The role of E-selectin, P-selectin, and very late activation antigen-4 in T lymphocyte migration to dermal inflammation.
T lymphocyte infiltration into inflamed tissues is thought to involve lymphocyte rolling on vascular endothelial cells. Because both selectin and alpha(4) integrin adhesion molecules can mediate leukocyte rolling, the contribution of these receptors to lymphocyte migration to inflammation was examined. The recruitment of (111)In-labeled spleen T cells to intradermal sites injected with IFN-gamma, TNF-alpha, LPS, poly inosine-cytosine, and Con A was measured in the rat, and the effect of blocking mAbs to E-selectin, P-selectin, very late activation Ag-4 (VLA-4), and LFA-1 was determined on this T cell migration in vivo. Anti-E-selectin and anti-P-selectin mAbs each inhibited 10-40 and 20-48%, respectively, of the T lymphocyte migration to the inflammatory sites, depending on the stimulus. Blocking VLA-4 inhibited 50% of the migration to all of the lesions except Con A. Treatment with both anti-VLA-4 and anti-E-selectin mAbs inhibited up to 85% of the lymphocyte accumulation, while P-selectin and VLA-4 blockade in combination was not more effective than VLA-4 blockade alone in TNF-alpha, IFN-gamma, LPS, and poly inosine-cytosine lesions. Inhibiting E-selectin, P-selectin, and VLA-4 together nearly abolished lymphocyte migration to all inflammatory sites. Anti-LFA-1 mAb strongly inhibited lymphocyte accumulation by itself, and this inhibition was not significantly further reduced by E- or P-selectin blockade. Thus, T cell migration to dermal inflammation is dependent on E-selectin, P-selectin, and VLA-4, likely because these three receptors are required for rolling of memory T lymphocytes, but VLA-4 and E-selectin are especially important for lymphocyte infiltration in these tissues.


Quantitative real-time ARMS-qPCR for mitochondrial DNA enables accurate detection of microchimerism in renal transplant recipients.
The presence of microchimerism in peripheral blood of solid organ transplant recipients has been postulated to be beneficial for allograft acceptance. Kinetics of donor cell trafficking and accumulation in pediatric allograft recipients are largely unknown. In this study, we implemented SNPs of the HVRs I and II of mitochondrial DNA to serve as molecular genetic markers to detect donor-specific cell chimerism after pediatric renal transplantation. Serial dilution of artificial chimeric DNA samples showed a linear correlation coefficient of R > 0.98 and a detection sensitivity of 0.01% with high reproducibility. Longitudinal semiquantitative analysis of donor-specific SNPs was then performed in peripheral blood mononuclear cells samples up to two yr post-transplant. Quantity of donor-specific cell chimerism in peripheral blood was highest in the early post-transplant period reaching values of ~10% after liver-kidney and 2.8% after renal transplantation. From one wk after transplantation, renal transplant patients exhibited an amount of donor-specific mtDNA ranging from 0.01% to 0.1%. We developed a highly accurate, sensitive, and rapid real-time quantitative PCR method using sequence-specific primers and fluorescent hydrolysis probes for the detection of at least 0.01% donor-specific cells in the recipient's peripheral blood after renal transplantation.


Cell type-specific glycosylation of Orai1 modulates store-operated Ca2+ entry.
N-glycosylation of cell surface proteins affects protein function, stability, and interaction with other proteins. Orai channels, which mediate store-operated Ca(2+) entry (SOCE), are composed of N-glycosylated subunits. Upon activation by Ca(2+) sensor proteins (stromal interaction molecules STIM1 or STIM2) in the endoplasmic reticulum, Orai Ca(2+) channels in the plasma membrane mediate Ca(2+) influx. Lectins are carbohydrate-binding proteins, and Siglecs are a family of sialic acid-binding lectins with immunoglobulin-like repeats. Using Western blot analysis and lectin-binding assays from various primary human cells and cancer cell lines, we found that glycosylation of Orai1 is cell type-specific. Ca(2+) imaging experiments and patch-clamp experiments revealed that mutation of the only glycosylation site of Orai1 (Orai1N223A) enhanced SOCE in Jurkat T cells. Knockdown of the sialyltransferase ST6GAL1 reduced α-2,6-linked sialic acids in the glycan structure of Orai1 and was associated with increased Ca(2+) entry in Jurkat T cells. In human mast cells, inhibition of sialyl sulfation altered the N-glycan of Orai1 (and other proteins) and increased SOCE. These data suggest that cell type-specific glycosylation influences the interaction of Orai1 with specific lectins, such as Siglecs, which then attenuates SOCE. In summary, the glycosylation state of Orai1 influences SOCE-mediated Ca(2+) signaling and, thus, may contribute to pathophysiological Ca(2+) signaling observed in immune disease and cancer.


Filter mesh size and food particle uptake by Daphnia.
Food size selection of four Daphnia, species (D. magna, D. hyalina, D. galeata, D. pulicaria) was investigated using spherical plastic beads as artificial food and with small bacteria. The size of the particles ranged from 0.1 to 35 μm with special emphasis to the particle diameters between 0.1 and 1 μm. In one set of experiments a mixture of differently sized particles was offered as food suspension and the selectivity of filtering was determined by comparing the size spectrum of the particles found in the gut contents with the spectrum in the food suspension. In a second series of experiments suspensions of uniformly sized particles were offered to single animals and their feeding activity was observed directly. In both types of experiments the mesh sizes of the filtering apparatus of the respective animals studied were measured after the experiments by, scanning electron microscopy. The mean sizes of the filter meshes were about 0.4-0.7 μm. In all experiments the size of the particles found in the gut or those which caused high feeding activities were larger than the smallest mesh sizes of the filters. As a consequence simple mechanical sieving provides a sufficient explanation for the mechanism of particle retention of the filtering process in Daphnia. D. magna was found to feed with high efficiency on suspended freshwater bacteria, the residual species investigated showed low filtering efficiencies when bacteria were offered as food.


Eliminating gene conversion improves high-throughput genetics in Saccharomyces cerevisiae.
Synthetic genetic analysis was improved by eliminating leaky expression of the HIS3 reporter and gene conversion between the HIS3 reporter and his3Delta1. Leaky expression was eliminated using 3-aminotriazole and gene conversion was eliminated by using the Schizosaccharomyces pombe his5+ gene, resulting in a 5- to 10-fold improvement in the efficiency of SGA.


Pneumatic retinopexy preceded by drainage of subretinal fluid for the treatment of severe bullous retinal detachment.
To compare the efficacy and safety outcomes of scleral buckling (SB) and drainage-injection-pneumoretinopexy (DIP), a modified pneumatic retinopexy technique, in which, before gas injection, subretinal fluid is drained with a simultaneous injection of balanced salt solution (BSS) in the vitreous chamber, for the treatment of severe superior bullous rhegmatogenous retinal detachment (SBRD). This prospective, randomized, comparative study included 58 eyes with severe SBRD that were randomized 1:1 to undergo SB or DIP. The main outcome measures included success rate, visual acuity, mean change in refractive error and surgery duration. The primary anatomic success rate was 93% for both procedures. Both groups showed significantly improved visual acuity after surgery. The change in refractive error and surgery duration was significantly higher in the SB group. Drainage-injection-pneumoretinopexy (DIP) appeared to be less traumatic, but with a longer persistence of subretinal fluid in a greater number of patients. Our findings suggested that both SB and DIP are safe and effective treatments yielding functional and anatomical recovery in patients with severe SBRD. However, the DIP technique may be easier and less costly, with a success rate similar to that of SB.


Percutaneous treatment of a popliteal bifurcation--the value of coronary devices and strategies.
In this case report, we describe the use of coronary techniques and devices in the treatment of a complex popliteal artery bifurcation. In particular, we demonstrate that the Venture wire control catheter is a useful tool not only in coronary lesions but also in wiring angulated peripheral lesions.


Comparison of laboratory methodologies for evaluating radiostrontium diffusion in soils: planar-source versus half-cell methods.
A planar-source method, initially designed to obtain diffusion coefficients in compacted clay, is adapted here to determine the apparent diffusion coefficient (D(a)) of radiostrontium in soils representative of the Spanish territory. Experiments were carried out by varying the moisture content (F(moist)), and bulk dry density (ρ(bulk)) of the soil samples, in order to study the influence of these soil packing parameters on D(a) values. The moisture in the soil samples was established as the percentage of occupancy of each soil's field capacity (OFC). For a similar OFC, D(a) values in the examined soils ranged by approximately one order of magnitude (e.g. from 6.2 × 10(-)(11) to 6.5 × 10(-)(12)m(2)s(-)(1), at 100% of OFC; from 3.0 × 10(-)(11) to 3.8 × 10(-)(12)m(2)s(-)(1), at 60% of OFC). For a given soil, D(a) values increased when water content was increased. F(moist), and tortuosity (τ) explained D(a) variability, with R(2) values usually over 0.9. However, no good simple or multiple regressions between the soil packing parameters and D(a) were obtained with the whole dataset of all soils, which indicated that soil sorption capacity affects the diffusion of reactive radionuclides in soils. The inclusion of calculated K(d) values in the multiple regressions improved the correlations in all cases. Finally, D(a) values were compared with those obtained by the application of a half-cell method. The values of D(a) obtained by the planar-source methods were systematically lower than the half-cell ones, with a good correlation between the D(a) derived from both methods (R(2)=0.98).


Caffeic acid phenethyl ester (CAPE), an active component of propolis, inhibits Helicobacter pylori peptide deformylase activity.
Helicobacter pylori (H. pylori) is a major causative factor for gastrointestinal illnesses, H. pylori peptide deformylase (HpPDF) catalyzes the removal of formyl group from the N-terminus of nascent polypeptide chains, which is essential for H. pylori survival and is considered as a promising drug target for anti-H. pylori therapy. Propolis, a natural antibiotic from honeybees, is reported to have an inhibitory effect on the growth of H. pylori in vitro. In addition, previous studies suggest that the main active constituents in the propolis are phenolic compounds. Therefore, we evaluated a collection of phenolic compounds derived from propolis for enzyme inhibition against HpPDF. Our study results show that Caffeic acid phenethyl ester (CAPE), one of the main medicinal components of propolis, is a competitive inhibitor against HpPDF, with an IC50 value of 4.02 μM. Furthermore, absorption spectra and crystal structural characterization revealed that different from most well known PDF inhibitors, CAPE block the substrate entrance, preventing substrate from approaching the active site, but CAPE does not have chelate interaction with HpPDF and does not disrupt the metal-dependent catalysis. Our study provides valuable information for understanding the potential anti-H. pylori mechanism of propolis, and CAPE could be served as a lead compound for further anti-H. pylori drug discovery.


Isolation and identification of hemostatic steroidal glycosides from Ypsilandra thibetica.
The phytoconstituents of the fraction with hemostatic activity of the 70% aqueous ethanol extract of Ypsilandra thibetica Franch. were investigated. As a result, fourteen previously unreported spirostanol saponins, ypsilandrosides Z1-Z14, and nine known analogues were isolated and characterized by MS, NMR, and chemical methods. Among them, ypsilandrosides Z1-Z4 (1-4) have a rare 12-O-β-d-glucopyranosyl group, while ypsilandrosides Z5-Z8 (5-8) possess a rare double bond between C-4 and C-5, and a hydroxyl or carbonyl located at the C-6. All isolates were further tested for their hemostatic activity. The results suggested that five spirostanol tetraglycosides show favorable inducing platelet aggregation activities. Among them, ypsilandroside G (16) displayed significant inducing platelet aggregation activity with an EC50 value of 57.17 μM. Furthermore, the preliminary structure-activity relationship of these spirostanol glycosides' hemostatic activity was discussed.


MR imaging correlates of white-matter pathology in a preterm baboon model.
Cerebral white-matter (WM) abnormalities on magnetic resonance imaging (MRI) correlate with neurodevelopmental disability in infants born prematurely. Quantitative histological measures of WM and ventricular volumes correlated with qualitative MRI scores of WM volume loss and ventriculomegaly. Diffuse astrocytosis was associated with signal abnormality on T(2)-weighted imaging and higher apparent diffusion coefficient in WM. Loss of oligodendrocytes was associated with lower relative anisotropy characterized by higher radial diffusivity values. The relationship between histopathology and MRI abnormalities was more pronounced in animals in the 28 d model, equivalent to the term human infant. MRI reflects microstructural and anatomical abnormalities that are characteristic of WM injury in the preterm brain, and these changes are more evident on MRI at term-equivalent postmenstrual age. We assessed the histopathological correlates of MRI abnormalities in a baboon model of premature birth. Baboons were delivered at 125 d of gestation (dg, term ~185 dg) and maintained in an animal intensive care unit for 14 (n = 26) or 28 d (n = 17). Gestational control animals were delivered at 140 dg (n = 9) or 153 dg (n = 4). Cerebral WM in fixed brains was evaluated using MRI, diffusion tensor imaging (DTI), and histopathology.


COVID-19 pneumonia causes lower testosterone levels.
To evaluate the testicular damage caused by COVID-19, we prospectively evaluated 44 patients who applied to the COVID-19 outpatient clinic between March 2020 and July 2020. Patients' ages, COVID-19 PCR results, presence of pneumonia, total testosterone, luteinising hormone (LH) and follicle-stimulating hormone (FSH) values were recorded. It was evaluated whether there were significant differences between people who were positive for COVID-19 and those who were not. Any differences between those who had COVID-19 pneumonia and those who did not were also recorded. There was no difference between the FSH, LH and testosterone values of the COVID-19 PCR positive and negative patients (p = 0.80, vp = 0.62, p = 0.56 respectively). However when LH values were separated as low, normal and high, LH values were statistically significantly higher in the COVID-19 PCR positive group (p = 0.04). Thoracic computed tomography was performed in 42 patients. Testosterone levels were significantly lower in patients with COVID-19 pneumonia (p = 0.01). When FSH, LH and testosterone values were separated as low, normal and high, there was no difference in FSH and LH values (p = 1, p = 0.2). Testosterone levels were found significantly lower in patients with COVID-19 pneumonia (p < .001). Testosterone levels seem to decrease during acute COVID-19 infection, especially in the patient group with viral pneumonia.


[Myocardial protective effect using membrane stabilization in ischemic heart arrest in hypothermia].
Membrane stabilization with steroid pretreatment, procaine, or both protect against postischemic left ventricular performance after one hour of topical hypothermic ischemic arrest, but do not prevent myocardial edema. Combining steroids and procaine provide no apparent added benefit, but procaine has the technical advantage of almost immediate cardioplegia.


An evaluation of endoscopic retrograde pancreatography (ERP) in chronic and relapsing acute pancreatitis.
The results of ERP carried out in a series of cases of established and suspected chronic and acute relapsing pancreatitis are presented. Radiological findings are divided into major and minor alterations of the pancreatic secretory system. X-ray findings are easy to interprete in chronic pancreatitis with major alterations. Minor anomalies of the pancreas are difficult to interprete in the absence of supporting evidence. Biliary tract involvement is useful for diagnosis of chronic pancreatitis.


Study of the association of atmospheric temperature and relative humidity with bulk tank milk somatic cell count in dairy herds using Generalized additive mixed models.
Elevated bulk tank milk somatic cell count (BMSCC) has a negative impact on milk production, milk quality, and animal health. Seasonal increases in herd level somatic cell count (SCC) are commonly associated with elevated environmental temperature and humidity. The Temperature Humidity Index (THI) has been developed to measure general environmental stress in dairy cattle; however, additional work is needed to determine a specific effect of the heat stress index on herd-level SCC. Generalized Additive Model methods were used for a flexible exploration of the relationships between daily temperature, relative humidity, and bulk milk somatic cell count. The data consist of BMSCC and meteorological recordings collected between March 2009 and October 2011 of 10 dairy farms. The results indicate that, an average increase of 0.16% of BMSCC is expected for an increase of 1°C degree of temperature. A complex relationship was found for relative humidity. For example, increase of 0.099%, 0.037% and 0.020% are expected in correspondence to an increase of relative humidity from 50% to 51%, 80% to 81%; and 90% to 91%, respectively. Using this model, it will be possible to provide evidence-based advice to dairy farmers for the use of THI control charts created on the basis of our statistical model.


System B0,(+)-mediated regulation of lysine transport in Caco-2 human intestinal cells.
We investigated whether lysine transport would be subject to adaptive regulation in Caco-2 human intestinal cells. The activity of Lys transport in Caco-2 cells decreased with increasing incubation time with 10 mM Lys. Among the two systems involved in Lys transport, the system b0,+ component was greatly decreased by incubating cells with 10 mM Lys, whereas the system y+ component did not change. These results suggest that system b0,+ mainly contributes to the adaptive regulation of Lys transport in Caco-2 cells.


Draft Genome Sequences of Two Multidrug-Resistant Acinetobacter baumannii Strains of Sequence Type ST92 and ST96.
The global epidemiology of multidrug-resistant Acinetobacter baumannii is dominated by a limited number of clones. Here, we announce the draft genome sequences of two multidrug-resistant A. baumannii strains, 1H8 and 4A3, representing the major epidemic clones, sequence type 92 (ST92) and ST96, respectively.


A rare case of coexistence of carcinoid tumor of appendix vermicularis and ileal endometriosis.
Carcinoid tumor is the most common tumor of appendix with overall good prognosis. Endometriosis is the implantation of endometrial glands and stroma outside the uterus. We here report the coexistence of carcinoid tumor of appendix and ileal endometriosis in a 37-year-old nulliparous woman who came to the emergency room with right lower abdominal pain mimicking acute appendicitis. The main clinical and laboratory findings included fever, leukocytosis and elevated ESR. With preoperative suspicion of acute appendicitis, laparatomy was performed and revealed apparently normal looking appendix, along with a nodule in the terminal ileum. Both the appendix and ileal nodule were removed. Histological examinations revealed carcinoid tumor of appendix and ileal endometriosis. The case was discharged 4 days after surgery with no pain and symptoms and remained symptom free for the 1 year period of follow up. Many cases of carcinoid tumor of the appendix and ileal endometriosis are diagnosed incidentally. Overall prognosis of these conditions is very good. Surgical treatment seems to be the best intervention for these disorders.


New phloroglucinol derivatives from the whole plant of Hypericum uralum.
Seven new phloroglucinol derivatives, uraliones L-R (1-7), were isolated from the whole plant of Hypericum urialum. The structures of new compounds were unambiguously elucidated by comprehensive spectroscopic analysis, and the absolute configurations of the vic-diol groups were determined by Mo2(OAc)4-induced electronic circular dichroism experiments. Their capability to reversal the multidrug resistance in doxorubicin-induced resistant MCF-7/DOX sublines showed that compounds 1, 5, 6, 7 exerted a potential effect of doxorubicin susceptibility.


[Breast implants: Supply on the French market].
The choice of an implant by a plastic surgeon is often based on marketing arguments, believes, and subjective reasons more than real high level evidence basis. Furthermore, we rarely compare manufacturers with each other objectively. Therefore our aim was to put together information coming from the different companies available in France in a single article.


Left sidedness and sleep difficulty: the alinormal syndrome.
Four indexes of laterality: handedness, footedness, eyedness, and earedness, were assessed in a sample of 1274 subjects. Left- and right-sided groups were compared on two aspects of self-reported sleep difficulty: trouble falling asleep and frequent night wakenings. The incidence of sleep difficulty was found to be elevated in the left-sided groups. The results are discussed in terms of a possible complex of behavioral deviations from the statistical norm, called the alinormal syndrome.


A functional proteomic analysis of secreted fibrinolytic enzymes from Bacillus subtilis 168 using a combined method of two-dimensional gel electrophoresis and zymography.
Here we describe a proteomic approach to detect fibrinolytic enzymes from the culture supernatant of Bacillus subtilis 168. Following isoelectric focusing without dithiothreitol, two gels, one for sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and the other for zymography, were run in parallel. After silver staining of SDS-PAGE and activity staining of zymography gel, the two gels were superimposed to detect protein spots that coincided with clear zones on the zymography gel. We identified four protein spots and characterized them with matrix-assisted laser desorption/ionization mass spectrometry. Database search revealed that four spots contained at least one of the extracellular serine proteases such as WprA and Vpr. This combined method of two-dimensional gel and zymography can be used as a powerful tool to detect proteases from various organisms.


Hexavalent chromium induces apoptosis in male somatic and spermatogonial stem cells via redox imbalance.
Hexavalent chromium [Cr(VI)], an environmental toxicant, causes severe male reproductive abnormalities. However, the actual mechanisms of toxicity are not clearly understood and have not been studied in detail. The present in vitro study aimed to investigate the mechanism of reproductive toxicity of Cr(VI) in male somatic cells (mouse TM3 Leydig cells and TM4 Sertoli cells) and spermatogonial stem cells (SSCs) because damage to or dysfunction of these cells can directly affect spermatogenesis, resulting in male infertility. Cr(VI) by inducing oxidative stress was cytotoxic to both male somatic cells and SSCs in a dose-dependent manner, and induced mitochondria-dependent apoptosis. Although the mechanism of Cr(VI)-induced cytotoxicity was similar in both somatic cells, the differences in sensitivity of TM3 and TM4 cells to Cr(VI) could be attributed, at least in part, to cell-specific regulation of P-AKT1, P-ERK1/2, and P-P53 proteins. Cr(VI) affected the differentiation and self-renewal mechanisms of SSCs, disrupted steroidogenesis in TM3 cells, while in TM4 cells, the expression of tight junction signaling and cell receptor molecules was affected as well as the secretory functions were impaired. In conclusion, our results show that Cr(VI) is cytotoxic and impairs the physiological functions of male somatic cells and SSCs.


Trends in twin preterm birth subtypes in the United States, 1989 through 2000: impact on perinatal mortality.
We examined trends in twin preterm birth <37 weeks following ruptured membranes (ROM), medically indicated preterm birth, and preterm birth following spontaneous onset of labor (PTL). We further examined whether the changes in preterm birth subtypes were associated with trends in twin perinatal mortality. We carried out a retrospective cohort study of 1,172,405 twin live births and stillbirths delivered in the US between 1989 and 2000. Trends in preterm birth subtypes and perinatal mortality (stillbirths at > or = 22 weeks plus neonatal deaths within 28 days) were examined through ecological logistic regression models after adjusting for confounders. Twin preterm birth among whites increased from 46.6% in 1989 to 1990 to 56.7% in 1999 to 2000, and from 56.1% to 61.0% among blacks over the same period. Medically indicated preterm birth increased by 50% (95% CI 49-52) among whites, and by 33% (95% CI 29-36) among blacks. PTL increased by 24% among whites, but remained fairly unchanged among blacks between the two periods. Preterm birth following ROM also did not change between the 2 periods among whites, but declined by 7% among blacks. Perinatal mortality among twin births declined by 41% (95% CI 38-44) among whites, and by 37% (95% CI 32-42) among blacks between 1989 and 1990 and 1999 and 2000. This mortality decline was most closely associated with the increase in medically indicated preterm birth among whites, and with the decrease in preterm birth following ROM among blacks. Temporal trends in twin preterm birth varied substantially based on underlying subtypes and race. The increase in medically indicated preterm birth is associated with a large reduction in perinatal mortality.


Japanese Patients Treated in the IMPERIAL Randomized Trial Comparing Eluvia and Zilver PTX Stents.
The purpose of the study is to report 12-month efficacy and safety results from the subgroup of Japanese patients in the prospective IMPERIAL 2:1 randomized controlled trial (RCT). The global IMPERIAL RCT was designed to compare performance of the Eluvia Drug-Eluting Vascular Stent System (Boston Scientific, Marlborough, MA, USA) with the Zilver PTX Drug-Eluting Peripheral Stent (Cook Medical, Bloomington, IN, USA) for treatment of femoropopliteal artery lesions. Patients with symptomatic (Rutherford category 2-4) disease were included. Post-procedural technical success was defined as delivery and deployment of the assigned study stent to the target lesion to achieve residual angiographic stenosis no greater than 30% by visual assessment. Twelve-month assessments included primary patency (core laboratory-assessed duplex ultrasound peak systolic velocity ratio ≤ 2.4 in the absence of clinically driven TLR or bypass of the target lesion) and major adverse events (MAEs). Fifty-six patients in the Eluvia group and 28 in the Zilver PTX group were treated at Japanese centers. Mean lesion length was 91.8 ± 38.0 mm for Eluvia and 87.4 ± 41.7 mm for Zilver PTX. Technical success was 100% for both groups. At 12 months, the observed primary patency rate was 90.9% for Eluvia and 84.6% for Zilver PTX. The 12-month MAE rate was 1.8% for Eluvia and 7.7% for Zilver PTX. All MAEs were clinically driven TLRs. The results show excellent vessel patency and a good safety profile up to 1 year in the subgroup of Japanese patients in IMPERIAL treated with Eluvia for femoropopliteal artery disease. Level 3; subgroup analysis of randomized trial. ClinicalTrials.gov, identifier NCT02574481.


Consequences of a decentralized healthcare governance model: measuring regional authority support for patient choice in Sweden.
What are the implications of a decentralized model of healthcare governance? This case study on patient choice in Sweden is an attempt to shed light on this issue. Due to decentralization and constitutional rights of self-determination, the regional authorities in Sweden, called County Councils (CCs), have far-reaching rights to manage the healthcare sector. The fact that patient choice is considered to be a soft law or a soft governance regulation, opens it up to regional variation. To examine the CCs level of support of patient choice, an index is presented. The Patient Choice Index (PCI) shows that there is extensive variation among the CCs. To explain the causes of these variations, a number of hypotheses are tested. The analyses imply that ideology and economy, and more specifically the CCs' governing majorities and running net profits, are major explanations for the level of support. A number of conclusions can be drawn from the results of this study. In short, the CCs appear to act according to a local point of view, which means that there is no functioning national patient choice standard, and thus patients do not have equal access to healthcare and patients' rights are unevenly distributed. Furthermore, the CCs' financial conditions and governing majorities seem to undermine equivalent reform realization in a national context. In summary, the results of this study emphasize the conflict between regional self-governance and national equality, which is particularly visible in the decentralized Swedish healthcare model.


The dependence of biliary methylmercury secretion on liver GSH and ligandin.
The biliary secretion of methylmercury was investigated in male rats which were given i.p. 400 mumoles/kg azathioprine or 96 mumoles/kg benziodarone 2 hr after the i.v. injection of 5 mumoles/kg MeHgCl. A group of rats were given 400 mg/kg trans-stilbene oxide (TSO) for 4 days before treatment with 10 mumoles/kg MeHgCl. A common link between these three compounds is their interference with ligandin. Azathioprine is a competitive inhibitor of glutathione S-transferase, benziodarone is covalently bound to ligandin and TSO is an inducer of liver ligandin. Although only azathioprine depletes liver GSH stores, both azathioprine and benziodarone inhibited the biliary secretion of methylmercury. As there is published proof that the reaction of MeHg+ with GSH does not require enzymatic help, the inhibitory effect of azathioprine and benziodarone confirms the role of ligandin in the transport of methylmercury or its GSH complex. However, the biliary secretion of methylmercury was increased only slightly by TSO pretreatment, but when 2 hr after the injection of MeHgCl animals received 2 mmoles/kg GSH, secretion increased twice as much in TWO pretreated than in control rats. This indicates the dual dependance of biliary methylmercury secretion on liver GSH and ligandin.


Picture-Induced Semantic Interference Reflects Lexical Competition during Object Naming.
With a picture-picture experiment, we contrasted competitive and non-competitive models of lexical selection during language production. Participants produced novel noun-noun compounds in response to two adjacently displayed objects that were categorically related or unrelated (e.g., depicted objects: apple and cherry; naming response: "apple-cherry"). We observed semantic interference, with slower compound naming for related relative to unrelated pictures, very similar to interference effects produced by semantically related context words in picture-word-interference paradigms. This finding suggests that previous failures to observe reliable interference induced by context pictures may be due to the weakness of lexical activation and competition induced by pictures, relative to words. The production of both picture names within one integrated compound word clearly enhances lexical activation, resulting in measurable interference effects. We interpret this interference as resulting from lexical competition, because the alternative interpretation, in terms of response-exclusion from the articulatory buffer, does not apply to pictures, even when they are named.


Intergenerational Risk of Parentification and Infantilization to Externalizing Moderated by Child Temperament.
The present study examined the intergenerational risk of instrumental filial responsibility in the first generation on children's externalizing behaviors in the next generation and examined difficult child temperament as a potential moderator of this association. Filial responsibility refers to children's instrumental or emotional caregiving roles (Kuperminc, Jurkovic, & Casey, 2009). Moderate levels of instrumental responsibility, such as age-appropriate responsibilities, may be normative whereas too much (parentification) or too little (infantilization) responsibility are associated with risk to development (Jurkovic, 1997), parenting, and offspring development (Nuttall, Valentino & Borkowski, 2012). Prior work has not isolated the unique effects of instrumental caregiving or identified the children most susceptible to intergenerational risk. A multi-site, longitudinal design assessed a diverse sample of first-time mothers and their children. Data from the present study (N=374) were drawn from the third trimester of pregnancy, 12-month and 36-month assessments. Results support the curvilinear association between maternal history of instrumental caregiving and offspring externalizing symptoms controlling for emotional caregiving. Difficult child temperament moderated the association. Maternal instrumental caregiving history increases risk to children's externalizing symptoms, particularly at high (parentification) and low (infantilization) levels of instrumental caregiving and when child temperament is easy rather than difficult.


Functional identification of the terpene synthase family involved in diterpenoid alkaloids biosynthesis in Aconitum carmichaelii.
Aconitum carmichaelii is a high-value medicinal herb widely used across China, Japan, and other Asian countries. Aconitine-type diterpene alkaloids (DAs) are the characteristic compounds in Aconitum. Although six transcriptomes, based on short-read next generation sequencing technology, have been reported from the Aconitum species, the terpene synthase (TPS) corresponding to DAs biosynthesis remains unidentified. We apply a combination of Pacbio isoform sequencing and RNA sequencing to provide a comprehensive view of the A. carmichaelii transcriptome. Nineteen TPSs and five alternative splicing isoforms belonging to TPS-b, TPS-c, and TPS-e/f subfamilies were identified. In vitro enzyme reaction analysis functional identified two sesqui-TPSs and twelve diTPSs. Seven of the TPS-c subfamily genes reacted with GGPP to produce the intermediate ent-copalyl diphosphate. Five AcKSLs separately reacted with ent-CPP to produce ent-kaurene, ent-atiserene, and ent-13-epi-sandaracopimaradie: a new diterpene found in Aconitum. AcTPSs gene expression in conjunction DAs content analysis in different tissues validated that ent-CPP is the sole precursor to all DAs biosynthesis, with AcKSL1, AcKSL2s and AcKSL3-1 responsible for C20 atisine and napelline type DAs biosynthesis, respectively. These data clarified the molecular basis for the C20-DAs biosynthetic pathway in A. carmichaelii and pave the way for further exploration of C19-DAs biosynthesis in the Aconitum species.


Social deprivation, population dependency ratio and an extended hospital episode - Insights from acute medicine.
Patients from deprived backgrounds have a higher in-patient mortality following an emergency medical admission; this study aimed to investigate the extent to which Deprivation status and the population Dependency Ratio influenced extended hospital episodes. All Emergency Medical admissions (75,018 episodes of 41,728 patients) over 12 years (2002-2013) categorized by quintile of Deprivation Index and Population Dependency Rates (proportion of non-working/working) were evaluated against length of stay (LOS). Patients with an Extended LOS (ELOS), >30 days, were investigated, by Deprivation status, Illness Severity and Co-morbidity status. Univariate and multi-variable risk estimates (Odds Rates or Incidence Rate Ratios) were calculated, using truncated Poisson regression. Hospital episodes with ELOS had a frequency of 11.5%; their median LOS (IQR) was 55.0 (38.8, 97.6) days utilizing 57.6% of all bed days by all 75,018 emergency medical admissions. The Deprivation Index independently predicted the rate of such ELOS admissions; these increased approximately five-fold (rate/1000 population) over the Deprivation Quintiles with model adjusted predicted admission rates of for Q1 0.93 (95% CI: 0.86, 0.99), Q22.63 (95% CI: 2.55, 2.71), Q3 3.84 (95% CI: 3.77, 3.91), Q4 3.42 (95% CI: 3.37, 3.48) and Q5 4.38 (95% CI: 4.22, 4.54). Similarly the Population Dependency Ratio Quintiles (dependent to working structure of the population by small area units) independently predicted extended LOS admissions. The admission of patients with an ELOS is strongly influenced by the Deprivation status and the population Dependency Ratio of the catchment area. These factors interact, with both high deprivation and Dependency cohorts having a major influence on the numbers of emergency medical admission patients with an extended hospital episode.


Testicular capillary blood flow in the impubertal lamb and the ram during the breeding and non-breeding seasons.
The testicular capillary blood flow was measured by the 133Xenon clearance technique in the Ile-de-France lambs and rams in Spring and Autumn. Anaesthetized animals were maintained in the supine position and 133Xe was injected into the testicle through the scrotal skin. In the adult, the blood-flow (ml/min./100 g) depended upon the season: 8.3 +/- 1.0 vs 12.7 +/- 0.7 in May and October (P less than 0.001). In the impubertal lamb (50 days old) regardless of the period of the year, the blood flow was the same as in the adult in the breeding season (11.4 +/- 1.2 vs 12.7 +/- 0.7). In prepubertal lambs (120 days old) the rapid increase in testicular weight was not correlated with an increase in the blood flow (9.4 +/- 0.7).


The association between sugar-sweetened beverages and milk intake with emotional and behavioral problems in children with autism spectrum disorder.
Emotional and behavioral problems are common in children with autism spectrum disorder (ASD). It's still unclear whether children with ASD have abnormal sugar-sweetened beverages (SSBs) and milk intake and whether this abnormality will affect their emotions and behavior remains unclear. The current study aims to investigate the association of SSBs and milk intake with emotional and behavioral problems in children with autism spectrum disorder (ASD). 107 children with ASD and 207 typical developing (TD) children aged 6-12 years old were recruited for the study. The frequency of SSBs and milk intake was assessed by a self-designed questionnaire. Emotional and behavioral problems were assessed by Strength and Difficulties Questionnaire (SDQ). Then, the linear regression model was produced to evaluate the association of SSBs and milk intake with emotional and behavioral problems. In the current study, there was no difference in frequency of SSBs intake between children with ASD and TD children (p > 0.05), and children with ASD consumed less milk compared to TD children (p < 0.05). After adjusting sex, age, maternal and paternal education, and monthly family income, we found a significant difference in each subscale score of SDQ in the two groups (p < 0.05). In children with ASD, higher frequent SSBs intake was positively associated with the scores of the emotional problem (p for trend <0.05), and lower frequent milk intake was inversely associated with the scores of prosocial behavior (p for trend <0.05). No interactive effects were found on SSBs and milk intake with emotional and behavioral problems (p for trend > 0.05). In children with ASD, frequency of SSBs and milk intake was associated with the emotional problem and prosocial behavior, respectively. Children with ASD should increase the frequency of milk intake and decrease the frequency of SSBs intake.


Methicillin-resistant Staphylococcus aureus infection in the obstetric setting.
Methicillin-resistant Staphylococcus aureus (MRSA) is an increasingly prevalent pathogen, both in the community and in hospitalized patients. The virulence of MRSA, coupled with its resistance to many frequently prescribed antibiotics, requires increased vigilance in the assessment and diagnosis of skin and soft tissue infections. This article reviews the epidemiology of MRSA and focuses on treatment of MRSA when it is diagnosed during pregnancy.


Measuring interface pressure: validity and reliability problems.
Health service providers rely on pressure-relieving and pressure-reducing products to prevent pressure ulcers. This review critically examines interface pressure measurements, most commonly used to evaluate patient support surfaces.


Comparing costs of standard Breast-Conserving Surgery to Oncoplastic Breast-Conserving Surgery and Mastectomy with Immediate two-stage Implant-Based Breast Reconstruction.
Conventional breast-conserving surgery (C-BCS) has equal oncological outcomes and superior cosmetic and patient-reported outcomes compared to mastectomy with immediate two-stage implant-based breast reconstruction (M-IBR). Oncoplastic breast-conserving surgery (OP-BCS) is increasingly being used, as it often has better cosmetic results and it enables larger tumour resection. However, OP-BCS and M-IBR compared to C-BCS lengthens operative time and might lead to more complications and consequently to additional costs. Therefore, this study aimed to compare costs and complication rates of C-BCS, OP-BCS and M-IBR. This single-centre, retrospective cohort study, calculated costs for all patients who had undergone breast cancer surgery between January 2014 and December 2016. Patient-, tumour- and surgery-related data of C-BCS, OP-BCS and M-IBR patients were retrieved by medical record review. Treatment costs were calculated using hospital financial data. Differences in costs and complications were analysed. A total of 220 patients were included: 74 patients in the C-BCS, 78 in the OP-BCS and 68 in the M-IBR group. From most expensive to least expensive, differences in total costs were found between C-BCS vs. OP-BCS and C-BCS vs. M-IBR (p=<0.01 and p=0.04, respectively). Costs of OP-BCS and M-IBR were comparable. Complication rates were 5.5% for C-BCS, followed by 17% for OP-BCS, and 34% for M-IBR (p<0.01). Considering total treatment costs, OP-BCS was financially non-inferior to M-IBR, whereas complication rates were higher following M-IBR. Therefore, when considering other benefits of OP-BCS, such as higher patient-reported outcomes and similar oncological outcomes, a shift from M-IBR to BCS using oncoplastic techniques seems justified.


[Study on the induction of chronical trichophytosis in small experimental animals for screening antimycotic agents. 3rd communication: the effect of cyclophosphamide on experimental trichophytosis in guinea pigs (author's transl)].
Elevated doses of the cytostatic cyclophosphamide (Endoxan) given daily for 6 weeks, resulted in a prolonged course of experimental trichophytosis in guinea-pigs. From this phenomenon, it may be concluded that the short self-healing course of this disease is due to a rapid triggering of immunoreactions. The fractionated treatment with cyclophosphamide at defined intervals (50 mg/kg initially and 30 mg/kg at 4-day intervals) did not result in any effect.


Cascade two-stage tumor re-oxygenation and immune re-sensitization mediated by self-assembled albumin-sorafenib nanoparticles for enhanced photodynamic immunotherapy.
As a promising modality for cancer therapy, photodynamic therapy (PDT) still acquired limited success in clinical nowadays due to the extremely serious hypoxia and immunosuppression tumor microenvironment. To ameliorate such a situation, we rationally designed and prepared cascade two-stage re-oxygenation and immune re-sensitization BSA-MHI148@SRF nanoparticles via hydrophilic and hydrophobic self-assembly strategy by using near-infrared photodynamic dye MHI148 chemically modified bovine serum albumin (BSA-MHI148) and multi-kinase inhibitor Sorafenib (SRF) as a novel tumor oxygen and immune microenvironment regulation drug. Benefiting from the accumulation of SRF in tumors, BSA-MHI148@SRF nanoparticles dramatically enhanced the PDT efficacy by promoting cascade two-stage tumor re-oxygenation mechanisms: (i) SRF decreased tumor oxygen consumption via inhibiting mitochondria respiratory. (ii) SRF increased the oxygen supply via inducing tumor vessel normalization. Meanwhile, the immunosuppression micro-environment was also obviously reversed by two-stage immune re-sensitization as follows: (i) Enhanced immunogenic cell death (ICD) production amplified by BSA-MHI148@SRF induced reactive oxygen species (ROS) generation enhanced T cell infiltration and improve its tumor cell killing ability. (ii) BSA-MHI148@SRF amplified tumor vessel normalization by VEGF inhibition also obviously reversed the tumor immune-suppression microenvironment. Finally, the growth of solid tumors was significantly depressed by such well-designed BSA-MHI148@SRF nanoparticles, which could be potential for clinical cancer therapy.


Continuous removal of single cell layers by tape stripping the stratum corneum - a histological study.
Studies on the penetration of toxicologically or pharmaceutically relevant substances through the skin and, more specifically, through the stratum corneum (s.c.) often rely on the well-established method of tape stripping. Tape stripping involves the removal of skin layers by means of adhesive tape, which is usually followed by quantification of dermally applied substances in these layers. However, the amount of s.c. removed by each individual tape strip is still a matter of scientific debate. While some studies imply that the amount of s.c. adhering to each tape strip decreases with increasing depth into the s.c., others observed a constant removal rate. All these studies rely on the quantification of the amount of s.c. captured on individual or pooled tape strips. Here, we present an approach whereby we measured the amount of s.c. remaining on excised porcine skin in the process of tape stripping. Staining and bloating of the s.c. allowed to measure its thickness and to count individual s.c. layers, respectively. Histologically, we show that the s.c. remaining on the skin decreased linearly as a function of strips taken. We found that each tape strip removes about 0.4 µm of s.c., which corresponds to approximately one cellular layer. With a high coefficient of determination (r2 > 0.95), we were able to linearly correlate the thickness of the remaining s.c., the number of remaining cell layers and the number of tape strips applied. Furthermore, we elaborate on possible reasons for the discrepancies reported in the scientific literature regarding the amount of s.c. removed by each tape strip.


Sources of black carbon during severe haze events in the Beijing-Tianjin-Hebei region using the adjoint method.
The Beijing-Tianjin-Hebei (BTH) region in China has been frequently suffering from severe haze events (observed daily mean surface fine particulate matter PM2.5 concentrations larger than 150 μg m-3) partially caused by certain types of large-scale synoptic patterns. Black carbon (BC), as an important PM2.5 component and a primarily emitted species, is a good tracer for investigating sources and formation mechanisms leading to severe haze pollutions. We apply GEOS-Chem model and its adjoint to quantify the source contributions to BC concentrations at the surface and at the top of the planetary boundary layer (PBL) during typical types of severe haze events for April 2013-2017 in BTH. Four types of severe haze events, mainly occurred in December-January-February (DJF, 62.3%) and in September-October-November (SON, 26.3%), are classified based on the associated synoptic weather patterns using principal component analysis. Model results reasonably capture the daily variations of BC measurements at three ground sites in BTH. The adjoint method attributes BC concentrations to emissions from different source sectors and from local versus regional transport at the model spatial and temporal resolutions. By source sectors, the adjoint method attributes the daily BC concentrations during typical severe haze events (in winter heating season) in Beijing largely to residential emissions (48.1-62.0%), followed by transportation (16.8-25.9%) and industry (19.1-29.5%) sectors. In terms of regionally aggregated source influences, local emissions in Beijing (59.6-79.5%) predominate the daily surface BC concentrations, while contributions of emissions from Beijing, Hebei, and outside BTH regions are comparable to the daily BC concentrations at the top of PBL (~200-400 m). Our adjoint analyses would provide a scientific support for joint regional and targeted control policies on effectively mitigating the particulate pollutions when the dominant synoptic weather patterns are predicted.


Gastric ulcers after endoscopic sclerosis of esophageal varices.
Two patients with bleeding esophageal varices underwent endoscopic sclerosis. Each developed a gastric ulcer of the fundic mucosa approximately 6-7 cm below the gastro-esophageal junction. It seems probable that these lesions were related to the retrograde flow of sclerosing solution into the venous system which drains the gastric mucosa.


Characteristics of Notch signaling pathway and its correlation with immune microenvironment in SCLC.
To explore the characteristics of Notch pathway in small cell lung cancer (SCLC), clarify the expression of delta-like protein 3 (DLL3) in SCLC patients undergoing surgical treatment, and explore the correlation between DLL3 expression and clinicopathological features, prognosis, and immune microenvironment. A total of 134 patients who received surgical treatment and were diagnosed as SCLC by postoperative histopathology were enrolled. All exon gene sequencing was performed in tumor tissues and adjacent normal tissues of 28 patients to clarify the genomic characteristics of SCLC. The expressions of DLL3 and programmed cell death 1 ligand 1 (PDL1) were detected by immunohistochemistry (IHC) in 101 postoperative pathological specimens. Notch receptor mutations are common, but the overall mutation rate of Notch ligand family is not high and mutually exclusive. The mutation status of Notch and Notch1 gene were not related to the prognosis. Notch1 gene mutation was significantly negatively correlated with the expression of PD-L1. DLL3 was highly expressed in SCLC and had no significant correlation with prognosis. There was a positive correlation between DLL3 expression and PD-L1 expression. Patients with positive DLL3 expression and no NOTCH 1 gene mutation had higher PD-L1 expression. SCLC patients with such characteristics may be more likely to benefit from immunotherapy. This study preliminarily explored the genomic characteristics and immune microenvironment of surgical resection of SCLC in China, and found the correlation between Notch gene mutation, DLL3 expression and PD-L1 expression, which provided a new idea for selecting appropriate treatment strategies for SCLC in the future.


Comparison of anteroposterior lip positions of the most-favored facial profiles of Korean and Japanese people.
A consensus on the contemporary perception of beauty might have been developed between different countries because of increased worldwide access to variations in pleasing facial profiles. The objectives of this study were to determine, assess, and compare the ranges of values of the most-favored facial profiles rated by young Korean and Japanese adults. Average profiles were constructed from the profiles of 30 Japanese men and women with normal occlusions. A series of 13 profiles each was developed for men and women. In the series, the average profile was located in the center (number 7), and the lips were protruded or retruded in 1-mm increments from the average profile. Forty-six Korean dental students and 52 Japanese dental students were asked to rate the top 3 most-favored profiles. Both the Korean and the Japanese dental students tended to select a slightly more retruded lip profile compared with the averages for men and women, and the tendency to prefer a more retruded lip position was evident for the women. These findings suggest that young Korean and Japanese adults prefer a retruded profile, even though their profiles have historically been characterized by more convex facial features.


Growth of the oleaginous microalga Aurantiochytrium sp. KRS101 on cellulosic biomass and the production of lipids containing high levels of docosahexaenoic acid.
We examined the growth of a novel oleaginous microalga, Aurantiochytrium sp. KRS101, using cellulosic materials as nutrients, and the resultant production of lipids containing high levels of docosahexaenoic acid (DHA). The microalgal strain could grow using either carboxymethylcellulose or cellobiose as a carbon source, and produced lipids containing high levels of DHA (49-58% of total fatty acids). In line with this growth behavior, carboxymethylcellulase and cellobiohydrolase activities were evident in both cell-free lysates and culture broths. Additionally, an industrial cellulosic biomass, palm oil empty fruit bunches (POEFB), a by-product of the palm oil industry, were utilized by the microalgal strain for cell growth and lipid production.


Evaluation of e-learning for medical education in low- and middle-income countries: A systematic review.
In low- and middle-income countries (LMICs), e-learning for medical education may alleviate the burden of severe health worker shortages and deliver affordable access to high quality medical education. However, diverse challenges in infrastructure and adoption are encountered when implementing e-learning within medical education in particular. Understanding what constitutes successful e-learning is an important first step for determining its effectiveness. The objective of this study was to systematically review e-learning interventions for medical education in LMICs, focusing on their evaluation and assessment methods. Nine databases were searched for publications from January 2007 to June 2017. We included 52 studies with a total of 12,294 participants. Most e-learning interventions were pilot studies (73%), which mainly employed summative assessments of study participants (83%) and evaluated the e-learning intervention with questionnaires (45%). Study designs, evaluation and assessment methods showed considerable variation, as did the study quality, evaluation periods, outcome and effectiveness measures. Included studies mainly utilized subjective measures and custom-built evaluation frameworks, which resulted in both low comparability and poor validity. The majority of studies self-concluded that they had had an effective e-learning intervention, thus indicating potential benefits of e-learning for LMICs. However, MERSQI and NOS ratings revealed the low quality of the studies' evidence for comparability, evaluation instrument validity, study outcomes and participant blinding. Many e-learning interventions were small-scale and conducted as short-termed pilots. More rigorous evaluation methods for e-learning implementations in LMICs are needed to understand the strengths and shortcomings of e-learning for medical education in low-resource contexts. Valid and reliable evaluations are the foundation to guide and improve e-learning interventions, increase their sustainability, alleviate shortages in health care workers and improve the quality of medical care in LMICs.


Incidence and genetic diversity of multi-drug resistant Listeria monocytogenes isolates recovered from fruits and vegetables in the Eastern Cape Province, South Africa.
We investigated the prevalence, genetic diversity and antibiogram profiles of Listeria monocytogenes (Lm) recovered from fruits and vegetables sourced from three District Municipalities in the Eastern Cape Province, South Africa after the recent listeriosis outbreak in the country. The procedure outlined by the International Organization for Standardization EN ISO 11290:2017 Parts 1 and 2 was adopted for the isolation of Lm from 140 vegetable samples. Molecular detection of the pathogen and the presence of 10 virulence-associated markers were assessed. Lm was detected in 42.86% of all the vegetable samples tested. Highest prevalence was recorded in tomato (65.52%) followed by spinach (56.67%), cabbage (38.10%), apple (36.84%), mushroom (29.41%) and carrot (10%). The virulence determinants including the inlA, inlC, prfA and plcA, hly, plcB genes were detected in all Lm isolates whereas, inlJ (88.35%), inlB (86.41%), mpl (92.23%) and actA (84.55%) respectively. High susceptibility (> 50) was observed to all antibiotics tested except for sulfamethoxazole (17.48%), streptomycin (38.84%), amoxicillin (41.75%) and erythromycin (43.69%). However, high resistance against sulfamethoxazole (80.58%), amoxicillin (58.25%) and erythromycin (49.52%) were observed. About 85.44% of Lm isolates showed multidrug-resistance phenotypes against the test antibiotics. Furthermore, twenty (20) resistance genes encoding tetracyclines, sulphonamides, phenicols, aminoglycosides, β-lactamases, and variants of the extended-spectrum of β-lactamases (ESBLs) resistance were detected among the Lm isolates. The sul2 (90.81), tetM (68.42%) sul1 (45.98%) were more prevalent among the resistant strains. The dendrogram signatures generating seven clades is an indication of the high genetic diversity among the isolates. We conclude that the presence of Lm in fruits and vegetables is a potential threat to the consumers and a potential public health hazard, particularly to the high-risk group of the population.


Modeling supramolecular assemblages.
There has been some progress (but not much) in simulating supramolecular assemblages in the past year. The two main technical advances have been, firstly, the establishment of a protocol for extracting equilibrium thermodynamic data from forced (i.e. nonequilibrium) simulations and experiments, and, secondly, the development of a method for accurately calculating the electrostatics of enormous systems. Some recent applications have demonstrated the increasing feasibility of performing meaningful simulations of very large systems.


Circulating interleukin 10 and interleukin-6 serum levels in rheumatoid arthritis patients treated with methotrexate or gold salts: preliminary report.
In order to evaluate the relationship between serum concentrations of interleukin-10 (IL-10), IL-6, and acute phase proteins in rheumatoid arthritis (RA) patients treated with methotrexate (MTX) or intramuscular gold (IMG) we determined IL-10, IL-6, C-reactive protein (CRP), alpha-1-acid glycoprotein (AGP) and alpha-1-antichymotrypsin (ACT) in the sera of 35 RA patients. IL-10 and IL-6 levels were evaluated using an enzyme-linked immunoassay (ELISA). AGP and ACT level were measured using rocket immunoelectrophoresis. IL-10 serum level was not increased in RA patients as compared to controls (58.7 +/- 18.1 pg/ml vs. 57.2 +/- 11.9 pg/ml). IL-6 level was significantly elevated (91.6 +/- 46.9 pg/ml vs. 45 +/- 19 pg/ml, p < 0.05). CRP was significantly increased as compared to healthy controls (35 +/- 19 mg/l vs. 3 +/- 2 mg/l, p < 0.05). Patients treated with MTX or IMG presented an increased level of IL-10 and decreased amounts of IL-6, as compared to those treated with NSAID only. However, only changes between patients treated with IMG and NSAID were found to be statistically significant. A good negative correlation between IL-10 and IL-6 serum level was found (r = -0.75, p < 0.05). A positive significant correlation between IL-6 serum level and CRP (r = 0.62, p < 0.05), AGP (r = 0.78, p < 0.05) and ACT (r = 0.45, p < 0.05) was established.(ABSTRACT TRUNCATED AT 250 WORDS)


Detergent-Free Simultaneous Sample Preparation Method for Proteomics and Metabolomics.
The integration of omics techniques has seen a step change in our understanding of biological systems. However, multiomics has been impaired by mutually exclusive omic separation methods and the destructive nature of the techniques when sample is limited. We describe Simultaneous Trapping (SiTrap), a simple and effective detergent-free method that facilitates direct measurement of the proteome and metabolome in the same sample extract. This "single-pot" multiomics processing is particularly beneficial in cases when sample amounts are limited or are heterogeneous, for example, tissue biopsies. We demonstrate the value of the SiTrap methodology as an essential multiomics tool in a proof-of-principle integrated study of renal cancer tissue biopsy samples. We believe SiTrap has the potential to become an indispensable tool in translational medical research.


In vitro activity of daptomycin against methicillin- and multi-resistant Staphylococcus haemolyticus invasive isolates carrying different mec complexes.
Fifty methicillin and multi-resistant Staphylococcus haemolyticus (MRSH) strains, were tested against daptomycin and comparators. Daptomycin showed an overall MIC(90) value of 1 mg/L, similar to that of quinopristin/dalfopristin and lower than the values for vancomycin (2 mg/L), linezolid (2 mg/L) and teicoplanin (32 mg/L). Eighteen strains showed heteroresistant subpopulations with teicoplanin, whereas two strains were also heteroresistant to vancomycin and these sub-populations retained susceptibility to daptomycin. Our results show the good in vitro activity of daptomycin in MRSH strains possessing a multi-resistant phenotype. Clinical data on daptomycin efficacy are necessary to confirm our in vitro findings.


Adolescent neurodevelopment.
The purpose of this article is to outline notable alterations occurring in the adolescent brain, and to consider potential ramifications of these developmental transformations for public policy and programs involving adolescents. Developmental changes in the adolescent brain obtained from human imaging work are reviewed, along with results of basic science studies. Adolescent brain transformations include both progressive and regressive changes that are regionally specific and serve to refine brain functional connectivity. Along with still-maturing inhibitory control systems that can be overcome under emotional circumstances, the adolescent brain is associated with sometimes elevated activation of reward-relevant brain regions, whereas sensitivity to aversive stimuli may be attenuated. At this time, the developmental shift from greater brain plasticity early in life to the relative stability of the mature brain is still tilted more toward plasticity than seen in adulthood, perhaps providing an opportunity for some experience-influenced sculpting of the adolescent brain. Normal developmental transformations in brain reward/aversive systems, areas critical for inhibitory control, and regions activated by emotional, exciting, and stressful stimuli may promote some normative degree of adolescent risk taking. These findings have a number of potential implications for public policies and programs focused on adolescent health and well-being.


Heavy metals in the clam Megapitaria squalida collected from wild and phosphorite mine-impacted sites in Baja California, Mexico: considerations for human health effects.
The "chocolate clam" Megapitaria squalida, is widely consumed by the population of several localities along the Pacific coast. Clams collected from seven stations in Bahía de la Paz, a bay within the Gulf of California, before and after the summer rainy season were analyzed for Pb, Ni, Cd, Mn, Zn, Cu, and Fe. The location of the sampling sites significantly affected the concentration of metals in clam tissues, but not in relation to the proximity to alleged contaminated sites. Clams from a site close to a phosphate mine had the highest levels of Pb, but only in April, and the highest concentrations of Cd were recorded in clams collected in areas with no anthropogenic activities. Clams from sites considered clean had higher levels of Cd, Fe, Zn, and Mn. The mean concentrations (microg/g dry weight) ranged from 0.1 to 7.8 for Pb, from 1.9 to 8.8 for Ni, from 1.5 to 11.1 for Cd, from 2.5 to 14.1 for Mn, from 47.2 to 64.6 for Zn, from 5.4 to 18.7 for Cu, and from 154 to 558 for Fe. Collecting clams in sites apparently pristine is no guarantee that metals will be in low concentrations.


Altered taste preference and loss of limbic-projecting serotonergic neurons in the dorsal raphe nucleus of chronically epileptic rats.
Mood disorders and major depression are frequently comorbid with epilepsy. While the nature of this comorbidity is not fully understood, multiple lines of evidence suggest that changes in serotonin (5-HT) neurotransmission may be an underlying mechanism. In this study, we tested the hypothesis that chronic epilepsy in rats can be associated with loss of 5-HT neurons in the dorsal raphe (DR) nuclear complex, the main source of 5-HT projections to the cerebral cortex, which would help to explain respective behavioral deficits. Epilepsy was induced using the kainate model of status epilepticus in adult Wistar rats. After a 3-month recovery period, all kainate-treated rats that had experienced status epilepticus showed spontaneous seizures and reduced sucrose preference (anhedonia), a core symptom of depression. No changes in the forced swim test were detected. The total numbers of 5-HT immunoreactive cells were estimated in all DR subdivisions of control and epileptic rats. Interestingly, epilepsy-related loss of 5-HT neurons (approximately 35%) was observed only in the interfascicular part of the DR complex, which is known to innervate brain regions involved in depression. These findings support the notion that mental health impairments observed in epilepsy may be related to loss of a specific population of the DR 5-HT neurons projecting to limbic brain areas.


CUIDAR-MaPre scale validation: A tool to measure the caregiving competence of mothers of premature infants.
To determine the validity and reliability of the CUIDAR instrument in mothers of premature infants. Cross-sectional validation study. The study was conducted in two stages. First stage: literature review, semantic adequacy, and judgement with 7 experts to establish content validity. In the second stage, the psychometric properties of the instrument were evaluated by exploratory factor analysis after its application to 207 mothers of premature infants. In the expert's judgment, the content validity index was higher than 0.8, which indicated adequate representativeness of the items. Agreement between judges was moderate with a Fleiss Kappa of 0.51. The exploratory factor analysis established the adequacy of the sample with a Kaiser-Mayer-Olkin statistic of 0.859 and Bartlett's test of sphericity 2953.9 (p = 0.000). After considering various scenarios, a 7-dimensional, 33-item model explained 57.9% of the variance, with an overall Cronbach's alpha of 0.852 and adequate goodness-of-fit indices. The goodness-of-fit tests allowed us to establish through statistical significance χ2 = 0.01, CFI = 0.92, BIC ≥ 10 and RMSEA = 0.05 indicating that the model has a good fit. A new model was identified based on the items and dimensions of the CUIDAR instrument, which allows us to assess the competence of mothers to care for their premature children in a valid and reliable way.


The role of MOF based nanocomposites in the detection of phenolic compounds for environmental remediation- A review.
Phenolic compounds would be the emerging pollutant by 2050, because of their wide spread applicability in daily life and therefore the adoption of suitable detection methods in which identification and separation of isomers is highly desirable. Owing to the fascinating features, Metal-organic framework (MOF), a class of reticular materials holds a large surface area with tunable shape and adjustable porosity will provide strong interaction with analytes through abundant functional groups resulting in high selectivity towards electrochemical determination of phenolic isomers. Nevertheless, the sensing performance can still be further improved by building MOF network (intrinsic resistance) with functional (conducting) materials, resulting in MOF based nanocomposite. Herein, this review provides the summary of MOF based nanocomposites for electrochemical sensing of phenolic compounds developed from 2015. In this review, we discussed the demerits of pristine MOF as electrode materials, and the requirement of new class of MOF with functional materials such as nanomaterials, carbon nanotubes, graphene and MXene. The history and evolution of MOF nanocomposite-based materials are discussed and also featured the impressive physical and chemical properties. Besides this review discusses the factors influencing the conducting pathway and mass transport of MOF based nanocomposite for enhanced sensing performance of phenolic compounds with suitable mechanistic illustrations. Finally, the major challenges governing the determination of phenolic compounds and the future advancements required for the development of MOF based electrodes for various applications are highlighted.


Middle bile duct cancer with portal vein tumor thrombus.
Tumor thrombus in the portal vein is a common complication of hepatocellular carcinoma, but an extremely rare complication of common bile duct cancer. A 78-year-old woman was referred to our department because of jaundice. Laboratory data showed severe liver dysfunction with high serum levels of total bilirubin and CA19-9. Computed tomography showed lesions in the middle bile duct and main portal vein. FDG PET scan and 3D imaging showed hot spots in the same location as those revealed by CT. Under a diagnosis of middle bile duct cancer with portal vein tumor thrombus, the patient underwent surgery. At laparotomy, the main tumor was found to be located in the middle bile duct with a tumor thrombus, 2 cm in diameter, in the main portal vein. The patient underwent pancreatoduodenectomy with thrombectomy. Histological examination showed that this thrombus had the same histological features as those of the main bile duct cancer (poorly differentiated adenocarcinoma). The postoperative course was uneventful and the patient is doing well without any signs of recurrence 18 months after surgery. To our knowledge, this is the first report of successful resection of middle bile duct cancer with portal vein tumor thrombus.


Cell-free protein synthesis enables high yielding synthesis of an active multicopper oxidase.
Multicopper oxidases (MCOs) are broadly distributed in all kingdoms of life and perform a variety of important oxidative reactions. These enzymes have potential biotechnological applications; however, the applications are impeded by low expression yields in traditional recombinant hosts, solubility issues, and poor copper cofactor assembly. As an alternative to traditional recombinant protein expression, we show the ability to use cell-free protein synthesis (CFPS) to produce complex MCO proteins with high soluble titers. Specifically, we report the production of MCOs in an Escherichia coli-based cell-free transcription-translation system. Total yields as high as 1.2 mg mL(-1) were observed after a 20-h batch reaction. More than 95% of the protein was soluble and activity was obtained by simple post-CFPS addition of copper ions in the form of CuSO4 . Scale-up reactions were achieved from 15 to 100 µL without a decrease in productivity and solubility. CFPS titers were higher than in vivo expression titers and more soluble, avoiding the formation of inclusion bodies. Our work extends the utility of the cell-free platform to the production of active proteins containing copper cofactors and demonstrates a simple method for producing MCOs.


A bradykinin antagonist abolishes beneficial effect of captopril on duration of survival after acute coronary artery ligation in hypertensive rats.
It has been recently suggested that bradykinin (BK) may act as a cardioprotective agent. In the present investigation, we evaluated the effects of captopril, an angiotensin-converting enzyme inhibitor (ACEI), and kinin B2 receptor antagonist, D-Arg-[Hyp3-D-Phe7]-BK, on the duration of survival after acute coronary artery ligation for 15 min in spontaneously hypertensive rats (SHR). The captopril treatment (16 and 32 ug/kg, i.v.) resulted in a significant (p < 0.05) increase in survival time of SHR as compared with saline-treated control SHR. Kinin B2 receptors antagonist (4 ug/kg, i.v.) pretreatment abolished (p > 0.05) the beneficial effect of captopril on survival time as compared to saline-treated control SHR. Both the ligation of coronary artery and captopril treatment resulted in a significant (p < 0.001) fall in systolic blood pressure (SBP), diastolic blood pressure (DBP) and heart rate (HR) of SHR as compared to the saline-treated control SHR. In addition, captopril administration caused a significant (p < 0.05) fall in the SBP, DBP and HR of SHR before ligation of the coronary artery (preligation). However, there was no significance (p > 0.05) in SBP, DBP and HR between saline- and kinin B2 receptor antagonist plus captopril-treated SHR during preligation. These finding might indicate that captopril possesses a cardioprotective property as demonstrated by increased in survival time of SHR. This beneficial effect of captopril is mediated via the kinin B2 receptor pathway because kinin B2 receptor antagonist pretreatment blocked the captopril-induced increase in survival time of SHR.


Risk management of HBsAg or anti-HCV positive healthcare workers in hospital.
Recommendations are made for controlling the transmission of the hepatitis B and hepatitis C viruses from healthcare workers to patients. These recommendations were based both on the literature and on experts' opinions, obtained during a Consensus Conference. The quality of the published information and of the experts' opinions was classified into 6 levels, based on the source of the information. The recommendations can be summarised as follows: all healthcare workers must undergo hepatitis B virus vaccination and adopt the standard measures for infection control in hospitals; healthcare workers who directly perform invasive procedures must undergo serological testing and the evaluation of markers of viral infection. Those found to be positive for: 1) HBsAg and HBeAg, 2) HBsAg and hepatitis B virus DNA, or 3) anti-hepatitis C virus and hepatitis C virus RNA must abstain from directly performing invasive procedures; no other limitations in their activities are necessary. Infected healthcare workers are urged to inform their patients of their infectious status, although this is left to the discretion of the healthcare worker; whose privacy is guaranteed by law. If exposure to hepatitis B virus occurs, the healthcare worker must undergo prophylaxis with specific immunoglobulins, in addition to vaccination.


Successful surgical treatment of intravascular ultrasonography catheter entrapment.
Coronary angiography (CAG) was performed in a 77-year-old woman who presented with chest discomfort. The CAG showed two diseased vessels. For treatment, the patient underwent angioplasty and stenting. During intravascular ultrasonography (IVUS) following stent deployment, the IVUS catheter became entrapped in the left anterior descending coronary artery, causing ischemic changes in the anterolateral wall, which were apparent on the electrocardiogram. The patient underwent emergency coronary artery bypass grafting and removal of the entrapped IVUS catheter.


Successful replacement of aortic root with valve-sparing technique and proximal arch in a patient with myelodysplastic syndrome.
Cardiac surgery in a patient with myelodysplastic syndrome (MDS) increases the risk of bleeding and infection. Here we report a case of a 70-year-old man with MDS who underwent successful replacement of the aortic root with the valve-sparing technique and proximal arch for aneurysmal dilatation from the aortic root to ascending aorta with moderate aortic valve regurgitation. Perioperatively, a transfusion of red blood cells and an infusion of a grannulocyte colony-stimulating factor were required for his serious erythrocytopenia and leukocytopenia. Bleeding tendency was so severe that re-exploration to control postoperative surgical bleeding was performed and a large amount of blood cells were transfused. There was no infection on the postoperative course. Perioperative management for cardiac surgery in patients with MDS must be carefully programmed by a co-operative team consisting of cardiovascular surgeons and hematologists.


Effect of Xiaoaiping injection on advanced hepatocellular carcinoma in patients.
To investigate the effect of Xiaoaiping Injection (XAP) on advanced hepatocellular carcinoma (HCC) in patients. Sixty-eight patients with advanced HCC were assigned to a control group of 36 and a treatment group of 32. The control group was treated with best supportive treatment (BST) and the treatment group was given XAP plus BST. XAP was administered daily by i.v. and the treatment course was lasted for 30 days for both groups. The immediate therapeutic efficacy, Karnofsky performance status (KPS) scores, and the changes in immunity indicators (CD3+, CD4+ and CD8+ T cells) were measured and compared before and after treatment. The progression-free survival (PFS) rate and overall survival (OS) rate in the 2 groups were analyzed. The immediate therapeutic efficacy and KPS of the treatment group were better than those in the control (P < 0.05). Patients in the treatment group had higher percentages of CD3 and CD4 T-lymphocytes in peripheral blood than those in the control group (P < 0.05). The median survival time was 27.0 weeks in the treatment group and 24.5 weeks in the control group. The 6-months cumulative survival rates in the treatment and control groups were 33.3% and 25.0%, respectively, with no significant difference (P > 0.05). The PFS was 18 weeks in the treatment group and 15 weeks in control group (P < 0.05). XAP enhances the quality of life (QOL) of patients with advanced HCC, improves their immunity and extends their PFS.


Functional responses to baclofen and 4,5,6,7-tetrahydroisoxazolo (5,4-c) pyridin-3-ol (THIP) in rats repeatedly treated with desipramine.
Subcutaneous chronic desipramine (DMI, 5 mg/kg once daily for 18 consecutive days) prevented subcutaneous THIP (20 mg/kg) reduction in body temperature but did not affect THIP behavioral depressant effect (open-field behavior). Repeated DMI treatment did not affect subcutaneous baclofen (2.5-10 mg/kg) reduction in body temperature and behavioral depression (open-field behavior).


Red cell metabolism in red and grey kangaroos.
Glucose utilization, lactate production and glutathione regeneration were measured in the red blood cells of 2 species of Australian Marsupials, Eastern grey Kangaroo (Macropus gigantus) and red kangaroo (Macropus rufus), and were found to be significantly lower in the red blood cells from grey than that of red kangaroos.


Activation of lymphocytes alters Fc receptor-beta 2-microglobulin interrelationship on the lymphocyte surface.
The effect of anti-beta 2-microglobulin (anti-B2Mi) on the expression of Fc receptors (FcR) of human lymphocytes was compared on resting and activated cells. Previously we reported that anti-B2Mi induces a "co-shedding" of FcR with the beta 2-microglobulin (B2Mi)-anti-B2Mi complexes when used under the conditions where the redistribution of membrane molecules is allowed (Sármay et al., Cell. Immunol. 56, 452, 1980; Sármay et al. Immunology 36, 339, 1979). Furthermore our group also described two types of FcR-bearing cells, one which shed their FcR during a temperature shift from 4 to 37 degrees C (FcRI+ cells) and the other which has an immobile type FcR under the same circumstances (FcRI+ cells) (Sándor et al., Immunology 38, 553, 1979; Sármay et al., Immunology 34, 315, 1978). In this work we have characterized the FcR released from the membrane as a consequence of anti-B2Mi treatment. We have found that they are the mobile, FcRI type. It was proved that the shedding of this FcRI is a consequence of the anti-B2MI-induced transformation of FcRII into the FcRI form on the membrane of the antibody-treated lymphocytes. On the activated T cells, however, anti-B2Mi is incapable of inducing the same phenomenon in the early phase of activation. In contrast, FcR expression is blocked by anti-B2Mi treatment similarly to that on resting lymphocytes, on the surface of activated B cells, or on activated T cells in the later phases of activation.


Relations between the consumption of antimicrobial growth promoters and the occurrence of resistance among Enterococcus faecium isolated from broilers.
The present study investigates, at farm level, the effect of the time-span between sampling and the last time a particular antimicrobial growth promoter (AGP) was included in the feed on the probability of selecting an AGP-resistant Enterococcus faecium isolate from a broiler flock. The probability that a randomly selected E. faecium isolate was resistant to avilamycin, erythromycin or virginiamycin was 0.91, 0.92 and 0.84, respectively if the isolate originated from a broiler flock fed either avilamycin- or virginiamycin-supplemented feed. As the time-span between sampling and the last AGP consumption increased, the probability of isolating an E. faecium isolate resistant to a particular AGP decreased (probability <0.2 within 3-5 years after last exposure to AGPs). The decrease in probability over time showed little farm-to-farm variation. The number of times a particular AGP was given to previous flocks reared in the same house had no effect on the probability of isolating a resistant isolate.


Model Selection and Estimation in the Matrix Normal Graphical Model.
Motivated by analysis of gene expression data measured over different tissues or over time, we consider matrix-valued random variable and matrix-normal distribution, where the precision matrices have a graphical interpretation for genes and tissues, respectively. We present a l(1) penalized likelihood method and an efficient coordinate descent-based computational algorithm for model selection and estimation in such matrix normal graphical models (MNGMs). We provide theoretical results on the asymptotic distributions, the rates of convergence of the estimates and the sparsistency, allowing both the numbers of genes and tissues to diverge as the sample size goes to infinity. Simulation results demonstrate that the MNGMs can lead to better estimate of the precision matrices and better identifications of the graph structures than the standard Gaussian graphical models. We illustrate the methods with an analysis of mouse gene expression data measured over ten different tissues.


The Ethical Sensitivity of Health Care Professionals Who Care For Patients Living With HIV Infection in Hunan, China: A Qualitative Study.
The level of ethical sensitivity of health care professionals who care for patients with HIV may shed light on ethical behaviors in HIV care. However, little research has determined how such professionals view ethical issues in clinical practice in China. The purpose of our qualitative descriptive study was to explore the ethical sensitivity of health care professionals in Hunan Province, China, and to discuss the existing deficiencies. We used purposive sampling to recruit 17 health care professionals who provided direct care to patients with HIV and conducted interviews with them. Interview transcripts were analyzed by thematic analysis. Informants showed certain sensitivities to ethical issues, but the majority also held stigmatizing attitudes toward patients with HIV, and exhibited ethics driven by HIV-related laws and regulations rather than ethical principles. There is room to improve the ethical sensitivity of health care professionals who care for patients with HIV in China.


"Caught in the Middle! Wealth Inequality and Conflict over Redistribution".
A vast literature documents that wealth inequality has risen throughout advanced democracies, especially the accumulation of wealth among the rich. Yet, instead of increasing wealth redistribution, governments have done the seemingly opposite. Key to understanding why democratic governments do not increase wealth redistribution in times of rising inequalities is to shed light on the public's preferences. In this paper, we map the public's redistributive preferences in fourteen countries based on new survey data. We show that traditional socioeconomic cleavages in preferences for wealth redistribution are undermined by diverging mobility expectations. People who expect to climb up the wealth distribution, mostly lower wealth groups, are less supportive of redistribution than people with high stakes of major wealth losses, mainly upper wealth groups. We show that future expectations among the rich and the poor have a highly moderating role for the class conflict over wealth redistribution. Moreover, the middle class, the decisive group in democracies, is highly unresponsive to future prospects. The findings suggest that the middle class does not have much to lose or to win, and therefore, wealth redistribution is of low salience among this group.


Comparison of potential cytoprotective action of sucralfate and cimetidine. Studies with experimental feline esophagitis.
The potential mucosal protective effects of a liquid sucralfate preparation and the histamine (H2)-antagonist cimetidine on acid-induced esophagitis were studied. Esophagitis was induced in adult cats using a constant infusion of 0.1 N hydrochloric acid at 1 ml/minute for 20 minutes. Mucosal lesions were evaluated by blinded investigators using both fiber-optic endoscopy and light microscopy. Histology was scored for basal cell hyperplasia, intraepithelial leukocytosis, and subepithelial leukocytosis. Liquid sucralfate given prior to acid infusion consistently prevented acid-induced lesions, demonstrated by quantitative histologic scoring. Although cimetidine did not show the same degree of protection as sucralfate, the results did show a trend towards a cytoprotective effect.


Fractal dimension of chromatin texture of squamous intraepithelial lesions of cervix.
The aim of this study was to explore the role of fractal dimension (FD) of chromatin texture in routinely stained Papanicolaou's smears and to distinguish the different grades of cervical intraepithelial lesions and normal cervical cells. We selected 14 each cases of normal, low grade cervical intra epithelial lesions (LSIL), and high-grade cervical intra epithelial lesions (HSIL) of Papanicolaou's stained cervical smears. Fractal dimension of the pseudo three-dimensional grey image of the nuclear chromatin was measured in 140 nuclei of each group. Mean FD of the normal cases, LSIL cases, and HSIL cases were 2.4225 ± 0.06410, 2.5159 ± 0.03291, and 2.5905 ± 0.06840, respectively. ANOVA test showed significant differences of mean FD in all these three groups (P < 0.000). Fractal dimension of the chromatin texture is easy to perform and can be done in routinely stained Papanicolaou's smear. It is reproducible and gives valuable information about the chromatin texture of the nucleus. In future, this promising variable can be incorporated along with other image morphometric features for accurate classification of dysplastic cells in cervical smear.


Pancreatitis and pancreatic cystosis in Cystic Fibrosis.
The pathologic effects of an altered cystic fibrosis transmembrane receptor (CFTR) protein on the exocrine pancreas is ubiquitous and of varying severity. In this section, pancreatitis and pancreatic cystosis are covered.


Geothermal energy integrated multi-effect evaporator (MEE) and multi-effect distillation (MED)-based desalination systems: an ecofriendly and sustainable solutions.
Desalination is a tried-and-true method for obtaining clean water from the ocean's brackish waters and recycling and reusing water. It requires a fair amount of energy, so it is necessary to create sustainable energy systems to lessen energy use and environmental impact. For thermal desalination procedures, thermal sources can be great heat sources. This paper's research focuses on thermoeconomically optimized multi-effect distillation and geothermal desalination systems. Collecting hot water from subsurface reservoirs is a well-established method of generating electricity through geothermal sources. Low-temperature geothermal sources, which have a temperature of less than 130 °C, can be utilized for thermal desalination systems, for example, multi-effect distillation (MED). Geothermal desalination is affordable, and it is possible to produce power simultaneously. Because it only uses clean, renewable energy and produces no greenhouse gasses or other pollutants, it is also safe for the environment. The viability of any geothermal desalination plant will be influenced by the location of the geothermal resource, feed water supply, cooling water source, water market, and concentrate disposal site. Geothermal energy can directly supply heat for a thermal desalination system or indirectly give electrical power to reverse the osmosis (RO) membrane-based desalination plant.


The nitrogen and energy metabolism of lactating cows given abomasal infusions of casein.
1. Four cows in early lactation were given continuous infusion into the abomasum of 0, 200, 400 or 600 g lactic casein/d according to a Latin-square design. Each period was of 14 d and the Latin square was followed by 7 d in which an infusion of 800 g glucose/d was given. The basal diet was given at a level which provided sufficient nitrogen and energy for 10 kg milk yield/d. 2. Infusion of casein resulted in significant increases in milk yield, milk N yield and milk energy yield; milk N increased progressively but milk energy reached a maximum at 400 g casein/d. Milk yields and composition when glucose was infused resembled those seen on the zero casein treatment. 3. N-balance measurements indicated a severe deficit (-20 g/d) on the zero casein treatment and a progressive increase to +7 g/d as casein increased; N equilibrium was achieved at about 400 g casein/d. The regression of net productive N on N intake (P less than 0.001) indicated that the efficiency of utilization of dietary N did not differ between treatments. 4. Heat production increased with increase in casein infused (P less than 0.05) but remained a constant proportion of the metabolizable energy (ME) intake. Energy balances were negative and did not differ significantly between treatments but calculation of the protein and fat components indicated a threefold increase in body fat mobilization in response to the first increment of casein. Milk yield adjusted to zero energy balance was significantly related to ME intake (P less than 0.001) but the efficiency of energy utilization was not affected by the level of casein infusion. 5. The concentrations of glucose, beta-hydroxybutyrate and non-esterified fatty acids in plasma did not differ between treatments but the concentration of urea in plasma increased markedly (P less than 0.05) at the highest level of casein addition. Insulin concentrations increased and growth hormone decreased (both P less than 0.05) with increase in casein infusion. 6. The concentration of total amino acids (AA) in plasma increased up to 400 g casein/d and then declined. Changes in concentration and in the ratio of essential:total AA indicated a very high extraction rate of essential AA at the lower levels of casein infusion. 7. The observed lactational responses are discussed in relation to the ratio of protein:energy in the absorbed nutrients.(ABSTRACT TRUNCATED AT 400 WORDS)


Factor V Leiden and G20210A prothrombin mutations are risk factors for very early recurrent miscarriage.
To determine whether there is an association between early recurrent miscarriage (before 10 weeks of pregnancy) and Factor V Leiden and G20210A prothrombin mutations. A prospective study. Department of Gynaecology and Obstetrics, Saint Antoine Hospital, Paris, France. Two groups of women: those with early unexplained recurrent miscarriage before 10 weeks of pregnancy (n = 260) and control healthy women without a previous history of thromboembolism (n = 240). Screening for defects in the protein C anticoagulant pathway was performed using the anticoagulant response to agkistrodon confortrix venom (ACV test). Protein C and Factor V Leiden mutation testing was performed for each low ACV level. Each sample was tested for the G20210A prothrombin mutation. Factor V Leiden and G20210A mutations were found to be associated with early recurrent spontaneous miscarriage before 10 weeks of pregnancy, the odds ratios being 2.4 (95% CI 1-5) and 2.7 (95% CI 1-7), respectively. Similar results were found whether or not women had had a previous live birth. Early recurrent miscarriage before 10 weeks of pregnancy is significantly associated with Factor V or G20210A prothrombin mutations. These results indicate a possible role for anticoagulant prevention in these early miscarriages.


Bottom-Up Two-Dimensional Electron-Capture Dissociation Mass Spectrometry of Calmodulin.
Two-dimensional mass spectrometry (2D MS) is a tandem mass spectrometry technique that allows data-independent fragmentation of all precursors in a mixture without previous isolation, through modulation of the ion cyclotron frequency in the ICR-cell prior to fragmentation. Its power as an analytical technique has been proven particularly for proteomics. Recently, a comparison study between 1D and 2D MS has been performed using infrared multiphoton dissociation (IRMPD) on calmodulin (CaM), highlighting the capabilities of the technique in both top-down (TDP) and bottom-up proteomics (BUP). The goal of this work is to expand this study on CaM using electron-capture dissociation (ECD) 2D MS as a single complementary BUP experiment in order to enhance the cleavage coverage of the protein under analysis. By adding the results of the BUP 2D ECD MS to the 2D IRMPD MS analysis of CaM, the total cleavage coverage increased from ~40% to ~68%. Graphical abstract .


Variables affecting postsurgical prognosis of thoracic myelopathy caused by ossification of the ligamentum flavum.
Ossification of the ligamentum flavum (OLF) may result in thoracic myelopathy (TM) because of narrowing of the spinal canal. Because symptoms vary and are subjective, diagnosis of TM caused by OLF is sometimes difficult when based on symptoms and physical examination. Posterior decompression is indicated in patients with TM caused by OLF because it is believed that surgery is the most effective treatment. However, surgical outcomes vary. We are unaware of reports of objective presurgical diagnostic parameters, such as neurologic and radiologic findings, relating to the postsurgical prognosis in patients with TM caused by OLF. To determine which presurgical and surgical variables were most closely related to postsurgical prognosis of TM caused by OLF. Retrospective review of the records of the cohort of patients who had undergone surgery from 1988 through 2008 at the University of Toyama Hospital for TM caused by OLF. Forty-one patients who had surgery for TM caused by OLF that was progressive, severe, or both and for which the diagnosis was based on clinical, radiologic, and pathologic evaluations. Relationship between the highest follow-up Japanese Orthopaedic Association (JOA) score for neurologic evaluation and of Hirabayashi's formula to indicate the extent of normalization after surgery with respect to the following 10 variables: age at surgery; sex; duration of presurgical symptoms; complications of diabetes mellitus; complications of hypertension; presence of presurgical hyperreflexia in either or both of the patellar tendon reflex and the Achilles tendon reflex; presurgical impairment of joint position sense in the big toes; number of levels affected by OLF; concurrent spinal lesions including ossification of the posterior longitudinal ligament; and intramedullary change of the spinal cord seen on magnetic resonance imaging (MRI). Multiple linear analyses were used to evaluate the variables related to postsurgical recovery. Presurgical impairment of joint position sense in the big toe was the most important predictor of the highest postsurgical JOA score and of the highest percentage recovery rate. The number of affected OLF levels also predicted the postsurgical highest JOA score, but not statistically significantly so. Age at surgery, sex, and duration of symptoms presurgically did not affect postsurgical recovery. Complications of diabetes mellitus or of hypertension did not affect percentage recovery rate. The difference between recovery rate in patients with or without concurrent spinal lesions was not significant. Presurgical hyperreflexia was not correlated with recovery. Postsurgical JOA scores and percentage recovery rates of scores in patients whose presurgical MRIs had shown intramedullary signal change were not statistically significantly different from those whose MRIs had not shown signal change. An excellent postoperative prognosis is not always possible in patients with TM caused by OLF. It may be important to check for impairment of joint position sense in the big toe, the number of levels affected by OLF, and presurgical intramedullary signal change on MRI before continuing to surgery.