had their BMD analyzed and compared. The effective rates of the treatment group and control group were 91.48% and 70.21%, respectively, with statistical significance (P less than 0.05). Compared with the same group before the treatment, the bone metabolic indexes (blood calcium, phosphorus, and alkaline phosphate) and the BMD of the femoral neck and lumbar vertebrae (L1-2, L3-4, L2-4) of both groups were all improved with statistical significance (P less than 0.05) after the treatment. The above indexes of the treatment group were all significantly higher than those of the control group, with statistical significance (P less than 0.05). Compared with the same group before treatment (P less than 0.05), the osteocalcin (OC) levels of both groups were increased, and the Cross-linked N-telopeptide of type 1 collagen (CTX-1) levels were decreased after the treatment. The OC level in the treatment group was higher when compared with the control group, while the CTX-1 level was lower compared to the control group (P less than 0.05). Moreover, no significant side-effects or adverse events were observed during the treatment and observation period. The Xianling Gubao Capsule possesses a therapeutic effect for BMD in osteoporosis patients, which can effectively increase their BMD, improve their bone metabolism, and control the loss of bone mass, therefore, can be used in clinical promotion and application.


Significance of Energy Conservation in Coupled-Trajectory Approaches to Nonadiabatic Dynamics.
Through approximating electron-nuclear correlation terms in the exact factorization approach, trajectory-based methods have been derived and successfully applied to the dynamics of a variety of light-induced molecular processes, capturing quantum (de)coherence effects rigorously. These terms account for the coupling among the trajectories, recovering the nonlocal nature of quantum nuclear dynamics that is completely overlooked in traditional independent-trajectory algorithms. Nevertheless, some of the approximations introduced in the derivation of some of these methods do not conserve the total energy. We analyze energy conservation in the coupled-trajectory mixed quantum-classical (CTMQC) algorithm and explore the performance of a modified algorithm, CTMQC-E, where some of the terms are redefined to restore energy conservation. A set of molecular models is used as a test, namely, 2-cis-penta-2,4-dienimium cation, bis(methylene) adamantyl radical cation, butatriene cation, uracil radical cation, and neutral pyrazine.


Effect of unilateral vagus blockade on antigen-induced airway obstruction.
Respiratory hypersensitivity and the effect of unilateral vagus blockade on the same, after the use of Ascaris extract aerosol, are studied in three boxer dogs with spontaneous reactivity to this aerosol. The dogs were exposed initially to Ascaris extract aerosol, and this exposure was repeated after unilateral vagus blockade and after its lavage. The principal parameters, deltaPoes (mm Hg)/100 ml TV, are given as a measurement of airway flow resistance and respiratory rates. The spontaneous respiratory distress observed in all the animals after exposure to the mentioned aerosol was avoided with unilateral blockade of the nervus vagus.


Polyphosphazenes as tunable and recyclable supports to immobilize alcohol dehydrogenases and lipases: synthesis, catalytic activity, and recycling efficiency.
The polyphosphazene {NP[O(2)C(12)H(7.5)(NH(2))(0.5)]}(n), prepared by reacting {NP[O(2)C(12)H(7.5)(NO(2))(0.5)]} with the Lalancette's reagent, was used for attaching enzymes such as alcohol dehydrogenase (ADH-A) and lipase (CAL-B). The resulting new biocatalysts exhibited great potential as tunable supports for enzymatic reactions in both aqueous and organic media. The material with immobilized ADH-A was as efficient as the commercial enzyme to perform stereoselective bioreductions of ketones in aqueous solutions and could be used for the reduction of various aliphatic and aromatic ketones up to 60 degrees C and recycled several times without significant loss of activity even after three months of storage. The biocatalyst obtained with CAL-B was more efficient than the free enzyme for kinetic resolutions in organic solvents and exhibited a moderately good capability of reutilization.


Co-delivery of evodiamine and rutaecarpine in a microemulsion-based hyaluronic acid hydrogel for enhanced analgesic effects on mouse pain models.
The aim of this study was to improve the analgesic effect of evodiamine and rutaecarpine, using a microemulsion-based hydrogel (ME-Gel) as the transdermal co-delivery vehicle, and to assess hyaluronic acid as a hydrogel matrix for microemulsion entrapment. A microemulsion was formulated with ethyl oleate as the oil core to improve the solubility of the alkaloids and was loaded into a hyaluronic acid-structured hydrogel. Permeation-enhancing effects of the microemulsion enabled evodiamine and rutaecarpine in ME-Gel to achieve 2.60- and 2.59-fold higher transdermal fluxes compared with hydrogel control (p<0.01). The hyaluronic acid hydrogel-containing microemulsion exhibited good skin biocompatibility, whereas effective ME-Gel co-delivery of evodiamine and rutaecarpine through the skin enhanced the analgesic effect in mouse pain models compared with hydrogel. Notably, evodiamine and rutaecarpine administered using ME-Gel effectively down-regulated serum levels of prostaglandin E2, interleukin 6, and tumor necrosis factor α in formaldehyde-induced mouse pain models, possibly reflecting the improved transdermal permeability of ME-Gel co-delivered evodiamine and rutaecarpine, particularly with hyaluronic acid as the hydrogel matrix.


Investigations into the origin of the molecular recognition of several adenosine deaminase inhibitors.
Inhibitors of adenosine deaminase (ADA, EC 126.96.36.199) are potential therapeutic agents for the treatment of various health disorders. Several highly potent inhibitors were previously identified, yet they exhibit unacceptable toxicities. We performed a SAR study involving a series of C2 or C8 substituted purine-riboside analogues with a view to discover less potent inhibitors with a lesser toxicity. We found that any substitution at C8 position of nebularine resulted in total loss of activity toward calf intestinal ADA. However, several 2-substituted-adenosine, 8-aza-adenosine, and nebularine analogues exhibited inhibitory activity. Specifically, 2-Cl-purine riboside, 8-aza-2-thiohexyl adenosine, 2-thiohexyl adenosine, and 2-MeS-purine riboside were found to be competitive inhibitors of ADA with K(i) values of 25, 22, 6, and 3 μM, respectively. We concluded that electronic parameters are not major recognition determinants of ADA but rather steric parameters. A C2 substituent which fits ADA hydrophobic pocket and improves H-bonding with the enzyme makes a good inhibitor. In addition, a gg rotamer about C4'-C5' bond is apparently an important recognition determinant.


Actin dynamics at sites of extracellular matrix degradation.
The degradation of extracellular matrix (ECM) by proteases is crucial in physiological and pathological cell invasion alike. In vitro, degradation occurs at specific sites where invasive cells make contact with the ECM via specialized plasma membrane protrusions termed invadopodia. Here we present an extensive morpho-functional analysis of invadopodia actively engaged in ECM degradation and show that they are actin comet-based structures, not unlike the well-known bacteria-propelling actin tails. The relative mapping of the basic molecular components of invadopodia to actin tails is also provided. Finally, a live-imaging analysis of invadopodia highlights the intrinsic long-term stability of the structures coupled to a highly dynamic actin turnover. The results offer new insight into the tight coordination between signalling, actin remodelling and trafficking activities occurring at sites of focalized ECM degradation by invadopodia. In conclusion, invadopodia-associated actin comets are a striking example of consistently arising, spontaneous expression of actin-driven propulsion events that also represent a valuable experimental paradigm.


Arthroscopic removal of osteochondral fragments from the proximal interphalangeal joint of the pelvic limbs in three horses.
Osteochondral fragments detected in the proximal interphalangeal joint in the pelvic limbs of 3 horses (2 Standardbreds and 1 Thoroughbred) caused joint enlargement and lameness. Fragments were removed by use of arthroscopy. Accurate placement of the arthroscope into the dorsal joint space was necessary to obtain an adequate view of the fragments. After surgery, 2 of the horses resumed racing without joint problems, and the third was in training to race. High-detail radiographs are necessary to detect osteochondral fragments in horses with joint enlargement or lameness localized to the proximal interphalangeal joint.


Of drug administration, war and oïkos: mediating cancer with nanomedicines.
This paper focuses on nano-enabled drug delivery systems (NDDS) in the context of cancer medicine. It regards NDDS as relational objects whose modes of existence are defined by their relationships with a complex biocultural environment that includes both the biological processes of our bodies and the values representations and metaphors our societies associate with cancer and cancer therapy. Within this framework the abundant use of war metaphors in NDDS --from 'smart bombs' to 'magic nano-bullets'--is discussed from various angles: in terms of therapeutic efficacy, it limits the potential of the technique by preventing the inclusion of the (patho)biological environment in the nanomedicine's mode of action. In terms of development opportunities, the military strategy of active specific targeting faces cost and complexity bottlenecks. In terms of ethical values, it favors the questionable image of cancer patients as 'fighters'. On the basis of these criticisms different metaphorical frameworks are suggested, in particular that of oïkos, whereby nanomedicine is reframed as a kind of domestic economy addressing the system-environment relationships of embodied processes with further imagination and care.


Small-bowel lymphoma and regional enteritis: radiographic similarities.
Lymphoma and regional enteritis may demonstrate strikingly similar patterns in the small bowel. Fifty cases of regional enteritis and small-bowel lymphoma were reviewed. Of these, there were 12 cases of both diseases in which a confident radiographic distinction could not be made. Both diseases may narrow the terminal ileum, present as inflammatory processes, and demonstrate nodular patterns. Other similarities include aneurysmal dilatation, several types of ulceration, fistula formation, mesenteric masses, and involvement of the terminal ileum either alone or in association with skip areas. Clinical implications and the pathologic processes responsible for the radiographic similarity between these entities are discussed.


Surgery Requiring Detailed Preoperative Simulation and Scar De-epithelialization to Repair Severe Postoperative Scarring from Gastroschisis.
We present the case of a patient with severe postoperative scarring from surgical treatment for gastroschisis, with the intestine located immediately under the dermal scar. Although many patients are unsatisfied with the results of scar repair treatment, few reports exist regarding severe or difficult cases involving the surgical repair of postoperative scar contracture. We achieved an excellent result via simulation involving graph paper drawings that were generated using computed tomography images as a reference, followed by dermal scar deepithelialization. The strategy described here may be useful for other cases of severe postoperative scar contracture after primary surgery for gastroschisis.


A particle swarm optimization approach for predicting the number of COVID-19 deaths.
The rapid spread of the COVID-19 pandemic has raised huge concerns about the prospect of a major health disaster that would result in a huge number of deaths. This anxiety was largely fueled by the fact that the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), responsible for the disease, was so far unknown, and therefore an accurate prediction of the number of deaths was particularly difficult. However, this prediction is of the utmost importance for public health authorities to make the most reliable decisions and establish the necessary precautions to protect people's lives. In this paper, we present an approach for predicting the number of deaths from COVID-19. This approach requires modeling the number of infected cases using a generalized logistic function and using this function for inferring the number of deaths. An estimate of the parameters of the proposed model is obtained using a Particle Swarm Optimization algorithm (PSO) that requires iteratively solving a quadratic programming problem. In addition to the total number of deaths and number of infected cases, the model enables the estimation of the infection fatality rate (IFR). Furthermore, using some mild assumptions, we derive estimates of the number of active cases. The proposed approach was empirically assessed on official data provided by the State of Qatar. The results of our computational study show a good accuracy of the predicted number of deaths.


[Quantitative method to describe the inner characteristics of hereditary nonpolyposis colorectal cancer family].
To establish a quantitative method to describe the inner characteristics of hereditary nonpolyposis colorectal cancer (HNPCC) family. All members of 25 HNPCC families with assembly of malignant tumors therein [with at least one patients with colorectal cancer (CRC)] in China underwent questionnaire survey. Other 32 HNPCC families with complete clinical data were collected from the published Chinese and foreign literatures related to clinical phenotype of Chinese HNPCC family. Altogether 57 HNPCC families fulfilling the Amsterdam Criteria (AC) I or II underwent analysis of the inner characteristics cumulatively. The following parameters were analyzed: familial median age when diagnosed as with the first malignant tumor (FMA-DFMT), familial median age when diagnosed as with the first CRC (FMA-DFCRC), familial proportion of CRC in first malignant tumors (FPCRC-FMT), familial proportion of CRC patients (FP-CRCP), number of involved generations, number of cancer patients, and type of family. In the ACI HNPCC families, the distribution patterns of both FMA-DFMT and FMA-DFCRC were not normal distribution. Most of the FMA-DFMT and FMA-DFCRC were from 35 years to 50 years with the medians of 44.0 years and 43.5 years respectively. The FPCRC-FMT and FP-CRCP were less than 0.6 in 13.2% (7/53) and 7.5% (4/53) of the families respectively. The FMA-DFMT and FMA-DFCRC were not correlated with FPCRC-FMT, FP-CRCP, number of involved generations and cancer patients, and type of family (all P > 0.05). Compared to the traditional methods, the features of HNPCC families can be accurately described by a series of quantitative parameters.


Evidence for the need of long-term antithrombotic therapy in patients with porcine heterograft heart valve.
The plasma levels of two platelet specific proteins, namely beta-thromboglobulin (beta TG) and platelet factor 4 (PT4), were investigated in 86 patients with different types of artificial valves, biological and disc, at different times after valve insertion. Significant differences were demonstrated for both proteins with increased age of the disc valve. On the other hand, no significant change in the high average levels was shown for patients with porcine heterograft (Hancock). The general view of anticoagulate or antiaggregate lasting only a few months after bioprosthesis insertion has to be carefully evaluated again.


Autophagy Prevents Osteocyte Cell Death under Hypoxic Conditions.
Hypoxia occurs under important clinical conditions such as cancers, heart disease, and ischemia. However, the relationship between hypoxia and autophagy in osteocytes is still unclear. The objective of the present study was to uncover the regulatory mechanisms that prevent regulated cell death, such as apoptosis, necrosis, and autophagy, under hypoxia. MLO-Y4 cells, a mouse osteocyte cell line, were exposed to various O2 partial pressures (PO2). Subsequently, the cells underwent apoptosis, autophagy, autophagic cell death, and/or necrosis, and thereby we designated PO2 = 2% as a representative hypoxic condition. Immunofluorescence staining showed an increase of LC3 and a decrease of p62 in MLO-Y4 cells exposed to hypoxia, indicating the induction of autophagy. We then hypothesized that β-estradiol (E2) and vitamin D play an important role in apoptosis and autophagy of osteocytes under hypoxia. 1,25α-dihydroxyvitamin D3 (VitD) protected MLO-Y4 cells from cell death and induced autophagy. However, E2 showed little effect. Finally, Western blotting for phosphorylated mTOR and Akt was carried out in order to investigate the altered autophagy signaling pathways affected by the addition of VitD and E2. However, neither E2 nor VitD were capable of recovering the decreased phosphorylation of those factors. Our results indicated that the effects of VitD on autophagy under hypoxia were dependent on the Akt and mTOR pathways. Thus, the results of the present study showed that VitD suppresses osteocyte cell death in an mTOR pathway-dependent manner in hypoxic conditions. This suggests the potential of VitD as a therapeutic intervention for diseases in which the cell death of osteocytes mainly occurs via hypoxia.


High-dose intravenous immunoglobulin treatment of multiple sclerosis.
A review of the pathological basis of multiple sclerosis is presented to see whether the many immunological effects if IVIg may exert some benefit and at what level. This is probably due to the wide spectrum of interactions between IVIg and the immune system, which are analyzed in this review. Macrophage Fc receptor saturation and block, anti-idiotypic effect, reduction of endothelial cell activation and superantigen-neutralizing antibodies are probably involved in the action of IVIg in dysimmune demyelinating diseases. Furthermore, IVIg promote remyelination in virus-induced experimental encephalomyelitis. Trials on IVIg in MS demonstrated a reduction of relapse rate (RR) and appearance of gadolinium-enhancing lesions on magnetic resonance imaging. Furthermore IvIg are regarded as a promising treatment to reduce RR in post-partum period. However, studies on secondary-progressive MS failed to demonstrate an IVIg effect on disability and IVIg failed to improve stabilized visual and motor deficits in two large trials.


Plutonium-fission xenon found in Earth's mantle
Data from mid-ocean ridge basalt glasses indicate that the short-lived radionuclide plutonium-244 that was present during an early stage of the development of the solar system is responsible for roughly 30 percent of the fissiogenic xenon excesses in the interior of Earth today. The rest of the fissiogenic xenon can be ascribed to the spontaneous fission of still live uranium-238. This result, in combination with the refined determination of xenon-129 excesses from extinct iodine-129, implies that the accretion of Earth was finished roughly 50 million to 70 million years after solar system formation and that the atmosphere was formed by mantle degassing.


A chiral ionic polymer for direct visual enantioselective recognition of α-amino acid anions.
A novel chiral ionic polymer exhibits high fluorescence enantioselectivity towards α-amino acid anions, and its solution appears bright green upon addition of (L)-α-amino acid anions, which can be clearly observed by the naked eye for direct visual enantioselective recognition.


Miniaturized multi-sensor loggers provide new insight into year-round flight behaviour of small trans-Sahara avian migrants.
Over the past decade, the miniaturisation of animal borne tags such as geolocators and GPS-transmitters has revolutionized our knowledge of the whereabouts of migratory species. Novel light-weight multi-sensor loggers (1.4 g), which harbour sensors for measuring ambient light intensity, atmospheric pressure, temperature and acceleration, were fixed to two long-distance migrant bird species - eurasian hoopoe (Upupa epops) and great reed warbler (Acrocephalus arundinaceus). Using acceleration and atmospheric pressure data recorded every 5 and 30 min, respectively, we aimed at reconstructing individual diurnal and seasonal patterns of flight activity and flight altitude and thereby, at describing basic, yet hitherto unknown characteristics of migratory flight behaviour. Furthermore, we wanted to characterise the variability in these migration characteristics between individuals, species and migration periods. The flight duration from breeding to sub-Saharan African non-breeding sites and back was more variable within than between the species. Great reed warblers were airborne for a total of 252 flight hours and thus, only slightly longer than eurasian hoopoes with 232 h. With a few exceptions, both species migrated predominantly nocturnally - departure around dusk and landing before dawn. Mean flight altitudes were higher during pre- than during post-breeding migration (median 1100 to 1600 m a.s.l.) and flight above 3000 m occurred regularly with a few great reed warblers exceeding 6000 m a.s.l. (max. 6458 m a.s.l.). Individuals changed flight altitudes repeatedly during a flight bout, indicating a continuous search for (more) favourable flight conditions. We found high variation between individuals in the flight behaviour parameters measured - a variation that surprisingly even exceeded the variation between the species. More importantly, our results have shown that multi-sensor loggers have the potential to provide detailed insights into many fundamental aspects of individual behaviour in small aerial migrants. Combining the data recorded on the multiple sensors with, e.g., remote sensing data like weather and habitat quality on the spatial and temporal scale will be a great step forward to explore individual decisions during migration and their consequences.


Rapid In-Field Volatile Sampling for Detection of Botrytis cinerea Infection in Wine Grapes.
Fungal infection of grape berries (Vitis vinifera) by Botrytis cinerea frequently coincides with harvest, impacting both the yield and quality of grape and wine products. A rapid and non-destructive method for identifying B. cinerea infection in grapes at an early stage prior to harvest is critical to manage loss. In this study, zeolitic imidazolate framework-8 (ZIF-8) crystal was applied as an absorbent material for volatile extraction from B. cinerea infected and healthy grapes in a vineyard, followed by thermal desorption gas chromatography-mass spectrometry. The performance of ZIF-8 in regard to absorbing and trapping the targeted volatiles was evaluated with a standard solution of compounds and with a whole bunch of grapes enclosed in a glass container to maintain standard sampling conditions. The results from the sampling methods were then correlated to B. cinerea infection in grapes, as measured and determined by genus-specific antigen quantification. Trace levels of targeted compounds reported as markers of grape B. cinerea infection were successfully detected with in-field sampling. The peak area counts for volatiles 3-octanone, 1-octen-3-one, 3-octanol, and 1-octen-3-ol extracted using ZIF-8 were significantly higher than values achieved using Tenax®-TA from field testing and demonstrated good correlation with B. cinerea infection severities determined by B. cinerea antigen detection.


[Morphometric characteristics of the sacrum in Mexican population. Its importance in lumbosacral fusion and fixation procedures].
the morphology and the morphometric characteristics of the sacrum and its components determine the size of pedicle implants in both width and length and the orientation of the screw at the time of implantation. The present study aimed to determine the morphometric characteristics of the sacrum in the Mexican population in order to establish safe approaches for the placement and orientation of the screws during lumbosacral instrumentation. morphometric characteristics were determined for 50 dry sacra distributed in 44 measurement parameters (39 linear and 5 angular) divided in five categories: 1) anterior and posterior sacral foramina; 2) S1 vertebral pedicle and intermediate sacral crest; 3) vertebral bodies and the general parameters of the sacrum; 4) S1 superior articular process facet and sacral canal, and 5) S1 pedicle approaches. the S1 pedicle average length was 25.00 mm ± 2.41, the S1 pedicle anterior and posterior average height was 20.68 mm ± 3.40 and 24.64 mm ± 3.77 respectively, the sacral canal dimensions on its superior opening were 15.13 mm ± 2.40 in the sagital diameter and 31.07 mm ± 2.65 for the transverse diameter, in S1 the anteriomedial screw trajectory average distance was 50.08 mm ± 3.72 with an average angle of 34.30° ± 4.1 from the screw entry point. the results from this study are important for the correct screw placement and position in lumbosacral instrumentation, and also for other procedures that involve the sacral region as a surgical and diagnostic target.


Contribution of resonance energy transfer to the luminescence quenching of upconversion nanoparticles with graphene oxide.
Upconversion nanoparticles (UCNP) are increasingly used due to their advantages over conventional fluorophores, and their use as resonance energy transfer (RET) donors has permitted their application as biosensors when they are combined with appropriate RET acceptors such as graphene oxide (GO). However, there is a lack of knowledge about the design and influence that GO composition produces over the quenching of these nanoparticles that in turn will define their performance as sensors. In this work, we have analysed the total quenching efficiency, as well as the actual values corresponding to the RET process between UCNPs and GO sheets with three different chemical compositions. Our findings indicate that excitation and emission absorption by GO sheets are the major contributor to the observed luminescence quenching in these systems. This challenges the general assumption that UCNPs luminescence deactivation by GO is caused by RET. Furthermore, RET efficiency has been theoretically calculated by means of a semiclassical model considering the different nonradiative energy transfer rates from each Er3+ ion to the GO thin film. These theoretical results highlight the relevance of the relative positions of the Er3+ ions inside the UCNP with respect to the GO sheet in order to explain the RET-induced efficiency measurements.


Advances with analgesics and NSAIDs for the treatment of spinal disorders.
One of the major developments with regard to chronic non-malignant pain in these last few years has been a better understanding of the mechanisms that act to maintain pain, while inferences about the pathophysiology have facilitated therapeutic decision-making. This chapter reviews the strength of evidence for the therapeutic effect of pharmacological symptomatic approaches using non-steroidal anti-inflammatory agents, opioids and co-analgesics in acute and chronic back pain with an emphasis on the results of randomized controlled trials as well as on the need for long-term comparative trials of drug efficacy, toxicity and compliance.


Sharing genetic test results of germline pathogenic variants of hereditary cancer with relatives: A single-center cross-sectional study.
This study aimed to determine whether Japanese cancer patients share test results of germline pathogenic variants of hereditary cancer with their relatives. This single-center cross-sectional study enrolled 21 Japanese patients who received results of germline pathogenic variants of hereditary cancer at least 6 months prior. All patients shared their test results with at least one relative, with the following sharing rates: 85.7% for first-degree relatives, 10% for second-degree relatives and 8.3% for third-degree relatives. Patients most commonly shared the information with their children aged >18 years (86.7%), followed by their siblings (73.6%), spouses (64.7%) and parents (54.5%). Three categories were extracted from qualitative analysis: 'characteristics of my cancer', 'knowledge and caution about inheritability' and 'utilization of medical care.' The rate of test result sharing with first-degree relatives was comparable with those in Europe and the USA. Patients with germline pathogenic variants also tended to share their test results more with their children and siblings than with their parents. Informing their relatives of the results was suggestive of the motivation to influence their relatives' health outcome and contribute to the well-being of their children and siblings.


N-C Axially Chiral Anilines: Electronic Effect on Barrier to Rotation and A Remote Proton Brake.
N-Aryl-N-methyl-2-tert-butyl-6-methylaniline derivatives exhibit a rotationally stable N-C axially chiral structure and the rotational barriers around an N-C chiral axis increased with the increase in electron-withdrawing character of para-substituent on the aryl group. X-ray crystal structural analysis and the DFT calculation suggested that the considerable change of the rotational barriers by the electron effect of para-substituents is due to the disappearance of resonance stabilization energy caused by the twisting of para-substituted phenyl group in the transition state. This structural property of the N-C axially chiral anilines was employed to reveal a new acid-decelerated molecular rotor caused by the protonation at the remote position (remote proton brake).


Assessing the efficacy of palliative radiation treatment schemes for locally advanced squamous cell carcinoma of the head and neck: a meta-analysis.
The objective to assess the outcomes from different palliative radiotherapy (RT) schedules in incurable head and neck cancer (HNC), to evaluate if there is a relationship between RT dose, technique, and fractionation with tumor response in contrast to the occurrence of adverse effects. Eligible studies were identified on Medline, Embase, the Cochrane Library, and annual meetings proceedings through June 2020. Following PRISMA and MOOSE guidelines, a cumulative meta-analysis of studies for overall response rate (ORR), overall survival (OS), progression-free survival (PFS), pain/dysphagia relief, and toxicity was performed. A meta-regression analysis was done to assess if there is a connection between RT dose, schedule, and technique with ORR. Twenty-eight studies with 1,986 patients treated with palliative RT due to incurable HNC were included. The median OS was 6.5 months [95% confidence interval (CI): 5.6-7.4], and PFS was 3.6 months (95% CI: 2.7-4.3). The ORR, pain and dysphagia relief rates were 72% (95% CI: 0.6-0.8), 83% (95% CI: 52-100%), and 75% (95% CI: 52-100%), respectively. Conventional radiotherapy (2D-RT) or conformational radiotherapy (3D-RT) use were significantly associated with a higher acute toxicity rate (grade ≥ 3) than intensity-modulated radiation therapy (IMRT) or stereotactic body radiation therapy (SBRT). On meta-regression analyses, the total biological effective doses (BED) of RT (p = 0.001), BED > 60 Gy10 (p = 0.001), short course (p = 0.01) and SBRT (p = 0.02) were associated with a superior ORR. Palliative RT achieves tumor response and symptom relief in incurable HNC patients. Short course RT of BED > 60 Gy using IMRT could improve its therapeutic ratio. SBRT should be considered when available.


[Energy metabolism in obese children].
Childhood obesity results from excessive dietary intake as compared with energy expenditure. This imbalance can result from either overeating or a constitutional decrease in one or several of the components of energy expenditure: resting metabolic rate, diet-induced thermogenesis, or exercise-related thermogenesis. Decreased energy expenditure is probably at least partly genetic in origin, contributing to the significant clustering of obesity in families. Management aims at reducing the imbalance by decreasing the caloric intake. Once the desired weight is achieved, intake must be adjusted to expenditure to avoid weight regain.