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Timaeus 11

[Device-assisted behavior therapy of 2 enuretic monozygotic sets of twins]. Two sets of identical twins with enuresis were treated with behavior therapy involving a conditioning apparatus. The surprising similarities in the course and outcome are described and discussed.

Estimation of biological occupational exposure limit values for selected organic solvents from logartihm of octarol water partition coefficient. For several organic solvents (solvents in short), biological occupational exposure limits (BOELs) have been established for un-metabolized solvents in urine, based on the solvent exposure-urinary excretion relationship. This study was initiated to investigate the possibiliy of estimating a BOEL from the Pow (the partition coefficient between n-octyl alcohol and water), a physico-chemical parameter. Data were available in the literatures for exposure-excretion relationship with regard to 10 solvents for men and 7 solvents for women. Statistical analysis revealed that the slopes (after correction for molecular weights and logarithmic conversion) of the exposure-excretion regression lines linearly correlated (p<0.01) with the log Pow values the respective solvents. No significant difference (p>0.05) was observed between men and women, and it was acceptable to combine the data for the two sexes. Thus the log Pow-log slope relation was represented by a single equation for both sexes. Based on the observations, procedures were established to estimate BOEL values from Pow. Successful estimations of BOELs for styrene, tetrahydrofuran and m-xylene (a representative of xylene isomers) were calculated as examples. The present study proposed promising procedures for estimation of a BOEL from the Pow.

The pursuit of precision pharmaceuticals: divergent effects of beta2 agonist isomers. Beta2 agonists are the most commonly used treatment for acute bronchoconstriction. However, during regular use there is a progressive decline of protective efficacy of bronchodilators. This progressive decline has long been considered anomalous because with short-acting beta agonists, there is no corresponding change in bronchodilator efficacy. Airway hyper-responsiveness is itself a feature of asthma and there maybe however, there may be an increase in airway hyper-responsiveness following regular use of beta2 agonist. Airway hyperresponsiveness could diminish the capacity of beta agonists to protect from or result in paradoxical bronchospasm and there effects of racemic salbutamol. There have been reports of increased morbidity and mortality associated with excessive use of beta(2) agonists. As all beta agonists used clinically are racemates composed of 1:1 mixtures of R and S isomers, conducted on the possible involvement of the isomers in hyper-responsiveness. Hyper-responsiveness cannot be attributed to the R isomer, whose capacity to activate beta adrenoceptors will nullify this effect. In contrast, extensive evidence indicated that the S isomer might cause hyper-responsiveness and potential airway inflammation. Further, the S isomer shows a propensity to activate human eosinophils and alter muscarinic M(2) receptor functions. The S isomer, which makes no contribution to therapeutic efficacy and may exacerbate asthma, might therefore be excluded from asthma therapy.

Axonal transport of neurofilament proteins in IDPN neurotoxicity. The neurofibrillary changes produced by IDPN are the consequence of the ability of the agent to impair the slow axonal transport of neurofilaments. The susceptibility of various neurons to this effect depends upon their neurofilament content; neurofilament-rich large caliber axons are severely affected. In motor neurons the half-velocities of neurofilament proteins are reduced 2-10 fold, while tubulin and other slow component constituents are only mildly altered. Optic nerve fibers are intermediate in vulnerability, and small neurofilament-poor fibers have little change in slow transport. The agent acts directly on the axon, and the transport defect is expressed all along the course of susceptible axons. Similar alterations in neurofilament transport have recently been found with 3,4-dimethyl-2,5-hexanedione, indicating that similar pathogenetic mechanisms can occur with toxic agents other than IDPN.

Selective reduction of hippocampal dentate frequency potentiation in aged rats with impaired place learning. Induction of posttetanic potentiation (PTP) and long-term potentiation (LTP) was analyzed in hippocampal slices obtained from a) young 6-month-old Sprague-Dawley (SD) rats, all of them performing well in the Morris Maze, and b) aged SD 20-month-old and Fischer 344 24-month-old rats showing different degrees of ability in the same test. After the application of an electrical tetanus 1 s, 100 Hz, 50 microA in the stratum radiatum, no significant differences were found in the percent of induction of both PTP and LTP in the CA1 area of hippocampal slices obtained from rats of different strains and ages. After the application of an electrical tetanus 1 s, 100 Hz, 50 microA in the stratum moleculare, a significant difference was found in the percent of dentate PTP induction in hippocampal slices obtained from rats of different ages. Specifically, dentate PTP induction was significantly (p < 0.01) higher in slices obtained from young SD rats, and from old SD rats with a better performance in the Morris maze, escape latency less than 10 s and 150 cm, than in slices obtained from old SD or Fischer 344 rats that had shown poor performance in the Morris Maze. On the contrary, no significant differences were found in the percent of dentate LTP in hippocampal slices obtained from rats of different strains and ages. The data demonstrate that the induction of hippocampal dentate high-frequency PTP is selectively reduced in old rats with impaired Morris Maze performance.

Characterization of antigen recognized by the monoclonal antibody (4F2): different molecular forms on human T and B lymphoblastoid cell lines. The monoclonal antibody 4F2 recognizes a disulfide-linked ricin-binding glycoprotein complex (Mr congruent to 125,000) composed of a sialylated heavy subunit (Mr congruent to 85,000 on T cell lines) and an unsialylated light subunit (Mr congruent to 41,000). The antigen (T85,41) recognized by 4F2 on T cell lines is structurally distinct from the antigen (B93, 41) on B cell lines. The heavy subunits, but not the light subunits, from all T cell lines examined were uniformly smaller in size than the heavy subunits from several B cell lines. This reflects differences in carbohydrate rather than protein represent in B93,41 compared with T85,41, because both heavy subunits have a common unglycosylated form (p65) and a common partially glycosylated precursor form (p68). Among non-T, non-B hematopoietic cell lines, the monocytoid line U-937 expressed an antigen that resembles B93,41, whereas the erythroleukemic line K-562 expressed an antigen more similar to T85,41. 4F2 recognizes a protein determinant on the heavy subunit (with or without N-linked glycosylation) and also the unglycosylated heavy subunit retains the ability to associate with light subunit. The light subunit itself contains no detectable N-linked carbohydrate. Unlike the transferrin receptor, synthesis of the antigen recognized by 4F2 on the promyelocytic cell line HL-60 did not diminish upon dimethylsulfoxide-induced differentiation, and thus is not tightly correlated with cell proliferation.

Postprandial sphincter of Oddi myoelectric activity and gallbladder emptying. Feeding initiates gallbladder emptying and bile delivery into the duodenum. It is not yet defined how the sphincter of Oddi regulates flow of bile into the duodenum during gallbladder emptying. The aim of this study was to assess postprandial spike burst activity in the sphincter of Oddi, while quantitating gallbladder emptying with noninvasive radioisotope imaging. Six adult opossums were prepared with bipolar electrodes in the sphincter of Oddi. After 2 weeks of recovery the animals were fasted overnight and positioned under a gamma camera, and myoelectric recordings were begun. After two cycles of the migrating motor complex (MMC), 2 mCi 99Tc-HIDA was infused intravenously and permitted to concentrate in the gallbladder for a period of 30 min. Subsequently, a 30-ml liquid meal, containing 0.9 g protein, 3.5 g carbohydrate, and 3.3 g fat, was instilled into the stomach. Sphincter of Oddi myoelectric activity (spike bursts/min) and gallbladder emptying (expressed as percentage of original 99Tc counts in the gallbladder) were measured at intervals for 120 min following feeding. Feeding resulted in prompt gallbladder emptying. Sphincter of Oddi spike burst activity was not altered significantly in the first 30 min after feeding, suggesting that motor activity in the sphincter of Oddi does not initially influence bile flow. Subsequently, spike burst activity increased progressively, suggesting that sphincter of Oddi motor activity may accelerate bile delivery into the duodenum during later phases of gallbladder emptying.

Multivalency in Drug Delivery-When Is It Too Much of a Good Thing? Multivalency plays a large role in many biological and synthetic systems. The past 20 years of research have seen an explosion in the study of multivalent drug delivery systems based on scaffolds such as dendrimers, polymers, and other nanoparticles. The results from these studies suggest that when it comes to the number of ligands, sometimes, to quote Shakespeare, "too much of a good thing" is an apt description. Recent theoretical studies on multivalency indicate that the field may have had a misplaced emphasis on maximizing binding strength where in fact it is the selectivity of multivalent drug delivery systems that is the key to success. This Topical Review will summarize these theoretical developments. We will then illustrate how these developments can be used to rationalize the immunoresponses and drug uptake mechanisms for multivalent systems and show the path forward toward the design of better multivalent drug delivery systems.

Nanoscale mechanobiology of cell adhesions. Proper physiological functions of cells and tissues depend upon their abilities to sense, transduce, integrate, and generate mechanical and biochemical signals. Although such mechanobiological phenomena are widely observed, the molecular mechanisms driving these outcomes are still not fully understood. Cell adhesions formed by integrins and cadherins receptors are key structures that process diverse sources of signals to elicit complex mechanobiological responses. Since the nanoscale is the length scale at which molecules interact to relay force and information, the understanding of cell adhesions at the nanoscale level is important for grasping the inner logics of cellular decision making. Until recently, the study of the biological nanoscale has been restricted by available molecular and imaging tools. Fortunately, rapid technological advances have increasingly opened up the nanoscale realm to systematic investigations. In this review, we discuss current insights and key open questions regarding the nanoscale structure and function relationship of cell adhesions, focusing on recent progresses in characterizing their composition, spatial organization, and cytomechanical operation.

[Effect of adrenaline, noradrenaline and acetylcholine on rabbit and human uterine activity in vivo (author's transl)]. Effects of estrogen (abbr. as E), Estrogen + Progesterone (E + P) and autonomic nerve trophic drugs on uterus were investigated in rabbit and human in vivo and the following results were obtained. 1) Spontaneous contraction in cornu and cervix of E treated rabbit were stronger than in those during pregnancy or treated with E + P. 2) 10(-5) g/kg Adrenaline caused a uniform response pattern in cornu and cervix of E treated rabbit, and the pattern could be divided into three phases. Phase I is supposed to be the contraction response through the alpha receptor, and phase II is presumed as the response that comprises a part of element identical with alpha adrenergic response, while phase III is the relaxation response through the beta 2 receptor. 3) Acetylcholine (ACh) 10(-3) g/kg and Neostigmine 10(-5) g/kg caused augmentation of contraction both in cornu and cervix of rabbit, but this effect was blocked by Atropine, suggesting the presence of parasympathetic control in cornu and cervix. 4) In human corpus and cervix, Phenylephrine and ACh augmented contraction but Terbutaline had reducing contraction, showing the similar phenomenon found in rabbit. From this, it was proven that the similar autonomic nerve controls could be present both in rabbit and human.

Intracerebroventricular administration of superFIT and its enantiomer to rats: evidence for in vivo acylation of [3H]DADL binding sites. SuperFIT is an high affinity acylating ligand derived from fentanyl. Previous studies suggested that a selective acylation of delta receptors (J. Med. Chem. 29:1087-1093, 1986) resulted from exposure of membranes to this and structurally related compounds. We report in this preliminary study that intracerebroventricular administration of either superFIT or its enantiomer 18 to 24 hours prior to sacrifice decreased the subsequent binding of [3H]DADL to both its higher and lower affinity binding sites.

Fenofibrate-induced hepatotoxicity: A case with a special feature that is different from those in the LiverTox database. We report a special case of fenofibrate-induced acute severe DILI with sudden onset and rapid recovery, which is different from those in the LiverTox database. The acute severe DILI occurred within only 4 days after fenofibrate initial treatment for hypertriglyceridemia. Liver enzyme levels eventually declined to normal within two weeks after the discontinuation of fenofibrate. Early detection of elevated hepatic enzymes after fenofibrate initial treatment helps physicians to avoid delayed diagnosis and subsequent treatment.

Alcohol expectancies pre-and post-alcohol use disorder treatment: Clinical implications. Modification of elevated positive expectations of alcohol consumption (alcohol outcome expectancies; AOEs) is a key feature of Cognitive Behaviour Therapy (CBT) approaches to Alcohol Use Disorders (AUDs). Despite extensive research supporting the efficacy of CBT for AUD, few studies have examined AOE change. This study aimed to assess AOE change following completion of CBT for AUD and its association with drinking behaviour. One-hundred and seventy-five patients who completed a 12-week CBT program for AUD were administered the Drinking Expectancy Questionnaire (DEQ) at pre-treatment assessment and upon completion of treatment. Abstinence was achieved by 108 (61.7%) of completing patients. For patients who lapsed, the mean proportion of abstinent days was 93%. DEQ scales assessing expectations of positive alcohol effects on tension reduction, assertiveness, and cognitive enhancement were significantly lower post-treatment (p<0.001). Expectations of negative effects on mood were higher post-treatment (p<0.001). The largest AOE change occurred on the tension reduction scale. Greater percentage of abstinent days over treatment was associated with lower pre-and post-treatment tension reduction expectancy scores (p<0.05). Drinking during treatment was associated with smaller changes in expectations of negative effects of alcohol on mood (p<0.05). Individuals who completed CBT treatment for AUD showed significant AOE change. Tension reduction and affective change expectancies may be particularly important for abstinence and useful markers of lapse risk.

MiR-125b-5p suppressed the glycolysis of laryngeal squamous cell carcinoma by down-regulating hexokinase-2. Laryngeal squamous cell carcinoma (LSCC) is the most common form of laryngeal carcinoma with poor prognosis. Exploring novel factors involved in the progression of LSCC is quite necessary for understanding the mechanisms and designing therapeutic strategies for LSCC. In this study, we showed that miR-125b-5p was significantly down-regulated in LSCC tissues and cell lines. The decreased expression of miR-125b-5p was associated with the tumor differentiation, metastasis and high clinical stage of the LSCC patients. Overexpression of miR-125b-5p suppressed the proliferation and induced apoptosis of LSCC cells. Bioinformatics analysis predicted hexokinase-2 (HK2), an essential enzyme involved in the glycolysis of cancer cells, as one of the downstream targets of miR-125b-5p. Further molecular studies showed that highly expressed miR-125b-5p bound the 3'-UTR of HK2 and decreased both the mRNA and protein levels of HK2. Consistent with the function of HK2 in glycolytic metabolism, overexpression of miR-125b-5p significantly suppressed the glucose consumption and lactate production of LSCC cells. Notably, restoration the expression of HK2 attenuated the inhibitory effect of miR-125b-5p on the glycolysis of LSCC cells. The inverse correlation between the expression of miR-125b-5p and HK2 in LSCC tissues further supported the involvement of miR-125b-5p-HK2 axis in the progression of LSCC. Collectively, these finding suggested the miR-125b-5p-HK2 pathway as a novel mechanism in regulating the glycolysis and progression of LSCC.

[Influence of qualitatively different fats on the level of cholesterol and phospholipids in the blood serum and liver on rats in choline-protein insufficiency]. The effect of lard and sunflower oil making part of a cirrhogenic ration with a high content of fat and deficient protein and choline on the level of total and esterified cholesterol and phospholipids in the blood serum and liver was studied. The experiments lasted for 150 and 210-240 days. Changes in the level of cholesterol and phospholipids in the blood serum and liver of the rats were noted to occur from the first days of developing fat dystrophy (fatty degeneration) of the liver, these changes gaining in intensity with lengthening of the test periods and progressive development of the pathological process. The quality of the fat influenced the extent of the upset cholesterol and phospholipids metabolism, since the saturated fat which accelerated and intensified the development of lipohepatosis and cirrhosis caused a significantly greater accumulation of the cholesterol ethers in the liver and reduction of these ethers, as well as of phospholipids in the serum. An addition of choline to the rations prevented the development of lipohepatosis, but failed to avert upsets of the lipids metabolism.

Water uptake and release from iodine-containing bone cement. Water uptake and release characteristics of PMMA cement containing the water-soluble contrast media iohexol or iodixanol have been investigated. The water uptake study revealed that iohexol had the highest uptake of water (3.7%) and that iodixanol had an uptake close to that of Palacos R (2.3% and 1.9%). The curves obtained showed the materials to follow classic diffusion theory, with an initial linearity with respect to t(1/2) making it possible to calculate the diffusion coefficients. This showed iohexol to have the lowest diffusion coefficient, Palacos R the highest, and iodixanol close to that of Palacos R. The release study showed that more iohexol than iodixanol was released from the bone cement; the long-term release was above 25 microg/mL for iohexol compared to slightly above 10 microg/mL for iodixanol. A microCT investigation showed that the risk of developing an observable radiolucent zone is negligible.

Dose reduction of hyoscine-N-butylbromide for double-contrast barium meal examinations--a prospective randomized study. A search of the literature suggests that the conventional 20 mg dose of intravenous hyoscine-N-butylbromide (HBB) for smooth muscle relaxation in double-contrast barium meal (DCBM) studies is largely empirical. This study analysed the merits of three different doses (5 mg, 10 mg, 20 mg) in the performance of routine DCBMs. One hundred and twenty DCBM examinations were prospectively and randomly allocated to receive one of three doses. Three parameters were measured for each examination: gastroduodenal distension, delay in gastric emptying and gastric antrum overlapping with barium-filled duodenal loops. Almost half the examinations using 5 mg produced undesirable duodenal-gastric overlay. Unacceptable early flooding of the duodenal bulb with barium was seen mostly with doses of 5 mg and 10 mg. Overall, the best results were obtained with 20 mg. The continued use of 20 mg HBB in routine DCBMs is recommended.

A report of unusually high blood ethanol and acetaldehyde levels in two surviving patients. Two men with unusually high blood acetaldehyde levels of 750 and 2410 micrograms/dl presented only mild symptomatology. Their blood ethanol levels, 730 and 1121 mg/dl, were also extraordinarily high. However, liver function tests demonstrated no abnormalities.

Simultaneous determination of catechols in thalamic slices with liquid chromatography/electrochemistry. A method was developed for the simultaneous determination of dopamine (DA), epinephrine (E), norepinephrine (NE), 3,4-dihydroxyphenylacetic acid (DOPAC) and 3-methoxy-4-hydroxyphenylglycol (MHPG), as well as L-3,4-dihydroxyphenylalanine (L-DOPA) with liquid chromatography (LC) using electrochemical (EC) detection. With a ODS column and a mobile phase consisting of a sodium acetate-citrate with heptasulfonic acid, this method was applied on simultaneous determination of catechols released from thalamic slices of ddY mouse. The pretreatment of the bathing medium required only centrifugation, and the supernatant was injected directly into the LCEC system. The high potassium stimulation of catecholaminergically innervated thalamic slices led to increase in the levels of DA, NE, DOPAC and MHPG, especially of NE, but not that of L-DOPA itself. In the present study, we designed to make simultaneous determination of catechols released from thalamic slices for estimation of the physiological status of catecholaminergic neuronal activity.

Maghemite functionalization for antitumor drug vehiculization. In this paper we describe the preparation and characterization of magnetic nanocomposites designed for applications in targeted drug delivery. Combining superparamagnetic behavior with proper surface functionalization in a single entity makes it possible to have altogether controlled location and drug loading, and release capabilities. The colloidal vehicles consist of maghemite (γ-Fe2O3) cores surrounded by a gold shell through an intermediate silica coating. The external Au layer confers the particles a high degree of biocompatibility and reactive sites for the transported drug binding. In addition, it permits to take advantage of the strong optical resonance, making it easy to visualize the particles or even control their payload release through temperature changes. The results of the analysis of relaxivity demonstrate that these nanostructures can be used as T2 contrast agents in magnetic resonance imaging (MRI), but the magnetic cores will be mainly useful in manipulating the particles using external magnetic fields. We describe how optical absorbance and electrokinetic data provide a followup of the progress of the nanostructure formation. Additionally, these techniques, together with confocal microscopy, are employed to demonstrate that the component nanoparticles are capable of loading significant amounts of the antitumor drug doxorubicin, very efficient in the chemotherapy of a wide range of tumors. Colon adenocarcinoma cells were used to test the in vitro release capabilities of the drug-loaded nanocomposites.

[Plasma levels of adiponectin and tumor necrosis factor-alpha in children with obesity]. To examine plasma adiponectin (ADPN) and tumor necrosis factor-alpha (TNF-alpha) levels and their correlation in children with obesity in order to investigate the roles of both in the development of childhood obesity. One hundred and forty-seven children with obesity and 118 normal children who were randomly sampled from five primary schools from the Kaifu District in Changsha were enrolled. Physical shape indexes, including height, weight, waist circumference, hip circumference, and waist to hip ratio (WHR) were measured. Body mass index (BMI) was calculated. Blood pressure was measured. Percentage of body fat (%BF) was measured with dual energy X-ray absorptiometry. Plasmal levels of ADPN and TNF-alpha were detected using ABC-ELISA. Blood concentrations of triglycerides (TG), total cholesterol (TC), high density lipoprotein-cholesterol (HDL-C) and low density lipoprotein-cholesterol (LDL-C) were measured by automatic biochemistry analyzer. Fasting blood glucose level was measured by glucose oxidase method. Fasting blood insulin level was assayed by radioimmunity. Homeostasis model assessment for insulin resistance (HOMA-IR) was performed. Plasma ADPN levels in obese children significantly decreased compared with those in normal children (8.12+/-2.54 mg/L vs 12.22+/-4.68 mg/L; p<0.05), and had a negative correlation with plasma TNF-alpha levels, BMI, WHR and HOMA-IR (p<0.01), and with %BF, fasting insulin, systolic blood pressure and TG (p<0.05). Plasma TNF-alpha levels in obese children significantly increased compared to normal children (171.38+/-34.33 ng/L vs 91.07+/-21.60 ng/L; p<0.01) and positively correlated with BMI, WHR, %BF, fasting insulin, HOMA-IR, TG and systolic blood pressure (p<0.01), and negatively with HDL (p<0.05). Multiple stepwise regression analysis showed that ADPN, BMI and TNF-alpha were main influential factors for %BF (R2=0.926, p<0.01). There was a significant interaction between ADPN and TNF-alpha (p<0.05). Plasma ADPN levels decreased and plasma TNF-alpha levels increased in children with obesity and both were main influential factors for %BF in children. There was an interaction between ADPN and TNF-alpha, suggesting that they both participate in the development of childhood obesity.

Effects of preoperative flavonoid supplementation on different organ functions in rats. Previously it has been reported that preoperative feeding preserves heart function in rats after intestinal ischemia-reperfusion. To further improve postoperative organ function, bioactive nutrition compounds were selected in vitro against the xanthine oxidase radical cascade, an enzyme suggested to play a key role in the induction of single- or multiple-organ dysfunction. Flavonoids were selected in vitro for their capacity to (1) inhibit xanthine oxidase, (2) scavenge superoxide, and (3) scavenge peroxylradicals. The most bioactive flavonoids were added to the preoperative nutrition to study their effect on postintestinal ischemia-reperfusion organ function. A combination of flavonoids selected on basis of effective flavonoid xanthine oxidase inhibition and superoxide scavenging resulted in increased superoxide scavenging. In vivo, the selected flavonoid mixture significantly lowered postischemic intestinal apoptosis and intestinal oxidative stress indicated by malondialdehyde concentration when compared with ischemia-reperfusion fasted and sham-fasted animals. Moreover, this flavonoid mixture significantly lowered plasma creatinine and urea concentration, both indicating a better postoperative kidney function. Furthermore, oxidative stress measured as this flavonoid mixture when compared with control significantly lowered plasma malondialdehyde concentration in fed rats. Coadministration of bioactive flavonoid mixture to preoperative nutrition, in contrast to fasting, attenuates ischemia-reperfusion injury by preserving kidney function in the rat and decreasing apoptosis in the intestine.

A molecular mechanism for combinatorial control in yeast: MCM1 protein sets the spacing and orientation of the homeodomains of an alpha 2 dimer. DNA recognition sequences for dimeric proteins typically contain two types of information. The first is the DNA sequence of each half-site, and the second is the arrangement of these half-sites. We show that dimers of the yeast homeodomain protein alpha 2, although able to read the first type of information, lack the ability to assess the second type. Rather, alpha 2 dimers bind with equal affinity to artificial operators in which the two half-sites are arrayed as inverted repeats, as direct repeats, or as everted (inside-out) repeats. We show that a second protein-MCM1-sets the exact spacing and orientation of the homeodomains in the alpha 2 dimer so that they accommodate only the geometry of the naturally occurring operators. These experiments show directly how the target specificity of a homeodomain protein is raised by an auxiliary protein, allowing it to distinguish the biologically correct operators from closely related sequences in the cell.

What is the impact of early rheumatoid arthritis on the individual? Rheumatoid arthritis has a significant impact on patients' physical, emotional and social functioning that often occurs very early in the disease with the onset of symptoms. Patients therefore come to their consultation with the rheumatologist, having often experienced these symptoms over a period of some months, with specific expectations (for reassurance and diagnosis) and their own understanding and beliefs about the aetiology and prognosis of their symptoms. Information and advice given by rheumatologists will be rejected by patients if it cannot be accommodated within these lay beliefs. The diagnosis itself can cause a variety of reactions, including relief, disbelief, anger, fear and devastation. Following diagnosis, patients are faced with the problems of adapting to a new self-concept, managing their symptoms and trying to assimilate the large amount of information that they are given about their disease, its treatment, preferred health behaviours, prognosis and so on. There are a number of ways in which health professionals can reduce this impact in early disease. Eliciting patients' lay beliefs about the cause of their symptoms will ensure that information given in the consultation is relevant to individual patients and is presented in a way that has meaning for them. Determining patients' expectations of the rheumatologist will ensure that patients' needs for information and reassurance are met and that unrealistic or inappropriate expectations can be discussed and re-negotiated. Understanding patients' attitudes towards treatment interventions will inform shared clinical decision-making and promote adherence. Obtaining this information in the context of a time-limited consultation can be assisted by the use of validated clinical tools, presented as self-completed questionnaires. Further research is needed to determine the content, frequency, timing and methodology of educational interventions in early rheumatoid arthritis and to improve the understanding of the complex interaction between lay beliefs and disease outcome.

[Hip revision arthroplasty (long-term results)]. To evaluate the risk factors after total hip replacement arthroplasty for rerevision and to analyze complications after hip revision surgery. We obtained data from 117 hip revisions and 12 hip rerevision arthroplasties performed in 1992-2001 in the Department of Orthopedics of Klaipeda Hospital. Special forms were filled in for every patient who participated in the study. Name, operation date, type of implants, operative technique, revision diagnosis, intraoperative and postoperative complications were recorded. All patients were checked for death until 2003. Hip revisions were performed for 77 (66%) women and 50 (44%) men in 1992-2001. We revised 22 (19%) cups, 6 (5%) stems, 86 (74%) total hip revisions; femoral head was exchanged for 3 patients. Revision diagnoses were: aseptic loosening in 106 (90%) cases, recurrent dislocations in 7 (6%) cases, and periprosthetic fractures in 4 (4%) cases. Patients' age varied from 26-82 years, average 63.5 years. In revision group only 8% of patients were less than 50 years old, compared to 33% in rerevision group. Morselized allografts and bone impaction technique for reconstruction of bone defects were used in 70 (60%) of cases. We rerevised one cup only for which revision morselized allografts were used. Eight (67%) rerevisions were performed after first 28 (24%) hip revisions. Patients, who underwent revision surgery being younger than 50 years old, were at higher risk for rerevision surgery. Revision with morselized bone allografts and bone impaction technique decreases number of rerevisions. Learning curve was steep and had great influence to our results.

Microradiography of in vivo remineralized lesions in human enamel. II. The purpose of this work was to investigate mineral deposition and redistribution in subsurface human artificial enamel lesions during in vivo remineralization period of 3 months. The enamel lesions were placed in lower prostheses of 30 patients, divided in 3 groups. Group A brushed daily with H2O; group B brushed with H2O and rinsed with a neutral 50 ppm F solution and group C brushed with a neutral 1500 ppm F toothpaste. The technique employed was microradiography. Initially the average vol % of mineral in the lesion body was 47%. After 3 months remineralization in vivo the vol % of mineral in the lesion body was for group A, B and C: 50.7, 48.7 and 53.1 vol %, respectively. The average lesion depth decreased for groups A, B and C 18, 13 and 25 microns respectively over 3 months. The original lesion depth was +/- 100 microns. The microradiographic data show conclusively that mineral is deposited "de novo" inside subsurface lesions. The remineralization percentages are for the control, rinse and brush group 20%, 15% and 31%, respectively.

Practical Application of Elastography in the Diagnosis of Thyroid Nodules in Children and Adolescents. Ultrasound elastography is a noninvasive method of imaging based on the estimation of the mechanical properties of tissue. Data in adults indicate that decreased flexibility in comparison to the surrounding healthy tissue is characteristic of malignancy (in most thyroid carcinomas, except for follicular thyroid carcinoma). The purpose of our study was to assess the deformation of thyroid nodules and to evaluate the usefulness of elastography in predicting malignant thyroid nodules in adolescent patients. We examined 47 children with 62 thyroid nodules. All patients underwent elastography and fine needle aspiration cytology (FNAC). Thirty-seven girls (79%) and 10 boys (21%) were included in the study. A strain ratio <2 was observed in 17 nodules (27% of the study group), a strain ratio between 2 and 4.9 in 34 nodules (55%) and a strain ratio >5 in 11 nodules (18%). According to cytological examination, 3 nodules (4.8% of the study group) were malignant. Two of them were hard (strain ratio ≥5), and 1 nodule had a strain ratio of 2. Our results suggest that elastography can be complementary to conventional ultrasonography and useful while making a decision about FNAC. At the same time, it should not replace the cytological assessment of thyroid nodules in children and adolescents.

Effect of protein nutrition on the mRNA content of insulin-like growth factor-binding protein-1 in liver and kidney of rats. Effect of quantity and nutritional quality of dietary proteins on the content of mRNA of insulin-like growth factor-binding protein-1 (IGFBP-1) was studied in rat liver and kidney. IGFBP-1 mRNA content per unit RNA increased in liver and kidney of rats fed on a protein-free diet and in those of fasted rats compared with that in the rats fed on a casein diet. When rats were given a gluten diet for 7 d, IGFBP-1 mRNA content in liver did not change significantly but that in kidney increased considerably compared with that in those organs of the rats fed on the casein diet. Because IGFBP-1 mRNA has been demonstrated both in liver parenchymal and non-parenchymal cells (Takenaka et al. 1991), the effect of the protein-free diet on these two types of cells has been studied. An increase in IGFBP-1 mRNA content under protein deprivation was observed in both liver parenchymal and non-parenchymal cells, suggesting that these two types of cells are regulated in a similar mode as far as IGFBP-1 mRNA content is concerned. The physiological and nutritional significance of the previously stated results on protein anabolism are discussed when considered together with our previous observations on the plasma concentrations of IGF-1 (Takahashi et al. 1990) and IGFBP (Umezawa et al. 1991) and insulin-like growth factor-1 mRNA content in liver (Miura et al. 1991).

Elective versus emergency surgery for patients with colorectal cancer. A prospective study of 570 patients presenting with colorectal cancer over a 6-year period was undertaken. Of these, 363 were admitted electively and 207 presented as emergencies. The outcome following elective admission was more favourable than after emergency admission. In the elective group the proportion of resected tumours was greater (77 versus 64 per cent, P less than 0.001), the operative mortality rate lower (9 versus 19 per cent, P less than 0.001) and the 5-year disease-related survival rate higher (37 versus 19 per cent, P less than 0.001). These differences may relate to the greater resection rates in the elective situation. Results of surgical intervention might be improved if emergency colorectal operations were undertaken by surgeons with more experience of this type of surgery.

[Immunotherapy: also in elderly patients ?] The emergence of immunotherapy has generated great enthusiasm in oncology improving the prognosis of pathologies such as melanoma, lung cancer, kidney cancer, bladder and head and neck cancers. This enthusiasm concerns also older patients in view of the good tolerance of immunotherapy in young people. However, advanced age is linked to changes in the immune system, called immunosenescence, which could have a negative impact on the efficacy and toxicity of immunotherapy treatment. Knowledge in terms of efficacy and tolerance is limited for geriatric patients, few being included in clinical studies. This article summarizes the experience of immunotherapy in large clinical trials. It appears that the immune checkpoint inhibitors are effective and well tolerated in the elderly.

Effect of exercise on stability of chronically enlarged motor units. Chronic denervation syndromes such as the post-polio syndrome are associated with progressive muscle weakness and fatigue after motoneuron death. Neither the etiology nor the management of these syndromes is clear. To address this issue, we partially denervated rat hindlimb muscles for 1 or 12 months and examined whether chronically enlarged motor units (MUs) become destabilized with time and further destabilized by daily running on exercise wheels. MU enlargement, measured electrophysiologically and morphologically was significantly reduced at 12 months in extensively denervated muscles, and to a lesser extent in moderately denervated muscles, as compared to the findings at 1 month. A 1-month period of running exercise further reduced the size of the chronically enlarged MUs in the extensively denervated muscles. We have therefore (1) successfully established a rat model of time-related MU size reduction, in which destabilization of chronically enlarged MUs results in loss of axonal terminals, and (2) demonstrated that nonphysiological activity has small but significant effects of further destabilizing the chronically enlarged MUs.

Selective coupling with K+ currents of muscarinic acetylcholine receptor subtypes in NG108-15 cells. The primary structures of two muscarinic acetylcholine receptor (mAChR) species, designated as mAChR I and mAChR II, have been elucidated by cloning and sequence analysis of DNAs complementary to the porcine cerebral and cardiac messenger RNAs, respectively. mAChR I and mAChR II expressed in Xenopus oocytes differ from each other both in acetylcholine-induced response and in antagonist binding properties. These results, together with the differential tissue location of the two mAChR mRNAs, have indicated that pharmacologically distinguishable subtypes of the mAChR represent distinct gene products. The primary structures of two additional mammalian mAChR species, designated as mAChR III and mAChR IV, have subsequently been deduced from the nucleotide sequences of the cloned cDNAs or genomic DNAs. We report here that mAChR I and mAChR III expressed in NG108-15 neuroblastoma-glioma hybrid cells, but not mAChR II and mAChR IV, efficiently mediate phosphoinositide hydrolysis, activation of a Ca2+-dependent K+ current and inhibition of the M-current, a voltage-dependent K+ current sensitive to muscarinic agonists.

Basophilic crisis in chronic myelogenous leukemia: case report and literature review in Japan. A 37-year-old female with Ph1-positive chronic myelogenous leukemia developed basophilic crisis 11 months after diagnosis of the disease. Splenomegaly was absent throughout most of the course. The survival duration from the blastic crisis was 5.5 months. Eleven cases in Japanese literature are reviewed.

Agonist specific effects of guanine nucleotides on muscarinic cholinergic receptors in rat anterior pituitary membranes. The effects of guanine nucleotides on the binding affinity of muscarinic cholinergic receptors for muscarinic agents were studied in rat anterior pituitary membranes using direct ligand binding methods with [3H]quinuclidinyl benzylate, GTP and Gpp(NH)p at a concentration of 0.1 mM markedly decreased the binding affinity of the agonist, oxotremorine, for the receptors but had no effect on the binding of the antagonist, atropine. Mg2+ (1 mM) on the other had markedly increased the binding affinity of oxotremorine but not that of atropine. Thus, it is conceivable that the release of the growth hormone or the inhibition of prolactin release by acetylcholine, which we and others have previously shown, is modulated by the opposite actions of guanine nucleotides and divalent metal ions such as Mg2+.

Immunostimulation with macrophage-activating lipopeptide-2 increased survival in murine pneumonia. Community-acquired pneumonia (CAP) is associated with high morbidity and mortality, and Streptococcus pneumoniae is the most prevalent causal pathogen identified in CAP. Impaired pulmonary host defense increases susceptibility to pneumococcal pneumonia. S. pneumoniae may up-regulate Toll-like receptor (TLR)-2 expression and activate TLR-2, contributing to pneumococcus-induced immune responses. In the current study, the course of severe murine pneumococcal pneumonia after pulmonary TLR-2-mediated immunostimulation with synthetic macrophage-activating lipopeptide-2 (MALP-2) was examined. Intratracheal MALP-2 application evoked enhanced proinflammatory cytokine and chemokine release, resulting in recruitment of polymorphonuclear neutrophils (PMN), macrophages, and lymphocytes into the alveolar space in WT, but not in TLR-2-deficient mice. In murine lungs as well as in human alveolar epithelial cells (A549), MALP-2 increased TLR-2 expression at both mRNA and protein level. Blood leukocyte numbers and populations remained unchanged. MALP-2 application 24 hours before intranasal pneumococcal infection resulted in increased levels of CCL5 associated with augmented leukocyte recruitment, and decreased levels of anti-inflammatory IL-10 in bronchoalveolar lavage fluid. Clinically, MALP-2-treated as compared with untreated mice showed increased survival, reduced hypothermia, and increased body weight. MALP-2 also reduced bacteremia and improved bacterial clearance in lung parenchyma, as examined by immunohistochemistry. In conclusion, pulmonary immunostimulation with MALP-2 before infection with S. pneumoniae improved local host defense and increased survival in murine pneumococcal pneumonia.

Microbial systems biology: new frontiers open to predictive microbiology. The field of Systems Biology is a rapidly evolving area of research. It follows on from the previous experimental and theoretical 'omics' revolution in biology. Now that we have through the use of these tools many 'indices' of biological systems available the next step is to actually start composing the systems that these indices specify. In this paper we will discuss the developments in the field of Systems Biology as they pertain to predictive food microbiology and give an example of state of the art current approaches. The data discussed in the case study deal with the resistance of the yeast Saccharomyces cerevisiae towards environmental temperature changes through adaptation of its metabolism, protein signalling and gene-expression. The results are integrated and its implications for the definition of new experiments discussed; the iteration between experiment driven model definition and model driven experimentation being characteristic for contemporary Systems Biology approaches. The stress condition discussed represents in no way a practical situation in food microbiology but what it teaches may well be applied in such cases. We will indicate how the latter may be achieved.

Broadening consent--and diluting ethics? Biobank research is potentially fruitful. It is argued that broad consent is acceptable for future research on biological material because a) the benefit is high, b) it pays respect to people's autonomy, c) it is consistent with current practices and d) because the risk is low. Furthermore, broad consent should be allowed if information is handled safely, people can withdraw and expanded research should be approved by an ethics review board. However, these arguments are flawed and the criteria for broad consent are either too restrictive to allow any research or fail to address important challenges with biobank research. Broad consent for biobank research can hide substantial ethical challenges and threaten trust in research. This does not mean that biobank research should be abandoned or that people cannot authorise future research on donated biological material.

[Cytotoxic action of alkylating agents in human tumor cells and its relationship to apoptosis]. Various anticancer agents have been known to induce apoptosis in certain types of human tumor cells. The fact that a variety of agents, which attack different cellular targets, induce common apoptotic cell death suggests that the nature of initial damage is not directly involved in apoptosis. The mechanism by which a damage leads to apoptosis is not known. However, modulation of this process may affect the outcome of anticancer drug treatment. This article briefly reviewed the studies of endogenous as well as exogenous factors which modulate apoptosis, and then described the characteristics of cell death induced by alkylating agents. O6-Alkylguanine, a major cytotoxic DNA damage produced by simple alkylating agents, can be repaired by the cellular enzyme O6-methylguanine-DNA methyltransferase (MGMT). About one-fifth of human tumor cell strains lack the MGMT activity and termed as Mer- cells. Mer- cells are hypersensitive to alkylating agents like chloroethyl nitrosoureas (CNUs), compared with repair-proficient Mer+ cells. It is suggested that identification of a factor which suppresses the MGMT gene expression in CNU-resistant Mer+ cells, may enable us to convert these Mer+ cells to Mer- phenotype, thus resulting in much higher sensitivity of Mer+ cells to CNUs.

Baseline Characteristics of the Fellow Eye in Patients with Neovascular Age-Related Macular Degeneration: Post Hoc Analysis of the VIEW Studies. The aim was to describe baseline characteristics of the fellow eye of patients with neovascular age-related macular degeneration (nAMD). A pooled, post hoc analysis of patients with nAMD enrolled in the VIEW studies was carried out. The VIEW studies compared intravitreal aflibercept (monthly or every 2 months after 3 monthly injections) with monthly ranibizumab. Baseline choroidal neovascularization (CNV) status of fellow eyes and baseline best-corrected visual acuity (BCVA) and lens status of all eyes were evaluated. Additional analyses evaluated the presence of drusen and pigment in fellow eyes. When comparing both eyes, baseline BCVA was worse in 23.8% of fellow eyes and in 75.2% of study eyes. Lens status of fellow eyes and study eyes was similar. Baseline visual acuity of the study eye and that of the fellow eye were not correlated. Most fellow eyes had signs of early AMD, with 34.6% (n = 843) of fellow eyes having evidence of scarring. In patients in the VIEW studies, most fellow eyes had evidence of AMD, highlighting the importance of examining both eyes, with close follow-up thereafter, in order to detect and treat CNV earlier as needed.

A program in Quickbasic for the estimation of cardiac output. The current program in Quickbasic provides a valid and reliable computational method for the estimation of cardiac output, using the CO2 rebreathe method. In addition, this program will save time through speed of execution. Furthermore, the program can be used with IBM microcomputers as well as IBM compatible microcomputers.

Clinical Science-linking basic science to disease mechanisms. For more than 50 years, Clinical Science has been at the interface linking basic science to disease mechanisms. Here, Rhian Touyz, the Editor-in-Chief, describes the journal, its aims and scope, and recent developments.

MEDLINE Search Strategies for Literature on Asian Americans/Pacific Islanders. PURPOSE OF THE REVIEW: The purpose of this study is to examine the professional health literature on Asian American/Pacific Islanders in MEDLINE, review the guiding indexing principles used in MEDLINE, and present suggestions on how to most effectively search for material in the database. SEARCH METHODS USED: The authors conducted database searches in MEDLINE and examined the National Library of Medicine indexing principles related to Asian Americans/Pacific Islanders to develop database search strategies. SUMMARY OF IMPORTANT FINDINGS: Two factors which contribute to the difficulty in identifying health literature on Asian Americans/Pacific Islanders are the small amount of material published when compared to other ethnic groups and the complex nature of indexing in MEDLINE that may create problems for less experienced database searchers. MAJOR CONCLUSIONS: Additional journal publications concerning Asian Americans/Pacific Islanders, a more thorough understanding of how the literature on this group is best retrieved from MEDLINE, and the development of more user&shy;friendly approaches to the National Library of Medicine databases will aid researchers interested in this ethnic group. KEY WORDS: Asian Americans, MEDLINE, periodicals, databases, bibliographic

On the mechanism of action of phenylalanine hydroxylase. The oxidation of 6-methyltetrahydropterin and tetrahydrobiopterin coupled to the formation of tyrosine by phenylalanine hydroxylase generates a precursor species to the quinonoid product that is tentatively identified as a 4a-hydroxy adduct based on its spectral similarity to the 4a-hydroxy-6-methyl-5-deazatetrahydropterin. The rate of appearance of this intermediate and that of tyrosine are equal and hydroxylase catalyzed in accord with the completion of the hydroxylation event. This observation, which confirms and extends an earlier one by Kaufman [Kaufman, S. (1975) in Chemistry and Biology of Pteridines (Pfleiderer, W., Ed.) p 291, Walter de Gruyter, Berlin], serves to link the reaction courses followed by pterin and pyrimidine cofactor analogues and supports the hypothesis that the 4a position is a site of O2 attachment. Thus, as expected, no prereduction of the enzyme was observed in anaerobic experiments utilizing stoichiometric amounts of enzyme and tetrahydropterin in the presence or absence of 1 mM phenylalanine. Activation of the hydroxylase by 1 mM lysolecithin leads to oxidation of the tetrahydropterin in the absence of phenylalanine. A ring-opened pyrimidine analogue of the tetrahydropterin, 2,5-diamino-4-[(meso-1-methyl-2-aminopropyl)amino]-6-hydroxypyrimidine, was studied to examine the possibility of tetrahydropterin ring opening in the enzymatic reaction prior to 4a-hydroxy adduct formation. However, no hydroxylase-catalyzed ring closure was observed.

Preliminary studies on the use of solid-phase immunosorbent techniques for the rapid detection of Wesselsbron virus (WSLV) IgM by haemagglutination-inhibition. Serum samples from 446 randomly selected persons belonging to different age groups and locations in Nigeria were tested for the presence of WSLV IgM using the flavivirus haemagglutination-inhibition (HI) test adopted to the solid-phase immunosorbent technique (SPIT). 61 (14%) persons had IgM to WSLV only, while 9 (2%) persons had heterologous IgM to WSLV and two other flaviviruses, namely yellow fever and Uganda S viruses. There was a high prevalence of IgM in people of younger age groups than those in older groups. The majority of the IgM positive sera (67 (96%) of the 70 positive sera reacted to high titres (>21:80). With the conventional HI tests, 314 (70%) of the total sera tested had HI antibodies to one or more flaviviruses (yellow fever, West Nile, Potiskum, Zika and Uganda S) out of which 305/314 (97%) had antibodies to 3 or more flaviviruses used in the tests. Although SPIT may not be as sensitive as the conventional HI test, it was found to be more specific and could be adopted for the detection of early WSLV infections in flavivirus hyperendemic environments.

A case report of an adolescent with cluster headaches following neck trauma: Coincidence or trigger? Posttraumatic headaches usually have tension-type or migraine-like characteristics. A correlation between head trauma and cluster headaches (CH) has been previously reported. CH in children are rare and require thorough differential diagnosis. We present an original case of a 15-year-old boy with cluster headaches associated with allodynia probably evoked by a neck trauma. Severe headache attacks started one month after neck trauma. At the beginning clinical presentation of our patient's headaches was very misleading. Headaches were bilateral and associated with infection. Initial diagnosis of sinusitis was made. During further observation headaches have become unilateral with typical for CH associated symptoms and additionally with allodynia. Other causes of secondary CH like cervicogenic headaches, brain tumor and vascular malformation have been excluded. The boy has undergone prophylactic treatment based on flunarizine and gabapentin with good result. Possible pathogenesis of our patient's headaches has been proposed and diagnostic traps discussed.

Patient-based surveying: a cost-effective approach for reaching large markets. Member-based surveying is an important tool for managed care companies to discern newer and better ways in which to keep their current members satisfied, develop products that will attract new members, and to gauge changes of course in health consumer opinion. This article discusses a consumer friendly and cost-effective method to survey members and the general public that has produced a very positive response for a modest investment. The response rate will likely improve over time as the method gains broader acceptance.

Lack of evidence of systemic inflammatory rheumatic disorders in symptomatic women with breast implants. Breast implants containing silicone have been used for approximately 30 years for breast augmentation or reconstruction. In general, the implants have been well tolerated and reports have indicated a high degree of patient satisfaction. Nonetheless, there have been anecdotal reports of patients with musculoskeletal complaints that have been attributed to silicone breast implants. To investigate this further, we prospectively examined 70 women with silicone breast implants who had complaints that they or their referring physicians thought were related to their implants. On clinical examination, the majority of the patients had fibromyalgia, osteoarthritis, or soft-tissue rheumatism. One patient had rheumatoid arthritis, which predated her implants, and one had Sjõgren's syndrome. Because many of our patients had myalgic symptoms, we further evaluated these patients by measuring circulating levels of soluble factors including interleukin-6, interleukin-8, tumor necrosis factor-alpha, soluble intercellular adhesion molecule-1, and soluble interleukin-2 receptor, which have been previously found to be elevated in patients with inflammatory diseases. We found that the levels of these molecules in women with silicone breast implants were not different from those seen in normal subjects and were significantly less than those seen when examining chronic inflammatory disorders such as rheumatoid arthritis or systemic lupus erythematosus. In summary, our clinical and laboratory evaluation of symptomatic breast implant patients argues against an association of silicone breast implants with a distinctive rheumatic disease or a systemic inflammatory disorder. Given these findings and the clinical picture, it is our impression that most symptomatic women with silicone breast implants have well-delineated noninflammatory musculoskeletal syndromes. Moreover, these data fail to support the concept that their symptoms are due to a systemic inflammatory response related to their implants.

Effects of haptic supplementation on postural stability in unilateral vestibular loss patients. The effects of haptic supplementation on postural stability during upright standing with vision were investigated in 11 unilateral vestibular loss (UVL) patients and compared to 12 age-marched controls. All the participants were instructed to grip a fixed or mobile stick. In the mobile conditions, the lower extremity of the stick was in contact with a slippery or a rough surface. Postural stability was assessed by the root mean square (RMS) and the velocity of the center of foot pressure (CoP) displacements in both antero-posterior (AP) and medio-lateral (ML) directions. Results showed that RMS was larger in UVL patients than in aged-matched participants in AP direction. However, in the mobile stick conditions, only the rough surface improved postural stability. In addition, RMS was more sensitive to haptic supplementation than CoP velocity. The present study confirms the importance of haptic information in the multi-sensory (re) weighting process underlying postural control in UVL patients.

Effects of methylphenidate and expectancy of ADHD children's performance, self-evaluations, persistence, and attributions on a cognitive task. The effects of 0.3 mg/kg methylphenidate (MPH) and expectancy regarding medication on the performance and task persistence of 60 boys with attention deficit hyperactivity disorder (ADHD) were investigated. In a balanced-placebo design, boys in 4 groups (received placebo/drug crossed with told placebo/drug) completed the task in success and failure conditions. Medication improved participants' task persistence following failure. Participants' task performance was not affected by whether they thought they had received medication or placebo. Children made internal attributions for success and made external attributions for failure, regardless of medication or expectancy. These findings confirm previous reports that it is the pharmacological activity of MPH that affects ADHD children's self-evaluations and persistence. The results contradict anecdotal reports that MPH causes dysfunctional attributions and confirm previous studies showing that medication does not produce adverse effects on the causal attributions of children with ADHD.

Disordered expression of HOX genes in human non-small cell lung cancer. We hypothesized that the disordered tissue architecture in cancer results from the cells executing the program designed during ontogeny in a spatio-temporally inappropriate manner. HOX genes are known as master regulators of embryonic morphogenesis, and encode transcription factors which regulate the transcription of the downstream genes to realize the program of body plan. In this study, we quantified the expression levels of 39 HOX genes in 41 human non-small cell lung cancer (non-SCLC) and non-cancerous lung tissues by a comprehensive analysis system based on the real-time RT-PCR method. We found that the expression levels of HOXA1, A5, A10 and C6 in squamous cell carcinoma tissues (and HOXA5 and A10 in adenocarcinoma tissues) were significantly higher than those in the non-cancerous tissues. Comparison of HOX gene expressions between adenocarcinoma and squamous cell carcinoma tissues showed higher expressions of HOXA1, D9, D10 and D11 in squamous cell carcinoma tissues than in adenocarcinoma tissues. Immunohistochemical analysis revealed that HOXA5 and A10 proteins were localized in the cytoplasm of tumor cells in both adenocarcinoma and squamous cell carcinoma tissues. These results suggest that the disordered patterns of HOX gene expressions were involved not only in the development of non-SCLC but also in the histologically aberrant diversity such as adenocarcinoma and squamous cell carcinoma.

Infections in the immunocompromised rheumatologic patient. Immunocompromised patients with rheumatic diseases have an increased risk of infections. A major risk factor for infection seems to be the immunosuppressive therapy used. Newer therapies for RA may lead to increased rates of infection by opportunistic pathogens such as Mycobacteria tuberculosis. Because disease manifestation may mimic signs and symptoms of infection, prompt diagnosis may be difficult. Familiarity with the likely infections and their causes should aid in obtaining the appropriate culture specimens.

External vs endoscopic approach for inverted papilloma of the sino-nasal cavities: a retrospective study of 136 cases. Endoscopic removal, with or without external technique, can be performed in a majority of inverted papilloma cases. This method has subsequent recurrence rates that are comparable to those of more aggressive external techniques and it is more cost efficient with less morbidity. To analyze the clinical outcomes of our 21-year experience (1986-2006) in treating inverted papillomas using different treatment modalities. The patients were divided into a conventional surgery group (CSG) and an endoscopic surgery group (ESG) and were staged according to the system developed by Krouse. A retrospective assessment was performed. The recurrence rates were 4.3% in ESG and 9.5% in CSG. There was no significant difference in the recurrence rates according to the treatment modality used and the Krouse stage in the two groups. Mean operation time was 72.93+/-18.51 min in the ESG and 112.02+/-56.52 min in the CSG. Mean period of hospital stay was 4.66+/-1.75 days in the ESG and 9.54+/-4.79 days in the CSG. The complication rate was 3.2% in the ESG and 33.3% in the CSG. There was a significant difference in the operation time, length of hospital stay, and complication rate in the two groups.

[The effects of cognitive behavioral anger management program on self-consciousness and anger in Korean military man]. The purpose of this study was to evaluate a cognitive behavioral anger management intervention in order to increase self-consciousness and decrease anger among Korean military men. A quasi-experimental design was used for this study. Ninety two soldiers were screened for unhealthy anger expression using a questionnaire. Among them, 26 soldiers who showed unhealthy anger expression were selected for this study. They were matched by rank and assigned to either a treatment or control group. The treatment group received the intervention three consecutive times, once a week and for 120 minutes per session. Participants were assessed before and after the intervention for anger (the State-Trait Anger Scale) and self-consciousness (Self-consciousness Scale). Data was analyzed using descriptive statistics, chi- square-test, Mann-Whitney test, and Wilcox on signed rank test. There was no statistically significant decrease in anger or increase in self-consciousness between the two groups following treatment. However, there was a significant increase in private self-consciousness in the treatment group after the intervention(p=.006). The cognitive behavioral anger management program improves private self-consciousness in soldiers. However, Additional research is needed to explore whether long-term intervention is more effective for anger control in the military setting. The findings from this study suggest that more attention should be given to mental health care for Korean soldiers.

An investigation of penetration depth control using parallel opposed ultrasound arrays and a scanning reflector. A theoretical study of penetration depth control in superficial hyperthermia utilizing parallel opposed linear ultrasound arrays and a double-faced (V-shaped) scanning reflector is presented. This is a dual array system (DAS), where one array operates at a low frequency and the other at a high frequency (1 and 5 MHz, respectively in this study). The arrays are positioned facing each other and both are aimed at a double-faced scanning reflector which distributes the energy over the scanned surface. Each reflecting surface is angled at 45 degrees with respect to the sound propagation direction so that both beams are deflected in the same direction toward the treatment volume. The system was designed to be compatible for combined operation with a medical linear accelerator for the delivery of simultaneous thermoradiotherapy. It is demonstrated that by varying the excitation magnitude of one array relative to the other, it is possible to control the magnitude of absorbed energy as a function of depth, and thus improved control of the heating pattern in all three spatial dimensions is obtained. This improvement is demonstrated with bio-heat transfer simulations which show how penetration depth control translates into control of temperature distributions. The simulations also show that the DAS is able to produce more uniform temperature distributions in highly perfused tissue.

Does matrix-assisted laser desorption/ionization mass spectrometry allow analysis of carbohydrate heterogeneity in glycoproteins? A study of natural human interferon-gamma. Interferon-gamma (IFN-gamma) is a dimeric, secretory glycoprotein produced by T-lymphocytes. The glycan micro-heterogeneity of natural human IFN-gamma was characterized by matrix-assisted laser desorption/ionization mass spectrometry (MALDI/MS) combined with glycosidase digestion. The glycan structures at the two potential glycosylation sites, asparagine 25 and 97, differ in composition and heterogeneity. The glycan at Asn 25 consists of a mixture of hybrid structures and fucosylated complex bi-, tri- and tetra-antennary structures, whereas the glycan at Asn 97 is more heterogeneous and consists of a mixture of high mannose structures, hybrid structures and unfucosylated complex bi- and tri-antennary structures. The contribution to the observed glycan heterogeneity by prompt and metastable fragmentation was evaluated by treatments with different exoglycosidases and by comparison of linear, reflected and delayed extraction MALDI/TOF mass spectra. Heterogeneity observed with the matrices alpha-cyano-4-hydroxycinnamic acid, 2,5-dihydroxybenzoic acid and 2,4,6-trihydroxyacetophenone was compared. Most of the heterogeneity can be attributed to native structure diversity and only to a minor extent to mass spectrometric fragmentation such as fragmentational loss of sialic acid residues.

Poisoning of sheep by seeds of Crotalaria retusa: acquired resistance by continuous administration of low doses. Seeds of Crotalaria retusa containing 6.84% (dry weight) of monocrotaline (MCT) were administered experimentally to sheep. Three sheep that received 136.8mg MCT/kg bw daily for 70 days had no clinical signs. Five out of six sheep ingesting single doses of 205.2 and 273.6mg MCT/kg bw died with acute (three sheep) or chronic intoxication (two sheep). Acute intoxicated sheep had periacinar liver necrosis and chronic intoxicated sheep liver fibrosis and megalocytosis. Another three sheep had no clinical signs after the ingestion of 20 daily doses of 136.8mg MCT/kg, followed by seven doses of 273.6mg MCT/kg, and one single dose of 342mg MCT/kg. These experiments demonstrated that sheep are susceptible to acute intoxication by MCT being intoxicated by a single oral dose of approximately 205.2mg/kg. In contrast, they develop strong resistance to MCT after the daily ingestion of non lethal doses (136.8mg/kg). It is suggested that chronic poisoning does not occur by the repeated ingestion of non acutely toxic doses, but probably by the ingestion of single toxic doses. It is also suggested that sheep do not become intoxicated with the ingestion of C. retusa in the vegetative non-seeding stage.

In vitro assessment of anticryptosporidial efficacy and cytotoxicity of adenosine analogues using a SYBR Green real-time PCR method. The aims of this study were to provide a cost-effective and valuable method for evaluating drug efficacy against Cryptosporidium parvum using a quantitative SYBR Green real-time PCR (qPCR) and to assess the efficacy of adenosine analogues as drug templates. C. parvum HNJ-1 strain growing in human ileocaecal adenocarcinoma cells was employed as an in vitro culture system. To normalize the DNA extraction efficiency, a specific plasmid was added to each sample before DNA purification; the genomic DNA of infected cells was quantified by qPCR using specific primers to confirm drug efficacy and cytotoxicity. To determine the mechanism of action, enzymatic inhibition analyses were conducted using C. parvum S-adenosyl-l-homocysteine hydrolase (CpSAHH) recombinant protein. The dose-dependent growth inhibition of C. parvum was confirmed; 50% effective concentrations of neplanocin A (NPA) and 2-fluoroadenosine (2FA) were 139 μM and 0.842 μM, respectively. Cytotoxicity evaluation showed that the 50% growth inhibition concentration of 2FA was 1.18 μM; NPA did not exhibit any cytotoxicity up to 200 μM. The screening system revealed the specific but marginal efficacy of NPA and showed 2FA to be cytotoxic. Recombinant CpSAHH inhibition analyses showed that NPA competitively inhibited CpSAHH activity (K(i )= 0.395 μM), whereas 2FA did not. This novel qPCR system confirmed not only drug efficacy against C. parvum but also cytotoxicity to host cells. Moreover, since the SYBR Green method is cost effective, it could therefore be used in a wide variety of clinical and research-oriented applications of Cryptosporidium analysis.

[Course of diabetic retinopathy and metabolic control with subcutaneous insulin infusion pump: 18-month study]. The effect of a good metabolic control in the natural history of diabetic retinopathy is discussed because, although the onset and the incidence are closely related to a bad metabolic control, there is no improvement related to a good control; progression having been reported with the good metabolic controls. 7 patients subjected to a strict control with continuous subcutaneous insulin infusion were compared with a group of 10 patients with a good conventional treatment in an 18 month study. The best metabolic control of the first group was obtained at 9, 12, 15 and 18 months (p less than 0,05). The evolution of retinopathy in this group did not change with the treatment and there was no proof of progression with the use of continuous subcutaneous infusion. Further follow-up evaluation is necessary to confirm this affirmation.

Large prostatic utricles and related structures, urogenital sinus and other forms of urethrovaginal confluence. The urethrograms and clinical records of 106 children with a large prostatic utricle or related structures, urogenital sinus in intersex disorders and other types of urethrovaginal confluence were reviewed. There were 27 boys with normal external genitalia, 19 cases of male hypospadias, 1 case of male pseudohermaphroditism, 7 cases of mixed gonadal dysgenesis, 1 case of true hermaphroditism, 32 cases of female pseudohermaphroditism, 11 normal girls with urethrovaginal confluence and 8 cases of cloacal malformation. Among the patients of the first 2 groups 10 had an imperforate anus, 7 the prune belly syndrome, 6 Down's syndrome and 2 posterior urethral valves.

Late complications of radiotherapy for nasopharyngeal carcinoma. To evaluate and assemble late complications of radiotherapy in cases of nasopharyngeal cancer. From October 2003 to January 2005, a prospective cohort study was done in a tertiary center, Chiang Mai University Hospital. Two hundred patients were evaluated for late complication according to the RTOG/EORTC late radiation morbidity scoring criteria. Of 200 patients, 131 were male (65.5%) and 69 female (34.5%). The mean age was 49.7+/-13.5 years (11-78). The mean pre- and post-treatment body mass indexes (BMI) were 22.5+/-4 (15-35.6), and 19.8+/-3.2 (12.9-34.5; P<0.05). Mean post-radiation period was 3.6+/-3.4 years (0.3-18.6 years). The radiation dosage ranged from 60 to 76Gy (mean 69Gy). Most of the patients (92%) had undifferentiated (50.5%) and poorly differentiated (41.5%) squamous cell carcinoma. Eighty-eight percent of the patients were in Stage III and IV. Chemotherapy was given to 145 patients (72.5%). The mean post-radiation period in the added chemotherapy group was lower than the group treated with radiation alone (2.9+/-2.7 years vs. 5.4+/-4.4 years, P<.05). The most common complication was dryness of mouth (97.5%); followed by hearing impairment (inner ear 82.5%). Added chemotherapy increased the complication severity significantly for the skin (P<0.05). The mean number of complications was 6.3+/-2.2 (range from 1 to 12). In this study, every patient had a more or less adverse reaction to radiation. Doctors need to be aware of these complications in order to prevent serious ones and to improve the patients' quality of life in the long term.

Pathologic basis of the sonographic appearance of the normal and malignant prostate. The hypoechoic nature of prostatic cancer is now well recognized. In fact, not all cancers are purely hypoechoic; many are isoechoic, and some have a mixed echogenicity. Rarely, we have seen a cancer that was predominantly hyperechoic. Other signs of disturbance of the normal internal anatomy of the prostate may suggest the diagnosis of prostate cancer and are particularly valuable in assessing patients with more advanced disease. Approximately one third of early-stage cancers detected by palpation or transurethral resection are isoechoic. These tumors are anteriorly located, small, and well differentiated and infiltrate among normal glands or are composed of malignant glands similar in size to normal acini. Not all hypoechoic areas within the prostate are cancer; both normal anatomic structures and various benign conditions may appear less echogenic than the normal prostatic parenchyma. A comprehensive understanding of normal prostatic anatomy and the morphology of prostate cancer is essential to the accurate interpretation of the sonogram. Precise interpretation of prostatic sonograms requires detailed correlations of high-quality images with pathologic examinations of the whole prostate. The development of accurate criteria for the sonographic diagnosis of both malignant and benign prostatic diseases can be achieved only by such studies. As the possibilities and limitations of transrectal ultrasonography become apparent from pathologic correlation, the role of ultrasound in the diagnosis of prostate cancer will be placed on a more rational basis.

The bacteriological composition of biomass recovered by flushing an operational drinking water distribution system. This study investigates the influence of pipe characteristics on the bacteriological composition of material mobilised from a drinking water distribution system (DWDS) and the impact of biofilm removal on water quality. Hydrants in a single UK Distribution Management Area (DMA) with both polyethylene and cast iron pipe sections were subjected to incremental increases in flow to mobilise material from the pipe walls. Turbidity was monitored during these operations and water samples were collected for physico-chemical and bacteriological analysis. DNA was extracted from the material mobilised into the bulk water before and during flushing. Bacterial tag-encoded 454 pyrosequencing was then used to characterize the bacterial communities present in this material. Turbidity values were high in the samples from cast iron pipes. Iron, aluminium, manganese and phosphate concentrations were found to correlate to observed turbidity. The bacterial community composition of the material mobilised from the pipes was significantly different between plastic and cast iron pipe sections (p < 0.5). High relative abundances of Alphaproteobacteria (23.3%), Clostridia (10.3%) and Actinobacteria (10.3%) were detected in the material removed from plastic pipes. Sequences related to Alphaproteobacteria (22.8%), Bacilli (16.6%), and Gammaproteobacteria (1.4%) were predominant in the samples obtained from cast iron pipes. The highest species richness and diversity were found in the samples from material mobilised from plastic pipes. Spirochaeta spp., Methylobacterium spp. Clostridium spp. and Desulfobacterium spp., were the most represented genera in the material obtained prior to and during the flushing of the plastic pipes. In cast iron pipes a high relative abundance of bacteria able to utilise different iron and manganese compounds were found such as Lysinibacillus spp., Geobacillus spp. and Magnetobacterium spp.

Drug Development for Hypertension: Do We Need Another Antihypertensive Agent for Resistant Hypertension? The prevalence of resistant hypertension is seemingly much lower than had been reported in early studies. Recent analyses suggest that <5 % of treated hypertensive patients remain uncontrolled if fully adherent to an optimized antihypertensive treatment. However, these patients do have increased cardiovascular risk and need effective therapeutic approaches. Drug development is a high-risk, complex, lengthy, and very expensive process. In this article, we discuss the factors that should be considered in the process of developing a new agent for treatment of resistant hypertension.

Large cerebral arteriovenous malformation presenting with venous ischemia in the contralateral hemisphere. Case report. The authors report a rare case in which a large cerebral arteriovenous malformation (AVM) located in the left parietooccipital region presented with venous ischemia in the contralateral hemisphere. A 74-year-old man was admitted to the hospital because he was experiencing a loss of appetite, disorientation, and left hemiparesis. Computerized tomography scans revealed a low-density area in the right temporal lobe. Angiography demonstrated a large AVM in the left parietooccipital lobe and dilation, stagnation, and meanders of cortical veins in the contralateral hemisphere. The authors speculated that the elevated sinus pressure caused by a huge venous return of blood from the AVM produced venous ischemia in the contralateral hemisphere.

Association of decreased expression of the macrophage scavenger receptor MARCO with tumor progression and poor prognosis in human hepatocellular carcinoma. The macrophage receptor with collagenous structure (MARCO) belongs to the scavenger receptor family; however, few studies have assessed their potentials in modulating inflammatory signaling other than the typical function of pattern recognition and phagocytic clearance. Interestingly, RNA-Seq analyses of hepatocellular carcinoma (HCC) have identified MARCO as one of the top 30 differentially expressed genes between cancerous and adjacent noncancerous tissues. However, no research has been performed to study MARCO in liver cancer. MARCO protein expression was evaluated by immunostaining liver tissue specimens collected from 88 HCC patients, 10 liver cirrhosis patients, 6 metastatic patients, and 5 healthy controls. All sections were reviewed by blinded observers followed by the interpretation of integral optical density per area as a measure of protein intensity. We observed significantly decreased expression of MARCO in intratumoral tissues of HCC compared with expression in peritumoral tissues. The expression of MARCO declined progressively as the disease condition was aggravated, with the highest expression found in healthy controls and the lowest found in patients with HCC metastasis. Furthermore, MARCO expression decreased along with tumor progression. MARCO+ cells co-localized with CD68+ cells, indicating predominant expression on macrophages. The overall survival rate was significantly increased in patients with high intratumoral MARCO expression compared with that of patients with low intratumoral MARCO expression. Our study is the first to demonstrate an association between MARCO expression and the progression and prognosis of HCC.

Self-Healing and Multistimuli-Responsive Hydrogels Formed via a Cooperation Strategy and Their Application in Detecting Biogenic Amines. We reported here a new platform of supramolecular hydrogels cross-linked by the cooperation of metal-ligand coordination and hydrophobic interaction. A salicylaldehyde benzoyl hydrazone-terminal poly(ethylene glycol) (2SBH-PEG) was synthesized and formed small micelles in an aqueous environment. Addition of Ni2+ connected the low-molecular-weight 2SBH-PEG into a metallopolymer via metal-ligand coordination and led to micelle aggregation, resulting in gelation due to the enhancement of hydrophobic interaction. The forming hydrogel, Ni-PEGel, exhibited rapid self-healing ability and reversible pH-responsive property. Because of the containing metal coordination bond, it was also sensitive to the strong competing ligands, such as ethylenediaminetetraacetic acid (EDTA) and pyridine. In addition, Ni-PEGel showed colorimetric changes when exposed to biogenic amine (BA) vapor. The color development of Ni-PEGel toward BAs makes it a good candidate in monitoring food spoilage.

Diglyceride kinase in human platelets. Human platelets contain diglyceride kinase, an enzyme that catalyzes the phosphorylation of diacylglycerol by adenosine 5'-triphosphate to yield phosphatidic acid. The majority of the platelet enzyme is particulate-bound, and membrane fractions of platelet homogenates have a higher specific activity than granule fractions. Both deoxycholate and magnesium are necessary for optimal enzyme activity. The K(m) of the enzyme for adenosine 5'-triphosphate is 1.3 mm, and the apparent K(m) for diacylglycerol is 0.4 mm. The pH optimum is 6.6-6.8 in imidazole-HCl or maleate-NaOH buffer. The enzyme activity of platelets from normal subjects was similar to the activity from patients with renal and hepatic failure.

Effects of cisapride on oesophageal transit of solids in patients with progressive systemic sclerosis. In most patients with progressive systemic sclerosis (PSS) the oesophagus is affected. Reflux symptoms are most frequent, whilst dysphagia also occurs. Cisapride, a prokinetic agent, may enhance motility along the gastrointestinal tract. The effects of cisapride on oesophageal transit were evaluated in 12 PSS patient using a solid-phase radionuclide oesophageal transit study. Each PSS patient was given cisapride 10 mg or placebo orally three times a day in a random, double-blind, crossover fashion. The results show that cisapride does not seem to have any impact on oesophageal transit in patients with PSS.

[Diagnostic use of laser Doppler flowmetry in patients with circulatory insufficiency]. Laser Doppler Flowmetry (LDF) is a method for continuous quantification of microvascular perfusion. The article briefly presents the principle of the method, and reviews the literature dealing with diagnostic use of LDF in patients with insufficient extremity circulation. The location and degree of vascular lesions can be evaluated, and non-invasive evaluation of peripheral vascular resistance performed in the vascular laboratory. Prospective human studies are needed before the clinical value of the method can be assessed.

Four keys to success (theory, implementation, evaluation, and resource/system support): high hopes and challenges in participation. In this article, I attempt to merge two themes. First, there is often a large gap between high hopes about impacts of policies or programs and the demonstrated results. I describe four keys/threats to success in any social problem area: theory, implementation, evaluation, and resource/system support. Second, I present theory and research from over 30 years of work on participation, conducted by my colleagues and myself that can illuminate and be illuminated by theory, implementation, evaluation, and resource/system support. I offer ideas for solutions that increase the probability of success. I conclude with the need to have high hopes tempered by theory and research to develop realistically ambitious solutions to social problems.

Laparoscopic approach for human islet transplantation into a defined liver segment in type-1 diabetic patients. Intra-portal islet transplantation is usually performed by cannulation of a mesenteric vein during laparotomy or through percutaneous trans-hepatic cannulation of a portal branch. In this study, we describe a new laparoscopic technique for intra-portal islet transplantation in a defined liver segment, as an alternative to the current procedures. Eighteen type-1 diabetic patients underwent laparoscopic re-permeabilisation of the umbilical vein, followed by catheterization of the left branch of the portal vein. The catheter was guided under fluoroscopic control into a chosen liver segment. It was then secured to the skin or connected to an implantable venous access device. Thereafter, the islet preparation was slowly injected. There was no rise in portal pressure. The median duration of the procedure was 85 min. The procedure was successful in 17 of 18 cases. There were no surgical complications. We conclude that this laparoscopic procedure is a feasible, convenient, and safe alternative method of islet transplantation. Moreover, it allows multiple deliveries of islets into the same liver segment.

Development of spatiotemporal mechanisms in infant vision. In adult spatiotemporal vision information is processed in parallel by a number of mechanisms tuned for orientation and spatial frequency. An examination of infant neuroanatomical data suggests that three major factors are involved in the development of these mechanisms: (1) Growth of foveal cone outer segments causes an increase in mechanism sensitivity. (2) Migration of foveal cones produces a change in spatial scale and a progressive shift of mechanism tuning towards higher spatial frequencies. (3) Development of cortical inhibition transforms low-pass into bandpass spatial frequency and orientation tuning. These changes are developed into a quantitative model which is shown to provide a coherent interpretation of many of the psychophysical data on infant vision.

Morphometrics of a neotropical sandfly subspecies, Lutzomyia carrerai thula. In spite of obvious and frequently observed morphological variation in geographic populations of sand flies, taxonomists are reluctant to create subspecies. In doing so they avoid confusion caused by the accumulation of new taxa, but they also obscure natural processes, some of them related to probable species emergence. We investigated here how far the partitioning of size, shape and form could be a relevant technique for exploring early evolutionary processes. We used a typical case of species, subspecies and cryptic species among three related taxa: Lutzomyia carrerai, its subspecies L. carrerai thula and L. yucumensis, a cryptic species of L. carrerai. Univariate and multivariate metric analyses showed global size differences, even between sympatric taxa (L. carrerai and L. yucumensis). When allometric effects were discounted, the subspecies L. c. thula still disclosed important differences from its putative type species, more pronounced than those existing between the two cryptic species, L. yucumensis and L. carrerai. A similar result was obtained after removing isometric size. These analyses question the validity of L. carrerai thula as a subspecies, and show that morphometrics may be a useful tool for separating simple geographic variation from evolutionary divergence.

Cardiovascular risk factors and relatedness in an Icelandic subpopulation. Theoretical and empirical studies suggest adverse effects of inbreeding on general vigour. The genetic architecture of physiological and biochemical cardiovascular risk factors is, furthermore, an unsolved issue. Our aim with this study is to investigate potential effects of inbreeding on stated risk factors in a relatively well demarcated Icelandic subpopulation. We used genealogical records to calculate coefficient of inbreeding and estimated the potential association of the coefficient with stated risk factors with known statistical methods. The results suggest absence of inbreeding depression with exception of HDL cholesterol.

Tumour-simulating squamous cell metaplasia (SCM) in necrotic areas of salivary gland tumours. Squamous cell metaplasia (SCM) adjacent to necrotic areas of salivary gland tumours must be distinguished from other types of SCM (focal SCM in the excretory ducts of salivary glands; necrotizing sialometaplasia; focal SCM within salivary gland tumours) in respect to the tissue structure. Based on the high cellular proliferation, arcade- or cord-like pseudoneoplastic SCM develops with stellate extension in the surrounding tissue and focal inclusion of goblet cell metaplasia. This proliferative SCM resembles the cellular demarcation of radicular dental cysts. In the Salivary Gland Register 8 cases of tumor-simulating SCM could be analysed which clinically and morphologically were suspect of squamous cell or mucoepidermoid carcinoma. Five cases were localized in the parotid gland, 2 cases in the submandibular gland and 1 case in the palatinal glands. Tumour-simulating SCM was developed in pleomorphic adenomas (5 cases) and in multifocal adenomatous oncocytic hyperplasia (3 cases).

A linkage map of distal mouse chromosome 12. To refine the linkage map of distal mouse Chromosome 12, we have identified DNA restriction fragment variants associated with a creatine kinase gene (Ck-3), the Akt proto-oncogene, an Abelson proviral integration site (D12N1), and the immunoglobulin heavy chain VH3609 variable region family (Igh-V36). The patterns of inheritance of these markers in backcross progeny and recombinant inbred mouse strains allowed their localization with respect to previously mapped genes to yield the linkage map: Aat-15.8 cM-Ck-3-0.9 cM-(Crip, Akt, Igh-C)-0.3 cM-(D12N1, Igh-V). This map confirms genetically the localization of the Igh-V gene complex distal to Igh-C on the chromosome. It differs from previous maps in placing D12N1 distal to Igh-C, and in suggesting that the Igh-V gene complex spans less than one centiMorgan (cM). Other DNA sequence variants detected with the creatine kinase probe allowed definition of four additional genetic loci: Ck-1 near Lmyc-1 on Chromosome 4; Ck-2 between Upg-1 and Hprt-ps1 (D17Rp10) on distal Chromosome 17; Ck-4 near Mpmv-17 and Mls-3 on Chromosome 16; and Ck-5 near Hba on Chromosome 11.

Changes in serum interleukin-6, C-reactive protein and thrombomodulin levels under periodontal ultrasonic debridement. This study aimed to compare the effect of single-visit full-mouth mechanical debridement (FMD) and quadrant-wise mechanical debridement (QMD) on the levels of serum interleukin (IL)-6, C-reactive protein (CRP) and soluble thrombomodulin. Thirty-six subjects with chronic periodontitis were randomly allocated to three groups: undergoing QMD, single-visit FMD with povidone iodine or with water. Serum IL-6 and soluble thrombomodulin were measured by enzyme-linked immunosorbent assay, and serum CRP was measured by the latex-enhanced nephelometric method. Serum IL-6 level increased significantly immediately after debridement in all the three groups, with this increase being greatest in the full-mouth groups. However, the increase in the full-mouth groups was not significantly higher than that of quadrant-wise group. In the quadrant-wise group, serum IL-6 level decreased significantly 1 month after debridement compared with baseline. Serum-soluble thrombomodulin decreased significantly in the full-mouth groups but not in the quadrant-wise group. Changes in CRP level were not significant at baseline or after debridement in all the three groups. FMD increased serum IL-6 and reduced serum-soluble thrombomodulin to a greater extent than QMD, suggesting that the former technique has stronger transient effects on systemic vascular endothelial functions than the latter.

The Effectiveness of Psychoeducational Interventions Focused on Sexuality in Cancer. Although sexual health is a common concern for oncology patients, no practical guidelines to sexual intervention exist, perhaps because of a lack of systematic reviews or meta-analyses. The objectives of this study were to determine the effect size for psychoeducational intervention focused on sexuality and to compare effect sizes according to intervention outcomes and characteristic. We explored quantitative evidence for the effects of sexual intervention for cancer patients or partners by using the electronic databases. Among them, we considered 15 eligible articles. The meta-analysis provided 133 effect sizes from 15 primary studies. The analysis revealed significant improvements after intervention, with a random-effects standardized mean difference of 0.75. Psychoeducational interventions focused on sexuality after cancer diagnosis were effective for compliance (2.40), cognitive aspect (1.29), and psychological aspect (0.83). Individual-based interventions (0.85) were more effective in improving outcomes than group approach and group combined with individual intervention. With regard to intervention providers, registered nurse only (2.22) and team approach including the registered nurse (2.38) had the highest effect size. Face-to-face intervention combined with telephone or the Internet (1.04) demonstrated a higher effect size than face-to-face (0.62) and telephone (0.58) independently. We conducted an analysis of data from various subgroups of preexisting studies, obtained an overall estimate of the effectiveness of the intervention, and compared its effectiveness across variables that affect intervention outcomes. These results provide empirical data for evidence-based practice and inform the development of useful intervention programs through a comprehensive review and meta-analysis of the results.

Finite-size radiation force correction for inviscid spheres in standing waves. Yosioka and Kawasima gave a widely used approximation for the acoustic radiation force on small liquid spheres surrounded by an immiscible liquid in 1955. Considering the liquids to be inviscid with negligible thermal dissipation, in their approximation the force on the sphere is proportional to the sphere's volume and the levitation position in a vertical standing wave becomes independent of the size. The analysis given here introduces a small correction term proportional to the square of the sphere's radius relative to the aforementioned small-sphere force. The significance of this term also depends on the relative density and sound velocity of the sphere. The improved approximation is supported by comparison with the exact partial-wave-series based radiation force for ideal fluid spheres in ideal fluids.

[Pulse wave velocity - a useful tool in assessing the stiffness of the arteries]. Measurement of pulse wave velocity (PWV) is a simple and noninvasive way to assess stiffness of the arteries. PWV measurement can refer to both the aorta and peripheral arterial vessels. Currently, the most clinically significant is the measurement of PWV between the carotid artery and the femoral artery, which is defined as the speed of the aortic pulse wave. Numerous studies have demonstrated the significance of prognostic PWV aortic measurement as a recognized exponent of subclinical organ damage both among the general population as well as among patients with increased cardiovascular risk, examining patients in detail with hypertension, diabetes, chronic renal failure. The prognostic value of PWV aortic measurement was reflected in the guidelines of the European Society of Cardiology (ESC) and the European Society of Hypertension (ESH). In clinical trials, the repeatability and reproducibility of PWV measurements were also evaluated, both parameters being considered satisfactory. The paper presents reports from studies on the significance of pulse wave velocity results in the prognosis assessment in different disease entities as well as in age groups.

[Treatable hereditary neuro-metabolic diseases]. Hereditary metabolic diseases may appear during adolescence or young adulthood, revealed by an apparently unexplained neurological or psychiatric disorder. Certain metabolic diseases respond to specific treatments and should be identified early, particularly in emergency situations where rapid introduction of a treatment can avoid fatal outcome or irreversible neurological damage. The main diseases leading to an acute neurological syndrome in the adult are urea cycle disorders, homocysteine metabolisms disorders and porphyria. More rarely, Wilson's disease, aminoacid diseases, organic aciduria, or pyruvate dehydrogenase deficiency, beta-oxidation disordes or biotin metabolism may be involved. Most emergency situations can be screen correctly with simple tests (serum ammonia, homocysteine, lactate, urinary prophyrines, acylcarnitine pattern, amino acid and organic acid chromatography). For chronic situations, the main treatable diseases are Wilson's disease, homocysteine, cerebrotendinous xanthomatosis, Refsum's disease, vitamin E deficiency, Gaucher's disease, Fabry's disease, and neurotransmitter metabolism disorders. We present treatable metabolic disorders as a function of the different clinical situations observed in adults.

[Imagination: its definition, purposes and neurobiology]. Imagination, distinct from imagery, memory, and cognition, is a poorly understood but fascinating cognitive ability of human beings. Herein, imagination is defined as 'the cognitive process which enables the individual to manipulate intrinsically generated phenomenal information in order to create a representation perceived by the mind's senses.' This definition is expanded within the context of the neurobiology of the brain and the possible purposes the imagination fulfills in daily living, human development, and normal behavior.

Analysis of telomerase processivity: mechanistic similarity to HIV-1 reverse transcriptase and role in telomere maintenance. The key protein subunit of the telomerase complex, known as TERT, possesses a reverse transcriptase (RT)-like domain that is conserved in enzymes encoded by retroviruses and retroelements. Structural and functional analysis of HIV-1 RT suggests that RT processivity is governed, in part, by the conserved motif C, motif E, and a C-terminal domain. Mutations in analogous regions of the yeast TERT were found to have anticipated effects on telomerase processivity in vitro, suggesting a great deal of mechanistic and structural similarity between TERT and retroviral RTs, and a similarity that goes beyond the homologous domain. A close correlation was uncovered between telomerase processivity and telomere length in vivo, suggesting that enzyme processivity is a limiting factor for telomere maintenance.

Development of a streamlined rat whole embryo culture assay for classifying teratogenic potential of pharmaceutical compounds. This study describes a novel rat whole embryo culture (rWEC) teratogenicity assay that applies a simplified experimental design and statistical prediction model, resulting in reduced animal requirements and increased throughput with low prediction error rate for classifying teratogenic potential of compounds. A total of 70 compounds (38 teratogens and 32 nonteratogens) were evaluated, and the prediction model was generated from a dataset of 59 compounds. The rWEC assay requires only one test concentration (1μM) and three structural endpoints (group average morphological scores of spinal cord, heart, and number of somite pairs), which are used in a recursive partition model for classifying teratogenic liability. The model fitting concordance between the WEC assay and in vivo outcome was 83% with a standard deviation (SD) of 4.9%. The predictivity for future compounds was evaluated by using two statistical methods. Fivefold cross-validation estimated the predictivity of this model at 73% (SD 5.8%). A second estimation of predictivity was obtained from an independent test set of 11 compounds that were not used to build the prediction model and reached 82% (SD 11.6%). The overall estimate for prediction concordance is 74% (SD 5.2%). There is no statistically significant difference (p value > 0.50) in the predictivity between this model and the model supporting European Center for the Validation of Alternative Methods WEC assay with predictivity of 80% (SD 10.6%). Overall, the streamlined WEC assay is estimated to reduce animal use and operational costs by more than 50%. It substantially improves results turnaround with no loss of predictivity.

[Primary hyperlipoproteinemias. Clinical, biological and physiopathological aspects]. Primary hyperlipoproteinemias are of great interest as for the physician, as for the searcher, because of their atherogenic properties; on the other hand, a new type of hyperlipoprotenemia, namely hyperalphalipoproteinemia, seems to be a protective factor against clinical complications of atherosclerosis. The clinical, biological and pathophysiologic aspects of these diseases are studied both from author's experience and from the literature data.

Effect of dendrimer generation on electron self-exchange kinetics between metal tris(bipyridine) core dendrimers. Here we report the first measurement of homogeneous electron transfer between oxidized and reduced metal tris(bipyridine) core dendrimers by NMR line-broadening; the results indicated that, as the generation of the dendrimer increased, the rate of self-exchange decreased.

Gallamine triethiodide selectively blocks voltage-gated potassium channels in Ranvier nodes. The effects of gallamine on ionic currents in single intact Ranvier nodes of the toad Xenopus were investigated. The following fully reversible effects were observed: 1. With a test concentration of 1 mmol/l the current-voltage relation of steady-state potassium currents, IK ss exhibited a complete block of IK ss up to about V = 110 mV; with stronger depolarisations the block was incomplete. The peak sodium currents, in contrast, were not affected. 2. At the same test concentration the potassium permeability constant PK was reduced by 92% from its normal value, while the sodium permeability constant PNa decreased by only 8%. 3. Concentration-response relations of the block of PK yielded an apparent dissociation constant of 30 micromol/l and a steepness parameter of unity. Patch-clamp experiments on cloned Kv1.1, Kv1.2, Kv1.3 and Kv3.1 channels yielded apparent dissociation constants of 86, 19, >>100 and 121 micromol/l, respectively. Our findings show that gallamine is particularly well suited for separating potassium and sodium currents in axonal current ensembles. They also strongly suggest that potassium currents in Ranvier nodes of Xenopus are mainly carried by an ensemble of Kv1.1 and 1.2 channels.

Cycling induced by functional electrical stimulation in children affected by cerebral palsy: case report. Recently, the efficacy of functional electrical stimulation (FES) cycling have been demonstrated on the improvement of strength and motor control in adults with stroke. FES-cycling, providing a repetitive goal-oriented task, could facilitate cortical reorganization and utilization of residual cortico-spinal pathways. These benefits could be more enhanced in children because of the greater plasticity and flexibility of their central nervous system. The aim of the present case report study was to explore the feasibility of FES-cycling in children with cerebral palsy (CP) and to provide a set of instrumental measures able to evaluate the effects of this novel treatment on cycling and walking ability. Interventional study. Two ambulant outpatient children with diplegic CP were recruited by the "E. Medea" Scientific Institute. Patients followed a FES-cycling treatment for 30 minutes a day, 3 days a week for 7 weeks. Pre and post treatment tests were performed, namely clinical measures and electromyographic, kinematic and oxygen expenditure analysis during gait and cycling. The treatment was safe, feasible and well accepted by the 2 children. After treatment both patients achieved a more symmetrical muscular strategy during voluntary cycling and gait and a significant reduction of muscle co-contractions during cycling. These improvements were corroborated by a decrease in oxygen expenditure during the post test for one of the two children, the less impaired, implying a better exploiting of bi-articular muscles. FES-cycling is feasible and safe and it may be an alternative rehabilitation method for diplegic CP patients. The set of instrumental measurements proposed seems to be a valuable tool for functional assessment to identify subclinical anomalies and improvements on cycling and gait in CP patients.

AGO4 is specifically required for heterochromatic siRNA accumulation at Pol V-dependent loci in Arabidopsis thaliana. In plants, 24 nucleotide long heterochromatic siRNAs (het-siRNAs) transcriptionally regulate gene expression by RNA-directed DNA methylation (RdDM). The biogenesis of most het-siRNAs depends on the plant-specific RNA polymerase IV (Pol IV), and ARGONAUTE4 (AGO4) is a major het-siRNA effector protein. Through genome-wide analysis of sRNA-seq data sets, we found that AGO4 is required for the accumulation of a small subset of het-siRNAs. The accumulation of AGO4-dependent het-siRNAs also requires several factors known to participate in the effector portion of the RdDM pathway, including RNA POLYMERASE V (POL V), DOMAINS REARRANGED METHYLTRANSFERASE 2 (DRM2) and SAWADEE HOMEODOMAIN HOMOLOGUE 1 (SHH1). Like many AGO proteins, AGO4 is an endonuclease that can 'slice' RNAs. We found that a slicing-defective AGO4 was unable to fully recover AGO4-dependent het-siRNA accumulation from ago4 mutant plants. Collectively, our data suggest that AGO4-dependent siRNAs are secondary siRNAs dependent on the prior activity of the RdDM pathway at certain loci.

Early tumor necrosis factor-alpha release from the pulmonary macrophage in lung ischemia-reperfusion injury. Tumor necrosis factor-alpha is a proinflammatory mediator required for the development of experimental lung ischemia-reperfusion injury. The alveolar macrophage is a rich source of tumor necrosis factor-alpha in multiple models of acute lung injury. The present study was undertaken to determine whether the alveolar macrophage is an important source of tumor necrosis factor-alpha in lung ischemia-reperfusion injury and whether suppression of its function protects against injury. Left lungs of Long-Evans rats underwent normothermic ischemia for 90 minutes and reperfusion for up to 4 hours. Treated animals received gadolinium chloride, a rare earth metal that inhibits macrophage function. Injury was quantitated via lung tissue neutrophil accumulation (myeloperoxidase content), lung vascular permeability, and bronchoalveolar lavage fluid leukocyte, cytokine, and chemokine content. Separate samples were generated for immunohistochemistry. Tumor necrosis factor-alpha secretion occurred at 15 minutes of reperfusion and was localized to the alveolar macrophage by immunohistochemistry. In gadolinium-treated animals, lung vascular permeability was reduced by 66% at 15 minutes (P <.03) of reperfusion and by 34% at 4 hours (P <.02) of reperfusion. Suppression of macrophage function resulted in a 35% reduction in lung myeloperoxidase content (P <.03) and similar reductions in bronchoalveolar lavage leukocyte accumulation. Tumor necrosis factor-alpha and microphage inflammatory protein-1alpha protein levels were markedly reduced in the bronchoalveolar lavage of gadolinium-treated animals by enzyme-linked immunosorbent assay. The alveolar macrophage secretes tumor necrosis factor-alpha protein by 15 minutes of reperfusion, which orchestrates the early events that eventually result in lung ischemia-reperfusion injury at 4 hours. Gadolinium pretreatment markedly reduces tumor necrosis factor-alpha elaboration, resulting in significant protection against lung ischemia-reperfusion injury.

Effects of a new mild shampoo for preventing hair loss in Asian by a simple hand-held phototrichogram technique. This study was conducted to evaluate the effects of a commercially available shampoo in Korean subjects with alopecia using a simple hand-held phototrichogram technique. Forty-four subjects with alopecia were enrolled and forty subjects continued for 16 weeks. In the test group, total hair counts increased significantly at weeks 8 and 16, and the number of shedding hair significantly decreased at week 16. Terminal hair counts significantly increased at week 8. In the control group, hair thickness and the number of vellus hairs significantly decreased at week 16. The number of total hairs significantly increased in the test group than in the control group at weeks 8 and 16. The number of shedding hairs significantly decreased in the test group than in the control group at week 16. Visual assessment using clinical digital images showed that the number of total hairs appeared to increase although there was no statistical significance. In this study, it was found that the test shampoo could prevent hair loss.

On construction of single-arm two-stage designs with consideration of both response and toxicity. When establishing a treatment in clinical trials, it is important to evaluate both effectiveness and toxicity. In phase II clinical trials, multinomial data are collected in m-stage designs, especially in two-stage ( m = 2 ) design. Exact tests on two proportions, p r for the response rate and p t for the nontoxicity rate, should be employed due to limited sample sizes. However, existing tests use certain parameter configurations at the boundary of null hypothesis space to determine rejection regions without showing that the maximum Type I error rate is achieved at the boundary of null hypothesis. In this paper, we show that the power function for each test in a large family of tests is nondecreasing in both p r and p t ; identify the parameter configurations at which the maximum Type I error rate and the minimum power are achieved and derive level-α tests; provide optimal two-stage designs with the least expected total sample size and the optimization algorithm; and extend the results to the case of m > 2 . Some R-codes are given in the Supporting Information.

Decrease of DNA methyltransferase 1 expression relative to cell proliferation in transitional cell carcinoma. In many common cancers such as transitional cell carcinoma (TCC), specific genes are hypermethylated, whereas overall DNA methylation is diminished. Genome-wide DNA hypomethylation mostly affects repetitive sequences such as LINE-1 retrotransposons. Methylation of these sequences depends on adequate expression of DNA methyltransferase I (DNMT1) during DNA replication. Therefore, DNMT1 expression relative to proliferation was investigated in TCC cell lines and tissue as well as in renal carcinoma (RCC) cell lines, which also display hypomethylation, as indicated by decreased LINE-1 methylation. Cultured normal uroepithelial cells or normal bladder tissue served as controls. In all tumor cell lines, DNMT1 mRNA as well as protein was decreased relative to the DNA replication factor PCNA, and DNA hypomethylation was present. However, the extents of hypomethylation and DNMT1 downregulation did not correlate. Reporter gene assays showed that the differences in DNMT1 expression between normal and tumor cells were not established at the level of DNMT1 promoter regulation. Diminished DNMT1:PCNA mRNA ratios were also found in 28/45 TCC tissues but did not correlate with the extent of DNA hypomethylation. In addition, expression of the presumed de novo methyltransferases DNMT3A and DNMT3B mRNAs was investigated. DNMT3B overexpression was observed in about half of all high-stage TCC (DNMT3B vs. tumor stage, chi(2): p = 0.03), whereas overexpression of DNMT3A was rarer and less pronounced. Expression of DNMT3A and DNMT3B in most RCC lines was higher than in TCC lines. Our data indicate that DNMT1 expression does not increase adequately with cell proliferation in bladder cancer. This relative downregulation probably contributes to hypomethylation of repetitive DNA but does not determine its extent alone.

The effect of misonidazole on some physiologic parameters in mice. The physiologic effects of misonidazole (Ro-07-0582) were studied in BALB/cKa mice injected i.p. at 0.5 to 1.5 mg/g b.wt. A 2--4 degree C reduction of body core temperature was observed in unanesthetized mice: the duration and degree of effect were dependent on dose. Normal core temperatures were restored when the serum level of misonidazole had fallen to 0.5 microM (100 micrograms/ml). Misonidazole (1 mg/g) produced a rapid postinjectional drop of heart rate (40%), respiration (45%) and body core (4 degrees C) temperatures which gradually returned to preinjection values 6 to 8 hr later. In addition, misonidazole administration (1 mg/g) enhanced the overall effect on body temperature induced by hexobarbital anesthesia by a factor of approximately 3. These results are discussed in relation to the use of mouse model tumor systems to give an estimate of the magnitude of the cytotoxic effect of misonidazole expected in humans.

Transcriptional analysis of differential carbohydrate utilization by Clostridium acetobutylicum. Transcriptional analysis was performed on Clostridium acetobutylicum with the goal of identifying sugar-specific mechanisms for the transcriptional regulation of transport and metabolism genes. DNA microarrays were used to determine transcript levels from total RNA isolated from cells grown on media containing eleven different carbohydrates, including two pentoses (xylose, arabinose), four hexoses (glucose, mannose, galactose, fructose), four disaccharides (sucrose, lactose, maltose, cellobiose) and one polysaccharide (starch). Sugar-specific induction of many transport and metabolism genes indicates that these processes are regulated at the transcriptional level and are subject to carbon catabolite repression. The results show that C. acetobutylicum utilizes symporters and ATP-binding cassette (ABC) transporters for the uptake of pentose sugars, while disaccharides and hexoses are primarily taken up by phosphotransferase system (PTS) transporters and a gluconate : H(+) (GntP) transporter. The transcription of some transporter genes was induced by specific sugars, while others were induced by a subset of the sugars tested. Sugar-specific transport roles are suggested, based on expression comparisons, for various transporters of the PTS, the ABC superfamily and members of the major facilitator superfamily (MFS), including the GntP symporter family and the glycoside-pentoside-hexuronide (GPH)-cation symporter family. Additionally, updates to the C. acetobutylicum genome annotation are proposed, including the identification of genes likely to encode proteins involved in the metabolism of arabinose and xylose via the pentose phosphate pathway.

Mossy fiber sprouting after recurrent seizures during early development in rats. In some children, epilepsy is a catastrophic condition, leading to significant intellectual and behavioral impairment, but little is known about the consequences of recurrent seizures during development. In the present study, we evaluated the effects of 15 daily pentylenetetrazol-induced convulsions in immature rats beginning at postnatal day (P) 1, 10, or 60. In addition, we subjected another group of P10 rats to twice daily seizures for 15 days. Both supragranular and terminal sprouting in the CA3 hippocampal subfield was assessed in Timm-stained sections by using a rating scale and density measurements. Prominent sprouting was seen in the CA3 stratum pyramidale layer in all rats having 15 daily seizures, regardless of the age when seizures began. Based on Timm staining in control P10, P20, and P30 rats, the terminal sprouting in CA3 appears to be new growth of axons and synapses as opposed to a failure of normal regression of synapses. In addition to CA3 terminal sprouting, rats having twice daily seizures had sprouting noted in the dentate supragranular layer, predominately in the inferior blade of the dentate, and had a decreased seizure threshold when compared with controls. Cell counting of dentate granule cells, CA3, CA1, and hilar neurons, with unbiased stereological methods demonstrated no differences from controls in rats with daily seizures beginning at P1 or P10, whereas adult rats with daily seizures had a significant decrease in CA1 neurons. Rats that received twice daily seizures on P10-P25 had an increase in dentate granule cells. This study demonstrates that, like the mature brain, immature animals have neuronal reorganization after recurrent seizures, with mossy fiber sprouting in both the CA3 subfield and supragranular region. In the immature brain, repetitive seizures also result in granule cell neurogenesis without loss of principal neurons. Although the relationship between these morphological changes after seizures during development and subsequent cognitive impairment is not yet clear, our findings indicate that during development recurrent seizures can result in significant alterations in cell number and axonal growth.

Similar distribution of simple sequence repeats in diverse completed Human Immunodeficiency Virus Type 1 genomes. The survey of simple sequence repeats (SSRs) has been extensively made in eukaryotes and prokaryotes. However, its still rare in viruses. Thus, we undertook a survey of SSRs in Human Immunodeficiency Virus Type 1 (HIV-1) which is an excellent system to study evolution and roles of SSRs in viruses. Distribution of SSRs was examined in 81 completed HIV-1 genome sequences which come from 34 different countries or districts over 6 continents. In these surveyed sequences, although relative abundance and relative density exhibit very high similarity, some of these sequences show different preference for most common SSRs and longest SSRs. Our results suggest proportion of various repeat types might be related to genome stability.

Novel avian leukosis virus-related endogenous proviruses from layer chickens: characterization and development of locus-specific assays. During the course of evolution, vertebrate genomes have been invaded and colonized by retroviruses. In humans, for example, endogenous retroviruses (long terminal repeat elements) occupy roughly twice as much sequence space as essential genes. There are numerous reports in the literature implicating endogenous proviruses in the modulation of host physiology. The fact that many of these host-virus interactions take place in a proviral locus-specific manner speaks to the need for rapid assays for element profiling. This report deals with the identification of novel elements belonging to a family of endogenous retroviruses, designated ALVE, that reside in the genome of the chicken and that are closely related to exogenous avian leukosis viruses. The study of ALVE elements in the chicken genome serves as a model system for understanding the interplay between endogenous viruses and their vertebrate hosts in general, including humans. In this report, we present locus-specific, diagnostic PCR-based assays for 2 novel ALVE elements. In addition, we characterize the proviral structures and examine the genomic environments of both novel elements along with a previously described element known as ALVE-NSAC-3.

[Colitis in the non-functioning rectosigmoid after establishment of an end-sigmoid colostomy]. In 11 patients with a sigmoid end colostomy (and one additional patient with an end ileostomy), we examined the endoscopic and microscopic aspects of both the dysfunctioned bowel and the colon proximal to the colostomy. The latter showed in none of the cases signs of inflammation, while in 7 patients a remarkable or even severe colitis (mimicking ulcerative colitis) could be demonstrated endoscopically and/or histologically - irrespective to the duration of the dysfunction (one month up til 11 years). In the four patients with restoration of the intestinal continuity, macroscopic and microscopic findings of the rectal mucosa became normal as soon as two weeks after reoperation. We conclude, that the "dysfunctioned bowel-colitis" is somehow related to the mucosa's contact to the fecal stream.

Knowledge, attitude, and practice about malaria: Socio-demographic implications for malaria control in rural Ghana. Despite continuing international attention to malaria prevention, the disease remains a global public health problem. We investigated socio-demographic factors influencing knowledge, attitudes, and practices about malaria in rural Ghana. Our survey looked at 354 households. Mean knowledge score was higher among individuals with a history of volunteers having visited their households to educate them about malaria; families with 4-6 members; and males. Households with at least one under-five-aged child also had significantly higher knowledge scores. Households with at least one pregnant woman evinced a positive attitude towards malaria prevention. National malaria control strategies have achieved positive results in the fight against malaria. Nonetheless, multipronged community-based health strategies that integrate malaria programs and population growth control initiatives may be able to reach by 2030 the sustainable development goal of eliminating malaria.