Bioinformatic analysis of highly consumed phytochemicals as P-gp binders to overcome drug-resistance.
P-glycoprotein (P-gp) is an adenosine triphosphate (ATP)-dependent membrane efflux pump for protecting cells against xenobiotic compounds. Unfortunately, overexpressed P-gp in neoplastic cells prevents cell entry of numerous chemotherapeutic agents leading to multidrug resistance (MDR). MDR cells may be re-sensitized to chemotherapeutic drugs via P-gp inhibition/modulation. Side effects of synthetic P-gp inhibitors encouraged the development of natural products. Molecular docking and density functional theory (DFT) calculations were used as fast and accurate computational methods to explore a structure binding relationship of some dietary phytochemicals inside distinctive P-gp binding sites (modulatory/inhibitory). For this purpose, top-scored docked conformations were subjected to per-residue energy decomposition analysis in the B3LYP level of theory with a 6-31g (d, p) basis set by Gaussian98 package. Consecutive application of computational techniques revealed binding modes/affinities of nutritive phytochemicals within dominant binding sites of P-gp. Blind docking scores for best-ranked compounds were superior to verapamil and rhodamine-123. Pairwise amino acid decomposition of superior docked conformations revealed Tyr303 as an important P-gp binding residue. DFT-based induced polarization analysis revealed major electrostatic fluctuations at the atomistic level and confirmed larger effects for amino acids with energy-favored binding interactions. Conformational analysis exhibited that auraptene and 7,4',7'',4'''-tetra-O-methylamentoflavone might not necessarily interact to P-gp binding sites through minimum energy conformations. Although there are still many hurdles to overcome, obtained results may propose a few nutritive phytochemicals as potential P-gp binding agents. Moreover; top-scored derivatives may have the chance to exhibit tumor chemo-sensitizing effects.


The role of gasless laparoscopy in differential diagnosis of acute abdomen.
The diagnosis of acute abdomen in the emergency setting, still remains a challenging problem. In these cases timely diagnosis and management is of great importance, while the anesthetic risk is high. The combination of the risk of an open laparotomy and the relative high likelihood of negative findings when performed, creates the need for a better approach. The alternative actually exists since 1911 when Eruheim made the first gasless laparoscopy. The aim of this study is to put back into the spotlight, gasless laparoscopy in the differential diagnosis of acute abdomen and to underline the advantages of this simple, cheap and very useful technique, especially in patients that require prompt diagnosis and have relative or absolute contraindications to general anesthesia or pneumoperitoneum. This study included 49 patients that were managed with gasless laparoscopy for the diagnosis of acute abdomen, from 2011 to 2013. Two techniques were used: the mechanical lift of the anterior abdominal wall and the LapVision device. From the 49 patients included in the study, 41 were diagnosed with gasless laparoscopy while in eight the results were uncertain or there wasn't any pathology involved. With both techniques used, sample of the intraperitoneal fluid or biopsy could be obtained. The gasless technique for laparoscopy is an extremely useful mean of diagnosis in emergency conditions, or for patients with contraindications to undergo laparoscopy by pneumoperitoneum. Requiring only local or regional anesthesia, this technique could easily find application in diagnosis and treatment, while avoiding unnecessary laparotomies. Hippokratia 2015, 19 (1): 69-72.


[Compartment syndrome--indication for a treatment error?].
The compartment syndrome is a complication caused by trauma or treatment, which indicates liability especially as a result of minor injuries or treatment. According to the outstanding importance of observation of the course of treatment the careful documentation also has to be stressed. However, remaining damages give no reason for an (apparent) evidence of a failure of treatment.


Communicating with external publics: managing public opinion and behavior.
In health care organizational settings public relations plays an important role in managing relationships with a variety of external publics as well as with society in general. Managing these relationships involves both reactive and proactive communication activities. Reactively, public relations responds to public issues, crises and concerns, as well as inquiries from the media and other social institutions. Proactively, public relations engages in deliberately planned campaigns and programs to inform, influence or change behaviors of targeted publics for a wide range of strategic purposes. These purposes include managing the organization's image and identity; influencing public policies; supporting health promotion and education; promoting fund raising and volunteerism; and managing organizational change and crises.


Stable components of sound fields in the ocean.
A method is proposed for finding the wave field components which are weakly sensitive to the sound speed perturbation in the ocean acoustic waveguides. Such a component is formed by a narrow beam of rays whose spread in vertical direction, up to the observation range, remains less than the vertical scale of perturbation. These rays pass through practically the same inhomogeneities and therefore their phases are incremented by the same amount. If the ray amplitudes vary insignificantly, then (i) the stable components of the monochromatic field in the perturbed and unperturbed waveguide differ by only a constant phase factor, and (ii) in the case of transient wave field the perturbation causes only an additional time delay of the stable component as a whole. It is shown how the stable components can be selected from the total wave field using the field expansions in the coherent states and in the normal modes. The existence of stable components is demonstrated by numerical simulation of sound field in a deep water waveguide. It turns out, that even though the assumptions (i) and (ii) are not met exactly, the stable components in the perturbed and unperturbed waveguides are quite close.


An NMR and X-ray study of the structure of the azo coupling product of 4-dimethylaminopent-3-en-2-one and benzenediazonium-tetrafluoroborate.
4-Dimethylaminopent-3-en-2-one reacts with two molecules of benzenediazonium-tetrafluoroborate to give compound 1. The structure of this compound was determined by means of X-ray analysis of its crystal and 1H, 13C and 15N NMR spectra of its solution in CDCl3. The molecule of this compound contains one azo group and one hydrazone group. The substance exists, both in crystal form and in solutions of concentrations above 0.1 mol l(-1), in the form of a dimer, in which the pair of molecules are bound by two hydrogen bonds N-H...N. On diluting the solution, the dimers decompose, the two forms being in an equilibrium that is rapid on the NMR time scale.


Evaluation of sexual and fertility dysfunction in spinal cord-injured men in Jamaica.
Sexual dysfunction and infertility are common in males with traumatic spinal cord injuries (SCIs). The objective of this study was to determine the prevalence of sexual dysfunction and infertility in males with traumatic SCI managed in Jamaica, as well as the therapeutic options offered. A cross-sectional study including males with traumatic SCI managed at the Sir John Golding Rehabilitation Centre, Kingston, Jamaica was carried out between 1 January and 31 December 2015. Sexual function was measured with the International Index of Erectile Function Questionnaire, and further information on social history, fertility desires and treatment options offered were collected. Data were analyzed using Stata 12 for Windows (College Station, TX, USA). The mean age of patients at the time of study was 38.8±15.3 years (range 19-71) with a mean duration of injury of 3.7±2.4 years (range 1.3-15.6). Of 45 patients with traumatic SCI surveyed, 90.7% had erectile dysfunction, with 62.8% being classified as severe and 73.3% of men were unable to ejaculate. Treatment for erectile and ejaculatory dysfunction was offered in only two patients, respectively. Most (71.1%) patients indicated that they wanted to have children in the future, however, no one had been referred for assisted reproductive techniques. Men with traumatic SCI have high rates of severe erectile and ejaculatory dysfunctions, but have preserved interests in maintaining fertility. Adherence to guidelines for sexual education for men with traumatic SCI in Jamaica and the Caribbean is needed.


Exploring the molecular and metabolic factors contributing to the adaptation of maize seedlings to nitrate limitation.
Crop production on soils containing sub-optimal levels of nitrogen (N) severely compromises yield potential. The development of plant varieties displaying high N use efficiency (NUE) will optimize N fertilizer use and reduce the environmental damage caused by excess N application. Maize is one of the most important crops cultivated worldwide. Identification of the genotypes with an enhanced NUE in the field is both time and resource consuming and sometime is difficult due to the regulation in the biotechnology programs. Identification of traits associated with adaptation to N limitation at an early vegetative stage which could reflect NUE at maturity is in need. We developed a hydroponic growth system and used it to test two genotypes that were different in their NUE at maturity under N limitation. One genotype SRG-200 showed a higher NUE than the other genotype SRG-100 and we used its hybrid SRG-150 as a reference for NUE. A number of phenotypic, molecular, and metabolic factors were tested using these three genetic lines at an early vegetative stage to determine which of these could be more indicative of predicting improved NUE at an early seedling stage. These include a transcriptional analysis which showed that the higher NUE in SRG-200 genotype is associated with higher transcript levels for the genes involved in nitrate transport, N assimilation, and GS and that the SRG-200 genotype maintained higher sugar content in leaves. Those identified in this study could be useful indicators for selecting promising maize lines at early stages to help develop elite varieties showing an enhanced NUE.


Rasa3 controls turnover of endothelial cell adhesion and vascular lumen integrity by a Rap1-dependent mechanism.
Rasa3 is a GTPase activating protein of the GAP1 family which targets R-Ras and Rap1. Although catalytic inactivation or deletion of Rasa3 in mice leads to severe hemorrhages and embryonic lethality, the biological function and cellular location of Rasa3 underlying these defects remains unknown. Here, using a combination of loss of function studies in mouse and zebrafish as well as in vitro cell biology approaches, we identify a key role for Rasa3 in endothelial cells and vascular lumen integrity. Specific ablation of Rasa3 in the mouse endothelium, but not in megakaryocytes and platelets, lead to embryonic bleeding and death at mid-gestation, recapitulating the phenotype observed in full Rasa3 knock-out mice. Reduced plexus/sprouts formation and vascular lumenization defects were observed when Rasa3 was specifically inactivated in mouse endothelial cells at the postnatal or adult stages. Similar results were obtained in zebrafish after decreasing Rasa3 expression. In vitro, depletion of Rasa3 in cultured endothelial cells increased β1 integrin activation and cell adhesion to extracellular matrix components, decreased cell migration and blocked tubulogenesis. During migration, these Rasa3-depleted cells exhibited larger and more mature adhesions resulting from a perturbed dynamics of adhesion assembly and disassembly which significantly increased their life time. These defects were due to a hyperactivation of the Rap1 GTPase and blockade of FAK/Src signaling. Finally, Rasa3-depleted cells showed reduced turnover of VE-cadherin-based adhesions resulting in more stable endothelial cell-cell adhesion and decreased endothelial permeability. Altogether, our results indicate that Rasa3 is a critical regulator of Rap1 in endothelial cells which controls adhesions properties and vascular lumen integrity; its specific endothelial cell inactivation results in occluded blood vessels, hemorrhages and early embryonic death in mouse, mimicking thus the Rasa3-/- mouse phenotype.


The effect of different doses of oxygen administration on oxygen saturation in patients with stroke.
American Stroke guidelines suggest that oxygen saturation after acute stroke should be maintained at 95% or higher. European recommendations include a dose of 2 to 4 L/minute via nasal cannulae. These recommendations are not based on controlled clinical studies. No consensus exists among stroke physicians regarding how much oxygen should be administered and which route should be selected. The aim of this study was to assess the effects of different doses and routes of oxygen administration on oxygen saturation in patients with stroke. Patients were recruited within 72 hours of admission with acute stroke. Oxygen saturation was assessed by pulse oximetry (Minolta Pulsox 3i) for 30 minutes on room air (baseline), 2 and 3 L/minute of oxygen via nasal cannulae, 24 and 35% oxygen via face mask, and, finally, on room air. Patients were asked about their preferred route of oxygen administration. Twenty-one patients with a mean age of 72.3 years (range: 46-87 years) were recruited. A total of 24% oxygen (face mask) increased saturation by 1%, 2 L/minute (nasal cannulae) and 35% (face mask) led to a 2% increase, and 3 L/minute (nasal cannulae) resulted in a 3% increase in saturation compared to baseline (p < 0.001). Oxygen saturations were similar in the first and last half-hours. Oxygen treatment has no significant effect on respiratory and heart rates. Most patients (71%) preferred nasal cannulae to face masks. In our patient population, there was a close dose-response relationship between the amount of oxygen given and the resultant changes in oxygen saturation.


Early diagnosis of pulmonary tuberculosis using serum biomarkers.
The early diagnosis of tuberculosis (TB) remains the biggest obstacle to the global TB control, TB being the second leading cause of infectious disease death worldwide. As such, one of the pioneering investigations is made by Xu et al. (Proteomics 2015, 15, 58-67), which is of promising clinical application significance when used in clinics and in TB screening in the population. Xu et al. revealed that statistical differences among three serum proteins (S100A9, SOD3, and MMP9) exist between TB cases and other lung disease cases. The combination of the three biomarkers could give 92.5% sensitivity and 95% specificity to discriminate TB from healthy controls.


The effects of whole grain cereals on tryptophan metabolism and intestinal barrier function: underlying factors of health impact.
This review aims to investigate the relationship between the health impact of whole grains mediated via the interaction with intestinal microbiota and intestinal barrier function with special interest on tryptophan metabolism, focusing on the role of the intestinal microbiota and their impact on barrier function. Consuming various types of whole grains can lead to the growth of different microbiota species, which in turn leads to the production of diverse metabolites, including those derived from tryptophan metabolism, although the impact of whole grains on intestinal microbiota composition results remains inconclusive and vary among different studies. Whole grains can exert an influence on tryptophan metabolism through interactions with the intestinal microbiota, and the presence of fibre in whole grains plays a notable role in establishing this connection. The impact of whole grains on intestinal barrier function is closely related to their effects on the composition and activity of intestinal microbiota, and SCFA and tryptophan metabolites serve as potential links connecting whole grains, intestinal microbiota and the intestinal barrier function. Tryptophan metabolites affect various aspects of the intestinal barrier, such as immune balance, mucus and microbial barrier, tight junction complexes and the differentiation and proliferation of epithelial cells. Despite the encouraging discoveries in this area of research, the evidence regarding the effects of whole grain consumption on intestine-related activity remains limited. Hence, we can conclude that we are just starting to understand the actual complexity of the intestinal factors mediating in part the health impacts of whole grain cereals.


Assessing child welfare under the Human Fertilisation and Embryology Act 2008: a case study in medicalisation?
This article reports on a study with staff working in assisted conception clinics in the UK about making welfare of the child (WOC) assessments pre-conception. This aspect of infertility treatment is obligatory under section 13(5) of the Human Fertilisation and Embryology Act, which was amended in 2008. The aim of the study was to find out how this change to the law had impacted on practice. In describing what we found, we also make a contribution to scholarship about the medicalisation of reproduction. S13(5) has often been discussed as a prime example of medicalisation, giving clinics power to grant or deny access to treatment on child welfare grounds, encompassing far more than purely clinical considerations. Yet, while such medicalisation may be entrenched in the law, our findings suggest this power is used with a very light touch. Further, while our interviewees offered near-universal support for the need to consider child welfare, this is now justified by concerns that address not only family form (e.g. the need for a father figure) but also the quality of interactions between parents and children. In this light we suggest that the concept of medicalisation may offer a rather blunt tool for understanding a far more complex reality.


Intracoronary beta-irradiation with liquid rhenium-188: results of the Taiwan radiation in prevention of post-pure balloon angioplasty restenosis study.
To assess the feasibility and short-term outcome of intracoronary irradiation after pure balloon angioplasty (POBA) of de novo and post-POBA restenotic lesions with a liquid beta-emitter (188)Re-filled balloon. Nonrandomized prospective study with contemporaneous control group in a single medical center. In the Taiwan Radiation in Prevention of Post-Pure Balloon Angioplasty Restenosis study, 40 patients underwent 14-Gy irradiation and 15 patients underwent 20-Gy irradiation at a tissue depth of 0.5 mm after POBA. Thirty control patients received a 5-min inflation with a perfusion balloon catheter after POBA. No procedural or in-hospital complications, or 30-day major adverse cardiac events were noted. Six-month angiographic restenosis rates were 49% in the 14-Gy group, 20% in the 20-Gy group, and 57% in the control group (p = 0.05, 20-Gy group vs control group). In the lesions with an arc of calcification of < 180 degrees, restenosis occurred in 15 of the 34 lesions (44%) in the 14-Gy group and in none of the 11 lesions (0%) in the 20-Gy group (p = 0.007). In a vessel with a reference diameter < 3.0 mm, restenosis occurred in 1 of the 8 lesions (13%) in the 20-Gy group, and in 8 of the 11 lesions (73%) in the control group (p = 0.02). In the post-POBA restenotic lesions, restenosis occurred in none of the six lesions (0%) in the 20-Gy group, and in five of the six lesions (83%) in the control group (p = 0.008). Post-POBA, catheter-based brachytherapy in nonstented native coronary artery with a (188)Re-filled balloon can effectively reduce target lesion restenosis with 20-Gy irradiation at a tissue depth of 0.5 mm and seems to be more effective in the treatment of lesions with an arc of calcification < 180 degrees, in a vessel with a reference diameter of < 3.0 mm, and in post-POBA restenotic lesions.


Maternal antepartum antibiotic administration and patterns of bacterial resistance in early preterm neonates.
The objective of this study was to determine the relationship between maternal antepartum antibiotic administration and antibiotic resistance patterns in preterm neonates admitted to the neonatal intensive care unit (NICU). This was a retrospective cohort study of women and their preterm neonates delivered at a single tertiary care center over a 5-year period. Women and neonates were included if they delivered between 23 weeks 0 days and 28 weeks 6 days of gestation and neonates were admitted to the NICU. Subjects were excluded if there was incomplete antibiotic administration data or incomplete laboratory or bacterial culture data for either mothers or neonates. Data collected from maternal and neonatal charts included the type, duration, and total number of antibiotics administered to subjects, neonatal culture results within the first 7 days of life, and bacterial antibiotic resistance information. Women with neonates that cultured positive for bacteria demonstrating antibiotic resistance were compared to those whose neonates did not have antibiotic-resistant bacteria. 79 women with 90 neonates met inclusion criteria. Of the 79 women, 71 (89.9%) received at least 1 antibiotic antepartum. 14 neonatal bacterial isolates were resistant to at least 1 antibiotic. Antibiotic-resistant bacteria were present in 11 neonates; 3 neonates had more than 1 resistant bacteria cultured. The most common resistant bacteria cultured were Coagulase-negative Staphylococcus (6/14, 42.9%), S. aureus (3/14, 21.4%), and E. coli (2/14, 14.3%). Enterobacter spp (2) and Klebsiella pneumoniae (1) made up the remainder. Of the 11 neonates with resistant bacteria isolated, 10 of their mothers received antibiotics antepartum. Neonates with antibiotic-resistant bacterial isolates were more likely to be born at lower gestational ages (24.6 vs 25.9 weeks, p = .013) and have lower mean birth weights (679.5 vs 849.3 g, p = .009) than those without resistant bacteria. In 8 of 11 (73%) neonates with resistant bacteria, the mother received an antibiotic to which the bacteria cultured were resistant: 6 coagulase-negative Staphylococcus, 1 MRSA, and 1 S. aureus. Although preterm neonates are often treated for presumed sepsis, they infrequently have positive bacterial cultures. In this study, those that had positive bacterial cultures for resistant bacteria were born at earlier gestational ages and had lower birth weights. These bacteria cultured in neonates are likely to be resistant to antibiotics received by mothers in the antepartum period. Careful selection of maternal and neonatal antibiotics in the preterm setting with consideration for local antibiotic resistance patterns is suggested.


Insights Into Patient Variability During Ivacaftor-Lumacaftor Therapy in Cystic Fibrosis.
Background: The advent of cystic fibrosis transmembrane conductance regulator protein (CFTR) modulators like ivacaftor have revolutionised the treatment of cystic fibrosis (CF). However, due to the plethora of variances in disease manifestations in CF, there are inherent challenges in unified responses under CFTR modulator treatment arising from variability in patient outcomes. The pharmacokinetic (PK) data available for ivacaftor-lumacaftor cystic fibrosis (CF) transmembrane conductance regulator (CFTR) modulator drug combination is limited. Methods: Secondary objectives were to identify (1) patient characteristics and (2) the interactions between ivacaftor-lumacaftor responsible for interindividual variability (IIV). Results: Peak plasma concentrations (Cmax) of ivacaftor - lumacaftor were >10 fold lower than expected compared to label information. The one-way ANOVA indicated that the patient site had an effect on Cmax values of ivacaftor metabolites ivacaftor-M1, ivacaftor-M6, and lumacaftor (p < 0.001, p < 0.001, and p < 0.001, respectively). The Spearman's rho test indicated that patient weight and age have an effect on the Cmax of lumacaftor (p = 0.003 and p < 0.001, respectively) and ivacaftor metabolite M1 (p = 0.020 and p < 0.001, respectively). Age (p < 0.001) was found to effect on Cmax of ivacaftor M6 and on Tmax of ivacaftor M1 (p = 0.026). A large impact of patient characteristics on the IIV of PK parameters Cmax and Tmax, was observed among the CF patients. Conclusion: Understanding the many sources of variability can help reduce this individual patient variability and ensure consistent patient outcomes.


The PLAG1 mRNA expression analysis among genetic variants and relevance to growth traits in Chinese cattle.
Pleomorphic adenoma gene 1 (PLAG1) encodes a developmentally regulated zinc finger protein, locating in growth-related QTNs. The mRNA expression of this gene was investigated in different tissues and from two different developmental periods, whilst to explore the functions of PLAG1 in growth traits of cattle. The results showed that PLAG1 was expressed in all examined tissues. However, PLAG1 expression levels in all examined tissues were significantly different between the 5-month fetus and 36-month adult cattle. Our juvenile results indicated PLAG1 is primarily expressed in embryonic tissues of Chinese cattle. Furthermore, two variations were identified. Association analysis revealed that the two variations were associated with growth traits (p < 0.05 or p < 0.01). These new findings provide a comprehensive overview of the critical roles of PLAG1 in growth traits modulation and can be highlighted as candidate molecular markers in cattle breeding.


Xanthan and glucomannan mixtures: synergistic interactions and gelation.
The synergistic interaction between xanthan and glucomannan in solution and in the gel phase has been studied by circular dichroism spectroscopy and differential scanning calorimetry. The study in solution of the polysaccharidic mixture indicates a preferred stoichiometry of the interaction corresponding to a weight fraction of xanthan around 0.55. This finding is in reasonable agreement with the differential scanning calorimetry measurements carried out on the gel phase. Models from conformational analysis based on these results were formulated in terms of 1:1 and 2:1 Konjac glucomannan/xanthan molecular assemblies. The experimental and calculation results clearly indicate the involvement of the side chains of xanthan and suggest that the ordered portions of the macromolecular complex in solution act in the gel phase as junction zones.


Short- and long-term outcomes following laparoscopic vs open surgery for pathological T4 colorectal cancer: 10 years of experience in a single center.
To evaluate the short-term and long-term outcomes following laparoscopic vs open surgery for pathological T4 (pT4) colorectal cancer. We retrospectively analyzed the short- and long-term outcomes of proven pT4 colorectal cancer patients who underwent complete resection by laparoscopic or open surgery from 2006 to 2015 at Guangdong General Hospital. A total of 211 pT4 colorectal cancer patients were included in this analysis, including 101 cases in the laparoscopy (LAP) group and 110 cases in the open surgery (OPEN) group [including 15 (12.9%) cases of conversion to open surgery]. Clinical information (age, gender, body mass index, comorbidities, American Society of Anesthesiologists score, etc.) did not differ between the two groups. In terms of blood loss, postoperative complications and rate of recovery, the LAP group performed significantly more favorably (P < 0.05). With regard to pT4a/b and combined organ resection, there were significantly more cases in the OPEN group (P < 0.05). The 3- and 5-year overall survival rates were 74.9% and 60.5%, respectively, for the LAP group and 62.4% and 46.5%, respectively, for the OPEN group (P = 0.060). The 3- and 5-year disease-free survival rates were 68.0% and 57.3%, respectively, for the LAP group and 55.8% and 39.8%, respectively, for the OPEN group (P = 0.053). Multivariate analysis showed that IIIB/IIIC stage, lymph node status, and CA19-9 were significant predictors of overall survival. PT4a/b, IIIC stage, histological subtypes, CA19-9, and adjuvant chemotherapy were independent factors affecting disease-free survival. Laparoscopy is safely used in the treatment of pT4 colorectal cancer while offering advantages of minimal invasiveness and faster recovery. Laparoscopy is able to achieve good oncologic outcomes similar to those of open surgery. We recommend that laparoscopy be carried out in experienced centers. It is still required to screen the appropriate cases for laparoscopic surgery, optimize the preoperative diagnosis process, and reduce the conversion rate. Multi-center, prospective, and large-sample studies are required to assess these issues.


[Inflammatory pseudotumor of liver--a clinical review of 15 cases].
Inflammatory pseudotumor rarely occurs in the liver. However, it is important to discriminate it from malignant hepatic tumor in order to avoid unnecessary surgery. We aimed to elucidate the characteristic features of this disease entity by analyzing our experiences and by reviewing the related literatures. Fifteen patients were enrolled during a recent three-year period. The patients were pathologically diagnosed with inflammatory pseudotumor of the liver, and their clinical and imaging findings were analyzed retrospectively. Our study population was composed of ten men and five women, and their mean age was 60.3+/-9.2 years. Their initial diagnoses were inflammatory pseudotumor (n=8), malignant tumors (n=3) and abscess (n=4). Twelve of 15 patients were associated with biliary diseases such as biliary stone, gallbladder cancer, empyema or cholangiocarcinoma. The most common symptom was abdominal pain. The most common CT and MR findings could be summarized as a delayed hyperattenuating mass with an internal hypoattenuating component. The tumors were solitary in 13 patients and multiple in two patients. The lesions regressed spontaneously in seven patients. Four patients were treated by antibiotics and 3 patients by surgical resection. Inflammatory pseudotumor of the liver seems to have relatively common clinical and imaging features, as described above. However, these features are not disease-specific; thus, preoperative histologic confirmation is necessary to avoid unnecessary surgery.


1% sulconazole cream v 2% miconazole cream in the treatment of tinea versicolor. A double-blind, multicenter study.
Sulconazole nitrate, a new imidazole derivative, was formulated at 1% concentration in a cream vehicle and compared with 2% miconazole nitrate cream in the treatment of tinea versicolor in a double-blind, multicenter, randomized, parallel clinical trial. At baseline, all of the 192 patients enrolled had a positive potassium hydroxide (KOH) preparation; itching was reported by 48% of the patients. The medications were applied twice daily for three weeks. Of 181 patients analyzed for efficacy at the end of the treatment trial, 93% of sulconazole-treated patients and 87% of miconazole-treated patients had become KOH negative. The complete clearing of tinea versicolor lesions occurred in 89% of sulconazole-treated patients and 82% of miconazole-treated patients. Both drugs were well tolerated with no systemic reactions reported. Drug-related adverse cutaneous reactions, predominantly transient itching, were reported in eight patients receiving sulconazole and in four patients receiving miconazole.


Serological responses to human virome define clinical outcomes of Italian patients infected with SARS-CoV-2.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the pandemic respiratory infectious disease COVID-19. However, clinical manifestations and outcomes differ significantly among COVID-19 patients, ranging from asymptomatic to extremely severe, and it remains unclear what drives these disparities. Here, we studied 159 sequentially enrolled hospitalized patients with COVID-19-associated pneumonia from Brescia, Italy using the VirScan phage-display method to characterize circulating antibodies binding to 96,179 viral peptides encoded by 1,276 strains of human viruses. SARS-CoV-2 infection was associated with a marked increase in immune antibody repertoires against many known pathogenic and non-pathogenic human viruses. This antiviral antibody response was linked to longitudinal trajectories of disease severity and was further confirmed in additional 125 COVID-19 patients from the same geographical region in Northern Italy. By applying a machine-learning-based strategy, a viral exposure signature predictive of COVID-19-related disease severity linked to patient survival was developed and validated. These results provide a basis for understanding the role of memory B-cell repertoire to viral epitopes in COVID-19-related symptoms and suggest that a unique anti-viral antibody repertoire signature may be useful to define COVID-19 clinical severity.


The Demographic Diversity of Food Intake and Prevalence of Kidney Stone Diseases in the Indian Continent.
Food intake plays a pivotal role in human growth, constituting 45% of the global economy and wellbeing in general. The consumption of a balanced diet is essential for overall good health, and a lack of equilibrium can lead to malnutrition, prenatal death, obesity, osteoporosis and bone fractures, coronary heart diseases (CHD), idiopathic hypercalciuria, diabetes, and many other conditions. CHD, osteoporosis, malnutrition, and obesity are extensively discussed in the literature, although there are fragmented findings in the realm of kidney stone diseases (KSD) and their correlation with food intake. KSD associated with hematuria and renal failure poses an increasing threat to healthcare infrastructures and the global economy, and its emergence in the Indian population is being linked to multi-factorial urological disorder resulting from several factors. In this realm, epidemiological, biochemical, and macroeconomic situations have been the focus of research, even though food intake is also of paramount importance. Hence, in this article, we review the corollary associations with the consumption of diverse foods and the role that these play in KSD in an Indian context.


Regulation of the Assembled Structure of a Flexible Porphyrin Derivative Containing Tetra Isophthalic Acids by Coronene or Different Pyridines.
Based on previous research, a new coassembly formed by a porphyrin derivative (IPETPP), which contains a flexible substituent of m-phthalic acid, is observed with coronene (COR) molecules at a higher concentration. Besides, a fresh IPETPP self-assembly formed at a lower concentration and another new coassembly with COR molecules are obtained. Moreover, the addition of a series of bipyridines alters the diamond arrangement of IPETPP, which enhances the stability of the two-component structures. It is unprecedented that bipyridine derivatives break intermolecular hydrogen bonds containing m-phthalic acid substituents. All the coassemblies are investigated by scanning tunneling microscopy on a highly oriented pyrolytic graphite. Combined with density functional theory, the formation mechanism of the assembled structures is revealed. These results would contribute to understanding the interfacial crystal behaviors and probably provide an efficient pathway to regulate the binary structures.


Memory disturbance in chronic progressive multiple sclerosis.
Forty-four patients with chronic progressive multiple sclerosis (MS) were compared with age- and education-matched control groups on a battery of clinical and experimental memory measures. Patients with MS performed substantially below the control groups on both immediate learning and delayed recall tasks, particularly in the retrieval of spatial information. The MS sample was subdivided into three groups using a cluster analytic procedure. One group (N = 9) performed well below expectations on memory tasks, exhibited signs of global cognitive disturbance, and had an atypical personality adjustment, characterized by irritability, social withdrawal, and apathy. A second group (N = 19) showed mild memory disturbance, associated with a greater use of psychotropic medications and a higher incidence of reactive depression. A third group (N = 16) performed normally on memory measures. The three groups of patients with MS did not differ in length or overall severity of illness.


Women's receptivity to church-based mobile mammography.
Mobile mammography can increase access to preventive screening and might be effective in church-based settings. Among 1,117 women ages 50 to 80 from 45 Los Angeles County churches, 31.7 percent said they would definitely use a mobile van at church, 21.9 percent would probably use one, 28.7 percent would probably not use one, and 17.6 percent would definitely not use one. The odds of saying yes to mobile mammography were six times higher for Spanish-speaking Latinas than for whites, over two times higher for English-speaking nonwhites than for whites, five times higher for the uninsured than for those with public or private health insurance, and three times higher for women who reported no mammogram in the previous 24 months than for women who reported a mammogram. Partnering with churches to provide mobile mammography offers the potential to increase screening adherence for traditionally underscreened women.


Ultrastructural features of Langerhans cells in clinically uninvolved skin of psoriatics.
Epidermal Langerhans cells (LC) from skin of clinically normal appearance in psoriatics were studied electron microscopically and compared with LC from the skin of healthy volunteers and from those with other dermatoses. Results show that LC from psoriatics display partly distinct cytoplasmic alterations. Moreover, about half of LC investigated were partly or mainly surrounded by clearly widened intercellular spaces, such that an immediate cellular contact with neighbouring keratinocytes was correspondingly decreased. Whether such LC are functionally altered remains to be clarified.


Effect of di-2-ethylhexyl sodium sulfosuccinate reversed micelles on the iron-tetrasulfonatophthalocyanine-catalyzed fluorogenic oxidation reaction of L-tyrosine with hydrogen peroxide.
The catalytic behavior of iron tetrasulfonatophthalocyanine (FeTSPc) for the oxidation reaction of L-tyrosine with H2O2 in a di-2-ethylhexyl sodium sulfosuccinate (AOT) reversed-micellar system (AOT/cyclohexane) was studied. It was indicated that the reversed micelles could not only enhance the catalytic activity of FeTSPc, but could also increase the fluorescence intensity of the product. Factors that may influence the catalytic reaction, including the concentration of AOT, the cosolubilized water, temperature and pH, were further examined. The possibility of its analytical application was also tested. Experimental results show that the calibration graphs for the determinations of FeTSPc and H2O2 under optimum conditions are linear over the range of 1.0 x 10-8 - 1.0 x 10(-6) mol L(-1) and 0.0 - 3.0 x 10(-6) mol L(-1), respectively, with detection limits of 1.1 x 10(-9) mol L(-1) and 3.1 x 10(-9) mol L(-1) for FeTSPc and H2O2, respectively.


Diagnosis, prognosis and awareness of dying in nursing homes: towards the Gold Standard?
In Western society and increasingly elsewhere, death has become medicalised and 'hospitalised' even when people are enduring deteriorating terminal conditions such as dementia and heart failure. In an attempt to rationalise and dignify the place and manner of death, evidence is emerging that the adoption of end-of-life care pathways and models can improve the experience of the end-of-life care across a range of care settings. Each of these demands skills and knowledge in the assessment and prediction of the dying trajectory. In this study, we report complexities facing relatives, residents and nursing home staff in the awareness, diagnosis and prediction of the dying trajectory. Data were collected and analysed within a broadly qualitative methodology. The contexts were two nursing homes in the Greater Manchester area, each at different stages of implementing 'Gold Standards Framework' approaches to planning end-of-life care with residents and their relatives. From 2008 to 2011 and with appropriate consent, data were collected by a mixture of interviews and participant observation with residents, relatives and staff. Appropriate ethics approvals were sought and given. Key emerging themes were diagnosis and awareness of dying in which there is no substitute for experience. Significant resource is needed to engage staff, residents and relatives/carers with the idea of advance care planning. Talking to residents and relatives about their feelings and wishes for care at the end of life remains especially difficult, but education and training in key skills and knowledge can engender confidence. Challenges include diagnosing and predicting dying trajectories. Advance care planning can reduce the distress from and number of inappropriate hospital admissions, but requires determination and consistent application of the approach. This can be very challenging in the face of staff rotation and the unpredictability both of the dying trajectory and the decision-making of some out of hours medical staff.


Colorectal Cancer Screening and State Health Insurance Mandates.
Colorectal cancer (CRC) is the third most deadly cancer in the USA. CRC screening is the most effective way to prevent CRC death, but compliance with recommended screenings is very low. In this study, we investigate whether CRC screening behavior changed under state mandated private insurance coverage of CRC screening in a sample of insured adults from the 1997 to 2008 Behavioral Risk Factor Surveillance Survey (BRFSS). We present difference-in-difference-in-differences (DDD) estimates that compare insured individuals age 51 to 64 to Medicare age-eligible individuals (ages 66 to 75) in mandate and non-mandate states over time. Our DDD estimates suggest endoscopic screening among men increased by 2 to 3 percentage points under mandated coverage among 51 to 64 year olds relative to their Medicare age-eligible counterparts. We find no clear evidence of changes in screening behavior among women. DD estimates suggest no evidence of a mandate effect on either type of CRC screening for men or women.


Validating the Role of Steroid in Analgesic Cocktail Preparation for Local Infiltration in Total Knee Arthroplasty: A Comparative Study.
Pain control after total knee arthroplasty (TKA) through local analgesic cocktail preparation has gained widespread popularity in recent times. Local steroids have potent anti-inflammatory effect leading to reduced postoperative swelling and pain which might increase the efficacy and duration of local infiltration analgesia. The aim is to evaluate whether the addition of local steroid to an injectable analgesic cocktail for periarticular infiltration leads to better pain control and knee range of motion (ROM) in the immediate postoperative period compared to patients who do not receive steroid in their cocktail. A prospective study was conducted in a group of 140 patients undergoing unilateral TKA between June 2017 and December 2017. All the patients in the study group received either periarticular infiltration with an analgesic cocktail (Group I, n = 70) or analgesic cocktail with 100 mg methylprednisolone (Group II, n = 70) for postoperative pain with ultrasound-guided adductor canal block (ACB). Patients were evaluated with visual analog scale (VAS) for pain at 8, 24, and 48 h postoperatively and ROM at 48 h after surgery. The SPSS 19.0 software (SPSS Inc., Chicago, IL, USA) was used for the statistical analysis. Student t-test has been used to find the pairwise significance. Group II had a statistically significant decrease in VAS scores at 8 h (P = 0.096), first postoperative day (P = 0.0001) and second postoperative day (P = 0.0001) as compared to Group I. However, there was no statistically significant difference seen with early ROM in both the groups at 48 h (P < 0.361). Patients who received steroid cocktail infiltration plus ACB had an improved and better postoperative analgesia in an early postoperative period of 24-48 h; however, there was no significant difference in clinical ROM and functional outcome when compared to the study group.


Superior mesenteric artery embolus.
We have presented a case of SMA embolization with early diagnosis and successful embolectomy. A high index of suspicion is necessary, since the relative paucity of early signs and symptoms often belies the gravity of the situation. Prompt angiography can corroborate the diagnosis and allow expeditious laparotomy. Although some authors have advocated nonoperative management of this problem, we believe a surgical approach offers the best chance for a successful resolution and for preventing devastating sequelae.


miRNAs in multiple myeloma--a survival relevant complex regulator of gene expression.
microRNAs regulate gene-expression in biological and pathophysiological processes, including multiple myeloma. Here we address i) What are the number and magnitude of changes in miRNA-expression between normal plasma cells and myeloma- or MGUS-samples, and the latter two? ii) What is the biological relevance and how does miRNA-expression impact on gene-expression? iii) Is there a prognostic significance, and what is its background? Ninety-two purified myeloma-, MGUS-, normal plasma cell- and myeloma cell line-samples were investigated using miChip-arrays interrogating 559 human miRNAs. Impact on gene-expression was assessed by Affymetrix DNA-microarrays in two cohorts of myeloma patients (n = 677); chromosomal aberrations were assessed by iFISH, survival for 592 patients undergoing up-front high-dose chemotherapy. Compared to normal plasma cells, 67/559 miRNAs (12%) with fold changes of 4.6 to -3.1 are differentially expressed in myeloma-, 20 (3.6%) in MGUS-samples, and three (0.5%) between MGUS and myeloma. Expression of miRNAs is associated with proliferation, chromosomal aberrations, tumor mass, and gene expression-based risk-scores. This holds true for target-gene signatures of regulated mRNAs. miRNA-expression confers prognostic significance for event-free and overall survival, as do respective target-gene signatures. The myeloma-miRNome confers a pattern of small changes of individual miRNAs impacting on gene-expression, biological functions, and survival.


Retzius-sparing Robotic-assisted Radical Prostatectomy Facilitates Early Continence Regardless of Neurovascular Bundle Sparing.
Retzius-sparing robotic-assisted radical prostatectomy (RARP) has had better results in early continence rate and comparable oncological safety compared to the retropubic approach. However, the role the neurovascular bundle (NVB) sparing plays in the rate of early continence after catheter removal remains unclear. In this study, we sought to compare the early continence rate between Retzius-sparing RARP and the retropubic approach RARP to assess whether NVB sparing affects the continence rate in patients with prostate cancer. This was a retrospective case series of 133 patients who underwent RARP from 2004 to 2017. 92 patients underwent retropubic RARP and 41 patents underwent Retzius-sparing RARP. All procedures were performed by a single surgical team in a single institution. Baseline patient characteristics were recorded and analyzed. Continence results and oncological outcomes were compared between the two groups. Continence outcome of Retzius-sparing RARP with NVB sparing was also analyzed. No differences in age, prostate size, pathology T stage, PSA, and NVB sparing were found between the two groups. The oncological results including surgical margin and biochemical recurrence rate at one year showed no difference between the two groups. With respect to immediate continence results, the Retzius-sparing group showed a better continence result compared to the retropubic approach (75.6% vs. 26.1 %, respectively, p<0.001) after catheter removal. However, there was no difference between the two groups after 6 months. Furthermore, no significant difference in immediate continence result was found in the Retzius-sparing group between patients with NVB sparing (75 %) and those without (75 % vs. 78%, respectively, p=1.00). Retzius-sparing RARP may provide a better immediate continent result compared to retropubic RARP. In Retzius-sparing RARP, NVB sparing did not enhance immediate continence after the operation.


Iron status of the preterm infant during the first year of life.
The iron status of 49 preterm infants (mean gestational age 33.1 weeks) was assessed serially during the 1st year of life. Haemoglobin concentration, serum ferritin, serum transferrin, serum iron, and transferrin saturation were measured on nine occasions in each infant. In 16 infants of gestational age 28-32 weeks the haemoglobin concentration was significantly lower at 3, 6, and 9 weeks when compared to 33 infants of gestational age 33-36 weeks. For all other measures of iron status there were no significant differences between these gestational age groups. For the entire group of 49 infants the mean haemoglobin concentration reached a nadir of 11.2 g/dl at 9 weeks. Mean serum iron and transferrin saturation reached peaks of 24 mumol/l and 65%, respectively, at 3 weeks. The mean serum ferritin remained over 100 micrograms/l until after 18 weeks. 13 infants (26%) had iron deficiency defined as either serum ferritin less than 10 micrograms/1 (n = 10) or transferrin saturation less than 10% (n = 5) or both (n = 3).


Pharmacogenetic study of methylenetetrahydrofolate reductase and thymidylate synthase in Japanese and assessment of ethnic and gender differences.
We investigated the four polymorphisms of the 5,10-methylenetetrahydrofolate reductase (MTHFR) and thymidylate synthase (TYMS) genes that are related to the pharmacologically active sites of methotrexate for the treatment of rheumatoid arthritis in 102 healthy Japanese adults and assessed the possibility of ethnic and gender differences. Polymorphisms of MTHFR C677T, A1298C, the two or three 28-bp tandem repeats in the TYMS 5'-untranslated regions (UTR), and the 6-bp deletion/insertion in the TYMS 3'-UTR were measured using polymerase chain reaction with restriction fragment length polymorphism method. Published data on allelic frequencies by ethnic group and gender were collected from Medline. Allelic frequencies in healthy Japanese adults were: MTHFR 677T allele 41%, MTHFR 1298C allele 22%, TYMS 5'-UTR 3R allele 84%, and TYMS 3'-UTR-6-bp allele 59%. Significant differences were found in the distribution of MTHFR C677T between black and Japanese populations, of TYMS 5'-UTR alleles between Caucasian or black and Japanese populations, and of TYMS 3'-UTR alleles between Caucasian and Japanese populations (p < 0.001). Moreover, a gender difference was found in TYMS 3'-UTR allelic frequency in Japanese (p = 0.015). Ethnic and gender variations in the distribution of these allelic frequencies may associate with the difference in the effects of methotrexate in rheumatoid arthritis patients.


Standing position improves arm and hand performance on un-affected side in hemiplegic patients.
The main objective of this study was to compare the hand and finger performance of stroke patients in standing and sitting positions. The study subjects were 11 males and 3 females with history of stroke (age, 68.6 ± 6.3 years, mean ± SD). Inclusion criteria were right-handedness before stroke, right hemiparesis due to left hemisphere lesion induced by stroke, at least 4 months between stroke and study enrollment, and ability to stand for more than 10 minutes. Tests of dexterity (peg board test), attention, unilateral spatial neglect, and cognition were conducted in comfortable sitting and standing positions. Seven subjects started in standing position, and the other seven subjects were tested first in sitting position. Tests in the first position were performed on one day, and repeated one week later but performed in a different position. The mean performance time on the peg board test in standing position was significantly faster than in sitting position (p=0.022). However, the results of the Trail making test-part A, line cancellation test, line bisection and Mini Mental State conducted in standing position were similar to those of sitting position. There were no differences between the first and second trial tests. Our results showed that standing position improved the functional performance of hand and arm on the un-affected side in stroke patients, but had no effects on consistent attention, unilateral spatial neglect, or cognition.


Inequality in the Distribution of Air Pollution Attributable Mortality Within Canadian Cities.
Recent studies have identified inequality in the distribution of air pollution attributable health impacts, but to our knowledge this has not been examined in Canadian cities. We evaluated the extent and sources of inequality in air pollution attributable mortality at the census tract (CT) level in seven of Canada's largest cities. We first regressed fine particulate matter (PM2.5) and nitrogen dioxide (NO2) attributable mortality against the neighborhood (CT) level prevalence of age 65 and older, low income, low educational attainment, and identification as an Indigenous (First Nations, Métis, Inuit) or Black person, accounting for spatial autocorrelation. We next examined the distribution of baseline mortality rates, PM2.5 and NO2 concentrations, and attributable mortality by neighborhood (CT) level prevalence of these characteristics, calculating the concentration index, Atkinson index, and Gini coefficient. Finally, we conducted a counterfactual analysis of the impact of reducing baseline mortality rates and air pollution concentrations on inequality in air pollution attributable mortality. Regression results indicated that CTs with a higher prevalence of low income and Indigenous identity had significantly higher air pollution attributable mortality. Concentration index, Atkinson index, and Gini coefficient values revealed different degrees of inequality among the cities. Counterfactual analysis indicated that inequality in air pollution attributable mortality tended to be driven more by baseline mortality inequalities than exposure inequalities. Reducing inequality in air pollution attributable mortality requires reducing disparities in both baseline mortality and air pollution exposure.


Characterization of monoclonal antibodies for identification of Borrelia japonica, isolates from Ixodes ovatus.
Monoclonal antibodies for identification of Borrelia japonica isolated from tick, Ixodes ovatus and long-tailed shrew, Sorex unguiculatus in Japan and Borrelia related to Lyme disease (Borrelia burgdorferi sensu lato) were prepared and characterized. All isolates belonging to B. japonica and isolates from I. dentatus and cottontail rabbit in North America reacted with MAb O1441b against flagellin which was prepared from immunized mice with strain HO14, type strain of B. japonica, but isolates from I. persulcatus, patient, and wood mouse, Apodemus speciosus ainu, in Japan, and isolates belonging to B. burgdorferi, B. garinii and B. afzelii from North America and Europe did not. Strains used in this study reacted with MAb P62 against common antigen which was prepared from immunized mice with strain NT24 isolated from I. persulcatus in Japan, but B. japonica did not. These MAbs are useful for identification and differentiation of B. japonica and B. burgdorferi sensu lato in Japan.


CD103+ tumor-infiltrating lymphocytes predict favorable prognosis in patients with esophageal squamous cell carcinoma.
As an indispensable factor in preventing the recirculation of tissue lymphocytes to the lymphatic and blood systems, the integrin CD103 has enabled the characterization of lymphocyte populations in non-lymphoid tissues and organs. However, the expression, distribution, and clinical significance of CD103+ tumor-infiltrating lymphocytes (TILs) in esophageal squamous cell carcinoma (ESCC) remain unclear. In the present study, we included tumor and adjacent non-tumor tissue specimens from 198 patients with ESCC who had undergone surgical resection. Immunohistochemistry and immunofluorescence were used to detect CD103+ TIL distribution, as well as the co-expression of CD103 and T cell markers and functional molecules. Kaplan-Meier analysis and the Cox proportional hazards model were used to estimate the prognostic value of CD103+ TILs. The results showed that CD103+ TILs were predominantly located in adjacent non-tumor tissues compared with tumor tissues (P < 0.0001). Immunofluorescence double staining revealed that CD8+ T cells, but not CD4+ T cells, comprised the majority of CD103-expressing cells. Most of these CD103-expressing cells co-expressed CTLA-4 and granzyme B rather than the exhaustion marker PD-1. High density of intratumoral CD103+ TIL is associated with longer overall survival (OS) and disease-free survival (DFS) in both the internal (OS, P = 0.0004 and DFS, P = 0.0002) and external (OS, P = 0.038 and DFS, P = 0.12) cohorts. Multivariate Cox analysis showed the density of CD103+ TILs was an independent positive prognostic factor for OS (hazards ratio [HR] = 0.406; P = 0.0003 in the internal cohort; HR = 0.328, P = 0.01, in the external cohort) and DFS (HR = 0.385; P = 0.0002 in the internal cohort; HR = 0.270, P = 0.003, in the external cohort). Our findings indicate that CD103+ TILs might play an important role in the tumor microenvironment, and intratumoral CD103+ TILs could serve as a promising prognostic marker in ESCC.


Stroke: A road map for subacute management.
Time is of the essence when a patient has signs and symptoms suggestive of a stroke or TIA. What should your initial approach and diagnostic work-up be?


Uric acid inhibits renal proximal tubule cell proliferation via at least two signaling pathways involving PKC, MAPK, cPLA2, and NF-kappaB.
The accumulation of uric acid, an end-product of purine metabolism, is responsible for the many deleterious effects observed in gouty arthritis, including renal injury. Here, we present evidence that under conditions of hyperuricemia (>10(-4) M uric acid) [(3)H]thymidine incorporation into primary renal proximal tubule cells (PTCs) is inhibited, and we delineate the signaling pathways involved. Elevated uric acid was observed to stimulate MAPK phosphorylation. The uric acid induced p38 MAPK phosphorylation was also blocked by H-7 (a PKC inhibitor), indicating that p38 MAPK was a downstream target of PKC. Evidence that cytoplasmic phospholipase A(2) (cPLA(2)) was involved further downstream included 1) the stimulatory effect of uric acid on [(3)H]-labeled arachidonic acid (AA) release; 2) the stimulation of AA release in response to uric acid was blocked by the PKC inhibitor H-7 as well as by the p38 MAPK inhibitor SB 203580; and 3) the uric acid-induced inhibition of [(3)H]thymidine incorporation was prevented by SB 203580, as well as by the cPLA(2) inhibitor arachidonyl trifluoromethyl ketone, and mepacrine (another PLA(2) inhibitor). Evidence of a uric acid-induced activation of NF-kappaB as well as PLA(2) was obtained. Moreover the uric acid-induced inhibition of [(3)H]thymidine incorporation was also blocked by two NF-kappaB inhibitors, pyrrolidine dithiocarbamate and SN 50. However, SN 50 did not block the uric acid induced [(3)H]AA release. Thus the inhibition of [(3)H]thymidine incorporation caused by uric acid can be explained by two distinct mechanisms, the activation of NF-kappaB as well as the activation of PLA(2).


Do Cerclage Cables Delay the Time to Bone Union in Patients with an Unstable Humeral Shaft Fracture Treated with Intramedullary Nails?
To evaluate the time to bone union after open reduction and internal fixation with cerclage cables followed by intramedullary nailing (IMN) for unstable humeral shaft fractures. Patients with a humeral shaft fracture treated by IMN were enrolled. One group of patients was treated via open reduction and internal fixation with cables followed by IMN (cable group; n=32), while the other group was treated with a conventional closed IMN (non-cable group; n=64). The length of time to bone union and functional scores [Disabilities of the Arm, Shoulder and Hand (DASH) and University of California, Los Angeles (UCLA) scores] were measured for all patients. No significant differences were found in terms of age, gender, injury type, or smoking history between the two groups, except for the type of fracture. The cable group had significantly more complex types of fracture than the non-cable group (p<0.001). The mean time to bone union was 3.9 months in the cable group, while in the non-cable group, it was 4.4 months (p=0.041). The incidence of postoperative complications, such as non-union, delayed union, and radial nerve palsy, was similar between the two groups (p>0.05). No differences were identified in terms of DASH and UCLA scores (28.8 and 32.1 in the cable group and 26.4 and 32.6 in the non-cable group, respectively; p=0.335 and 0.264). In unstable humeral shaft fractures treated by IMN, open reduction and internal fixation with additional cerclage cables do not delay the length of time to bone union or increase the rate of other complications.


Does oral ciprofloxacin affect the structure of thoracic aorta in adult and senile male albino rats? A clue to fluoroquinolones-induced risk of aortic dissection.
In this study, the effect of oral ciprofloxacin on the structure of the thoracic aorta in rats was investigated. Twenty four male albino rats were divided into 4 groups (6 rats/group): group I (adult control), group II (adult rats treated with ciprofloxacin), group III (senile control), and group IV (senile rats treated with ciprofloxacin). Rats in groups II and IV received ciprofloxacin via oral gavage in a daily dose of 3.5 mg/kg/d for 14 days, while control rats received equivalent amount of distilled water used to dissolve the drug. After 2 weeks, all rats were sacrificed, thoracic aortae were dissected, and half of the specimens were processed for paraffin sections and examined by light microscopy. The other half of the specimens were prepared for scanning electron microscopy. Sections from rats treated with ciprofloxacin showed evident damaging effect on aortic wall particularly in (group IV). Aortic intima showed, focal desquamation of the lining epithelium. Tunica media exhibited loss of the normal concentric arrangement and degeneration of the smooth muscle cells. Immune staining for alpha smooth muscle actin showed muscle damage. Interestingly, some sections in (group IV) showed out-pouch (aneurysm like) of the aortic wall. There was dense collagen fibers deposition. Scanning electron microscopic observations of (group IV) revealed uneven intima, adherent blood cells and fibrin filaments to damaged intima, and out-pouch formation. It was concluded that oral ciprofloxacin caused deleterious structural changes in the thoracic aortic wall of rats explaining clinical observations of fluoroquinolones induced risk of aortic dissection and aneurysm.


Investigation of a sugar N-formyltransferase from the plant pathogen Pantoea ananatis.
Pantoea ananatis is a Gram-negative bacterium first recognized in 1928 as the causative agent of pineapple rot in the Philippines. Since then various strains of the organism have been implicated in the devastation of agriculturally important crops. Some strains, however, have been shown to function as non-pathogenic plant growth promoting organisms. To date, the factors that determine pathogenicity or lack thereof between the various strains are not well understood. All P. ananatis strains contain lipopolysaccharides, which differ with respect to the identities of their associated sugars. Given our research interest on the presence of the unusual sugar, 4-formamido-4,6-dideoxy-d-glucose, found on the lipopolysaccharides of Campylobacter jejuni and Francisella tularensis, we were curious as to whether other bacteria have the appropriate biosynthetic machinery to produce these unique carbohydrates. Four enzymes are typically required for their biosynthesis: a thymidylyltransferase, a 4,6-dehydratase, an aminotransferase, and an N-formyltransferase. Here, we report that the gene SAMN03097714_1080 from the P. ananatis strain NFR11 does, indeed, encode for an N-formyltransferase, hereafter referred to as PA1080c. Our kinetic analysis demonstrates that PA1080c displays classical Michaelis-Menten kinetics with dTDP-4-amino-4,6-dideoxy-d-glucose as the substrate and N10 -formyltetrahydrofolate as the carbon source. In addition, the X-ray structure of PA1080c, determined to 1.7 Å resolution, shows that the enzyme adopts the molecular architecture observed for other sugar N-formyltransferases. Analysis of the P. ananatis NFR11 genome suggests that the three other enzymes necessary for N-formylated sugar biosynthesis are also present. Intriguingly, those strains of P. ananatis that are non-pathogenic apparently do not contain these genes.


Leptin and uric acid as predictors of metabolic syndrome in jordanian adults.
Metabolic syndrome (MetS) is a set of interrelated metabolic risk factors that increase the risk of cardiovascular morbidity and mortality. Studies regarding the specificity and sensitivity of serum levels of leptin and uric acid as predictors of MetS are limited. The aim of this study was to evaluate the serum levels of leptin and uric acid in terms of their specificity and sensitivity as predictors of MetS in the studied Jordanian group. In this cross sectional study, 630 adult subjects (308 men and 322 women) were recruited from the King Hussein Medical Center (Amman, Jordan). The diagnosis of MetS was made according to the 2005 International Diabetes Federation criteria. Receiver operating characteristic curves were used to determine the efficacy of serum levels of leptin and uric acid as predictors of MetS in the studied Jordanian group. Study results showed that for identification of subjects with MetS risk, area under the curve (AUC) for leptin was 0.721 and 0.683 in men and women, respectively. Serum uric acid levels in men showed no significant association with any MetS risk factors and no significant AUC, while uric acid AUC was 0.706 in women. Serum leptin levels can be useful biomarkers for evaluation of the risk of MetS independent of baseline obesity in both men and women. On the other hand, serum uric acid levels predicted the risk of MetS only in women.


Subfunctionalization of duplicate mitf genes associated with differential degeneration of alternative exons in fish.
The microphthalmia-associated transcription factor (MITF) exists in at least four isoforms. These are generated in higher vertebrates using alternative 5' exons and promoters from a single gene. Two separate genes (mitf-m and mitf-b), however, are present in different teleost fish species including the poeciliid Xiphophorus, the pufferfishes Fugu rubripes and Tetraodon nigroviridis, and the zebrafish Danio rerio. Fish proteins MITF-m and MITF-b correspond at both the structural and the expression levels to one particular bird/mammalian MITF isoform. In the teleost lineage subfunctionalization of mitf genes after duplication at least 100 million years ago is associated with the degeneration of alternative exons and, probably, regulatory elements and promoters. For example, a remnant of the first exon specific for MITF-m is detected within the pufferfish gene encoding MITF-b. Retracing the evolutionary history of mitf genes in vertebrates uncovered the differential recruitment of new introns specific for either the teleost or the bird/mammalian lineage.


Anion Sensing by Fluorescent Expanded Calixpyrroles.
Expanded calixpyrrole-type macrocycles, calix[2]benzo[4]pyrroles, bearing fluorescent moieties attached via conjugated vinyl spacers, have been synthesized from the corresponding formyl derivatives through Knoevenagel condensation. The anion-binding properties of the resulting fluorescent macrocycles have been studied by means of NMR, UV/Vis, and fluorescence spectroscopies. Our main focus has been on dicarboxylates matching the size of the binding cavity of the calix[2]benzo[4]pyrrole skeleton. The observed anion-binding properties were compared with those of the regular calix[4]pyrroles bearing identical fluorophores. Surprisingly, the parent calix[4]pyrroles appear to be equally efficient, if not more so, for sensing anions such as dicarboxylates. Affinity constants determined for various anions and dianions show the sensors S1-S5 to be highly cross-reactive. The cross-reactivity of the sensors was utilized in a microchip-based array, which showed perfect (100 %) classification of 18 analytes utilizing only five sensors. Finally, the same array was used to quantitatively analyze dicarboxylates such as oxalate and malonate. The data from the array were subjected to linear regression, allowing the determination of various concentrations of dianions with low error (<2 %).


Risk factors associated with hemorrhagic cerebrovascular accident: A cross-sectional study in patients from a hospital in Peru.
In Peru, cardiovascular accidents (CVA) cause around 15% of premature death, with an increase in CVA due to the prevalence of risk factors for CVA in the Peruvian population. Hemorrhagic CVA presents higher mortality compared to ischemic. This research aimed to identify the risk factors associated with hemorrhagic CVA. We carried out a retrospective cross-sectional study using the medical records of patients with a diagnosis of CVA treated at the Regional Hospital of Ica during the years 2018 and 2019. Independent variables included age, sex, type 2 diabetes, dyslipidemia, hypertension, smoking, obesity, and intracranial carotid artery calcification. To identify factors associated with an increased probability for hemorrhagic CVA compared to ischemic CVA, a generalized linear model with logit link and binomial family, obtaining the odds ratio (OR) and its 95% confidence interval (CI). we evaluated the data from 132 patients. Of them, 46 (34.85%) had hemorrhagic CVA. Only systolic blood pressure (OR: 1.04; 95% CI: 1.02-1.06) and hypertension (OR: 0.29; 95% CI: 0.10-0.89) were significantly associated with hemorrhagic CVA compared to ischemic CVA. Hypertension is associated with hemorrhagic CVA compared to ischemic CVA. These results are consistent with the literature.


Loss of local capture of the pulmonary vein myocardium after antral isolation: prevalence and clinical significance.
Capture of the myocardial sleeves of the pulmonary veins (PV) during PV pacing is mandatory for assessing exit block after PV isolation (PVI). However, previous studies reported that a significant proportion of PVs failed to demonstrate local capture after PVI. We designed this study to evaluate the prevalence and the clinical significance of loss of PV capture after PVI. Thirty patients (14 redo) undergoing antral PVI were included. Before and after PVI, local PV capture was assessed during circumferential pacing (10 mA/2 milliseconds) with a circular multipolar catheter (CMC), using EGM analysis from each dipole of the CMC and from the ablation catheter placed in ipsilateral PV. Pacing output was varied to optimize identification of sleeve capture. All PVs demonstrated sleeve capture before PVI, but only 81% and 40% after first time and redo PVI, respectively (P < 0.001 vs. before PVI). In multivariate analysis, absence of spontaneous PV depolarizations after PVI and previous PVI procedures were associated with less PV sleeve capture after PVI (40% sleeve capture, P < 0.001 for both). Loss of PV local capture by design was coincident with the development of PV entrance block and importantly predicted absence of acute reconnection during adenosine challenge with 96% positive predictive value (23% negative predictive value). Loss of PV local capture is common after antral PVI resulting in entrance block, and may be used as a specific alternate endpoint for PV electrical isolation. Additionally, loss of PV local capture may identify PVs at very low risk of acute reconnection during adenosine challenge.


Albendazole Induced Recurrent Acute Toxic Hepatitis: A Case Report.
Drug induced acute toxic hepatitis can be idiosyncratic. Albendazole, a widely used broad spectrum antiparasitic drug is generally accepted as a safe drug. It may cause asymptomatic transient liver enzyme abnormalities but acute toxic hepatitis is very rare. Case Report : Herein, we present the case of 47 year old woman with recurrent acute toxic hepatitis after a single intake of albendazole in 2010 and 2014. The patient was presented with symptoms and findings of anorexia, vomiting and jaundice. For diagnosis, other acute hepatitis etiologies were excluded. Roussel Uclaf Causality Assessment Method (RUCAM) score was calculated and found to be 10, which meant highly probable drug hepatotoxicity. Within 2 months, all pathological findings came to normal. There are a few reported cases of albendazole induced toxic hepatitis, but at adults, there is no known recurrent acute toxic hepatitis due to albendazole at this certainty according to RUCAM score. Physicians should be aware of this rare and potentially fatal adverse effect of albendazole.


Acute myelomonocytic leukemia with dysplastic bone marrow eosinophils showing t(5;17)(q13;q11) and a secondary chromosomal aberration, inv(16)(p13q22).
inv(16)(p13q22) is associated with de novo acute myelomonocytic leukemia with dysplastic bone marrow eosinophils (AMML Eo), which has a relatively favorable clinical course with a longer remission duration and better survival prospects. On the other hand, t(5; 17)(q13;q11), although relatively rare, has been reported to be a component of complex chromosomal abnormalities in myelodysplastic syndromes and secondary acute myeloid leukemia (AML). We treated a 29-year-old woman with the first reported case of de novo AMML Eo with inv(16)(p13q22) in addition to t(5; 17)(q13;q11). Although she attained complete remission (CR) immediately after induction therapy, the disease recurred 1 year after the completion of consolidation therapies. She underwent HLA-matched unrelated allogeneic bone marrow transplantation (UBMT), together with a myeloablative conditioning regimen, after achieving a second CR and has survived without a recurrence for more than 24 months since UBMT. In general, certain secondary chromosomal abnormalities are associated with the phenotype of the disease, which retains its essential biologic characteristics established by the primary abnormality. Accordingly, the primary nature of the leukemic cells in this case differs from the findings for core-binding factor AML with inv(16)(p13q22). We believe this report is the first of de novo AMML Eo with t(5; 17)(q13;q11) showing as a secondary chromosomal aberration with inv(16)(p13q22).


Electrochromism in Isoreticular Metal-Organic Framework Thin Films with Record High Coloration Efficiency.
The power of isoreticular chemistry has been widely exploited to engineer metal-organic frameworks (MOFs) with fascinating molecular sieving and storage properties but is underexplored for designing MOFs with tunable optoelectronic properties. Herein, three dipyrazole-terminated XDIs (X = PM (pyromellitic), N (naphthalene), or P (perylene); DI = diimide) with different lengths and electronic properties are prepared and employed as linkers for the construction of an isoreticular series of Zn-XDI MOFs with distinct electrochromism. The MOFs are grown on fluorine-doped tin oxide (FTO) as high-quality crystalline thin films and characterized by X-ray diffraction (XRD) and scanning electron microscopy (SEM). Due to the constituting electronically isolated XDI linkers, each member of the isoreticular thin film series exhibits two reversible one-electron redox events, each at a distinct electrochemical potential. The orientation of the MOFs as thin films as well as their isoreticular nature results in identical cation-coupled electron hopping transport rates in all three materials, as demonstrated by comparable apparent electron diffusion coefficients, Deapp. Upon electrochemical reduction to either the [XDI]•- or [XDI]2- state, each MOF undergoes characteristic changes in its optical properties as a function of linker length and redox state of the linker. Operando spectroelectrochemistry measurements reveal that Zn-PDI@FTO (PDI = perylene diimide) thin films exhibit a record high coloration efficiency of 941 cm2 C-1 at 746 nm, which is attributed to the maximized Faradaic transformations at each electronically isolated PDI unit. The electrochromic response of the thin film is retained to more than 99% over 100 reduction-oxidation cycles, demonstrating the applicability of the presented materials.


Diverting attention suppresses human amygdala responses to faces.
Recent neuroimaging studies disagree as to whether the processing of emotion-laden visual stimuli is dependent upon the availability of attentional resources or entirely capacity-free. Two main factors have been proposed to be responsible for the discrepancies: the differences in the perceptual attentional demands of the tasks used to divert attentional resources from emotional stimuli and the spatial location of the affective stimuli in the visual field. To date, no neuroimaging report addressed these two issues in the same set of subjects. Therefore, the aim of the study was to investigate the effects of high and low attentional load as well as different stimulus locations on face processing in the amygdala using functional magnetic resonance imaging to provide further evidence for one of the two opposing theories. We were able for the first time to directly test the interaction of attentional load and spatial location. The results revealed a strong attenuation of amygdala activity when the attentional load was high. The eccentricity of the emotional stimuli did not affect responses in the amygdala and no interaction effect between attentional load and spatial location was found. We conclude that the processing of emotional stimuli in the amygdala is strongly dependent on the availability of attentional resources without a preferred processing of stimuli presented in the periphery and provide firm evidence for the concept of the attentional load theory of emotional processing in the amygdala.


Scratch resistance of polycarbonate containing ZnO nanoparticles: effects of sliding direction.
Abrasive wear resistance of injection molded polycarbonate (PC) and polycarbonate + zinc oxide nanocomposites containing 0.5 wt% ZnO nanoparticles was determined as a function of the sliding direction with respect to injection flow. First we have performed single scratch testing under progressively increasing the load applied. Then sliding wear testing consisting of 15 successive scratches along the same groove was performed. Neat PC shows anisotropic behavior, with instantaneous penetration depth more than 50% higher in the direction parallel to the melt injection flow than in the transverse direction. Viscoelastic recovery after scratching of neat PC is also higher in the longitudinal than in the transverse direction, hence final residual depth values are similar in both directions. The addition of ZnO nanoparticles reduces the instantaneous penetration depth in the longitudinal direction but lowers viscoelastic recovery so that the residual depth is large. In the transverse direction, the scratch resistance is similar for neat PC and the nanocomposite. Dynamic mechanical analysis, SEM/FIB results and wear mechanisms from SEM observations of wear scars are discussed. Below the glass transition region the nanocomposite has distinctly higher storage modulus E' than PC--a clear reinforcement effect. However, the addition of ZnO nanoparticles to the polymer increases the material brittleness at room temperature by a factor of 2.72.


Relating movement recurrence and expressive timing patterns in music performances.
In this study the movement patterns of ten expert musicians are quantitatively related to expressive timing patterns and the music structure during performances. The hypothesis is that ancillary gestures recurrently employed are closely related to expressive intentions, and that the expressive content imposed in key musical passages is thus reflected in the patterns of gestural recurrence. A movement and an audio analysis of 30 clarinet performances of a Brahms' excerpt are compared. Results show direct correlations between the recurrence pattern of clarinetists' ancillary movements and expressive bar duration manipulations employed by them, associated with melodic phrasing and harmonic transitions.


PLGA/BGP/Nef porous composite restrains osteoclasts by inhibiting the NF-κB pathway, enhances IGF-1-mediated osteogenic differentiation and promotes bone regeneration.
Novel bone substitutes are urgently needed in experimental research and clinical orthopaedic applications. There are many traditional Chinese medicines that have effects on bone repair. However, application of natural medicines in traditional Chinese medicine to bone tissue engineering and its mechanism were rarely reported. In this study, the osteogenic ability of bioactive glass particles (BGPs) and the osteogenic and osteoclastic ability of neferine (Nef) were fused into PLGA-based bone tissue engineering materials for bone regeneration. BGPs were prepared by spray drying and calcination. Particles and Nef were then mixed with PLGA solution to prepare porous composites by the phase conversion method. Here we showed that Nef inhibited proliferation and enhanced ALP activity of MC3T3-E1 cells in a dose- and time-dependent manner. And the composites containing Nef could also inhibit RANKL-induced osteoclast formation (p < 0.05). Mechanistically, the PLGA/BGP/Nef composite downregulated the expression of NFATC1 by inhibiting the NF-κB pathway to restrain osteoclasts. In the other hands, PLGA/BGP/Nef composite was first demonstrated to effectively activate the IGF-1R/PI3K/AKT/mTOR pathway to enhance IGF-1-mediated osteogenic differentiation. The results of animal experiments show that the material can effectively promote the formation and maturation of new bone in the skull defect site. The PLGA/BGP/Nef porous composite can restrain osteoclasts by inhibiting the NF-κB pathway, enhance IGF-1-mediated osteogenic differentiation and promotes bone regeneration, and has the potential for clinical application.


Mitosis-dependent protein expression in neuroblastoma cell line N1E-115.
Systematic work on differential protein expression in mitosis is limited, and we therefore used neuroblastoma cells (N1E-115) incubated with either colcemid or nocodazole to arrest mitosis. Proteins were identified by MALDI-TOF/TOF and nano-LC-ESI-MS/MS with subsequent quantification of spot volumes with specific software. Immunoblotting was used for verification of selected proteins. Levels of 10 individual proteins were increased and levels of 6 proteins were decreased concordantly by both treatments. These proteins were constituents of heat shock and chaperone, cytoskeleton, proteasomal, heterochromatin, and DNA replication signaling as well as housekeeping and metabolic systems. Identification of mitosis-dependent proteins is of importance for the interpretation of previous work and for designing future experiments.


Reducing contraband in a psychiatric hospital through the use of a metal detector.
A private, free-standing, nonprofit psychiatric hospital installed a metal detector and a screening procedure to prevent weapons and other proscribed items from being carried into the hospital by visitors. A wide variety of metal objects was discovered, including knives, ammunition, and hand tools. Visitors did not object to the procedure. As an unexpected benefit of the screening, unauthorized smoking in the hospital decreased.


Generalized Lenard chains, separation of variables, and superintegrability.
We show that the notion of generalized Lenard chains naturally allows formulation of the theory of multiseparable and superintegrable systems in the context of bi-Hamiltonian geometry. We prove that the existence of generalized Lenard chains generated by a Hamiltonian function defined on a four-dimensional ωN manifold guarantees the separation of variables. As an application, we construct such chains for the Hénon-Heiles systems and for the classical Smorodinsky-Winternitz systems. New bi-Hamiltonian structures for the Kepler potential are found.


The Psychometric Properties in the Chinese Version of the Reasons for Living Inventory and the Relationship with Suicidal Behaviors Among Psychiatric Patients in Taiwan.
This study examines the reliability, factor structure, convergent, and construct validities of the Mandarin Chinese version of the Reasons For Living Inventory (RFL) among Taiwanese psychiatric patients. Demographical characteristics of patients who hold these adaptive cognitions and differences on the level of endorsement between suicidal and non-suicidal individuals were also investigated. All adult patients that had visited the psychiatric ambulatory clinic or had been admitted to the psychiatric ward in a general hospital in Taiwan over a 3-month period were consecutively invited to complete an inventory that included background information, the Mandarin Chinese versions of the RFL, the Suicidal Behaviors Questionnaire-Revised (SBQ-R), and the Beck Hopeless Scale (BHS). Of the 254 respondents aged 19 to 65 years, 47.2% had suicidal ideations or attempts within the past year. The original six-factor structure of the American version was confirmed to be acceptable. The Cronbach α was 0.964.Total scores on RFL were inversely and significantly correlated with that from BHS. Multivariate analysis with demographic data and items from SBQ-R revealed that higher scores on the RFL have been associated with married, have children or religious beliefs, fewer past and current suicidal ideations and attempts, fewer histories of suicidal threats, and a less self-reported likelihood of future suicide in our sample. The Mandarin version of the RFL inventory showed acceptable psychometric properties and could distinguish suicidal patients from non-suicidal ones.


Ureteral injuries in gynaecologic oncology surgery procedures.
This study presents ureteral injuries in gynecologic oncology surgical procedures performed at the Department of Obstetrics and Gynecology in Novi Sad, in the period from 1991 to 2001. Intraoperative ureteral injuries were recorded in 4 (1%) patients, including: partial ureteral dissection, bilateral ureteral ligation and complete ureteral dissection bellow the lower pole. In 3 (75%) cases, injuries were recognized immediately, and surgical reparation was performed. The patient with bilateral ureteral ligation presented with increased creatinine levels, anuria and development of hydronephrosis detected by ultrasonography 24 h later. Leading reasons for operative ureteral injuries include inadequate experience of surgeons, carelessness during surgery, wrong indication and wrong approach to ureter. Preparation of ureter with minimal trauma, precise localization and visualization of the complete ureteral length, as well as preservation of its vascular network, are of utmost importance in prevention of injuries.


Nanocellulose-Based Sustainable Dyeing of Cotton Textiles with Minimized Water Pollution.
This research aims at minimizing environmental pollution by effluents discharged from current textile dyeing processes. The reduction of pollution is approached with a nanofibrillated cellulose (NFC) dyeing method. In the commonly used exhaust reactive dye bath cotton dyeing process, water effluents are contaminated with unreacted dyes and dyeing formulation auxiliaries amid the consumption of 20 weight units of water per weight unit of colored textile products. It was recently demonstrated that using reactive dye-colored NFC hydrogels-an aqueous dispersion of the NFC pigment-a sustainable dye carrier-results in 6-fold reduction in consumption of water and auxiliaries. Here, we report further developments of this technology. Cotton fabrics and NFC hydrogels inherit a fraction of soluble polysugars that react and conjugate with the reactive dyes. These soluble dye-conjugated polysugars are released into the wastewater, thus resulting in water pollution and also in reduced efficiency of the dyeing process. We demonstrate here that post-treatment of NFC-colored cotton textiles with polycarboxylic acid secures permanent chemical grafting of the soluble dye-labeled polysugars and forms chemical cross-links with the NFC fibers on the cotton fabric via the esterification reaction. This combination leads to the improvement of dye fixation by 30% and reduces the dye discharge in the washing stage by 60%. This enhancement is approached without compromising the stiffness and breathability of the fabrics. The advanced textile method is tested for a series of reactive dyes covering the entire visual spectrum range.


Photoheterotrophic growth of Agmenellum quadruplicatum PR-6.
The unicellular cyanobacterium Agmenellum quadruplicatum PR-6 grows in the presence of light on agar containing 10 microM 3-(3,4 dichlorophenyl)-1,1-dimethylurea and 1 to 30 mM glycerol. A derivative strain, PR-6G2, was tolerant of 100 mM glycerol. Photoheterotrophic growth conditions had little effect on transformation competence but did decrease the viability of single cells plated onto agar, particularly cells of the parent strain.


Synthetic Biology between Self-Regulation and Public Discourse: Ethical Issues and the Many Roles of the Ethicist.
This article discusses the roles of ethicists in the governance of synthetic biology. I am particularly concerned with the idea of self-regulation of bioscience and its relationship to public discourse about ethical issues in bioscience. I will look at the role of philosophical ethicists at different levels and loci, from the "embedded ethicist" in the laboratory or research project, to ethicists' impact on policy and public discourse. In a democratic society, the development of governance frameworks for emerging technologies, such as synthetic biology, needs to be guided by a well-informed public discourse. In the case of synthetic biology, the public discourse has to go further than merely considering technical issues of biosafety and biosecurity, or risk management, to consider more philosophical issues concerning the meaning and value of "life" between the natural and the synthetic. I argue that ethicists have moral expertise to bring to the public arena, which consists not only in guiding the debate but also in evaluating arguments and moral positions and making normative judgments. When ethicists make normative claims or moral judgments, they must be transparent about their theoretical positions and basic moral standpoints.


Improved expansion of human bone marrow-derived mesenchymal stem cells in microcarrier-based suspension culture.
Human bone marrow-derived mesenchymal stem cells (hBM-MSCs) have potential clinical utility in the treatment of a multitude of ailments and diseases, due to their relative ease of isolation from patients and their capacity to form many cell types. However, hBM-MSCs are sparse, and can only be isolated in very small quantities, thereby hindering the development of clinical therapies. The use of microcarrier-based stirred suspension bioreactors to expand stem cell populations offers an approach to overcome this problem. Starting with standard culture protocols commonly reported in the literature, we have successfully developed new protocols that allow for improved expansion of hBM-MSCs in stirred suspension bioreactors using CultiSpher-S microcarriers. Cell attachment was facilitated by using intermittent bioreactor agitation, removing fetal bovine serum, modifying the stirring speed and manipulating the medium pH. By manipulating these parameters, we enhanced the cell attachment efficiency in the first 8 h post-inoculation from 18% (standard protocol) to 72% (improved protocol). Following microcarrier attachment, agitation rate was found to impact cell growth kinetics, whereas feeding had no significant effect. By serially subculturing hBM-MSCs using the new suspension bioreactor protocols, we managed to obtain cell fold increases of 10³ within 30 days, which was superior to the 200-fold increase obtained using the standard protocol. The cells were found to retain their defining characteristics after several passages in suspension. This new bioprocess represents a more efficient approach for generating large numbers of hBM-MSCs in culture, which in turn should facilitate the development of new stem cell-based therapies.


The influence of preoperative deformity on valgus correction angle: an analysis of 503 total knee arthroplasties.
We prospectively studied variations in valgus correction angle (VCA) and the influence of preoperative limb deformity on VCA in 503 consecutive total knee arthroplasties done in 393 patients. The percentage of limbs that had VCA values less than 5° was 10.9%, and that with VCA values greater than 7° was 44.9%. The percentage of limbs with VCA greater than 7° was significantly more in varus knees, and that with VCA less than 5° was significantly more in valgus knees; preoperative deformity showed a significant correlation with VCA. Choosing a fixed-routine VCA of 5° to 7° may cause an unacceptable planning error that may be minimized by individualizing VCA or using computer navigation.


[Determination of the trace levels of urinary fibrinopeptides by high-performance capillary electrophoresis].
To establish a high-performance capillary electrophoresis (HPCE)-based method for detection of trace amount of urinary fibrinopeptide A and B (FPA and FPB, respectively) as the specific molecular markers of thrombus formation in vivo. The HPCE system consisted of a 25 cm x 50 microm (inner diameter) coated capillary column, 0.1 mol/L phosphoric acid buffer (pH 2.5) and a UV-detector (wavelength at 190 nm). To improve the sensitivity and reproducibility, solid-phase extraction of FPA and FPB in the urine was performed using a Sep-pak C18 column, with a synthetical fibrinopeptide B-Tyr (FPB-Tyr) as the internal standard. With this HPCE method, optimal separations of FPA, FPB and FPB-Tyr was achieved within 16 min, with the migration time of 7.28 min, 14.31 min and 15.22 min, respectively. The adjusted peak area ratios of FPA or FPB and the internal standard showed good linearity with the corresponding concentrations of FPA or FPB spiked in the urine(R>0.99). Under the above chromatography conditions, the minimum detection concentration of FPA and FPB in untreated urine was 30 microg/L and 40 microg/L, respectively, and the assay precision and recovery of FPA and FPB were acceptable. The method we established is reliable and specific for separation and identification of fibrinopeptides and other bioactive peptides.


Subarachnoid hemorrhage in the subacute stage: elevated apparent diffusion coefficient in normal-appearing brain tissue after treatment.
To prospectively evaluate whether subarachnoid hemorrhage (SAH) is associated with a change in the apparent diffusion coefficient (ADC) in normal-appearing brain parenchyma. Institutional review board approval and informed consent were obtained for all patient and volunteer studies. One hundred patients (48 men, 52 women; mean age, 52 years +/- 12 [standard deviation]) with aneurysmal SAH underwent conventional and diffusion-weighted magnetic resonance (MR) imaging at a mean of 9 days +/- 3 after SAH to evaluate possible lesions caused by SAH, treatment of SAH, and vasospasm. Aneurysms were treated surgically (n = 70) or endovascularly (n = 30) before MR imaging. Diffusion-weighted MR imaging was performed at 1-year follow-up in 30 patients (10 men, 20 women; mean age, 51 years +/- 11). Thirty healthy age-matched volunteers (11 men, 19 women; mean age, 54 years +/- 16) underwent MR imaging with an identical protocol. ADC values were measured bilaterally in the gray and white matter (parietal, frontal, temporal, occipital lobes; cerebellum; caudate nucleus; lentiform nucleus; thalamus; and pons) that appeared normal on T2-weighted and diffusion-weighted MR images. Linear mixed model was used for comparison of ADC values of supratentorial gray matter and white matter; general linear regression analysis was used for comparison of ADC values of cerebellum and pons. In patients with SAH, the ADC values in normal-appearing white matter, with a single exception in the frontal lobe (P = .091), were significantly higher than they were in healthy volunteers (P </= .011). The differences disappeared by 1 year, except in parietal white matter (P = .045). The ADC values of cortical gray matter did not significantly differ between patients and volunteers (P >/= .121). SAH and its treatment may cause global mild vasogenic edema in white matter and deep gray matter that is undetectable on T2-weighted and diffusion-weighted MR images but is detectable by measuring the ADC value in the subacute stage of SAH.


Evaluation of cancer service screening: case referent studies recommended.
Various cancer screening trials, randomised or otherwise controlled, have demonstrated reductions in cancer mortality. As a consequence, population screening programmes have been implemented. In the mean time, major advances are being made in early detection and treatment modalities of specific cancers and pre-cancers. The impact of these improvements should have bearing on the beneficial effect of periodical screening in preventing cancer death. To monitor these dynamics in the effectiveness of screening, case-referent studies are designed. The effectiveness is estimated by calculating an odds ratio indicating the cancer death rate in screened versus not screened invitees. The major criticisms of case referent studies are potential selection bias and confounding bias of the odds ratio. By properly designing and applying sensitivity analyses these biases can be minimised.