Increasing nerve agent treatment efficacy by P-glycoprotein inhibition.
One of the shortcomings of current treatment of nerve agent poisoning is that not all drugs effectively penetrate the blood-brain barrier (BBB), whereas most nerve agents easily do. P-glycoprotein (Pgp) efflux transporters at the BBB may contribute to this aspect. It was previously shown that Pgp inhibition by tariquidar enhanced the efficacy of nerve agent treatment when administered as a pretreatment. In the present study soman-induced seizures were also substantially prevented when the animals were intravenously treated with tariquidar post-poisoning, in addition to HI-6 and atropine. In these animals, approximately twice as much AChE activity was present in their brain as compared to control rats. The finding that tariquidar did not affect distribution of soman to the brain indicates that the potentiating effects were a result of interactions of Pgp inhibition with drug distribution. In line with this, atropine appeared to be a substrate for Pgp in in vitro studies in a MDR1/MDCK cell model. This indicates that tariquidar might induce brain region specific effects on atropine distribution, which could contribute to the therapeutic efficacy increase found. Furthermore, the therapeutic enhancement by tariquidar was compared to that of the less specific and less potent Pgp inhibitor cyclosporine A. This compound appeared to induce a protective effect similar to tariquidar. In conclusion, treatment with a Pgp inhibitor resulted in enhanced therapeutic efficacy of HI-6 and atropine in a soman-induced seizure model in the rat. The mechanism underlying these effects should be further investigated. To that end, the potentiating effect of nerve agent treatment should be addressed against a broader range of nerve agents, for oximes and atropine separately, and for those at lower doses. In particular when efficacy against more nerve agents is shown, a Pgp inhibitor such as tariquidar might be a valid addition to nerve agent antidotes.


Cloning of a big defensin gene and its response to Vibrio parahaemolyticus challenge in the noble scallop Chlamys nobilis (Bivalve: Pectinidae).
The noble scallop Chlamys nobilis has been an important marine cultured bivalve in the Southern Sea of China for decades. However, large-scale mortality events often occurred during the scallop' cultivation. As one of AMPs (antimicrobial peptides), big defensin is an important component of the innate immunity against pathogenic microorganisms in invertebrates. In order to investigate whether the big defensin can play a role in the immune defense against pathogenic microorganisms in noble scallop, a big defensin gene from the hemocytes of Chlamys nobilis (CnBD) was cloned, and the mRNA level was measured after an acute Vibrio parahaemolyticus challenge of 36 h. The CnBD cDNA contains an open reading frame (ORF) of 381 bp encoding a peptide of 126 amino acids residues. The deduce amino acid sequence of CnBD shows a high similarity with that from Argopecten irradians and displays common features of big defensin, indicating that CnBD is a new member of the big defensin family. Compared with the control group, the relative mRNA level of CnBD was significantly up-regulated at 3, 24 and 36 h. The present result indicated that CnBD played an immune role against bacterial infection in noble scallop.


Chemical grafting of biphenyl self-assembled monolayers on ultrananocrystalline diamond.
We have investigated the formation of self-assembled monolayers (SAMs) of 4'-nitro-1,1-biphenyl-4-diazonium tetrafluoroborate (NBD) onto ultrananocrystalline diamond (UNCD) thin films. In contrast to the common approach to modify diamond and diamond-like substrates by electrografting, the SAM was formed from the saturated solution of NBD in acetonitrile by pure chemical grafting. Atomic force microscopy (AFM), X-ray photoelectron spectroscopy (XPS), cyclic voltammetry (CV), and near edge X-ray absorption fine structure spectroscopy (NEXAFS) have been used to verify the direct covalent attachment of the 4'-nitro-1,1-biphenyl (NB) SAM on the diamond substrate via stable C-C bonds and to estimate the monolayer packing density. The results confirm the presence of a very stable, homogeneous and dense monolayer. Additionally, the terminal nitro group of the NB SAM can be readily converted into an amino group by X-ray irradiation as well as electrochemistry. This opens the possibility of in situ electrochemical modification as well as the creation of chemical patterns (chemical lithography) in the SAM on UNCD substrates and enables a variety of consecutive chemical functionalization for sensing and molecular electronics applications.


Expression and characterization of RNA-dependent RNA polymerase of Dendrolimus punctatus tetravirus.
Dendrolimus punctatus tetravirus (DpTV) has been identified as a new member of the genus Omegatetravirus of the family Tetraviridae that may be related serologically to Nudaurelia capensis virus (NomegaV). To establish the function of DpTV RNA genome and to better understand the mechanism of viral replication, the putative RNA-dependent RNA polymerase (RdRp) domain has been cloned and expressed in Escherichia coli. The recombinant protein was purified on a Ni-chelating HisTrap affinity column and demonstrated to initiate viral RNA synthesis in a primer-independent manner but not by terminal nucleotidyle transferase activity in the presence of Mg2+ and RNA template. Mutation of the GDD to GAA interferes with the residues at the polymerase active site and metal ions, and thus renders the polymerase inactive.


[Histological and immunohistochemical investigations with capsular contracture after breast augmentation with smooth silicone gel implants].
A prospective study was performed to analyse the cellular and molecular composition of fibrous capsules around silicone breast implants. The necessity of an exact histological classification for comparing objectively the different findings of capsular contracture is shown. The prospective study (investigation time 1/2003 to 6/2005) included 24 female patients (average age: 40+/-12 years) with contracture after bilateral cosmetic breast augmentation with smooth silicone gel implants (Mentor). In each patient the baker score was determined preoperatively. Samples of capsular tissue from all patients were evaluated histologically and immunohistochemically and classified according to the histological classification introduced by Wilflingseder and co-workers. All capsules showed the same basic histological structure with a three-layer composition. For the correlation analysis we had to exclude one patient with repeated implant change. There was no correlation between the patient's age, time of implantation, length of implant period, and capsular contracture. Greater amounts of silicone particles were associated with increased degrees of capsular contracture (Baker: r = 0.687, n = 23, p < or = 0.001; Wilflingseder: r = 0.784, n = 23, p < or = 0.001). High silicone amounts were associated with an increased local inflammation (r = 0.489, n = 23, p , 0.05). A moderate to severe local inflammation was found in 23 patients (95.8%). In summary, there was a positive correlation (r = 0.797, n = 23; p , or = 0.001) between the clinical classification (Baker score I to IV) and the histological classification (Wilflingseder score I to IV). We demonstrated in our study, in spite of using implants with high gel cohesiveness (fourth generation), the presence of vacuolated macrophages with microcystic structures containing silicone and silicone particles in the capsular tissue. Greater capsular thickness was associated with an increased number of silicone particles ans silicone-loaded macrophages in the peri-implant capsule. The histological classification introduced by Wilflingseder and co-workers takes into consideration this pathogenetic mechanism of inflammatory reaction which seems to be one of the major key factors in the development of capsular contracture.


Paraneoplastic secondary hypertension due to a renin-secreting desmoplastic small round cell tumor: A case report.
Desmoplastic small round cell tumor (DSRCT) is a rare and aggressive malignancy with a poor outcome that occurs in adolescents and young adults; <200 cases of DSRCT have been reported. Renin-producing tumors are also rare and cases of extrarenal renin-producing tumors are even rarer. The present study describes the case of a 20-year-old male that was diagnosed with DSRCT and presented with severe hypertension and hypokalemia, as well as metabolic alkalosis. The plasma renin activity (PRA) level was identified to be markedly elevated (normal range in standing and supine positions, 1.3-4.0 ng/ml/h and 0.15-2.33 ng/ml/h, respectively) and the plasma aldosterone level was also increased (normal range in standing and supine positions, 4.0-31.0 ng/dl and 1.0-1.6 ng/dl, respectively). The symptoms of the patient were consistent with the renin-secreting tumor triad, which comprises hypertension, hypokalemia and elevated PRA. Paraneoplastic syndromes must always be considered in cancer patients exhibiting unusual clinical findings, despite their rarity. The current patient was diagnosed with paraneoplastic secondary hypertension due to the presence of disseminated renin-secreting DSRCT. The patient was treated with the VAC/IE regimen (vincristine, adriamycin, cyclophosphamide, ifosfamide and etoposide) for six cycles. Following this treatment, the serum renin and aldosterone levels fell to within the normal range and the patient's blood pressure was normalized without antihypertensive medication. Although an immunohistochemical evaluation of renin was not conducted as the sample size was inadequate, the present study demonstrated that the tumor had produced renin. The biosynthesis of renin was identified by the presence of mRNA that coded for the renin precursor, which was observed in the ascites of the patient. The current study describes, to the best of our knowledge, the first reported case of paraneoplastic secondary hypertension in a patient presenting with a renin-producing DSRCT.


Gingival wound healing: an essential response disturbed by aging?
Gingival wound healing comprises a series of sequential responses that allow the closure of breaches in the masticatory mucosa. This process is of critical importance to prevent the invasion of microbes or other agents into tissues, avoiding the establishment of a chronic infection. Wound healing may also play an important role during cell and tissue reaction to long-term injury, as it may occur during inflammatory responses and cancer. Recent experimental data have shown that gingival wound healing is severely affected by the aging process. These defects may alter distinct phases of the wound-healing process, including epithelial migration, granulation tissue formation, and tissue remodeling. The cellular and molecular defects that may explain these deficiencies include several biological responses such as an increased inflammatory response, altered integrin signaling, reduced growth factor activity, decreased cell proliferation, diminished angiogenesis, reduced collagen synthesis, augmented collagen remodeling, and deterioration of the proliferative and differentiation potential of stem cells. In this review, we explore the cellular and molecular basis of these defects and their possible clinical implications.


PD-L1 expression in non-small cell lung cancer: heterogeneity by pathologic types, tissue sampling and metastasis.
Programmed cell death ligand-1 (PD-L1) is a predictive marker of anti-PD-1/PD-L1 therapy response. Intra-tumour heterogeneity of PD-L1 expression has been reported in non-small cell lung cancer (NSCLC), but comprehensive studies regarding the determination of PD-L1 expression in different materials are still lacking. Therefore, we aimed to compare PD-L1 expression in paired tumour samples and in different specimen types. A total of 1,002 resected NSCLC specimens, 35 biopsy specimens and 54 endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) samples were performed PD-L1 immunohistochemistry (IHC) testing using the 22C3 assay. PD-L1 expression was evaluated using the tumour proportion score (TPS) and categorized into three levels: negative (TPS <1%), low expression (TPS 1-49%) and high expression (TPS ≥50%). A total of 1,002 resected NSCLC specimens, including 852 adenocarcinomas (ADCs) and 150 squamous cell carcinomas (SCCs); 35 paired biopsy and resected samples; 54 paired cell block and biopsy samples; 53 paired blocks from the same resected tissue and 49 paired primary and metastatic lesion samples were included in this study. Interestingly, high PD-L1 expression was significantly more frequent in poorly differentiated subtypes than in well-differentiated subtypes in the ADC subgroup (P<0.001). In the SCC subgroup, high PD-L1 expression was significantly more associated with the nonkeratinizing type than the keratinizing type (P=0.001). PD-L1 expression differed between cell blocks and matched biopsy specimens (discordance rate =11.1%, 6/54) and between biopsy and matched resected specimens (discordance rate =31.4%, 11/35). PD-L1 expression differed between different paraffin blocks from the same resected specimen (discordance rate =35.8%, 19/53), and the discordance rate of PD-L1 expression between primary tumours and matched lymph node metastases was 28.6% (14/49). Discordant PD-L1 expression is not uncommon in NSCLC and warrants additional studies and serious consideration when interpreting PD-L1 test results. Initial negative test results may lead to repeat PD-L1 testing in additional samples or the use of a different clone if necessary.


Role of Fcgamma receptors in glomerulonephritis.
Many forms of glomerulonephritis involve immune complex localization in the kidney. Fcgamma receptors (FcgammaR) expressed on the surface of leukocytes bind the Fc (constant) portion of IgG. They link immune complex deposition to innate immune responses, including phagocytosis, cytokine release, formation of reactive oxygen species, and antibody-dependent cytotoxicity. Activator and inhibitor FcgammaR co-exist on the surface of cells and set thresholds for immune responses. Inhibitor FcgammaR also have a specific role in the maintenance of B cell tolerance. Studies of gene-targeted mice lacking specific FcgammaR have demonstrated that animals lacking activator FcgammaR on circulating leukocytes were protected from immune complex induced glomerular injury, both in models of systemic lupus erythematosus (SLE) and anti-glomerular basement membrane antibody disease. In contrast, mice lacking inhibitor FcgammaR developed SLE-like auto-immunity on certain genetic backgrounds and were more susceptible to anti-glomerular basement membrane disease, with evidence of enhanced immune responses and dysregulated effector cells. There is also evidence for FcgammaR dysfunction in human SLE and for an association of 'low-binding' polymorphisms of FcgammaR with SLE. In the future, therapeutic possibilities may exist for the manipulation of the FcgammaR pathway in the treatment of glomerulonephritis.


Spectral power ratio as a measure of EEG changes in mild cognitive impairment due to Alzheimer's disease: a case-control study.
Adopting preventive strategies in individuals with subclinical Alzheimer's disease (AD) has the potential to delay dementia onset and reduce healthcare costs. Thus, it is extremely important to identify inexpensive, scalable, sensitive, and specific markers to track disease progression. The electroencephalography spectral power ratio (SPR: the fast to slow spectral power ratio), a measure of the shift in power distribution from higher to lower frequencies, holds potential for aiding clinical practice. The SPR is altered in patients with AD, correlates with cognitive functions, and can be easily implemented in clinical settings. However, whether the SPR is sensitive to pathophysiological changes in the prodromal stage of AD is unclear. We explored the SPR of individuals diagnosed with amyloid-positive amnestic mild cognitive impairment (Aβ+aMCI) and its association with both cognitive function and amyloid load. The SPR was lower in Aβ+aMCI than in the cognitively unimpaired individuals and correlated with executive function scores but not with amyloid load. Hypothesis-generating analyses suggested that aMCI participants with a lower SPR had an increased probability of a positive amyloid positron emission tomography. Future research may explore the potential of this measure to classify aMCI individuals according to their AD biomarker status.


Incorporation of fullerene derivatives into smectite clays: a new family of organic-inorganic nanocomposites.
Three fulleropyrrolidine derivatives, characterized by the presence of positive charges, were introduced in the interlayer space of montmorillonite. The composites were characterized by powder X-ray diffraction and differential thermal and thermogravimetric (DTA-TGA) analysis, in conjunction with FTIR, UV-Vis, Raman, and (57)Fe-Mössbauer spectroscopies. Organophilic derivatives were intercalated into organically modified clays, while water-soluble fulleropyrrolidines were introduced into the clay galleries through ion exchange. The experiments, complemented by computer simulations, show that not all the clay-clay platelets are intercalated by the fullerene derivatives and that a sizable amount of charge transfer takes place between the host and the guests.


The incorporation of long-chain fatty acids into phospholipids of respiring slices of rat cerebrum.
1. Respiring slices of adult rat cerebrum have been shown to incorporate long-chain (14)C-labelled fatty acids into phospholipid. 2. Labelling was almost entirely confined to lecithin and ethanolamine phospholipid, only traces being present in serine phospholipid. 3. Palmitic acid, oleic acid and linoleic acid were incorporated more actively into lecithin than into ethanolamine phospholipid, but the converse was found with stearic acid. 4. All four acids labelled the 1- and 2-positions of both lipids; palmitic acid, oleic acid and linoleic acid were approximately evenly distributed, but stearic acid was incorporated predominantly at the 1-position. 5. It is considered that incorporation is most likely brought about through acylation of endogenously derived lysophosphatides. 6. The possible implications of this pathway of lipid metabolism in nervous tissue are discussed.


Cystic lymphangioma: trauma may be a significant cause?
Cystic lymphangioma is a rare congenital anomaly of the lymphatic system. Its embryopathogenesis is still controversial. Most lesions present in infancy or early childhood with a swelling found in the head and neck region. We report the case of a woman who presented with a cystic swelling in the left supraclavicular region that appeared after left side thyroidectomy. Surgical excision achieved complete removal. Histology showed the lesion to be a cystic lymphangioma. It can be hypothesized that an embryogenetic origin of the adult lymphangioma is associated with some precipitating trauma such as surgery.


Autologous and Nonautologous Blood Transfusion in Patients with Ruptured Ectopic Pregnancy and Severe Blood Loss.
There are some theoretical concerns for the use of intraoperative cell salvage (ICS) in patients with ectopic pregnancy. This study aimed to observe the impact of ICS on the coagulation function and clinical outcomes of patients with ruptured ectopic pregnancy and severe blood loss. This was a retrospective study of 225 patients with ruptured ectopic pregnancy and severe blood loss treated at the Third Affiliated Hospital of Guangxi Medical University between January 2012 and May 2016. Patients were grouped according to ICS (n = 116) and controls (n = 109, allogenic transfusion and no transfusion). Compared with controls, patients with ICS had shorter hospitalization (P = 0.007), lower requirement for allogenic blood products (P < 0.001), and higher hemoglobin levels at discharge (P < 0.001). There were no complications/ adverse reactions. In the ICS group, hemoglobin at discharge (-6.5%, P = 0.002) and thrombin time (-3.7%, P = 0.002) were decreased 24 h after surgery, while 24 h APTT was increased (+4.6%, P < 0.001). In the control group, hemoglobin at discharge (-16.8%, P < 0.001) was decreased after surgery and 24 h APTT was increased (+2.4%, P = 0.045). At discharge, hemoglobin levels were higher in the ICS group (P < 0.001). ICS was associated with good clinical outcomes in patients with ruptured ectopic pregnancy and severe blood loss.


In vitro transformation of rodent cells by K-region derivatives of polycyclic hydrocarbons.
The K-region epoxides and cis-dihydrodiols derived from benz(a)anthracene and from dibenz(a,h)-anthracene have been found to be more active in the production of malignant transformation in hamster embryo cells than the hydrocarbons or the corresponding K-region phenols. The K-region epoxides derived from benz(a)-anthracene and from 3-methylcholanthrene were also active in transforming a clone of ventral prostate cells from the C3H mouse that was not readily transformed by the parent hydrocarbons. The phenols were the most toxic compounds tested but did not transform cells; this confirms that toxicity and transformation are not directly related events. The results obtained support the view that metabolism of polycyclic hydrocarbons precedes toxicity and transformation in rodent cells in culture.


Newborn Screening for Mitochondrial Carnitine-Acylcarnitine Cycle Disorders in Zhejiang Province, China.
Background: Disorders of mitochondrial carnitine-acylcarnitine cycle is a heterogeneous group of hereditary diseases of mitochondrial β-oxidation of fatty acids tested in NBS program in Zhejiang province, China. Large-scale studies reporting disorders of mitochondrial carnitine-acylcarnitine cycle among Chinese population in NBS are limited. The aim of this study was to explain the incidence and biochemical, clinical, and genetic characteristics of disorders of mitochondrial carnitine-acylcarnitine cycle in NBS. Methods: From January 2009 to June 2021, 4,070,375 newborns were screened by tandem mass spectrometry. Newborns with elevated C0 levels and/or C0/(C16 + C18) ratios were identified as having CPT1D, whereas those with decreased C0 levels and/or C0/(C16 + C18) ratios and/or elevated C12-C18:1 level were identified as having CPT2D or CACTD. Suspected positive patients were further subjected to genetic analysis. All confirmed patients received biochemical and nutritional treatment, as well as follow-up sessions. Results: Overall, 20 patients (12 with CPT1D, 4 with CPT2D, and 4 with CACTD) with disorders of mitochondrial carnitine-acylcarnitine cycle were diagnosed by NBS. The overall incidence of these disorders was one in 203,518 newborns. In toal, 11 patients with CPT1D exhibited increased C0 levels and C0/(C16 + C18) ratios. In all patients of CPT2D, all long chain acyl-carnitines levels were elevated except for case 14 having normal C12 levels. In all patients with CACTD, all long chain acyl-carnitines levels were elevated except for case 17 having normal C12, C18, and C18:1 levels. Most patients with CPT1D were asymptomatic. Overall, two of 4 patients with CPT2D did not present any clinical symptom, but other two patients died. In 4 cases with CACTD, the disease was onset after birth, and 75% patients died. In total, 14 distinct mutations were identified in CPT1A gene, of which 11 were novel and c.1910C > A (p.S637T), c.740C > T (p.P247L), and c.1328T > C (p.L443P) were the most common mutations. Overall, 3 novel mutations were identified in CPT2 gene, and the most frequent mutation was c.1711C > A (p.P571T). The most common variant in SLC25A20 gene was c.199-10T > G. Conclusion: Disorders of mitochondrial carnitine-acylcarnitine cycle can be detected by NBS, and the combined incidence of these disorders in newborns was rare in Zhejiang province, China. Most patients presented typical acylcarnitine profiles. Most patients with CPT1D presented normal growth and development, whereas those with CPT2D/CACTD exhibited a high mortality rate. Several novel CPT1A and CPT2 variants were identified, which expanded the variant spectrum.


"Nothing more to be done": palliative care versus experimental therapy in advanced cancer.
Patients suffering from advanced, incurable cancer often receive from their doctors proposals to enroll in a clinical trial of an experimental therapy. Experimental therapies are increasingly perceived not as a highly problematic approach but as a near-standard way to deal with incurable cancer. There are, however, important differences in the diffusion of these therapies in Western countries. The large diffusion of experimental therapies for malignant disease in the United States contrasts with the much more restricted diffusion of these therapies in the United Kingdom. The difference between the two reflects differences in the organization of health care in these countries and distinct patterns of the professionalization of medical oncology in America and in Britain. The high density and great autonomy of medical oncologists in the United States encourages there the diffusion of experimental therapies (regarded by some as expensive and inefficient); the lower density of these specialists in the United Kingdom and their task as consultants and not primary caregivers, favors the choice of more conservative (for some, too conservative) treatments. Theoretically, the decision as to whether patients suffering from advanced, incurable cancer will be steered toward an experimental therapy or toward palliative care depends on the values and beliefs of these patients and their physicians. In practice, however, such choice does not depend exclusively on the individual's cultural background and ethical values, but is also strongly affected by the--culturally conditioned--professional and institutional structure of medicine.


Combined 2D and 3D-QSAR, molecular modelling and docking studies of pyrazolodiazepinones as novel phosphodiesterase 2 inhibitors.
Selective inhibition of phosphodiesterase 2 (PDE2) in cells where it is located elevates cyclic guanosine monophosphate (cGMP) and acts as novel analgesic with antinociceptive activity. Three-dimensional quantitative structure-activity relationship (QSAR) studies for pyrazolodiazepinone inhibitors exhibiting PDE2 inhibition were performed using comparative molecular field analysis (CoMFA), comparative molecular similarity indices analysis (CoMSIA) and Topomer CoMFA, and two-dimensional QSAR study was performed using a Hologram QSAR (HQSAR) method. QSAR models were generated using training set of 23 compounds and were validated using test set of nine compounds. The optimum partial least squares (PLS) for CoMFA-Focusing, CoMSIA-SDH, Topomer CoMFA and HQSAR models exhibited good 'leave-one-out' cross validated correlation coefficient (q(2)) of 0.790, 0.769, 0.840 and 0.787, coefficient of determination (r(2)) of 0.999, 0.964, 0.979 and 0.980, and high predictive power (r(2)(pred)) of 0.796, 0.833, 0.820 and 0.803 respectively. Docking studies revealed that those inhibitors able to bind to amino acid Gln859 by cGMP binding orientation called 'glutamine-switch', and also bind to the hydrophobic clamp of PDE2 isoform, could possess high selectivity for PDE2. From the results of all the studies, structure-activity relationships and structural requirements for binding to active site of PDE2 were established which provide useful guidance for the design and future synthesis of potent PDE2 inhibitors.


Single thermal scan digital system for deep level transient spectroscopy.
We have developed a micro-controller based Deep Level Transient Spectroscopy (DLTS) system to identify the deep-level defects in semiconductors. It consists of Arduino-Due, a capacitance meter, and interface circuits. In addition, we have also developed the algorithms needed for the entire signal processing. It is not limited to Arduino-Due but can be implemented using other micro-controllers also. We have used Arduino-Due to generate the filling pulse and monitor the capacitance, temperature, data acquisition, timing control, and signal processing. The sequence of generating the filling pulse, reading the data, and signal processing is controlled digitally rather than by analog sampling circuits and timers. The minimum pulse width generated using Arduino-Due is 50 ns; the pulse width generation depends on various hardware and software parameters and their integration. The resolution in reading the data is 0.8 mV/unit. The time delays in reading the data are appropriately taken care of in the system. The whole experiment can be completed in a single temperature cycle within 2-3 h. The system is simple, inexpensive, in an easy-to-use platform, and less time-consuming; minimizes possible errors; and improves accuracy. The measurements using the "micro-controller based DLTS system" are verified by fabricating (Au) gold-doped silicon (Si) p-n junction samples (Au is a well-understood defect in Si). Using the Arduino-Due based DLTS system, we calculated the energy, the capture cross section, and the concentration of trap levels. The results are in good agreement with the literature, indicating the versatility of the system.


Photonic Artifacts in Ratiometric Luminescence Nanothermometry.
Ongoing developments in science and technology require temperature measurements at increasingly higher spatial resolutions. Nanocrystals with temperature-sensitive luminescence are a popular thermometer for these applications offering high precision and remote read-out. Here, we demonstrate that ratiometric luminescence thermometry experiments may suffer from systematic errors in nanostructured environments. We place lanthanide-based luminescent nanothermometers at controlled distances of up to 600 nm from a Au surface. Although this geometry supports no absorption or scattering resonances, distortion of the emission spectra of the thermometers due to the modified density of optical states results in temperature read-out errors of up to 250 K. Our simple analytical model explains the effects of thermometer emission frequencies, experimental equipment, and sample properties on the magnitude of the errors. We discuss the relevance of our findings in several experimental scenarios. Such errors do not always occur, but they are expected in measurements near reflecting interfaces or scattering objects.


One-step, low-temperature fabrication of CdS quantum dots by watermelon rind: a green approach.
We investigated the one-step synthesis of CdS nanoparticles via green synthesis that used aqueous extract of watermelon rind as a capping and stabilizing agent. Preliminary phytochemical analysis depicted the presence of carbohydrates which can act as capping and stabilizing agents. Synthesized CdS nanoparticles were characterized using UV-visible, Fourier transform infrared spectroscopy, X-ray diffraction, EDX, dynamic light scattering, transmission electron microscopy, and atomic force microscopy techniques. The CdS nanoparticles were found to be size- and shape-controlled and were stable even after 3 months of synthesis. The results suggest that watermelon rind, an agro-waste, can be used for synthesis of CdS nanoparticles without any addition of stabilizing and capping agents.


Effect of ultraviolet light C on bacterial colonization in chronic wounds.
Ultraviolet light C (light wavelength 200 nm to 290 nm) has been shown to kill cultures of antibiotic resistant strains of bacteria such as methicillin-resistant Staphylococcus aureus. To evaluate the ability of ultraviolet light C to reduce the amount and type of bacteria present in chronically infected ulcers, as well as to establish the test-retest reliability of the semi-quantitative swab technique, a prospective, one-group, pre-post treatment study was conducted among patients receiving treatment in several in- and outpatient facilities and nursing homes. Individuals with chronic ulcers exhibiting at least two signs of infection and critically colonized with bacteria (n = 22) received a single 180-second treatment using an ultraviolet light C lamp (wavelength = 254 nm) placed 1 inch from the wound bed. Semi-quantitative swabs taken immediately before and after UVC treatment were used to assess changes in the bacterial bioburden present within the wound bed. Results demonstrated excellent test-retest reliability of the semi-quantitative swab technique used to evaluate the type and amount of bacteria present in chronic wounds (Cohen's kappa = 0.92). Assessment of wound bioburden using semi-quantitative swabs revealed a statistically significant (P <0.0001) reduction in the relative amount of bacteria following a single treatment of ultraviolet light C. The greatest reduction in semi-quantitative swab scores following ultraviolet light C treatment were observed for wounds colonized with the bacteria Pseudomonas aeruginosa and wounds colonized with only one species of bacteria. Significant (P <0.05) reductions in the relative amount of bacteria also were observed in 12 ulcers in which methicillin-resistant Staphylococcus aureus was present. These results confirm previous laboratory studies and demonstrate that ultraviolet light C can kill bacteria such as Pseudomonas aeruginosa, Staphylococcus aureus, and methicillin-resistant Staphylococcus aureus present in superficial layers of chronic wounds.


Naproxen in rheumatoid arthritis. A controlled trial.
The efficacy of naproxen in treating rheumatoid arthritis patients was evaluated in a double-blind clinical trial using aspirin as the control drug. The study was conducted at seven centers and involved 80 patients. After an unequivocal increase in disease activity during a drug-free period, patients were randomly assigned to either drug and continued in the trial for 16 weeks. Some patients took low maintenance doses of corticosteroids, or gold salts, or both throughout the trial. Both test drugs significantly decreased disease activity as measured by a number of ways. By objective measurements, naproxen was as effective as aspirin, although patients in the naproxen-treated group entered the trial with more severe disease. By some subjective evaluations, naproxen was considered more effective than aspirin. Although patients taking naproxen had less frequent gastrointestinal side effects and fewer symptoms VIIIth nerve toxicity, the differences were not statistically significant. We conclude that naproxen is a useful addition to the physician's armamentarium for the treatment of rheumatoid arthritis.


Tuning behaviour of slotted vernier widely tunable lasers.
A detailed thermo-optic model combining the 1D transfer matrix method and a 3D finite element method is developed and used to simulate a widely tunable vernier laser based on surface etched slots. The model is used to investigate the experimentally observed tuning patterns. At low injection currents, carrier tuning dominates, while at high currents, thermal tuning is the dominant mechanism. These lasers are very simple to fabricate and have a wide tuning over 50 nm, but SMSR and linewidth performance is not yet optimised. Simulations give an insight into the observed tuning efficiency and linewidth performance of the lasers, with high carrier densities in the grating regions being identified as a key area, which is presently limiting these parameters.


Overexpression of NEIL3 associated with altered genome and poor survival in selected types of human cancer.
Base excision repair, which is initiated by the DNA N-glycosylase proteins, is the frontline for repairing potentially mutagenic DNA base damage. Several base excision repair genes are deregulated in cancer and affect cellular outcomes to chemotherapy and carcinogenesis. Endonuclease VIII-like 3 (NEIL3) is a DNA glycosylase protein that is involved in oxidative and interstrand crosslink DNA damage repair. Our previous work has showed that NEIL3 is required to maintain replication fork integrity. It is unknown whether NEIL3 overexpression could contribute to cancer phenotypes, and its prognostic value and use as potential drug target remain unexplored. Our analysis of cancer genomics data sets reveals that NEIL3 frequently undergoes overexpression in several cancers. Furthermore, patients who exhibited NEIL3 overexpression with pancreatic adenocarcinoma, lung adenocarcinoma, lower grade glioma, kidney renal clear cell carcinoma, and kidney papillary cell carcinoma had worse overall survival. Importantly, NEIL3 overexpressed tumors accumulate mutation and chromosomal variations. Furthermore, NEIL3 overexpressed tumors exhibit simultaneous overexpression of homologous recombination genes (BRCA1/2) and mismatch repair genes (MSH2/MSH6). However, NEIL3 overexpression is negatively correlated with tumor overexpressing nucleotide excision repair genes (XPA, XPC, ERCC1/2). Our results suggest that NEIL3 might be a potential prognosis marker for high-risk patients, and/or an attractive therapeutic target for selected cancers.


Association of macroscopic gut inflammation with disease activity, functional status and quality of life in ankylosing spondylitis.
The aim of this cross-sectional study was to evaluate the frequency of intestinal inflammation and its association with disease activity, functional status and quality of life in patients with ankylosing spondylitis (AS). A total of 25 patients with AS had undergone ileocolonoscopy and concomitant histological study. Clinical and demographical parameters, BASDAI, BASFI, and SF-36 scores were compared between patients with and without macroscopic gut inflammation (MGI). Colonoscopic study revealed MGI in 9 patients and macroscopically normal gut mucosa in 16 patients. On histological examination, of 25 patients 20 had gut inflammation, mostly in ileum. BASDAI score was higher (P < 0.05), SF-36 pain and physical scores, and chest expansion measurement were lower (P = 0.00, P = 0.01, P = 0.01), duration of morning stiffness was longer (P = 0.01) in patients with MGI. Serum C-reactive protein, erytrocyte sedimentation rate levels were similar between groups (P > 0.05). There is high prevalence of histological gut inflammation in AS patients. More active disease should suggest gut inflammation in AS patients.


Biointerface mineralization generates ultraresistant gut microbes as oral biotherapeutics.
Despite the fact that oral microecologics are effective in modulating the gut microbiome, they always suffer from multiple insults during the journey from manufacture to arrival at the intestine. Inspired by the protective mechanism of mineralization, we describe a cytocompatible approach of biointerface mineralization that can generate an ultraresistant and self-removable coating on bacterial surface to solve these challenges. Mineral coating endows bacteria with robust resistances against manufacture-associated oxygen exposure, ultraviolet irradiation, and 75% ethanol. Following oral ingestion, the coating is able to actively neutralize gastric acid and release encapsulated bacteria through spontaneous yet rapid double-decomposition reaction. In addition to acid neutralization, the generated calcium ions can trigger micellar aggregation of bile acid, enabling dual exemptions from the insults of gastric acid and bile acid to achieve uncompromised bacterial viability. Further supported by the therapeutic efficacy of coated bacteria toward colitis mice, biointerface mineralization provides a versatile platform for developing next-generation living oral biotherapeutics.


[Primary Adenocarcinoma of the Bladder at the Vesicocutaneostomy Site Occuring 30 Years after the Operation].
We report a rare case of primary adenocarcinoma in an 82-year-old man that developed 30 years after vesicocutaneostomy was performed to treat pelvic fractures and urethral injury sustained in a traffic accident. He was lost to follow-up after the surgery. However, he presented again at our hospital with gross hematuria. We detected adenocarcinoma at the edge of the vesicocutaneostomy site in the cystoscopic examination and biopsy findings through the stoma. Computed tomography revealed no evidence of metastasis. We conducted radical cystectomy and abdominal wall resection around the vesicocutaneostomy site and ileal conduit formation. Histopathological examination of surgical specimens revealed primary adenocarcinoma of enteric metaplasia origin and skin involvement. The pathological diagnosis was T4b N0 M0 (stage IV) adenocarcinoma of the bladder. In our case, chronic irritation at the stoma was thought to have induced enteric metaplasia of the bladder epithelium and adenocarcinoma. Although the only symptom exhibited was mild gross hematuria, our case was of advanced cancer with skin involvement. Primary adenocarcinoma of the bladder is rare, and only a few cases of adenocarcinoma associated with vesicocutaneostomy have been reported. However, careful examination should be performed to avoid overlooking malignant tumors in cases with bleeding from the vesicocutaneostomy site.


Worry versus anxiety. Is there really a difference?
The similarities and distinctions between the constructs of worry and anxiety were examined in a sample of 189 university students. Three worry scales and four measures of anxiety were compared in relation to measures of negative affect, personal control, and problem-solving style. Although measures of worry and anxiety were highly correlated, negative affect (e.g. depression, confusion) tended to be more closely related to anxiety than to worry, whereas problem-solving style tended to be more closely related to worry than to anxiety. Personal control did not show a differential relationship to anxiety or worry. When the definition of anxiety was restricted to somatic anxiety, however, negative affect, perceived problem-solving abilities, and personal control were more strongly related to worry than to anxiety. Implications of these results are discussed in light of current definitions and measurement of these constructs.


Treatment patterns and health care resource utilization associated with dalfampridine extended release in multiple sclerosis: a retrospective claims database analysis.
Although previous studies have demonstrated the clinical benefits of dalfampridine extended release (D-ER) tablets in patients with multiple sclerosis (MS), there are limited real-world data on D-ER utilization and associated outcomes in patients with MS. The objective of this study was to evaluate treatment patterns, budget impact, and health care resource utilization (HRU) associated with D-ER use in a real-world setting. A retrospective claims database analysis was conducted using the HealthCore Integrated Research Database(SM). Adherence (measured by medication possession ratio, or [MPR]) and persistence (measured by days between initial D-ER claim and discontinuation or end of follow-up) were evaluated over 1-year follow-up. Budget impact was calculated as cost per member per month (PMPM) over the available follow-up period. D-ER and control cohorts were propensity-score matched on baseline demographics, comorbidities, and MS-related resource utilization to compare walking-impairment-related HRU over follow-up. Of the 2,138 MS patients identified, 1,200 were not treated with D-ER (control) and 938 were treated with D-ER. Patients were aged 51 years on average and 74% female. Approximately 82.6% of D-ER patients were adherent (MPR >80%). The estimated budget impact range of D-ER was $0.014-$0.026 PMPM. Propensity-score-matched D-ER and controls yielded 479 patients in each cohort. Postmatching comparison showed that the D-ER cohort was associated with fewer physician (21.5% vs 62.4%, P<0.0001) and other outpatient visits (22.8% vs 51.4%, P<0.0001) over the 12-month follow-up. Changes in HRU from follow-up to baseline were lower in the D-ER cohort for metrics including walking-impairment-related hospitalizations and emergency department visits. The majority of D-ER patients were adherent to treatment. D-ER utilization was associated with fewer walking-impairment-related physician and outpatient visits, with lower HRU increase over time. The budget impact of D-ER was low.


Postnatal uterine development in the rat: estrogen and antiestrogen effects on luminal epithelium.
We examined the effects of the synthetic estrogens, diethylstilbestrol (DES) and ethynylestradiol (EE), and the triphenylethylene antiestrogen, clomiphene citrate (CC), on uterine growth and development in the rat. These compounds, unlike estradiol, do not bind significantly to rat serum alphafetoprotein (AFP). Administration of DES or EE during the period of normal uterine gland genesis (postnatal days 10-14) induced luminal epithelium hypertrophy and increased uterine wet weight. The durations of these responses were dose-related. By day 26, luminal epithelium cell numbers were significantly depressed, compared to controls. Uterine gland development was delayed 6 to 9 days, depending upon estrogen dose, and the numbers of uterine glands ultimately achieved were generally less than in untreated control animals. While a daily dose of 0.1 micrograms CC/rat did not alter uterine development, 10 micrograms CC/rat caused prolonged luminal epithelium hypertrophy and inhibited uterine gland genesis without inducing the large increases in uterine weight or the decreases in luminal epithelium cell number seen after estrogen exposure. The number of stromal cells was significantly increased on day 26 after CC exposure. Together with previous studies, these data demonstrate the greater potency and developmental stage specificity of non-AFP-bound estrogens with respect to altering uterine gland development. In addition, these data suggest that the disruptive influence of antiestrogens on gland genesis may be mediated through an indirect influence on the uterine stroma.


Predictors and outcomes of unplanned readmission to a different hospital.
To examine patient, hospital and market factors and outcomes associated with readmission to a different hospital compared with the same hospital. A population-based, secondary analysis using multilevel causal modeling. Acute care hospitals in California in the USA. In total, 509 775 patients aged 50 or older who were discharged alive from acute care hospitals (index hospitalizations), and 59 566 who had a rehospitalization within 30 days following their index discharge. No intervention. Thirty-day unplanned readmissions to a different hospital compared with the same hospital and also the costs and health outcomes of the readmissions. Twenty-one percent of patients with a rehospitalization had a different-hospital readmission. Compared with the same-hospital readmission group, the different-hospital readmission group was more likely to be younger, male and have a lower income. The index hospitals of the different-hospital readmission group were more likely to be smaller, for-profit hospitals, which were also more likely to be located in counties with higher competition. The different-hospital readmission group had higher odds for in-hospital death (8.1 vs. 6.7%; P < 0.0001) and greater readmission hospital costs ($15 671.8 vs. $14 286.4; P < 0.001) than the same-hospital readmission group. Patient, hospital and market characteristics predicted different-hospital readmissions compared with same-hospital readmissions. Mortality and cost outcomes were worse among patients with different-hospital readmissions. Strategies for better care coordination targeting people at risk for different-hospital readmissions are necessary.


Individual chaperones required for Yop secretion by Yersinia.
Pathogenic yersiniae secrete anti-host proteins called Yops, by a recently discovered Sec-independent pathway. The Yops do not have a classical signal peptide at their N terminus and they are not processed during membrane translocation. The secretion domain is nevertheless contained in their N-terminal part but these domains do not resemble each other in the different Yops. We have previously shown that YopE secretion requires SycE, a 15-kDa acidic protein acting as a specific cytosolic chaperone. Here we show that the gene downstream from yopH encodes a 16-kDa acidic protein that binds to hybrid proteins made of the N-terminal part of YopH and either the bacterial alkaline phosphatase or the cholera toxin B subunit. Loss of this protein by mutagenesis led to accumulation of YopH in the cytoplasm and to a severe and selective reduction of YopH secretion. This protein thus behaves like the counterpart of SycE and we called it SycH. We also engineered a mutation in lcrH, the gene upstream from yopB and yopD, known to encode a 19-kDa acidic protein. Although this mutation was nonpolar, the mutant no longer secreted YopB and YopD. The product of lcrH could be immunoprecipitated together with cytoplasmic YopD. lcrH therefore seems to encode a YopD-specific chaperone, which we called SycD. Determination of the dependence of YopB on SycD requires further investigation. SycE, SycH, and SycD appear to be members of a new family of cytosolic chaperones required for Yop secretion.


[Rb(18-crown-6)][Rb([2.2.2]-cryptand)]Rb(2)Sn(9)·5NH(3).
The crystal structure of the title compound, poly[[(4,7,13,16,21,24-hexa-oxa-1,10-diaza-bicyclo-[8.8.8]hexa-cosa-ne)rubidium] [[(1,4,7,10,13,16-hexa-oxacyclo-octa-deca-ne)rubidium]di-μ-rubidium-μ-nona-stannide] penta-ammonia], {[Rb(C(18)H(36)N(2)O(6))][Rb(3)Sn(9)(C(12)H(24)O(6))C(12)H(24)O(6))]·5NH(3)}(n) represents the first ammoniate of a Zintl anion together with two different chelating substances, namely 18-crown-6 and [2.2.2]-cryptand. The involvement of these large mol-ecules in the crystal structure of [Rb(18-crown-6)][Rb([2.2.2]-cryptand)]Rb(2)Sn(9)·5NH(3) leads to the formation of a new structural motif, namely one-dimensionally extended double strands running parallel to [100] and built by Sn(9) (4-) cages and Rb(+) cations. The double strands are shielded by 18-crown-6 and [2.2.2]-cryptand. The cations are additionally coordin-ated by ammonia mol-ecules. One of the four independent Rb(+) cations is disordered over two sets of sites in a 0.74 (2):0.26 (2) ratio.


[Effect of lentivirus-mediated hIL-24 gene on proliferation, migration and invasion of keloid fibroblasts].
To investigate the effect of hIL-24 gene on proliferation, migration and invasion activity of human keloid fibroblasts (KFs). hIL-24 gene was cloned into lentivirus vector, then the lentivirus particles expressing hlL-24 were infected into KF cells. Real-time PCR and Western blot were performed to examine the expression of hIL-24 in lentivirus infected cells. The growth ability was detected by MTT assay. The cell cycle was analyzed by flow cytometry, The invasion and migration were detected by matrigel invasion assay and wound healing assay. Comparing to controls group and KF-NC group, the expression levels of hIL-24 mRNA and protein were both significantly up-regulated after 4 days of hIL-24 lentivims infection. Comparing with the KF-NC group, MTT assay showed that the A490 of KF-hlL-24 group was down-regulated after lentivims infection ( P < 0. 05 ). Comparing with the KF-NC group, Cell cycle test revealed hlL-24 gene could block KF cells in G1 [(75. 40 ±2. 10)% ] , the proportion of KF cells was decreased in S phase [(4. 96 ± 1. 60)% ] and G2 phase [(0.01 ± 0.01)% ]. After KF cells were infected(P <0.01). Transfection of hlL-24 lentivirus inhibited the migration and invasion activity of KF cells. Lentivirus-mediated hlL-24 gene efficiently inhibits proliferation, cell cycle progression, migration and invasion activity of KF cells.


Occurrence and characterization of yeasts isolated from artisanal Fiore Sardo cheese.
The occurrence of yeast microflora in artisanal Fiore Sardo cheese during ripening was studied. Mean yeast counts ranged from 2.64+/-1 log(10) cfu ml(-1) in milk to 0.65+/-1 log(10) cfu g(-1) in 9 months cheese, with the higher counts observed in 48-h-old cheese. Strains belonging to the prevalent species Debaryomyces hansenii, Kluyveromyces lactis, Geotrichum candidum, Candida zeylanoides and Candida lambica were selected for technological and genotypic characterization. All D. hansenii strains fermented glucose and assimilated lactate, a high percentage assimilated citrate and only a few showed proteolytic and lipolytic activity. All K. lactis strains were able to both assimilate and ferment lactose, to assimilate lactate and to exhibit proteolytic activity on casein. G. candidum assimilated lactate and some strains showed proteolytic and lipolytic activity. C. zeylanoides showed lipolytic activity on tweens and the majority of strains assimilated citrate. C. lambica fermented glucose and assimilated lactate. Considering their diffusion and technological characteristics, an important role for K. lactis and G. candidum in the early stages of the ripening process and for D. hansenii after the first month of ripening can be suggested. RAPD-PCR analysis with M13 primer grouped the isolates in well-separated clusters with their type strains and confirmed the previous phenotypic identification. The high intraspecific homogeneity observed in tested strains could be explained by their isolation from a common substrate and from neighbouring geographical areas. This preliminary study allowed us to isolate autochthon yeast strains showing particular properties which can contribute to the production of typical cheese taste and flavour.


Study on pruritus in hemodialysis patients and the antipruritic effect of neurotropin: plasma levels of substance P, somatostatin, IgE, PTH and histamine.
It has been reported that Neurotropin can markedly improve pruritus in patients undergoing hemodialysis (HD). In order to elucidate the probable causes of pruritus and the antipruritic effect of Neurotropin, various biochemical parameters in the plasma of patients before and during HD were investigated. Forty-three patients undergoing HD were divided into three groups. Eighteen patients had suffered no episode of pruritus (group A), 17 patients had on-going pruritus (group B) and the remaining 8 patients had experienced improvement of pruritus following Neurotropin treatment (group C). The mean concentration of substance P was in only B group significantly increased with HD only in B group, indicating that substance P could be one of the causes of pruritus in patients undergoing HD. Neurotropin appears to exert its antipruritic effect by lowering the level of substance P. The change in parathyroid hormone (PTH) level during HD was not significant in any of the groups, but the mean concentration of PTH in group B was higher than that of group A, indicating that PTH may also be one of the causes of pruritus.


Regional distribution of alpha- and gamma-type endorphins in rat brain.
The regional distribution of Met-enkephalin, beta-endorphin and alpha- and gamma-type endorphins in rat brain was investigated. To that end, brains were dissected into anatomically defined areas. Acetic acid tissue extracts were fractionated using an HPLC system suitable for separation of endorphins and peptide concentrations were subsequently measured by specific radioimmunoassay systems. The distribution of Met-enkephalin and beta-endorphin through the brain was fairly uneven and in accordance with results obtained by others. The peptides alpha-endorphin, gamma-endorphin, des-Tyr-alpha-endorphin (DT alpha E) and des-Tyr-gamma-endorphin (DT gamma E) were detectable in almost all brain areas. Their distribution, however, appeared to be uneven. Hypothalamus and septum showed the highest levels of alpha- and gamma-type endorphins. These regions also contained high amounts of beta-endorphin, underscoring a precursor function of this peptide in the formation of alpha- and gamma-type fragments. In general, levels of alpha-endorphin were higher than those of des-Try-alpha-endorphin, whereas the opposite was found for gamma- and des-Tyr-gamma-endorphin.


[Synthesis of novel beta-aminoalcohols containing nabumetone moiety with potential antidiabetic activity].
Twenty five new beta-aminoalcohols containing nabumetone moiety were prepared via the reduction of potassium borohydride with a convenient and efficient procedure, starting from beta-aminoketones that have been synthesized by our group. Their chemical structures were determined by IR, MS, 1H NMR, 13C NMR, HR-MS and antidiabetic activities were screened in vitro. Preliminary results revealed that the antidiabetic activity of most beta-aminoalcohols were better than that of the corresponding beta-aminoketones. Although most compounds showed weak antidiabetic activity, the alpha-glucosidase inhibitory activity of compounds 5hd(1) and 5id(2) reached 74.37% and 90.15%, respectively, which were superior to the positive control. The relative peroxisome proliferator-activated receptor response element (PPRE) activity of five compounds were more than 60%, among them compound 5ca possessed the highest activity (112.59%). As lead molecules of antidiabetic agents, compounds 5hd(1), 5id(2) and 5ca deserve further study.


Necrotizing soft tissue infections (NSTIs): literary review and description of a Fournier syndrome case.
A 62 y.o. male with tight fimosis, swelling, redness, pain on palpating and necrosis of the penis and scrotum was admitted in our clinic, (FGSI = 6) with periferic vasculopathy; and diabetes mellitus type II and he was in dialysis treatment before the hospitalization. The patient was HCV affected. In 24 hours he underwent radical surgical debridement with excision of all necrotic material from penis and scrotum up to the subdermal layer and tissue of doubtful viability for about 75% of the skin and circumcision. In third, fifth and seventh postoperative days he underwent to local infusion of autologous PLT growth factors. The patient was discharged in 9th postoperative day and FGSI was still 6; the skin and subdermal tissue was barely reskined, with low homogeneous granulation, edema was heavely reduced. In our case, deviation from homeostasis status at admission was the main worrying factor. We found that diabetes mellitus and renal dysfunction at admission was also important risk factor for FG. "E.Coli" was the most common organism isolated from patient wound cultures. The FGSI is an objective and easy to apply score method to quantify the metabolic status and can be used to evaluate therapeutic options and assess results.


Alcohol advertising and youth.
The question addressed in this review is whether aggregate alcohol advertising increases alcohol consumption among college students. Both the level of alcohol-related problems on college campuses and the level of alcohol advertising are high. Some researchers have concluded that the cultural myths and symbols used in alcohol advertisements have powerful meanings for college students and affect intentions to drink. There is, however, very little empirical evidence that alcohol advertising has any effect on actual alcohol consumption. The methods used in this review include a theoretical framework for evaluating the effects of advertising. This theory suggests that the marginal effect of advertising diminishes at high levels of advertising. Many prior empirical studies measured the effect of advertising at high levels of advertising and found no effect. Those studies that measure advertising at lower, more disaggregated levels have found an effect on consumption. The results of this review suggest that advertising does increase consumption. However, advertising cannot be reduced with limited bans, which are likely to result in substitution to other available media. Comprehensive bans on all forms of advertising and promotion can eliminate options for substitution and be potentially more effective in reducing consumption. In addition, there is an increasing body of literature that suggests that alcohol counteradvertising is effective in reducing the alcohol consumption of teenagers and young adults. These findings indicate that increased counteradvertising, rather than new advertising bans, appears to be the better choice for public policy. It is doubtful that the comprehensive advertising bans required to reduce advertising would ever receive much public support. New limited bans on alcohol advertising might also result in less alcohol counteradvertising. An important topic for future research is to identify the counteradvertising themes that are most effective with youth.


Prioritization of risk genes for Alzheimer's disease: an analysis framework using spatial and temporal gene expression data in the human brain based on support vector machine.
Background: Alzheimer's disease (AD) is a complex disorder, and its risk is influenced by multiple genetic and environmental factors. In this study, an AD risk gene prediction framework based on spatial and temporal features of gene expression data (STGE) was proposed. Methods: We proposed an AD risk gene prediction framework based on spatial and temporal features of gene expression data. The gene expression data of providers of different tissues and ages were used as model features. Human genes were classified as AD risk or non-risk sets based on information extracted from relevant databases. Support vector machine (SVM) models were constructed to capture the expression patterns of genes believed to contribute to the risk of AD. Results: The recursive feature elimination (RFE) method was utilized for feature selection. Data for 64 tissue-age features were obtained before feature selection, and this number was reduced to 19 after RFE was performed. The SVM models were built and evaluated using 19 selected and full features. The area under curve (AUC) values for the SVM model based on 19 selected features (0.740 [0.690-0.790]) and full feature sets (0.730 [0.678-0.769]) were very similar. Fifteen genes predicted to be risk genes for AD with a probability greater than 90% were obtained. Conclusion: The newly proposed framework performed comparably to previous prediction methods based on protein-protein interaction (PPI) network properties. A list of 15 candidate genes for AD risk was also generated to provide data support for further studies on the genetic etiology of AD.


Effects of orally administered ritodrine on carbohydrate and lipid metabolism in pregnant patients with abnormal glucose tolerance.
The metabolic effects of a widely used betamimetic agent (ritodrine) were studied in two groups of pregnant patients with abnormal glucose tolerance. No significance modification of various metabolic parameters was detected when the drug was orally administered in standard doses for at least 1 week. The possible reasons for this finding are discussed. Following the absence of any diabetogenic effect, a prolonged use of betamimetics to achieve tocolysis seems to be safe even in patients with metabolic disorders.


Marine-Derived Biocatalysts: Importance, Accessing, and Application in Aromatic Pollutant Bioremediation.
The aim of the present review is to highlight the potential use of marine biocatalysts (whole cells or enzymes) as an alternative bioprocess for the degradation of aromatic pollutants. Firstly, information about the characteristics of the still underexplored marine environment and the available scientific tools used to access novel marine-derived biocatalysts is provided. Marine-derived enzymes, such as dioxygenases and dehalogenases, and the involved catalytic mechanisms for the degradation of aromatic and halogenated compounds, are presented, with the purpose of underpinning their potential use in bioremediation. Emphasis is given on persistent organic pollutants (POPs) that are organic compounds with significant impact on health and environment due to their resistance in degradation. POPs bioaccumulate mainly in the fatty tissue of living organisms, therefore current efforts are mostly focused on the restriction of their use and production, since their removal is still unclear. A brief description of the guidelines and criteria that render a pollutant POP is given, as well as their potential biodegradation by marine microorganisms by surveying recent developments in this rather unexplored field.


'You get out what you put in'.
Chris O'Connor trained at the Nightingale School of Nursing at St Thomas' Hospital in London, qualifying as a mental health nurse in 1993. He worked in acute psychiatry, and learning disabilities and older people's services, before becoming head of nursing practice for a London mental health trust. His current role is nurse consultant for dementia and older people at East Surrey Hospital.


A Review of Price Transparency Policy and Evaluation of Hospital Compliance in Orthopedic Sports Medicine.
Background: In 2019, the Centers for Medicare and Medicaid Services (CMS) announced that beginning January 1, 2021, hospitals would be required to post pricing information in a usable format for patients via diagnosis-related group (DRG) or charge description master (CDM) sheets. Purpose/Questions: We hypothesized the new price transparency rule would pose challenges for many health care facilities. We therefore sought to find out how much pricing information was available before the rule took effect and how usable it was for patients receiving sports medicine care. Methods: In late 2019, we randomly selected 100 general hospitals (GH) from the CMS hospital list and an additional 21 orthopedic hospitals (OH). The DRG and/or CDM sheets were obtained from hospital websites. Pricing information for 6 sports medicine procedures (rotator cuff repair, shoulder arthroscopy, knee arthroscopy, anterior cruciate ligament reconstruction, meniscal repair, and steroid injection) was evaluated in qualitative and quantitative form. Results: Pricing information was provided by 74% of GH and 86% of OH. The price of steroid injections was frequently reported in usable form, with 80% by GH and 78% by OH. The remaining procedures were reported by less than 27% of GH and 40% of OH. For each procedure, component pricing was provided by at least 60% of GH and 78% of OH. No facility provided a pricing calculator or payer-type specific rates. Conclusions: Prior to the enactment of the new price transparency rule in January 2021, most facilities provided some pricing information to patients. However, reporting rates in sports medicine were low and the available data were of little use to patients.


Outcomes of two different treatment modalities in mild to moderate keratoconus.
To describe visual and refractive outcomes of intrastromal corneal ring segments (ICRS) and toric implantable collamer lenses (TICL) implantation in cases of mild and moderate keratoconus. A prospective descriptive interventional case series. 40 eyes were allocated into two groups. First group (20 eyes) was treated with corneal collagen crosslinking (CXL) 1 month after ICRS implantation and the second group was treated using TICL after 1 year of CXL. Both groups showed statistically significant improvement in spherical equivalent, cylindrical refraction, uncorrected visual acuity (UCVA) and best corrected visual acuity (BCVA) over the follow-up period. Both ICRS and TICL are effective in treatment of mid and moderate keratoconus with more predictable visual results with TICL.


Development and characterization of poly(1-vinylpyrrolidone-co-vinyl acetate) copolymer based polymer electrolytes.
Gel polymer electrolytes (GPEs) are developed using poly(1-vinylpyrrolidone-co-vinyl acetate) [P(VP-co-VAc)] as the host polymer, lithium bis(trifluoromethane) sulfonimide [LiTFSI] as the lithium salt and ionic liquid, and 1-ethyl-3-methylimidazolium bis(trifluoromethylsulfonyl) imide [EMImTFSI] by using solution casting technique. The effect of ionic liquid on ionic conductivity is studied and the optimum ionic conductivity at room temperature is found to be 2.14 × 10(-6) S cm(-1) for sample containing 25 wt% of EMImTFSI. The temperature dependence of ionic conductivity from 303 K to 353 K exhibits Arrhenius plot behaviour. The thermal stability of the polymer electrolyte system is studied by using thermogravimetric analysis (TGA) while the structural and morphological properties of the polymer electrolyte is studied by using Fourier transform infrared (FTIR) spectroscopy and X-ray diffraction analysis (XRD), respectively.


YM116, 2-(1H-imidazol-4-ylmethyl)-9H-carbazole, decreases adrenal androgen synthesis by inhibiting C17-20 lyase activity in NCI-H295 human adrenocortical carcinoma cells.
The concentrations of androstenedione and dehydroepiandrosterone, products of C17-20 lyase, in the medium after a 6-hr incubation of NCI-H295 cells were decreased by YM116 (2-(1H-imidazol-4-ylmethyl)-9H-carbazole) (IC50: 3.6 and 2.1 nM) and ketoconazole (IC50: 54.9 and 54.2 nM). 17Alpha-hydroxyprogesterone, a product of 17alpha-hydroxylase, was increased by YM116 (1-30 nM) and by ketoconazole (10-300 nM) and then was decreased at higher concentrations of both agents (IC50: 180 nM for YM116, 906 nM for ketoconazole), indicating that YM116 and ketoconazole were 50- and 16.5-fold more specific inhibitors of C17-20 lyase, respectively, than 17alpha-hydroxylase. Compatible with these findings, progesterone, a substrate of 17alpha-hydroxylase, was increased by these agents. Cortisol production was inhibited by YM116 and ketoconazole (IC50: 50.4 and 80.9 nM, respectively). YM116 was a 14-fold more potent inhibitor of androstenedione production than cortisol production, whereas ketoconazole was a nonselective inhibitor of the production of both steroids. YM116 and ketoconazole inhibited the C17-20 lyase activity in human testicular microsomes (IC50: 4.2 and 17 nM, respectively). These results demonstrate that YM116 reduces the synthesis of adrenal androgens by preferentially inhibiting C17-20 lyase activity.


Intravenous nicardipine for treatment of postcoarctectomy hypertension in children.
Our objective was to evaluate the efficacy of intravenous (IV) nicardipine for the treatment of postcoarctectomy hypertension in children with coarctation of the aorta. We carried out a retrospective review in a pediatric intensive care unit at a tertiary care children's hospital. The patients were children with coarctation of the aorta treated for postcoarctectomy hypertension. Children with postcoarctectomy hypertension defined as a systolic blood pressure >95th percentile for age measured by indwelling arterial catheter were treated with IV nicardipine. We measured change in mean arterial blood pressure (MAP), mean systolic and diastolic blood pressure, and mean heart rate (HR) from baseline after initiating treatment with IV nicardipine. The outcome measure was a reduction in MAP and mean systolic and diastolic blood pressure after treatment with IV nicardipine. During a 4-year period, 10 children met the study criteria. Median age was 3.25 months (range, 0.25 to 180 months). Initial median treatment dose of IV nicardipine was 1.0 micro g/kg/min (range, 0.5 to 6 micro g/kg/min); median dose used to control hypertension was 1.5 micro g/kg/min (range, 0.25 to 6 micro g/kg/min). Median duration of therapy was 26.3 h (range, 13 to 49 h). Treatment with IV nicardipine resulted in a 26.5% decrease in MAP from baseline during the first hour of treatment ( p = 0.0006). Mean systolic blood pressure decreased from 133 to 105 mmHg ( p = 0.005), and mean diastolic blood pressure decreased from 75 to 52.5 mmHg ( p = 0.001) during the first hour of therapy with nicardipine. There was a significant reduction ( p = 0.0005) in MAP during continued treatment with IV nicardipine. The mean HR of 150 remained unchanged during the first hour of therapy with nicardipine, and no significant change in mean HR or adverse effects was noted during continued therapy. Two children receiving other antihypertensive therapy demonstrated further reduction in their blood pressure when IV nicardipine was initiated. Tachycardia and hypotension were not observed in any child treated with IV nicardipine. We concluded that IV nicardipine reduced MAP with no significant change in mean HR and no adverse effects in patients with postcoarctectomy hypertension. Nicardipine produced a further reduction in MAP in children receiving other antihypertensive agents. Nicardipine is an effective agent for treatment of postcoarctectomy hypertension in children with coarctation of the aorta.


The Ibr-7 derivative of ibrutinib exhibits enhanced cytotoxicity against non-small cell lung cancer cells via targeting of mTORC1/S6 signaling.
Ibrutinib is a small molecule drug that targets Bruton's tyrosine kinase in B-cell malignancies and is highly efficient at killing mantle cell lymphoma and chronic lymphocytic leukemia. However, the anti-cancer activity of ibrutinib against solid tumors, such as non-small cell lung cancer (NSCLC), remains low. To improve the cytotoxicity of ibrutinib towards lung cancer, we synthesized a series of ibrutinib derivatives, of which Ibr-7 exhibited superior anti-cancer activity to ibrutinib, especially against epithelial growth factor receptor (EGFR) wild-type NSCLC cell lines. Ibr-7 was observed to dramatically suppress the mammalian target of Rapamycin complex 1 (mTORC1)/S6 signaling pathway, which is only slightly affected by ibrutinib, thus accounting for the superior anti-cancer activity of Ibr-7 towards NSCLC. Ibr-7 was shown to overcome the elevation of Mcl-1 caused by ABT-199 mono-treatment, and thus exhibited a significant synergistic effect when combined with ABT-199. In conclusion, we used a molecular substitution method to generate a novel ibrutinib derivative, termed Ibr-7, which exhibits enhanced anti-cancer activity against NSCLC cells as compared with the parental compound.


Great Institutions in Cardiothoracic Surgery: The University of Minnesota.
With the loyal support of the chair of Surgery, Dr. Owen H. Wangensteen, the University of Minnesota cardiac surgery program led the way at the dawn of cardiac surgery when Dr F. John Lewis performed the first open heart surgery in the world using hypothermia while repairing an atrial septal defect on September 2, 1952. Soon after, Dr C. Walt Lillehei performed the first repair of a ventriculoseptal defect in the world using cross-circulation on March 26, 1954. Collaborating with Dr Richard DeWall in 1955, they developed the DeWall-Lillehei bubble oxygentor which was used at the University of Minnesota and many other centers worldwide for years to come, making open heart surgery safe and tractable. Dr Vincent Gott, a resident working in the laboratory of Lillehei, developed a method to treat complete heart block using ventricular pacing with a Grass physiological stimulator, and this led to a collaboration with Earl Bakken, founder of the Medtronic Corporation, to develop a temporary pacemaker. The program was fertile ground for many notable trainees, including Dr Norman Shumway, the "Father of Heart Transplant", and Dr Christiaan Barnard who performed the first heart transplant in the world. The collegial and forward thinking nature of the cardiac surgery program continues in the current training program today.


Peripheral TH-17 cells in children with allergic rhinitis: preliminary report.
Th17 is a subset of T helper lymphocytes and exerts pro-inflammatory activities. Recently, it has been reported that serum IL-17 levels are high in the most severe patients with birch allergy studied both outside and during the pollen season. This study aims to compare the frequency of peripheral IL-17-producing T cells in children with allergic rhinitis and in healthy controls. Ten children with allergic rhinitis and 5 healthy non-allergic subjects were evaluated. Th17 were evaluated by intracellular staining in ex-vivo T cell compartment. Ex- vivo PBMNC evaluation showed that allergic patients had higher frequencies of IL-17 producing T cells, both concerning CD4+ and CD8+ cells. In particular, there is a subset co-expressing IL-17 and IFN-gamma both for CD4+ and CD8+ cells. In conclusion, this preliminary study suggests a possible role of Th-17 cells in the response to allergens in children.


Ultrastructure of the "transitional" mucosa adjacent to large bowel carcinoma.
The transitional mucosa immediately adjacent to large bowel carcinoma was examined in 13 patients by scanning electron microscopy (SEM), and this was correlated with transmission electron microscopy (TEM) and light microscopy (LM). Marked abnormalities were present in this mucosa in 9/13 patients with distortion and loss of the normal architecture. Examination of adenomas showed abnormalities also to be present adjacent to the neoplastic mucosa. In all patients, the transitional mucosa was compared with two pieces of normal mucosa; in one patient, typical changes of transitional mucosa were found in this region. In the remaining patients, normal mucosa by SEM was found to consist to large deep furrows (primary crypts) as well as the crypts of Lieberkuhn (secondary crypts). The secondary crypts structure showed marked individual variation between patients but one type was present in nine patients. It is uncertain whether this is a pattern with a high incidence in the general population, or whether patients with this type of mucosa are particularly predisposed to large bowel carcinoma. SEM may, therefore, play a part in identifying patients particularly likely to develop large bowel carcinoma.


Olanzapine associated weight gain, hyperglycemia and neuroleptic malignant syndrome: case report.
We describe here a case of olanzapine associated weight gain, hyperglycemia and neuroleptic malignant syndrome in a 64 year-old woman with a significant medical history. Eighteen weeks after initiating olanzapine, Mrs X lost glycemic control, exhibited signs and symptoms consistent with neuroleptic malignant syndrome and gained 8.9 kg. We suggest that utilization of olanzapine in the less medically stable geriatric patient be implemented with vigilant monitoring for such complications mentioned above.


Effects of plasmid amplification and recombinant gene expression on the growth kinetics of recombinant E. coli.
An experimental study was undertaken to identify and quantitate the effects of plasmid amplification and recombinant gene expression on Escherichia coli growth kinetics. Identification of these effects was possible because recombinant gene expression and plasmid copy number were controlled by different mechanisms on plasmid pVH106/172. Recombinant gene expression of the lactose operon structural genes was under the control of the lac promoter and was activated by the addition of the chemicals, IPTG and cyclic AMP, to the fermentation medium. Plasmid content was amplified in a separate fermentation by increasing culture temperature since the plasmid replicon was temperature-sensitive. A final fermentation was performed in which both plasmid content and recombinant gene expression were induced simultaneously by adding chemicals and raising the culture temperature. Recombinant growth rates were found to be reduced by the expression of high levels of recombinant lac proteins in the chemical induction experiments and by the amplification of plasmid levels in the temperature induction experiment. High expression of recombinant lac proteins following chemical induction was accompanied by a loss in recombinant cell viability. In the plasmid amplification experiment, the recombinant cells did not lose viability but the recombinant product yields were much lower than those achieved in the chemical induction experiments. Combining temperature and chemical induction increased the recombinant product yield by a factor of 4400 but also lowered cellular growth rates by 70%.


Dimerization of the DYT6 dystonia protein, THAP1, requires residues within the coiled-coil domain.
Thanatos-associated [THAP] domain-containing apoptosis-associated protein 1 (THAP1) is a DNA-binding protein that has been recently associated with DYT6 dystonia, a hereditary movement disorder involving sustained, involuntary muscle contractions. A large number of dystonia-related mutations have been identified in THAP1 in diverse patient populations worldwide. Previous reports have suggested that THAP1 oligomerizes with itself via a C-terminal coiled-coil domain, raising the possibility that DYT6 mutations in this region might affect this interaction. In this study, we examined the ability of wild-type THAP1 to bind itself and the effects on this interaction of the following disease mutations: C54Y, F81L, ΔF132, T142A, I149T, Q154fs180X, and A166T. The results confirmed that wild-type THAP1 associated with itself and most of the DYT6 mutants tested, except for the Q154fs180X variant, which loses most of the coiled-coil domain because of a frameshift at position 154. However, deletion of C-terminal residues after position 166 produced a truncated variant of THAP1 that was able to bind the wild-type protein. The interaction of THAP1 with itself therefore required residues within a 13-amino acid region (aa 154-166) of the coiled-coil domain. Further inspection of this sequence revealed elements highly consistent with previous descriptions of leucine zippers, which serve as dimerization domains in other transcription factor families. Based on this similarity, a structural model was generated to predict how hydrophobic residues in this region may mediate dimerization. These observations offer additional insight into the role of the coiled-coil domain in THAP1, which may facilitate future analyses of DYT6 mutations in this region.


Using the behaviour change wheel and person-based approach to develop a digital self-management intervention for patients with adrenal insufficiency: the Support AI study protocol.
Most patients with Adrenal insufficiency (AI) require lifelong glucocorticoid replacement. They need to increase glucocorticoids during physical illness or major stressful situations and require parenteral hydrocortisone in the event of an adrenal crisis. Patients with AI have impaired quality of life and high mortality; approximately 1 in 6-12 patients are hospitalised at least once/year from a potentially preventable adrenal crisis. Adoption of self-management behaviours are crucial; these include adherence to medication, following "sick day rules" and associated behaviours that aid prevention and treatment of adrenal crisis such as symptom monitoring, having extra tablets, carrying a medical-alert ID and injection kit, and self-injecting when necessary. Current patient education is ineffective at supporting self-management behaviour change or reducing adrenal crisis-related hospitalisations. This research study aims to gain an in-depth understanding of the barriers and enablers to self-management for patients with AI and to develop an evidence-based digital self-management behaviour change intervention. The study is conducted in accordance with the MRC Framework for developing complex interventions. Underpinned by the Behaviour Change Wheel (BCW), the Theoretical Domains Framework (TDF), and the Person-Based Approach, this research will be conducted in two phases: Phase 1 will involve a sequential qualitative/quantitative mixed-methods study involving focus group interviews followed by a cross-sectional survey with patients with AI recruited from patient advocacy groups and endocrine clinics in the UK. Phase 2 will develop the Support AI, a website-based digital behaviour change intervention (DBCI) informed by Phase 1 findings to support self-management for patients with AI. The most appropriate behaviour change techniques (BCTs) will be selected utilising a nominal group technique with an Expert Panel of 10-15 key stakeholders. The design of the Support AI website will be guided by the Person-Based Approach using an Agile iterative "think-aloud" technique with 12-15 participants over 3 usability testing iterations. A theory- and evidence-based digital behaviour change intervention will be developed which will be tested in a feasibility randomised trial following completion of this study. The projected benefit includes cost-effective health care service (reduced hospitalisations and demand for specialist services) and improved health outcomes and quality of life for patients with AI.


Modulation of collagen fibrillogenesis by tenascin-X and type VI collagen.
Tenascin-X (TNX) is an extracellular matrix glycoprotein. We previously demonstrated that TNX regulates the expression of type VI collagen. In this study, we investigated the binding of TNX to type I collagen as well as to type VI collagen and the effects of these proteins on fibrillogenesis of type I collagen. Full-length recombinant TNX, which is expressed in and purified from mammalian cell cultures, and type VI collagen purified from bovine placenta were used. Solid-phase assays revealed that TNX or type VI collagen bound to type I collagen, although TNX did not bind to type VI collagen, fibronectin, or laminin. The rate of collagen fibril formation and its quantity, measured as increased turbidity, was markedly increased by the presence of TNX, whereas type VI collagen did not increase the quantity but accelerated the rate of collagen fibril formation. Combined treatment of both had an additive effect on the rate of collagen fibril formation. Furthermore, deletion of the epidermal growth factor-like (EGF) domain or fibrinogen-like domain of TNX attenuated the initial rate of collagen fibril formation. Finally, we observed abnormally large collagen fibrils by electron microscopy in the skin from TNX-deficient (TNX-/-) mice during development. These findings demonstrate a fundamental role for TNX and type VI collagen in regulation of collagen fibrillogenesis in vivo and in vitro.


Metabolic Fingerprint of PS3-Induced Resistance of Grapevine Leaves against Plasmopara viticola Revealed Differences in Elicitor-Triggered Defenses.
Induction of plant resistance against pathogens by defense elicitors constitutes an attractive strategy to reduce the use of fungicides in crop protection. However, all elicitors do not systematically confer protection against pathogens. Elicitor-induced resistance (IR) thus merits to be further characterized in order to understand what makes an elicitor efficient. In this study, the oligosaccharidic defense elicitors H13 and PS3, respectively, ineffective and effective to trigger resistance of grapevine leaves against downy mildew, were used to compare their effect on the global leaf metabolism. Ultra high resolution mass spectrometry (FT-ICR-MS) analysis allowed us to obtain and compare the specific metabolic fingerprint induced by each elicitor and to characterize the associated metabolic pathways. Moreover, erythritol phosphate was identified as a putative marker of elicitor-IR.


Gender and obesity modify the impact of salt intake on blood pressure in children.
Most modifiable risk factors for high blood pressure (BP), such as obesity and salt intake, are imprinted in childhood and persist into adulthood. The aim of our study was to evaluate the intake of salt in children and to assess its impact on BP taking into account gender and nutritional status. A total of 298 children aged 8-9 years were evaluated in a cross-sectional study. Anthropometric measurements and 24-h ambulatory monitoring were performed, and salt intake was determined by 24-h urinary sodium excretion. The average estimated salt intake among the entire cohort of children enrolled in the study was 6.5 ± 2.2 g/day, and it was significantly higher in boys than in girls (6.8 ± 2.4 vs. 6.1 ± 1.9 g/day, respectively; p = 0.018) and in overweight/obese children than in normal weight children (6.8 ± 2.4 vs. 6.1 ± 2.0 g/day, respectively; p = 0.006). Salt intake exceeded the upper limit of the US Dietary Reference Intake in 72% of children. Daytime systolic BP increased by 1.00 mmHg (95% confidence interval 0.40-1.59) per gram of daily salt intake in overweight/obese boys, but not in normal weight boys or in girls. Our results demonstrate an extremely high salt intake among 8- to 9-year-old Portuguese children. Higher salt intake was associated with higher systolic BP in boys, specifically in those who were overweight/obese. Longitudinal studies are needed to further evaluate the causal relationship between obesity and high BP and the mechanism by which salt intake modulates this relationship. Nonetheless, based on our results, we urge that dietary salt reduction interventions, along with measures to fight the global epidemic of obesity, be implemented as early in life as possible.


[The role of Angelica polysaccharides in inducing effector molecule release by peritoneal macrophages].
To observe the effect of Angelica polysaccharides on effector molecule production by peritoneal macrophages. Macrophages were isolated from the peritoneal cavity of BALB/c mice and the primary culture was performed. MTT colorimetry and spectrophotometry were used to examine the effects of Angelica polysaccharides on the releases of effector molecules, such as nitric oxide(NO), tumor necrosis factor-alpha(TNF-alpha), and reactive oxygen species(ROS) as well as inducible nitric oxide synthase (iNOS) and lysozyme(LSZ) activity by peritoneal macrophages. Angelica polysaccharides could promote the releases of NO, TNF-alpha and ROS from macrophages and improved iNOS and LSZ activities in macrophages. However, Angelica polysaccharides had no direct cytotoxicity to tumor cells, but the cultural supernatant of macrophages cocultured with Angelica polysaccharides could kill L929 cells. Angelica polysaccharides can promote the releases of NO, TNF-alpha and ROS by macrophages. Angelica polysaccharides may indirectly play the role of anti-tumors through increased TNF-alpha production by macrophages.


The putative single-stranded DNA-binding protein of the filamentous bacteriophage, Ifl. Amino acid sequence of the protein and structure of the gene.
The protein product corresponding to the gene located in the region of the coliphage Ifl genome shown to contain the code for the single-stranded DNA (ssDNA)-binding proteins of all filamentous phages so far studied has been isolated from infected bacterial cells and its amino acid sequence determined. The mature protein contains 95 amino acids (calculated molecular mass 10553 Da). Its sequence corresponds to that predicted from the DNA sequence but lacks the initiating methionine residue. Although there is little direct sequence homology between the phage Ifl protein and the ssDNA-binding proteins of the other filamentous phages that have been studied, computer-based comparisons of various physical and structural parameters showed that the phage Ifl protein contains a domain that is closely related to domains in the coliphage T4 gene 32 protein and the Pseudomonas phage Pfl ssDNA-binding protein and suggest that the Ifl protein does have a ssDNA-binding function although we were unable to show this directly.


Inertial Sensors to Assess Gait Quality in Patients with Neurological Disorders: A Systematic Review of Technical and Analytical Challenges.
Gait disorders are major causes of falls in patients with neurological diseases. Understanding these disorders allows prevention and better insights into underlying diseases. InertiaLocoGraphy (ILG) -the quantification of gait by using inertial measurement units (IMUs) -shows great potential to address this public health challenge, but protocols vary widely and normative values of gait parameters are still unavailable. This systematic review critically compares ILG protocols, questions features extracted from inertial signals and proposes a semeiological analysis of clinimetric characteristics for use in neurological clinical routine. For this systematic review, PubMed, Cochrane and EMBASE were searched for articles assessing gait quality by using IMUs that were published from January 1, 2014 to August 31, 2016. ILG was used to assess gait in a wide range of neurological disorders - including Parkinson disease, mild cognitive impairment, Alzheimer disease, cerebral palsy, and cerebellar atrophy - as well as in the faller or frail older population and in people presenting rheumatological pathologies. However, results have not yet been driving changes in clinical practice. One reason could be that studies mainly aimed at comparing pathological gait to healthy gait, but there is stronger need for semiological descriptions of gait perturbation, severity or prognostic assessment. Furthermore, protocols used to assess gait using IMUs are too many. Likely, outcomes are highly heterogeneous and difficult to compare across large panels of studies. Therefore, homogenization is needed to foster the use of ILG to assess gait quality in neurological routine practice. The pros and cons of each protocol are emphasized so that a compromise can be reached. As well, analysis of seven complementary clinical criteria (springiness, sturdiness, smoothness, steadiness, stability, symmetry, synchronization) is advocated.


Daboxin P, a phospholipase A2 of Indian Daboia russelii venom, modulates thrombin-mediated platelet aggregation.
Daboxin P, reported earlier from the venom of Daboia russellii, disturbs the blood coagulation cascade by targeting factor X and factor Xa. The present study exhibits that Daboxin P also inhibits platelet aggregation induced by various agonists. The thrombin-induced platelet aggregation was inhibited maximum whereas inhibition of collagen-induced platelet aggregation was found to be 50% and no inhibition of adenosine diphosphate (ADP) and arachidonic acid-induced aggregation was observed. Daboxin P dose-dependently inhibited the thrombin-induced platelet aggregation with Anti-Aggregation 50 (AD50 ) dose of 55.166 nM and also reduced the thrombin-mediated calcium influx. In-silico interaction studies suggested that Daboxin P binds to thrombin and blocks its interaction with its receptor on the platelet surface. Quenching of thrombin's emission spectrum by Daboxin P and electrophoretic profiles of pull-down assay further reveals the binding between Daboxin P and thrombin. Thus, the present study demonstrates that Daboxin P inhibits thrombin-induced platelet aggregation by binding to thrombin.


Endonasal ethmoidectomy and bifrontal craniotomy with craniofacial approach for resection of frontoethmoidal osteoma causing tension pneumocephalus.
Tension pneumocephalus is an unusual, potentially life-threatening complication of frontal fossa tumors. We present an uncommon case of a frontoethmoidal osteoma causing a tension pneumocephalus and neurological deterioration prompting a combined endonasal ethmoidectomy and bifrontal craniotomy with craniofacial approach for resection. A 68-year-old man presented with a 1-week history of worsening headache, slowness of speech, and increasing confusion. Standard computed tomography scan revealed a marked tension pneumocephalus with ventricular air and 1-cm midline shift to the right. Further studies showed a calcified left ethmoid mass and a left anterior cranial-base defect. A team composed of neurosurgery and otolaryngology performed a combined endonasal ethmoidectomy and bifrontal craniotomy with craniofacial approach to resect a large frontoethmoid bony tumor. No abscess or mucocele was identified. The skull base defect was repaired with the aid of a transnasal endoscopy, a titanium mesh, and a pedunculated pericranial flap. Postoperatively, the pneumocephalus and the patient's symptoms completely resolved. Pathology was consistent with a benign osteoma. This is an uncommon case of a frontoethmoidal osteoma associated with tension pneumocephalus. Recognition of this entity and timely diagnosis and treatment, consisting of an endonasal ethmoidectomy and a bifrontal craniotomy with craniofacial approach, may prevent potential life-threatening complications.


circMET promotes NSCLC cell proliferation, metastasis, and immune evasion by regulating the miR-145-5p/CXCL3 axis.
In recent years, circular RNAs (circRNAs) have been increasingly reported to play a crucial role in the proliferation, migration, and invasion of non-small-cell lung cancer (NSCLC) cells. However, the circRNA MET (circMET) oncogenic mechanism that drives NSCLC development and progression remains largely unknown. In this study, the present results demonstrated that circMET expression was significantly higher in NSCLC tissues than in peritumoral tissues using quantitative real-time polymerase chain reaction. Notably, NSCLC patients with a large tumor diameter, poor differentiation and lymphatic metastasis had high RNA levels of circMET. Moreover, high circMET expression served as an independent risk factor for short overall survival (OS) and progression-free survival (PFS) in NSCLC patients. Next, we validated that circMET overexpression can enhance NSCLC cell proliferation, metastasis, and immune evasion in vitro. Mechanistically, our study uncovers that circMET acts as a miR-145-5p sponge to upregulate CXCL3 expression. Collectively, circMET regulates the miR-145-5p/CXCL3 axis and serves as a novel, promising diagnostic and prognostic biomarker in patients with NSCLC.


Efficient Retrieval of Massive Ocean Remote Sensing Images via a Cloud-Based Mean-Shift Algorithm.
The rapid development of remote sensing (RS) technology has resulted in the proliferation of high-resolution images. There are challenges involved in not only storing large volumes of RS images but also in rapidly retrieving the images for ocean disaster analysis such as for storm surges and typhoon warnings. In this paper, we present an efficient retrieval of massive ocean RS images via a Cloud-based mean-shift algorithm. Distributed construction method via the pyramid model is proposed based on the maximum hierarchical layer algorithm and used to realize efficient storage structure of RS images on the Cloud platform. We achieve high-performance processing of massive RS images in the Hadoop system. Based on the pyramid Hadoop distributed file system (HDFS) storage method, an improved mean-shift algorithm for RS image retrieval is presented by fusion with the canopy algorithm via Hadoop MapReduce programming. The results show that the new method can achieve better performance for data storage than HDFS alone and WebGIS-based HDFS. Speedup and scaleup are very close to linear changes with an increase of RS images, which proves that image retrieval using our method is efficient.


Enantiopure versus Racemic Naphthalimide End-Capped Helicenic Non-fullerene Electron Acceptors: Impact on Organic Photovoltaics Performance.
Impact of the enantiopurity on organic photovoltaics (OPV) performance was investigated through the synthesis of racemic and enantiomerically pure naphthalimide end-capped helicenes and their application as non-fullerene molecular electron acceptors in OPV devices. A very strong increase of the device performance was observed by simply switching from the racemic to the enantiopure forms of these π-helical non-fullerene acceptors with power conversion efficiencies jumping from 0.4 to about 2.0 % in air-processed poly(3-hexylthiophene)-based devices, thus highlighting the key role of enantiopurity in the photovoltaic properties.