Safety and efficacy of living donor liver preservation with HTK solution.
In living donor liver transplantation (LDLTx) organ procurement is usually well controlled, and allows to assess liver preservation and graft function under standardized conditions. Because publications on histidine-tryptophan-ketoglutarate (HTK) solution are limited, we prospectively studied its safety and efficacy in a consecutive series of LDLTx. Twenty-four patients received 22 right, 1 left, and 1 left lateral lobe graft. Liver preservation was done by gravity perfusion with HTK through portal vein, and hepatic artery, and flushing of bile ducts. Total ischemia time was 191 +/- 68 minutes. There was no primary nonfunction, and all partial liver grafts showed good recovery: peak aspartate aminotransferase 577 U/L, total bilirubin 15.15 mg/dL, and partial thromboplastin time 49.37 seconds. One graft was lost from parenchymal fracture secondary to portal hyperperfusion after 6 days, and the patient was salvaged with retransplantation. Thirty-day mortality, including sudden cardiac death, pancreatitis, and hepatic artery rupture, was not related to graft dysfunction. Eight of 24 recipients developed early biliary leakage. There was no late ischemic type biliary lesion. These results confirm that HTK solution is safe and effective when used in LDLTx. Potential advantages of HTK in comparison to other preservation solutions are low potassium concentration, low viscosity, no particles, in situ perfusion, no need to flush before reperfusion, improved biliary protection, better recovery of microcirculatory changes, ready to use, and lower costs. Because the risk-benefit ratio is of particular importance in LDLTx the use of HTK solution should be encouraged.


Animal fecal carriership and biotypes of Staphylococcus aureus.
Staphylococcus aureus was found in 44% of the rectal swabs from 377 pigs and in 12% of the swabs from 147 cows. Seventy-one percent of the isolates from pigs showed fibrinolytic activity and grew in colonies of the negative violet type on crystal violet agar. In this group, 47% of the isolates coagulated both human and bovine plasmas and were characterized as intermediate type, whereas 24% coagulated human plasma and were classified as human biotype A. Among the fibrinolysin-negative isolates, 15, 12, and 2% were identifiable as animal biotypes B, C, and E, respectively. The cow isolates were classified as intermediate type (51%), human biotype A (40%), and animal biotype C (9%).


Factors associated with adaptation level in the older adult residential care facilities: a path analysis.
It has become very common for older adults to relocate to residential care facilities. Yet whether older adults adapt to life in a long-term care residential facility through perception, reflection, and conscious behavioral choices is a challenging social issue. Previous research has shown that adaptation is influenced by physical, mental, psychological, social systems, and other debris factors. However, existing knowledge is often based on unidirectional relationships between these factors and adaptation. Few studies have formally examined bivariate relationships between these factors, and the influence of adaptation between these factors internally remains unclear. Therefore, there is a need to examine the structural causality of adaptation in residential care facilities influenced by a combination of physical, emotional, social and psychological factors, life satisfaction, and social support. The present cross-sectional study recruited older adults from three residential care facilities in Henan province, China, through convenience sampling. The Chinese Nursing Home Adjustment Scale (NHAS), Geriatric Depression Scale-15 (GDS-15) and Social Support Scale (SSRS), Satisfaction with Life Scale (SWLS), and Barthel Index were employed to measure the older adult' adjustment level, depression level, social support, satisfaction with life, and self-care ability of the BMC, respectively. The relationships between depression, social support, self-care, satisfaction with life, and adaptation were analyzed and a structural equation model was developed. A total of 210 participants completed the questionnaire. The model demonstrated an acceptable fit of the data. The results showed that the difference between life satisfaction and depression on the level of adaptation was 60 and 23%, respectively. Social support and life satisfaction had a positive direct effect on the level of adaptation, both showing a positive correlation with the level of adaptation. Depression, on the other hand, have a direct effect on the level of adaptation and showed a negative correlation with the level of adaptation. Self-care ability indirectly influenced adaptation mediated by social support. Social support has a positive impact on both life satisfaction and depression, which in turn promotes adaptation. As a major source of social support, family members and nursing home staff in residential care facilities can enhance social support for older people through improved interaction, which can have a meaningful and positive impact on levels of adjustment. The model demonstrates the strengthening and weakening of social support, self-care, life satisfaction, and depression levels, which can help inform the development of relevant care health strategies for older people to promote levels of adjustment and improve quality of life.


Spiroindolone Analogues as Potential Hypoglycemic with Dual Inhibitory Activity on α-Amylase and α-Glucosidase.
Inhibition of α-amylase and α-glucosidase by specified synthetic compounds during the digestion of starch helps control post-prandial hyperglycemia and could represent a potential therapy for type II diabetes mellitus. A new series of spiroheterocyclic compounds bearing oxindole/benzofuran/pyrrolidine/thiazolidine motifs were synthesized via a 1,3-dipolar cyclo-addition reaction approach. The specific compounds were obtained by reactions of chalcones having a benzo[b]furan scaffold (compounds 2a-f), with a substituted isatin (compounds 3a-c) and heterocyclic amino acids (compounds 4a,b). The target spiroindolone analogues 5a-r were evaluated for their potential inhibitory activities against the enzymes α-amylase and α-glucosidase. Preliminary results indicated that some of the target compounds exhibit promising α-amylase and α-glucosidase inhibitory activity. Among the tested spiroindolone analogues, the cycloadduct 5r was found to be the most active (IC50 = 22.61 ± 0.54 μM and 14.05 ± 1.03 μM) as α-amylase and α-glucosidase inhibitors, with selectivity indexes of 0.62 and 1.60, respectively. Docking studies were carried out to confirm the binding interaction between the enzyme active site and the spiroindolone analogues.


Hydration of Caffeine at High Temperature by Neutron Scattering and Simulation Studies.
The solvation of caffeine in water is examined with neutron diffraction experiments at 353 K. The experimental data, obtained by taking advantage of isotopic H/D substitution in water, were analyzed by empirical potential structure refinement (EPSR) in order to extract partial structure factors and site-site radial distribution functions. In parallel, molecular dynamics (MD) simulations were carried out to interpret the data and gain insight into the intermolecular interactions in the solutions and the solvation process. The results obtained with the two approaches evidence differences in the individual radial distribution functions, although both confirm the presence of caffeine stacks at this temperature. The two approaches point to different accessibility of water to the caffeine sites due to different stacking configurations.


Ruptured abdominal aortic aneurysm in computed tomography.
The aim of the study is presentation the usefulness of CT examination in evaluation of ruptured abdominal aortic aneurysms. Material comprises a group of six patients (two women and four men) aged 52-79 years, examined in the 2nd Department of Radiology, Medical University of Lublin between the year 1997 and 2002. In all patients US examination and CT was performed. USG was performed with a Hitachi EUB 410 apparatus. CT was performed with Somatom AR. T scanner by Siemens, with two matrixes, 512 x 512 and 320 x 320 pixels. High resolution reconstruction algorithm was used with the possibility of performing spatial reformations. Five- and 10 mm-axial sections were performed before and after administering of contrast agents. Delayed scans were performed to reveal extravasations of the contrast agent. In three cases axial sections and MPR reconstructions revealed the presence of the periaortic haematoma with active extravasation of the contrasted blood. The ruptured aneurysm in two cases was associated with extensive retroperitoneal haematoma. The periaortic haematoma extended along the wall of the aneurysm. In one case the haematoma was localized mainly in front of aorta. In one case of aneurysm of abdominal aorta and iliac arteries, the rupture or left iliac artery with large retroperitoneal haematoma in the pelvis and intensive extravasation of contrasted blood was seen. The US examination with Power Doppler and Duplex facilitate in three cases evaluation of aneurysm localization. The rupture of abdominal aortic aneurysm is life-threatening condition, in vast majority of cases resulting in patient's death. In cases of acute rupture the clinical symptoms and CT examination of stable patients are essential. In chronic rupture the early diagnosis is very important. The main role plays CT examination, which enables revealing of the aneurysm, precise evaluation of the leakage, retroperitoneal haematoma, vertebral destruction and dislocation of aorta and kidneys.


Mechanism Study of Stress Corrosion Behavior under Tensile and Compressive Stresses for Welded Joint Used in Nuclear Turbine Rotor.
Stress corrosion damage containing pitting and cracking was investigated for NiCrMoV steel-welded joint used in nuclear turbine rotor in 3.5% NaCl solution. The U-bend specimen containing tensile face and compressive face was adopted which was conducive to study the effects of stress on pitting and stress corrosion cracking. On tensile surface of U-bend specimen, pit grew in open environment and was converted into crack covered with passivated film. Interestingly, corrosion pit was also found on compressive surface, which might attribute to this location creating enclosed environment causing Cl- to diffuse hardly. Then, pit grew under the occluded oxide crust composed of special crystalline corrosion products. When pit approached to critical size, crack initiated from it. The critical size of pit for crack initiation from pit was 35 μm on tensile surface and 95 μm on compressive surface. The sensitivity of crack initiation in tensile surface was higher than that in compressive surface. Then, cracking on compressive surface was controlled by slip dissolution mechanism, that is, dislocation outcrop generated through plastic deformation during manufacturing and absorbed Cl- in enclosed environment to accelerate metal dissolution and film rupture. Thereupon, the stress corrosion cracking on compressive surface was able to be maintained. The findings compared corrosion damage modes caused by the two kinds of stress and emphasized the nonignorable role of compressive stress on stress corrosion damage.


Transfusion-Transmitted Babesia microti.
Because testing of donors for Babesia microti has become available, it is important to determine the kinds of patients who should receive B microti-tested blood. We searched PubMed, AABB abstracts, and FDA Web site to identify all cases of transfusion-transmitted babesiosis (TTB). Cases were analyzed for underlying medical condition, age, presence of spleen, and reason for transfusion in relation to 5 classes of recipient outcome severity. Sixty-seven reports included 256 transfusion cases where donor tested positive for B microti, 165 of which resulted in TTB. Sixty recipients did not develop disease or become test positive, and test results were not known for 31 more. The 165 cases of TTB involved hematologic (19%), neonate (10%), cardiovascular (8%), and gastrointestinal (6%) patients. Thirty-two (19%) of the 165 infected patients died with death attributed to babesiosis in 25 of the cases. Nine (5%) were asymptomatic, 27 (16%) were symptomatic but had uncomplicated disease, and 16 (10%) had complicated disease. The severity of disease was mixed among many disease categories. Patients >65 years of age included the largest number of recipients (59/165, 36%) and deaths (11/32, 34%), although deaths occurred in other age groups as well. TTB cases were predominantly due to red cells (133 of 140 specified units), with red blood cell units processed in a variety of ways and at all storage duration. TTB with complicated babesiosis and/or death occurred in patients of all age groups and with a variety of underlying medical conditions.


Evaluation of a Specialised Counselling Service for Perinatal Bereavement.
We aimed to evaluate the outcomes of Petals: a charitable organisation in Cambridgeshire. Petals provides counselling for women and couples who have suffered perinatal bereavement, or trauma during pregnancy or birth. This paper attempts to evaluate the effect of counseling interventions at this difficult time. Outcomes were recorded in 107 patients using the CORE (Clinical Outcomes in Routine Evaluation) system. CORE was developed to assess the effectiveness of psychological therapies. CORE-OM (CORE Outcome Measure) involves a questionnaire that assesses subjective well-being, symptoms/problems, function, and risk to self and others. The CORE-OM questionnaire was completed before and after the counselling sessions. The CORE-OM scores were summated into a global representation of severity. Severity decreased in all patients. Symptoms of psychological pathology were also decreased in all cases. Offering a free specialised counselling for parents suffering perinatal loss seems to be associated with an improvement in psychological outcomes. It is possible that it is more effective among a clinical population. However, we are uncertain of the natural history of the psychological problems this group of clients are experiencing. Having a control group would show how much of any natural improvement is due to the therapy; conversely, it is possible that without intervention these problems worsen with time, so a control group could actually amplify the effect.


Metamaterial graphene sensors for the detection of two food additives.
Food safety is an important consideration for the food industry and for daily life, and food additives are essential in the modern food industry. Graphene-based metamaterial sensors are of great value and have potential applications in the detection of food additives, due to their ultra-sensitivity. This paper proposes a metasurface sensor consisting of graphene and dual elliptical ring resonators (Gr-DERRs) sensor for the detection of two common food additives. The limit of detection (LOD) for Sudan I solution is 581.43 fg/ml and, for taurine, 52.86 fg/ml. This ultra-sensitive detection is achieved by exploiting the unique electromagnetic properties of electromagnetically induced transparency (EIT) resonance, together with the Fermi energy level of graphene moving to the Dirac point, resulting in a dramatic change in the dielectric environment. The Gr-DERRs sensor has brings significant improvement in the detection of food additives with detection limits reduced to the femtogram level.


[SOCIAL IMPACT BONDS FOR HEALTH PROMOTION AND PREVENTIVE MEDICINE].
The World Health Organization (WHO) has declared obesity a global epidemic. WHO sheds much light on this matter in its publications on health promotion and preventative medicine. Lack of physical activity, an unbalanced diet and an unhealthy lifestyle are the leading causes of developing obesity and chronic diseases. In Israel, the growing rate of obesity is a reason for concern. About 500,000 diabetics, mainly as a result of obesity, live in Israel today and by 2030 the number is expected to rise to 2,000,000. Every third child born is expected to develop diabetes by the time they reach the age of 40 unless a profound change is made in health policy. The State of Israel recognizes its responsibility in promoting awareness against obesity as well as its role in prevention. In spite of the country's recognition of the problem, it still has not managed to implement long term solutions which address the issue. Therefore, creative and innovative solutions are called for. The social impact bond (SIB), a newly developed financial model is a possible solution. This model suggests the entry of private investors into the public sector, a field which is within the responsibility of the government. The private investor will be in charge of running a social program on a topic which will be finalized with the government. The private investor and the government will have a contract outlining the program and the criteria for the evaluation and the success of the program. To note, the private investor will only be paid according to the success of the program. Thus the purpose of SIB is in motion processes and is set to serve as a model for several years, and then the authorities will take over the responsibility and continue with the program that the SIB handled. In March 2016, a new SIB was launched in Israel to prevent Type 2 diabetes. This involves 2250 pre-diabetic adults who are at risk to develop Type 2 diabetes and will be identified by their Health Maintenance Organizations (HMOs, Clalit and Leumit) through blood tests. The participants will take part in an intensive intervention wellness program during 3 years. This SIB aims to prevent the onset of diabetes. If successful, and a significant reduction in Type 2 diabetes is found, there will be substantial savings for the HMOs and the National Insurance Institute, which will in turn repay the investors for their expenses, according to the signed contract. This SIB will serve as a pilot project for diabetes prevention and if successful, this model can be adopted for other projects in preventive medicine and health promotion. Thereby, we may be facing a dramatic change in the paradigm of funding national health services in Israel.


Topoisomerase I deregulation in laryngeal squamous cell carcinomas based on tissue microarray analysis.
Topoisomerases (types: I/IIa-b/IIIa-b) represent a super-family of nucleic enzymes involved in the DNA replication, transcription, recombination, and also chromosome topological formation. Topoisomerase's I (Topo I- gene location: 20q12) aberrant expression is a frequent genetic event in a variety of solid malignancies. Topo I inhibition promotes cell death due to DNA damage and for this reason it is a target for specific targeted chemotherapy (camptothecin, topotecan, irinotecan). Our aim was to investigate the role of abnormal Topo I protein expression in laryngeal squamous cell carcinomas (LSCC) in which there are very limited data regarding the influence of the marker. Using tissue microarray (TMA) technology, 50 formalin-fixed, paraffin-embedded primary laryngeal SCCs were cored and re-pembedded into one recipient block. Immunohistochemistry was performed using anti- Topo I antibody. Digital image analysis was also implemented for evaluating objectively the protein expression levels on the corresponding stained nuclei. Topo I protein overexpression (moderate to high staining intensity values) was observed in 32/50 (64%) tissue cores, whereas low expression rates were detected in 18/50 (36%) cases. Topo I overall expression was strongly associated with the differentiation grade of the examined tumors (p=0.021). No other statistical correlations were identified. Topo I overexpression is observed in a significant subset of LSCCs affecting the level of differentiation in them. Additional molecular studies focused on the mechanism of Topo I gene/protein deregulation (i.e. amplification, abnormal epigenetic promoter methylation, mRNA aberrant expression) are necessary discriminating the eligible patients for applying specific chemotherapeutic strategies based on anti-Topo I agents.


Cloning, purification, crystallization and preliminary X-ray crystallographic analysis of a cyclophilin A-like protein from Piriformospora indica.
Cyclophilins are widely distributed both in eukaryotes and prokaryotes and have a primary role as peptidyl-prolyl cis-trans isomerases (PPIases). This study focuses on the cloning, expression, purification and crystallization of a salinity-stress-induced cyclophilin A (CypA) homologue from the symbiotic fungus Piriformospora indica. Crystallization experiments in the presence of 56 mM sodium phosphate monobasic monohydrate, 1.34 M potassium phosphate dibasic pH 8.2 yielded crystals that were suitable for X-ray diffraction analysis. The crystals belonged to the orthorhombic space group C222(1), with unit-cell parameters a = 121.15, b = 144.12, c = 110.63 Å. The crystals diffracted to a resolution limit of 2.0 Å. Analysis of the diffraction data indicated the presence of three molecules of the protein per asymmetric unit (V(M) = 4.48 Å(3) Da(-1), 72.6% solvent content).


Association between COVID-19 and vaccination on menstrual cycle.
To evaluate changes in the menstrual pattern of women of reproductive age infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or vaccinated against coronavirus disease 2019 (COVID-19). A cross-sectional study at the University of Campinas, Brazil using Google questionnaire applied from December 2021 through February 2022, disseminated through snowball technique. Participants responded about characteristics of their menstrual cycle before the pandemic and before COVID-19 vaccination, and then about characteristics of their cycle 3 months after infection with SARS-CoV-2 and 3 months after vaccination. Our primary outcome was a binary indicator of changes in the menstrual cycle. We used multivariate regression analysis to identify factors associated with menstrual changes. We received 1012 completed questionnaires and 735 (72.7%) were from women aged between 20 and 39 years, 745 (73.6%) were White and 491 (48.6%) lived with a partner. A total of 419 (41.6%) of the women reported SARS-CoV-2 infection; however, only two of them were hospitalized, and 995 (98.8%) of women had at least one dose of COVID-19 vaccine. About menstrual characteristics, 170 (41.3%) reported changes after having COVID-19 and 294 (29.9%) after COVID-19 vaccination, respectively. Few years of schooling, lower income, and non-white ethnicity were related to higher reports of menstrual changes after COVID-19. Menstrual changes after COVID-19 vaccination were associated with not using contraception. Higher body mass index was associated with irregularities in cyclicity and bleeding days, after COVID-19 and COVID-19 vaccination, respectively. Our results corroborated the stability of the menstrual cycle after having COVID-19 or COVID-19 vaccination; however, there is a potential relationship between menstrual changes and socioeconomic factors as well as contraceptive use.


Long-term survival and germination of Bacillus thuringiensis var. kurstaki in a field trial.
Long-term survival, dispersal, and germination of Bacillus thuringiensis var. kurstaki DMU67R has been investigated in a field trial. An experimental cabbage plot was sprayed with DMU67R in 1993 and allowed to lie fallow since. The investigations reported here were carried out from 1997 to 2000 in this plot. High persistence of DMU67R for 7 years in the bulk soil of the plot has been demonstrated. The numbers have not significantly reduced since 1994, stabilizing around 6.6 x 10(2) cfu/g from 1996 to 2000. Horizontal dispersal of DMU67R in the 1994-1999 period was limited. Vertical dispersal occurred from 1994 to 1999, as 77% of the population of DMU67R occurred in the 0-2 cm layer in 1994, while only 22% of the population was found there in 1999. Most of the population in 1999 was present homogeneously in the upper 6 cm of the soil profile. Germination, as evidenced by the ratio of DMU67R cfu before and after heat treatment, was not observed in the bulk soil. However, in the rhizospheres of dandelion (Taraxacum officinalis) and quackgrass (Agropyron repens), 40 and 50% of DMU67R was present as vegetative germinated cells, respectively. No germination occurred in the rhizosphere of red fescue (Festuca rubra). The material from the gut of the earthworm species Lumbricus rubellus, Lumbricus terrestris, and Apporrectodea caliginosa and from a tipulid larvae from the plot also contained vegetative cells of DMU67R. Further investigations of A. caliginosa showed that germination seemed to be restricted to the gut and that sporulation occurred after defecation. The germination of DMU67R in rhizospheres and in the gut of nontarget invertebrates suggests that survival in the soil of B. thuringiensis is a dynamic process involving germination, cell divisions, and sporulation in specific microhabitats.


Clinical responses and improvement of some laboratory parameters following polymyxin B-immobilized fiber treatment in septic shock.
Direct hemoperfusion using a polymyxin B-immobilized fiber column (PMX; Toray Industries Inc., Tokyo, Japan) was first developed in 1994 and has since been used for the treatment of septic shock. Positive clinical data, such as an increase in systolic blood pressure (SBP) and an improved Pao2/Fio2 ratio, have also been reported. We treated 27 septic shock patients using DHP-PMX. The patients were separated into two groups for analysis: those whose Pao2/Fio2 ratio increased after DHP-PMX (9 cases) and those whose Pao2/Fio2 ratio did not increase after DHP-PMX (18 cases). The patients were also separated into two other groups for analysis: those whose SBP increased by more than 30 mm Hg immediately after DHP-PMX (15 cases) and those whose SBP did not increase by more than 30 mm Hg after DHP-PMX (12 cases). The Pao2/Fio2 ratio increased significantly after DHP-PMX in the groups showing improved 2AG and PAI-1 levels (p = 0.0040). The SBP increased significantly in the group showing improved HMGB-1 levels (p < 0.0001). We observed a relationship between hemodynamic improvement and increase of the serum HMGB-1 levels and between improvement of respiratory functions and increase of the serum 2-AG and PAI-1 levels in septic shock patients treated with DHP-PMX.


HDL in infectious diseases and sepsis.
During infection significant alterations in lipid metabolism and lipoprotein composition occur. Triglyceride and VLDL cholesterol levels increase, while reduced HDL cholesterol (HDL-C) and LDL cholesterol (LDL-C) levels are observed. More importantly, endotoxemia modulates HDL composition and size: phospholipids are reduced as well as apolipoprotein (apo) A-I, while serum amyloid A (SAA) and secretory phospholipase A2 (sPLA2) dramatically increase, and, although the total HDL particle number does not change, a significant decrease in the number of small- and medium-size particles is observed. Low HDL-C levels inversely correlate with the severity of septic disease and associate with an exaggerated systemic inflammatory response. HDL, as well as other plasma lipoproteins, can bind and neutralize Gram-negative bacterial lipopolysaccharide (LPS) and Gram-positive bacterial lipoteichoic acid (LTA), thus favoring the clearance of these products. HDLs are emerging also as a relevant player during parasitic infections, and a specific component of HDL, namely, apoL-1, confers innate immunity against trypanosome by favoring lysosomal swelling which kills the parasite. During virus infections, proteins associated with the modulation of cholesterol bioavailability in the lipid rafts such as ABCA1 and SR-BI have been shown to favor virus entry into the cells. Pharmacological studies support the benefit of recombinant HDL or apoA-I mimetics during bacterial infection, while apoL-1-nanobody complexes were tested for trypanosome infection. Finally, SR-BI antagonism represents a novel and forefront approach interfering with hepatitis C virus entry which is currently tested in clinical studies. From the coming years, we have to expect new and compelling observations further linking HDL to innate immunity and infections.


β-Catenin regulates hepatic mitochondrial function and energy balance in mice.
Wnt signaling regulates hepatic function and nutrient homeostasis. However, little is known about the roles of β-catenin in cellular respiration or mitochondria of hepatocytes. We investigated β-catenin's role in the metabolic function of hepatocytes under homeostatic conditions and in response to metabolic stress using mice with hepatocyte-specific deletion of β-catenin and their wild-type littermates, given either saline (sham) or ethanol (as a model of binge drinking and acute ethanol intoxication). Under homeostatic conditions, β-catenin-deficient hepatocytes demonstrated mitochondrial dysfunctions that included impairments to the tricarboxylic acid cycle and oxidative phosphorylation (OXPHOS) and decreased production of adenosine triphosphate (ATP). There was no evidence for redox imbalance or oxidative cellular injury in the absence of metabolic stress. In mice with β-catenin-deficient hepatocytes, ethanol intoxication led to significant redox imbalance in the hepatocytes and further deterioration in mitochondrial function that included reduced OXPHOS, fatty acid oxidation (FAO), and ATP production. Ethanol feeding significantly increased liver steatosis and oxidative damage, compared with wild-type mice, and disrupted the ratio of nicotinamide adenine dinucleotide. β-catenin-deficient hepatocytes also had showed disrupted signaling of Sirt1/peroxisome proliferator-activated receptor-α signaling. β-catenin has an important role in the maintenance of mitochondrial homeostasis, regulating ATP production via the tricarboxylic acid cycle, OXPHOS, and fatty acid oxidation; β-catenin function in these systems is compromised under conditions of nutrient oxidative stress. Reagents that alter Wnt-β-catenin signaling might be developed as a useful new therapeutic strategy for treatment of liver disease.


[Natural killer cell activity in patients with nasopharyngeal carcinoma].
In 1984 and 1985, a total of 30 patients with biopsy confirmed nasopharyngeal carcinoma (NPC) were randomly selected for studies on natural killer cell (NK) activity. Control study on 30 normal subjects were also done. Lymphocyte separation was done by centrifuge of heparinized peripheral blood with Ficoll-Hypaque and monocytes were removed by Petri dish adhesion. K562 cells were used as target cells of NK activity. The lymphocyte-target reaction of 4 hours was done and the ratio was 50:1, 25:1 and 12.5:1. The results of 50:1 was taken as the NK activity. The mean value of NK activity in NPC patients was 34.8 +/- 22.7%, this is significantly different (t = 2.90, p less than 0.01) from 51.6 +/- 22.1% of the controls. If NK activity of 20% or more are taken for the normal standard, then the positive rate in NPC patients was 63.3% and that in the controls was 90.0%. The difference is significant, as chi 2 = 4.56, p less than 0.05. The NK activity in NPC patients is not correlated with the sex and age of the patients, the disease extent and the EB virus associated antibody titers.


[What should medical decision be based on?].
Medical decision making is basically related to three criteria: 1) estimated effectiveness in terms of objective and subjective results: 2) equity related to the concept of justice in the societal context; 3) legitimacy according to the willingness to pay of the society, its resource availability and the fraction of its income that is allowed to be spent for health care. A worsening dilemma is unescapable between a utilitarian medical project, and the traditional hippocratic rule of rescue no matter what the cost may be. Every care taker should be involved to give a clear account of medical decision in order to generate and adopt some acceptable view for a reliable implementation with respect to equity and justice.


ACTIVATION OF COAGULATION AND FIBRINOGEN LOSS AFTER USING AN EXTRACORPOREAL CIRCULATION.
Alterations of the coagulation potential of heparinized blood after using an extracorporeal circulation have been studied by means of a toluidine blue-calcium chloride reagent. This technique was originally used to detect the effect of activation by contact on the coagulation mechanism in heparinized blood. It has been shown that it also detects, in the presence of heparin, the clotpotentiating effect of blood cell contents liberated in vitro by mechanical trauma to blood. Variable destruction of platelets, red cells, and white cells occurred in heparinized sheep blood recirculated in a heart-lung machine in vitro. This was accompanied by increased clotting potential. Complete coagulation was prevented by heparin and fibrinogen levels remained unaltered. Similar enhancement of the coagulation potential and destruction of blood cells were detected in the blood of heparinized patients and sheep after perfusion for open-heart surgery. The coagulation changes were usually transient, and impaired coagulation associated with significant fibrinogen loss was detected in most samples taken after the neutralization of heparin. It is suggested that the coagulation changes are due to activation by contact of the coagulation mechanism during perfusion and to the clot-accelerating effect of blood cell contents. The results support the hypothesis that coagulation defects and fibrinogen loss after using an extracorporeal circulation are due, at least in part, to intravascular coagulation. This is thought to occur, especially during neutralization of heparin, while the coagulation mechanism is hyperactive.


Endostatin blocks vascular endothelial growth factor-mediated signaling via direct interaction with KDR/Flk-1.
Endostatin, a fragment of collagen XVIII, is a potent anti-angiogenic protein, but the molecular mechanism of its action is not yet clear. We examined the effects of endostatin on the biological and biochemical activities of vascular endothelial growth factor (VEGF). Endostatin blocked VEGF-induced tyrosine phosphorylation of KDR/Flk-1 and activation of ERK, p38 MAPK, and p125(FAK) in human umbilical vein endothelial cells. Endostatin also inhibited the binding of VEGF(165) to both endothelial cells and purified extracellular domain of KDR/Flk-1. Moreover, the binding of VEGF(121) to KDR/Flk-1 and VEGF(121)-stimulated ERK activation were blocked by endostatin. The direct interaction between endostatin and KDR/Flk-1 was confirmed by affinity chromatography. However, endostatin did not bind to VEGF. Our findings suggest that a direct interaction of endostatin with KDR/Flk-1 may be involved in the inhibitory function of endostatin toward VEGF actions and responsible for its potent anti-angiogenic and anti-tumor activities in vivo.


Induced membrane technique in the treatment of infected tibial bone defect: A retrospective study.
To investigate the effect of the induced membrane technique (IMT) in the treatment of infected tibial bone defect. IMT is a 2-stage procedure dedicated to reconstruction of bone defects of the limbs. Treating injuries of the tibia characterized by segmental bone loss, severe damage to the soft tissue, and a conjoining infection is a challenge using IMT. A retrospective study was performed among the patients treated using IMT for infected tibial bone defect between 2017 and 2020. The complications were recorded, and the bone defect union and the functional results were evaluated by Paley method. All patients were followed up for at least 1 year. We included 12 patients (11 males) with a mean age of 44.5 years (range 19-65). The mean length of bone defect was 26.7 mm (range 10-60). The mean interval between the stage 1 and the stage 2 of the procedure was 11.8 weeks (range 4-32). At a mean follow-up of 18.08 months (range 12-32), bone union was achieved in all cases in a mean time of 8 months (range 5-16) without infection recurrence, where 1 patient received additional bone grafting. The joint function recovered well for the patients and the rate of functionally excellent and good results was 9/12. IMT in the treatment of infected tibial bone defect offers the advantages of simple operation, use of a smaller amount of autograft bone, and low recurrence rate of infection.


Comparative genome analysis of Salmonella enterica serovar Gallinarum biovars Pullorum and Gallinarum decodes strain specific genes.
Salmonella enterica serovar Gallinarum biovar Pullorum (bvP) and biovar Gallinarum (bvG) are the etiological agents of pullorum disease (PD) and fowl typhoid (FT) respectively, which cause huge economic losses to poultry industry especially in developing countries including India. Vaccination and biosecurity measures are currently being employed to control and reduce the S. Gallinarum infections. High endemicity, poor implementation of hygiene and lack of effective vaccines pose challenges in prevention and control of disease in intensively maintained poultry flocks. Comparative genome analysis unravels similarities and dissimilarities thus facilitating identification of genomic features that aids in pathogenesis, niche adaptation and in tracing of evolutionary history. The present investigation was carried out to assess the genotypic differences amongst S.enterica serovar Gallinarum strains including Indian strain S. Gallinarum Sal40 VTCCBAA614. The comparative genome analysis revealed an open pan-genome consisting of 5091 coding sequence (CDS) with 3270 CDS belonging to core-genome, 1254 CDS to dispensable genome and strain specific genes i.e. singletons ranging from 3 to 102 amongst the analyzed strains. Moreover, the investigated strains exhibited diversity in genomic features such as virulence factors, genomic islands, prophage regions, toxin-antitoxin cassettes, and acquired antimicrobial resistance genes. Core genome identified in the study can give important leads in the direction of design of rapid and reliable diagnostics, and vaccine design for effective infection control as well as eradication. Additionally, the identified genetic differences among the S. enterica serovar Gallinarum strains could be used for bacterial typing, structure based inhibitor development by future experimental investigations on the data generated.


Electrochemically functionalized carbon nanotubes and their application to rechargeable lithium batteries.
Electrochemical polymerization of N-vinyl carbazole (VC) on carbon nanotube (CNT) films was studied by cyclic voltammetry (CV) in LiClO4/acetonitrile solutions. Comparing the cyclic voltammograms recorded on a blank Pt electrode with those obtained when single- or multi-walled carbon nanotube (SWNT or MWNT) films were previously deposited onto the Pt electrode, a downshift of the VC reduction peak potential is observed in the latter case. The influences of monomer concentration, type of solvent, and supporting electrolyte on the polymerization conditions and electrochemical properties of these composite materials are also investigated. The morphological aspects of poly(N-vinyl carbazole) (PVC)-functionalized CNTs are revealed by transmission electron microscopy (TEM) studies. A covalent functionalization of carbon nanotubes with PVC is invoked as a result of attenuated total reflection infrared (ATR-IR) spectroscopic studies. Using PVC-functionalized CNTs as a positive electrode and an electrolytic solution containing LiPF6, the charge-discharge characteristics of the rechargeable lithium cells are determined. High specific discharge capacity (approximately 45 and 115 mA h g(-1)) is reported for PVC-functionalized single- and multi-walled carbon nanotubes, respectively.


Heart valve and arterial tissue engineering.
In the industrialized world, cardiovascular disease alone is responsible for almost half of all deaths. Many of the conditions can be treated successfully with surgery, often using transplantation techniques; however, autologous vessels or human-donated organs are in short supply. Tissue engineering aims to create specific, matching grafts by growing cells on appropriate matrices, but there are many steps between the research laboratory and the operating theatre. Neo-tissues must be effective, durable, non-thrombogenic and non-immunogenic. Scaffolds should be bio-compatible, porous (to allow cell/cell communication) and amenable to surgery. In the early days of cardiovascular tissue engineering, autologous or allogenic cells were grown on inert matrices, but patency and thrombogenicity of grafts were disappointing. The current ethos is toward appropriate cell types grown in (most often) a polymeric matrix that degrades at a rate compatible with the cells' production of their own extracellular matrical proteins, thus gradually replacing the graft with a living counterpart. The geometry is crucial. Computer models have been made of valves, and these are used as three-dimensional patterns for mass-production of implant scaffolds. Vessel walls have integral connective tissue architecture, and application of physiological level mechanical forces conditions bio-engineered components to align in precise orientation. This article reviews the concepts involved and successes achieved to date.


Singlet Oxygen: Discovery, Chemistry, C60 -Sensitization.
This review article refers to the discovery of excited molecular oxygen, in particular on its lower singlet excited state (1 Δg , 1 O2 ). After a short report on singlet oxygen generation, the review is focused on the chemistry of this reactive species. Specifically, the three major reactions of 1 O2 with unsaturated organic substrates, namely the [4 + 2] and [2 +2] cycloadditions as well as the ene reaction, are reviewed. The proposed mechanisms of these reactions, through the years, based on experimental and computational work, have been presented. Selected examples of singlet oxygen-synthetic applications are also mentioned. The [60]fullerene and fullereno-materials photosensitized oxidations in homogeneous, as well as in heterogeneous conditions, are also comprehensively discussed. Finally, the self-sensitized photooxidation of open cage fullerenes as well as fullerenes bearing oxidizable groups is reported.


Antipsychotic-induced weight gain and therapeutic response: a differential association.
This study investigated the association between antipsychotic-induced weight gain and therapeutic response to haloperidol and three commonly used atypical neuroleptic medications in schizophrenia and schizoaffective disorder. The subjects were 151 patients enrolled in a double-blind experiment with a duration of 14 weeks comparing the therapeutic efficacy of haloperidol (n = 36), clozapine (n = 38), olanzapine (n = 38), and risperidone (n = 39). Absolute and relative (%) gain in body weight and body mass index (BMI) was determined for the entire duration of the double-blind treatment period; therapeutic response was assessed by the total score and the individual subscales of the Positive and Negative Symptom Scale. Compared with the pretreatment baseline, results indicated that for olanzapine and clozapine, therapeutic response was closely related to an absolute and relative gain in weight and to a gain in BMI. No association between weight gain and therapeutic response was found for risperidone and haloperidol. These findings suggest that patients who are likely to have the maximal benefits of olanzapine or clozapine treatment for symptom alleviation are at the highest risk of a clinically significant increase in weight gain.


Findings and accomplishments of ATSDR's Superfund-mandated Substance-Specific Applied Research Program.
Priority research needs determined by the Agency for Toxic Substances and Disease Registry (ATSDR) for the agencies top-ranked hazardous substances are being filled via regulatory mechanisms, private sector voluntarism, and university-based research. To date, 17 studies have been completed, 12 are ongoing, and 12 are currently planned. Under the direction of the Substance-Specific Applied Research Program (SSARP), ATSDR-supported research has filled research needs that significantly improved the information base available for making appropriate public health decisions. With the knowledge and understanding gained from this research, health professionals are better able to identify and interdict significant exposure and mitigate toxicity when exposure occurs. Thus, the SSARP has played, and continues to play, a vital role in contributing towards improving ATSDR's efforts to meet its mission and goals in environmental public health. In addition to addressing research needs of interest to ATSDR, findings from the program have contributed to the overall scientific knowledge about the effects of toxic substances in the environment.


Monitoring furosemide in racehorses participating in an EIPH program.
Analytical procedures were developed to monitor furosemide concentrations in post-race serum and urine samples obtained from horses participating in an exercise-induced pulmonary haemorrhage (EIPH) program. High performance liquid chromatography with ultraviolet light detection proved a reliable, sensitive method for measuring urinary furosemide concentrations up to 12 h after administration of either 150 or 250 mg of the drug to race horses. However, this method was unreliable for determination of serum furosemide concentration. High performance liquid chromatography with fluorescence detection proved a reliable, sensitive method for measuring serum furosemide concentration in horses administered 250 mg of the diuretic, permitting detection of approximately 5-10 ng/ml 6 h after treatment. This method was applied to field conditions where furosemide was administered to horses (between 150 and 250 mg intravenously) 4 h prior to the race. Analytical results assisted in establishing a threshold concentration of 85 ng/ml for serum furosemide. It was found that serum furosemide concentrations are a valid measure of compliance with furosemide administration in the EIPH program.


Biomass smoke exposure as a serious health hazard for women.
Lung diseases caused by biomass exposure cause a significant health hazard particularly amongst women. The present study was designed to investigate biomass exposure in women suffering from lung disease. A total of 100 women [mean (SD) age: 55.13 (17.65) years] hospitalized for chronic obstructive pulmonary disease (COPD), asthma, bronchiectasis, tuberculosis or interstitial lung disease were included in this study conducted between September 2008-March 2009 in three chest disease clinics at Sureyyapasa Chest Diseases and Chest Surgery Training and Research Hospital. Data collection on biomass exposure was based on application of hospital-based survey questionnaire including items on occupation, level of education, place of birth (location, region), exposure to biomass fuel fumes for heating and cooking purposes (animal dung, wood, charcoal, dried plant) and years of exposure with animal dung, wood, charcoal, dried plant. COPD in 22% patients, lung carcinoma in 12%, bronchitis in 8%, tuberculosis in 26%, and interstitial lung disease in 17% were the diagnosis for hospitalization. The most identified occupation was housewifery 86%. Active, former and non-smokers composed 6%, 22% and 72% of the population. Birth place was village in 67% patients while districts in 9%. According to regional distribution, the most common place of birth was Central Anatolia region in (29%). Exposure to biomass fuels was identified in all of patients including wood (92%), animal dung (30%), charcoal (23%), and dry plant (23%). Mean (SD) years of exposure was identified to be 52.6 (17.9) years for wood, 40.8 (17.9) years for animal dung, 48.1 (20.8) years for dry plant and 38.5 (21.4) years for charcoal. The most common type of biomass exposure was wood in village (97%), city (79%) and county (89%). Findings indicating impact of biomass exposure in women seem to emphasize the need for analytic epidemiologic studies assessment measuring biomass exposure levels-particularly for women and young children.


Structural basis for the selective activation of Rho GTPases by Dbl exchange factors.
Activation of Rho-family GTPases involves the removal of bound GDP and the subsequent loading of GTP, all catalyzed by guanine nucleotide exchange factors (GEFs) of the Dbl-family. Despite high sequence conservation among Rho GTPases, Dbl proteins possess a wide spectrum of discriminatory potentials for Rho-family members. To rationalize this specificity, we have determined crystal structures of the conserved, catalytic fragments (Dbl and pleckstrin homology domains) of the exchange factors intersectin and Dbs in complex with their cognate GTPases, Cdc42 and RhoA, respectively. Structure-based mutagenesis of intersectin and Dbs reveals the key determinants responsible for promoting exchange activity in Cdc42, Rac1 and RhoA. These findings provide critical insight into the structural features necessary for the proper pairing of Dbl-exchange factors with Rho GTPases and now allow for the detailed manipulation of signaling pathways mediated by these oncoproteins in vivo.


GammaTile®: Surgically targeted radiation therapy for glioblastomas.
Glioblastoma is the most common primary malignant neoplasm of the central nervous system in adults. Standard of care is resection followed by chemo-radiation therapy. Despite this aggressive approach, >80% of glioblastomas recur in proximity to the resection cavity. Brachytherapy is an attractive strategy for improving local control. GammaTile® is a newly US FDA-cleared device which incorporates 131Cs radiation emitting seeds in a resorbable collagen-based carrier tile for surgically targeted radiation therapy to achieve highly conformal radiation at the time of surgery. Embedding encapsulated 131Cs radiation emitter seeds in collagen-based tiles significantly lowers the technical barriers associated with traditional brachytherapy. In this review, we highlight the potential of surgically targeted radiation therapy and the currently available data for this novel approach.


New insights into the genetics of neuroblastoma.
Neuroblastoma is a genetically and clinically heterogeneous tumor of childhood, arising from precursor cells of the sympathetic nervous system. It is still a challenging cancer for pediatric oncology, as some tumors will spontaneously regress, while others will become refractory to all forms of therapy. The clinical course of this disease is greatly influenced by both patient age and the genetic abnormalities that occur within the tumors. MYCN (v-myc myelocytomatosis viral related oncogene, neuroblastoma derived (avian)) amplification and loss of chromosome 11q heterozygosity have been known to be indicative of poor prognosis. In this article, we review how mutations and structural alterations in specific genes contribute to inheritable predisposition to neuroblastoma and/or to aggressive disease pathogenesis, as well as implications for diagnosis and therapy. These genes include PHOX2B (paired-like homeobox 2b), ALK (anaplastic lymphoma receptor tyrosine kinase), and ATRX (alpha thalassemia/mental retardation syndrome X-linked).


Unconventional criticality, scaling breakdown, and diverse universality classes in the Wilson-Cowan model of neural dynamics.
The Wilson-Cowan model constitutes a paradigmatic approach to understanding the collective dynamics of networks of excitatory and inhibitory units. It has been profusely used in the literature to analyze the possible phases of neural networks at a mean-field level, e.g., assuming large fully connected networks. Moreover, its stochastic counterpart allows one to study fluctuation-induced phenomena, such as avalanches. Here we revisit the stochastic Wilson-Cowan model paying special attention to the possible phase transitions between quiescent and active phases. We unveil eight possible types of such transitions, including continuous ones with scaling behavior belonging to known universality classes-such as directed percolation and tricritical directed percolation-as well as six distinct ones. In particular, we show that under some special circumstances, at a so-called "Hopf tricritical directed percolation" transition, rather unconventional behavior is observed, including the emergence of scaling breakdown. Other transitions are discontinuous and show different types of anomalies in scaling and/or exhibit mixed features of continuous and discontinuous transitions. These results broaden our knowledge of the possible types of critical behavior in networks of excitatory and inhibitory units and are, thus, of relevance to understanding avalanche dynamics in actual neuronal recordings. From a more general perspective, these results help extend the theory of nonequilibrium phase transitions into quiescent or absorbing states.


[The rights of the child in family and in society: cartography of laws and resolutions].
This research is a documental review of laws, resolutions and others documents related to children and adolescents' rights existing in Brazil and overseas, aiming thus a comprehension and greater knowledge about the child and his rights. The documents chosen were: 1959's Pronouncement of Child Rights; 1988's Federal Constitution of Brazil; 1988's Letter of Hospitalized Child: 1990's Statute of Child and Adolescent; and the Rights of Child and Adolescent hospitalized (Resolution 41/95). We did floating reading of all documents, mentioning relevant articles to theme, highlighting some considerations. We conclude that already exist legislations that protect the right of child, though it is necessary to ensure the use of these rights.


Current and novel approaches to treat patients presenting with ST elevation myocardial infarction.
Primary percutaneous coronary intervention (PCI) represents the gold-standard treatment for patients presenting with an ST-elevation myocardial infarction (STEMI). Acute myocardial infarction is a complex clinical scenario, and an appropriate therapeutic approach could be represented by a balanced integration between healthcare system and medical competence. In this review we discuss how a primary PCI network, and the new therapeutic options could be coupled in order to obtain improved clinical outcomes. The present report will focus on three main issues related to STEMI patients, namely, out of hospital management, primary PCI and pharmacological treatment. Expert commentary: A possible correct approach to a patient presenting a STEMI could be considered as a stepwise process, given by 5 steps: reducing the time to reperfusion; dual antiplatelet administration; radial access; new generation drug eluting stent implantation; long term management.


Timosaponin AIII Suppresses Hepatocyte Growth Factor-Induced Invasive Activity through Sustained ERK Activation in Breast Cancer MDA-MB-231 Cells.
Background. The aim of this study was to investigate the mechanisms by which Timosaponin AIII (TAIII) is able to inhibit HGF-induced invasion activity in the triple negative breast cancer cell line MDA-MB-231. Methods. After pretreatment with different concentrations (10(-6)~10(-8) M) of TAIII, the cells were treated with hepatocyte growth factor (HGF, 15 ng/mL). At different time intervals after coincubation, various parameters, including the expression of c-Met, ERK, COX2, and MMP-9, which were assessed by Western blotting or by real-time PCR, were analyzed. In addition, invasive activity was also monitored. Results. HGF was found to induce c-MET activation and ERK activation, together with increased COX2 protein expression; these changes were followed by a subsequent increase in invasive activity. TAIII was found to suppress HGF-induced invasive activity and COX2 gene expression in a concentration-dependent manner (10(-6)~10(-8) M) in parallel with increases in the phosphoforms of c-Met and ERK after TAIII treatment. The mechanisms by which TAIII suppresses HGF-induced invasive activity were demonstrated to include sustained cytoplasmic and nuclear ERK activation; these led to a suppression of nuclear ATF2 activation, which was followed by downregulation of COX2 and MMP-9 transcription. Conclusion. TAIII suppresses HGF-induced invasive activity in MDA-MB-231 cells via sustained ERK activation.


Wavy Two-Dimensional Conjugated Metal-Organic Framework with Metallic Charge Transport.
Two-dimensional conjugated metal-organic frameworks (2D c-MOFs) have emerged as a new class of crystalline layered conducting materials that hold significant promise for applications in electronics and spintronics. However, current 2D c-MOFs are mainly made from organic planar ligands, whereas layered 2D c-MOFs constructed by curved or twisted ligands featuring novel orbital structures and electronic states remain less developed. Herein, we report a Cu-catecholate wavy 2D c-MOF (Cu3(HFcHBC)2) based on a fluorinated core-twisted contorted hexahydroxy-hexa-cata-hexabenzocoronene (HFcHBC) ligand. We show that the resulting film is composed of rod-like single crystals with lengths up to ∼4 μm. The crystal structure is resolved by high-resolution transmission electron microscopy (HRTEM) and continuous rotation electron diffraction (cRED), indicating a wavy honeycomb lattice with AA-eclipsed stacking. Cu3(HFcHBC)2 is predicted to be metallic based on theoretical calculation, while the crystalline film sample with numerous grain boundaries apparently exhibits semiconducting behavior at the macroscopic scale, characterized by obvious thermally activated conductivity. Temperature-dependent electrical conductivity measurements on the isolated single-crystal devices indeed demonstrate the metallic nature of Cu3(HFcHBC)2, with a very weak thermally activated transport behavior and a room-temperature conductivity of 5.2 S cm-1. Furthermore, the 2D c-MOFs can be utilized as potential electrode materials for energy storage, which display decent capacity (163.3 F g-1) and excellent cyclability in an aqueous 5 M LiCl electrolyte. Our work demonstrates that wavy 2D c-MOF using contorted ligands are capable of intrinsic metallic transport, marking the emergence of new conductive MOFs for electronic and energy applications.


Enhancing data integration with text analysis to find proteins implicated in plant stress response.
High throughput genomic studies can identify large numbers of potential candidate genes, which must be interpreted and filtered by investigators to select the best ones for further analysis. Prioritization is generally based on evidence that supports the role of a gene product in the biological process being investigated. The two most important bodies of information providing such evidence are bioinformatics databases and the scientific literature. In this paper we present an extension to the Ondex data integration framework that uses text mining techniques over Medline abstracts as a method for accessing both these bodies of evidence in a consistent way. In an example use case, we apply our method to create a knowledge base of Arabidopsis proteins implicated in plant stress response and use various scoring metrics to identify key protein-stress associations. In conclusion, we show that the additional text mining features are able to highlight proteins using the scientific literature that would not have been seen using data integration alone. Ondex is an open-source software project and can be downloaded, together with the text mining features described here, from www.ondex.org.


Penetration of tobramycin sulfate in the aqueous humor of the rabbit.
The intraocular penetration of tobramycin sulfate, a new aminoglycoside antibiotic, was evaluated in rabbits following subconjunctival injection. The mean tobramycin sulfate concentration in the aqueous humor 60 minutes after a single 5-mg dose was 5.5 mug/ml, as compared to a mean concentration of 6.7 mug/ml following a single 10-mg dose. These levels exceed the minimal inhibitory concentration (MIC) for most Pseudomonas species and a variety of other Gram-negative bacilli recovered from clinical infection. No anterior segment changes that may be attributed to the antibiotic could be demonstrated in the injected eye.


Adaptation to stroke: a longitudinal study of depressive symptoms, physical health, and coping process.
The purposes of this study were to describe the natural history of adaptation to stroke and to identify survivor and caregiver predictors of depressive symptoms. Data were collected for 53 stroke survivors at four times from acute rehabilitation (T1) to 2 years post discharge (T4). Significant improvement occurred in depressive symptoms and perception of health, but change in the rate of depression was not significant. Family functioning became less healthy. Significant predictors of greater levels of depressive symptoms were lower levels of total support, finding meaning, and avoidance coping (T1) and lower levels of family functioning and belonging support (T4). Treatments to promote adaptation can be developed based on these predictors.


The value of home support for cancer patients: a study.
The Community Oncology Project (COPE) was initiated to investigate home support from a trained oncology nurse at various stages of treatment. Patients who received home support during treatment responded better than those having visits after treatment had finished. The author discusses the patients' continuing need for home support and the issues of dependency that this raises.


IL-33 and the intestine: The good, the bad, and the inflammatory.
Interleukin-33 (IL-33) is a member of the IL-1 cytokine family that has been widely studied since its discovery in 2005 for its dichotomous functions in homeostasis and inflammation. IL-33, along with its receptor suppression of tumorigenicity 2 (ST2), has been shown to modulate both the innate and adaptive immune system. Originally, the IL-33/ST2 signaling axis was studied in the context of inducing type 2 immune responses with the expression of ST2 by T helper 2 (TH2) cells. However, the role of IL-33 is not limited to TH2 responses. Rather, IL-33 is a potent activator of TH1 cells, group 2 innate lymphoid cells (ILC2s), regulatory T (Treg) cells, and CD8+ T cells. The intestine is uniquely important in this discussion, as the intestinal epithelium is distinctively positioned to interact with both pathogens and the immune cells housed in the mucosa. In the intestine, IL-33 is expressed by the pericryptal fibroblasts and its expression is increased particularly in disease states. Moreover, IL-33/ST2 signaling aberrancy is implicated in the pathogenesis of inflammatory bowel disease (IBD). Accordingly, for this review, we will focus on the role of IL-33 in the regulation of intestinal immunity, involvement in intestinal disease, and implication in potential therapeutics.


Angiotensin II receptors subtypes mediate diverse gene expression profile in adult hypertrophic cardiomyocytes.
1. Although the systemic and cardiac renin-angiotensin systems are known to be activated in the setting of pressure overload, the actions and signaling mechanisms of angiotensin (Ang) II via AT(1) and AT(2) receptors in hypertrophic cardiomyocytes (CM) remain largely unclear. 2. Hypertrophic CM were prepared from rats with aortic banding for 8 weeks, cultured and then treated as follows: (i) 1 micromol/L AngII for 24 h; (ii) 10 micromol/L losartan (an AT(1) receptor antagonist) for 1 h followed by 1 micromol/L AngII for 24 h; and (iii) 10 micromol/L PD123319 (an AT(2) receptor antagonist) for 1 h followed by 1 micromol/L AngII for 24 h. Changes in the expression of genes following stimulation of AT(1) and AT(2) receptors specific to G-protein-coupled receptor (GPCR) signaling pathways were tested using GEArray (Superarray, Bethesda, MD, USA). The effects of AngII, acting via AT(1) and AT(2) receptors, on the expression of tumour necrosis factor (TNF)-alpha, interleukin (IL)-1beta and IL-6 were confirmed by reverse transcription-polymerase chain reaction and radioimmunoassay. 3. The genes regulated via stimulation of AT(1) receptors were mainly restricted to the signaling pathways including cAMP/protein kinase (PK) A, Ca(2+), PKC, protein tyrosine kinase, mitogen-activated protein kinases, phosphatidylinositol 3-kinase and nuclear factor-kappaB. In addition to these pathways related to activation of AT(1) receptors, four additional signaling pathways were found to be associated with stimulation of AT(2) receptors, including phospholipase C, nitric oxide/cGMP, Rho and Janus kinase/signal transducer and activator of transcription. Blockade of AT(2) receptors decreased the mRNA and protein expression of TNF-alpha and IL-1beta, whereas blockade of AT(1) receptors had no such effect. 4. In conclusion, in hypertrophic CM, AngII leads to distinct signaling responses mediated by AT(1) and AT(2) receptors. Stimulation of AT(2) receptors appears to have a greater influence on GPCR-signaling than stimulation of AT(1) receptors. Angiotensin II enhances the synthesis and secretion of TNF-alpha and IL-1beta in hypertrophic CM, which is mediated by AT(2), but not AT(1), receptors.


Combined antiallodynic effect of Neurotropin® and pregabalin in rats with L5-spinal nerve ligation.
In this study, we investigated the combined effect of Neurotropin® and pregabalin for L5-spinal nerve ligation (L5-SNL) model in rats and thiopental-induced sleep in mice. The left fifth lumbar nerve of rats was tightly ligated with silk sutures under pentobarbital anesthesia. The hindpaw withdrawal threshold was measured by application of von Frey filaments. Thiopental sodium was intravenously administered in mice and sleeping time was measured. In L5-SNL rats, an isobolographic analysis was performed to clarify the combined antiallodynic effect of Neurotropin and pregabalin 14 days after ligation in rats. In isobolographic analysis and thiopental-induced sleep test, Neurotropin and pregabalin were orally administered to coincide with the timing of the peak effect of each drug. Neurotropin (50-200 NU/kg) and pregabalin (2.5-10mg/kg) showed a dose-dependent antiallodynic action in L5-SNL rats. The antiallodynic effect of pregabalin was reversed by intrathecal injection of yohimbine or ondansetron. Isobolographic analysis suggested that the combined antiallodynic effect of Neurotropin and pregabalin in L5-SNL rats may have been more than a mere additive effect. Neurotropin (50-400 NU/kg) had no effect on thiopental-induced sleeping time whereas pregabalin (30-100mg/kg) significantly prolonged it. When the dose of pregabalin was 30 mg/kg, Neurotropin (50-400 NU/kg) did not further exacerbate the prolongation effect of pregabalin on thiopental-induced sleep. It was suggested that when Neurotropin was administered in combination with pregabalin, it might provide more effective pain relief than that obtained with each agent alone in neuropathic pain without aggravating adverse effects of pregabalin.


Physiological, Biochemical, and Metabolic Responses to Short and Prolonged Saline Stress in Two Cultivated Cardoon Genotypes.
Cultivated cardoon is a multipurpose crop with adaptability to limiting environments. Two genotypes ("Bianco Avorio" and "Spagnolo") were comparatively characterized in response to short and prolonged 100 mM NaCl stress in hydroponics. Salt induced no growth variations between genotypes or symptoms of NaCl toxicity, but boosted ABA accumulation in roots and leaves. Both genotypes had high constitutive phenol content, whose major components were depleted upon 2 days of stress only in "Bianco Avorio". Prolonged stress stimulated accumulation of proline, phenylpropanoids, and related transcripts, and non-enzymatic antioxidant activity. Decreased antioxidant enzymes activities upon short stress did not occur for APX in "Spagnolo", indicating a stronger impairment of enzymatic defenses in "Bianco Avorio". Nonetheless, H2O2 and lipid peroxidation did not increase under short and prolonged stress in both genotypes. Overall, the two genotypes appear to share similar defense mechanisms but, in the short term, "Bianco Avorio" depends mainly on non-enzymatic antioxidant phenylpropanoids for ROS scavenging, while "Spagnolo" maintains a larger arsenal of defenses. Upon prolonged stress, proline could have contributed to protection of metabolic functions in both genotypes. Our results provide cues that can be exploited for cardoon genetic improvement and highlight genotypic differences for breeding salinity tolerant varieties.


The association between maternal nonylphenol exposure and parity on neonatal birth weight: a cohort study in Taiwan.
The aim of this study was to explore the association between NP exposure and parity and their effect on neonatal birth weight. A cohort of pregnant women was established in a medical center in North Taiwan. Urinary NP concentration was determined by high-performance liquid chromatography coupled with fluorescent detection and adjusted using creatinine. A multivariable regression model was fit to determine the association between the maternal NP level in each trimester and neonatal birth weight. The odds ratios (ORs) of infant birth weight below the 10th, 25th, and 50th percentiles, comparing pregnant women with the different NP exposure levels, was estimated using a logistic regression. Of the 162 pregnant women in the study, 99 were multiparas and 63 were primiparas. After adjusting for other covariates, the NP level in the second trimester had a significant association with birth weight in the primiparas (β = -182.49 g, p value = 0.02). The OR of low infant birth weight, comparing pregnant women with different NP levels, was increased by decreasing the cutoff percentile for birth weight (OR = 1.18 for the 50th percentile, 2.12 for the 25th percentile, and 7.81 for the 10th percentile). The odds of primiparas with high NP level having a low neonatal birth weight increased to 3.87, 11.77, and 9.40 for the three different percentiles (p value < 0.05). Maternal NP exposure level is associated with an increased risk of low neonatal weight. Primiparas are especially at risk, and the second trimester of pregnancy may be the critical stage of exposure.


Observed brightness distributions in overcast skies.
Beneath most overcasts, clouds' motions and rapidly changing optical depths complicate mapping their angular distributions of luminance L(v) and visible-wavelength radiance L. Fisheye images of overcast skies taken with a radiometer-calibrated digital camera provide a useful new approach to solving this problem. Maps calculated from time-averaged images of individual overcasts not only show their brightness distributions in unprecedented detail, but they also help solve a long-standing puzzle about where brightness maxima of overcasts are actually located. When combined with simulated radiance distributions from MODTRAN4, our measured radiances also let us estimate the gradients of cloud thickness observed in some overcasts.


Aqueous Solubility Enhancement for Bioassays of Insoluble Inhibitors and QSPR Analysis: A TNF-α Study.
The aim of this study is to improve the aqueous solubility of a group of compounds without interfering with their bioassay as well as to create a relevant prediction model. A series of 55 potential small-molecule inhibitors of tumor necrosis factor-alpha (TNF-α; SPD304 and 54 analogues), many of which cannot be bioassayed because of their poor solubility, was used for this purpose. The solubility of many of the compounds was sufficiently improved to allow measurement of their respective dissociation constants (Kd). Parameters such as dissolution time, initial state of the solute (solid/liquid), co-solvent addition (DMSO and PEG3350), and sample filtration were evaluated. Except for filtration, the remaining parameters affected aqueous solubility, and a solubilization protocol was established according to these. The aqueous solubility of the 55 compounds in 5% DMSO was measured with this protocol, and a predictive quantitative structure property relationship model was developed and fully validated based on these data. This classification model separates the insoluble from the soluble compounds and predicts the solubility of potential small-molecule inhibitors of TNF-α in aqueous solution (containing 5% DMSO as co-solvent) with an accuracy of 81.2%. The domain of applicability of the model indicates the type of compounds for which estimation of aqueous solubility can be confidently predicted.


Post-translational fate of CAN1 permease of Saccharomyces cerevisiae.
To study the post-translational fate of arginine permease (Can1p), the gene coding for this transport protein was placed behind a constitutive promoter of plasma membrane ATPase (PMA1) and furnished with a Myc tag. In exponential-phase cells the amount of Can1p is constant, although turnover can be demonstrated. A rapid decrease in transport activity during the early stationary phase is paralleled by a corresponding net degradation of the protein. The amount of Can1p present in exponential cells grown on various nitrogen sources is the same, except in arginine-grown cells, in which the amount of the protein is markedly lower. This occurs solely when arginine serves as nitrogen source but not as an immediate consequence of, for example, arginine addition to cells growing on other nitrogen sources. it was demonstrated that Can1p is phosphorylated. Since Can1p expression under the PMA1 promoter is glucose-dependent, the amount of the permease expressed in high-glucose-grown cells is higher than in low-glucose-grown ones. Only a part of the Can1p overexpressed in high-glucose-grown cells is phosphorylated, while in low-glucose-grown cells the phosphorylated form probably represents the majority of Can1p. The permease phosphorylation or dephosphorylation is not related to transinhibition.


[Sports activity in heart disease: synthesis of new recommendations].
The practice of moderate and regular sports is beneficial for health, and should then always be promoted. The intensive practice of sports, especially for competition, increases the risk of cardiovascular events in patients with heart disease. Facing to a patient with heart disease requiring a certificate of non-contra-indication for sports practice, the cardiologist can sometimes consider himself/herself helpless for managing accurately the situation. Recently, recommendations have been published and summarized herein, in order to guide the final decision.


Citrulline metabolism in plants.
Citrulline was chemically isolated more than 100 years ago and is ubiquitous in animals, plants, bacteria, and fungi. Most of the research on plant citrulline metabolism and transport has been carried out in Arabidopsis thaliana and the Cucurbitaceae family, particularly in watermelon which accumulates this non-proteinogenic amino acid to very high levels. Industrially, citrulline is produced via specially optimized microbial strains; however, the amounts present in watermelon render it an economically viable source providing that other high-value compounds can be co-extracted. In this review, we provide an overview of our current understanding of citrulline biosynthesis, transport, and catabolism in plants additionally pointing out significant gaps in our knowledge which need to be closed by future experimentation. This includes the identification of further potential enzymes of citrulline metabolism as well as obtaining a far better spatial resolution of both sub-cellular and long-distance partitioning of citrulline. We further discuss what is known concerning the biological function of citrulline in plants paying particular attention to the proposed roles in scavenging of excess NH4+ and as a compatible solute.


Genome size as a predictor of guard cell length in Arabidopsis thaliana is independent of environmental conditions.
The recent discovery of a strong positive relationship between angiosperm genome size and stomatal guard cell length (GCL) opens the possibility of using plant fossil guard cell size as a proxy for changes in angiosperm genome size over periods of environmental change. The responses of GCL to environmental stimuli are currently unknown and may obscure this predictive relationship. Here, we investigated the effects of environmental variables (atmospheric CO2, drought, relative humidity, irradiance, ultraviolet radiation and pathogen attack) on GCL in the model plant Arabidopsis thaliana to quantify environmentally induced variation. GCL responded to all variables tested, but the changes incurred did not significantly impinge on the predictive capability of the relationship.


Post-translational and transcriptional regulation of DMT1 during P19 embryonic carcinoma cell differentiation by retinoic acid.
Studies were performed to determine the regulation of DMT1 (divalent metal transporter 1) during RA (retinoic acid)-induced differentiation of P19 embryonic carcinoma cells. Protein and mRNA expression for the +/-IRE (iron response element) forms of DMT1, but not the 1A isoform, were down-regulated within the first few hours upon removal of RA, at which time the cells began to differentiate. The turnover of the +/-IRE isoforms of DMT1 protein during this period was found to be dependent on both the proteasomal and lysosomal pathways. Changes in mRNA levels were shown to be regulated by nitric oxide produced by the induction of neuronal nitric oxide synthase after removal of RA. Nitric oxide functions by inhibiting NF-kappaB (nuclear factor kappaB) nuclear translocation and the subsequent binding to the putative NF-kappaB response element (at -19 to -23) within the 1B promoter. Gel-shift analysis and chromatin immunoprecipitation assay indicated that nuclear NF-kappaB is capable of binding to this response element and that binding decreases during early stages of differentiation. Luciferase reporter gene assay demonstrated that a mutation in this binding domain leads to decreased activity. These results demonstrate that during neuronal differentiation of P19 cells, there is a decrease in specific isoforms of DMT1 via both post-translational and transcriptional mechanisms.


Salvage radiotherapy for biochemical recurrence after radical prostatectomy.
To evaluate the clinical outcome of salvage radiotherapy (RT) for biochemical recurrence after radical prostatectomy (RP) at our institution. Between March 1999 and January 2004, 37 patients had salvage RT for prostate-specific antigen (PSA) failure after RP, including eight who had had neoadjuvant hormone therapy. After surgery, PSA was measured with ultrasensitive immunoassays. In all patients RT was delivered to the prostatic bed at a total dose of 60 Gy with a four-field box technique. The median (range) PSA level before salvage RT was 0.146 (0.06-3.216) ng/mL and RT was started at a PSA level of <0.5 ng/mL in 34 of the 37 patients (92%). With a median follow-up of 31.9 (0-69.8), months, 11 patients (30%) had disease progression after RT and the 3- and 5-year progression-free probability was 74% and 54%, respectively. Univariate analysis showed that clinical and pathological tumour stages and PSA level before RT (>0.15 vs < or = 0.15 ng/mL) were significant predictors of disease progression. There were no late adverse events related to RT. Salvage RT for biochemical failure after RP at a low PSA level, using ultrasensitive immunoassays for monitoring, is a reasonably effective treatment. A relatively low radiation dose (60 Gy) seems to be effective.


Effect of Hibiscus sabdariffa extract on high fat diet-induced obesity and liver damage in hamsters.
Obesity is a chronic metabolic disorder associated with an increase in adipogenesis and often accompanied with fatty liver disease. In this study, we investigated the anti-obesity effects of Hibiscus sabdariffa water extract (HSE) in vivo. Eight-weeks-old male mice were divided into six groups (n=8 per group) and were fed either normal feed, a high fat diet (HFD), HFD supplemented with different concentrations of HSE, or HFD supplemented with anthocyanin. After 10 weeks of feeding, all the blood and livers were collected for further analysis. Mesocricetus auratus hamster fed with a high-fat diet developed symptoms of obesity, as determined from their body weight change and from their plasma lipid levels. Meanwhile, HSE treatment reduced fat accumulation in the livers of hamsters fed with HFD in a concentration-dependent manner. Administration of HSE reduced the levels of liver cholesterol and triglycerides, which were elevated by HFD. Analysis of the effect of HSE on paraoxonase 1, an antioxidant liver enzyme, revealed that HSE potentially regulates lipid peroxides and protects organs from oxidation-associated damage. The markers of liver damage such as serum alanine aminotransferase and aspartate aminotransferase levels that were elevated by HFD were also reduced on HSE treatment. The effects of HSE were as effective as treatment with anthocyanin; therefore the anthocyanins present in the HSE may play a crucial role in the protection established against HFD-induced obesity. In conclusion HSE administration constitutes an effective and viable treatment strategy against the development and consequences of obesity.


Evidence for a new class of defects in highly n-doped Si: donor-pair-vacancy-interstitial complexes.
Electron channeling experiments performed on individually scanned, single columns of atoms show that in highly n-type Si grown at low temperatures the primary electrically deactivating defect cannot belong to either the widely accepted class of donor-vacancy clusters or a recently proposed class of donor pairs. First-principles calculations suggest a new class of defects consisting of two dopant donor atoms near a displaced Si atom, which forms a vacancy-interstitial pair. These complexes are consistent with the present experimental results, the measured open volume of the defects, the observed electrical activity as a function of dopant concentration, and the enhanced diffusion of impurities in the presence of deactivated dopants.


Incidence of rotator cuff tears in shoulder dislocations and results of therapy in older patients.
In older patients we documented the incidence of additional injuries in shoulder dislocations in a non-randomised, prospective study and compared the results of conservative and of operative therapy of rotator cuff tears. Between 1993 and 1999 a total of 87 patients were prospectively enrolled. In the case of documented tears of the rotator cuff in combination with symptoms persisting after conservative therapy patients were free to decide between surgical and conservative treatment. Patients were monitored for function, subjective stability, and satisfaction over a minimum follow-up period of 1 year. In 54% of the patients enrolled a cuff tear was documented; the frequency increased with advancing age to 100% in patients over the age of 70. Surgical treatment of the cuff tears resulted in better function and satisfaction. There were three recurrences in the conservative treatment group, while no recurrences were documented in surgically treated patients. The significant benefit of cuff repair was confirmed by regression analysis. In this selected patient group, we believe surgical repair of the symptomatic rotator cuff tear should be discussed with the patient.


Characterization of Low-Molecular-Weight Heparins by Strong Anion-Exchange Chromatography.
Currently, detailed structural characterization of low-molecular-weight heparin (LMWH) products is an analytical subject of great interest. In this work, we carried out a comprehensive structural analysis of LMWHs and applied a modified pharmacopeial method, as well as methods developed by other researchers, to the analysis of novel biosimilar LMWH products; and, for the first time, compared the qualitative and quantitative composition of commercially available drugs (enoxaparin, nadroparin, and dalteparin). For this purpose, we used strong anion-exchange (SAX) chromatography with spectrophotometric detection because this method is more helpful, easier, and faster than other separation techniques for the detailed disaccharide analysis of new LMWH drugs. In addition, we subjected the obtained results to statistical analysis (factor analysis, t-test, and Newman-Keuls post hoc test).


Variation in survival after diagnosis of breast cancer in Switzerland.
Survival after diagnosis of cancer is a key criterion for cancer control. Major survival differences between time periods and countries have been reported by the EUROCARE studies. We investigated whether similar differences by period and region existed in Switzerland. Survival of 11,376 cases of primary invasive female breast cancer diagnosed between 1988 and 1997 and registered in seven Swiss cancer registries covering a population of 3.5 million was analysed. Comparing the two periods 1988-1992 and 1993-1997, age-standardized 5 year relative survival improved globally from 77% to 81%. Furthermore, multivariate analysis adjusting for age, tumour size and nodal involvement identified regional survival differences. Survival was lowest in the rural parts of German-speaking eastern Switzerland and highest in urbanised regions of the Latin- and German-speaking northwestern parts of the country. This study confirms that survival differences are present even in a small and affluent, but culturally diverse, country like Switzerland, raising the issue of heterogeneity in access to care and quality of treatment.


Association Between Marital Status and Racial Disparities in Esophageal Cancer Care.
This study was designed to examine the impact of marital status on racial disparities in esophageal cancer care. We performed a secondary analysis of data collected from the state cancer registry maintained by the Michigan Department of Health and Human Services. We identified patients with an esophageal cancer diagnosis between January 1, 2000, and December 31, 2013. χ2 test and logistics regression were used to analyze 6,809 patients who met our eligibility criteria. Statistical significance was defined as P ≤ .05. Approximately 88.4% of our patients were White and 11.6% were Black. A significantly higher number of White patients were married when compared with Blacks (62.9% v 31.8%, respectively; P < .0001). There was no significant difference in cancer staging between the 2 groups (P = .0671). Married Blacks had similar rates of esophagectomy, chemotherapy, and radiation as married Whites. Both single groups had lower rates of esophagectomy and chemotherapy than married Whites, but single Blacks were the least likely to undergo esophagectomy. Single patients were more likely to refuse treatment. Marital status differs significantly in Black and White patients with esophageal cancer and may help explain racial disparities in cancer care. Further research is needed to explore reasons for care underutilization in single patients and whether these differences translate into clinical outcomes.


Rejection of the genus name Methanothrix with the species Methanothrix soehngenii Huser et al. 1983 and transfer of Methanothrix thermophila Kamagata et al. 1992 to the genus Methanosaeta as Methanosaeta thermophila comb. nov. Opinion 75.
The Judicial Commission of the International Committee on Systematics of Prokaryotes has decided to place the genus Methanothrix with the species Methanothrix soehngenii Huser et al. 1983 on the list of nomina rejicienda, based on the fact that it is not represented by an axenic culture and contravenes Rule 31a of the International Code of Nomenclature of Bacteria. The species Methanothrix thermophila is transferred to the genus Methanosaeta as Methanosaeta thermophila (Kamagata et al. 1992) Boone and Kamagata 1998 comb. nov.


Technetium-99m N,N'-bis(2-mercapto-2-methylpropyl)-2-aminobenzylamine: technetium-99m complexes of a novel bis(aminoethanethiol) ligand.
A new N2S2 ligand system, N,N'-bis(2-mercapto-2-methylpropyl)-2- aminobenzylamine, U-BAT, 1, containing uneven amine groups (two amine groups with different pKa values) for complexing [TcVO]3+, was prepared. The reaction of this novel ligand with [99mTc]pertechnetate, in the presence of stannous tartrate as the reducing agent, produces the neutral and lipid-soluble [99mTc]TcVO(U-BAT), TcS2C15H23N2O, 2. However, when the same reaction was carried out at a higher pH, 9-10, and with 30 min of heating (100 degrees C), a second neutral but more lipid-soluble complex, [99mTc]TcVO(OU-BAT), TcS2C15H21N2O, 3, was isolated. The X-ray crystallography data of the 99Tc complexes show square pyramidal coordination with N2S2 as the base and the Tc = O in the apical position. Compound 3 can be derived from 2 by an oxidation of the ligand to form an imine. After iv injection into rats, the neutral and lipid-soluble technetium-99m complexes showed significant brain uptake, 1.54 and 1.07% dose/organ at 2 min for [99mTc]TcVO(U-BAT) and TcVO(OU-BAT), respectively. The novel Tc chemistry of this new ligand system may provide a useful foundation for designing Tc complexes with a built-in redox mechanism.


Effects of endothelial nitric oxide synthase gene expression on the tumor biology of human oral carcinoma SCC-25 cells.
Stable transfection of endothelial nitric oxide synthase (eNOS) cDNA in human oral carcinoma SCC-25 cells was performed. Two eNOS-expressing clones were isolated, and both were shown to have increased eNOS expression as assayed by Northern and Western analyses. Furthermore, a nitrite assay indicated that nitric oxide production in eNOS-transfected cells was increased. The growth rate and plating efficiency of eNOS-transfected cells in vitro were lower than that of the wild-type parental or vector control-transfected cells as assayed by growth curves, [3H]thymidine incorporation, and standard plating efficiency assays in L-arginine-rich medium. However, when these cancer cells were inoculated into nude mice, tumor size of eNOS-transfected cells was smaller during the first 25 days but increased later as compared to tumor size of parental and vector control-transfected cells. It is not clear whether the later increase in tumor size was due to an increase in SCC-25 cancer cell proliferation, normal stromal cell proliferation, or both. These results show significant effects of overexpression of eNOS on tumor growth in vitro and in vivo.


Alternative states of Amoebae. Studies on Nuclear RNA and DNA synthesis.
Actively proliferating Amoebae were kept in the interphase part of the cell cycle for prolonged periods by restricting the food supply. When the cells were returned to normal food supply, the clones failed to grow exponentially. The clones in this period of growth phase were in an 'alternative state' as opposed to their normal state of active proliferation. Nuclear RNA and DNA synthesis of cells in this alternative state was studied. Nuclei from cells in this alternative state were implanted into normal cells to study the effects on the synthesizing activities of the host cells. The results showed that there was a marked reduction in DNA and RNA synthesis in the host nucleus in the binucleated cells.


Electrospun Poly-L-Lactic Acid Scaffolds Surface-Modified via Reactive Magnetron Sputtering Using Different Mixing Ratios of Nitrogen and Xenon.
Controlled regeneration processes involving tissue growth using the surface and structure of scaffolds, are actively used in tissue engineering. Reactive magnetron sputtering is a versatile surface modification method of both metal and polymer substrates, as the properties of the formed coatings can be modified in a wide range by changing the process parameters. In magnetron sputtering, the working gas and its composition have an influence on the chemical composition and physical characteristics of the obtained coatings. However, there are no studies addressing the influence of the nitrogen/xenon gas mixture ratio in direct current magnetron sputtering on the deposition rate, physicochemical and in vitro properties of surface-modified biocompatible poly-L-lactic acid scaffolds. In this study, the application of mixtures of nitrogen and xenon in various ratios is demonstrated to modify the surface of non-woven poly-L-lactic acid scaffolds by direct current magnetron sputtering of a titanium target. It has been found that the magnetron sputtering parameters chosen do not negatively influence the morphology of the prepared scaffolds, but increase the hydrophilicity. Moreover, quantitative spectroscopic analysis results indicate that the formed coatings are primarily composed of titanium oxide and titanium oxynitride compounds and is dependent on the gas mixture ratio only to a certain extent. Atomic force microscopy investigations of the roughness of the fibers of the electrospun scaffolds and the thickness of the coatings formed on them show that the considerable variations observed in the intrinsic fiber reliefs are due to the formation of a fine layer on the fiber surfaces. The observed decrease in roughness after plasma modification is due to temperature and radiation effects of the plasma. In vitro experiments with human osteosarcoma cells show that the scaffolds investigated here have no cytotoxic effect on these cells. The cells adhere and proliferate well on each of the surface-modified electrospun scaffolds, with stimulation of cell differentiation in the osteogenic direction.


The clinical course of sarcoidosis: presentation, diagnosis, and treatment in a large white and black cohort in the United States.
Although numerous reports have described the clinical features of sarcoidosis in various ethnic and racial groups, many have been limited by small size, homogenous populations, and relatively short follow-up periods. We report the clinical characteristics of a large, race-sex-age diverse cohort of sarcoidosis clinic patients followed in a large university medical center for an extended period of time. This study included clinical data for sarcoidosis patients followed over a 12-year period at a sarcoidosis clinic at the Medical University of South Carolina. 1774 sarcoidosis patients were identified. Black females were more common (44%) than other race/gender combinations (p = 0.01). The diagnosis of sarcoidosis occurred > 3 months after the onset of symptoms in 48% of the cohort and > 1 year after the onset of symptoms in 25%. Anti-sarcoidosis treatment was required in 61% of the patients. Pulmonary function improved over time and the median corticosteroid requirement lessened. Compared to whites, blacks had more advanced radiographic stages of sarcoidosis (p < 0.0001), more organ involvement (p < 0.0001), and more frequently required anti-sarcoidosis medication (p < 0.0001). Compared to women, men had more advanced radiographic stages of sarcoidosis (p < 0.0001). The analysis indicates that sarcoidosis tends to improve over time in terms of pulmonary function and medication requirements. The disease was found to be more severe in blacks than whites. Treatment was not necessarily required. These results provide a comprehensive model of the course and treatment of sarcoidosis in the clinical setting.


An exploratory retrospective assessment of a quantitative measure of diabetes risk: medical management and patient impact in a primary care setting.
Primary care providers with limited time and resources bear a heavy responsibility for chronic disease prevention or progression. Reliable clinical tools are needed to risk stratify patients for more targeted care. This exploratory study examined the care of patients who had been risk stratified regarding their likelihood of clinically progressing to type 2 diabetes. This was a retrospective chart review pilot study conducted to assess a primary care provider's use of a risk screening test. In this quality improvement project, the result of the risk screening was examined in relation to its influence on medical management and clinical impact on patients at risk for diabetes. All providers were board certified in family medicine and had more than 10 years clinical experience in managing diabetes and prediabetes. No specific clinical practice guidelines were mandated for patient care in this pilot study. Physicians in the practice group received an orientation to the diabetes risk measure and its availability for use in a pilot study to be conducted over a 6-month period. We identified the 696 nondiabetic adults in family practices who received a risk screening test (PreDx(®), a multi-marker blood test that estimates the 5-year likelihood of conversion to type 2 diabetes) between June and November 2011 for a 6-month sample. A comparison group of 2,002 patients from a total database of 3.2 million patients who did not receive the risk test was randomly selected from the same clinical database after matching for age, sex, selected diagnoses, and metabolic risk factors. Patient groups were compared for intensity of care provided and clinical impact. Compared to patients with a similar demographic and diagnostic profile, patients who had the risk test received more intensive primary care and had better clinical outcome than comparison patients. Risk-tested patients were more likely to return for follow-up visits, be monitored for relevant cardio-metabolic risk factors, and receive prescription medications with P<0.001. Further, intensity of care was associated with the level of risk test result: patients with moderate or high scores were more likely to return for follow-up visits and receive prescription medications than patients with low scores. All P-values for comparison patients between the low and moderate groups, low and high groups, and moderate and high groups resulted in P<0.001. Risk-tested patients were more likely than their comparison group counterparts to achieve weight reduction, lowered blood pressure, and improved blood glucose and cholesterol as demonstrated by P-values of <0.001. Use of a risk stratification test in primary care may help providers to more effectively identify high risk patients, manage diabetes risk, increase patient involvement in diabetes risk management, and improve clinical outcomes. A randomized controlled study is the next step to investigate the impact of diabetes risk stratification in primary care.