Critical review of psychosocial interventions in cancer care.
The need for a large variety of psychosocial interventions is enhanced as increasing numbers of patients with cancer have longer survival. This article reviews the four interventions used most commonly: (1) education, (2) behavioral training, (3) individual psychotherapy, and (4) group interventions. It examines the outcomes of each type of intervention. This comprehensive review of the intervention literature reveals the availability of a wide range of options for patients with cancer and their potential psychological and physical health benefits.


Brain metastases in patients with ALK+ non-small cell lung cancer: clinical symptoms, treatment patterns and economic burden.
Brain metastases (BM) are highly prevalent among anaplastic lymphoma kinase positive (ALK+) non-small cell lung cancer (NSCLC) patients; yet little is known about their real-world treatment patterns and clinical and economic burdens. This study aimed to describe these patients' treatment patterns, symptoms, and costs. Retrospective study pooling data from three large administrative databases in the US (08/2011-06/2013). ALK+ NSCLC patients with BM and continuous enrollment for ≥ 60 days before and ≥ 30 days after the first observed BM diagnosis were identified by pharmacy records for crizotinib among patients with lung cancer and BM diagnostic codes. Treatment patterns, symptoms, healthcare resource utilization, and costs, before and after BM diagnosis. Of the 213 crizotinib patients with BM diagnoses meeting the selection criteria, 23.0% had BM prior to NSCLC diagnosis; 47.4% had BM prior to crizotinib initiation; 19.2% during crizotinib treatment; and 10.3% post-crizotinib treatment. For those diagnosed with BM after NSCLC diagnosis, the median time between the NSCLC and BM diagnoses was 88 days. Following the first observed BM diagnosis, 88.7% used chemotherapy, 63.4% had radiotherapy, and 31.9% had stereotactic radiosurgery. The prevalence of BM-related symptoms substantially increased post-BM-diagnosis: fatigue (from 15% to 39%), headaches (from 5% to 24%), and depression (from 5% to 15%). Monthly costs per patient averaged $5983 before the BM diagnosis and $22,645 after diagnosis. Patients' resource utilization increased significantly post-BM-diagnosis, with a 3-fold increase in OP visits and a 6-fold increase in IP stays. Post-BM-diagnosis costs were driven by pharmacy (42.0%), inpatient (29.6%), and outpatient costs (26.0%). The study sample was limited to crizotinib-treated patients. Post-BM-diagnosis, patients experience high symptom burden. Post-BM-diagnosis, treatment is highly variable and costly: average monthly costs per patient almost quadrupled post-BM-diagnosis.


Accuracy of hospital discharge coding data for the surveillance of drain-related meningitis.
Surveillance of healthcare-associated infections is labor intensive and complex. Discharge coding is an accessible source of information that may support detection of cases. For drain-related meningitis, however, discharge coding data had low sensitivity (32%) and positive predictive value (35%) and could neither replace nor improve existing complex surveillance systems.


Surveillance for homicide among intimate partners--United States, 1981-1998.
A substantial percentage of all homicides in the United States are committed by intimate partners of the victims. Among females, approximately 1 in 3 homicides are intimate partner homicides (IPHs). Intimate partner homicides cannot be tracked by using death certificates because death certificates do not record the victim's relationship to the perpetrator. This report summarizes information regarding IPHs that occurred in the United States during 1981-1998. This report is based on Supplemental Homicide Reports (SHRs) collected by the Federal Bureau of Investigation (FBI) as part of their Uniform Crime Reporting System. SHRs are filed voluntarily by police departments for homicides occurring within their jurisdiction. SHRs include demographic variables regarding victims and perpetrators, their relationship, and weapon(s) used. Data from the SHR file were weighted by comparison with homicide data from death certificates to compensate for underreporting. IPHs were restricted to victims aged > or = 10 years. The risk for death from IPH among males was 0.62 times the risk among females. However, the rate among black males was 1.16 times the rate among black females. Among racial groups, rates among blacks were highest, and the rates among Asian or Pacific Islanders were lowest. Rates were highest among females aged 20-49 years and among males aged 30-59 years. During the study period, rates among white females decreased 23%, and rates among white males decreased 61.9%. Rates among black females decreased 47.6%, and rates among black males decreased 76.4%. Highest rates occurred in the southern and western states among both white and black females. A graded increase in IPH risk occurred with community population size. Approximately 50% of IPHs were committed by legal spouses and 33% by boyfriends or girlfriends for both male and female victims. IPH rates were less than expected during the months of January, October, and November. Although total homicide rates have fluctuated during 1981-1998, IPH rates have decreased steadily during this period, and among certain subpopulations, the decrease has been substantial. Decreases are temporally associated with the introduction of social programs and legal measures to curb intimate partner violence, but a causal relationship has not been established. Likewise, no confirmed explanation exists for the greater decrease in rates among males compared with rates among females. The differences in IPH rates by race indicate that economic, social, and cultural factors are involved. The analysis by community population size and state demonstrates that regional sociocultural differences might be involved also. Access to firearms might be a key factor in both male and female IPHs. The descriptive epidemiology of IPH is changing rapidly and should continue to be monitored. Understanding the reasons forthe recent decreases in IPHs might help identify methods for primary and secondary prevention and further reduce IPH rates.


Over-replication of DNA in S phase Chinese hamster ovary cells after DNA synthesis inhibition.
Agents that inhibit DNA synthesis increase the frequency of methotrexate resistance and gene amplification in cultured mammalian cells. Chinese hamster ovary cells blocked with hydroxyurea rereplicated dihydrofolate reductase gene sequences within a single cell cycle upon release from the block (Mariani, B.D., and Schimke, R.T. (1984) J. Biol. Chem. 259, 1901-1910). Perturbation of DNA synthesis was postulated to result in misfiring of replicon initiation, subsequent over-replication of DNA sequences, and amplification of specific genes. To test this hypothesis, we have exposed Chinese hamster ovary cells pulsed with bromodeoxyuridine to three agents that inhibit DNA synthesis and enhance gene amplification: UV irradiation, hydroxyurea, and aphidicolin. After release from the block, the progression of cells throughout the cell cycle was analyzed by flow cytometry through simultaneous measurement of total cellular DNA content and bromodeoxyuridine-labeled DNA. Although the cell cycle effects varied depending on the agent used for the block, in all cases a subset of cells that were in S phase at the time of the block exhibited DNA histograms with greater than 4C DNA content at various times after release and prior to cell division. Cells with the excess DNA were approximately 10-fold more resistant to methotrexate compared to treated cells with normal DNA content or untreated cells. Therefore, cells in S phase at the time of the block produce excess DNA per cell prior to division, and this over-replicated DNA may be relevant to gene amplification and drug resistance.


A novel K+ competitive acid blocker, YH4808, sustains inhibition of gastric acid secretion with a faster onset than esomeprazole: randomised clinical study in healthy volunteers.
YH4808, a K+ -competitive acid blocker, is under clinical development for the treatment of acid-related disorders, such as gastroesophageal reflux disease. To determine the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of YH4808, compared to placebo and esomeprazole. This double-blind, randomised, placebo- and active comparator (esomeprazole)-controlled study was conducted with 123 healthy male volunteers. We evaluated YH4808 (30-800 mg) properties, administered in single (N=55) and multiple (N=24) oral doses, and recorded the effects on 24-hour intragastric acidity. Results were compared to placebo (N=20) and esomeprazole 40 mg (N=24). Plasma YH4808 exposure increased dose-proportionally and declined in a multi-phasic manner. YH4808 ≥200 mg/d maintained intragastric acidity at pH >4 for longer times than esomeprazole during both day and night (%Time at pH >4: >70% vs 58% of a 24-hour period, respectively; and >50% vs 33% of a 9-hour night respectively). A twice-daily regimen of YH4808 more effectively controlled intragastric pH at night than a once-daily regimen. In evaluating the mean areas under the intragastric pH-time curves in 15-minute intervals for 2 hours after dosing, we found that YH4808 had a faster onset than esomeprazole. Moreover, unlike esomeprazole, YH4808 PK and PD were not significantly affected by the CYP2C19 genotype of the subjects. YH4808 was well-tolerated at all doses administered. This study showed that YH4808 produced a rapid, sustained suppression of gastric secretion with good tolerability. The results at YH4808 ≥200 mg/d provide a rationale for further clinical investigations in populations with acid-related diseases.


Self-similarity and quasi-idempotence in neural networks and related dynamical systems.
Self-similarity across length scales is pervasively observed in natural systems. Here, we investigate topological self-similarity in complex networks representing diverse forms of connectivity in the brain and some related dynamical systems, by considering the correlation between edges directly connecting any two nodes in a network and indirect connection between the same via all triangles spanning the rest of the network. We note that this aspect of self-similarity, which is distinct from hierarchically nested connectivity (coarse-grain similarity), is closely related to idempotence of the matrix representing the graph. We introduce two measures, ι(1) and ι(∞), which represent the element-wise correlation coefficients between the initial matrix and the ones obtained after squaring it once or infinitely many times, and term the matrices which yield large values of these parameters "quasi-idempotent". These measures delineate qualitatively different forms of "shallow" and "deep" quasi-idempotence, which are influenced by nodal strength heterogeneity. A high degree of quasi-idempotence was observed for partially synchronized mean-field Kuramoto oscillators with noise, electronic chaotic oscillators, and cultures of dissociated neurons, wherein the expression of quasi-idempotence correlated strongly with network maturity. Quasi-idempotence was also detected for macro-scale brain networks representing axonal connectivity, synchronization of slow activity fluctuations during idleness, and co-activation across experimental tasks, and preliminary data indicated that quasi-idempotence of structural connectivity may decrease with ageing. This initial study highlights that the form of network self-similarity indexed by quasi-idempotence is detectable in diverse dynamical systems, and draws attention to it as a possible basis for measures representing network "collectivity" and pattern formation.


Prolonged incubation period in neonatal Pasteurella multocida meningitis and bacteremia.
Pasteurella multocida, often found as part of the human oral flora and in finger/toenails, also exists in many animals, especially cats, dogs, and pigs. Although rare, pasteurella infection in neonates can cause serious systemic disease, such as meningitis. In this article, a 23-day-old girl presented with decreased appetite and irritability for >2 days. Eighteen days previously her pet cat had jumped onto the left side of her head while she was sleeping. On laboratory data C-reactive protein was high, and on cerebrospinal fluid (CSF) analysis leukocyte count was extremely high, with low glucose and high protein. P. multocida grew out of the blood and CSF cultures, and she was successfully treated with antibiotics for 3 weeks. Although pasteurellosis rarely occurs, it can sometimes lead to life-threatening situations, so parents should exercise caution when having pets around their children.


Pax3 and Pax7 are expressed in commissural neurons and restrict ventral neuronal identity in the spinal cord.
Pax3 and Pax7 are transcription factors sharing high sequence identity and overlapping patterns of expression in particular in the dorsal spinal cord. Analysis of Pax3 and Pax7 double mutant mice demonstrates that both genes share redundant functions to restrict ventral neuronal identity in the spinal cord. In their absence, the En1 expression domain is expanded dorsally but that of Evx1 is not affected. In addition, Pax3 and Pax7 are expressed in commissural neurons and double mutant embryos exhibit highly reduced ventral commissure. Our findings reveal two distinct regulatory pathways for spinal cord neurogenesis, only one of which is dependent on Pax3/7 and 6.


A novel T cell cytokine stimulates interleukin-6 in human osteoblastic cells.
Rheumatoid arthritis (RA) is an autoimmune disease characterized by a heavy lymphocytic infiltration into the synovial cavity, resulting in the secretion of a variety of cytokines which ultimately leads to destruction of joint tissue. Among the infiltrating cells are activated T cells which produce specific cytokines capable of osteoclast progenitor cell expansion, fusion, and activation. Cultures of activated human T cells and human osteoblasts (hOBs) were used to study the possibility that lymphokines may act on osteoblasts to produce the osteoclastogenic factor interleukin-6 (IL-6). Purified T cells were activated with a combination of anti-CD3 and anti-CD28 antibodies, cocultured with hOBs in direct physical contact or separated by a transwell system, and conditioned media (CM) were assayed for IL-6 production. After a 72 h incubation period, activated T cell-hOB interaction resulted in a 100-fold increase of IL-6 production over basal levels. The immunosuppressant cyclosporine A (CsA) inhibited T cell tumor necrosis factor alpha and IL-6 production but did not inhibit the T cell induction of IL-6 from hOB. Assay of activated T-cell CM on hOB revealed that a soluble factor, not cell-cell contact, was the major inducer of IL-6. The induction of IL-6 mRNA by both activated T cell CM and CsA-treated activated T cell CM was confirmed by Northern blot analysis. Neutralizing antibodies to IL-13 and IL-17 did not affect IL-6 production. These findings suggest that activated T cells produce a novel, potent, IL-6 inducing factor that may be responsible for the bone loss observed in RA patients.


Histone H1o in developing rat brain cells.
Histone H1o was found both in neuronal and oligodendrocyte rat-brain nuclei fractionated by sucrose-gradient isopycnic centrifugation. This histone was absent during the early stages of development when the brain cells were still proliferating, but it appeared in significant amounts in the terminally differentiated cells.


Integrin triplets of marine sponges in human brain receptor heteromers.
Based on our theory, we have discovered main triplets of amino acid residues in cell-adhesion receptors of marine sponges, which appear also as homologies in several receptor heteromers of human brain. The obtained results strengthen our hypothesis that these triplets may "guide-and-clasp" receptor-receptor interactions.


Frequency of isolation of various subtypes and antimicrobial resistance of Shigella from urban slums of Karachi, Pakistan.
Shigellosis remains a major public health problem in developing countries. Antimicrobial resistance has complicated the empirical treatment. Knowledge of serotypes is crucial in vaccine development, as cross-protection between various serotypes is limited. Therefore we conducted a prospective study to determine the frequency of isolation of Shigella serotypes and antimicrobial resistance. Stool samples from 8155 individuals, collected through a surveillance study conducted in four slums of Karachi from January 2002 to March 2004, were cultured. Shigella was isolated in 394 (4.8%) of 8155 patients presenting with diarrhea. Two hundred and forty-two (62%) isolates were Shigella flexneri, 72 (18%) were Shigella sonnei, 43 (11%) were Shigella boydii, and 37 (9%) were Shigella dysenteriae. Thirteen S. flexneri serotypes were identified, of which the most frequent were 2a (38), 6 (37), and 1b (25), followed by 2b (23). Only 22 (5.6%) Shigella isolates were found to be pan-susceptible. Large proportions of isolates were resistant to co-trimoxazole (89% S. flexneri, 81% S. dysenteriae, 80% S. sonnei, and 56% S. boydii) and ampicillin (87% S. flexneri, 68% S. dysenteriae, 35% S. boydii, and 4% S. sonnei). Concurrent circulation of multiple strains with high resistance is worrying and mandates surveillance at the national level to facilitate the control of shigellosis.


[Four cases of 5-fluorouracil-related hyperammonemia in patients with large intestinal cancer and multiple liver metastases, including a case of hyperammonemia treated using hemodialysis].
Systemic chemotherapy based on 5-fluorouracil (5-FU) is a standard treatment for unresectable or recurrent large intestinal cancer. Although hyperammonemia is a known side effect of 5-FU that can cause serious pathological conditions, only a few cases have been reported. We describe 4 cases of 5-FU-related hyperammonemia with impairment of consciousness in patients who received 5-FU chemotherapy for large intestinal cancer with multiple liver metastases. Hemodialysis was effective in 1 severe case. There have been no detailed reports on the use of hemodialysis for hyperammonemia caused by 5-FU. Renal dysfunction is considered to be a risk factor for hyperammonemia caused by 5-FU and it is necessary to pay particular attention in patients with renal dysfunction who receive chemotherapy with 5-FU. Here we summarize our cases together with 16 previously reported cases of hyperammonemia caused by 5-FU in Japan.


The labelling of dispensed medicines for the elderly patient: a pilot survey.
The problems that elderly patients encounter when managing their own drugs were approached from the point of view of the understanding that these patients have of the labels on dispensed medicines. Thirty medically qualified volunteers at Burton District Hospital Centre were used to evaluate the adequacy of the present handwritten, labelling system for elderly out-patients by the use of a questionnaire. Further, by means of structured interviews with thirty elderly out-patients and a discriminating test procedure, the proposed, new, typed, labelling system was compared with two other labelling systems, the ability of the patients to understand the labels determined and the efficiency of the proposed, new system tested. The trends indicated by this pilot survey are that the present system of handwritten labels is inadequate and inefficient. Medical staff may repeatedly go over instructions and patients identify their drugs by means other than the label. Regardless of the quality of the label the regimen for a particular patient often determines the necessity for repeat instructions. Further, the proposed, typed, labelling system was ranked last by staff and patients when compared with two other systems (Ladywell and Thomas). The ability of patients to understand typed labels was very low. A new labelling system based on these trends is proposed.


Cultural-developmental tasks and adolescent development: theoretical and methodological considerations.
The focus of this paper is to clarify the oft-used concept of developmental tasks and place it within a cultural context. The role of "cultural-developmental" tasks in the development and modification of the adolescent's social-cognitive functioning is discussed, as are the respective roles of both individual and contextual-environmental factors in the production of these competencies. A theory which includes the individual's activity as an essential mediator between the individual and the context is outlined. Preliminary research supporting this view is then presented. Finally, some possibilities for assessing cultural-developmental tasks (from the adolescent's point of view) are discussed.


Residue dynamics of acephate and methamidophos in urban dooryard citrus foliage, Pompano Beach, Florida--August-September 1978.
Residues of acephate and its toxic metabolite methamidophos, attributable to the State-Federal program for eradication of the citrus blackfly (CBF) [Aleurocanthus woglumi Ashby] on citrus foliage, were assessed in urban areas in Pompano Beach, Florida. Eighteen dooryard citrus trees were sampled on two line transects, each ca 1.6 km long, along two city streets. The trees were sampled twice monthly for five months, beginning before chemical treatments were applied, continuing through the acephate treatment period, and ending when residues decreased below the limits of detection. Acephate and methamidophos residues, as high as 302.5 ppm and 15.8 ppm, respectively, were detected on leaves within one day after the first of a series of three treatments. Significant conversion of acephate to methamidophose was observed. Of the 143 samples collected, 114 contained measurable residues of both compounds; methamidophos accounted for an average of 19 percent of the total residues. Both compounds degraded rapidly, however, and residues averaged below 1 ppm approximately four weeks after the third treatment in the series. Average foliar half-lives for acephate and methamidophos were 8.93 days (SD = 2.52) and 8.40 days (SD = 2.55), respectively.


CT of hepatic tumors: prevalence and specificity of retraction of the adjacent liver capsule.
The purpose of this study was to describe the CT features of capsular retraction of the liver adjacent to hepatic tumors and to test the hypothesis that this finding is specific for malignant hepatic tumors. We first retrospectively reviewed the CT scans of eight patients with pathologically proved malignant hepatic tumors (five secondary and three primary) who had CT scans that showed retraction of the overlying liver capsule. Then, using criteria developed from the first eight cases, we prospectively studied 253 patients with pathologically proved hepatic tumors (75 benign, 178 malignant) to determine the prevalence of retraction of the liver capsule shown by CT and the specificity of this finding for malignant hepatic tumors. CT scans in the first eight patients showed two types of capsular retraction. In seven patients, the retracted liver capsule was smooth and regular. In one patient, capsular retraction was associated with central ulceration extending to and eroding the liver capsule. Four of 253 patients studied prospectively had hepatic tumors with associated capsular retraction (prevalence, 2%). In those four cases, the retracted liver capsule was smooth and regular. All four tumors were malignant (one fibrolamellar hepatocellular carcinoma, two carcinoid tumors, one colorectal metastasis). Capsular retraction of the liver adjacent to hepatic tumors is an uncommon CT finding that appears to be specific for malignant hepatic tumors.


Selectin, platelet plays a critical role in granulocyte access to the pregnant mouse uterus under physiological and pathological conditions.
Leukocyte recruitment to the pregnant mouse uterus is associated with highly regulated patterns of expression of vascular adhesion receptors. One striking observation is the localized expression of mucosal vascular addressin cell adhesion molecule (MADCAM1) and selectin, platelet (SELP, formerly P-selectin) by maternal vessels in the vascular zone (VZ) during the first half of pregnancy. From midgestation onwards, endothelial cells lining the maternal vessels of the VZ in addition express vascular cell adhesion molecule-1 (VCAM1). The predominant cell population within these vessels is monocyte-like cells. Granulocytes and low numbers of lymphocytes are also present. Murine fetal trophoblast cells are almost devoid of adhesion molecules, including SELP. In contrast, spontaneous abortions of allogeneic pregnancies are characterized by dramatic upregulation of SELP on maternal VZ vessels and on fetal trophoblast cells. Upregulation of SELP is associated with a dramatic influx of highly activated granulocytes, which infiltrate the vessels and tissue of the VZ and the trophoblast. The majority of the activated granulocytes within the trophoblast undergo nuclear fragmentation, which can be detected by TUNEL staining. To demonstrate that SELP is involved in the recruitment of granulocytes to the pregnant uterus, we undertook long-term in vivo inhibition studies using a monoclonal antibody to inhibit the contribution of SELP to leukocyte trafficking to the decidua. In addition, the pregnant uteri of syngeneic Selp(-/-) x Selp(-/-) mice were investigated and compared to the controls. Our results clearly demonstrate the importance of SELP for granulocyte access to the pregnant mouse uterus under physiological and pathological conditions.


Release of alkaline phosphatase from human osteosarcoma cells by phosphatidylinositol phospholipase C: effect of tunicamycin.
Alkaline phosphatase (orthophosphoric-monoester phosphohydrolase [alkaline optimum], EC 3.1.3.1) expressed in two human osteosarcoma cell lines (Saos-2 and KTOO5) in culture was the tissue nonspecific type and was released from the plasma membrane by phosphatidylinositol (PI) phospholipase C. Despite a difference of 10-fold between the two cell lines in the amount of alkaline phosphatase expressed, the phospholipase solubilized nearly all of the phosphatase from resuspended cells of the two lines. Alkaline phosphatase released with Nonidet-P40 from Saos-2 cells had a Mr of 445,000 by gradient gel electrophoresis in the absence of detergent; that released by PI-phospholipase C was 200,000. The subunit Mr of both solubilized forms was 86,000. Thus, tetrameric alkaline phosphatase in the membrane is attached by a PI-glycan moiety and is converted to dimers when released by PI-phospholipase C. Tunicamycin treatment of Saos-2 cells in culture affected the release of alkaline phosphatase by a high concentration of PI-phospholipase C, but not by a low concentration; both the rate and extent of release were lower from treated cells. However, the enzyme released from the treated cells was in two forms with different molecular weights; it seems that both glycosylated and nonglycosylated dimers were transported to the cell surface and incorporated into the plasma membrane. Glycosylation does not appear to be necessary for alkaline phosphatase to be anchored in the membrane via PI.


Factors that affect voluntary vaccination of children in Japan.
Some important vaccinations are not included in the routine childhood immunization schedule in Japan. Voluntary vaccinations are usually paid as an out-of-pocket expense. Low voluntary vaccination coverage rates and high target disease incidence are assumed to be a consequence of voluntary vaccination. Therefore, this study aimed to explore factors associated with voluntary vaccination patterns in children. We conducted an online survey of 1243 mothers from a registered survey panel who had at least one child 2 months to <3 years of age. The voluntary vaccination mainly correlated positively with annual household income and mothers' positive opinions about voluntary vaccinations, but negatively with number of children. Financial support, especially for low income households and households with more than one child, may motivate parents to vaccinate their children. Communication is also an important issue. More opportunities for education and information about voluntary vaccinations should be provided to mothers without distinguishing between voluntary and routine vaccination.


'People who need people': attachment and professional caregiving.
From the perspective of attachment theory, this paper discusses individual differences in the quality of caregiving by direct-care staff for persons with intellectual disabilities. Theoretical arguments and findings from related literature are cited to support the probable role of professionals' own attachment experiences and their mental representations thereof. Case examples are drawn from a study on video-based interaction guidance for direct-care staff in group homes for persons with multiple, serious disabilities. These examples illustrate how interventions may avoid attachment-related defences against changing the quality and affective mutuality of personal contact with clients. However, the possibility is discussed that in parallel processes, quality management systems and institutional culture may selectively reinforce care patterns associated with insecure, dismissing attachment, while failing to reward the positive contribution that sensitive, affectively attuned caregiving makes to wellbeing of persons with disabilities.


Heterologous Prime-Boost Enhances the Antitumor Immune Response Elicited by Plant-Virus-Based Cancer Vaccine.
New cancer vaccine strategies are required to vanquish the self-tolerance and elicit robust immune responses against tumor-associated antigens and/or neoantigens. Contemporary approaches in nanomedicine center on the use of a single nanocarrier modified with multiple copies of multiple different functional domains, e.g., epitopes for vaccines. Therefore, we set out to develop a combinatorial approach toward the next-generation concept of epitope delivery: a prime-boost strategy in which the same epitope is delivered using different nanocarriers. We tested this concept in the setting of HER2+ breast cancer. We synthesized HER2-based cancer vaccines using three icosahedral plant viruses as carriers and evaluated the immune response as a result of repetitive, homologous immunization using BALB/c mice. Two of the vaccines induced a Th2-predominant response and the other a Th1-predominant response. To enhance the immunogenicity of the vaccines, we developed a heterologous prime-boost strategy with each of the vaccines administered only once, yielding higher titers of HER2-specific immunoglobulins and increasing the toxicity of the antisera toward cancer cells. The prime-boost also induced a Th1-predominant response. An in vivo tumor challenge showed that the prime-boost regimen reduced tumor growth and improved survival in mice. This novel strategy to elicit robust immune responses against weakly immunogenic antigens in principle could be broadly applicable to cancers and other diseases.


[The application of no nasal packing after functional endoscopic sinus surgery in type I and type II chronic sinusitis].
The subjective sensation of the patients and the treatment effect were compared prospectively between the no nasal packing group and the common nasal packing group. The patients were divided into no nasal packing group and nasal packing group matched for the type of chronic sinusitis. All patients received operation of functional endoscopic sinus surgery. The patients of no nasal packing group were given thoroughly bleeding control without nasal packing, while the patients of nasal packing group received nasal packing with sponge after hemostatic seaweed covering of wound. The nasal stents in nasal packing group were removed two days after operation, and the other treatments were all identical in the two groups. The clinical symptoms and treatment effect were compared between the two groups using visual analog scale. The levels of headache, rhinalgia, nasal obstruction, bleeding and nasal secretions volume at different time points, such as 1 day, 2 days and 3 days after operation, were evaluated and compared, as well as the recovering of operative region, such as crustal, secretion, reaction film, mucosal edema, vesicle and blockage of the sinus ostium. At the 1st day after operation, the degrees of headache, rhinalgia and nasal obstruction in the no nasal packing group were milder than the nasal packing group, and the differences have statistical significance. Two days after operation, the degrees of headache, rhinalgia and nasal obstruction, as well as the volume of bleeding and nasal secretions in the no nasal packing group were milder and lower than the nasal packing group, and the differences have statistical significance. Three days after operation, the differences of the indexes above were not statistically significant. The scores of total bleeding volume during the 3 days after operation showed no statistically significant difference between the two groups. Thirty-four patients were cured in no nasal packing group with the average epithelialization time of (10.7 +/- 2.6) weeks. Thirty-two patients were cured in nasal packing group with the average epithelialization time of (10.6 +/- 2.9) weeks. The difference of average epithelialization time between the two groups was not statistically significant. No nasal packing could relieve the discomfort caused by nasal packing and avoid the rebleeding and pain when removing the nasal stents. No nasal packing has obvious superiority than common nasal packing, and is effective in the treatment of depression. It is be appropriate for type I and type II chronic sinusitis patients without systemic disease with limited economic conditions.


Effects of Inserting Thiophene as a π-Bridge on the Properties of Naphthalene Diimide-alt-Fused Thiophene Copolymers.
On the basis of naphthalene diimide (NDI) units connected to thiophene (T), thienothiophene (TT), or dithienothiophene (DTT) units via a thiophene π-bridge, three new copolymers-PDTNDI-T, PDTNDI-TT, and PDTNDI-DTT, respectively-were synthesized and used in the fabrication of all-polymer solar cells (all-PSCs). The relationships between the structures of the polymers and their optoelectronic properties and photovoltaic performances as electron acceptors in all-PSCs were investigated in detail. As the number of copolymerized heteroaromatic rings in the DTNDI-based polymers increased, the power conversion efficiencies of the resulting all-PSCs were found to decrease. This decreasing trend in the photovoltaic performance is opposite to the results reported previously for NDI-based polymers lacking the thiophene π-bridge and naphthodithiophene diimide-based polymers. In addition, the three polymers were found to exhibit distinct molecular orientations: a face-on orientation for PDTNDI-T and edge-on orientations for PDTNDI-TT and PDTNDI-DTT. Our results indicate that large fused aromatic rings are not necessarily advantageous in the design of NDI-based polymers containing π-conjugated bridges.


Effects of pointing on the recall of simultaneous and sequential visuospatial arrays: a role for retrieval strategies?
The present four experiments examined the effects of pointing movements towards the target locations in a modified free recall task. Three factors were manipulated: the order of the move/no-move trials (blocked or mixed), the type of stimuli presentation (simultaneous or sequential) and the size of the to-be-recalled configurations (7-9 and 5-7 items). Results showed that pointing significantly decreased visuospatial performance both with a mixed and a blocked design. However, in the blocked condition the interference effect of pointing was load-dependent (being inversely related to array size) and occurred only when participants pointed to all stimuli in the first block. Post hoc analyses supported the conclusion that pointing movements interfered with the on-line development of appropriate retrieval strategies, like parsing the configurations into smaller chunks or creating global visual images.


Solid-phase organic synthesis of polyisoprenoid alcohols with traceless sulfone linker.
Solid-phase organic synthesis of polyprenols with a traceless sulfone linker is described. The polymer-bound benezenesulfinate is first linked with the "tail" building blocks of isoprenyl chlorides via S-alkylation. With use of dimsyl anion as an appropriate base, the polymer-bound alpha-sulfonyl carbanion is generated and coupled with other "body" building blocks in an efficient manner. After repeated processes and a global palladium-catalyzed desulfonation with LiEt 3BH as the reducing agent, the desired polyprenols with various chain lengths and geometrical configurations are obtained in 32-59% overall yields. The solid-phase synthesis offers the advantage in facile isolation of polyprenols without tedious operation or time-consuming purification.


Tracking the evolution of cancer methylomes.
Cellular transformation in cancer has long been associated with aberrant DNA methylation, most notably, hypermethylation of promoter sequences. A new study uses a clever approach of selective high-resolution profiling to follow DNA methylation over a time course of cellular transformation and challenges the notion that hypermethylation in cancer arises in an orchestrated fashion.


Genetic differences between primary larynx and pharynx carcinomas and their matched lymph node metastases by multiplex ligation-dependent probe amplification.
Lymph nodes metastasis is a major risk factor related to poor survival in larynx and pharynx carcinomas. The aim of this study is to search for markers of lymph node involvement analyzing the genetic differences between primary larynx and pharynx squamous cell carcinomas and their corresponding lymph node metastases. Twenty-five primary tumors and their corresponding lymph node metastases were examined. DNA copy number changes of 37 genes were analyzed by multiplex ligation-dependent probe amplification (MLPA). Loss of CDKN2A (9p21) occurred in 14 out of 25 pairs (56%) of primary tumor and lymph node metastases. Loss of LMNA (1q21) was exclusively detected in 8 lymph node samples (32%). Loss of CTNNB1 (3p22) and gain of CDKN2D (19p13) were also significantly more frequent in lymph node metastases. Other aberrations related to lymph node metastases were loss of MFHAS1 (8p23), RECQL4 (8q24) and gain of N33 (8p22) and TP53 (17p13). Primary tumor and corresponding lymph node metastases showed common genetic changes. However, the lymph node metastases presented with a number of additional alterations. Acquisition of these alterations may play a role in lymphatic metastasis development.


Double minute chromosomes and homogeneously staining regions in tumors taken directly from patients versus in human tumor cell lines.
There is increasing evidence that copies of amplified oncogenes or drug-resistant genes located on extrachromosomal DNA (e.g. double minutes and/or episomes) can be eliminated from mammalian tumor cell lines by treatment of the cells with low concentrations of hydroxyurea. However, amplified oncogenes or drug-resistant genes located in an intrachromosomal site (such as in a homogeneously staining region (HSR)) cannot be eliminated from the cells. A question which arises is do primary human tumors have extrachromosomal DNA present often enough to make elimination of that extrachromosomal DNA a potentially important therapeutic strategy? To address that question we have reviewed published cytogenetic analyses of 200 tumors taken directly from patients to determine the percentage of primary human tumors which have amplified genes present on extrachromosomal DNA (present in the form of double minutes [DMs]) vs the percentage of tumors which have amplified genes located on an intrachromosomal site (in the form of HSRs). Of the 200 primary human tumors reviewed, 91% contained DMs only, 6.5% contained HSRs, and 2.5% contained both. Of interest, in a parallel review of 109 cell lines with cytogenetic and/or molecular evidence of gene amplification, 60.6% contained DMs, 26.6% contained HSRs, and 12.8% contained both. These data indicate that DMs are the predominant cytogenetic marker for gene amplification in patients, but are present less frequently in established cell lines. These findings indicate that ongoing efforts to eliminate amplified drug-resistant genes or oncogenes contained on DMs (or precursors of DMs) from tumor cells may be relevant for in vivo situations.


Perioperative mechanical circulatory support for transplantation.
Mechanical circulatory assistance has become a necessary supplement to more conventional means of hemodynamic support as a shortage of donor organs and associated increase in waiting time have contributed to an increased incidence of hemodynamic deterioration in potential transplant recipients. This review summarizes the experience with circulatory support before and after transplantation of the Utah Transplantation Affiliated Hospitals (UTAH) Cardiac Transplant Program and draws conclusions on the efficacy of one program's use of mechanical circulatory support. Between March 1985 and October 1990, 401 patients were accepted for first-time heart transplantation by the UTAH program. One hundred and eighty patients (46%) were supported before transplantation with conventional hemodynamic therapies, 72 patients (18%) with oral enoximone, 96 patients (25%) with intravenous inotropes, and 34 patients (9%) with an intraaortic balloon; nine patients (2%) required centrifugal blood pump circulatory support. Not included in these statistics are 10 patients awaiting transplantation as of October 10, 1990. Thirty-eight candidates (10%) died awaiting transplantation, 329 (84%) received transplantation, and 24 (6%) were removed from the transplantation list for other reasons. Ten patients (3%) required mechanical circulatory support after transplantation with 38% of this group surviving 1 year after after transplantation. No single factor, including either hemodynamic support before transplantation or donor heart ischemic time, was found to be predictive of the need for mechanical circulatory support after transplantation. One-year survival rates after transplantation of patients requiring mechanical circulatory support before transplantation (86%) were not significantly different than for all transplant patients (88%). The experience of the UTAH Cardiac Transplant Program shows that with the judicious use of mechanical circulatory support transplant patients with advanced forms of hemodynamic support can have as equal a probability of survival as patients who undergo elective transplantation.


Application of waste ashes to agricultural land--effect of incineration temperature on chemical characteristics.
Incineration is one of the most important methods of municipal waste disposal. During incineration, various reactions of composition and decomposition may occur; the physical and chemical properties of municipal wastes may change to a great extent. In the present study, 15 samples, including food scraps (FS), animal wastes (AW) and sewage sludges (SS) were collected from various places in Japan, incineration treatments at 500 degrees C, 850 degrees C and 1000 degrees C were conducted in laboratory, and pH, EC, P content, various P forms, anions and soluble metals were determined. The results indicated that average pH increased by 1.09, 1.84, 2.27 and EC decreased by 4.6, 4.6, 5.6 ds m(-1) at 500 degrees C, 850 degrees C, 1000 degrees C, respectively, pH increased in the sequence of AM > SS > FS, and the decrease rate of EC was in the order of FS > SS > AM. Compared with no treatment (NT), water-soluble P decreased greatly at all three temperatures; available P increased at 500 degrees C, but decreased to the original level at 850 degrees C and 1000 degrees C; the amount of Ca-P, Fe-P and Al-P decreased and residual insoluble P increased greatly at 850 degrees C and 1000 degrees C; no significant change of total P was found at all three temperatures. However, water-soluble HPO4(2-) and Cl- decreased greatly, the decrease ratio of Cl- was in the sequence of SS > FS > AM at 500 degrees C, and FS > SS > AM at 850 degrees C and 1000 degrees C; no significant difference was found for HPO4(2-) among all three treatment temperatures; water-soluble SO4(2-) decreased at 1000 degrees C, but there was no significant change at 500 degrees C and 850 degrees C. Moreover, water-soluble Na, Mg, K, Ti, Mn, Fe, Ga, Cd, Zn, Ba, Pb, Sr, W and 0.1 M HNO3 soluble Al, K, Cr, Mn, Fe, Zn, Sr, Ba, Pb, Be, Ga, Rb, Cd, Sn, Sb, Ta, Tl, Bi, Na, Co, Ni, Sc, Cs decreased, but water-soluble Ca, Cr, Co, Ni and 0.1 M HNO3 soluble Cu, Ca, V, Mo, W, Th, U, Hf increased at 500 degrees C, 850 degrees C or 1000 degrees C.


A colorimetric assay method for Co2+ based on thioglycolic acid functionalized hexadecyl trimethyl ammonium bromide modified Au nanoparticles (NPs).
A simple, rapid and sensitive colorimetric assay method for detection of Co(2+) through thioglycollic acid (TGA) functionalized hexadecyl trimethyl ammonium bromide (CTAB) modified Au NPs has been discovered in our work. TGA functionalized CTAB modified Au NPs can be aggregated quickly in the presence of Co(2+) through a cooperative metal-ligand interaction. Transmission electron microscope (TEM), energy dispersive X-ray spectroscopy (EDS), and UV-vis spectra were used to characterize the Au NPs aggregation. The presence of Co(2+) is monitored by a colorimetric response of functionalized Au NPs, and had a detection limit of 3.0 × 10(-7) M. Moreover, the selectivity of this method has been investigated by comparing with other metal ions (Hg(2+), Na(+), Cu(2+), Cd(2+), Ba(2+), Pb(2+), Mn(2+), Ni(2+), Zn(2+), Fe(2+) and Fe(3+)).


Rapid hematopoietic recovery after coinfusion of autologous-blood stem cells and culture-expanded marrow mesenchymal stem cells in advanced breast cancer patients receiving high-dose chemotherapy.
Multipotential mesenchymal stem cells (MSCs) are found in human bone marrow and are shown to secrete hematopoietic cytokines and support hematopoietic progenitors in vitro. We hypothesized that infusion of autologous MSCs after myeloablative therapy would facilitate engraftment by hematopoietic stem cells, and we investigated the feasibility, safety, and hematopoietic effects of culture-expanded MSCs in breast cancer patients receiving autologous peripheral-blood progenitor-cell (PBPC) infusion. We developed an efficient method of isolating and culture-expanding a homogenous population of MSCs from a small marrow-aspirate sample obtained from 32 breast cancer patients. Twenty-eight patients were given high-dose chemotherapy and autologous PBPCs plus culture-expanded MSC infusion and daily granulocyte colony-stimulating factor. Human MSCs were successfully isolated from a mean +/- SD of 23.4 +/- 5.9 mL of bone marrow aspirate from all patients. Expansion cultures generated greater than 1 x 10(6) MSCs/kg for all patients over 20 to 50 days with a mean potential of 5.6 to 36.3 x 10(6) MSCs/kg after two to six passages, respectively. Twenty-eight patients were infused with 1 to 2.2 x 10(6) expanded autologous MSCs/kg intravenously over 15 minutes. There were no toxicities related to the infusion of MSCs. Clonogenic MSCs were detected in venous blood up to 1 hour after infusion in 13 of 21 patients (62%). Median time to achieve a neutrophil count greater than 500/microL and platelet count >/= 20,000/microL untransfused was 8 days (range, 6 to 11 days) and 8.5 days (range, 4 to 19 days), respectively. This report is the first describing infusion of autologous MSCs with therapeutic intent. We found that autologous MSC infusion at the time of PBPC transplantation is feasible and safe. The observed rapid hematopoietic recovery suggests that MSC infusion after myeloablative therapy may have a positive impact on hematopoiesis and should be tested in randomized trials.


Optimization of the structure of polyurethanes for bone tissue engineering applications.
Polyurethanes containing 22-70 wt.% hard segments were developed and evaluated for bone tissue engineering applications. Aliphatic poly(ester-urethanes) were synthesised from poly(epsilon-caprolactone) diol with different molecular masses (M= approximately 530, 1250 and 2000 Da), cycloaliphatic diisocyanate 4,4'-methylenebis(cyclohexyl isocyanate) and ethylene glycol as a chain extender. Changes in macromolecule order with increasing hard segment content were observed via modulated differential scanning calorimetry. Depending on the hard segment content, a gradual variation in polyurethane surface properties was revealed by Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy and static contact angle measurements. As the hard segments content increased the polyurethane surface exhibited more phase separation, a higher content of urethane moieties and higher hydrophilicity. The biocompatibility results indicated that proliferation of human bone-derived cells (HBDC) cultured in vitro improved with increasing hard segment content while the osteogenic potential of HBDC decreased with increasing hard segment content.


[Method of quantitative assessment of morphological changes in the central nervous system].
The author present a variant of quantitative assessment of the degree of morphological changes in the central nervous system neurons. It is suggested that the following groups of the changed neurons should be distinguished: swollen neuron with the initial manifestations of breaking large tigroid lumps into smaller ones; swollen neuron with marked phenomena of breaking large tigroid lumps into smaller ones and initial phenomena of hypochromatosis; swollen neuron with total tigrolysis with hyper- and hypochromatosis; dehydrated hyperchromic neuron; vacuolized neuron; contracted atrophic neuron; perished neuron. Each of the mentioned groups is given a mark, characterizing the degree of morphological changes. A formula for the assessment of the degree of morphological changes for individual formations and zones of the central nervous system is suggested.


Characterization of receptors for cholecystokinin and related peptides in mouse cerebral cortex.
The characteristics of cholecystokinin (CCK) binding to its receptors in a particulate membrane fraction of mouse cerebral cortex were studied by employing biologically active radioiodinated CCK prepared by conjugation with 125I-Bolton-Hunter (125I-BH) reagent. At 24 degrees C binding was rapid, reversible, and linearly related to protein content. Binding was maximal at acidic pH (6.5) and reduced by the presence of monovalent cations. Under physiological conditions (pH 7.4, 118 mM-NaCL, 4.7 mM-KCl) Scatchard plots of CCK binding were linear with a KD value of 1.27 nM and binding capacity of 115 fmol/mg protein. Optimal binding required the presence of both Mg2+ and EGTA, and was inhibited by the addition of micromolar concentrations of Cu2+ (ID50 = 30 microM). The cortical receptor recognized all major forms of CCK, with an order of potency of: cholecystokinin octapeptide (CCK8) greater than CCK greater than cholecystokinin tetrapeptide (CCK4). Desulfated cholecystokinin octapeptide (dCCK8) had a 10-fold lower affinity than CCK8. Dibutyryl cyclic GMP, a potent competitive inhibitor of CCK binding to receptors in pancreas, was not a specific inhibitor of CCK binding to brain receptors. These present results support the concept that CCK may function as a regulatory peptide in brain, and that the cortical CCK receptor is different from the receptors mediating the peripheral action of CCK.


Manipulation of glutathione stores in rat hepatic stellate cells does not alter collagen synthesis.
Hepatic stellate cells are resistant to the fibrogenic effects of lipid hydroperoxides in primary culture. Recent studies from our laboratory suggest that antioxidants, particularly glutathione, play a role in this resistance. We have observed that glutathione accumulates rapidly in stellate cells during primary culture; in the current study, we investigated whether glutathione modulates stellate cell collagen synthesis. Stellate cells from normal rat liver were plated in primary culture and maintained for 7 days. From day 4 through day 7, the cells were treated with L-buthionine sulfoximine (BSO) to deplete glutathione stores. BSO profoundly diminished stellate cell glutathione but had no effect on morphology, viability, or basal levels of collagen synthesis and gene expression. When cultured stellate cells were incubated with the putative fibrogenic mediator 4-hydroxynonenal or iron/ascorbate, little or no increase in collagen synthesis occurred regardless of glutathione content. In contrast, iron/ascorbate induced collagen synthesis by cultured fibroblasts. The data indicate that stellate cells strongly resist oxidant- and lipid peroxide-induced collagen synthesis in primary culture. They demonstrate that the mechanism of this resistance does not involve glutathione.


Mst1 deletion reduces hyperglycemia-mediated vascular dysfunction via attenuating mitochondrial fission and modulating the JNK signaling pathway.
Diabetes is a leading cause of microvascular complications, such as nephropathy and retinopathy. Recent studies have proposed that hyperglycemia-induced endothelial cell dysfunction is modulated by mitochondrial stress. Therefore, our experiment was to detect the upstream mediator of mitochondrial stress in hyperglycemia-treated endothelial cells with a focus on macrophage-stimulating 1 (Mst1) and mitochondrial fission. Our data illuminated that hyperglycemia incubation reduced cell viability, as well as increased apoptosis ratio in endothelial cell, and this alteration seemed to be associated with Mst1 upregulation. Inhibition of Mst1 via transfection of Mst1 siRNA into an endothelial cell could sustain cell viability and maintain mitochondrial function. At the molecular levels, endothelial cell death was accompanied with the activation of mitochondrial oxidative stress, mitochondrial apoptosis, and mitochondrial fission. Genetic ablation of Mst1 could reduce mitochondrial oxidative injury, block mitochondrial apoptosis, and repress mitochondrial fission. Besides, we also found Mst1 triggered mitochondrial dysfunction as well as endothelial cell damage through augmenting JNK pathway. Suppression of JNK largely ameliorated the protective actions of Mst1 silencing on hyperglycemia-treated endothelial cells and sustain mitochondrial function. The present study identifies Mst1 as a primary key mediator for hyperglycemia-induced mitochondrial damage and endothelial cell dysfunction. Increased Mst1 impairs mitochondrial function and activates endothelial cell death via opening mitochondrial death pathway through JNK.


School Indicators of Violence Experienced and Feeling Unsafe of Dutch LGB Versus Non-LGB Secondary Students and Staff, 2006-2010.
Gender and sexual orientation are expressed in heterosexual, lesbian (L), gay (G), bisexual (B), transgender (T), or queer (Q) interests and behavior. Compared with heterosexual persons, LGBTQ persons seem to experience more antisocial behavior, including negative discrimination and violence. To assess differences in LGBTQ-related discrimination in schools, the question for this research is "Do the degrees of violence experienced and feeling unsafe of LGBTQ students and staff in a school differ from those of non-LGBTQ students and staff in the same school?" Secondary analysis was carried out on data from a Dutch national digital monitor survey on safety in secondary schools. In 2006, 2008, and 2010, participation amounted to 570 schools, 18,300 teaching and support staff, and 216,000 students. Four indicators were constructed at the school level: two Mokken Scale means assessing severity of violence experienced and two Alpha Scale means assessing feeling unsafe. Analysis of mean differences showed that LGB students experienced more violence and felt less safe than non-LGB students; LGB staff felt less safe in school than non-LGB staff. When LGB students experienced more violence at school than non-LGB students, LGB students also felt less safe than non-LGB students for all 3 years. No such relationships existed for LGB staff, or between LGB staff and LGB students. No significant relationships were found between the four LGB school indicators and contextual school variables. The outcomes and uniqueness of the study are discussed. Recommendations are made to improve assessment and promote prosocial behavior of students and staff in schools.


[Changes in the level of cortisol in the blood of rabbits during self stimulation].
The time-course of changes in the blood plasma cortisol level during activation of the positive reinforcement system was studied in experiments on adult chinchilla male rabbits. The self-stimulation status of the brain lateral hypothalamus was utilized as a model for positive reinforcement. The basal cortisol level in intact rabbits, determined by means of radioimmunoassay, was equal to 5.31 +/- 0.87 micrograms% over a period of 10 to 2 hours p.m. The blood collection procedure, using the method of the ear marginal vein dissection, increases the cortisol concentration 30 minutes after blood collection by 19.4%, i.e. augments its level up to 6.37 +/- 0.90 micrograms%. A significant rise (P less than 0.01) of hormone release into the blood (two-fold) is seen 5 to 15 minutes following the self-stimulation test. Cortisol level remains heightened 1 hour after the self-stimulation experiment. The intensity of the corticotropic activity was not dependent on the hypothalamus, stimulated by force or by animals themselves. On the basis of the data obtained it is concluded that the hormonal response is directly dependent both on hypothalamic electric stimulation and on the motivative mechanism activation. The very positive reinforcement, timing to the post-stimulating period and being of full value only during the adaptive behavioral act, is not stress-inducing.


Knemometry.
Knemometry provides a powerful tool for observation of short-term growth patterns. Failure of response to growth-promoting therapies in the short term predicts a poor statural response, but the relationship of the lower leg growth suppression seen with oral and inhaled corticosteroids, and the clinical implications in the longer term, remain unclear. The accumulating evidence suggests that there are measurable biochemical and clinical effects with some inhaled corticosteroids (e.g. beclomethasone dipropionate and budesonide), when given at the upper end of the recommended conventional dose range (18) and for long-term prophylaxis, and certainly at the higher starting doses. It is imperative, therefore, that all children receiving inhaled corticosteroids should have their growth monitored carefully and that the lowest effective dose of corticosteroid should be used.


Regulation of the interaction of actin filaments with microtubule-associated protein 2 by calmodulin-dependent protein kinase II.
Phosphorylation of microtubule-associated protein 2 (MAP 2) by Ca2+-, calmodulin-dependent protein kinase II (protein kinase II) inhibited the actin filament cross-linking activity of MAP 2. This inhibition required the presence of ATP, Mg2+, Ca2+ and calmodulin. The minimal concentration of MAP 2 required for gel formation of actin filaments was increased with increasing amounts of phosphate incorporated into MAP 2, and the phosphorylated MAP 2, into which 10.3 mol of phosphate/mol of protein had been incorporated, did not cause actin filaments to gel under the experimental conditions used. The phosphorylation of MAP 2 by Ca2+-, phospholipid-dependent protein kinase (protein kinase C) and cAMP-dependent protein kinase also inhibited the actin filament cross-linking activity of MAP 2. The extent and rate of phosphorylation of MAP 2 by protein kinase II were higher than those of the phosphorylation by protein kinase C and cAMP-dependent protein kinase. The interaction of actin filaments with MAP 2 was inhibited more by the actions of protein kinase II and protein kinase C than by cAMP-dependent protein kinase. The actin filament cross-linking activity of MAP 2 phosphorylated either by protein kinase II, cAMP-dependent protein kinase or protein kinase C was retrieved when phosphorylated MAP 2 was treated by protein phosphatase. These results indicate that the interaction of actin filaments with MAP 2 is regulated by the phosphorylation-dephosphorylation of MAP 2.


Temporal glucocorticoid treatment: modulation of periodic endometrial responses during decidualization and pregnancy in rats.
The synthetic glucocorticoid, dexamethasone (Dex) was administered subcutaneously (1.5 mg/day/rat) in 3-days pretreatment regimens (Days 2-4, 4-6, 6-8, 8-10 and 10-12) to pseudopregnant rats in which decidualization was surgically induced and to pregnant rats. Variability in endometrial growth during decidualization and in the fetoplacental homeostasis of pregnancy was assessed at the end of each treatment period (Days 4, 6, 8, 10 and 12). During decidualization, endometrial growth (wet weight, protein and DNA) displayed significant (p < 0.05) time-dependent inhibitory profiles which rose steeply from Day 4 to Day 6 and declined thereafter to Day 10 in fairly well defined linear patterns. For the endometrial enzymes (isocitrate dehydrogenase, alkaline phosphatase and the matrix metalloproteinases--72 and 92 kDa), although the inhibitory patterns were inconsistent, a Days 6-8 treatment regimen seemed to be critical. By contrast Dex treatment induced progressive inhibition in serum progesterone concentrations from Day 2, to peak levels by Day 12. This indicates that time-related Dex inhibition of endometrial growth appeared not to be progesterone-mediated since the endometrial and progesterone inhibitory profiles were not in synchrony. The inhibitory effect of Dex under the pregnancy status demonstrated that birth potentials, fetal and placental weights, all had similar response patterns which rose from Day 4 to Day 8 and then underwent reductions to Day 12. Collectively, the results indicate that there was time dependency in growth inhibition by Dex at the endometrial and fetoplacental levels. Maximal sensitivity to drug exposure essentially coincided with the immediate post-traumal (decidualization) and postimplantation (pregnancy) periods.


Revisiting the Cutoff Criteria of Intelligibility in Context Scale-Traditional Chinese.
Background This study evaluated the validity of the Intelligibility in Context Scale-Traditional Chinese (ICS-TC) and explored its potential as a screening tool for speech sound disorder (SSD) in Cantonese-speaking children in Hong Kong. Method The parents of 789 Cantonese-speaking children aged between 2;4 (years;months) and 6;9 completed the ICS-TC. Children were categorized into 2 groups: (a) an SSD group whose initial consonant scores in a standardized assessment were equal to or lower than -1.33 SD and (b) a non-SSD group whose scores were higher than -1.33 SD. The screening accuracy of ICS-TC using a previously proposed cutoff was appraised. A cutoff score for each age group was determined when the effect of age on the ICS-TC mean scores was significant and the corresponding screening accuracy was appraised. Results When the previously proposed cutoff was applied to the whole sample, sensitivity and specificity were unsatisfactory. Given the significant age effect, new cutoff scores for each age group were estimated. The new cutoff scores only led to remarkably improved screening accuracy for Age Group 4 (4;0-4;5) but little to no improvement for other age groups. Conclusions There is limited clinical use of ICS-TC as a screening tool with a single cutoff score for children at different ages. Its clinical utility might be limited to children of about 4 years of age, where ICS-TC scores demonstrated the best differentiation between children with and without speech concerns. Future studies could refine the screening criteria to further minimize the number of false positives.


The impact of school support on depression among adolescent orphans: a cluster-randomized trial in Kenya.
The objective of this study was to determine if a school support intervention for adolescent orphans in Kenya had effects on mental health, a secondary outcome. In this paper, we analyzed data from a 4-year cluster-randomized trial of a school support intervention (school uniforms, school fees, and nurse visits) conducted with orphaned adolescents in Siaya County, western Kenya, who were about to transition to secondary school. 26 primary schools were randomized (1:1) to intervention (410 students) or control (425 students) arms. The study was longitudinal with annual repeated measures collected over 4 years from 2011 to 2014. We administered five items from the 20-item Center for Epidemiologic Studies Depression Scale Revised, a self-reported depression screening instrument. The intervention prevented depression severity scores from increasing over time among adolescents recruited from intervention schools. There was no evidence of treatment heterogeneity by gender or baseline depression status. The intervention effect on depression was partially mediated by higher levels of continuous school enrollment among the intervention group, but this mediated effect was small. School support for orphans may help to buffer against the onset or worsening of depression symptoms over time, promoting resilience among an important at-risk population.


Portal vein thrombosis after total knee replacement: a case report.
We present a 74-year-old woman who developed a portal vein thrombosis following an elective total knee replacement. She had atrial fibrillation for which she was taking warfarin for anticoagulation. Seven days prior to surgery, she was instructed to discontinue warfarin and replace it with prophylactic low-molecular-weight heparin. On postoperative day 1, routine blood tests revealed deranged hepatic synthetic function, despite standard anticoagulation management. Doppler ultrasonography confirmed a portal vein thrombosis. She was treated with therapeutic doses of low-molecular-weight heparin until her international normalised ratio reached therapeutic levels. Her liver function results had normalised 2 weeks later. Portal vein thrombosis is a potentially fatal complication that is reversible if identified and treated early.


[Characteristics of war wound infection].
War wounds are the most complex type of non-targeted injuries due to uncontrolled tissue damage of varied and multifold localizations, exposing sterile body areas to contamination with a huge amount of bacteria. Wound contamination is caused by both the host microflora and exogenous agents from the environment (bullets, cloth fragments, dust, dirt, water) due to destruction of the host protective barriers. War wounds are the consequence of destructive effects of various types of projectiles, which result in massive tissue devitalization, hematomas, and compromised circulation with tissue ischemia or anoxia. This environment is highly favorable for proliferation of bacteria and their invasion in the surrounding tissue over a relatively short period of time. War wounds are associated with a high risk of local and systemic infection. The infection will develop unless a timely combined treatment is undertaken, including surgical intervention within 6 hours of wounding and antibiotic therapy administered immediately or at latest in 3 hours of wound infliction. Time is a crucial factor in this type of targeted combined treatment consisting of surgical debridement, appropriate empirical antimicrobial therapy, and specific antitetanic prophylaxis. Apart from exposure factors, there are a number of predisposing factors that favor the development of polymicrobial aerobic-anaerobic infection. These are shock, pain, blood loss, hypoxia, hematomas, type and amount of traumatized tissue, age, and comorbidity factors in the wounded. The determinants that define the spectrum of etiologic agents in contaminated war wounds are: wound type, body region involved, time interval between wounding and primary surgical treatment, climate factors, season, geographical area, hygienic conditions, and patient habits. The etiologic agents of infection include gram-positive aerobic cocci, i. e. Staphylococcus spp, Streptococcus spp and Enterococcus spp, which belong to the physiological flora of the human skin and mucosa; gram-negative facultative aerobic rods; members of the family Enterobacteriacea (Escherichia coil, Proteus mirabilis, Klebsiella pneumoniae, Enterobacter cloacae), which predominate in the physiological flora of the intestines, transitory flora of the skin and environment; gram-negative bacteria, i. e. Pseudomonas aeruginosa, Serratia marcescens, Acinetobacter calcoaceticus - A. baumanii complex; environmental bacteria associated with humid environment and dust; anaerobic gram-positive sporogeneous rods Clostridium spp, gram-negative asporogeneous rods Bacteroides spp and gram-positive anaerobic cocci; Peptostreptococcus spp and Peptococcus spp. The latter usually colonize the intestine, primarily the colon, and the skin, while clostridium spores are also found in the environment. Early empirical antibiotic therapy is used instead of standard antibiotic prophylaxis. Empirical antimicrobial therapy is administered to prevent the development of systemic infection, gas gangrene, necrotizing infection of soft tissue, intoxication and death. The choice of antibiotics is determined by the presumed infective agents and localization of the wound. It is used in all types of war wounds over 5-7-10 days. The characteristics of antibiotics used in war wounds are the following: broad spectrum of activity, ability to penetrate deep into the tissue, low toxicity, long half-life, easy storage and application, and cost effectiveness. The use of antibiotics is not a substitution for surgical treatment. The expected incidence of infection, according to literature data, is 35%-40%. If the time elapsed until surgical debridement exceeds 12 hours, or the administration of antibiotics exceeds 6 hours of wound infliction, primary infection of the war wound occurs (early infection) in more than 50% of cases. The keys for the prevention of infection are prompt and thorough surgical exploration of the wound, administration of antibiotics and antitetanic prophylaxis, awareness of the probable pathogens with respect to localization of the wound, and optimal choice of antibiotics and length of their administration.


Cryocooler based test setup for high current applications.
A cryo-cooler based cryogenic test setup has been designed, fabricated, and tested. The setup incorporates two numbers of cryo-coolers, one for sample cooling and the other one for cooling the large magnet coil. The performance and versatility of the setup has been tested using large samples of high-temperature superconductor magnet coil as well as short samples with high current. Several un-calibrated temperature sensors have been calibrated using this system. This paper presents the details of the system along with results of different performance tests.


Implementing Lean in Academic Primary Care.
Lean is emerging as a quality improvement (QI) strategy in health care, but there has been minimal adoption in primary care teaching practices. This study describes a strategy for implementing Lean in an academic family medicine center and provides a formative assessment of this approach. A case study of the University of North Carolina Family Medicine Center that used the Consolidated Framework for Implementation Research to guide a formative evaluation. The implementation strategy included partnering with Lean content experts and creating a leadership team; planning and completing QI events and Lean training modules; and evaluating and reporting activities related to QI and training. During the initial period of Lean implementation, there was (1) minimal to no change in the quality of care as determined by the Preventive Care Index (46-48); (2) a decrease patient appointment cycle time from 89 minutes to 65 minutes; (3) an increase in overall practice productivity from $8144 to $9160; (4) a decrease in patient satisfaction from 94% to 91%; and (5) an increase in monthly visit volume from 4112 to 5076. Lean had an uneven effect on QI in an academic primary care practice during the first year of implementation.


Analyzing Seasonal Variations in Suicide With Fourier Poisson Time-Series Regression: A Registry-Based Study From Norway, 1969-2007.
Seasonal variation in the number of suicides has long been acknowledged. It has been suggested that this seasonality has declined in recent years, but studies have generally used statistical methods incapable of confirming this. We examined all suicides occurring in Norway during 1969-2007 (more than 20,000 suicides in total) to establish whether seasonality decreased over time. Fitting of additive Fourier Poisson time-series regression models allowed for formal testing of a possible linear decrease in seasonality, or a reduction at a specific point in time, while adjusting for a possible smooth nonlinear long-term change without having to categorize time into discrete yearly units. The models were compared using Akaike's Information Criterion and analysis of variance. A model with a seasonal pattern was significantly superior to a model without one. There was a reduction in seasonality during the period. Both the model assuming a linear decrease in seasonality and the model assuming a change at a specific point in time were both superior to a model assuming constant seasonality, thus confirming by formal statistical testing that the magnitude of the seasonality in suicides has diminished. The additive Fourier Poisson time-series regression model would also be useful for studying other temporal phenomena with seasonal components.


Freeze-fracture study of Trichomonas vaginalis.
The freeze-fracture technique was used to analyse the organization of the plasma membrane, as well as membranes of cytoplasmic organelles, of the pathogenic protozoan Trichomonas vaginalis. Rosettes formed by 4 to 14 intramembranous particles were seen on the fracture faces of the membrane lining the anterior flagella as well as in fracture faces of the plasma membrane enclosing the anterior region of the protozoan and in cytoplasmic organelles. Special organization of the membrane particles were also seen in the region of association of the recurrent flagellum to the cell body.


Paraphaeobacter pallidus gen. nov., sp. nov., isolated from seawater.
A Gram-stain-negative, aerobic, rod-shaped bacterium with a single polar flagellum, designated strain DCSW07T, was isolated from the surface water of the Bohai Sea, China. Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain DCSW07T shared highest similarity (96.97 %) with Phaeobacter gallaeciensis DSM 26640T, formed a lineage within the family Rhodobacteraceae and was distinct from the most closely related genera Phaeobacter and Pseudooceanicola (96.6-96.8 and 95.8-96.2 % 16S rRNA gene sequence similarity, respectively). Optimal growth occurred in the presence of 6 % (w/v) NaCl, at pH 6.0 and at 28 °C. Strain DCSW07T contained phosphatidylcholine, phosphatidylethanolamine, an unidentified phospholipid and two unidentified polar lipids as the major polar lipids, and C18 : 1ω7c as the main fatty acid (>10 % of the total). The DNA G+C content of strain DCSW07T was 64.8 mol%. On the basis of this polyphasic study, strain DCSW07T is considered to represent a novel species of a new genus in the Roseobacter clade of the family Rhodobacteraceae, for which the name Paraphaeobacter pallidus gen. nov., sp. nov. is proposed. The type strain of Paraphaeobacter pallidus is DCSW07T (=KCTC 52369T=MCCC 1K03197T=JCM 31458T=CGMCC 1.15762T).


Fluorescence in situ hybridization for identification and visualization of microorganisms in infected heart valve tissue as addition to standard diagnostic tests improves diagnosis of endocarditis.
In infective endocarditis (IE), identification of the causative organism and consecutive treatment are crucial for patient survival. Although the macroscopic aspect resembles infected tissue, standard diagnostic tests often fail to allow one to identify bacteria. Fluorescence in situ hybridization (FISH) is a molecular, culture-independent technique that allows one to identify and visualize microorganisms within tissue and to recognize their morphology, number and activity. We analysed the diagnostic benefit of FISH/polymerase chain reaction (PCR) by comparing its results to those of standard diagnostic tests. From September 2015 to April 2018, 128 patients underwent first-time or redo valve surgery to treat IE. Patients were designated according to the modified Duke criteria as definite (n = 61), possible (n = 34) or rejected (n = 33) IE. Tissue specimens obtained intraoperatively were analysed using FISH/PCR in addition to undergoing standard diagnostic testing and PCR alone. We used blood cultures to detect microorganisms in 67/128 patients; valve cultures, in 34/128; PCR, in 67/128; histopathological diagnosis showed IE in 72/128 cases. We were able to detect microorganisms in 103/128 cases using FISH/PCR, with 55/61 in definite IE. Furthermore, we were able to identify 26 cases of bacterial biofilm using FISH/PCR, despite antibiotic treatment of 61 in the definite, 13 in the possible and 1 in the rejected group, including 8/33 patients in the rejected group with active bacteria. In all cases, the patient's therapy was altered. FISH/PCR was used to identify microorganisms in cases in which standard diagnostic tests failed to provide sufficient results for various reasons. Furthermore, FISH/PCR enabled us to identify bacterial biofilms and to differentiate between active versus degraded bacteria, thus indicating the impact of treatment. Therefore, we suggest FISH/PCR as an additional diagnostic tool in IE alongside standard diagnostic tests.


Combined surgical and radiation therapy for invasive carcinoma of the cervix.
Results of combined surgical and radiation therapy for invasive carcinoma in 266 patients treated between 1945 and 1970 are presented. Treatment protocol included radical Wertheim hysterectomy, Taussig node dissection, and deep pelvic irradiation. All cases were staged according to the International Staging System. The five-year survival for patients with disease in stages I, II, and III was 80.5%. All of the 32 patients with cervical stump carcinoma or cervical carcinoma complicated by pregnancy survived. Of the 52 patients with lymph node metastasis, 55.7% survived.


Design and testing of a 750MHz CW-EPR digital console for small animal imaging.
This paper describes the development of a digital console for three-dimensional (3D) continuous wave electron paramagnetic resonance (CW-EPR) imaging of a small animal to improve the signal-to-noise ratio and lower the cost of the EPR imaging system. A RF generation board, an RF acquisition board and a digital signal processing (DSP) & control board were built for the digital EPR detection. Direct sampling of the reflected RF signal from a resonator (approximately 750MHz), which contains the EPR signal, was carried out using a band-pass subsampling method. A direct automatic control system to reduce the reflection from the resonator was proposed and implemented in the digital EPR detection scheme. All DSP tasks were carried out in field programmable gate array ICs. In vivo 3D imaging of nitroxyl radicals in a mouse's head was successfully performed.


Mixed poly(vinyl pyrrolidone)-based drug-loaded nanomicelles shows enhanced efficacy against pancreatic cancer cell lines.
We report in this paper on the enhanced efficacy of a physical mixture of two single anti-cancer loaded nanomicelles against PANC-1 and BxPC-3. Poly(vinyl pyrrolidone-b-polycaprolactone) (PVP-b-PCL) and poly(vinyl pyrrolidone-b-poly(dioxanone-co-methyl dioxanone)) (PVP-b-P(DX-co-MeDX)) were synthesized and successfully loaded with various anti-cancer drugs - gemcitabine (GEM), doxorubicin.HCl (DOX.HCl), doxorubicin.NH2 (DOX), 5-fluorouracil (5-FU) and paclitaxel (PTX). Spherical micelles of size 160-477 nm were obtained as characterized by DLS while sizes determined by TEM were in the range 140-250 nm. The hydrophobic drugs had a higher loading percentage efficiency compared to hydrophilic drugs in the trend PTX>DOX>5-FU>GEM>DOX.HCl whereas the drug release pattern followed the reverse trend in accordance with decreased polymer-drug interaction as quantified by the binding constant and micellar drug location. Cellular uptake studies showed that nanomicelles are taken up by pancreatic cancer cells into the cytoplasm and nucleus. The free nanomicelles were confirmed to be non-cytotoxic. A physical mixture of GEM loaded micelles and DOX.HCl loaded micelles of comparable size showed significantly higher cytotoxicity than either the free drug mixture or the individual single drug loaded micelles as confirmed by their IC50 values.


Sex-specific endocrine-disrupting effects of three halogenated chemicals in Japanese medaka.
Several halogenated chemicals are found in an array of products that can cause endocrine disruption. Human studies have shown that endocrine responses are sex specific, with females more likely to develop hypothyroidism and males more likely to have reproductive impairment. The objective of this study was to assess sex differences on thyroid and estrogenic effects after exposure of Japanese medaka (Oryzias latipes, SK2MC) to halogenated compounds. This strain is an excellent model for these studies as sex can be determined non-destructively a few hours postfertilization. Medaka embryos were exposed to sublethal concentrations of Tris(1,3-dichloro-2-propyl) phosphate (TDCPP, 0.019 mg/L), perfluorooctanoic acid (PFOA, 4.7 mg/L) and its next generation alternative, perfluorobutyric acid (PFBA, 137 mg/L). Methimazole (inhibits thyroid hormone synthesis) and the thyroid hormone triiodothyronine served as reference controls. Fish were exposed throughout embryo development until 10 days postfertilization. Females displayed significantly larger swim bladders (which are under thyroid hormone control) after exposure to all chemicals with the exception of triiodothyronine, which caused the opposite effect. Females exposed to TDCPP and PFOA had increased expression of vitellogenin and exposure to PFOA upregulated expression of multiple thyroid-related genes. Upregulation of estrogenic-regulated genes after exposure to TDCPP, PFOA and methimazole was only observed in males. Overall, our results suggest that females and males show an estrogenic response when exposed to these halogenated chemicals and that females appear more susceptible to thyroid-induced swim bladder dysfunction compared with males. These results further confirm the importance of considering sex effects when assessing the toxicity of endocrine-disrupting compounds.


School performance of children in kinship care.
This study represents the first comprehensive assessment of the school performance of children placed in the care of a relative, an arrangement termed kinship care. The educational programs, academic achievement, and cognitive and language skills of the children were assessed with a teacher questionnaire and standardized tests. Compared to their peers, high rates of grade retention and participation in special and remedial education, as well as significant academic achievement, cognitive, and language deficits were found. Most teachers, however, reported that educational services were appropriate and several interventions had proven successful. Analyses of predictor variables showed that placement at a later age and fewer children in the home were associated with higher academic achievement. Results are reviewed in the context of other foster care studies, and recommendations are made regarding future research and educational needs of children in kinship care.


Developmental toxicity studies of caprolactam in the rat and rabbit.
Caprolactam was evaluated for developmental toxicity potential in both rats and rabbits by the oral route. In rats dosed on days 6-15 of gestation with 100, 500 or 1000 mg/kg/day of caprolactam, the maternal survival rate was significantly lower in the high-dose group and implantation efficiencies were slightly lower in the 100 and 1000 mg/groups (but not the 500 mg/kg) than in the control. The incidence of fetal death was comparable for all groups, and the incidence of fetal viability was considerably lower in the high-dose group (but not the mid or low) than in the control group. Visceral anomalies and one visceral variant were observed in one 100 mg/kg and one 500 mg/kg pup, respectively. The anomalies included exencephaly, an incomplete left eyelid, microphthalmia (right), and a protruding tongue. No skeletal anomalies were observed. It was concluded that caprolactam at levels up to at least 500 mg/kg of body weight produced no teratogenic effects in the Fischer 344 rats. In rabbits receiving 50, 150 or 250 mg/kg caprolactam on days 6-28 of gestation, the pregnancy rate in all groups was at least 80%. The numbers of corpora lutea, live and dead fetuses, resorptions, the sex ratio and the pre- and post-implantation losses were not significantly different among the test and control groups. The incidence of major malformations and of minor skeletal anomalies was unaffected by treatment with caprolactam. Maternal weights were depressed in the group receiving 250 mg/kg. Treatment of a separate group with a positive control substance (6-aminonicotinamide) resulted in significantly (P less than 0.001) increased incidences of major malformations, minor visceral anomalies and minor skeletal anomalies. Maternal toxicity in terms of mortality was observed in pregnant rabbits treated with caprolactam at a dose of 250 mg/kg/day. Fetotoxicity was evidenced by lower fetal weights at the 150 and 250 mg/kg/day levels, and an increased incidence of thirteenth ribs was observed at the 250 mg/kg/day dose level. Neither embryotoxicity nor teratogenicity occurred at any dose level.


Association of Hashimoto's thyroiditis and thyroid cancer.
The association of Hashimoto's thyroiditis and thyroid cancer remains an active focus of research and controversy. Since it was first proposed in 1955, numerous studies have explored the epidemiology and etiology of these concurrent disease processes. The lymphocytic infiltration of Hashimoto's thyroiditis is frequently encountered in thyroid glands resected for a neoplasm. The most frequent association is noted with papillary thyroid cancer. Several recent studies performed on patients undergoing thyroidectomy with coexisting Hashimoto's thyroiditis report an increased prevalence of papillary thyroid cancer, with a favorable disease profile and an improved prognosis, particularly in women. Conversely, some population-based studies using fine-needle aspiration biopsy data report no linkage between serologic Hashimoto's thyroiditis and thyroid cancer, yet they are limited by the lack of definitive pathology. On the other hand, the significantly increased incidence of primary thyroid lymphomas in patients with Hashimoto's thyroiditis strongly suggests a pathogenetic link between this autoimmune disorder and malignant thyroid lymphoma. The lymphocytic infiltration of Hashimoto's thyroiditis is frequently associated with papillary thyroid cancer and may indeed be a risk factor for developing this type of cancer. Nonetheless, a pathogenesis linking these diseases remains unclear. The relationship between thyroid lymphoma and Hashimoto's thyroiditis appears to be well established.


The biological role of haptoglobin and behaviour of this protein in different diseases, with special attention paid to brain stroke.
Haptoglobin (Hp) is an alpha 2 glycoprotein, the presence of which was determined in blood serum in 1940 by Polonovski and Jayle. Smithies showed genetically conditioned polymorphism of haptoglobin (4, 16). Molecular heterogeneity of haptoglobin is demonstrated by three main phenotypes: Hp 1-1, Hp 2-2, Hp 2-1. Haptoglobin is a glycoprotein with tetrametric structure. Haptoglobin 1-1 is composed of two alpha (light) chains with 9,000 molecular mass including 83 amino acids and two beta (heavy) chains with 40,000 molecular mass including 245 amino acids. Alpha chains are connected with each other by two sulfurous bonds which also connect alpha chains with beta chains (3, 4).


Effect of nitrate and incubation conditions on the production of catalase and nitrate reductase by staphylococci.
The objective of this work was to study the production of catalase and nitrate reductase by staphylococci in order to understand their role in lipid oxidation during sausage manufacturing. Catalase and nitrate reductase were measured in resting cells and supernatants of staphylococci grown in different conditions. All staphylococci (except S. warneri) synthetized nitrate reductase. In static condition, the synthesis was maximal during exponential growth phase, whereas in shaking condition, the synthesis was maximal at the beginning of stationary phase. The production of nitrate reductase was increased in presence of nitrate, this effect was particularly important for the two S. carnosus strains which exhibited the highest activity. For all staphylococci, the production of catalase was maximal at the end of the exponential growth phase. The lowest amount of catalase was produced by S. warneri and the highest by S. carnosus. Only S. xylosus 873 and S. saprophyticus 852 released high amounts of catalase in the supernatant growth. Staphylococci produced higher amounts of catalase in shaking conditions. Addition of nitrate in the growth media favoured the synthesis of catalase, with a pronounced effect for S. carnosus. Nitrate also favoured the release of catalase.


Effects of different concentrations and volumes of formalin on pain response in rats.
Formalin test is commonly used in animal model to assess injury-produced pain response. If the total amount of formaldehyde is fixed, its concentration and volume can be easily adjusted. We evaluated the effect of two sets of three solutions of formalin (one set of same dose of formaldehyde at different concentration and volume, i.e. 2.5%--100 microL, 5%--50 microL, 10%--25 microL, and another set of same volume but at different concentrations, i.e. 2.5%--100 microL, 5%--100 microL, and 10%--100 microL) on the injury-produced pain response in rat. Male Sprague-Dawley rats weighing 250-300 g were used. Following injection of formalin (n = 8 in each group) or saline (n = 6, control), the flinching frequencies and time spent in licking or biting the injected hind-paw in the early phase 1 (0-5 min after injection) and the late phase 2 (20-60 min after injection) were recorded. Sham-injection rats (n = 5) underwent subcutaneous insertion of the needle, but no substance was injected. Flinching in phase 1 and 2 was more frequent in the 2.5%--100 microL and 5%--50 microL groups than in the control group (P < 0.05). Licking (or biting) time in phase 2 in all these three groups was longer than the control group (P < 0.05). In the groups of another set of three different solutions (2.5%--100 microL, 5%--100 microL, and 10%--100 microL), flinching in phase 1 and phase 2 was also more frequent than the control group (P < 0.05). Regarding lick behavior of another set, it occurred more frequently in 2.5%--100 microL group in phase 1 and in 2.5%--100 microL group as well as 5%--100 microL group in phase 2 than the control group (P < 0.05). The 10%--25 microL formalin produces fewer flinching responses than other concentrations. Flinching was a biphasic behavior which was more spontaneous and active than was licking. The volume of formalin was a more important factor than the concentration of formalin in the generation of the active biphasic flinching response in the rat model.


Effects of a small dose of triazolam on P300 and resting EEG.
The aim of the present study was to clarify whether cognitive impairments caused by benzodiazepines (BDZs) are a consequence of their specific direct effects on cognitive function or whether they are explained as secondary effects of increased sleepiness. Ten healthy men (mean age, 33.9 years) participated in two experimental sessions in a randomized cross-over, double-blind study: in one session subjects were given a placebo and in the other they were given 0.125 mg triazolam (TRZ). Each experimental session was conducted on 1 day. After a pre-drug EEG recording and an event-related potential (ERP) recording, under an oddball paradigm, subjects took the TRZ or placebo orally at 1000 hours. Thereafter, EEG and ERP recording sessions, following the same procedure as the pre-drug sessions, were conducted at 1, 2, 4, 6 and 8 h after drug administration. The EEG and ERP recordings from Cz and Pz referred to the bilaterally linked ear electrodes were used. We found that P300 latency was significantly prolonged in TRZ condition at 2 h (Pz) and 4 h (Cz and Pz) after TRZ, and that the P300 amplitude was significantly reduced at 2 h (Cz and Pz) and 4 h (Pz) after TRZ, compared to the same times after placebo. The absolute power values for the theta (4-7 Hz), alpha 1 (8-9 Hz), and alpha 2 (10-12 Hz) bands did not differ at any measurement time between the treatments. Only the beta band (13-19 Hz) power value was significantly elevated after the TRZ administration (versus placebo). No significant sedative effects were detected in subjective measurements. These results indicate that a single oral dose of 0.125 mg TRZ caused cortical changes without distinct general sedation or subjective sleepiness.


Assessment of simple marker-free genetic transformation techniques in alfalfa.
Methods to avoid the presence of selectable marker genes (SMG) in transgenic plants are available but not implemented in many crop species. We assessed the efficiency of simple marker-free Agrobacterium-mediated transformation techniques in alfalfa: regeneration without selection, or marker-less, and co-transformation with two vectors, one containing the SMG and one containing a non-selected gene. To easily estimate the efficiency of marker-less transformation, the nptII and the GUS markers were used as non-selected genes. After Agrobacterium treatment, somatic embryos were regenerated without selection. The percentage of transgenic embryos was determined by a second cycle of regeneration using the embryos as starting material, in the presence of kanamycin, by PCR screening of T1 progenies, and by the GUS test. In two experiments, from 0 to 1.7% of the somatic embryos were transgenic. Co-transformation was performed with two vectors, one with the hemL SMG and one with the unselected nptII gene, each carried by a different culture of Agrobacterium. Only 15 putative co-transformed plants were regenerated from two experiments, with an average co-transformation percentage of 3.7. Southern blot hybridizations and/or T(1) progeny segregation were used to confirm transgene integration, and qPCR was also used to estimate the T-DNA copy number. In the T(1) progenies obtained by crossing with a non-transgenic pollinator, marker-free segregants were obtained. Both marker-free approaches showed very low efficiency.


Hierarchical ZnO-Ag-C composite porous microspheres with superior electrochemical properties as anode materials for lithium ion batteries.
Hierarchical ZnO-Ag-C composite porous microspheres are successfully synthesized by calcination of the preproduced zinc-silver citrate porous microspheres in argon. The carbon derives from the in situ carbonization of carboxylic acid groups in zinc-silver citrate during annealing treatment. The average particle size of ZnO-Ag-C composite porous microspheres is approximate 1.5 μm. When adopted as the electrode materials in lithium ion batteries, the obtained composite porous microspheres display high specific capacity, excellent cyclability, and good rate capability. A discharge capacity as high as 729 mA h g(-1) can be retained after 200 cycles at 100 mA g(-1). The excellent electrochemical properties of ZnO-Ag-C are ascribed to its unique hierarchical porous configuration as well as the modification of silver and carbon.


The effect of glucosamine-chondroitin supplementation on glycosylated hemoglobin levels in patients with type 2 diabetes mellitus: a placebo-controlled, double-blinded, randomized clinical trial.
With increasing use of glucosamine-containing supplements for the treatment of osteoarthritis, there is increasing concern in the medical community about possible toxic effects. The present study was undertaken to determine whether glucosamine supplementation altered hemoglobin A1c concentrations in patients with well-controlled diabetes mellitus. To evaluate possible effects of glucosamine supplementation on glycemic control in a selected population of patients with type 2 diabetes mellitus. Placebo-controlled, double-blinded, randomized clinical trial. Outpatient, diabetes monitoring clinic. Patients were typically elderly patients, evenly divided between men and women. Most of the patients were being treated with 1 or 2 drugs for glycemic control. In daily doses for 90 days, patients received either placebo or a combination of 1500 mg of glucosamine hydrochloride with 1200 mg of chondroitin sulfate (Cosamin DS; Nutramax Laboratories Inc, Edgewood, Md). Main Outcome Measure Hemoglobin A1c levels before and after 90 days of therapy. There were 4 withdrawals from the glucosamine-treated group. Three were related to comorbidities (myocardial infarction, congestive heart failure, and atrial fibrillation) and 1 to a possible adverse reaction (excessive flatus). No other patient reported any adverse effects of glucosamine therapy, and no patient had any change in their diabetes management. Mean hemoglobin A1c concentrations were not significantly different between groups prior to glucosamine therapy. Posttreatment hemoglobin A1c concentrations were not significantly different between groups, nor were there any significant differences within groups before and after treatment. This study demonstrates that oral glucosamine supplementation does not result in clinically significant alterations in glucose metabolism in patients with type 2 diabetes mellitus.