Association of prenatal exposure to phenols and parabens with birth size: A systematic review and meta-analysis.
Phenols and parabens are endocrine-disrupting chemicals and are widely used in daily life products due to their antibacterial action. Previous studies suggest associations of prenatal exposure to phenols and parabens with fetal development; however, such findings are rare and inconsistent. The aim of this review and meta-analysis is to estimate the associations between maternal exposure to phenols and parabens and birth size. We identified 21 relevant studies that met the inclusion criteria through databases of PubMed, Cochrane, EMBASE and Qvid Medline. The last search was in July 3, 2019. The heterogeneity and possibility of publication bias among included studies were assessed by Q-statistic and Begg's test, respectively. Meta-analysis revealed that prenatal exposure to triclosan [number of studies (n) = 12, regression coefficient (β) = -0.04 g; 95% confidence interval (CI): -0.139, 0.059], benzophenone-3 (n = 10, β = -0.001 g; 95% CI: -0.013, 0.012), bisphenol A (n = 9, β = -0.049 g; 95% CI: -0.199, 0.101), 2-4-dichlorophenols (n = 6, β = -14.124 g; 95% CI: -29.971, 1.723), 2-5-dichlorophenols (n = 6, β = -0.061 g; 95% CI: -0.196, 0.074) and parabens were negatively associated with fetal birth weight. Most of them were insignificant. Inconsistent and insignificant associations were detected between exposure to phenols and parabens and other birth outcomes. Subgroup analysis suggested that heterogeneity in our meta-analysis was mainly attributed to the studies conducted in developed countries and samples collected in the second trimester. Insignificant and controversial associations of maternal exposure to phenols and parabens with birth size were observed in our study. The study design and methods of the included studies are inconsistent, and the effects of environmental pollutants on human health are complex. Further cohort studies with large samples and a consistent approach are thus required to evaluate the associations of maternal exposure to phenols and parabens with birth size.


Thiosulphate and hydroxocobalamin prophylaxis in progressive cyanide poisoning in guinea-pigs.
The duration of action of the cyanide antidotes sodium thiosulphate and hydroxocobalamin was investigated in guinea-pigs after prophylactic administration before a long-term infusion of NaCN. The parameter for the diminution of the antidote action was the point of time at which the concentration of HCN in the exhaled air of the animals exceeded 100 nmol/kg per min. The time taken to reach this threshold level in the control animals was 12 min. While the threshold level could be extended only to 35 min with hydroxocobalamin (300 mg/kg i.v.) the protective action of sodium thiosulphate (100, 500 and 1000 mg/kg i.v.) persisted dose dependently for about 1, 2 and 4 h, respectively. Additionally we found a plasma half-life of sodium thiosulphate in guinea-pigs of 26 min. This value corresponds approximately to the plasma half-life of sodium thiosulphate in humans given in the literature. Because of the large injection volume necessary, sodium thiosulphate is not suitable for prophylactic use in man.


One pot synthesis of metal ion anchored alginate-gelatin binary biocomposite for efficient Cr(VI) removal.
Biopolymers are widely used for the removal of chromium from aqueous medium but it possesses limitations like poor sorption capacity and low stability. To overcome the limitations of biopolymers and to improve their properties, the present study was designed in such a way to develop a novel sorbent with enhanced chromium sorption capacity and better stability by synthesizing metal ion cross-linked binary biocomposites using biopolymers like alginate and gelatin cross-linked with Ca2+, Ce3+ and Zr4+ ions namely Ca@AlgGel, Ce@AlgGel and Zr@AlgGel composites. The functional groups, agglomeration, surface area, surface morphology, elemental analysis and thermal stability of the composites were investigated by FTIR, TEM, BET, SEM with EDAX and TGA analysis. The chromium removal studies of the biocomposites were carried out in batch mode. The sorption process was optimized by varying the influencing aspects like contact time, dosage, presence of common ions, pH, initial chromium concentration and temperature. The maximum sorption capacity of Ca@AlgGel, Ce@AlgGel and Zr@AlgGel composites were found to be 19.40, 24.50 and 25.40 mg/g, respectively. The sorption data was fitted by using Freundlich, Langmuir and Dubinin-Radushkevich (D-R) isotherms. Thermodynamic parameters indicate the nature of chromium sorption. The suitability of the composite materials was also tested under the field conditions.


A transient-kinetic study of the nitrogenase of Klebsiella pneumoniae by stopped-flow calorimetry. Comparison with the myosin ATPase.
The pre-steady-state kinetics of MgATP hydrolysis by nitrogenase from Klebsiella pneumoniae were studied by stopped-flow calorimetry at 6 degrees C and at pH 7.0. An endothermic reaction (delta Hobs. = +36 kJ.mol of ATP-1; kobs. = 9.4 s-1) in which 0.5 proton.mol of ATP-1 was released, has been assigned to the on-enzyme cleavage of MgATP to yield bound MgADP + Pi. The assignment is based on the similarity of these parameters to those of the corresponding reaction that occurs with rabbit muscle myosin subfragment-1 (delta Hobs. = +32 kJ.mol of ATP-1; kobs. = 7.1 s-1; 0.2 proton released.mol of ATP-1) [Millar, Howarth & Gutfreund (1987) Biochem. J. 248, 683-690]. MgATP-dependent electron transfer from the nitrogenase Fe-protein to the MoFe-protein was monitored by stopped-flow spectrophotometry at 430 nm and occurred with kobs. value of 3.0 s-1 at 6 degrees C. Thus, under these conditions, hydrolysis of MgATP precedes electron transfer within the protein complex. Evidence is presented that suggests that MgATP cleavage and subsequent electron transfer are reversible at 6 degrees C with an overall equilibrium constant close to unity, but that, at 23 degrees C, the reactions are essentially irreversible, with an overall equilibrium constant greater than or equal to 10.


The use of ethology in clinical nursing research.
Although the pragmatic implications for observational research in nursing are profound, these techniques are underused. In this article the methods of ethology, or the systematic detailed study of behavior, and its application to clinical nursing research are described. The authors suggest that ethology may be used to explore behavior in cognitively impaired, elderly patients, psychiatric patients, and infants. The authors also suggest that ethology is suited for examining subconscious or transitory phenomena, such as pain responses, that are unsuited to self-report methods.


Sulfated modification of hyaluronan tetrasaccharide enhances its antitumor activity on human lung adenocarcinoma A549 cells in vitro and in vivo.
Hyaluronan (HA) is a glycosaminoglycan polymer involved in cell phenotype change, inflammation modulation, and tumor metastasis progression. HA oligosaccharides have a higher solubility and drug-forming ability than polysaccharides. HA tetrasaccharide was reported as the smallest fragment required for inhibiting triple-negative breast cancer, but the anti-tumor activity of HA tetrasaccharide (HA4) and its sulfated derivatives in lung cancer is still unknown. In this study, HA4 was prepared via HA degradation by chondroitinase ABC (CSABC), while its sulfated derivatives were prepared by sulfur pyridine trioxide complex in N, N-dimethylformamide (DMF). Then, the anti-tumor activity was detected via MTT assay and xenograft tumor experiments, while the expression level change of apoptosis genes was analyzed by qRT-PCR. Electrospray mass spectrometry (ESI-MS) analysis showed several HA4 sulfated derivatives, GlcA2GlcNAc2 (SO3H)n contains 0-6 sulfation groups, which mainly contain 3-6, 2-3, and 0-1 sulfation groups were classified as HA4S1, HA4S2, and HA4S3, respectively. After the addition of 1.82 mg/mL HA4, HA4S1, HA4S2, and HA4S3, the cell viability of A549 cells was reduced to 81.2 %, 62.1 %, 50.3 %, and 65.9 %, respectively. Thus, HA4S2 was chosen for further measurement, the qRT-PCR results showed it significantly up-regulated the expression of genes in the apoptosis pathway. Moreover, HA4S2 exhibited stronger antitumor activity than HA4 in vivo and the tumor inhibition rate reached 36.90 %. In summary, this study indicated that the CSABC enzyme could effectively degrade HA into oligosaccharides, and sulfation modification was an effective method to enhance the antitumor activity of HA tetrasaccharides.


Urbanization and Population Genetic Structure of the Panama City crayfish (Procambarus econfinae).
For species with geographically restricted distributions, the impacts of habitat loss and fragmentation on long-term persistence may be particularly pronounced. We examined the genetic structure of Panama City crayfish (PCC), Procambarus econfinae, whose historical distribution is limited to an area approximately 145 km2, largely within the limits of Panama City and eastern Bay County, FL. Currently, PCC occupy approximately 28% of its historical range, with suitable habitat composed of fragmented patches in the highly urbanized western portion of the range and managed plantations in the more contiguous eastern portion of the range. We used 1640 anonymous single-nucleotide polymorphisms to evaluate the effects of anthropogenic habitat modification on the genetic diversity and population structure of 161 PCC sampled from across its known distribution. First, we examined urban habitat patches in the west compared with less-developed habitat patches in the east. Second, we used approximate Bayesian computation to model inferences on the demographic history of eastern and western populations. We found anthropogenic habitat modifications explain the genetic structure of PCC range-wide. Clustering analyses revealed significant genetic structure between and within eastern and western regions. Estimates of divergence between east and west were consistent with urban growth in the mid-20th century. PCC have low genetic diversity and high levels of inbreeding and relatedness, indicating populations are small and isolated. Our results suggest that PCC have been strongly affected by habitat loss and fragmentation and management strategies, including legal protection, translocations, or reintroductions, may be necessary to ensure long-term persistence.


Study of a stream in Argentina with a high concentration of microplastics: Preliminary analysis of the methodology.
This study presents for the first time results about the microplastic concentration and their origin in a stream of the Pampas region in Argentina, receiving wastewater of an intermediate city. The most appropriate procedure to analyze and quantify the microplastics in the studied system is the use of an oxidative digestion process using a 30% H2O2 solution to eliminate the organic matter in the samples. A high quantity of MPs, on the order of millions of microplastics per m3 of water, was estimated in the Langueyú stream. 56% of the microplastics correspond to fibers with diameters between 10 and 15 μm and lengths less than 500 μm, while 44% are fragments with sizes of tens of micrometers. Raman microspectroscopy was used to identify the type of fibers. The characteristics of the microplastic fibers released in a wash load test are comparable with those observed in the Langueyú stream, in particular, the average sizes and the distribution of the diameters of the MPFs are similar. The processes in the sewage treatment plant, prior to their discharge in the stream, would affect the color of the fibers and their length.


Current concepts in the evaluation, diagnosis and management of acute infectious diarrhea.
Despite recent advances in our understanding of the pathogenesis of enteric diseases, acute infectious diarrhea remains a major cause of morbidity and mortality worldwide. Infection is the most common cause of acute diarrhea. Some causes of infectious diarrhea also result in serious long-term sequelae such as hemolytic uremic syndrome, Guillain-Barré syndrome and malnutrition. A better understanding of bacterial pathogenesis has grown increasingly important because of the emergence of new pathogens and the growing problems of resistance among enteric pathogens and other enteric flora. Non-antimicrobial approaches to therapy have become increasingly important with the emergence of serious antimicrobial resistance, such as vancomycin-resistant enterococcal colonization of the gastrointestinal tract. Finally, new understanding of how intestinal bacteria cause disease is revealing that enteric infections might trigger damage to epithelial cells or the intestinal barrier, or disrupt intestinal barrier and absorptive function (without necessarily causing overt diarrhea); thus, enteric infections might be far more important as emerging causes of malnutrition than has been previously appreciated. Therefore, diarrhea is both a cause and an effect of malnutrition. Treatment in most cases of bacterial and viral diseases consists of correcting fluid loss and electrolyte imbalance by oral or parenteral rehydration. Prevention of enteric illness by virtue of improved hygiene and provision of sanitation and water treatment is impractical in most developing countries, where morbidity and mortality rates are highest. For this reason, development of vaccines against the most important gastrointestinal infections remains a high priority.


Comparison between single-segment Isobar EVO dynamic stabilization and Isobar TTL dynamic stabilization in the treatment of lumbar degenerative diseases: a single center retrospective study over 4 years.
Posterior instrumented fusion is the most widely accepted surgical treatment for spinal stenosis and disc herniation. However, fusion can affect daily activities due to lumbar stiffness. In recent years, dynamic stabilization has been introduced to overcome the drawbacks of fusion, however, it is inconclusive whether dynamic stabilization requires the maintenance of a level of activity that is closer to the physiological state of activity for better clinical efficacy. The purpose of this study was to compare the effectiveness of dynamic stabilization with different levels of activity (Isobar EVO and TTL) in the treatment of spinal stenosis and disc herniation. This study retrospectively reviewed 80 consecutive patients with lumbar degenerative diseases who were undergoing surgical treatment between March 2014 and July 2018. 41 patients (EVO group) and 39 patients (TTL group) underwent fenestrated decompression with Isobar EVO stabilization and Isobar TTL stabilization, respectively. Clinical outcomes, radiographic data, and postoperative complications were compared between the two groups. At an average follow-up of 52.23 ± 2.97 months, there were no significant differences in the oswestry disability index (ODI) (P > 0.05). The visual analog scale for back pain (VASback) and visual analog scale for the leg pain (VASleg) of the EVO group were lower compared with the TTL group (P < 0.05). The range of motion (ROM) of operated segments were significantly higher in the EVO group as compared to the TTL group (P < 0.05). The intervertebral space height (ISH) of upper adjacent segments were significantly higher in the EVO group as compared to the TTL group (P < 0.05). The overall complications were less in the EVO group, but the difference was not statistically significant (P > 0.05). Both Isobar EVO dynamic stabilization and TTL dynamic stabilization can improve clinical outcomes of patients with spinal stenosis and disc herniation. Isobar EVO has advantages over Isobar TTL in terms of improving low back and leg pain, maintaining mobility of the operated segment, and preventing further degeneration of the upper adjacent segment.


Combined iron (III) chloride/sodium citrate with enzymatic hydrolysis for xylo-oligosaccharides and monosaccharides production from poplar.
Currently, the production of xylo-oligosaccharides (XOS) from lignocelluloses by chelating system hydrolysis has not been investigated. Herein, iron (III) chloride/sodium citrate (IC/SC) chelating system hydrolysis and xylanase hydrolysis were used to produce XOS from poplar. Then, the delignification of IC/SC-hydrolyzed poplar was performed by p-toluenesulfonic acid (p-TsOH) pretreatment to increase the accessibility of cellulase. The results demonstrated that 42.3% of XOS with an extremely low by-product (xylose/XOS = 0.11) was produced from poplar by 50 mM IC/SC hydrolysis (molar ratio of 1:1, 170 °C, 60 min) and xylanase hydrolysis. The second step IC/SC hydrolysis and xylanase hydrolysis of poplar increased the yield of XOS to 51.3%. Finally, the glucose yield of p-TsOH-pretreated poplar (60% p-TsOH, 70 °C, 30 min) was greatly increased from 37.5% to 83.8% by cellulase hydrolysis with Tween 80 addition. The novel strategy proposed in this work was feasible for XOS and monosaccharides production from poplar.


Computational analysis of looping of a large family of highly bent DNA by LacI.
Sequence-dependent intrinsic curvature of DNA influences looping by regulatory proteins such as LacI and NtrC. Curvature can enhance stability and control shape, as observed in LacI loops formed with three designed sequences with operators bracketing an A-tract bend. We explore geometric, topological, and energetic effects of curvature with an analysis of a family of highly bent sequences, using the elastic rod model from previous work. A unifying straight-helical-straight representation uses two phasing parameters to describe sequences composed of two straight segments that flank a common helically supercoiled segment. We exercise the rod model over this two-dimensional space of phasing parameters to evaluate looping behaviors. This design space is found to comprise two subspaces that prefer parallel versus anti-parallel binding topologies. The energetic cost of looping varies from 4 to 12 kT. Molecules can be designed to yield distinct binding topologies as well as hyperstable or hypostable loops and potentially loops that can switch conformations. Loop switching could be a mechanism for control of gene expression. Model predictions for linking numbers and sizes of LacI-DNA loops can be tested using multiple experimental approaches, which coupled with theory could address whether proteins or DNA provide the observed flexibility of protein-DNA loops.


Serum from hypercholesterolemic patients treated with atorvastatin or simvastatin inhibits cultured human smooth muscle cell proliferation.
We evaluated the pharmacological activity of whole-blood serum from atorvastatin- vs. simvastatin- (both 40 mg/day) treated hypercholesterolemic patients (n=10) on cultured smooth muscle cell (SMC) proliferation and cholesterol biosynthesis, as related to lipid-lowering effect. Patients received either single or 2-weeks repeated doses of both simvastatin and atorvastatin, following a randomised, double-blind, cross-over design. Blood samples were collected before drug administration and at the scheduled intervals after administration, and the obtained serum was separated by centrifugation, sterilized and frozen until assayed. Cultured SMC were supplemented with medium plus 15% of separate serum sampled from the patients, and grown for 72 h. Proliferation was assayed by a Coulter Counter, while cholesterol biosynthesis was measured by the incorporation of 14C-acetate into cholesterol, under the same experimental conditions. Atorvastatin was more active vs. simvastatin in reducing total- (-28.3% vs. -20.7%; p=0.045) and LDL-cholesterol (-39.8% vs. -30.1%; p=0.011) after a 2-weeks regimen. Serum from atorvastatin-treated patients inhibited SMC proliferation vs.t=0 after both single (AUC -21.6%) and repeated (AUC -26.9%) doses, while serum from simvastatin-treated patients inhibited SMC proliferation only after repeated doses (AUC -24.5%). Interestingly, in the same experimental conditions, the serum concentrations of both statins (and of their active metabolites) were constantly below the detection limits, as shown from the lack of inhibition of cholesterol biosynthesis. The absence of any significant association between the lipid-lowering effects and the inhibition of SMC proliferation, together with no detectable active statin in the serum, suggests that these effects are elicited through independent mechanisms.


[Testicular tissue vitrification: evolution or revolution?].
Preservation of reproductive health is a major concern for patient long-term quality of life. While sperm freezing has proven to be effective to preserve fertility after puberty, cryopreservation of immature testicular tissue (ITT) is emerging as a promising approach for fertility preservation in young boys. Slow-freezing (SF) is the conventional method used to preserve ITT and has resulted in the birth of mice offspring. In humans, methods to preserve ITT are still at the research stage. Controlled SF using dimethyl sulfoxide showed preservation of proliferative spermatogonia after thawing in a xenotransplantation model used to evaluate the efficiency of freezing and thawing procedures. However, spermatogonial recovery was low and normal differentiation could not be achieved. Both freezing/thawing and the environment of the xenotransplantation model may be implicated. Indeed, with SF, ice crystal formation could damage tissue and cells. For this reason, vitrification, leading to solidification of a liquid without crystallization, may be a promising alternative. ITT vitrification has been investigated in different species and shown spermatogonial survival and differentiation to the round or elongated spermatids stage. Offspring were also recently obtained after vitrification and allotransplantation in avians, confirming the potential of vitrification for fertility preservation. In humans, vitrification appears to be as efficient as SF in terms of spermatogonial survival and initiation of differentiation after xenotransplantation. However, before validation of such fertility preservation methods, completion of normal spermatogenesis and the fertilization capacity of sperm retrieved from cryopreserved and transplanted tissue should be fully investigated.


Enzymatic changes in the cerebrospinal fluid as indices of pathological change.
Enzymatic determinations in cerebrospinal fluid (CSF) of lactic dehydrogenase (LDH), creatine phosphokinase (CPK) and creatine kinase BB (CK-BB) were performed on 94 patients presenting with a range of disorders of the central nervous system. Enzyme results from 37 patients undergoing myelography were used as controls. The highest concentration of these enzymes appeared in patients with the most severe brain injury. In head-injured patients with a Glasgow Coma Score (GCS) of 3 to 7, only the CK-BB correlated with the degree of injury and with the ultimate outcome. Within the subgroup of spinal cord injuries none of the enzymes correlated with the severity of neurological injury. However, patients with acute spinal cord trauma who demonstrated CSF CK-BB values greater than 10 U/litre had never recovered. The present study confirms that CSF CK-BB seems to be a sensitive index of acute brain damage, but it reflects best the extent of CNS tissue disruption rather than the severity of neurological deficits.


Impact of HIV infection on access to cancer care and survival among women with invasive cervical cancer in Côte d'Ivoire: A prospective cohort study.
To assess the impact of HIV on access to invasive cervical cancer (ICC) care and overall survival (OS) in a time of universal access to antiretroviral therapy (ART). A cohort of women prospectively diagnosed with ICC was consecutively recruited from 2018 to 2020 in public/private cancer centers in Côte d'Ivoire. Follow-up data were collected through facility- and phone-based approaches. Logistic and Cox regression models allowed analysis of factors associated with access to cancer care and OS, respectively. Overall, 294 women with ICC aged 50 years (interquartile range [IQR] 43-60) were enrolled, including 21.4% of women living with HIV (WLHIV), 87% being on ART. An advanced ICC clinical stage (III-IV) was less frequent in WLHIV (63.5% vs. 77.1% in HIV-uninfected women; P = 0.029). Cancer care was initiated in 124 (42.2%) women (54.0% in WLHIV; 39.0% in HIV-uninfected; P = 0.030). Factors independently associated with access to cancer care were International Federation of Gynecology and Obstetrics (FIGO) stage I-II (adjusted odds ratio [aOR] 3.58, 95% CI 2.01-6.38) and no treatment by traditional healers prior to ICC diagnosis (aOR 3.69, 95% CI 1.96-6.96). The 2-year OS was 37.9% (95% CI 30.0-47.9). HIV status was not predictive of mortality (adjusted hazard ratio [aHR] 0.98, 95% CI 0.60-1.69). An advanced clinical stage was the only measured predictor of death (aHR 1.59, 95% CI 1.02-2.47). In a time of universal access to ART, HIV infection was not associated with OS among women with ICC in Côte d'Ivoire. Higher access to cancer care in WLHIV might be mediated by enhanced access to ICC screening services, supporting the need to expand these services to other types of healthcare facilities.


Small gold nanorods laden macrophages for enhanced tumor coverage in photothermal therapy.
One of the challenges to adopt photothermal ablation clinically is optimization of the agent delivery in vivo. Herein, a cell-mediated delivery and therapy system by employing macrophage vehicles to transport 7 nm diameter Au nanorods (sAuNRs) is described. Owing to the small size, the sAuNRs exhibit much higher macrophage uptake and negligible cytotoxicity in comparison with commonly used 14 nm diameter AuNRs to achieve healthy BSA-coated sAuNRs-laden-macrophages. By delivering BSA-coated sAuNRs to the entire tumor after intratumoral injection, the BSA-coated sAuNRs-laden-macrophages show greatly improved photothermal conversion almost everywhere in the tumor, resulting in minimized tumor recurrence rates compared to free BSA-coated sAuNRs. Our findings not only provide a desirable approach to improve the photothermal therapy efficiency by optimizing the intratumoral distribution of the agents, but also expedite clinical application of nanotechnology to cancer treatment.


Will plant movements keep up with climate change?
In the face of anthropogenic climate change, species must acclimate, adapt, move, or die. Although some species are moving already, their ability to keep up with the faster changes expected in the future is unclear. 'Migration lag' is a particular concern with plants, because it could threaten both biodiversity and carbon storage. Plant movements are not realistically represented in models currently used to predict future vegetation and carbon-cycle feedbacks, so there is an urgent need to understand how much of a problem failure to track climate change is likely to be. Therefore, in this review, we compare how fast plants need to move with how fast they can move; that is, the velocity of climate change with the velocity of plant movement.


Hazard report. Flammable material introduced into draeger ventilator and anesthesia unit flow sensors could ignite, posing risks to patients.
In rare cases, when flammable material is introduced into the Spirolog or SpiroLife flow sensor used with Draeger Medical ventilators and anesthesia units, the material could ignite, posing the risk of patient injury or device damage. Users can reduce this risk by carefully inspecting circuit components before use, by not introducing flammable products into the circuit during use, and by strictly complying with the company's instructions to allow the sensors to dry completely following alcohol disinfection.


Molecular Pathways: At the Crossroads of Cancer Epigenetics and Immunotherapy.
Epigenetic regulation allows heritably modulating gene expression profiles without modifying the primary sequence of gDNA. Under physiologic conditions, epigenetic patterns determine tissue-specific gene expression landscapes, gene imprinting, inactivation of chromosome X, and preservation of genomic stability. The most characterized mediators of epigenetic inheritance are gDNA methylation and histone posttranslational modifications that cooperate to alter chromatin state and genome transcription. According to these notions, it is not surprising that cancer cells invariantly deploy epigenetic alterations to achieve gene expression patterns required for neoplastic transformation and tumor progression. In this context, the recently uncovered use of epigenetic alterations by cancer cells to become stealth from the host's immune recognition has significant immunobiologic relevance in tumor progression, and it appears to have potential clinical usefulness. Indeed, immune evasion is among the major obstacles to further improve the efficacy of cancer immunotherapies and to increase long-lasting disease control. Luckily, different "epigenetic drugs" able to revert these "epimutations" are available, some of which have already been approved for clinical use. Here, we summarize the immunomodulatory activities of epigenetic drugs that lead to improved immune recognition of cancer cells and focus on the potential of this class of agents in improving the anticancer activity of novel immunotherapies through combinatorial epigenetic immunotherapy approaches.


Syntheses and antitumor activity of cis-restricted combretastatins: 5-membered heterocyclic analogues.
A series of cis-restricted combretastatin analogues with 5-membered heterocycles were synthesized and their inhibitory activity against microtubule assembly and cytotoxic activity against the colon 26 adenocarcinoma cancer cell line were evaluated. Some of the heterocyclic analogues showed potent antitubulin activity and cytotoxicity. Compounds 16 and 35 showed marked tumor growth suppression in the colon 26 murine tumor model.


The Optimizing Care Model: Final findings of a novel community pharmacy practice model to enhance patient care delivery using technician product verification.
The community pharmacy represents a convenient health care access point for patients and is increasingly used to deliver direct patient care services; however, several barriers exist that hinder widespread patient service implementation and scalability. Such barriers include scope of practice restrictions, a dearth of sustainable payment models, lack of pharmacist capacity given other responsibilities, and workflow models developed for dispensing medications rather than clinical care. In an effort to overcome the lack of pharmacist time and capacity, further task delegation to pharmacy technicians has been suggested. The primary objective of this study was to present the final outcomes of the Optimizing Care Model's impact. The model's impact on pharmacist patient care, workday composition, and rates of product selection errors not identified during final product verification are reported. The Optimizing Care Model is an innovative approach to community pharmacy practice aiming to foster a new patient-centered care delivery model that expands clinical service delivery and fosters collaboration across health care settings through task delegation, primarily through technician product verification (TPV). To investigate the impact of its sustained implementation, a quasi-experimental, 1-group pretest-posttest design was used. Outcomes assessed included medication errors, clinical activities, and workday composition. Six chain and 3 independent pharmacies completed the final, continuation phase of the study. Overall pharmacist time spent delivering patient care services increased significantly upon implementation of the Optimizing Care Model (21% vs. 43%; P < 0.05), whereas pharmacist time spent performing dispensing-related activities decreased significantly (67% vs. 37%; P < 0.05). Total undetected error rates were significantly less in the Optimizing Care Model phase compared with the traditional model (0.05% vs. 0.01%; P < 0.001). This study presented the final results of a 2-year assessment of the Optimizing Care Model. Results reaffirmed initial published findings that the model and its use of TPV increase the array and frequency of direct patient care services rendered while resulting in lower undetected error rates. Final project results of the Optimizing Care Model demonstrate increased clinical service delivery versus the traditional model, while also improving patient safety with lower rates of undetected dispensing errors within the Optimizing Care Model. The Optimizing Care Model continues to show promise as a future practice model for community pharmacies.


Pressure variation of the lateral diffusion in lipid bilayer membranes.
A pressure-induced decrease of the lateral diffusion in pure and cholesterol containing phosphatidylcholine bilayer membranes has been determined by the excimer formation technique using pyrene as probe molecule. The experimental results at pressures up to 150 bars are described satisfactorily by the free volume theory of a molecular transport in liquids. A pressure increase of extrapolated 575 bars decreases the lateral diffusion of lipids by a factor of two in pure dipalmitoylphosphatidylcholine membranes. Higher pressures are necessary to induce the same effect in cholesterol containing membranes. This result is interpreted by the condensing effect of cholesterol in fluid bilayer membranes.


Occupational exposure to blood and body fluids among nursing studentshv in clinical internship.
During their academic activities, nursing students are required to carry out clinical internships during which they can be exposed to contamination by bloodborne pathogens. Objective. The study was carried out to determine the prevalence and associated factors of occupational exposure to biological material potentially infected by blood in a population of nursing students. A cross-sectional design was used in this study and a self-administered questionnaire was provided to students. The research work was conducted from February 20, 2022, to March 15, 2022. The questionnaire was completed by 119 students. A total of 94 (78.99%) of the participants were female with a mean age of 20.46±1.16 years. 48 (40.34%) exposures were recorded with corresponding incidence rates of 0.4 exposures/person/year. With at least one accidental exposure to blood in 21 (43.75%) students. The OR analysis made by year of study showed that the ratio between the exposure risk was lower than 1 with P>0.05. The comparison between the different nursing specialties showed a significant difference between the students of General Nurses and Family and Community Health Nurses. The variables associated with exposures to blood were: female sex and personal protective equipment. During their clinical training, nursing students face several types of risks including biological through blood. In order to prevent the occurrence of these incidents, the consequences of which can be fatal, it is necessary to invest in training sessions and our institute should set up a local management unit for following the exposed students.


The effect of an acute or chronic treatment with indomethacin on the blood pressure of DOCA/salt and spontaneously hypertensive rats.
The intravenous infusion of indomethacin (5 mg/kg/min) for 10 min did not modify the systolic blood pressure of conscious, unrestrained doca/salt hypertensive, spontaneously hypertensive (SH) and normotensive Wistar (NW) rats. However, this dose of indomethacin was sufficient to prevent completely the hypotensive action of arachidonic acid in these animals. The chronic administration of indomethacin to doca/salt treated- and young SH rats was without any effect on the development of hypertension in these animals. These results suggest a limited role for endogenous PGs during the development of these two types of hypertension.


An admittance-controlled amplified force tracking scheme for collaborative lumbar puncture surgical robot system.
The accurate sensing and display of the delicate needle-tissue interaction force to the operator is desirable for needle insertion procedures. It not only plays a significant role in the surgical treatment effect, but also has a great significance in improving surgical safety and reducing the incidence of complications. However, the direct detection of the interaction force between the tissue and needle tip by placement of a force sensor is challenging owing to the constraints of miniaturisation, cost, and sterilisation. In this study, a new position-based force-to-motion controller with magnified force feedback is presented to provide augmented force perception to the operator during needle insertion on the soft tissue. Furthermore, the demonstration to the position-based low level motion controller is more suitable for needle insertion surgical requirements in the cooperative robotic system. The proposed controller was experimentally validated by a collaborative lumbar puncture robotics system. Additionally, to provide hand tremor rejection for the stable manipulation of the puncture needle, it was demonstrated that the proposed amplified feedback force controller allowed a safer object interaction with the robotic needle insertion assistance. The results of the experiment show that a desirable interaction force profile is perceived by the operator during the overall insertion task operation. The admittance gain for the simplified admittance controller has a significant impact on the operator's ability to accurately control the applied force.


Electrical PD, short-circuit current and fluxes of Na and Cl across avian intestine.
In vitro measurements were made of transmural potential difference (PD), short-circuit current (Isc), resistance and unidirectional fluxes of 22Na and 36Cl across the duodenum, jejunum, ileum and colon of normal sodium-replete domestic fowl (Gallus domesticus). The PD ranged from about 1 mV across the duodenum to 8 mV across the colon while the Isc was, respectively, 2.8 and 64 microA X cm-2. The jejunum and ileum exhibited values between these extremes. Unidirectional fluxes (under short-circuit conditions) of Na and Cl were lowest across the duodenum where there was no evidence of active transport of these ions. Unidirectional fluxes of Na and Cl were less across the jejunum than across the ileum or colon. A net active transport of Na (but not Cl) was observed in the ileum (= 106% of the Isc) and colon (= 50% of Isc). The possible physiological significance of these observations in the domestic fowl are discussed and are compared to that of a mammal, the rabbit.


[The role of CSF markers in the early diagnosis of Alzheimer's disease].
Biomarkers in cerebrospinal fluid (CSF) are being used increasingly to diagnose early Alzheimer's disease (AD). A CSF profile that is suggestive of ad is an abnormal ratio of the proteins Ab1-42 to total tau. To describe the prevalence and prognosis of a CSF profile in patients without dementia but with subjective memory problems and mild cognitive impairments (MCI) at a memory clinic. A multi-centre study. A European multi-centre study showed that a CSF AD profile was often present in patients with subjective complaints and patients with MCI . The CSF AD profile predicted a decline in cognition and daily functioning over a period of 3 years in patients with MCI. Patients with amnestic MCI and a CSF AD profile developed AD more often within this period than patients without this profile. CSF markers suggestive of ad are common in persons without dementia. It may be possible to use these markers for the prognosis of patients who have MCI .


Cross-border emergence of clonal lineages of ST38 Escherichia coli producing the OXA-48-like carbapenemase OXA-244 in Germany and Switzerland.
Carbapenemase-producing Gram-negative bacteria cause infections that are difficult to treat and represent a rising threat to healthcare systems worldwide. This study analysed isolates of Escherichia coli (E. coli), a species associated with nosocomial-acquired and community-acquired infections, from hospitals in Germany and Switzerland exhibiting a slight decrease in susceptibility to carbapenems. E. coli strains from Germany and Switzerland, obtained mainly in 2019, were first screened for carbapenemase genes by PCR and subsequently whole-genome-sequenced and analysed for their clonal relationship using multilocus sequence typing, single nucleotide polymorphisms, virulence and antibiotic-resistance gene content. The analysis revealed the presence of extended β-lactamase (ESBL)-producing E. coli clones producing OXA-244, a point-mutation derivative of OXA-48, with a predominance of isolates exhibiting the sequence type (ST) ST38 in both Germany and Switzerland. These clustered exclusively into two distinct lineages: one encoding CTX-M-27, a recently emerged extended-spectrum β-lactamase, and the other CTX-M-14b. All OXA244/CTX-M-27 ST38 isolates harboured the Dr adhesin operon and a representative isolate exhibited a diffuse adherence (DAEC) phenotype and was invasive for Hela cells. Clonal lineages of ST38 are members of E. coli phylogenetic group D commonly associated with extra-intestinal infections. Their increased isolation in two different European countries indicates ongoing spread of ST38 ESBL-producing and OXA-244-producing E. coli clonal lineages. It is possible that members of the multidrug-resistant DEAC ExPEC group have expanded globally, but that this is currently underreported because of the inherent difficulty in detecting isolates expressing the OXA-244 allele.


Evolution of virulence: interdependence, constraints, and selection using nested models.
Natural selection acts on virus populations at two distinct but interrelated levels: within individual hosts and between them. Studies of the evolution of virulence typically focus on selection acting at the epidemiological or between-host level and demonstrate the importance of trade-offs between disease transmission and virulence rates. Within-host studies reach similar conclusions regarding trade-offs between transmission and virulence at the level of individual cells. Studies which examine selection at both scales assume that between- and within-host selection are necessarily in conflict. We explicitly examine these ideas and assumptions using a model of within-host viral dynamics nested within a model of between-host disease dynamics. Our approach allows us to evaluate the direction of selection at the within- and between-host levels and identify situations leading to conflict and accord between the two levels of selection.


Dose and time dependence of chromosomal aberration yields of bone marrow cells in male Chinese hamsters after a single i.p. injection of aflatoxin B1.
The frequency of chromosomal aberrations in bone marrow cells, after a single i.p. aflatoxin B1 (AFB1) dose, was examined in male Chinese hamsters (Cricetulus griseus). There was a significant increase in aberrant cells within 5 days of administration of a dose of 0.1 micrograms-5 mg AFB1/kg, and on the 36th day. After a single dose of 5 mg AFB1/kg the enhanced frequency of aberrant cells was monitored up to day 104 with no sign of a decrease to control level. The results indicate that the minimum mutagenic effect of an AFB1 dose in this system is 0.1 micrograms/kg. Attention is drawn to the long-term presence of chromosomal aberrations even after a single i.p. exposure to AFB1.


The molecular interaction of a copper chelate with human P-glycoprotein.
One of the major reasons for multidrug resistance (MDR) in cancer is the overexpression of P-glycoprotein (P-gp, ABCB1), a drug efflux pump. A novel copper complex, namely, copper (II) N-(2-hydroxyacetophenone) glycinate (CuNG) previously synthesized and characterized by the authors had been tested in this study. In a cell-based assay system with human MDR1 cDNA overexpressed mouse fibroblast NIH MDR1-G185 cell line, we demonstrated that this metal complex can directly interact with this transporter. As CuNG increased cellular accumulation of doxorubicin in P-gp-expressing cells, we presumed that of CuNG may be potential to reverse P-gp-mediated drug resistance probably by lowering the P-gp expression at the protein as well as mRNA level. Interestingly, our studies on UIC2 (a conformation sensitive monoclonal antibody) binding assay indicated the direct interaction of CuNG with P-gp. However, CuNG did not compete for the substrate binding as photoaffinity labeling of P-gp with a substrate analog [(125)I] iodoarylazidoprazosin ([(125)I] IAAP) showed approximately twofold increase in [(125)I] IAAP binding in presence of CuNG. In vitro study showed that CuNG significantly stimulated P-gp-specific ATPase activity in isolated membrane preparations from NIH MDR1-G185 cells. This result further confirmed the CuNG-P-gp direct interaction. This study also demonstrated that CuNG has a drug interaction site different from verapamil-, vinblastine- and progesterone-binding sites on P-gp. Taken together, this is the first report of molecular interaction of any Schiff's base metal chelate CuNG with human P-gp. This information may be useful to design more efficacious nontoxic metal-based drugs as MDR-reversing agents.


Tetanus in a rural Ethiopian hospital.
Despite the widespread availability of a safe and effective vaccine, tetanus continues to be a significant public health problem in the developing countries.


Giant cystic abdominal masses in children.
In this pictorial essay the common and uncommon causes of large cystic and cyst-like abdominal masses in children are reviewed. We discuss and illustrate the following: mesenchymal hamartoma, choledochal cyst, hydrops of the gallbladder, congenital splenic cyst, pancreatic pseudocyst, pancreatic cystadenoma, hydronephrosis, multicystic dysplastic kidney, multilocular cystic nephroma, adrenal hemorrhage, mesenteric and omental cysts, gastrointestinal duplication cyst, meconium pseudocyst, ovarian cysts and cystic neoplasms, hematocolpos, urachal cysts, appendiceal abscess, abdominal and sacrococcygeal teratoma, and CSF pseudocyst. We also describe imaging features and clues to the diagnosis.


An updated meta-analysis of transanal drainage tube for prevention of anastomotic leak in anterior resection for rectal cancer.
Anastomotic leakage (AL) is one of the most serious complications after anterior resection for rectal cancer. Transanal drainage tube (TDT) placement is widely used to reduce AL, but its efficacy remains controversial. We performed a meta-analysis to evaluate the effectiveness of TDT for prevention of AL, using updated evidence. Randomized controlled trials (RCTs) and cohort studies evaluating the effectiveness of TDT for prevention of AL after anterior resection for rectal cancer were identified by using a predefined search strategy. Meta-analysis was performed to estimate the pooled rates of AL, reoperation, anastomotic bleeding and mortality separately. One RCT and ten cohort studies which including 1170 cases with TDT and 1262 cases without TDT were considered eligible for inclusion. Meta-analysis showed that the TDT group was associated with a significant lower rates of AL (RR: 0.42, 95% CI: 0.31-0.58, P < 0.00001) and reoperation (RR: 0.29, 95% CI: 0.19-0.45, P < 0.00001). There was no significant difference in anastomotic bleeding rate and mortality between the two groups. TDT placement is associated with significant lower rates of AL and reoperation, hence it is likely to be an effective method of preventing and reducing AL after rectal cancer surgery.


Duodenojejunal intussusception secondary to duodenal tumors.
Duodenojejunal intussusception secondary to duodenal tumors is an uncommon entity. The classic coiled-spring appearance, fairly visible in the jejunum, is not apparent in the duodenum due to its fixed position. This explains why the intussusception is located superiorly in the genu inferius and inferiorly in the duodenojejunal junction. This aspect should not be confused with two separated masses.


Influence of human cytomegalovirus on immune reconstitution after bone marrow transplantation.
HCMV infection diagnosed by the highly sensitive polymerase chain reaction (PCR) technology in blood, urine and skin biopsies of patients after bone marrow transplantation (BMT) correlated with the reconstitution of peripheral blood lymphocytes and dermal immunohistological alterations to evaluate the interaction of viral infection with the recovery of the immune system, as well as with the induction or aggravation of graft-versus-host disease (GVHD). In a prospective study 73% of 63 patients showed viremia at a median time of 25 days after BMT. Only 44% of these cases that also presented with a higher frequency of acute GVHD symptoms developed HCMB disease later on. In the skin, similar immunohistological alternations, as well as frequent primary local HCMV infection before the development of cutaneous signs of GVHD, was found, suggesting the direct involvement of anti-HCMV immune responses in the induction of GVHD-associated organ lesions.


Role of ghrelin axis in colorectal cancer: a novel association.
Recently discovered orexigenic peptide, ghrelin, which is primarily produced by gastrointestinal tract, has been implicated in the malignant cell proliferation and invasion, presumably through an autocrine/paracrine mechanism. This study was aimed to identify the role of endogenously produced ghrelin in colorectal cancer progression. Malignant intestinal epithelial cells differentially over-express ghrelin receptors and produce more ghrelin as compared to normal human colonocytes, leading to their enhanced proliferative and invasive behavior. Though, systemically available endocrine ghrelin levels in patients with colorectal cancer do not exhibit significant correlation with any tumor stage or grade, however, locally produced autocrine tissue ghrelin strongly correlates both with advancing colorectal malignancy in a stage-dependent manner and BMI of the colorectal patients. We conclude that ghrelin might play an important role in promoting colorectal malignancy.


Effects of MK-801 on vicarious trial-and-error and reversal of olfactory discrimination learning in weanling rats.
The effects of dizocilpine maleate (MK-801) on vicarious trial-and-error (VTE), and on simultaneous olfactory discrimination learning and its reversal, were observed in weanling rats. The term VTE was used by Tolman (The determiners of behavior at a choice point. Psychol. Rev. 1938;46:318-336), who described it as conflict-like behavior at a choice-point in simultaneous discrimination learning. It takes the form of head movements from one stimulus to the other, and has recently been proposed by Amsel (Hippocampal function in the rat: cognitive mapping or vicarious trial-and-error? Hippocampus, 1993;3:251-256) as related to hippocampal, nonspatial function during this learning. Weanling male rats received systemic MK-801 either 30 min before the onset of olfactory discrimination training and its reversal, or only before its reversal. The MK-801-treated animals needed significantly more sessions to acquire the discrimination and showed significantly fewer VTEs in the acquisition phase of learning. Impaired reversal learning was shown only when MK-801 was administered during the reversal-learning phase, itself, and not when it was administered throughout both phases.


Pain during Mogen or PlastiBell circumcision.
Routine neonatal circumcision can be a painful procedure. Although analgesia for circumcision has been studied extensively, there are few studies comparing which surgical technique may be associated with the least pain and discomfort when carried out by pediatric trainees. We studied two commonly used techniques for circumcision to determine which was associated with less pain and discomfort. In a randomized, prospective, but not blinded study, newborns were circumcised either by Mogen clamp or by PlastiBell. All received dorsal nerve blocks with lidocaine. Fifty-nine well, term, newborn infants at San Francisco General Hospital were studied from 1997 to 1998. Circumcisions were carried out mostly by interns and residents in family practice and pediatrics. Pain was assessed by measuring duration of the procedure and by a simple behavioral score done sequentially. Dorsal nerve blocks were judged to be fully effective in over 70% of cases. Neither Mogen nor PlastiBell was associated with greater pain per 3-minute time period, but the PlastiBell technique on average took nearly twice as long as the Mogen procedure (20 vs 12 minutes). We judged that 60% of the infants had pain or discomfort associated with the procedure that was excessive. Residents and interns universally preferred the Mogen technique over the PlastiBell because of the former's simplicity. During the procedure, Mogen circumcision is associated with less pain and discomfort, takes less time, and is preferred by trainees when compared with the PlastiBell.


Amount of CMS Reduction in Facility Reimbursement Following Removal of Total Hip Arthroplasty From the Inpatient-Only List Far Exceeds Reduction in Actual Care Cost.
Starting in 2020, Centers for Medicare and Medicaid Services (CMS) removed total hip arthroplasty (THA) from the inpatient-only list, resulting in an average of $1637 per case reduction in facility reimbursement. The purpose of this study is to determine whether the reduction in reimbursement is justified by comparing the difference in true facility costs between inpatient and outpatient THA. We identified a consecutive series of 5271 primary THA procedures from 2015 to 2019. Itemized procedural costs were calculated using a time-driven activity-based costing algorithm. Outpatient procedures were defined as those with less than a 24-hour length of stay. We compared patient demographics, comorbidities, and itemized costs between inpatient and outpatient procedures. A multivariate analysis was performed to determine the independent effect of outpatient status on true facility costs. There were 783 (14.9%) outpatient THA procedures. The outpatient THA procedures incurred lower mean personnel ($1428 vs $2226, P < .001), supply ($4713 vs $4739, P < .001), and overall facility costs ($6141 vs $6595, P < .001) when compared with the same THA procedures done inpatient. When controlling for confounding variables, outpatient status was associated with a reduction in total facility costs of $825 (95% confidence interval, $734-$916, P < .001). The reduction in CMS reimbursement far exceeds the $825 per-patient cost savings that can be achieved by a facility by performing THA as an outpatient. CMS should reconsider the Outpatient Prospective Payment System classification of THA to better incentivize surgeons to perform THA as a lower-cost outpatient procedure when safe and appropriate.


Mechanical properties derived from phase separation in co-polymer hydrogels.
Hydrogels can be synthesized with most of the properties needed for biomaterials applications. Soft, wettable, and highly permeable gels with a practically unlimited breadth of chemical functionalities are routinely made in the laboratory. However, the ability to make highly elastic and durable hydrogels remains limited. Here we describe an approach to generate stretchy, durable hydrogels, employing a high polymer-to-crosslink ratio for extensibility, combined with an aggregating copolymer phase to provide stability against swelling. We find that the addition of aggregating co-polymer can produce a highly extensible gel that fails at 1000% strain, recovers from large strains within a few minutes, maintains its elasticity over repeated cycles of large amplitude strain, and exhibits significantly reduced swelling. We find that the gel׳s enhanced mechanical performance comes from a kinetically arrested structure that arises from a competition between the disparate polymerization rates of the two components and the aggregation rate of the unstable phase. These results represent an alternative strategy to generating the type of stretchy elastomer-like hydrogels needed for biomedical technologies.


Two-monkey fMRI setup for investigating multifaceted aspects of social cognition and behavior involving a real-live conspecific.
While brain research over the past decades has shed light on the neural correlates of social cognition and behavior in human and non-human primates, most of this research has been performed in virtual settings requiring subjects to observe pictures or recorded videos instead of observing or interacting with another real-live individual. Here we present a two-monkey fMRI setup, allowing examining whole brain responses in macaque monkeys while they observe or interact face-to-face with another real-live conspecific. We tested this setup by comparing overall brain responses during observation of conspecific hand actions in a virtual (observation of recorded videos of actions) or live context (observation of a real-live conspecific performing actions). This dyadic monkey fMRI setup allows examining brain-wide responses in macaque monkeys during different aspects of social behavior, including observation of real-live actions and sensations, social facilitation, joint-attention and social interactions.


Synergism in ternary complex formation between the dimeric glycoprotein p67SRF, polypeptide p62TCF and the c-fos serum response element.
Transcriptional regulation of the c-fos proto-oncogene requires the serum response element (SRE) which is complexed by a multi-protein assembly observed both in vitro and in vivo. Two protein factors, p67SRF and p62TCF (previously called p62), are required to interact with the SRE for efficient induction of c-fos by serum. By quantitative band shift electrophoresis we measure at least a 50-fold increase in SRE affinity for p67SRF/p62TCF over p67SRF alone. Stoichiometrically we determine that the ternary complex with p62TCF involves p67SRF in dimeric form. We demonstrate that p67SRF is a glycosylated nuclear transcription factor carrying terminal N-acetylglucosamine (GlcNAc) as a post-translational modification. A proteolytic limit digestion product, approximately 13 kd in size, was generated from the p67SRF-SRE complex. This p67SRF-core domain binds SRE, can dimerize with p67SRF and is still able to form a ternary complex with p62TCF. Therefore, three functional activities can be ascribed to this small p67SRF-core domain: specific DNA binding, dimerization and interaction with p62TCF. We demonstrate that these functions map within the p67SRF core fragment containing the region between amino acids 93 and 222.


Lateral approach is a more aesthetical option for radical resection of BSCC: assessment of its surgical, oncological, functional, and aesthetic outcomes.
The purpose of this study was to introduce a modified lateral approach for combined radical resection of buccal squamous cell carcinoma (BSCC) and evaluate its surgical, oncological, functional, and aesthetic outcomes in comparison with the conventional lower-lip splitting approach. This single-center study retrospectively reviewed 80 patients with BSCC, of which 37 underwent the lateral approach and 43 underwent the conventional approach. Surgical, functional, oncological, and aesthetic evaluations, as well as follow-ups, were recorded and compared. Compared to the conventional approach group, the lateral approach group had a longer surgical time (P = 0.000), but there was no significant difference in other surgical and oncological parameters. Moreover, the scar in the head and neck had a significantly discreet appearance in the lateral approach group, whose satisfaction was better than those in the conventional approach group (P = 0.000). Other oral function parameters, postoperative mouth-opening, and 3-year survival rate were not significantly different between the two groups. The lateral approach could provide superior aesthetic results while maintaining equal surgical, functional, and oncological outcomes compared to the conventional approach for radical resection of BSCC.


Effect of lung-density correction in treatment planning for tangential-fields breast irradiation: a case report.
We report on the effect of lung-density correction on dose distribution in a transverse slice containing the isocenter for tangential-fields breast irradiation. In this case study we analyzed the target coverage as well as hot spots for four types of treatment plans: Plan 1 assumes uniform unit density throughout, Plan 2 utilizes all the treatment parameters of Plan 1, but takes into account the lower lung density. Plan 3 is generated by optimizing the dose distribution in the presence of the lower lung density, and Plan 4 is an improvement on Plan 3 by using custom instead of standard wedges. Our analysis shows that consideration of the lower lung density is important for optimal treatment planning for the breast and that specially designed wedges can improve the dose distribution.


Single-molecule diffusometry reveals no catalysis-induced diffusion enhancement of alkaline phosphatase as proposed by FCS experiments.
Theoretical and experimental observations that catalysis enhances the diffusion of enzymes have generated exciting implications about nanoscale energy flow, molecular chemotaxis, and self-powered nanomachines. However, contradictory claims on the origin, magnitude, and consequence of this phenomenon continue to arise. To date, experimental observations of catalysis-enhanced enzyme diffusion have relied almost exclusively on fluorescence correlation spectroscopy (FCS), a technique that provides only indirect, ensemble-averaged measurements of diffusion behavior. Here, using an anti-Brownian electrokinetic (ABEL) trap and in-solution single-particle tracking, we show that catalysis does not increase the diffusion of alkaline phosphatase (ALP) at the single-molecule level, in sharp contrast to the ∼20% enhancement seen in parallel FCS experiments using p-nitrophenyl phosphate (pNPP) as substrate. Combining comprehensive FCS controls, ABEL trap, surface-based single-molecule fluorescence, and Monte Carlo simulations, we establish that pNPP-induced dye blinking at the ∼10-ms timescale is responsible for the apparent diffusion enhancement seen in FCS. Our observations urge a crucial revisit of various experimental findings and theoretical models--including those of our own--in the field, and indicate that in-solution single-particle tracking and ABEL trap are more reliable means to investigate diffusion phenomena at the nanoscale.


Renal failure secondary to angiomyolipoma. Case of Forme-Fruste tuberous sclerosis.
A fifty-four-year-old woman without the clinical features of tuberous sclerosis underwent nephrectomy at age thirty-three years for angiomyolipoma, and twenty-one years later severe renal failure developed. At necropsy the remaining kidney had extensive angiomyolipomatous involvement; not until the brain was examined was the diagnosis of tuberous sclerosis made. To date, this would appear to be the third case without clinical tuberous sclerosis in which renal involvement was the sole clinical expression of tuberous sclerosis, and the seventh reported instance of renal failure due to renal angiomyolipomatous hamartomatous transformation.


[Analysis of Percutaneous Biopsy of 41 Small Lung Lesions].
When lung cancer screening work extensively developed in recent years, more and more small lung lesions were found in clinic. The aim of this study is to analysis computed tomography (CT) guided percutaneous biopsy for lung small lesions (diameter<2 cm) on results, complications and prognosis. Choose CT guided percutaneous lung biopsy were performed in 41 cases of pulmonary peripheral lesions, single lesion in 39 cases, multiple lesions in 2 cases, 5-20 (13.1±5.2) mm in maximum diameter, depth from lung surface 1-45 (16.5±13.7) mm, ground-glass opacity (GGO) components 0%-100% (66.8%±35.2%). 41 patients and 43 biopsies successfully obtained pathological tissue. Atypical adenomatous hyperplasia in 3 cases, squamous carcinoma in 1 case, adenocarcinoma in 37 cases( carcinoma in situ in 7 cases, micro-invasive carcinoma in 5 cases, invasive adenocarcinoma in 25 cases, double primary lung cancer in 2 cases), inflammatory lesions in 2 cases. Except 2 cases of inflammatory lesions are in follow-up, biopsy and surgical pathology alignment (specificity) was 100%. 41 patients occurred complications related to percutaneous biopsy. Pneumothorax were in 22 cases, drainage required in 2 cases. There were 17 cases with hemoptysis, accounting for 39.5% incidence are self-limited. Intracranial air embolism occurred in 2 cases by 4.6% incidence. They were fully recovered. For small lung lesions, CT guided percutaneous biopsy is technically feasible. However, for small lung lesions especially pure GGO biopsy, it is still need to be cautious.


CD155/SRC complex promotes hepatocellular carcinoma progression via inhibiting the p38 MAPK signalling pathway and correlates with poor prognosis.
Hepatocellular carcinoma (HCC) is a prevalent malignancy with poor prognosis. As a cell adhesion molecule, poliovirus receptor (PVR/CD155) is abnormally overexpressed in tumour cells, and related to tumour proliferation and invasion. However, the potential role and mechanism of CD155 have not yet been elucidated in HCC. Immunohistochemistry, RT-PCR and Western blot assays were used to determine CD155 expression in HCC cell lines and tissues. Cell Counting Kit-8 and colony formation assays were used to examine cell proliferation. Transwell and wound healing assays were used to evaluate cell migration and invasion. Cell apoptosis and cycle distribution were assessed by flow cytometry. Cox regression and Kaplan-Meier analyses were performed to explore the clinical significance of CD155. The role of CD155 in vivo was evaluated by establishing liver orthotropic xenograft mice model. RNA sequencing, bioinformatics analysis and co-immunoprecipitation assay were used to explore the downstream signalling pathway of CD155. CD155 was upregulated in HCC tissues and represented a promising prognostic indicator for HCC patients (n = 189) undergoing curative resection. High CD155 expression enhanced cell proliferation, migration and invasion, and contributed to cell survival in HCC. CD155 overexpression also induced epithelial-mesenchymal transition in HCC cells. CD155 function in HCC involved SRC/p38 MAPK signalling pathway. CD155 interacted with SRC homology-2 domain of SRC and promoted SRC activation, further inhibiting the downstream p38 MAPK signalling pathway in HCC. CD155 promotes HCC progression via the SRC/p38 MAPK signalling pathway. CD155 may represent a predictor for poor postsurgery prognosis in HCC patients.


Multimodal imaging for the detection and characterization of liver lesions in a mouse model of neuroendocrine tumor.
The aim of this study was to compare in vivo magnetic resonance imaging (MRI) and ex vivo autoradiography with histopathological results for the detection and characterization of liver lesions in an experimental model of human neuroendocrine tumors. Intestinal STC-1 endocrine tumor cells were injected into 30 nude mice to achieve hepatic dissemination. Seven to 30 days after injection, T2-weighted in vivo images covering the entire liver were acquired with a 7-T system. Autoradiographs were also obtained in 28 mice after injection of fluorodeoxyglucose (18F-FDG). The autoradiographic liver samples were then stained with an antichromogranin antibody before histological analysis. Tumor size and the hepatic tumor fraction were measured using the three imaging modalities. Metastatic tumors visualized on the histological liver sections ranged in size from 50 microm (day 7) to 3 mm (day 30). The hepatic tumor fraction increased with time, reaching 30% of the hepatic surface area on day 30. Visual analysis revealed variable tumor distribution and type (solid and/or cystic). On MRI, lesions were identified from day 12 (about 100 icrom in diameter) and the hepatic tumor fraction was up to 48% at day 30. The smallest lesions (350 microm in diameter) were also detected at day 12 on the autoradiographs. There was good correlation between tumor fractions determined from autoradiographic and histological data. In vivo, MRI appears to be well suited to the follow-up of liver lesions in a mouse model of neuroendocrine tumor. Preliminary results using 18F-FDG in this animal model are promising, showing differences in FDG uptake.


NHC to aNHC rearrangement by an organotin sulphide cation.
An intramolecularly P=O-coordinated dicationic diorganotin sulphide is presented. In solution, it shows a monomer-dimer equilibrium.


Pharmacological effects of β-d-mannuronic acid (M2000) on miR-146a, IRAK1, TRAF6 and NF-κB gene expression, as target molecules in inflammatory reactions.
Impaired expression and function of microRNAs (miRNAs) are involved in the pathogenesis of many autoimmune and inflammatory diseases. Moreover, there is a close relationship between TLRs and miRNAs and impairment in regulating their expression which can play a vital role in the immunopathogenesis of many inflammatory reactions. This research aimed to study the pharmaceutical effects of M2000 (β-d-mannuronic acid) on the expression of miR-146a and its two target molecules (IRAK1 and TRAF6), and the transcription factor NF-κB in the HEK-Blue hTLR2 cell line. The cytotoxicity of M2000 was assessed by the MTT assay, and the qRT-PCR technique was employed in the presence and absence of M2000 treatment to measure gene-expression levels of miR-146a, IRAK1, TRAF6, and NF-κB. MTT assay indicated that M2000 (before the concentration of 500μg/ml) had no cytotoxic effect on HEK-Blue hTLR2 cells. Our results showed that M2000 at low and high doses (5 and 25μg/well) could significantly reduce gene expression levels of miR-146a (p<0.01). Furthermore, it was found that this medication at two different doses could considerably decrease IRAK1 and TRAF6 gene expression (p<0.001). Moreover, this study revealed that expression level of NF-κB also significantly declined at these two doses (p<0.01). This study for the first time shows that M2000 as a novel NSAID with immunosuppressive properties is able to modify TLR signaling through suppressing the adaptor molecules IRAK1 and TRAF6, the transcription factor NF-κB and miR-146a as a new therapeutic approach.


Increased expression of inflammation-related genes in cultured preadipocytes/stromal vascular cells from obese compared with non-obese Pima Indians.
The specific contributions made by the various cell types in adipose tissue to obesity, particularly obesity-related inflammation, need to be clarified. The aim of this study was to elucidate the potential role of adipocyte precursor cells (preadipocytes/stromal vascular cells [SVC]). We performed Affymetrix oligonucleotide microarray expression profiling of cultured abdominal subcutaneous preadipocytes/SVC isolated from the adipose tissue of 14 non-obese (BMI 25+/-4 kg/m2) and 14 obese (55+/-8 kg/m2) non-diabetic Pima Indian subjects. Quantitative real-time PCR (RT-PCR) was used to verify the differential expression of several genes in an independent group of subjects. We identified 218 differentially expressed genes with p values less than 0.01. Microarray expression profiling revealed that the expression of inflammation-related genes was significantly upregulated in preadipocytes/SVC of obese individuals. Quantitative RT-PCR confirmed the upregulation of IL8, CTSS, ITGB2, HLA-DRA, CD53, PLA2G7 and MMP9 in preadipocytes/SVC of obese subjects. The upregulation of inflammation-related genes in preadipocytes/SVC of obese subjects may increase the recruitment of immune cells into adipose tissue and may also result in changes in the extracellular matrix (tissue remodelling) to accommodate adipose tissue expansion in obesity.


Plurimodal emergence and plurivoltinism of Central European populations of Nemurella pictetii (Plecoptera: Nemouridae).
Nemurella pictetii Klapálek, 1900 (Plecoptera: Nemouridae) has bi-or trimodal emergence patterns in Central Europe. The emergence threshold temperature is about 8°C. Egg development is direct. The slopes of regressions describing its temperature dependence do not differ significantly between English, Norwegian and German populations, but the intercepts (i.e., the incubation period at 0°C) do. Regular sampling of a benthic population near Schlitz, in Hesse, West Germany, showed that part of the offspring of the first emergence group grew quickly and produced a second emergence peak. The remaining offspring of the first generation grew more slowly and overwintered, together with the offspring of the second emergence peak. This population exhibits partial bivoltinism. The potential for bivoltinism was also shown in laboratory rearings of a German population at a constant 14°C: many eggs yielded normal adults after about 120 days. Larval growth rates were up to 2.2% body length day-1, much higher than for English Nemurella (unimodal emergence), or any other stonefly. The thermal sum (degree-days above 0°C) accumulated between the two emergence peaks, at the German sites studied, resembled cumulated degree-days in a laboratory culture. For an Austrian population with trimodal emergence, degree-days accumulated in the field were lower, suggesting a lower temperature demand and partial trivoltinism. This is the only case of confirmed plurivoltinism in Plecoptera. Nemurella pictetii seems to have lost seasonal life cycle cues, enabling the opportunistic use of favourable local conditions. Population synchrony appears to be regulated by the thermal demand for development and the emergence threshold temperature.


Use of indigenous and indigenised medicines to enhance personal well-being: a South African case study.
An estimated 27 million South Africans use indigenous medicines (Mander, 1997, Medicinal plant marketing and strategies for sustaining the plant supply in the Bushbuckridge area and Mpumalanga Province. Institute for Natural Resources, University of Natal. Pietermaritzburg, South Africa). Although herbal remedies are freely available in amayeza stores, or Xhosa chemists, for self-medication, little is known about the motivations of consumers. According to African belief systems, good health is holistic and extends to the person's social environment. The paper makes a distinction between traditional medicines which are used to enhance personal well-being generally and for cultural purposes, on the one hand, and medicines used to treat physical conditions only, on the other. Drawing on an eight-month study of Xhosa chemists in Eastern Cape Province, South Africa, in 1996, the paper identifies 90 medicines in stock which are used to enhance personal well-being. Just under one-third of all purchases were of medicines to enhance well-being. Remedies particularly popular included medicines believed to ward off evil spirits and bring good luck. The protection of infants with medicines which repel evil spirits is a common practice. Consumer behaviours indicate that the range of medicines available is increased by indigenisation of manufactured traditional medicines and cross-cultural borrowing. Case studies confirm that self- and infant medication with indigenous remedies augmented by indigenised medicines plays an important role in primary health care by allaying the fears and anxieties of everyday life within the Xhosa belief system. thereby promoting personal well-being.


Characterization of HIV-1-specific antibodies and HIV-1-crossreactive antibodies to platelets in HIV-1-infected haemophiliac patients.
Sera from HIV-1-infected haemophiliacs were examined for human immunodeficiency virus (HIV) specific antibodies and for platelet crossreactive antibodies. Using HIV sepharose 4B affinity columns for serum absorption, antibodies against various HIV antigens, including HIV lysate. HIV-p24 and HIV-gp120, were eluted either by low or by high pH buffer. The eluates were examined by ELISA for HIV specificity and by flow cytometry for platelet crossreactivity. Two types of HIV antibodies could be eluted, i.e. acid-sensitive and alkaline-sensitive antibodies. HIV antibodies were obtained in 26/29 acid eluates and in 25/29 of the alkaline eluates from HIV-lysate columns; 96% (25/26) of the acid-eluted antibodies were HIV-specific but 48% (12/ 25) of the alkaline-eluted antibodies also showed crossreactivity to platelets. Of the 20 alkaline-eluted HIV-p24 antibodies, 40% (8/20) reacted specifically with HIV-p24 and 60% (12/20) were platelet crossreactive. In contrast, of the alkaline-eluted HIV-gp120 antibodies (n=17), 88% (15/17) were HIV gp120-specific and only 12% (2/17) were platelet crossreactive. Western blot analysis of platelets demonstrated that the anti-p24 antibodies recognized three bands with approximate molecular weights of 72000 to 95000. 69% of the serum antiplatelet antibodies showed platelet glycoprotein IIbIIIa specificity. Anti-HIV antibodies could be eluted from platelets. Hence, platelet crossreactive antibodies in HIV infection are primarily alkaline-sensitive and are associated predominantly with HIV p24 antibody; these antibodies may play a role in the immune thrombocytopenia of HIV-infected haemophiliacs.


[Etiology of acute and chronic bronchopulmonary diseases in children. II. A study of the specific immune response by counterimmunoelectrophoresis and the complement fixation and passive hemagglutination reactions].
Specific immune response to Streptococcus pneumoniae and Haemophilus influenzae has been studied in 158 children with acute pneumonia and pleuritis and 128 children with chronic pneumonia by countercurrent immunoelectrophoresis (CIE) and in the complement fixation (CFT) and passive hemagglutination (PHA) tests. The use of CIE leads to the detection of antibodies to H. influenzae in 23.7% of children with acute pneumonia and in 46.9% of children with chronic pneumonia. In the CFT antibodies to H. influenzae are also more often detected in children with chronic pneumonia (48%) than in those with acute respiratory infections (12.2%). In the PHA test high titers of antibodies to type b H. influenzae capsular polysaccharide occur in 11.9% of children with acute pneumonia and in 8.2% of children with chronic pneumonia.


New cellular and extracellular amphipathic antigen from Actinomyces viscosus NY1.
A new type of amphipathic antigen was isolated from culture supernatants and cells of Actinomyces viscosus NY1 and partially characterized as a fatty acid-substituted heteropolysaccharide. Similar components have been detected serologically in other strains of Actinomyces.


Somatic Embryogenesis in Araucaria angustifolia (Bertol.) Kuntze (Araucariaceae).
This chapter deals with the features of somatic embryogenesis (SE) in Araucaria angustifolia, an endangered and native conifer from south Brazil. In this species SE includes the induction and proliferation of embryogenic cultures composed of pro-embryogenic masses (PEMs), which precede somatic embryos development. A. angustifolia SE model encompasses induction, proliferation, pre-maturation, and maturation steps. Double-staining with acetocarmine and Evan's blue is useful to evaluate the embryonic somatic structures. In this chapter we describe A. angustifolia SE protocols and analyzes morphological features in the different SE developmental stages.


Intraindividual comparison of 1.0 M gadobutrol and 0.5 M gadopentetate dimeglumine for time-resolved contrast-enhanced three-dimensional magnetic resonance angiography of the upper torso.
To compare the signal characteristics and bolus dynamics of 1.0 M gadobutrol and 0.5 M Gd-DTPA for time-resolved, three-dimensional, contrast-enhanced (CE) MRA of the upper torso. Ten healthy volunteers were examined with time-resolved three-dimensional CE-MRA (scan time per three-dimensional data set: 0.86 second; voxel size: 3.6 x 2 x 6.3 mm(3)). Each volunteer underwent eight individual examinations after intravenous injection of 0.05 and 0.1 mmol/kg body weight (b.w.) of 1.0 M gadobutrol and 0.5 M Gd-DTPA using two injection rates (2.5 and 5 mL/second). The data analysis included quantitative measurements of the peak signal-to-noise ratio (SNR) and bolus dispersion (full width at half maximum (FWHM)) in the pulmonary artery, left atrium, and thoracic and abdominal aortas. No significant differences in the peak SNR and bolus dispersion were observed between gadobutrol and Gd-DTPA for all dose levels and injection rates in any of the vascular segments. For both contrast agents a dose of 0.1 mmol/kg b.w. injected with 5 mL/second achieved the highest SNR in all vascular segments. For the imaging parameters used in this study, higher-concentrated gadolinium chelates offer no relevant advantages for time-resolved three-dimensional CE-MRA of the upper torso.


LC method for the direct and simultaneous determination of four major furan derivatives in coffee grounds and brews.
The simultaneous quantification of two potential genotoxic hydroxymethyl furan derivatives in coffee (furfuryl alcohol and 5-hydroxymethylfurfural) alongside their carboxylic acid derivatives (2-furoic acid and 5-hydroxymethyl furoic acid, respectively) was carried out. Their extraction from ground roasted coffee using sonication, simple shaking or heat-assisted shaking lead to similar results. A minimum of 97.3% of the four furan derivatives were extracted during the first extraction cycle using water, whereas methanol showed considerably lower extraction efficiency. A simple high-performance liquid chromatography method coupled with diode array detection was developed for the simultaneous determination and was applied to roasted coffee extracts or brews. No sample pre-treatment except for centrifugation was needed. The diode array detector was used to assess the purity of the peaks of interest in analyzed samples against authentic standards. The linearity according to Mandel, accuracy (recovery ≥ 89.9%) and precision (inter- and intraday relative standard deviation ≤ 4.5%) were checked. The values for the limit of detection and quantification ranged within 0.11-0.76 and 0.35-2.55 μg/mL, respectively. Filtered and espresso brews were analyzed for the four furan derivatives where furfuryl alcohol showed double the concentration of 5-hydroxymethylfurfural and about ten times the concentrations of 2-furoic acid or 5-hydroxymethyl furoic acid.


Sustained hemodynamic improvement during long-term therapy with levodopa in heart failure: role of plasma catecholamines.
Long-term therapy with oral sympathomimetic amines in patients with heart failure has been limited by the eventual development of diminished pharmacologic efficacy. However, a previous investigation in five subjects with heart failure suggested that long-term ingestion of levodopa, which is decarboxylated endogenously to dopamine, produces a sustained improvement in cardiac function. In the present study, levodopa was administered orally (1.5 to 2.0 g) to 14 patients with heart failure while hemodynamic responses and plasma catecholamines were monitored. Initially, an increase in cardiac index and stroke volume index was accompanied by a decline in systemic vascular resistance, mean pulmonary capillary wedge pressure and mean right atrial pressure. Heart rate and mean arterial pressure were unchanged. Plasma concentrations of dopamine rose substantially after drug ingestion and correlated significantly with changes in cardiac index (r = 0.73, p less than 0.05). After 12 weeks of treatment with levodopa, the changes in cardiac index, stroke volume index, systemic vascular resistance and plasma dopamine levels persisted (n = 12 patients). Moreover, a significant decrease occurred in the heart rate at rest. Although there was an initial tendency for plasma norepinephrine concentrations to increase, a return to control levels was documented after long-term treatment. Thus, tolerance to the hemodynamic actions of levodopa did not develop during long-term administration of the drug. The hemodynamic responses observed can be ascribed to the activation of beta 1-adrenoceptors and dopamine1 receptors by dopamine generated from levodopa. The dopamine2 activity of dopamine does not appear to be responsible for the improvement in cardiac performance produced by levodopa.


Relationship between brain and liver oxidative state and maximum lifespan potential of different fish species.
The aim of the present study is to determine whether a relationship exists between the maximum lifespan potential (MLSP) of different fish species (Squalius pyrenaicus, Cyprinus carpio, Carassius auratus, Luciobarbus sclateri and Oncorhynchus mykiss) and the oxidative state of brain and liver. For this purpose, the activity of the antioxidant enzymes superoxide dismutase (SOD), catalase, glutathione peroxidase (GPX), glutathione reductase (GR), glutathione S-transferase (GST) and DT-diaphorase (NAD(P)H:quinone oxidoreductase1) were measured together with the lipid peroxidation degree (malondialdehyde, MDA) in liver and brain tissues of the collected species. Only the brain tissue manifested a higher activity of the antioxidant enzymes superoxide dismutase, glutathione peroxidase, and glutathione S-transferase in addition to a negative correlation between the values of MDA and MLSP among the different fish species. Hypotheses are proposed from the analysis of the obtained results that open new areas of research and converge on the importance of the theory of free radicals in the processes that condition the maximum life expectancy of an animal species.


Depression in bipolar disorder versus major depressive disorder: results from the National Epidemiologic Survey on Alcohol and Related Conditions.
To compare the clinical features and course of major depressive episodes (MDEs) occurring in subjects with bipolar I disorder (BD-I), bipolar II disorder (BD-II), and major depressive disorder (MDD). Data were drawn from the National Epidemiologic Survey on Alcohol and Related Conditions (2001-2002), a nationally representative face-to-face survey of more than 43000 adults in the USA, including 5695 subjects with lifetime MDD, 935 with BD-I and lifetime MDE, and 494 with BD-II and lifetime MDE. Differences on sociodemographic characteristics and clinical features, course, and treatment patterns of MDE were analyzed. Most depressive symptoms, family psychiatric history, anxiety disorders, alcohol and drug use disorders, and personality disorders were more frequent-and number of depressive symptoms per MDE was higher-among subjects with BD-I, followed by BD-II, and MDD. BD-I individuals experienced a higher number of lifetime MDEs, had a poorer quality of life, and received significantly more treatment for MDE than BD-II and MDD subjects. Individuals with BD-I and BD-II experienced their first mood episode about ten years earlier than those with MDD (21.2, 20.5, and 30.4 years, respectively). Our results support the existence of a spectrum of severity of MDE, with highest severity for BD-I, followed by BD-II and MDD, suggesting the utility of dimensional assessments in current categorical classifications.


Molecular characteristics of natural organic matter in the groundwater system with geogenic iodine contamination in the Datong Basin, Northern China.
Natural organic matter (NOM) plays an important role in the iodine mobilization in the groundwater system. In this study, the groundwater and sediments from iodine affected aquifers in the Datong Basin were collected to perform chemistry analysis and molecular characteristics of NOM by Fourier transform ion cyclotron resonance mass spectrometer (FT-ICR-MS). Total iodine concentrations in groundwater and sediments ranged from 1.97 to 926.1 μg/L and 0.001-2.86 μg/g, respectively. A positive correlation was observed between DOC/NOM and groundwater/sediment iodine. FT-ICR-MS results showed that the DOM in the high-iodine groundwater system is characterized by less aliphatic and more aromatic compounds with higher NOSC, indicating the features of more unsaturated larger molecule structures and more bioavailability. Aromatic compounds could be the main carriers of sediment iodine and were easily absorbed on amorphous iron oxides to form the NOM-Fe-I complex. More aliphatic compounds, especially those containing N/S, experienced a higher degree of biodegradation, which further mediated the reductive dissolution of amorphous iron oxides and the transformation of iodine species, thereby causing the release of iodine into groundwater. The findings of this study provide some new insights into the mechanisms of high-iodine groundwater.


Electrophoretic deposition of cellulose nanocrystals (CNs) and CNs/alginate nanocomposite coatings and free standing membranes.
This study presents the electrophoretic deposition (EPD) of cellulose nanocrystals (CNs) and CNs-based alginate composite coatings for biomedical applications. The mechanism of anodic deposition of CNs and co-deposition of CNs/alginate composites was analyzed based on the results of zeta-potential, Fourier transform infrared spectroscopy and scanning electron microscopy (SEM) analyses. The capability of the EPD technique for manipulating the orientation of CNs and for the preparation of multilayer CNs coatings was demonstrated. The nanotopographic surface roughness and hydrophilicity of the deposited coatings were measured and discussed. Electrochemical testing demonstrated that a significant degree of corrosion protection of stainless steel could be achieved when CNs-containing coatings were present. Additionally, the one-step EPD-based processing of free-standing CNs/alginate membranes was demonstrated confirming the versatility of EPD to fabricate free-standing membrane structures compared to a layer-by-layer deposition technique. CNs and CNs/alginate nanocomposite coatings produced by EPD are potential candidates for biomedical, cell technology and drug delivery applications.


Effects of adrenaline, isoprenaline and forskolin on pregnant human myometrial preparations.
1. The effects of adrenaline, isoprenaline and forskolin upon the evoked contractions of field-stimulated preparations of human, pregnant, isolated myometrium have been examined. Specimens were obtained at lower segment Caesarean section from patients at 31 (n = 1) and 36-40 (n = 10) weeks of gestation. 2. Adrenaline enhanced the electrically evoked contractions of all preparations studied, indicating that its predominant action on these pregnant myometrial tissues was at alpha- and not beta-adrenoceptors. 3. Isoprenaline in concentrations at and below 10 mumol/l produced inhibitory effects in eight of 11 experiments. In the remaining three experiments, tissues were not responsive to the inhibitory effects of isoprenaline. 4. In all preparations exposed to higher concentrations of isoprenaline (30 or 100 mumol/l), its effects were excitatory. 5. Forskolin produced inhibitory effects on preparations from all uteri, including those from which tissues unresponsive to isoprenaline had been obtained. 6. It is suggested that forskolin in the concentrations which were effective in this study produced its inhibitory effects largely through activation of adenylate cyclase. This implies that the lack of an inhibitory response of some preparations to isoprenaline was not due to reduced activity of the adenylate cyclase system, but that the failure of isoprenaline to produce an inhibitory effect could be due to diminished numbers of beta-adrenoceptors and/or increased numbers of alpha-adrenoceptors, or to a defect in the coupling of the receptors to the adenylate cyclase system. Alternatively, the presence of an endogenous antagonist of the effects of isoprenaline (for example, an eicosanoid), could mask its inhibitory effects. 7. The absence of an inhibitory effect of isoprenaline on some specimens of human gravid myometrium could have clinical implications, in view of the widespread use of beta 2-adrenoceptor agonists as uterine relaxants.


Identification of a new oat β-amylase by functional proteomics.
Oat (Avena sativa L.) seed extracts exhibited a high degree of catalytic activity including amylase activities. Proteins in the oat seed extracts were optimized for their amylolytic activities. Oat extract with amylolytic activity was separated by SDS-PAGE and a major protein band with an apparent molecular mass of 53 kDa was subjected to tryptic digestion. The generated amino acid sequences were analyzed by liquid chromatography–tandem mass spectrometry (LC/ESI/MS/MS) and database searches. These sequences were used to identify a partial cDNA from expressed sequence tags (ESTs) of A. sativa L. Based upon EST sequences, a predicted full-length gene was identified, with an open reading frame of 1464 bp encoding a protein of 488 amino acid residues (AsBAMY), with a theoretical molecular mass of 55 kDa identified as a β-amylase belonging to the plant β-amylase family. Primary structure of oat β-amylase (AsBAMY) protein indicated high similarity with other β-amylase from other cereals such as wheat (Triticum aestivum), barley (Hordeum vulgare), and rye (Secale cereale) with two conserved Glu residues (E184 and E378) assigned as the "putative" catalytic residues which would act as an acid and base pair in the catalytic process. In addition, a 3D-model of AsBAMY was built from known X-ray structures and sequence alignments. A similar core (β/α)8-barrel architecture was found in AsBAMY like the other cereal β-amylases with a specific location of the active site in a pocket-like cavity structure made at one end of this core (β/α)8-barrel domain suggesting an accessibility of the non-reducing end of the substrate and thus confirming the results of AsBAMY exo-acting hydrolase.


Are the changes in diagnostic criteria for gestational diabetes mellitus reflected in perinatal outcomes? A retrospective assessment.
Gestational diabetes mellitus (GDM) is glucose intolerance first diagnosed during pregnancy not due to overt diabetes. Recent changes to the diagnostic guidelines have been shown to increase the apparent occurrence of GDM. The aim of this study was to compare retrospectively the neonatal outcomes between groups defined using the new and old criteria to assess the impact of guideline changes on pregnancy outcomes. The study was of singleton babies delivered of 641 women, who had oral glucose tolerance testing and pregnancy care at a single tertiary centre between 2011 and 2015. Compared to the population of women not now considered to have GDM by International Association of Diabetes and Pregnancy Study Groups criteria (two-hour glucose concentration ≤8.4 mmol/L), neonates born to women with the new lower fasting criterion (5.1-5.4 mmol/L) and/or the new 60-min group (glucose ≥10 mmol/L) combined were significantly more likely to have birthweight ≥90th percentile (22% vs 5%, P < 0.0001). In contradistinction, there was a significant excess number of small-for-dates babies (birthweight ≤10th percentile) in all subgroups previously diagnosed and treated for GDM by the Australian Diabetes in Pregnancy Society criteria (17% vs 7%, P = 0.001). Rates for lower uterine segment caesarean section, admission to the neonatal intensive care unit / special care nursery and Apgar scores at one and five minutes were not statistically different across all groups. Outcomes support the lowering of the fasting criterion to extend management of GDM to limit growth of large birthweight neonates. An unexpected outcome was that in women previously treated for GDM, there were increased numbers of low-birthweight neonates.


Listeriosis.
The incidence, clinical picture, natural history, epidemiology and sequelae of perinatal listeriosis are discussed along with treatment and diagnosis.


Advanced SPARQL querying in small molecule databases.
In recent years, the Resource Description Framework (RDF) and the SPARQL query language have become more widely used in the area of cheminformatics and bioinformatics databases. These technologies allow better interoperability of various data sources and powerful searching facilities. However, we identified several deficiencies that make usage of such RDF databases restrictive or challenging for common users. We extended a SPARQL engine to be able to use special procedures inside SPARQL queries. This allows the user to work with data that cannot be simply precomputed and thus cannot be directly stored in the database. We designed an algorithm that checks a query against data ontology to identify possible user errors. This greatly improves query debugging. We also introduced an approach to visualize retrieved data in a user-friendly way, based on templates describing visualizations of resource classes. To integrate all of our approaches, we developed a simple web application. Our system was implemented successfully, and we demonstrated its usability on the ChEBI database transformed into RDF form. To demonstrate procedure call functions, we employed compound similarity searching based on OrChem. The application is publicly available at https://bioinfo.uochb.cas.cz/projects/chemRDF.


Modeling the transport of CO2, N2, and their binary mixtures through highly permeable silicalite-1 membranes using Maxwell-Stefan equations.
Carbon dioxide (CO2) is the main contributor to global warming; therefore, research efforts aim at its capture. Membranes, in particular, zeolite membranes offer a promising approach for CO2 separation and capture. Membranes are typically characterized by their selectivity and permeance that are highly dependent on the operating conditions namely, total feed pressure and composition. Therefore, more reliable characterization parameters are required such as Maxwell- Stefan exchange diffusivities. In this work, a model based on Maxwell-Stefan equations and Extended Langmuir isotherm was developed to investigate the transport of binary mixtures of CO2 and N2 through thin silicalite-1 membranes. The exchange diffusivities, D12 and D21, of CO2 and N2 were determined at different total feed pressures and feed compositions. All gas separation tests were conducted at stage cut not exceeding 5%. The single component diffusivities of CO2 and N2 required by the model were found experimentally using the results of the respective single gas permeation tests. The results displayed that as CO2 concentration in the feed increased from 15% to 85%, the values of D12 and D21 decreased from 2.8 × 10-10 to 1.1 × 10-10 m2/s and 2.8 × 10-10 to 1.3 × 10-10 m2/s, respectively, while the N2 permeance decreased by about one order of magnitude from 2.7 × 10-7 to 2.4 × 10-8 mol/m2.s.Pa. Consequently, the exchange diffusivities showed considerably smaller dependence on the operating conditions compared to the permselectivity and permeance. Hence, they are more appropriate in describing the intrinsic transport characteristics of silicalite-1 membranes.