Replacement of Pork Meat with Pork Head Meat for Frankfurters.
The effect of reducing pork meat concentrations from 50% to 30% and replacing it with up to 20% pork head meat on chemical composition, cooking characteristics, physicochemical and textural properties, apparent viscosity, and sensory characteristics of frankfurters was determined. The highest moisture content in frankfurters was found in the control and T1 (frankfurter with 45% pork meat + 5% pork head). Protein and fat contents in frankfurters with pork head meat added were significantly (p<0.05) higher than those in the control. When the concentration of pork head meat was increased from 0% to 20%, cooking loss, total expressible fluid separation, fat separation, and pH of frankfurters were increased, while the lightness, redness, yellowness, and apparent viscosity of frankfurters were decreased. Ash contents, cohesiveness, color, and tenderness of sensory characteristics of frankfurters added with different amounts of pork meat or pork head meat were not significantly (p>0.05) different from those of the control or there treatments. Frankfurters in T4 (frankfurter with 30% pork meat + 20% pork head) had the lowest (p<0.05) hardness and gumminess. The hardness and gumminess of frankfurters in other treatments were not significantly different (p>0.05) from that in the control. Frankfurters with higher pork head meat concentrations had lower flavor, juiciness, and overall acceptability scores. Therefore, replacing pork meat with pork head meat in the formulation could successfully produce results similar to those of control frankfurters. The best results were obtained when 10% pork head meat was used to replace pork meat.


Assessing the safety features of electronic patient medication record systems used in community pharmacies in England.
To evaluate the ability of electronic patient medication record (ePMR) systems used in community pharmacies in England to detect and alert users about clinical hazards, errors and other safety problems. Between September 2012 and November 2012, direct on-site observational data about the performance of ePMR systems were collected from nine sites. Twenty-eight scenarios were developed by consensus agreement between a general practitioner and two community pharmacists. Each scenario was entered into the ePMR system, and the results obtained from the assessment of six unique systems in nine sites, in terms of the presence or absence of an alert, were recorded onto a prespecified form. None of the systems produced the correct responses for all of the 28 scenarios tested. Only two systems provided an alert to penicillin sensitivity. No dose or frequency check was observed when processing a prescription for methotrexate. One system did not warn about nonsuitability of aspirin prescribed to a child of 14 years of age. In another system, it was not possible to record a patient's pregnancy status. None of the six systems provided any warning for diclofenac overdose, high initiation dose of morphine sulfate or significant dose increase. Only one of the systems did not produce any spurious alerts. The performance of the ePMR systems tested was variable and suboptimal. The findings suggest the need for minimum specifications and standards for ePMR systems to ensure consistency of performance.


Binding regions of outer membrane protein A in complexes with the periplasmic chaperone Skp. A site-directed fluorescence study.
Periplasmic Skp facilitates folding and membrane insertion of many outer membrane proteins (OMPs) into the outer membrane of Gram-negative bacteria. We have examined the binding sites of outer membrane protein A (OmpA) from Escherichia coli in its complexes with the membrane protein chaperone Skp and with Skp and lipopolysaccharide (LPS) by site-directed fluorescence spectroscopy. Single-Trp OmpA mutants, W(n)-OmpA, with tryptophan at position n in the polypeptide chain were isolated in the unfolded form in 8 M urea. In five beta(x)W(n)-OmpA mutants, the tryptophan was located in beta-strand x, in four l(y)W(n)-OmpA mutants, in outer loop y, and in three t(z)W(n)-OmpA mutants in turn z of the beta-barrel transmembrane domain (TMD) of OmpA. PDW(286)-OmpA contained tryptophan in the periplasmic domain (PD). After dilution of the denaturant urea in aqueous solution, spectra indicated a more hydrophobic environment of the tryptophans in beta(x)W(n) mutants in comparison to l(y)W(n)-OmpA and t(z)W(n)-OmpA, indicating that the loops and turns form the surface of hydrophobically collapsed OmpA, while the strand regions are less exposed to water. Addition of Skp increased the fluorescence of all OmpA mutants except PDW(286)-OmpA, demonstrating binding of Skp to the entire beta-barrel domain but not to the PD of OmpA. Skp bound the TMD of OmpA asymmetrically, displaying much stronger interactions with strands beta(1) to beta(3) in the N-terminus than with strands beta(5) to beta(7) in the C-terminus. This asymmetry was not observed for the outer loops and the periplasmic turns of the TMD of OmpA. The fluorescence results demonstrated that all turns and loops l(1), l(2), and l(4) were as strongly bound to Skp as the N-terminal beta-strands. Addition of five negatively charged LPS per one preformed Skp.W(n)-OmpA complex released the C-terminal loops l(2), l(3), and l(4) of the TMD of OmpA from the complex, while its periplasmic turn regions remained bound to Skp. Our results demonstrate that interactions of Skp.OmpA complexes with LPS change the conformation of OmpA in the Skp complex for facilitated insertion and folding into membranes.


Spin-polarized quantum pumping in bilayer graphene.
We study adiabatic quantum pumping in bilayer graphene where two-barrier potentials are weakly modulated as pumping parameters. Comparing the results with those for a normal quantum pump of non-chiral quasiparticles, we find that the chirality of quasiparticles in bilayer graphene heavily affects the pumped current through chiral tunnelling. When an exchange splitting induced by the proximity of a ferromagnetic insulator is introduced, the pumped current becomes spin-polarized. It is interesting that an almost 100% polarized charge current and a pure spin current with vanishing charge current can all be achieved under suitable conditions. The experimental feasibility and the interlayer asymmetric effect in bilayer graphene caused by the gate and the ferromagnet structures are also discussed. The results are useful for spintronics applications based on graphene.


Inhibition of inducible nitric oxide synthase attenuates interleukin-1 beta induced vascular hyporeactivity in the rabbit.
Inhibition of nitric oxide (NO) synthesis has been indicated to improve vasopressor-responsiveness and to increase blood pressure in most septic models. However, numerous adverse effects of non-selective NO synthase (NOS) inhibition have been reported, and the effect of NOS inhibition on vascular responsiveness to vasodilators has not been well studied. Using an isometric tension measurement system of vascular rings, we evaluated the effects of an inducible NOS (iNOS) inhibitor, L-canavanine (L-CAN) and a non-selective NOS inhibitor, NG-nitro-L-arginine methyl ester (L-NAME) on interleukin-1 beta (IL-1 beta)-induced vascular hyporeactivity in the four different rabbit arteries. Pretreatment of IL-1 beta inhibited phenylephrine (Phe)-induced vascular constriction in the carotid artery (CA, 49% of control), pulmonary artery (PA, 66%), femoral artery (FA, 71%) and in the renal artery (RA, 83%). A combination of NOS inhibitors attenuated the vascular hyporeactivity to Phe in all arteries. Pretreatment of IL-1 beta also inhibited acetylcholine (Ach)-induced vascular relaxation in FA, RA and CA. In PA, the rings were inversely constricted after Ach administration. The combination of IL-1 beta with L-CAN, but not with L-NAME, attenuated the Ach-induced vasorelaxation to the control level in all arteries. These data suggest that the selective inhibition of iNOS attenuates the direct endothelial damage induced by IL-1 beta in vitro.


Frailty and Comorbidities Among Survivors of Adolescent and Young Adult Cancer: A Cross-Sectional Examination of a Hospital-Based Survivorship Cohort.
Cancer survivors are at increased risk for the early development of age-related chronic medical conditions compared with peers without a history of cancer; however, little is known regarding the burden of these conditions among survivors of adolescent and young adult (AYA) cancers. In response, we sought to determine the prevalence of specific comorbidities and frailty among AYAs (15-39 years old at diagnosis) enrolled in a cancer survivorship cohort. Using a cross-sectional survey of a tertiary medical center-based cancer survivorship cohort, we determined the prevalence of specific comorbidities and frailty using the survey-based FRAIL assessment. In separate models adjusting for age, we estimated prevalence ratios (PRs) for the associations between patient characteristics and (1) any comorbidity and (2) frailty or prefrailty using log-binomial models. We identified 271 AYA cancer survivors, most of whom were 30-39 years old at survey (57%). A majority of survivors (n = 163, 60%) reported having at least one comorbidity with the most common being depression (28%), anxiety (27%), asthma (17%), high cholesterol (15%), and hypertension (15%). Of the 184 AYA survivors at least 1 year from cancer diagnosis, 19 (10%) were classified as frail and 39 (21%) as prefrail. Survivors who were smokers (PR 2.0, 95% confidence interval [CI]: 1.16-3.56); obese (PR 1.7, 95% CI: 1.10-2.55); uninsured (PR 2.7, 95% CI: 1.63-4.59); or who reported comorbid depression or anxiety (PR 2.4, 95% CI: 1.51-3.67) were more likely to be frail or prefrail. The prevalence of frailty and comorbidities is high among AYA cancer survivors suggestive of accelerated aging.


Theoretical musings.
There is more to theory in biology than replicating the results of experiments - the best theory papers help experimentalists to identify which of their results might be general and to plan a path through the maze of all possible future experiments.


Increment of immunogenicity after third dose of a homologous inactivated SARS-CoV-2 vaccine in a large population of patients with autoimmune rheumatic diseases.
To determine the immunogenicity of the third dose of CoronaVac vaccine in a large population of patients with autoimmune rheumatic diseases (ARD) and the factors associated with impaired response. Adult patients with ARD and age-balanced/sex-balanced controls (control group, CG) previously vaccinated with two doses of CoronaVac received the third dose at D210 (6 months after the second dose). The presence of anti-SARS-CoV-2 S1/S2 IgG and neutralising antibodies (NAb) was evaluated previously to vaccination (D210) and 30 days later (D240). Patients with controlled disease suspended mycophenolate mofetil (MMF) for 7 days or methotrexate (MTX) for 2 weekly doses after vaccination. ARD (n=597) and CG (n=199) had comparable age (p=0.943). Anti-S1/S2 IgG seropositivity rates significantly increased from D210 (60%) to D240 (93%) (p<0.0001) in patients with ARD. NAb positivity also increased: 38% (D210) vs 81.4% (D240) (p<0.0001). The same pattern was observed for CG, with significantly higher frequencies for both parameters at D240 (p<0.05). Multivariate logistic regression analyses in the ARD group revealed that older age (OR=0.98, 95% CI 0.96 to 1.0, p=0.024), vasculitis diagnosis (OR=0.24, 95% CI 0.11 to 0.53, p<0.001), prednisone ≥5 mg/day (OR=0.46, 95% CI 0.27 to 0.77, p=0.003), MMF (OR=0.30, 95% CI 0.15 to 0.61, p<0.001) and biologics (OR=0.27, 95% CI 0.16 to 0.46, p<0.001) were associated with reduced anti-S1/S2 IgG positivity. Similar analyses demonstrated that prednisone ≥5 mg/day (OR=0.63, 95% CI 0.44 to 0.90, p=0.011), abatacept (OR=0.39, 95% CI 0.20 to 0.74, p=0.004), belimumab (OR=0.29, 95% CI 0.13 to 0.67, p=0.004) and rituximab (OR=0.11, 95% CI 0.04 to 0.30, p<0.001) were negatively associated with NAb positivity. Further evaluation of COVID-19 seronegative ARD at D210 demonstrated prominent increases in positivity rates at D240 for anti-S1/S2 IgG (80.5%) and NAb (59.1%) (p<0.0001). We provide novel data on a robust response to the third dose of CoronaVac in patients with ARD, even in those with prevaccination COVID-19 seronegative status. Drugs implicated in reducing immunogenicity after the regular two-dose regimen were associated with non-responsiveness after the third dose, except for MTX. Trial registration number NCT04754698.


[Detection of bovine, goat, pig and chicken derived ingredients in animal products with universal PCR-microarray method].
We analyzed the sequence of vertebrate molecular marker genes, then we selected the mitochondrial DNA (mtDNA) 16S rRNA gene as marker gene. In order to detect four kinds of animal-derived ingredients, which including bovine, goat, pig and chicken. We utilized a pair of universal primers, designed four sets of species-specific microarray probes and two pairs of quality control probes. We optimized the PCR amplifications and hybridization conditions, therefore these four kinds of animal-derived ingredients could be rapid and accurate detected by this approach. The detection limits were all reaches 1 pg. We established the detection platform of these four kinds of animal-derived ingredients. This universal PCR-microarray assay provides a new method for the identification of animal-derived ingredients in the import-export field.


Urethral recurrence in patients following orthotopic urinary diversion.
We present our experience with urethral recurrence of transitional cell carcinoma following cystectomy and orthotopic urinary diversion in a contemporary series. Between June 1995 and December 2001, 415 patients underwent radical cystectomy for transitional cell carcinoma. Of those patients 196 (47.2%) received an orthotopic urinary diversion. Demographics, clinical characteristics, pathological stage and patient outcomes were reviewed. Mean followup was 34.1 months (range 0.3 to 97.3). Of the 196 patients who underwent orthotopic diversion 59 (30.1%) had T3 or greater disease on final pathological evaluation. Thirteen patients (6.6%) were found to have prostatic urethral involvement while 83 (42.3%) had elements of carcinoma in situ. No patient with prostatic urethral involvement had subsequent urethral recurrence. Overall only 1 patient (0.5%) had urethral recurrence of transitional cell carcinoma following orthotopic urinary diversion. The urethral recurrence rate in patients with orthotopic diversion was less than in patients with ileal conduit creation during the same period (2.1%). The overall disease recurrence rate following orthotopic diversion was 31.6% (62 of 196). Urethral recurrence following orthotopic neobladder was rare in this series despite using selection criteria that were less stringent than those of other comparable series. Overall disease recurrence was relatively high in patients with high risk pathological features but urethral recurrence in this group with orthotopic urinary diversion remained low.


[Ethanol affects the function of gamma-aminobutyric acid transporter I in mice brain].
It has been suggested that GABAergic system was involved in ethanol tolerance and addiction. Our previous work indicated both acute and chronic ethanol treatment enhanced the activity of GABA transporters in mouse brain. However, the expression level of GAT1 in CNS does not change, neither does the affinity of GABA transporters. In the present study, we demonstrated that GAT1 distribution on presynaptic membrane was altered after acute and chronic ethanol administration. Furthermore, the phosphorylation levels of GAT1 on three sites including Ser, Tyr and Thr were decreased. These data suggested that ethanol enhanced the function of GATs by means of inducing GAT1 redistribution in the cell and dephosphorylation may play a role in this process.


Histological re-evaluation of 101 intraoral salivary gland tumors by an EORTC-study group.
Tumors of the salivary glands constitute a heterogeneous group of lesions of great morphologic variation and for this reason present many difficulties in histologic classification. The histologic slides of 101 consecutive intraoral salivary gland tumors of the Department of Oral Pathology of the Free University in Amsterdam were reviewed, retrospectively, by an EORTC-study group on salivary gland tumors. Complete concurrence of diagnosis was reached in 54 cases. In 33 cases there were minor disagreements, mostly related to subclassification. Major disagreements, relating to benign versus malignant, occurred in eight cases (7.9 per cent).


Comparison of two second-generation anti-hepatitis C virus ELISA on 21431 US blood donor samples.
We have compared two different second-generation (2.0) enzyme-linked immunosorbent assays (ELISA) for the presence of antibodies to hepatitis C virus (anti-HCV) in blood from volunteer, unpaid donors. At two separate blood centres, a total of 21,431 donor samples were tested with Abbott Anti-HCV 2.0 ELISA and Ortho Anti-HCV 2.0 ELISA. Samples found to be repeatedly reactive were tested by supplemental/investigational assays. MATRIX HCV (Abbott) and anti-HCV RIBA II (Ortho/Chiron), to 'confirm' the presence of anti-HCV. Discordant ELISA samples were additionally tested by the polymerase chain reaction (PCR) for the presence of HCV RNA. The Abbott anti-HCV assay had a repeatedly reactive rate of 0.59% (127/21,431) and the Ortho anti-HCV assay 0.51% (110/21,431). Overall agreement between assays was 99.76%, 72/127 (56.7%) of Abbott repeatedly reactive samples confirmed on MATRIX and 61/127 (48.0%) on RIBAII; 70/110 (63.6%) of Ortho repeatedly reactivate samples confirmed on MATRIX and 61/110 (55.5%) on RIBA II. Discordant ELISA samples tested by PCR yielded negative results. Hence the two ELISA had equal sensitivity, as defined by detection of true positive samples; the slightly lower specificity of the Abbott Anti-HCV 2.0 ELISA may be owing to culling of donors with a false positive test by Ortho's Anti-HCV 1.0 and 2.0 ELISA tests (the routine tests in place at each blood centre). A sample found to be repeatedly reactive by two different ELISA tests for anti-HCV is likely to be a true positive and may not require further 'confirmatory' testing.


Iatrogenic bladder stone formation on absorbable suture 3-years after radical prostatectomy.
Vesical calculi formation on absorbable sutures is rare. The case of a 68-year-old white man, who had formed a large bladder stone on absorbable suture 3 years after radical prostatectomy, is reported. Endoscopic lithotripsy of the bladder calculi was performed and the suture was removed.


Increased expression of interleukin-4 receptors on psoriatic epidermal cells.
Abnormal keratinocyte proliferation and differentiation, the main characteristics of psoriasis, may be induced and maintained by cytokines produced by activated resident and recruited inflammatory cells in lesional skin. As the epidermal cytokine profile is clearly altered in psoriasis and because increased expression of interleukin-4 receptor (IL-4R) has been reported in some epithelial proliferative diseases, we investigated the expression of IL-4R on psoriatic epidermal cells (ECs). The expression of IL-4R on freshly isolated ECs from healthy skin and untreated psoriatic lesions was studied by immunostaining using an IL-4R-specific antibody and by examining their capacity to bind biotinylated recombinant human IL-4 using flow cytometry. The number of IL-4R+ ECs and the number of binding sites per cell were significantly increased on psoriatic ECs as compared with healthy control ECs. Immunostaining confirmed these results, whereby staining was mainly observed in the lower epidermal layers. In addition, an increased IL-4R mRNA expression was also observed in psoriatic epidermis using a digoxigenin-labeled IL-4R RNA probe. In short-term in vitro cultures, lipopolysaccharide/phorbol-myristate-acetate-stimulated and unstimulated psoriatic ECs did not produce any immunoreactive IL-4. The results of this study together with the reported increased expression of IL-4R in epithelial neoplasias suggest an association between overexpression of IL-4R and abnormal keratinocyte activation and proliferation.


Long non-coding RNAs in haematological malignancies.
Long non-coding RNAs (lncRNAs) are functional RNAs longer than 200 nucleotides in length. LncRNAs are as diverse as mRNAs and they normally share the same biosynthetic machinery based on RNA polymerase II, splicing and polyadenylation. However, lncRNAs have low coding potential. Compared to mRNAs, lncRNAs are preferentially nuclear, more tissue specific and expressed at lower levels. Most of the lncRNAs described to date modulate the expression of specific genes by guiding chromatin remodelling factors; inducing chromosomal loopings; affecting transcription, splicing, translation or mRNA stability; or serving as scaffolds for the organization of cellular structures. They can function in cis, cotranscriptionally, or in trans, acting as decoys, scaffolds or guides. These functions seem essential to allow cell differentiation and growth. In fact, many lncRNAs have been shown to exert oncogenic or tumor suppressor properties in several cancers including haematological malignancies. In this review, we summarize what is known about lncRNAs, the mechanisms for their regulation in cancer and their role in leukemogenesis, lymphomagenesis and hematopoiesis. Furthermore, we discuss the potential of lncRNAs in diagnosis, prognosis and therapy in cancer, with special attention to haematological malignancies.


Assessment of coronary artery flow velocity pattern as a long-term predictor of left ventricular function and cardiac events after percutaneous coronary intervention in anterior acute myocardial infarction.
Coronary flow velocity (CFV) can be used to assess short-term left ventricular function recovery and the clinical prognosis of patients with acute myocardial infarction (AMI). We evaluated CFV as a predictor of long-term left ventricular function recovery and cardiac events in patients with anterior wall AMI. CFV pattern of the distal left anterior descending (LAD), wall motion score index (WMSI) and left ventricular ejection fraction (LVEF) were recorded at the points of time within 24 hours, 3 days, 6 months, and 3 years after percutaneous coronary intervention (PCI) in 50 consecutive patients with anterior wall AMI. The clinical data were collected. Patients were divided into two groups based on diastolic deceleration time (DDT) 3 days after PCI. Compared with 3 days, LVEF and WMSI in group A (DDT>600 ms, n=20) improved in 6 months and 3 years (p<0.01), but they were unchanged in group B (DDT< or =600 ms, n=30). The incidence of cardiac events was higher in group B than in group A during 6 months (p<0.01).With a 3-year follow up, the incidence of chronic heart failure was higher in group B than in group A (p=0.009). CFV could be used as a predictor of long-term left ventricular function recovery and cardiac events in patients with anterior wall AMI.


Immunomodulatory Activity and Protective Effects of Polysaccharide from Eupatorium adenophorum Leaf Extract on Highly Pathogenic H5N1 Influenza Infection.
The development of novel broad-spectrum, antiviral agents against H5N1 infection is urgently needed. In this study, we evaluated the immunomodulatory activities and protective effect of Eupatorium adenophorum polysaccharide (EAP) against the highly pathogenic H5N1 subtype influenza virus. EAP treatment significantly increased the production of IL-6, TNF- α , and IFN- γ both in vivo and in vitro as measured by qPCR and ELISA. In a mouse infection model, intranasal administration of EAP at a dose of 25 mg/kg body weight prior to H5N1 viral challenge efficiently inhibited viral replication, decreased lung lesions, and increased survival rate. We further evaluated the innate immune recognition of EAP, as this process is regulated primarily Dectin-1 and mannose receptor (MR). These results indicate that EAP may have immunomodulatory properties and a potential prophylactic effect against H5N1 influenza infection. Our investigation suggests an alternative strategy for the development of novel antiinfluenza agents and benefits of E. adenophorum products.


Acoustic characteristics of the clothes used for a wearable recording device.
There has been increasing attention in the literature to wearable acoustic recording devices, particularly to examine naturalistic speech in disordered and child populations. Recordings are typically analyzed using automatic procedures that critically depend on the reliability of the collected signal. This work describes the acoustic amplitude response characteristics and the possibility of acoustic transmission loss using several shirts designed for wearable recorders. No difference was observed between the response characteristics of different shirt types or between shirts and the bare-microphone condition. Results are relevant for research, clinical, educational, and home applications in both practical and theoretical terms.


The current status of primary hepatocyte culture.
Recently, there have been significant advances toward the development of culture conditions that promote proliferation of primary rodent hepatocytes. There are two major methods for the multiplication of hepatocytes in vitro: one is the use of nicotinamide, the other is the use of a nutrient-rich medium. In the medium containing a high concentration of nicotinamide and a growth factor, primary hepatocytes can proliferate well. In this culture condition small mononucleate cells, which are named small hepatocytes, appear and form colonies. Small hepatocytes have a high potential to proliferate while maintaining hepatic characteristics, and can differentiate into mature ones. On the other hand, combining the nutrient-rich medium with 2% DMSO, the proliferated hepatocytes can recover the hepatic differentiated functions and maintain them for a long time. In this review I describe the culture conditions for the proliferation and differentiation of primary hepatocytes and discuss the small hepatocytes, especially their roles in liver growth.


[Experiences in the treatment of tumour of base of the tongue with high dose rate interstitial radiotherapy on the basis of a retrospective analysis]
PURPOSE: To describe the role, the execution and the importance of interstitial radiotherapy in the irradiation of the base of tongue cancer. MATERIAL AND METHODS: Between January, 1993 and December, 1998 nineteen patients with primary squamous cell cancer of the base of tongue (1 T1N0, 3 T2N0, 2 T3N0, 2 T3N2, 3 T4N0, 6 T4N1, 2 T4N2) were managed with brachytherapy partly with definitive intention combined with teletherapy (60-66 Gy) as a boost, partly as a single postoperative treatment. Irradiation was carried out by HDR after-loading (Ir-192) unit, using rigid needle or flexible plastic catheter. The treatment plan was made by PLATO 3D brachytherapy planning system. In case of boost the mean total dose of brachyherapy was 22 Gy (12-30 Gy), in postoperative treatment it was 27 Gy (24-30 Gy). RESULTS: 6-8 weeks after the definitive radiotherapy the CT/MR showed complete remission in 67% and partial remission in 33% of the patients. Of all treated patients during the mean follow-up period (30 months) the local tumour control was 42%. Five patients (26%) died in local failure. Six patients (32%) are alive with tumour. Osteoradionecrosis and fistula did not occur. CONCLUSIONS: In the oncological treatment of the advanced base of tongue tumour the combination of percutan and interstitial radiotherapy seems to be very advantageous,because it improves not only the curability, but the patients' quality of life as well.


Race and Ethnicity in the Social Work Grand Challenges.
Race, ethnicity, and racism (RER) are interconnected with the critical problems tackled in the Grand Challenges for Social Work (GCSW). Yet, the extent to which the GCSW discuss the central role of RER is less clear. This article investigates how the GCSW integrate RER in their discourse. Using content analysis, authors examined all 21 concept papers that comprise the 12 initial GCSW to determine their attention to RER. Authors assessed whether each paper made any reference to race or ethnicity, whether race or ethnicity was considered as a primary theme, and whether racism was mentioned. Nine GCSW had at least one paper that mentioned race or ethnicity; seven had at least one paper that treated race and ethnicity as a major construct. Five GCSW contained at least one paper that discussed racism's impacts on their topical interests. None of the papers analyzed in the study defined or specified their conceptualization of racism. The GCSW are strategically positioned to widen and deepen social work's focus on RER, and the recent adoption of the 13th GCSW to "Eliminate racism" is an important first step. Authors encourage the social work field to embrace a more explicit, renewed, and continued commitment to eradicating systemic racism.


1-D infinite array of metalloporphyrin cages.
The reaction of Co(II) with 5,15-dipyridyl-10,20-diphenylporphyrin (H(2)DPyP) produces the first metal-organic coordination polymer supported by a trans meso-bifunctional porphyrin ligand. Formulated empirically as [Co(3)(DPyP)(3)] x 4DMF, this compound exhibits a ribbonlike coordination network consisting of tetranuclear metalloporphyrin cages. The DMF guest molecules fill the intra-ribbon cages as well as the inter-ribbon space. Evacuation of [Co(3)(DPyP)(3)] x 4DMF at 130 degrees C generates [Co(3)(DPyP)(3)] that retains crystallinity, as shown by its powder X-ray diffraction pattern, which is consistent with that of [Co(3)(DPyP)(3)] x 4DMF.


[Evolutionary medicine: an introduction. Evolutionary biology, a missing element in medical teaching].
The aim of this brief review article is to help to reconcile medicine with evolutionary biology, a subject that should be taught in medical school. Evolutionary medicine takes the view that contemporary ills are related to an incompatibility between the environment in which humans currently live and their genomes, which have been shaped by diferent environmental conditions during biological evolution. Human activity has recently induced acute environmental modifications that have profoundly changed the medical landscape. Evolutionary biology is an irreversible, ongoing and discontinuous process characterized by periods of stasis followed by accelerations. Evolutionary biology is determined by genetic mutations, which are selected either by Darwinian selective pressure or randomly by genetic drift. Most medical events result from a genome/environment conflict. Some may be purely genetic, as in monogenic diseases, and others purely environmental, such as traffic accidents. Nevertheless, in most common diseases the clinical landscape is determined by the conflict between these two factors, the genetic elements of which are gradually being unraveled Three examples are examined in depth:--The medical consequences of the greenhouse effect. The absence of excess mortality during recent heat waves suggests that the main determinant of mortality in the 2003 heatwave was heatstroke and old age. The projected long-term effects of global warming call for research on thermolysis, a forgotten branch of physiology.--The hygiene hypothesis postulates that the exponential rise in autoimmune and allergic diseases is linked to lesser exposure to infectious agents, possibly involving counter-regulatory factors such as IL-10.--The recent rise in the incidence of obesity and type 2 diabetes in rich countries can be considered to result from a conflict between a calorie-rich environment and gene variants that control appetite. These variants are currently being identified by genome-wide analysis. Biological evolution should be taken into account in future holistic health policies.


Potential role of heparin in prevention of liver metastasis from colon cancer.
The case of a 59 year-old man with sigmoid colon cancer and synchronous liver metastases is described in this report. Sigmoid colectomy and partial hepatectomy were performed, and hepatic arterial cannulation was done for prevention of hepatic recurrence. Heparin was injected to prevent catheter-related clots, and no anticancer drugs were used. He did well without signs of recurrence for 5 years after the initial operation. After we stopped the heparin administration, recurrence was detected in the liver. The patient underwent repeat hepatectomy, and he is now doing well without recurrence 2 years after the second operation. The clinical course of this case suggests that heparin may prevent liver metastasis of colorectal cancer.


Highlighting the difference in nanostructure between domain-forming and domainless protic ionic liquids.
Nanoheterogeneity in some ionic liquids is a known phenomenon, but quantifying or sometimes even identifying it is not a straightforward task. We compared several known and suggested some novel approaches to identify and characterize domain segregation using the results of atomistic simulations. 10 ammonium-based protic ionic liquids with different propensity to form segregated polar and apolar domains as suggested by experimental studies were considered. They include butyl-, propyl-, 2-methoxyethylammonium nitrate, butyl- and propylammonium hydrogen sulfate, butylammonium thiocyanate (domain-forming liquids), ethylammonium and pyrrolidinium nitrate (weakly pronounced segregation), methylammonium and 2-hydroxyethylammonium nitrate (domainless liquids). Molecular dynamics simulations were performed using models based on the OPLS-AA force field with scaled ion charges. Results show that domains can be recognized and the characteristic domain length scale can be determined from peaks of Ripley's functions, peaks and large-period oscillations of finite-volume radial distribution function integral, or difference of such integrals for polar and apolar atoms, and peaks of local atom density variance. These peaks disappear with increasing temperature due to the disruption of segregated domains. In domain-forming liquids, apolar atoms are more homogeneously distributed in space than polar atoms. In addition, the probability of molecular-sized cavity formation is significantly higher in apolar domains, which determines better solubility of apolar species in domain-forming ILs. The suggested approaches can be applied to various nanostructured liquids including both ionic and molecular solvents and mixtures, as well as other systems with mesoscale ordering.


Does a family history of male breast cancer influence risk perception and use of genetic testing?
We sought to determine differences in risk perception and use of genetic testing in these individuals compared with those with a family history of female breast cancer (FHxFBC) in a population-based cohort. Data from the 2005 National Health Interview Survey were used to assess risk perception and use of genetic counseling in individuals with a family history of male breast cancer (FHxMBC) versus those with a FHxFBC. Of the 2429 individuals with a first-degree relative with breast cancer surveyed, 21 (0.7%) had a FHxMBC, whereas 2408 (99.3%) had a FHxFBC. Women who had a FHxMBC perceived themselves as being at higher risk for developing breast cancer than those with a FHxFBC (61.5 vs 46.5%, P = 0.011). Fewer individuals with a FHxMBC had heard about genetic testing than those with a FHxFBC (38.4 vs 50.8%, P = 0.322). Of these, none of the individuals with a FHxMBC discussed this with their physician (vs 13% of individuals with a FHxFBC, P = 0.004) and none underwent genetic testing (vs 3% of individuals with a FHxFBC, P = 0.009). Women with a FHxMBC perceive this as being associated with increased cancer risk, but few discuss this with their physicians. Physicians should be proactive in discussing risk with these patients.


A Three-Component Reaction for the Synthesis of 1-Azabicyclo[3.1.0]hexane-3-enes.
A novel and simple synthesis of 1-azabicyclo[3.1.0]hexane-3-ene derivatives is described. The synthesis is carried out via a simple three-component reaction between aryl aldehydes, malononitrile, and hydroxylamine hydrochloride in water. Eco-friendliness, excellent product yields, short reaction time, inexpensive and readily available starting materials, and interesting reaction and products are the main advantages of this method.


Excess iron: considerations related to development and early growth.
What effects might arise from early life exposures to high iron? This review considers the specific effects of high iron on the brain, stem cells, and the process of erythropoiesis and identifies gaps in our knowledge of what molecular damage may be incurred by oxidative stress that is imparted by high iron status in early life. Specific areas to enhance research on this topic include the following: longitudinal behavioral studies of children to test associations between iron exposures and mood, emotion, cognition, and memory; animal studies to determine epigenetic changes that reprogram brain development and metabolic changes in early life that could be followed through the life course; and the establishment of human epigenetic markers of iron exposures and oxidative stress that could be monitored for early origins of adult chronic diseases. In addition, efforts to understand how iron exposure influences stem cell biology could be enhanced by establishing platforms to collect biological specimens, including umbilical cord blood and amniotic fluid, to be made available to the research community. At the molecular level, there is a need to better understand stress erythropoiesis and changes in iron metabolism during pregnancy and development, especially with respect to regulatory control under high iron conditions that might promote ineffective erythropoiesis and iron-loading anemia. These investigations should focus not only on factors such as hepcidin and erythroferrone but should also include newly identified interactions between transferrin receptor-2 and the erythropoietin receptor. Finally, despite our understanding that several key micronutrients (e.g., vitamin A, copper, manganese, and zinc) support iron's function in erythropoiesis, how these nutrients interact remains, to our knowledge, unknown. It is necessary to consider many factors when formulating recommendations on iron supplementation.


Phase II Trial and Correlative Genomic Analysis of Everolimus Plus Bevacizumab in Advanced Non-Clear Cell Renal Cell Carcinoma.
Purpose The decreased effectiveness of single-agent targeted therapies in advanced non-clear cell renal cell carcinoma (ncRCC) compared with clear cell renal cell carcinoma (RCC) supports the study of combination regimens. We evaluated the efficacy of everolimus plus bevacizumab in patients with metastatic ncRCC. Patients and Methods In this single-center phase II trial, treatment-naive patients received everolimus 10 mg oral once per day plus bevacizumab 10 mg/kg intravenously every 2 weeks. The primary end point was progression-free survival (PFS) at 6 months. Correlative analyses explored candidate tissue biomarkers through next-generation sequencing. Results Thirty-five patients were enrolled with the following histologic subtypes: chromophobe (n = 5), papillary (n = 5), and medullary (n = 2) RCC and unclassified RCC (uRCC, n = 23). The majority of patients had papillary growth as a major component (n = 14). For 34 evaluable patients, median PFS, overall survival, and objective response rate (ORR) were 11.0 months, 18.5 months, and 29%, respectively. PFS varied by histology ( P < .001), and ORR was higher in patients with significant papillary (seven of 18) or chromophobe (two of five) elements than for others (one of 11). Presence of papillary features were associated with benefit, including uRCC, where it correlated with ORR (43% v 11%), median PFS (12.9 v 1.9 months), and overall survival (28.2 v 9.3 months; P < .001). Several genetic alterations seemed to segregate by histology. In particular, somatic mutations in ARID1A were seen in five of 14 patients with papillary features but not in other RCC variants. All five patients achieved treatment benefit. Conclusion The study suggests efficacy for this combination in patients with ncRCC characterized by papillary features. Distinct mutational profiles among ncRCCs vary according to specific histology.


Polysaccharide from Ziyang Selenium-Enriched Green Tea Prevents Obesity and Promotes Adipose Thermogenesis via Modulating the Gut Microbiota.
The objective of the current study was to explore the potential mechanism of Ziyang selenium-enriched green tea polysaccharide (Se-GTP) against obesity. The results showed that Se-GTP significantly alleviated obesity and related metabolic disorders caused by high-fat diet (HFD) in mice. 16S rRNA gene sequencing results revealed that Se-GTP improved gut microbiota disturbance of obese mice and facilitated proliferation of probiotics such as Bacteroides, Bifidobacterium, Lactobacillus, and Akkermansia. In addition, the colonic content of succinate, a product of microbial metabolite in connection with adipocyte thermogenesis, was significantly enhanced by Se-GTP treatment. Therefore, Se-GTP facilitated brown adipose tissue (BAT) thermogenesis and inguinal white adipose tissue (iWAT) browning in obese mice, which could be revealed by increased expressions of thermogenic marker proteins UCP1, PGC-1α, and CIDEA in BAT and iWAT. Interestingly, Se-GTP intervention also observably increased the content of M2-like macrophages in iWAT of obese mice. To summarize, the results of this study are the first to show that Se-GTP can stimulate the browning of iWAT and BAT thermogenesis to counteract obesity, which may be pertinent with the alteration of gut microbiota in obese mice.


Expression of type X collagen and capillary endothelium in condylar cartilage during osteogenic transition--a comparison between adaptive remodelling and natural growth.
Adaptive remodelling of the condylar cartilage in response to mandibular protrusion constitutes the rationale for bite-jumping appliances to solicit growth modification. By investigating the expression of type X collagen and capillary endothelium, this study was designed to evaluate the osteogenic transition of chondrogenesis during adaptive remodelling of condylar cartilage and compare it with that under natural condylar growth. One hundred female Sprague-Dawley rats, 35 days of age, were divided into five experimental groups (n = 15, fitted with bite-jumping appliances) where condylar adaptation was created by forward repositioning of the mandible, and five control groups (n = 5) where the condyles underwent natural growth. The animals were sacrificed at 3, 7, 14, 21 and 30 days and 7 mum serial sections of the condyles were processed for in situ hybridization and immunohistochemical analyses. The expression of type X collagen in the hypertrophic zone and capillary endothelium in the erosive zone of condylar cartilage were examined to evaluate osteogenic transition, a critical programme leading to endochondral ossification. The results showed that (1) The temporal pattern of the expression of type X collagen and capillary endothelium during condylar adaptation coincided with that during natural condylar growth. (2) The amount of the expression of these two factors during condylar adaptation was significantly higher than that during natural growth (P < 0.001). It is suggested that condylar adaptation in growing rats triggered by mandibular forward positioning enhances osteogenic transition which eventually results in increased bone formation.


Early effect of surgery on quality of life in women with operable breast cancer.
Quality of life (QOL) after a diagnosis of breast cancer varies considerably across individuals. The treatment modality of the patients significantly contributes to their QOL. The present study reports the initial findings on the early effects of surgery in patients with breast cancer. Two hundred and fifty-one women with breast cancer undergoing surgery were interviewed prior to and after the surgery using the Functional Assessment of Cancer Therapy for Breast (FACT-B). Trial Outcome Index (TOI) was calculated besides total and subscale scores. The results were analyzed using paired t-test and two-sample paired Wilcoxon signed rank test. Multivariate analysis was carried out using repeated measures general liner model with 2-way interactions. Significant reduction in physical well-being (P = 0.001), functional well-being (P = 0.00) and the breast-specific subscale (P = 0.000) was observed after surgery. No significant change was observed in social or emotional well-being. Total FACT scores and TOI too showed significant declines (P = 0.000; and P = 0.000 respectively) on univariate analysis. Multivariate analysis, however, showed no difference in QOL after surgery, but QOL was significantly poor among women undergoing mastectomy. Results of the present study indicate no significant change in overall QOL immediately after the surgery, probably reflecting strong family and social support for these women. QOL was significantly better among women undergoing breast conservation compared with mastectomy.


Nurse manager succession planning: a concept analysis.
The current nursing leadership pipeline is inadequate and demands strategic succession planning methods. This article provides concept clarification regarding nurse manager succession planning. Attributes common to succession planning include organizational commitment and resource allocation, proactive and visionary leadership approach, and a mentoring and coaching environment. Strategic planning, current and future leadership analysis, high-potential identification, and leadership development are succession planning antecedents. Consequences of succession planning are improved leadership and organizational culture continuity, and increased leadership bench strength. Health care has failed to strategically plan for future leadership. Developing a strong nursing leadership pipeline requires deliberate and strategic succession planning.


On the Need for New Measures of Phylogenomic Support.
The scale of data sets used to infer phylogenies has grown dramatically in the last decades, providing researchers with an enormous amount of information with which to draw inferences about evolutionary history. However, standard approaches to assessing confidence in those inferences (e.g., nonparametric bootstrap proportions [BP] and Bayesian posterior probabilities [PPs]) are still deeply influenced by statistical procedures and frameworks that were developed when information was much more limited. These approaches largely quantify uncertainty caused by limited amounts of data, which is often vanishingly small with modern, genome-scale sequence data sets. As a consequence, today's phylogenomic studies routinely report near-complete confidence in their inferences, even when different studies reach strongly conflicting conclusions and the sites and loci in a single data set contain much more heterogeneity than our methods assume or can accommodate. Therefore, we argue that BPs and marginal PPs of bipartitions have outlived their utility as the primary means of measuring phylogenetic support for modern phylogenomic data sets with large numbers of sites relative to the number of taxa. Continuing to rely on these measures will hinder progress towards understanding remaining sources of uncertainty in the most challenging portions of the Tree of Life. Instead, we encourage researchers to examine the ideas and methods presented in this special issue of Systematic Biology and to explore the area further in their own work. The papers in this special issue outline strategies for assessing confidence and uncertainty in phylogenomic data sets that move beyond stochastic error due to limited data and offer promise for more productive dialogue about the challenges that we face in reaching our shared goal of understanding the history of life on Earth.[Big data; gene tree variation; genomic era; statistical bias.].


Anionic subsite of active center of Torpedo acetylcholinesterase constructs a part of its conformational epitope.
To study the structure-activity relationship of Torpedo acetylcholinesterase (AChE) and explore whether the anionic subsite of the active center is a constituent of the conformational epitope of enzyme. Using ELISA and enzyme inhibition test to examine the effect of 1-methyl-2-hydroxyiminomethylpyridium chloride (2-PAM), an anionic subsite probe of AChE, on the immunoreactivity between Torpedo AChE and its monoclonal antibody (McAb) 3F3. McAb 3F3 did not react with 2-PAM-AChE complex. 2-PAM decreased the inhibitory rate of McAb 3F3 on AChE in a concentration-dependent fashion, but did not dissociate the McAb 3F3-AChE complex. Anionic subsite of the active center of Torpedo AChE constructs a part of its conformational epitope.


A dynamic population model incorporating a variety of urban functions.
"This paper aims to investigate the theoretical background of Allen and Sanglier's model, slightly modifying it. We construct a dynamic two-city population model in which there are different types of urban functions in the cities. Population dynamics of both cities are expressed in terms of a system of differential equations of the logistic type, taking account of spatial interaction between them. For this model, both the existence condition and the globally asymptotic stability of the equilibrium state are theoretically explored. Then configurations of equilibrium population distribution that correspond to different combinations of the numbers of types of urban functions in two cities are also examined. Finally, some numerical simulations are done in order to supplement the theoretical considerations."


Question-aware transformer models for consumer health question summarization.
Searching for health information online is becoming customary for more and more consumers every day, which makes the need for efficient and reliable question answering systems more pressing. An important contributor to the success rates of these systems is their ability to fully understand the consumers' questions. However, these questions are frequently longer than needed and mention peripheral information that is not useful in finding relevant answers. Question summarization is one of the potential solutions to simplifying long and complex consumer questions before attempting to find an answer. In this paper, we study the task of abstractive summarization for real-world consumer health questions. We develop an abstractive question summarization model that leverages the semantic interpretation of a question via recognition of medical entities, which enables generation of informative summaries. Towards this, we propose multiple Cloze tasks (i.e. the task of filing missing words in a given context) to identify the key medical entities that enforce the model to have better coverage in question-focus recognition. Additionally, we infuse the decoder inputs with question-type information to generate question-type driven summaries. When evaluated on the MeQSum benchmark corpus, our framework outperformed the state-of-the-art method by 10.2 ROUGE-L points. We also conducted a manual evaluation to assess the correctness of the generated summaries.


Incomplete holism in pre-registration nurse education: the position of the biological sciences.
There is an ongoing debate in nurse education concerning the role and delivery of the biological sciences in the nursing curriculum. One of the fundamental questions raised by this debate asks how best can teachers impart biological knowledge in a manner that can be readily applied by students and qualified nurses to inform their clinical practice. This paper will include a discussion of some of the features of pre-registration education that may have influenced the manner in which biological sciences are perceived, taught and used by nurses. It will be argued that nursing may have developed a form of incomplete holism and that this may be in part responsible for the challenges that remain to be met within this area of the nursing curriculum. As a response to incomplete holism an innovative approach within pre-registration education will be introduced. This development involves the use of linked teaching sessions which aim to develop the analytical skills necessary to apply physiological knowledge to nursing practice.


Role of zinc in the pathogenesis of attention-deficit hyperactivity disorder: implications for research and treatment.
The dopamine transporter is regulated by zinc (Zn2+), which directly interacts with the transporter protein as a potent non-competitive blocker of substrate translocation (dopamine transport inward and outward). The fact that dysfunction of the dopamine transporter is involved in the pathogenesis of attention-deficit hyperactivity disorder (ADHD) is interesting in the context of studies that suggest the involvement of zinc deficiency in patients with ADHD. In this article, we present a hypothesis exploring the causative mechanism of zinc deficiency in ADHD and why zinc might be beneficial as a supplementary medication and/or adjunct to psychostimulants (methylphenidate, amfetamine) in zinc-deficient ADHD patients. The hypothesis is based on published in vitro observations that the human dopamine transporter contains a high-affinity zinc binding site (His-193, His-375, Glu-396) on its extracellular face that modulates transporter function, and in vivo studies suggesting that response to stimulants is reduced in zinc-deficient ADHD patients. It seems likely that zinc supplementation in zinc-deficient ADHD patients improves the binding status of insufficiently occupied zinc binding sites on the dopamine transporter. We propose to test our hypothesis by recruiting zinc-deficient ADHD patients who will undergo positron emission tomography with the 11C-raclopride displacement method to investigate whether zinc increases extracellular dopamine levels.


Safety considerations for IMRT: executive summary.
This report on intensity-modulated radiation therapy (IMRT) is part of a series of white papers addressing patient safety commissioned by the American Society for Radiation Oncology's (ASTRO) Target Safely Campaign. The document has been approved by the ASTRO Board of Directors, endorsed by the American Association of Physicists in Medicine (AAPM) and American Association of Medical Dosimetrists (AAMD), and reviewed and accepted by the American College of Radiology's Commission on Radiation Oncology. This report is related to other reports of the ASTRO white paper series on patient safety which are still in preparation, and when appropriate it defers to guidance that will be published by those groups in future white papers. This document takes advantage of the large body of work on quality assurance and quality control principles within radiation oncology whenever possible. IMRT provides increased capability to conform isodose distributions to the shape of the target(s), thereby reducing dose to some adjacent critical structures. This promise of IMRT is one of the reasons for its widespread use. However, the promise of IMRT is counterbalanced by the complexity of the IMRT planning and delivery processes, and the associated risks, some of which have been demonstrated by the New York Times reports on serious accidents involving both IMRT and other radiation treatment modalities. This report provides an opportunity to broadly address safe delivery of IMRT, with a primary focus on recommendations for human error prevention and methods to reduce the occurrence of errors or machine malfunctions that can lead to catastrophic failures or errors.


Paradoxical movement of rat vocal folds following recurrent laryngeal nerve injury.
To establish a rat model with paradoxical vocal fold movement to understand the detailed etiology and physiology of laryngeal synkinesis by evaluating vocal fold movement and by electromyography. Adult Wistar rats were used. The recurrent laryngeal nerve was transected, anastomosed, and the anastomotic portion was placed in a silicone tube. At 2, 4, and 10 weeks after the treatment (n = 30), we performed laryngoscopy and electromyography. The vocal fold movement was recorded, the hemiglottal area was measured, and the Δarea was calculated by subtracting the area during expiration from that during inhalation. We evaluated the ratio of the Δarea on the treated side to that of the normal side. After laryngoscopy, electromyography of the thyroarytenoid and posterior cricoarytenoid muscles was performed. The mean Δareas were 1.5 ± 3.4%, 2.3 ± 21.5%, and 0.7 ± 31.8% at 2, 4, and 10 weeks after anastomosis, respectively. Eighteen of 18 rats indicated synkinetic reinnervation at 4 and 10 weeks. Regarding vocal fold mobility, 8 of 18 animals showed paradoxical movement, and 5 of 18 exhibited impaired mobility. We have established an animal model of paradoxical movement following recurrent laryngeal nerve injury. This model may be useful in studying laryngeal synkinesis.


Buoyancy regulation and the potential for vertical migration in the oceanic cyanobacterium trichodesmium.
Diel protein and carbohydrate content in Trichodesmium thiebautii was measured to evaluate the relationship to buoyancy status. Carbohydrate:protein ratio was the best predictor of buoyancy and fit a cosine curve with increasing values during the day and decreasing values at night in cycles that paralleled observed diel buoyancy patterns. This ratio also increased in short-term experiments as a function of light and increased in parallel with decreasing positive buoyancy. We used changes in this ratio to estimate the potential for vertical migration. Whereas limited vertical excursions in the upper 70 m are possible, deeper migrations appear unlikely unless respiration rates decrease significantly. N:P ratios in sinking and floating colonies were used to test for the P acquisition at depth (vertical migration). We noted that pooled N:P ratios were not significantly different between sinking and ascending colonies (N:P = 65.6 and 66.3, respectively) collected along the northern Australian coast, much like published results from north of Hawaii. Highly significant differences (p <0.0001) were observed in the western Gulf of Mexico between sinking and ascending colonies (N:P = 87.0 and 43.5, respectively) and provide the best direct evidence to date of vertical migration for P acquisition. Our physiological data on compositional changes during buoyancy reversals suggest a complex relationship between light and nutrients. It appears likely that light and P metabolism interact to regulate the vertical extent of migrations, with deep vertical migration regulated by P metabolism superimposed on a mixed-layer light-driven migration. The variability in N:P ratios suggests that care should be taken in assuming buoyancy reversals always result in P acquisition in this oceanic cyanobacterium.


Contrast-enhanced ultrasound for the diagnosis of hepatocellular carcinoma in adults with chronic liver disease.
Hepatocellular carcinoma occurs mostly in people with chronic liver disease. Worldwide, it ranks sixth in terms of incidence of cancer, and fourth in terms of cancer-related deaths. Contrast-enhanced ultrasound (CEUS) is used as an add-on test to confirm the presence of focal liver lesions suspected as hepatocellular carcinoma after prior diagnostic tests such as abdominal ultrasound or measurement of alpha-foetoprotein, or both. According to guidelines, a single contrast-enhanced imaging investigation, with either computed tomography (CT) or magnetic resonance imaging (MRI), may show the typical hepatocellular carcinoma hallmarks in people with cirrhosis, which will be sufficient to diagnose hepatocellular carcinoma. However, a significant number of hepatocellular carcinomas show atypical imaging features, and therefore, are missed at imaging. Dynamic CEUS images are obtained similarly to CT and MRI images. CEUS differentiates between arterial and portal venous phases, in which sonographic hepatocellular carcinoma hallmarks, such as arterial hyperenhancement and subsequent washout appearance, are investigated. The advantages of CEUS over CT and MRI include real-time imaging, use of contrast agents that do not contain iodine and are not nephrotoxic, and quick image acquisition. Despite the advantages, the use of CEUS in the diagnostic algorithm for HCC remains controversial, with disagreement on relevant guidelines. There is no clear evidence of the benefit of surveillance programmes in terms of overall survival as the conflicting results can be a consequence of an inaccurate detection, ineffective treatment, or both. Therefore, assessing the diagnostic accuracy of CEUS may clarify whether the absence of benefit could be related to underdiagnosis. Furthermore, an assessment of the accuracy of CEUS for the diagnosis of hepatocellular carcinoma is needed for either diagnosing hepatocellular carcinoma or ruling it out in people with chronic liver disease who are not included in surveillance programmes. 1. To assess the diagnostic accuracy of contrast-enhanced ultrasound (CEUS) for the diagnosis of hepatocellular carcinoma of any size and at any stage in adults with chronic liver disease, in a surveillance programme or in a clinical setting. 2. To assess the diagnostic accuracy of CEUS for the diagnosis of resectable hepatocellular carcinoma in people with chronic liver disease and identify potential sources of heterogeneity in the results. We used standard, extensive Cochrane search methods. The last date of search was 5 November 2021. We included studies assessing the diagnostic accuracy of CEUS for the diagnosis of hepatocellular carcinoma in adults with chronic liver disease, with cross-sectional designs, using one of the acceptable reference standards, such as pathology of the explanted liver, and histology of resected or biopsied focal liver lesion with at least a six-month follow-up. We used standard Cochrane methods to screen studies, extract data, and assess the risk of bias and applicability concerns, using the QUADAS-2 checklist. We used the bivariate model and provided estimates of summary sensitivity and specificity. We assessed the certainty of the evidence using GRADE. We presented uncertainty-of-the-accuracy estimates using 95% confidence intervals (CIs). We included 23 studies with 6546 participants. Studies were published between 2001 and 2021. We judged all 23 studies at high-risk of bias in at least one domain, and 13/23 studies at high concern for applicability. Most studies used different reference standards to exclude the presence of the target condition. The time interval between the index test and the reference standard was rarely defined. We also had major concerns on their applicability due to the characteristics of the participants. - CEUS for hepatocellular carcinoma of any size and stage: sensitivity 77.8% (95% CI 69.4% to 84.4%) and specificity 93.8% (95% CI 89.1% to 96.6%) (23 studies, 6546 participants; very low-certainty evidence). - CEUS for resectable hepatocellular carcinoma: sensitivity 77.5% (95% CI 62.9% to 87.6%) and specificity 92.7% (95% CI 86.8% to 96.1%) (13 studies, 1257 participants; low-certainty evidence). The observed heterogeneity in the results remains unexplained. The sensitivity analyses, including only studies with clearly prespecified positivity criteria and only studies in which the reference standard results were interpreted with no knowledge of the results about the index test, showed no differences in the results. We found that by using CEUS, as an add-on test following abdominal ultrasound, to diagnose hepatocellular carcinoma of any size and stage, 22% of people with hepatocellular carcinoma would be missed, and 6% of people without hepatocellular carcinoma would unnecessarily undergo further testing or inappropriate treatment. As to resectable hepatocellular carcinoma, we found that 23% of people with resectable hepatocellular carcinoma would incorrectly be unresected, while 8% of people without hepatocellular carcinoma would undergo further inappropriate testing or treatment. The uncertainty resulting from the high risk of bias of the included studies, heterogeneity, and imprecision of the results and concerns on their applicability limit our ability to draw confident conclusions.


Neocarzinostatin: report of a phase II clinical trial.
Fifty-three patients received intensive treatment with neocarzinostatin in doses of 3500 units/m2 by iv bolus infusion daily for 5-14 days. The response rate for 22 patients with leukemia was 9%. One complete and one partial remission were observed among nine patients with chronic myelogenous leukemia in blast cell crisis. None of the 31 patients with solid tumors responded to treatment. With this dose schedule, prolonged thrombocytopenia and cumulative bone marrow toxicity limit the intensity and duration of neocarzinostatin therapy. Acute allergic reactions occurred in 28% of the treatment courses, and three patients developed anaphylaxis during the second or third course of therapy.


Adenosine-5'-triphosphate-sulfurylase from Arabidopsis thaliana and Escherichia coli are functionally equivalent but structurally and kinetically divergent: nucleotide sequence of two adenosine-5'-triphosphate-sulfurylase cDNAs from Arabidopsis thaliana and analysis of a recombinant enzyme.
ATP-sulfurylase, the first enzyme of sulfate assimilation, catalyzes the formation of adenosine-5'-phosphosulfate from ATP and sulfate. Here we report that the higher plant, Arabidopsis thaliana, contains a three-member, expressed gene family encoding plastid localized forms of ATP sulfurylase. Three cDNAs from A. thaliana, designated APS1, APS2, and APS3, were isolated by their ability to functionally complement a met3 (ATP sulfurylase) mutant strain of Saccharomyces cerevisiae (yeast). The nucleotide sequence of APS1 was reported previously (1). APS2 and APS3, reported here, have 476- and 465-codon open-reading frames encoding 53.6- and 52.0-kDa polypeptides, respectively. The translation products of both clones are highly homologous to APS1 (66 and 86% identity, respectively) over their entire lengths, including amino terminal sequences resembling transit peptides for plastid localization. Both clones are less homologous to MET3 (25 and 30% identity, respectively). Genomic blot analysis of A. thaliana revealed only three genes with homology to the APS cDNAs and RNA blot analysis showed that APS1 is the most highly expressed member of this gene family. The APS polypeptides share homology with ATP-sulfurylases from fungi, a marine worm and a chemoautotrophic bacterium, but, not from Escherichia coli or Rhizobium meliloti. Analysis of recombinant APS3 showed that the protein is structurally and kinetically similar to fungal ATP-sulfurylase, but very different from the E. coli enzyme. The APS3 polypeptide is a homotetramer with specific activities (mumol primary product x mg protein-1 at pH 8.0, 25 degrees C) for 2.9 for APS synthesis, 30.1 for molybdolysis, and 48.7 for ATP synthesis. Despite the sequence, structural, and kinetic differences between higher plant and E. coli ATP-sulfurylases, APS2 and APS3 are able to functionally complement E. coli cysD and cysN (ATP-sulfurylase) mutant strains.


Enzymic Properties of Ribulose-1,5-bisphosphate Carboxylase/Oxygenase Purified from Rice Leaves.
The enzymic properties of ribulose 1,5-bisphosphate (RuBP) carboxylase/oxygenase purified from rice (Oryza sativa L.) leaves were studied. Rice RuBPcarboxylase, activated by preincubation with CO(2) and Mg(2+) like other higher plant carboxylases, had an activation equilibrium constant (K(c)K(Mg)) of 1.90 x 10(5) to 2.41 x 10(5) micromolar(2) (pH 8.2 and 25 degrees C). Kinetic parameters of carboxylation and oxygenation catalyzed by the completely activated enzyme were examined at 25 degrees C and the respective optimal pHs. The K(m)(CO(2)), K(m)(RuBP), and V(max) values for carboxylation were 8 micromolar, 31 micromolar, and 1.79 units milligram(-1), respectively. The K(m)(O(2)), K(m)(RuBP), and V(max) values for oxygenation were 370 micromolar, 29 micromolar, and 0.60 units milligram(-1), respectively.Comparison of rice leaf RuBP carboxylase with other C(3) plant carboxylases showed that it had a relatively high affinity for CO(2) but the lowest catalytic turnover number (V(max)) among the species examined.


[Synchronized anterograde perfusion during percutaneous transluminal coronary angioplasty: preliminary clinical study].
A new circulatory system, "physiologic anteroperfusion system", has been developed and tested in 6 patients with significant proximal coronary artery stenosis. Prolonged and safe balloon inflation was possible without any ischemic signs. The system consists of an electronic cardiac synchroperfusor which, by activating a pulsatile unit, permits increased diastolic anteroperfusion of autologous blood under physiologic pressure through low-profile standard angioplasty catheters. This study reports the results obtained in 6 patients during proximal prolonged percutaneous transluminal coronary angioplasty. Four men and two women suffering from severe exertional angina pectoris, with normal resting left ventricular function, no collaterals and excellent apical two-dimensional four-chamber echocardiographic views were studied. After a 90 +/- 10 seconds of control occlusion under continuous monitoring of hemodynamics, electrocardiograms (3 to 4 leads), two-dimensional echo and chest pain grading, a second balloon inflation protected by the physiologic anteroperfusion system at a flow rate of 44 +/- 12 ml/min was performed for fifteen minutes. The ischemic signs present in the myocardium depending on the occluded artery were totally abolished during prolonged inflation protected by physiologic anteroperfusion system. All the patients were successfully dilated and were discharged from hospital the following morning without cardiac enzyme elevation or signs of central or peripheral hemolysis. Conclusion, in 6 patients with severe proximal coronary artery stenosis, safe prolonged proximal angioplasty without signs of ischemia was performed using a new simple physiologic anteroperfusion system, which allows active diastolic flow-pressure controlled autologous arterial blood perfusion, through standard low profile catheters.


Serological and molecular analysis of serotype O foot-and-mouth disease virus isolated from disease outbreaks in India during 1987-91.
Foot-and-mouth disease virus (FMDV) type O outbreaks have been reported frequently in vaccinated cattle in India. Twenty-five field isolates, recovered from outbreaks in vaccinated and unvaccinated cattle between 1987 and 1991, were analyzed in relation to the vaccine strain (R2/75) by complement fixation, serum neutralization and partial nucleotide sequencing of the VP1 gene. These sequences were compared with the viral sequences in GenEMBL database. Although the Indian type O viruses were close to the European type O1 viruses, they constituted a separate group of type O FMDVs. One of the field viruses, isolated from an outbreak in vaccinated cattle and designated as BAK/90, showed significant serological and nucleotide sequence variations from the vaccine strain. Phylogenetic analysis showed that the BAK/90 and R2/75 viruses belong to separate subgroups. The other isolates were found to be serologically related to both the BAK/90 and the vaccine strain. The BAK/90 strain gave broader antigenic coverage, showed better immunogenicity, and yielded larger amounts of 146S particles in suspension cultures as compared with R2/75. Taken together, these results favour inclusion of the BAK/90 strain in the vaccine to provide adequate protection against the field variants of type O FMDV currently circulating in India.


Synthesis and biological evaluation of novel curcuminoid derivatives.
Curcuminoids have been reported to possess multiple bioactivities, such as antioxidant, anticancer and anti-inflammatory properties. Three novel series of curcuminoid derivatives (11a-h, 15a-h and 19a-d) with enhanced bioactivity have been synthesized. Among the synthesized compounds, 11b exhibited the most significant activity with an MIC of 0.5 µM /mL against selected medically important Gram-positive cocci (S. aureus and S. viridans) and Gram-negative bacilli (E. coli and E. cloacae). The derivatives exhibited remarkable results in an antioxidant test with an IC50 2.4- to 9.3-folder smaller than curcuminoids. With respect to antiproliferative activity against Hep-G2, LX-2, SMMC7221 and MDA-MB-231, the derivatives exhibited an effect stronger than curcuminoids with an IC50 ranging from 0.18 to 4.25 µM.


[Reoperation of primary tissue failure of bioprosthesis in the mitral position].
The surgical results of 38 patients who underwent reoperation for primary tissue failure of bioprosthesis in the mitral position between May 1982 and June 1990 were analyzed to determine the risk factors affecting the hospital mortality. The type of bioprostheses requiring reoperation were Hancock valve in 21 patients, Liotta valve in 15 patients and Mitroflow valve in 2 patients. Twenty-five preoperative and perioperative variables were collected and analyzed by univariate statistics using chi 2 test or Student's test. Four of thirty eight patients died postoperatively in the hospital, yielding an overall mortality of 10.5%. The causes of hospital mortality were low output syndrome in 2 patients and multiple organ failure in 2 patients. By univariate analysis, male, NYHA IV class, prosthetic stenosis, hepatic failure, renal failure, and pulmonary failure were risk factors predictive of high hospital mortality. In spite of recent improvement of surgical technique and myocardial protection, the hospital mortality of patients with NYHA IV class and advanced organ failure still remains unacceptable. Therefore, it is essential to perform reoperation for primary tissue failure of bioprosthesis before severe myocardial decompensation occurs. To accomplish this goal, patients with bioprosthesis who survived beyond the certain time should be followed periodically using echocardiogram.


Endoscopic Resection of Pediatric Skull Base Tumors: An Evidence-Based Review.
Objectives To perform a systematic review examining experiences with endoscopic resection of skull base lesions in the pediatric population, with a focus on outcomes, recurrence, and surgical morbidities. Methods PubMed/MEDLINE, Cochrane Library, Embase, and Web of Science databases were evaluated. Studies were assessed for level of evidence. Bias risk was evaluated using the Cochrane Bias tool, Grades of Recommendation, Assessment, Development and Evaluation (GRADE), and Methodological Index for Non-Randomized Studies (MINORS) criteria. Patient characteristics, pathology, site of primary disease, presenting symptoms, stage, procedure specific details, and complications were evaluated. Results were reported using the Preferred Reporting Systems for Systematic Reviews and Meta-Analysis guidelines. Results Ninety-three studies met criteria for inclusion, encompassing 574 patients with skull base tumors. The GRADE and MINORS criteria determined the overall evidence to be moderate quality. The most common benign and malignant pathologies included juvenile nasopharyngeal angiofibromas ( n = 239) and chondrosarcomas ( n = 11) at 41.6 and 1.9%, respectively. Of all juvenile nasopharyngeal angiofibroma tumors, most presented at stage IIIa and IIIb (25.8 and 27.3%, respectively). Nasal obstruction (16.5%) and headache (16.0%) were common symptoms at initial presentation. Surgical approaches included endoscopic endonasal ( n = 193, 41.2%) and endoscopic extended transsphenoidal ( n = 155, 33.1%). Early (< 6 weeks) and late (>6 weeks) complications included cerebrospinal fluid leak ( n = 36, 17.3%) and endocrinopathy ( n = 43, 20.7%). Mean follow-up time was 37 months (0.5-180 months), with 86.5% showing no evidence of disease and 2.1% having died from disease at last follow-up. Conclusion Endoscopic skull base surgery has been shown to be a safe and effective method of treating a variety of pediatric skull base tumors. If appropriately employed, the minimally invasive approach can provide optimal results in the pediatric population.


[Leaf anatomy of the subtribe Conceveibinae (Euphorbiaceae)].
A comparative study of the leaf anatomy of the subtribe Conceveibinae was carried out. Leaves show a similar structural arrangement in all species, however, there are small variations among the taxa that allow definitions of species or groups. It is not possible to recognize infrageneric divisions or to maintain some genera as different from Conceveiba. The analysis included the study of 11 characters of taxonomic importance of the leaf: the form, the size and the apex of the papillae of the lower side of the blade, the number of layers of the palisade parenchyma, the presence or absence of the midrib pith, the number of vascular bundles of petiole as well as the central cylinder and the medulla, and the presence or absence of the sclerenchyma in the different levels of the petiole. The results are evaluated from a taxonomical point of view. With leaf anatomy characters only, it is possible to separate the genus Conceveiba in the subtribe.


Discovery of Natural Product-Based Fungicides (II): Semisynthesis and Biological Activity of Sarisan Attached 3-Phenylisoxazolines as Antifungal Agents.
Many phytopathogenic fungi cause severe damage to crop yields. In continuation of our research aimed at the discovery and development of natural products-based fungicides, a series of thirty-one sarisan attached 3-phenylisoxazolines were synthesized and evaluated for their antifungal activities against five phytopathogenic fungi (B. cinerea, C. lagenarium, A. solani, F. solani, and F. graminearum). Among all title sarisan derivatives, compounds IV2, IV14 and IV23 showed potent antifungal activity against some phytopathogenic fungi. In particular, compound IV2 exhibited a broad-spectrum and more potent antifungal activity against A. solani, F. solani, and F. graminearum than the commercial fungicide Hymexazol. In addition, compounds IV2, IV14 and IV23 also displayed relative low toxicity on normal NRK-52E cells. This work will give some insights into the development of sarisan derivatives as new fungicide candidates in plant protection.


[Arrhythmia in the long-term follow-up after intracardiac repair of tetralogy of Fallot].
The long-term success of intracardiac repair of tetralogy of Fallot is hampered by the occurrence of arrhythmias. The aim of the present study was to determine the incidence of arrhythmias after intracardiac repair of tetralogy of Fallot and their correlation with surgical and clinical findings. The study group consisted of 54 patients, 35 males and 19 females. They underwent repair at a mean age of 51 months (range 17 to 117 months). The median age at the time of study was 9.4 years (range 5 to 14 years), and the mean duration of follow-up was 4.3 years (range 2.8 to 9.0 years) after surgery. The follow-up study included routine ECG, 24 hour Holter, echocardiography and exercise testing. The incidence of ventricular arrhythmia was 33 percent, and 1 patient had non-sustained ventricular tachycardia. All patients with elevated right ventricular pressure had ventricular arrhythmias, and 28% of patients with normal right ventricular pressure had ventricular arrhythmias (P < 0.05). 53% of patients had significant ventricular arrhythmias when the duration of cardiopulmonary bypass was > or = 90 minutes, as opposed to 23% when it was < 90 minutes (P < 0.05). There was no significant difference in prevalence of ventricular arrhythmias between mild pulmonary regurgitation and severe pulmonary regurgitation (21% vs 40%, P > 0.05). No significant difference was found in the incidence of ventricular arrhythmias between follow-up in five years and more than five years (32% vs 34%, P > 0.05). Age at surgery correlated with the prevalence of ventricular arrhythmias (r = -0.221, P < 0.05). Eight patients (15%) had supraventricular arrhythmias. The frequency of ventricular arrhythmias correlated with elevated right ventricular systolic pressure, the duration of cardiopulmonary bypass, and the age at surgery. No correlation was found between pulmonary regurgitation and the duration of follow-up. Exercise-induced frequent multiform premature ventricular complexes were associated with abnormal hemodynamic status and high risk of ventricular tachycardia.


Passive nitrate transport by root plasma membrane vesicles exhibits an acidic optimal pH like the H(+)-ATPase.
The net initial passive flux (J(Ni)) in reconstituted plasma membrane (PM) vesicles from maize (Zea mays) root cells was measured as recently described (P. Pouliquin, J.-P. Grouzis, R. Gibrat ¿1999 Biophys J 76: 360-373). J(Ni) in control liposomes responded to membrane potential or to NO(3)(-) as expected from the Goldman-Hodgkin-Katz diffusion theory. J(Ni) in reconstituted PM vesicles exhibited an additional component (J(Nif)), which was saturable (K(m) for NO(3)(-) approximately 3 mM, with J(Nifmax) corresponding to 60 x 10(-9) mol m(-2) s(-1) at the native PM level) and selective (NO(3)(-) = ClO(3)(-) > Br(-) > Cl(-) = NO(2)(-); relative fluxes at 5 mM: 1:0.34:0.19). J(Nif) was totally inhibited by La(3+) and the arginine reagent phenylglyoxal. J(Nif) was voltage dependent, with an optimum voltage at 105 mV at pH 6.5. The activation energy of J(Nif) was high (129 kJ mol(-1)), close to that of the H(+)-ATPase (155 kJ mol(-1)), and J(Nif) displayed the same acidic optimal pH (pH 6.5) as that of the H(+) pump. This is the first example, to our knowledge, of a secondary transport at the plant PM with such a feature. Several properties of the NO(3)(-) uniport seem poorly compatible with that reported for plant anion channels and to be attributable instead to a classical carrier. The physiological relevance of these findings is suggested.


[Cervico-vaginal and endometrial cytology in the screening for endometrial cancer].
In contrast to cervical cancer, no routine mass screening programs for the early detection of endometrial cancer have been organized. All of the methods used by cytologists for studying endometrial changes have limitations. Cervicovaginal smears allow diagnosis of, at best, 60% to 70% of carcinomas of the endometrium. Intrauterine sampling is another possible method. It consists of direct aspiration of uterine cavity, scraping or brushing of the mucosa or uterine washing. Any method of endometrial sampling is imperfect, even dilatation and curettage has been shown to miss endometrial carcinoma. The lack of an effective, inexpensive and easy-to-use sampling method is the reason for the nonexistent decline in the incidence of invasive endometrial carcinoma.


99mTc-depreotide scintigraphy versus 18F-FDG-PET in the diagnosis of radioiodine-negative thyroid cancer.
Papillary and follicular thyroid cancer were found recently to express somatostatin receptors (SSTRs). (99m)Tc-depreotide binds with high affinity to SSTRs 2, 3, and 5. The aim of this study was to evaluate the feasibility of applying (99m)Tc-depreotide scintigraphy to search for radioiodine-negative thyroid cancer; comparison is made to a standard approach using (18)F-fluorodeoxyglucose-positron emission tomography ((18)F-FDG-PET). Ten radioiodine-negative patients with suspicion of recurrent or metastatic thyroid cancer were investigated with (99m)Tc-depreotide scintigraphy and (18)F-FDG-PET, performed with a time interval that ranged from 1-8 wk. Locoregional recurrence and metastases were confirmed by ultrasonography and/or computed tomography, together with cytology or histological examination in selected cases. True-positive results were obtained in nine patients (90%) with (99m)Tc-depreotide scintigraphy and in seven patients (70%) with (18)F-FDG-PET. (99m)Tc-depreotide scintigraphy gave better results in terms of detection of recurrent or metastatic disease compared with (18)F-FDG-PET in three patients, whereas (18)F-FDG-PET identified metastatic disease that was not seen with (99m)Tc-depreotide in only one patient. (99m)Tc-depreotide scintigraphy portrayed lesions in three patients with negative morphological imaging. Results indicate a potential value of (99m)Tc-depreotide scintigraphy for the diagnosis of thyroid cancer in the setting of detectable thyroglobulin and negative radioiodine scan. Furthermore, (99m)Tc-depreotide adds complementary information regarding the SSTR status of lesions, which may be helpful for individual therapy planning in this group of patients, which is hard to manage clinically.


Near-field scanning optical microscopy studies of L-alpha-dipalmitoylphosphatidylcholine monolayers at the air-liquid interface.
The phase structure in L-alpha-dipalmitoylphosphatidylcholine-20 mol% fluorescent 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate Langmuir monolayers dispersed on a 2 M sucrose solution subphase is studied with near-field scanning optical microscopy (NSOM). Cantilevered NSOM probes operating in a tapping-mode feedback or an optical interferometric feedback mode are capable of tracking the air-sucrose solution interface. At the micrometre scale, the NSOM fluorescence images reveal lipid domain features similar to those observed previously in supported Langmuir-Blodgett (LB) monolayers. At the submicrometre scale, the small nanometric lipid islands seen in LB films are not observed at the air-sucrose interface. This supports a mechanism in which domain formation in LB films can be induced by means of the transfer process onto the solid support. Progress towards extending these studies to films at the air-water interface using the optical interferometric feedback method is also discussed.


Formation of black pigment gallstone in a hamster model of experimental cirrhosis.
The relationship between liver cirrhosis and the pathogenesis of black pigment stones has not been clarified. We attempted to induce black pigment stone formation in the gallbladders of hamsters. Male golden hamsters were divided into a cirrhosis group and a control group. Liver cirrhosis was induced by administering drinking water containing thioacetamide. The control group was given tap water. Gallstones at 48 weeks after treatment were examined by stereoscopic microscopy and scanning electron microscopy. The copper content of the black pigment stones was analysed by atomic absorption spectrophotometry. Black pigment stones in the gallbladder were detected in 25% of the cirrhosis group. Their surface and cross-section appeared amorphous. Black pigment stones contained copper. We confirmed the formation of gallstones in an animal model of cirrhosis by thioacetamide. Our findings may contribute to the clarification of the relationship between the pathogenesis of black pigment stones and the pathophysiology of liver cirrhosis.


Active semi-supervised community detection based on must-link and cannot-link constraints.
Community structure detection is of great importance because it can help in discovering the relationship between the function and the topology structure of a network. Many community detection algorithms have been proposed, but how to incorporate the prior knowledge in the detection process remains a challenging problem. In this paper, we propose a semi-supervised community detection algorithm, which makes full utilization of the must-link and cannot-link constraints to guide the process of community detection and thereby extracts high-quality community structures from networks. To acquire the high-quality must-link and cannot-link constraints, we also propose a semi-supervised component generation algorithm based on active learning, which actively selects nodes with maximum utility for the proposed semi-supervised community detection algorithm step by step, and then generates the must-link and cannot-link constraints by accessing a noiseless oracle. Extensive experiments were carried out, and the experimental results show that the introduction of active learning into the problem of community detection makes a success. Our proposed method can extract high-quality community structures from networks, and significantly outperforms other comparison methods.


Cell wall proteome of pathogenic fungi.
A fast development of a wide variety of proteomic techniques supported by mass spectrometry coupled with high performance liquid chromatography has been observed in recent years. It significantly contributes to the progress in research on the cell wall, very important part of the cells of pathogenic fungi. This complicated structure composed of different polysaccharides, proteins, lipids and melanin, plays a key role in interactions with the host during infection. Changes in the set of the surface-exposed proteins under different environmental conditions provide an effective way for pathogens to respond, adapt and survive in the new niches of infection. This work summarizes the current state of knowledge on proteins, studied both qualitatively and quantitatively, and found within the cell wall of fungal pathogens for humans, including Candida albicans, Candida glabrata, Aspergillus fumigatus, Cryptococcus neoformans and other medically important fungi. The described proteomic studies involved the isolation and fractionation of particular sets of proteins of interest with various techniques, often based on differences in their linkages to the polysaccharide scaffold. Furthermore, the proteinaceous contents of extracellular vesicles ("virulence bags") of C. albicans, C. neoformans, Histoplasma capsulatum and Paracoccidioides brasiliensis are compared, because their production can partially explain the problem of non-classical protein secretion by fungi. The role assigned to surface-exposed proteins in pathogenesis of fungal infections is enormously high, thus justifying the need for further investigation of cell wall proteomes.


Hysterectomy and Adenextomy via transvaginal natural orifice transluminal endoscopic surgery (vNOTES): A UK perspective with a case series of 33 patients.
To evaluate operative outcomes of hysterectomy +/- adnexectomy by Trans-vaginal Natural Orifice Endoscopic Surgery (vNOTES) in a case series of 33 patients. It was a prospective case series study carried out in Darent Valley and Benenden Hospital, to our knowledge, the first units in the United Kingdom to have undertaken VNOTE Hysterectomy. We collected data on a private shared drive noting patient demographics, indications for surgery, operation outcomes and patient follow-up details. Between January and December 2018, 33 patients underwent surgery between two units. Indications for surgery included dysfunctional uterine bleeding, endometrial hyperplasia, pelvic pain, post-menopausal bleeding, prophylactic surgery in BRCA positive patients and one grade 1 stage 1 endometrial cancer in whom laparoscopic hysterectomy was technically difficult and complicated by previous midline laparotomy. Ages ranged from 35 to 75 and BMI from 20-53. Mean operation time was 68.5 min and mean blood loss intraoperatively was 269mls. 15.2% (n = 5) had a blood loss equal or more than 500 mls. There were no intraoperative complications and no conversions to open surgery. The median visual analogue pain score at 6 h post operatively and at discharge was 0. All patients received regular Paracetamol and Ibuprofen and opiate based analgesics were only used on an as required basis. Postoperative complication which included failed trial without catheter, urinary tract infection and urinary dysfunction were reported by four women (12.4%). Only 2 patients re-presented to hospital over a 30-day period and neither required inpatient management. Hysterectomy by vNOTES has advantages over traditional laparoscopic and vaginal hysterectomy that include reduced requirement for intra-abdominal insufflation and head down, absence of trocar related injuries and easier operative access in patients with morbid obesity, or previous abdominal surgery such as midline laparotomy or mesh hernia repair. In addition, both tubes and ovaries can be removed easily due to easier access and visibility and there is no requirement for vaginal descent in order to do so. Plans for a comparative study between laparoscopic hysterectomy and vNOTES hysterectomy are underway.


Cell-surface engineering with GPI-anchored proteins.
Protein engineering of cell surfaces is a potentially powerful technology through which the surface protein composition of cells can be manipulated without gene transfer. This technology exploits the fact that proteins that are anchored by glycoinositol phospholipids (GPIs), when purified and added to cells in vitro, incorporate into their surface membranes and are fully functional. By substituting 3'-mRNA end sequence of naturally GPI-anchored proteins (i.e., a sequence that contains the signals that direct GPI anchoring) for endogenous 3'-mRNA end sequence, virtually any protein of interest can be expressed as a GPI-anchored derivative. The GPI-anchored product then can be purified from transfectants and the purified protein used to "paint" any target cell. Such protein engineering or "painting" of the cell surface offers several advantages over conventional gene transfer. Among these advantages are that 1) GPI-anchored proteins can be painted onto cells that are difficult to transfect, 2) cells can be altered immediately without previous culturing, 3) the amount of protein added to the surface can be precisely controlled, and 4) multiple GPI-anchored proteins can be sequentially or concurrently inserted into the same cells. Emerging applications for the technology include its use for the analysis of complex cell-surface interactions, the engineering of antigen presenting cells, the development of cancer vaccines, and possibly the protection against graft rejection.


Malaria in children and women of childbearing age: infection prevalence, knowledge and use of malaria prevention tools in the province of Nyanga, Gabon.
There is little information on the social perception of malaria and the use of preventative measures in Gabon, especially in rural areas. Adequate knowledge of malaria prevention and control can help in reducing the burden of malaria among vulnerable groups, particularly pregnant women and children under 5 years old living in malaria-endemic settings. This study was designed to assess the prevalence of malaria and the knowledge and attitude towards this disease in households in Nyanga Province. A cross-sectional study was conducted to assess malaria knowledge, prevention practices and prevalence of the malaria infection in five departments of Nyanga Province. Plasmodial infection was diagnosed in children ≤ 5 years of age and women aged 15-49 years using rapid diagnostic tests. A questionnaire was administered randomly to women aged 15-49 years and to the parents or guardians of children aged ≤ 5 years in 535 households during a 2-week period in March 2018. Overall, the respondents' socio-demographic characteristics, knowledge of malaria, malaria prevention practices and malaria prevalence were evaluated and compared across the five departments. Data from a total of 1,307 participants were included in this study, including 631 women of childbearing age (61 of them pregnant) and 676 children. Practically the entire (97.7%) interviewed population had heard about malaria and attributed the cause of malaria to a mosquito bite (95.7%). This survey revealed that the reported rate of reported bed-net use was 73.3%. The study observed an average malaria parasite prevalence of 13.9%. All departmental capitals of Nyanga Province had a significant level of malaria infection except for Mayumba where no plasmodial infection was found. High malaria prevalence is found in the departmental capital cities of Nyanga Province. This study reveals that respondents have a high knowledge of the malaria symptoms, its mode of transmission and preventive measures. Despite this high level of knowledge of the disease and its preventive measures, the incidence of malaria remains relatively high in this rural community highlighting the need for other types of interventions.


White matter impairment in chronic heroin dependence: a quantitative DTI study.
Exposure to addictive drugs has been associated with disrupted brain white matter integrity. A few studies have examined the white matter deficits in heroin users; however, the results were influenced by the use of substitution drugs such as methadone and buprenorphine. The present study assessed the alteration in white matter integrity and heroin-related neuropathology in heroin dependents who had not received any replacement therapy using quantitative diffusion tensor imaging (DTI). The study comprised 17 heroin-dependent (HD) subjects and 15 matched healthy controls (HC). Fractional anisotropy (FA) and eigenvalues (λ┴, λ||) of white matter in the whole brain were measured and compared using a voxel-based analysis. The correlation between DTI measurements in identified regions and history of heroin exposure was tested by partial correlation analysis. Compared with HCs, HD subjects displayed decreased FA in the bilateral frontal lobe sub-gyrus, cingulate gyrus, medial frontal gyrus, extra-nuclear, left temporal lobe sub-gyrus and right superior frontal gyrus. Among these regions, the HD group had significantly increased λ┴ in the bilateral frontal lobe sub-gyrus, cingulate gyrus and extra-nuclear relative to the HC group. There were no group differences in λ||. In addition, there were no significant correlations between duration of heroin use or accumulated dosage and FA or λ┴ values. In conclusion, chronic heroin-dependent subjects had widespread disruption of white matter structural connectivity located mainly in anterior and superior regions of the brain. Damage to myelin other than axons was the primary pathological feature in the brain of the heroin user.