Psychosocial stress of patients with port wine stains and expectations of dye laser treatment.
Port wine stains can be treated successfully with the dye laser in most cases. The indication for treatment is made on the basis of the emotional stress arising from the port wine stain. Studies of the extent of psychosocial stress to date have led to contradictory results. To address the question how many patients with port wine stain suffer psychosocial stress and how this group can further be characterized. Moreover, the specific expectations of treatment were to be elucidated. During dye laser treatment, 76 patients with port wine stains were evaluated by questionnaires regarding (a) emotional well-being, (b) quality of life, (c) body perception and (d) disease-specific stress and expectations of therapy. Patients with port wine stains showed significantly higher emotional stress than healthy controls. They were particularly impaired in quality of life with respect to their social life and felt less attractive than a healthy control group. Patients with high emotional stress placed high hopes on the laser therapy with regard to chances of employment and social contacts. The data point to the need for thorough patient consultation prior to laser therapy in order to avoid excessive expectations. Psychological consultation is recommended for emotionally labile PWS patients.


Bilabial contact pressure and oral air pressure during tracheoesophageal speech.
This study compared bilabial contact pressure (CPsp) and oral air pressure (Po) for /p/, /b/, and /m/ produced by tracheoesophageal (TE) versus laryngeal speakers. Nonspeech maximum bilabial contact pressures (CPmax) were measured to calculate the percentage of the range utilized for bilabial phonemes. Ten TE speakers and 10 laryngeal speakers produced syllables and sentences loaded with bilabial phonemes. The CPsp was measured with a miniature pressure transducer on the lower lip while the Po was simultaneously measured with a catheter in the corner of the mouth coupled to a differential pressure transducer. The speakers completed a nonspeech lip-press task with the contact pressure transducer in place. The TE speakers produced bilabial phonemes with significantly higher CPsp and Po than did laryngeal speakers. There was no difference in CPmax between the groups. The percentage of the contact pressure range utilized for bilabial phonemes was significantly higher for TE speakers. The increased CPsp and Po exhibited by TE speakers may reflect an attempt to overexaggerate articulation, although an alternate explanation related to neoglottal and oral aerodynamics must also be considered in future work. Subsequent studies evaluating the relationships between magnitude of articulatory contact pressure, phoneme intelligibility, and speaker's sense of effort should contribute to a better understanding of TE speech demands and may guide novel interventions to facilitate TE speech intelligibility.


Procedure for characterization of creatine kinase variants on agarose electrophoretograms.
Electrophoretograms of atypical creatine kinase (EC 2.7.3.2, CK) isoenzymes may be difficult to interpret. In addition, their presence may cause discrepancies between results by immunological determinations for mass or activity and those by electrophoresis. Here we outline procedures to use in characterizing apparently atypical CK isoenzymes observed after electrophoresis, as illustrated by a CK isoenzyme variant that migrated as CK-MB.


In vitro and in vivo activity of olamufloxacin (HSR-903) against Legionella spp.
The activity of the fluoroquinolone olamufloxacin (HSR-903) against Legionella spp. was studied in vitro and in vivo. The olamufloxacin MIC at which 50% of isolates are inhibited (MIC50) for 81 different Legionella spp. strains (59 type strains and 22 clinical isolates) was 0.008 mg/L, which was identical to sparfloxacin, whereas the MIC50s for erythromycin, levofloxacin and ciprofloxacin were 0.25, 0.032 and 0.032 mg/L, respectively. Olamufloxacin and sparfloxacin (at 0.008 mg/L) inhibited intracellular growth and subsequent cytotoxicity of L. pneumophila 80-045 in J774.1 macrophages, whereas levofloxacin and ciprofloxacin did not, at the same concentration. When olamufloxacin was given to the infected guinea pigs orally (5 mg/kg of body weight), peak levels in the lung were 3.02 mg/kg at 2 h post-administration, with a half-life of 3.41 h and an AUC0-12 of 12.31 mg.h/kg. The 2 day post-infection bacterial burden of the lung in the animals treated with olamufloxacin (5 and 1.25 mg/kg given orally twice a day) was much lower than in those treated with levofloxacin (same dose as olamufloxacin) or erythromycin (10 mg/kg given orally twice a day). When treated with olamufloxacin (5 mg/kg given orally twice a day) for 7 days, 11 of 12 L. pneumophila-infected guinea pigs survived for 14 days post-infection, as did all 12 guinea pigs treated with levofloxacin (5 mg/kg given orally twice a day) for 7 days. In contrast, only two of 12 animals treated with erythromycin survived and 10 of 11 died in the physiological saline group. Olamufloxacin was as effective as levofloxacin in a guinea pig model of Legionnaires' disease. These data warrant further study of whether olamufloxacin is an option for the treatment of Legionella infections.


Facilitation of the withdrawal reflex by repeated transcutaneous electrical stimulation: an experimental study on central integration in humans.
In the present human study, we aimed to investigate the facilitation of both the subjective pain responses, and the withdrawal reflex to consecutive transcutaneous electrical stimuli as measures of temporal summation. The frequency (0.5-20 Hz) and intensity (0.4-0.8 times the reflex threshold, xRT) of the electrical stimuli were systematically varied. When using repeated stimulation, the stimulus intensity that evoked pain was lower than that required by a single stimulus (temporal summation). Temporal summation leading to pain was found to depend significantly upon both frequency and intensity (e.g. stimulation at 1 Hz caused summation at 0.8 x RT, whereas stimulation at 20 Hz caused summation at 0.6 x RT). The strongest reflex facilitation, and hence the strongest pain intensity was obtained for stimulation at 10-20 Hz at an intensity of 0.8 x RT. In conclusion, the results of the present human study demonstrate clearly that a stimulus that is perceived as a localised, repetitive tactile tap can be integrated and cause severe pain. This suggests that pathologically generated sparse nociceptive afferent activity causes strong pain by central integration. This might be one mechanism to explain why clinical conditions can become excruciatingly painful despite the fact that the pathophysiological changes seem to be marginal (e.g. minor nerve trauma).


The effect of left internal mammary artery utilization on short-term outcomes after coronary revascularization.
The purpose of this study was to determine whether use of the left internal mammary artery (LIMA) during coronary revascularization influences short-term morbidity in all patients undergoing revascularization, as well as in patients over the age of 75 years, female patients, and patients with diabetes. The study also explored variability in the utilization of LIMA grafts across an entire state. Using the Clinical Outcomes Assessment Program (COAP) of the state of Washington, procedural outcomes were compared for patients receiving and patients not receiving LIMA grafts as part of revascularization procedures from January 1, 1999 to December 31, 2000. Mortality and major complications were examined, both as unadjusted rates and after adjusting for baseline patient risk factors. A total of 16 centers performed 8,797 nonemergent coronary artery revascularizations, including 81.7% with LIMA grafts. The use of a LIMA graft was associated with a significantly lower mortality (3.7% No LIMA vs 1.6% LIMA), as well as decreases in ventricular arrhythmias, need for postoperative dialysis, need for transfusions, ventilator dependence, and length of hospital stay. These trends were true for the population as a whole as well as for all subgroups analyzed, and they persisted after correcting for differences in comorbid conditions. In addition, there was wide variability in the use of LIMA grafts from center to center in the state. The use of LIMA grafts for coronary revascularization is associated with decreased mortality and morbidity. Despite these advantages, there is great variability in its application across the state of Washington.


Dietary phosphorus transcriptionally regulates 25-hydroxyvitamin D-1alpha-hydroxylase gene expression in the proximal renal tubule.
Synthesis of the hormone 1,25-dihydroxyvitamin D, the biologically active form of vitamin D, occurs in the kidney and is catalyzed by the mitochondrial cytochrome P450 enzyme, 25-hydroxyvitamin D-1alpha-hydroxylase (1alpha-hydroxylase). We sought to characterize the effects of changes in dietary phosphorus on the kinetics of renal mitochondrial 1alpha-hydroxylase activity and the renal expression of P450c1alpha and P450c24 mRNA, to localize the nephron segments involved in such regulation, and to determine whether transcriptional mechanisms are involved. In intact mice, restriction of dietary phosphorus induced rapid, sustained, approximately 6- to 8-fold increases in renal mitochondrial 1alpha-hydroxylase activity and renal P450c1alpha mRNA abundance. Immunohistochemical analysis of renal sections from mice fed the control diet revealed the expression of 1alpha-hydroxylase protein in the proximal convoluted and straight tubules, epithelial cells of Bowman's capsule, thick ascending limb of Henle's loop, distal tubule, and collecting duct. In mice fed a phosphorus-restricted diet, immunoreactivity was significantly increased in the proximal convoluted and proximal straight tubules and epithelial cells of Bowman's capsule, but not in the distal nephron. Dietary phosphorus restriction induced a 2-fold increase in P450c1alpha gene transcription, as shown by nuclear run-on assays. Thus, the increase in renal synthesis of 1,25-dihydroxyvitamin D induced in normal mice by restricting dietary phosphorus can be attributed to an increase in the renal abundance of P450c1alpha mRNA and protein. The increase in P450c1alpha gene expression, which occurs exclusively in the proximal renal tubule, is due at least in part to increased transcription of the P450c1alpha gene.


Interleukin-1-like immunoreactivity in peripheral tissues.
Rabbit antisera were raised against a synthetic peptide corresponding to the amino acid residues 169-194 in the murine interleukin-1 sequence. Immunoreactive varicose fibers were observed in the vas deferens, urinary bladder, gastrointestinal tract, and coeliac-superior mesenteric ganglion complex of the rat. Fibers were also encountered around blood vessels in several organs including the thymus, spleen, lymph nodes, liver, and kidney.


Perinatal Biochemical Confirmation of Smoking Status by Trimester.
Tobacco use during pregnancy is the most modifiable risk factor associated with poor pregnancy outcomes. Self-reported tobacco use has been demonstrated to have high misclassification rates. The aims were to examine misclassification rates of perinatal tobacco use during each trimester of pregnancy and 8 weeks postpartum, and to evaluate characteristics associated with misclassification of tobacco use status. This is secondary analysis of a prospective, multicenter trial of pregnant women, and it includes participants who were biochemically identified as tobacco users during their first trimester (N = 103). Each trimester and once postpartum, tobacco use was assessed via self-report and validated using a cutoff of 100 ng/mL for urine cotinine via NicAlert test strips to indicate current use. Those who self-reported as nonusers but were identified as users via urine cotinine were considered misclassified; misclassification rates were determined for each time period. Logistic regression assessed maternal factors associated with misclassification status. Misclassification rates declined from 35.0% at first trimester to 31.9% and 26.6% at the second and third; the postpartum rate was 30.4%. These rates did not differ significantly from each other at the 0.05 level. Race/ethnicity was associated with misclassification status; white/non-Hispanic women were 87% less likely to be misclassified (p < .001). Misclassification of prenatal smoking status decreases as pregnancy progresses, though the observed rate change was not significant. Minority women may be at particular risk for non-disclosure of tobacco use. Biochemical validation should be considered when assessing perinatal tobacco use via self-report, given high misclassification rates throughout the perinatal period. These results demonstrate that regardless of trimester, more than one-quarter of tobacco-using pregnant women may not disclose tobacco use throughout pregnancy and early postpartum. Although the rate of misclassification decreased from first to third trimester and then increased in the immediate postpartum, these changes in misclassification rates were not significant. Minority groups may be at particular risk of misclassification compared with white/non-Hispanic women. Biochemical validation is warranted throughout pregnancy to encourage cessation as tobacco use is one of the most easily-modified risk factors for poor birth outcomes.


Involvement of beta-endorphin in the modulation of paw inflammatory edema in the rat.
This study investigates the role of the opiod receptors and of the opioid peptide beta-endorphin in the development of yeast-induced inflammation in the rat paw. Pretreatment with the opioid receptor antagonist naltrexone (10 mg/kg i.p.) exacerbates the paw edema, while morphine pretreatment (5 and 10 mg/kg) reduces it. In addition, the intravenous injection of a specific anti-beta-endorphin antibody aggravates the yeast-induced inflammation. On the contrary, both the kappa-opioid receptor antagonist MR 1452 (2.5, 5 and 10 mg/kg i.p.) and the delta-opioid receptor antagonist ICI 174-864 (2.5, 5 and 10 mg/kg i.p.) do not interfere with the inflammatory process. After intraplantar injection, naltrexone, morphine and the anti-beta-endorphin antibody do not interfere with the yeast-induced inflammatory edema. Our data suggest that beta-endorphin exerts an inhibitory regulation on the inflammatory responses through the activation of mu-opioid receptors probably located on immune cells, rather than in the paw.


Extent of mitochondrial DNA sequence variation in Atlantic cod from the Faroe Islands: a resolution of gene genealogy.
Variation in a 250 base pair (bp) fragment of the mitochondrial cytochrome b (cyt b) has been used extensively for population studies in Atlantic cod Gadus morhua. To study the shape of the gene genealogy and the nature of the polymorphism, sequences of another region of the cyt b gene and the TP intergenic spacer were added, making a total of 566 bp from 74 cod from the Faroe Islands. A total of 44 segregating sites defined 41 haplotypes, many at frequencies greater than 5%. Haplotype diversity was 0.97 and nucleotide diversity 0.73% per base. A topology referred to as a constellation gene genealogy was observed with four major haplotypes at high frequencies, from each of which a number of rare variants were derived. A young relative age of the haplotypes was gauged from the structure of the genealogy. The variation was mostly at synonymous sites within the coding region and thus likely to be neutral or under weak purifying selection. By comparative analysis this also applies to the TP spacer. Applying the locus to study population variation in the Faroe Islands by AMOVA revealed that the overall areas and localities within areas accounted for none of the variation, and all the variation was due to differences among individuals.


Sequential FISH analysis with rDNA genes and Ag-NOR banding in the lady beetle Olla v-nigrum (Coleoptera: Coccinellidae).
We have characterized the meiosis of Olla v-nigrum by standard analysis, performed a NOR study using NOR banding, FISH of rDNA genes and sequential FISH/AgNOR analysis, and adapted the FISH methodology to Coccinellidae. The chromosome number determined at metaphase I was n = 9 + Xyp. At zygotene it was possible to identify the sex vesicle which presented a deeply stained heteropycnotic block. Chromosome X is much larger than the y and the two combine, forming a "parachute" in metaphase I. FISH analysis using a probe of rDNA genes 18S, 28S and 5.8S of D. melanogaster was used to map the genes in the sex vesicle. The NOR band showed high gene activity in this region. These results were confirmed using sequential FISH/Ag NOR analysis. The data obtained for Olla v-nigrum agree with the classical hypothesis raised to explain the type of sex chromosome association in a parachute format (Xyp) as being due to the presence of nucleolar material. The chromosome number and parachute configuration during metaphase I in this species agree with the basic karyotype of most Coleopterans. The major adaptation of the FISH method was the simultaneous denaturation and hybridization that permitted preservation of chromosome morphology, an essential factor when the chromosomes are small.


Studies on AK-5 tumor: further characterization of rat histiocytoma.
Properties of a transplantable rat histiocytoma which behaves like a macrophage-like cell, have been described. The AK-5 grows as ascites as well as solid subcutaneous tumor. The ascites from one animal can give between 10(8) and 10(9) cells whereas the subcutaneous tumor grows between 20 and 40 cm3 size. These cells possess various degradative enzymes, macrophage markers and glucocorticoid receptors. Beside histopathology the surface topography and ultrastructure of these cells are described.


Potent bystander effect in suicide gene therapy using neural stem cells transduced with herpes simplex virus thymidine kinase gene.
The herpes simplex virus thymidine kinase (HSVtk)/ganciclovir suicide gene therapy system has been considered as one of the most promising therapeutic strategies for malignant gliomas. We have been using HSVtk gene-transduced neural stem cells (NSCtk) that possess an ability to migrate toward a tumor mass for the treatment of experimental brain tumors. In the present study, we evaluated the potency of anti-tumor effect mediated by the bystander effect between NSCtk and C6 glioma cells in the HSVtk/ganciclovir suicide gene therapy system. NSCtk and C6 glioma cells were mixed at various ratios (NSCtk:C6 cell ratios of 1:1 to 1:64) and the bystander effect was evaluated both under in vitro and in vivo conditions. In vitro co-culture experiment showed a complete tumor growth inhibition at the NSCtk:C6 ratios as low as 1:16. In vivo co-implantation study in the rat brain showed no visible tumors at the NSCtk:C6 ratios as low as 1:16 and all those rats survived more than 100 days. The results clearly demonstrated an extremely potent bystander effect between NSCtk and C6 cells, and the minimum number of NSCtk cells needed for the treatment of tumors was roughly estimated.


[Treatment of multiple myeloma with high-dose chemotherapy and transplantation of autologous hematopoietic stem cells and subsequent maintenance therapy with interferon alfa-2b or interferon alfa 2b and dexamethasone. Report of the ongoing study of the "4W" Czech Myeloma Group].
We report our results with high-dose chemotherapy in previously untreated multiple myeloma patients (4 courses of VAD chemotherapy, collection of PBSC after priming with cyclophosphamide, 5 g/m2, high-dose chemotherapy with melphalan, 200 mg/m2). Second transplantation was indicated only for patients who did not achieve remission after the first high-dose therapy (paraprotein lower than 25% of the pretreatment value). For the second transplantation melphalan (200 mg/m2) with methylprednisolone (1.5 g for 5 days) were used as conditioning regimen. After high-dose therapy all patients were randomized into two arms of maintenance therapy: interferon alpha-2b or sequential maintenance therapy (interferon alpha-2b for 3 months followed after 4 week pause by 40 mg of dexamethasone days 1-4, 10-13 and 20-23. The administration of interferon alpha was resumed four weeks after the last dexamethasone for next three months. The maintenance therapy continued for 48 months or until the progression. Fifty-five patients were enrolled in the study from January 1996 to August 1997. Thirty-five patients have undergone the first transplantation and 57% of them reached complete remission. There were 10% of non-responders after the first high-dose regimen. The mean time to reach white blood cell count above 1 x 10(9)/L after the application of high dose melphalan and platelets more than 50 x 10(9)/L were 12.2 (range 6-16 days) and 12.4 (range 0-25 days), respectively. Grade 4 mucositis according to SWOG classification requiring total parenteral nutrition was presented in 40% of the patients. The mean number of 1 unit of platelets and 2 units of packed red blood cells transfusions were given within the posttransplant period. Early transplant related mortality was 3%. This paper describes the response and tolerance of each particular step of therapy. The follow-up has been too short to evaluate event-free and overall survivals.


Validity and reliability of spinal cord monitoring in neuromuscular spinal deformity surgery.
Somatosensory evoked potentials (SSEPs) have become a standard of care in surgery for spinal deformity. Recent reports in the literature have suggested SSEP monitoring is not efficacious in surgeries for patients with neuromuscular disease. Electrophysiologic data were retrospectively analyzed from 74 patients with various neuromuscular disorders undergoing spinal-deformity surgery from 1989 through February 1995 at this medical center. The monitoring protocol included SSEPs recorded from multiple sites located cortically, subcortically, and peripherally. Neurogenic motor evoked potentials (NMEPs) were also employed. Anesthetic regimens were controlled for compatibility with evoked potential monitoring. Use of this intraoperative monitoring protocol resulted in reliable data for 95% of the patient population having baseline responses. Findings suggest that evoked potentials can be used effectively during surgery for neuromuscular spinal deformity. Use of a specific protocol allowed acquisition of reliable data intraoperatively, suggesting these methods are a valid means of monitoring neurologic status.


A comparison of cycle control with monophasic levonorgestrel/ethinylestradiol 100 micrograms/20 micrograms versus triphasic norethindrone/ethinylestradiol 500-750-1000 micrograms/35 micrograms: a multicenter, randomized, open-label study.
This multicenter, randomized, open-label study was undertaken to compare the effects on menstrual cycle control of two oral contraceptive regimens: monophasic levonorgestrel (LNG) 100 micrograms/ethinylestradiol (EE) 20 micrograms (Alesse or Loette) and triphasic norethindrone (NET) 500-750-1000 micrograms/EE 35 micrograms (OrthoNovum 7/7/7). Healthy women with normal menstrual cycles were enrolled and completed up to four cycles of study medication. A total of 384 cycles in the LNG/EE group and 400 cycles in the NET/EE group were evaluable for analysis of cycle control. For all treatment cycles, the percentage of cycles classified as normal was consistently higher in the LNG/EE group than in the NET/EE group. By cycle 4, 69.9% of cycles with LNG/EE and 54.4% with NET/EE (p < 0.05) were normal. In individual cycles, consistently lower occurrences of intermenstrual bleeding (total bleeding and/or spotting) were seen for the LNG/EE group, although these differences were not statistically significant. Withdrawal bleeding characteristics were comparable between the two groups, except for the length of the latent period, which was significantly longer in the LNG/EE group. The incidence of treatment-emergent adverse events was similar in the two groups. This study indicates that the monophasic LNG/EE 100 micrograms/20 micrograms provides better cycle control than the multiphasic NET/EE product, despite its lower EE dose.


Modes of Seoul virus infections: persistency in newborn rats and transiency in adult rats.
To understand the mode of persistent infection of Seoul virus in rodents, we examined the distribution of the virus genome and antibody production in infected rats. When 1-day-old rats were inoculated with the KI-83-262 strain, the S segment of viral genome was detected in sera, clots, lungs and kidneys from 3 to 184 days post inoculation (d.p.i.) by nested reverse transcriptase PCR. On the other hand, when 7-week-old rats were infected with this virus, viral genome was detected only in the lungs from 3 to 50 d.p.i. The neutralizing antibody titers of rats inoculated at 1-day of age were higher than those of rats inoculated at 7 weeks of age. In both age groups, however, the IgG avidity of antibody increased along with the course of infection. We found that urban rats (Rattus norvegicus) infected early in life harbored the virus for more than 6 months.


Potential improvements of lung and prostate MLC tracking investigated by treatment simulations.
Intrafraction tumor motion during external radiotherapy is a challenge for the treatment accuracy. A novel technique to mitigate the impact of tumor motion is real-time adaptation of the multileaf collimator (MLC) aperture to the motion, also known as MLC tracking. Although MLC tracking improves the dosimetric accuracy, there are still residual errors. Here, we investigate and rank the performance of five prediction algorithms and seven improvements of an MLC tracking system by extensive tracking treatment simulations. An in-house-developed MLC tracking simulator that has been experimentally validated against an electromagnetic-guided MLC tracking system was used to test the prediction algorithms and tracking system improvements. The simulator requires a Dicom treatment plan and a motion trajectory as input and outputs all motion of the accelerator during MLC tracking treatment delivery. For lung tumors, MLC tracking treatments were simulated with a low and a high modulation VMAT plan using 99 patient-measured lung tumor trajectories. For prostate, tracking was also simulated with a low and a high modulation VMAT plan, but with 695 prostate trajectories. For each simulated treatment, the tracking error was quantified as the mean MLC exposure error, which is the sum of the overexposed area (irradiated area that should have been shielded according to the treatment plan) and the underexposed area (shielded area that should have been irradiated). First, MLC tracking was simulated with the current MLC tracking system without prediction, with perfect prediction (Perfect), and with the following five prediction algorithms: linear Kalman filter (Kalman), kernel density estimation (KDE), linear adaptive filtering (LAF), wavelet-based multiscale autoregression (wLMS), and time variant seasonal autoregression (TVSAR). Next, MLC tracking was simulated using the best prediction algorithm and seven different tracking system improvements: no localization signal latency (a), doubled maximum MLC leaf speed (b), halved MLC leaf width (c), use of Y backup jaws to track motion perpendicular to the MLC leaves (d), dynamic collimator rotation for alignment of the MLC leaves with the dominant target motion direction (e), improvements 4 and 5 combined (f), and all improvements combined (g). All results are presented as the mean residual MLC exposure error compared to no tracking. In the prediction study, the residual MLC exposure error was 47.0% (no prediction), 45.1% (Kalman), 43.8% (KDE), 43.7% (LAF), 42.1% (wLMS), 40.1% (TVSAR), and 36.5% (Perfect) for lung MLC tracking. For prostate MLC tracking, it was 66.0% (no prediction), 66.9% (Kalman), and 63.4% (Perfect). For lung with TVSAR prediction, the residual MLC exposure error for the seven tracking system improvements was 37.2%(1), 38.3%(2), 37.4%(3), 34.2%(4), 30.6%(5), 27.7%(6), and 20.7%(7). For prostate with no prediction, the residual MLC exposure error was 61.7%(1), 61.4%(2), 55.4%(3), 57.2%(4), 47.5%(5), 43.7%(6), and 38.7%(7). For prostate, MLC tracking was slightly better without prediction than with linear Kalman filter prediction. For lung, the TVSAR prediction algorithm performed best. Dynamic alignment of the collimator with the dominant motion axis was the most efficient MLC tracking improvement except for lung tracking with the low modulation VMAT plan, where jaw tracking was slightly better.


Addressing Moderate Interpersonal Hatred Before Addressing Forgiveness in Psychotherapy and Counseling: A Proposed Model.
This paper addresses the problem of pressure on a person to forgive that often makes forgiveness impossible or superficial. It proposes that clients who are unwilling or unable to forgive can still be encouraged to let go of interpersonal hatred because it is psychologically harmful to them. The issue of forgiving the person toward whom the hatred is directed can be treated more easily later, after the hatred has been removed or at least much reduced. The present theoretical approach distinguishes between anger and hatred; it provides a brief understanding of the origin of hatred from an object relations perspective with a focus on splitting. The emphasis is on moderate interpersonal hatred, since severe hatred raises special difficulties. The question of when a person has sufficient freedom to let go of moderate hatreds is addressed. This is followed by identifying reasons why people enjoy hatred, and how hatred provides some short-term psychological rewards. Finally, different psychological harms caused by hatred are identified. Overcoming interpersonal hatred by praying for those you hated is presented; the effect of such prayer on reducing splitting is especially noted. The conclusion is a descriptive summary of stages to be used in treating clients' hatreds before addressing forgiveness.


Foveal Sparing in Central Retinal Dystrophies.
To describe foveal sparing (FS) in central retinal dystrophies (RD). Participants for this retrospective study were identified from the retinal dystrophy database of the Department of Ophthalmology at Radboud University Medical Center. FS was defined as an intact foveal structure surrounded by at least 180° of chorioretinal atrophy, and a best-corrected visual acuity (BCVA) of <1.0 logMAR (>20/200 Snellen). Eligible eyes were identified using fundus autofluorescence (FAF) images, and FS was confirmed using near-infrared reflectance (NIR) imaging and spectral-domain optical coherence tomography when available. Clinical and demographic data were extracted from medical records. We performed quantification of FS and chorioretinal atrophic areas using semiautomated software on fundus autofluorescence and NIR images. We calculated the chronologic change using eye-wise linear regression. We identified 36 patients (56 eyes) with FS. RDs included: Stargardt disease (STGD1;20 patients), central areolar choroidal dystrophy (CACD; 7 patients), mitochondrial retinal dystrophy (MRD; 6 patients), pseudo-Stargardt pattern dystrophy (PSPD; 3 patients). Median age at first presentation was 60 (interquartile range [IQR] 54-63) years. Median BCVA at first presentation ranged from 20/25 Snellen in STGD1, to 20/38 Snellen in MRD. Progression of the chorioretinal atrophic area ranged from 0.26 (0.25-0.28) mm/year in PSPD, to 0.14 (0.11-0.22) in CACD. Change in FS area over time was similar between the different dystrophies. The presence of FS in different RDs suggests a disease-independent mechanism that prolongs the survival of the fovea. The associated preservation of BCVA is important for the individual prognosis and has implications for the design of therapeutic trials for RDs.


Echistatin: the refined structure of a disintegrin in solution by 1H NMR and restrained molecular dynamics.
The structure of the disintegrin echistatin has been determined by 1H NMR, distance geometry calculations and restrained molecular dynamics simulations. The structure has been refined from the preliminary distance geometry calculations with the inclusion of additional 1H NMR data and hydrogen bonds identified in early stages of the molecular dynamics calculations. The calculations reported here allow a distinction to be made between the two possible disulfide bridging patterns-echistatin is crosslinked as follows: Cys2-Cys11, Cys7-Cys32, Cys8-Cys37, Cys20-Cys39. The final set of structures gives an average pairwise root mean square distance of 0.100 nm (calculated over the backbone atoms of residues Ser4-Cys20 and Asp30-Pro40). The core of echistatin is a well defined though irregular structure, composed of a series of non-classical turns crosslinked by the disulfide bridges and stabilised by hydrogen bonds. The RGD sequence is located in a protruding loop whose stem is formed by two rigid, hydrogen-bonded strands (Thr18-Cys20, Asp30-Cys32). The RGD sequence is connected to this structure by short, flexible segments. High (but not unlimited) mobility is probably necessary for fast recognition and fitting to the integrin receptors. Sequence variability among the disintegrins is found in the segments flanking the RGD sequence, suggesting that these may be important in conferring specificity for the receptors.


Acute lymphoblastic leukemia in patients over 59 years of age. Experience in a single center over a 10-year period.
We report data of 29 consecutive patients aged 60 years or older with newly diagnosed acute lymphoblastic leukemia (ALL) treated at a single center between 1983 and 1992. Immunophenotyping was performed in 26 patients. According to the immunological classification used at the time of diagnosis, 14 had common-ALL, two had T-ALL, six had null-ALL, three had myeloid antigen-positive ALL with both lymphoid and myeloid markers, and one had B-ALL. One patient died before therapy could be instituted. Twenty-four patients received intensive induction chemotherapy. Nine of these patients died during the first 8 weeks, eight due to infections and one due to liver failure after asparaginase. In 14 of the remaining patients treated intensively, scheduled treatment was discontinued prematurely due to treatment-related toxicity and was replaced by milder chemotherapy. Four patients aged 75-77 years were treated with vincristine and prednisone. Only one patient who completed a whole study protocol survived more than 5 years. Twelve of the 28 patients treated with chemotherapy achieved complete remissions. The median survival was 5 months (range 1-103+). Median survival in patients with CR was 9.0 months. Actuarial survival is 3%. Our data demonstrate a poor prognosis in ALL patients over 59 years of age. The reasons were a high mortality during intensive induction therapy due to toxicity of treatment and a short remission duration.


[Frontal stage in cervicofacial lift: the "helmet crest" technique associated with rapid expansion].
The frontal level is generally the less and the last concerned in facial ageing and the classical incisions of the cervicofacial facelift provide no changes in the frontal and glabellar wrinkles. To avoid such residual defects, the authors perform for the lost ten years an important push back of a central band of the vertex (the so called "Helmet crest") by means of a bilateral triangular excision subsequently closed by VY. This push back needs a very large undermining in the subgalea plan, from the eyebrow and glabellar region to the crest of the hemet itself. The VY closure is now really facilitated by a rapid expansion obtained by a special T shaped expander which allows not only cutaneous expansion but also aponeurotic expansion of the reputedly inextensible galea. This technique avoids the coronal incision and its serious sequelae and may be carried technique out at the same time as cervicofacial face lift. It allows a personal, equilibrated tension of the facial mask which is the essential condition for a good presentation of natural expression of the face.


Towards co-evolution of membrane proteins and metabolism.
Primordial metabolism co-evolved with the earliest membrane peptides to produce more environmentally fit progeny. Here, we map a continuous, evolutionary path that connects nascent biochemistry with simple, membrane-bound oligopeptides, ion channels and, further, membrane proteins capable of energy transduction and utilization of energy for active transport.


Induction of apoptosis by Phenothiazine derivatives in V79 cells.
Phenothiazine derivatives chlorpromazine (cpz) and trifluoperazine (tfp) were found to induce apoptosis, abnormal cell cycle and expression of p53 in Chinese hamster lung fibroblast V79 cells. Both the drugs can induce apoptosis when cells are treated with drug at a concentration of 10 microg/ml within 4 h, as detected by propidium iodide staining and DNA fragmentation analysis. Flow cytometric analysis revealed that the apoptotic response is mediated by a loss of G(1) population of cells. In Western blot analysis, p21 is induced and p53 is accompanied by additional bands. Also indirect immunolabeling of single cells revealed that p21 is accumulated from cytoplasm into nucleus after the drug treatment and the intensities of p53 increased. Our findings demonstrate for the first time that phenothiazine derivatives, in addition to their cytotoxic effects, could induce apoptosis, an observation that has important clinical implications.


Strength and endurance of the pelvic floor muscles in continent women: an observational study.
To describe the maximal strength and endurance of the pelvic floor muscles in a cohort of women with no history of incontinence; and to determine the effect of age, parity, hormonal status, previous gynaecological surgery and regular performance of pelvic floor muscle exercises on the strength and endurance of these muscles. Preliminary cross-sectional observational study. Faculty of Health Sciences, University of Sydney, Australia. Twenty-eight women aged 19 to 58 years, 16 of whom were under 40 years of age. Participants were excluded if they had a history of incontinence or were currently menstruating. Pelvic floor muscle strength assessed using a perineometer, and pelvic floor muscle endurance above 60% of maximal voluntary contraction. The effect of age, parity, hormonal status, previous gynaecological surgery and regular performance of pelvic floor muscle exercises on the strength and endurance of these muscles. Maximum strength of the pelvic floor muscles was not correlated with endurance (r=0.21, P=0.290) or age (r=-0.31, P=0.107); however, it was influenced by parity (r=-0.44, P=0.020). Endurance was significantly and positively correlated with age (r=0.38, P=0.048). This study provides preliminary data that age and parity may be important factors in pelvic floor muscle performance in women who are continent. A larger study that considers the variability associated with these variables will provide useful guidelines for prescription of exercise.


Cranioplasty using allogeneic perforated demineralized bone matrix with autogenous bone paste.
The efficacy of allogeneic perforated demineralized bone matrix with autogenous bone paste in the treatment of full-thickness cranial defects was evaluated in 10 consecutive patients between June 1998 and December 1998. The skull defects resulted from trauma in 9 patients and removal of a cranial tumor in 1 patient. The size of the skull defects ranged from 8 x 6 cm to 11 x 12.5 cm. Follow-up averaged 33 months for all patients. Postimplantation evaluations included serial photographs, repeated physical examination, and three-dimensional computed tomography for all patients. Visual inspection of the implanted biomaterial 6 months later was possible in 1 patient. The contour of the reconstructed skull was acceptable aesthetically without any secondary depression noted during the follow-up period. Three-dimensional computed tomographic scans taken 2 years after implantation indicated that the allogeneic perforated demineralized bone matrix provided a matrix for new bone formation with remarkable osteoinductive potential for new bone formation. The autogenous bone paste was able to caulk the demineralized bone matrix and fill the contour irregularities and gaps of the reconstructed cranium. The results from this clinical study indicated that allogeneic perforated demineralized bone matrix with autogenous bone paste is a promising alternative to an autogenous bone graft and or alloplastic material for cranioplasty.


A clinical test of lumbopelvic control: development and reliability of a clinical test of dissociation of lumbopelvic and thoracolumbar motion.
LBP is often associated with changes in motor control. Some subgroups of LBP have been argued to have a compromised ability to dissociate lumbopelvic movement from that of the thoracolumbar junction. Clinical methods to evaluate this task may aid identification of this LBP subgroup and determine the utility of this information to guide clinical interventions. The study aimed to develop a clinical test to assess the ability to dissociate lumbopelvic movement from that of the thoracolumbar junction, and to evaluate the inter-rater reliability of the test in individuals with and without low back pain (LBP) when performed by experienced and novice therapists. A clinical scale was developed to characterise quality of performance of lumbopelvic motion with limited motion at the thoracolumbar junction. Inter-tester repeatability was measured in three experiments. Test outcomes for pain-free controls were compared between three assessors with different amounts of clinical experience. Test scores for LBP participants were compared between two assessors, and between assessments undertaken from video recordings. Agreement between assessors was tested with weighted Kappa Coefficient. The test had acceptable reliability in pain-free and LBP participants, but was better when undertaken by experienced therapists. Kappa index ranged from 0.81 to 0.66 for live assessments, and 0.62 for video assessments. The results showed that the test is reliable when performed by experienced assessors. The test can assess thoracolumbar movements in different groups of individuals.


Knockout of p75(NTR) impairs re-myelination of injured sciatic nerve in mice.
Remyelination is an important aspect of nerve regeneration after nerve injury but the underlying mechanisms are not fully understood. The neurotrophin receptor, p75(NTR), in activated Schwann cells in the Wallerian degenerated nerve is up-regulated and may play a role in the remyelination of regenerating peripheral nerves. In the present study, the role of p75(NTR) in remyelination of the sciatic nerve was investigated in p75(NTR) mutant mice. Histological results showed that the number of myelinated axons and thickness of myelin sheath in the injured sciatic nerves were reduced in mutant mice compared with wild-type mice. The myelin sheath of axons in the intact sciatic nerve of adult mutant mice is also thinner than that of wild-type mice. Real-time RT-PCR showed that mRNA levels for myelin basic protein and P0 in the injured sciatic nerves were significantly reduced in p75(NTR) mutant animals. Western blots also showed a significant reduction of P0 protein in the injured sciatic nerves of mutant animals. These results suggest that p75(NTR) is important for the myelinogenesis during the regeneration of peripheral nerves after injury.


Temperature effects on adsorption and diffusion dynamics of CH3CH2(ads) and H3C-C≡C(ads) on Ag(111) surface and their self-coupling reactions: ab initio molecular dynamics approach.
Density functional theory (DFT)-based molecular dynamics (DFTMD) simulations in combination with a Fourier transform of dipole moment autocorrelation function are performed to investigate the adsorption dynamics and the reaction mechanisms of self-coupling reactions of both acetylide (H3C-C(β)≡C(α) (ads)) and ethyl (H3C(β)-C(α)H2(ads)) with I(ads) coadsorbed on the Ag(111) surface at various temperatures. In addition, the calculated infrared spectra of H3C-C(β)≡C(α)(ads) and I coadsorbed on the Ag(111) surface indicate that the active peaks of -C(β)≡C(α)- stretching are gradually merged into one peak as a result of the dominant motion of the stand-up -C-C(β)≡C(α)- axis as the temperature increases from 200 K to 400 K. However, the calculated infrared spectra of H3C(β)-C(α)H2(ads) and I coadsorbed on the Ag(111) surface indicate that all the active peaks are not altered as the temperature increases from 100 K to 150 K because only one orientation of H3C(β)-C(α)H2(ads) adsorbed on the Ag(111) surface has been observed. These calculated IR spectra are in a good agreement with experimental reflection absorption infrared spectroscopy results. Furthermore, the dynamics behaviors of H3C-C(β)≡C(α)(ads) and I coadsorbed on the Ag(111) surface point out the less diffusive ability of H3C-C(β)≡C(α)(ads) due to the increasing s-character of Cα leading to the stronger Ag-Cα bond in comparison with that of H3C(β)-C(α)H2(ads) and I coadsorbed on the same surface. Finally, these DFTMD simulation results allow us to predict the energetically more favourable reaction pathways for self-coupling of both H3C-C(β)≡C(α)(ads) and H3C(β)-C(α)H2(ads) adsorbed on the Ag(111) surface to form 2,4-hexadiyne (H3C-C≡C-C≡C-CH3(g)) and butane (CH3-CH2-CH2-CH3(g)), respectively. The calculated reaction energy barriers for both H3C-C≡C-C≡C-CH3(g) (1.34 eV) and CH3-CH2-CH2-CH3(g) (0.60 eV) are further employed with the Redhead analysis to estimate the desorption temperatures approximately at 510 K and 230 K, respectively, which are in a good agreement with the experimental low-coverage temperature programmed reaction spectroscopy measurements.


Adjunctive measures in rhinoplasty.
Modern day rhinoplasty demands more than a plan for a new nose. It requires consideration of the individual in terms of a new facial image. Adjacent skeletal and soft tissue weaknesses must be evaluated along with the primary nasal deformity. Frequently facial disharmonies may be corrected with relatively simple operative procedures or with cosmetics. When the procedure does not measurably increase the operative time, postoperative morbidity, or financial cose of the rhinoplasty, it will be more readily accepted by the patient. These criteria are considered in the suggested methods of chin augmentation with alloplastic implants and reduction mentoplasty, utilizing the intraoral subapical horizontal osteotomy of the mandible. At times, simple methods of camouflage will be inadequate. Significant jaw disharmony with unacceptable occlusion requires the interdisciplinary teamwork of the orthodontist, the surgeon, and possibly the prosthodontist. In these cases rhinoplasty waits upon skeletal and dental realignment. Almost without exception, the rhinoplasty patient appreciates and profits from the surgeon's concern over her general appearance. Advice regarding skin care, makeup, hair styling, and facial rejuvenation frequently aids that person in attaining a happy and satisfying rhinoplastic experience.


Development of two high-performance liquid chromatographic methods for the analysis and characterization of insulin and its degradation products in pharmaceutical preparations.
Two high-performance liquid chromatography methods either in reversed-phase or as size exclusion separation mode were developed and validated for the analysis of insulin and its degradation products in pharmaceutical preparations. The results show the reliability of the analytical methods for the intended used. The static and dynamic light scattering were used to characterize the insulin and its derivatives. The absolute molecular weight of human insulin monomer and dimer were 5800 and 12400 Da respectively whereas its z-average root mean square radius were 21.6+/-0.4 and 40.5+/-0.7 nm, respectively. In contrast, the hydrodynamic diameter varied between 2.69 and 5.50 nm, depending of the association behavior of insulin.


[A case-control study of the impact of tuberculosis on the quality of life of patients].
A prospective study was conducted on 72 patients of pulmonary tuberculosis (TB) and 201 healthy controls in a third level hospital. The HRQoL questionnaire (12-Item Short Form Health Survey, SF-12) was used to assess the QoL at the onset of treatment DOTS. Patients with TB had significantly lower mean scores than controls for overall QoL (51.1 +/- SD 22.6) versus 75.9 (+/- SD 17.6), p < 0.0001. The most affected domains were physical and psychological. Active TB patients shown difficulties in activities of daily living and alterations of the psychological state.


Priming us and them: automatic assimilation and contrast in group attitudes.
Social judgment theory holds that a person's own attitudes function as reference points, influencing the perception of others' attitudes. The authors argue that attitudes themselves are influenced by reference points, namely, the presumed attitudes of others. Whereas exposure to a group that acts as a contextual reference should cause attitude assimilation, exposure to a group that acts as a comparative reference should cause attitude contrast. In Study 1, participants subliminally primed with their political ingroup or outgroup endorsed more extreme political positions than did controls. Study 2 demonstrated that prime types known to uniquely facilitate assimilation and contrast enhanced the polarization effect in the ingroup and outgroup conditions, respectively. Study 3 established an important boundary condition for whether group salience produces attitude assimilation or contrast by showing that perceived closeness to the elderly moderates the direction and strength of the group priming effect. The results suggest that the transition from assimilation to contrast occurs when a group ceases to function as a context and becomes a comparison point. Implications for social judgment theory, assimilation and contrast research, and conflict escalation are discussed.


Impact of flexible sigmoidoscopy on physician compliance with colorectal cancer screening protocol.
The flexible sigmoidoscope may represent a partial solution to the longstanding problem of physician and patient noncompliance with sigmoidoscopy for the detection of colorectal cancer. A three-year longitudinal audit of medical records revealed at least a sevenfold increase in the number of sigmoidoscopies performed after the introduction of flexible sigmoidoscopy to a salaried medical group. This procedure has made a significant contribution to patient care and resident education in the UCLA family practice residency program.


Sodium hyaluronate as an aid in microvascular surgery.
The purpose of this study was to compare the suture of a microvascular anastomosis with and without the aid of sodium hyaluronate. The divided femoral arteries of ten Sprague-Dawley rats were sutured using sodium hyaluronate on one side. Operating time, bleeding, and patency rates were studied and compared. No significant differences were found in the measured parameters. However, the clinical impression is that the use of sodium hyaluronate facilitates the suture of a microanastomosis.


Ocular spherical aberration and theoretical through-focus modulation transfer functions calculated for eyes fitted with two types of varifocal presbyopic contact lens.
Through focus modulation transfer functions (MTFs) are compared for six different cases: an aberration free eye, an eye suffering from typical amounts of undercorrected spherical aberration, and each of such eyes wearing either a Hydrocurve II or PS45 varifocal contact lens. It is assumed that the measured power profiles of the varifocal lenses, which are typical of centre distance and centre-near designs, can be approximated to primary spherical aberration, that the lenses are well centred, and that the spherical aberrations of each lens and eye are additive. It is found that in general, with a 4 mm pupil, reasonable modulation transfer is maintained over a greater focal range (by about 1 dioptre) with the varifocal-wearing eyes. This implies that useful vision will be given over a greater range of object distances, as required by the presbyope. However, the maximal modulation transfer with a varifocal is degraded compared with that of the eye alone. Since the amount and sign of ocular spherical aberration may vary with the individual, it would be expected that any particular design of varifocal would be more successful with some wearers than with others.


Feasibility and acceptability of a computer-based tool to improve contraceptive counseling.
The objective was to test the feasibility and acceptability of a computerized tool, Smart Choices, designed to enhance the quality of contraceptive counseling in family planning clinics. The tool includes (a) a questionnaire completed by patients and summarized in a printout for providers and (b) a birth control guide patients explore to learn about various contraceptive methods. In 2 family planning clinics, we conducted interviews with 125 women who used the Smart Choices computerized tool and 7 providers. Smart Choices integrated into clinic flow well in one clinic, but less well in the other, which had very short waiting times. Patients were generally enthusiastic about Smart Choices, including its helpfulness in preparing them and their providers for the counseling session and increasing their knowledge of contraceptive methods. Providers varied in how much they used the printout and in their opinions about its usefulness. Some felt its usefulness was limited because it overlapped with the clinic's intake forms or because it did not match with their concept of counseling needs. Others felt it provided valuable information not collected by intake forms and more honest information. Some found Smart Choices to be most helpful with patients who were unsure what method they wanted. Smart Choices is feasible to implement and well received by patients, but modifications are needed to increase provider enthusiasm for this tool. The Smart Choices tool requires refinement before widespread dissemination.


The effects of electrical and controlled atmosphere stunning methods on meat and liver quality of geese.
The objective of this research was to investigate the effects of electrical and gas stunning on the meat and liver quality characteristics of liver geese. Sixty birds were slaughtered at 12 wk of age, in groups of 20 at three different times. Thirty birds each were subjected to one of the two stunning methods. Deboned breast fillets and thigh muscles were evaluated for hemorrhaging, amount of blood in the veins, and color by using a visual grading system. Livers were removed from carcasses during evisceration and were subsequently graded. Besides external color and hemorrhaging, the degree of liver weight loss due to removal of blood vessels was also determined. The use of controlled atmosphere stunning significantly reduced the incidence of muscle hemorrhages when compared to electrical stunning. However, no significant difference was found for color or amount of blood remaining in the veins of muscles between geese receiving electrical or controlled atmosphere stunning. The hemorrhaging and color scores of livers from gas-stunned birds did not differ from those of electrically stunned birds. As for the liver weight loss caused by removal of veins and capillaries, stunning treatment had no significant effect on this parameter. These results suggest that controlled atmosphere stunning produced slightly better quality goose meat but did not improve liver quality when compared to the electrical stunning method used.


Tuberculosis in HIV-infected persons in British Columbia during the HAART era.
Prior to the introduction of highly active antiretroviral therapy (HAART), active tuberculosis (TB) was a major contributor to HIV-related morbidity and mortality in Canada and other low-incidence regions. We performed this study to examine TB incidence, clinical manifestations and screening uptake in HIV-infected TB patients during the era of HAART therapy. We performed a retrospective study on all HIV-infected TB patients in British Columbia over a 10-year period (2003-2012). Demographic and clinical characteristics were extracted along with screening and treatment outcomes. Trends in provincial TB incidence, HIV testing and HAART prevalence were also examined. In total, 2,839 TB cases were identified in BC during this period, including 129 HIV-infected TB patients. Surprisingly, only 64 HIV-infected TB patients (50%) had a documented screening tuberculin skin test (TST) prior to TB diagnosis. Of the 39 HIV-infected TB patients with prior TST positivity, 38 (97.4%) had not completed a course of isoniazid preventive therapy. TB incidence decreased significantly in the HIV-infected population of BC over the study period, from 1.9 to 0.5 TB cases per 1,000 HIV-infected individuals (p<0.001). The incidence of HIV-TB decreased significantly over the past decade despite suboptimal latent TB infection screening and prevention practices. This decrease in TB incidence is likely attributable to the increased uptake of HAART. Consideration should be given to intensifying prevention efforts to accelerate TB elimination in HIV-infected populations in low-incidence regions.


Molecular insights into the interactions of GF-17 with the gram-negative and gram-positive bacterial lipid bilayers.
The cationic antimicrobial peptide GF-17, a 17-mer-derived peptide from human cathelicidin LL-37, has a significant strength in the killing of the methicillin-resistant Staphylococcus aureus and Escherichia coli strains. Herein, we conducted a series of all-atom molecular dynamics simulations to investigate the ability of GF-17 in perturbing the model membranes of the gram-positive, S. aureus, and gram-negative, E. coli, bacteria. We also explored the contributions of the specific residues in the peptide activity. The molecular dynamics results indicated that the peptide is stabilized on the membrane surface and rapidly binds to the phosphate headgroups of the model membranes through the electrostatic interactions and hydrogen bonds. Furthermore, both polar and nonpolar interactions are energetically favored for the binding with the membrane surface. The research also revealed the important roles of the phenylalanine residues in the early insertion of the peptide into the bacterial model membranes. In addition, the results demonstrated that the central residues Arg23 and Lys25 played a critical role in the binding of GF-17 to both gram-negative and gram-positive model membranes, in excellent agreement with experimental studies. This study emphasizes on the pivotal role of basic residues in prompt association of the peptide on the model membrane surface and on the significance of residues Phe17, Ile24, Phe27, and Val32 in hydrophobic interactions. Therefore, our observations provide insights into the membrane-GF-17 interactions at atomic details that are useful to develop potent antimicrobial peptides targeting multidrug-resistant bacteria.


A systematic review on randomized control trials on rennin angiotensin aldosterone system inhibitors role in managing hypertension among hemodialysis patients.
Randomized control trials (RCTs) are considered as most rigors way of determining the cause-effect relationship of a treatment and outcome. Activation of rennin angiotensin aldosterone system (RAAS) is an important contributor to hypertension in hemodialysis patients. The prevalence of hypertension in hemodialysis patients varies from 60% to 80% and hypertension management alone with conventional hemodialysis is insufficient. Hence, the current review was aimed to investigate the effect of RAAS inhibitors in managing hypertension among hemodialysis patients in a randomized control trial. Using PUBMED and EMBASE databases, randomized control trial with primary or secondary outcomes related to the effect of RAAS inhibitors on blood pressure among hemodialysis patients were included for analysis. The current review also assessed the quality of reporting of RCT. A total of eight RCT met inclusion criteria for current review. According to modified jaded scale, one (12.5%) study scored four points for quality reporting, whereas two (25%) studies scored one point that was the least score. The mean score for all included studies was 2.25. Six (75%) of the eight RCT included, involved ARB in hypertension management among hemodialysis patients, whereas two (25%) studies involved angiotensin-converting enzyme (ACE) inhibitors. Of the siz RCT involving ARB, two (33.3%) RCT also included ACE inhibitors comparison group. Altogether six (75%) studies report a reduction in blood pressure with the use of RAAS inhibitors compared to control group; however, of the six studies, two (33.3%) reported that the reduction in blood pressure was not significant. Whereas, two (25%) studies reported no reduction in blood pressure compared to the control group. The findings from current review do not indicate a clear pattern for a role of RAAS inhibitors for hypertension control among hemodialysis patients.


Increased muscle pain sensitivity in patients with tension-type headache.
Nociceptive mechanisms in tension-type headache are poorly understood. The aim was to investigate the pain sensitivity of pericranial muscles and a limb muscle in patients with tension-type headache. Experimental muscle pain was induced by standardized infusions of 0.5 ml of 1 M hypertonic saline into two craniofacial muscles (anterior temporalis (TPA) and masseter (MAS)) and a limb muscle (anterior tibial (TA)) in 24 frequent episodic tension-type headache patients (FETTH), 22 chronic tension-type headache patients (CTTH) and 26 age and gender matched healthy subjects. Headache patients were examined twice, both on days with and on days without headache. The pressure pain thresholds (PPTs) were determined before and after infusions. The subjects continuously reported intensity of saline-induced pain on an electronic visual analogue scale (VAS) and the perceived area of pain was drawn on anatomical maps. Headache patients demonstrated significantly lower PPTs, higher saline-evoked VAS pain scores and greater pain areas than healthy subjects at all the tested muscle sites (P<0.05). There was a significant gender difference for the PPTs in all three groups of participants (P<0.05) and for VAS pain scores in the CTTH patients (P<0.05). There was no difference in pain sensitivity between FETTH and CTTH or between patients with or without headache. In conclusion, the present study demonstrates the presence of generalized pain hypersensitivity both in FETTH and CTTH compared to controls which is unrelated to actual headache status and extends to include responses to longer-lasting stimuli which are clinically highly relevant. Gender differences in deep pain sensitivity seem to be a consistent finding both in healthy controls and patients with tension-type headache.


[Stone Cone® in ureteroscopic ballistic lithotripsy of proximal ureteral stones].
Stone Cone® (Microvasive-Boston Scientific Corp, USA) is a device which prevents retrograde calculus migration during endoscopic ureterolithotripsy. We have studied the safety and efficacy of this device in endoscopic ureterolithotripsy with ballistic energy in proximal ureteral stones. MATERIALS AND METHODS. From 01/02/2006 to 01/02/2008 we carried out 36 ureterorenoscopies (URS) for proximal ureteral stones (average age: 46, range: 15-73). A ballistic energy was used for stones fragmentation. In 18 patients (Group A) we carried out URS with the aid of Stone Cone®, which was not used in the other 18 patients (Group B). Semirigid 8 Ch or 10 Ch Storz ureteroscope and ballistic lithotriptor Swiss Lithoclast Master EMS® were used. In cases of migration, edema, and ureteral damage, a ureteral stent was used. RESULTS. In Group B patients (URS performed without Stone Cone®) the migration of the whole stone, or of clinically significant fragments, occurred 8 times (45%). All of these patients underwent external shockwave lithotripsy (ESWL) at a center equipped with a lithotriptor. A ureteral stent was placed in 14 cases (78%). In Group A, the migration of a stone requiring ESWL treatment occurred only once (5%). The ureteral stent was placed 8 times (45%). We had no significant complications during the procedure. CONCLUSIONS. The Stone Cone® is a safe and easy-to-use device. The cost of this device can be balanced by the reduction of postoperative ESWL treatments for lithiasic fragments pushing up into the kidneys (p<0.01), and of ureteral stent applications at the end of the procedure (p<0.05).


Understanding the structure of humpback whale songs (L).
Structured sound sequences produced by humpback whales are described in the literature as hierarchically organized songs. Despite the prevalence of such descriptions, there is no direct evidence that humpback songs are hierarchically structured. It is suggested here that songs may instead be heterarchically structured, in which case traditional approaches to analyzing songs may obscure their organizational and acoustical features. An alternative framework for characterizing patterns within songs is presented, derived from models of humpback whale sound production, that characterizes rhythmic and sequential regularities in the sound sequences produced by singing whales in terms of interacting cycles of breathing and internal air recirculation.


Intralesional bleomycin injections for the palliation of epistaxis in hereditary hemorrhagic telangiectasia.
Epistaxis is a common complication in patients with hereditary hemorrhagic telangiectasia. Its treatment is generally aimed at controlling the frequency and severity of nasal hemorrhage and involves surgery, transcatheter embolization, topical treatment, or a combination. Despite this multitude of treatment methods, the long-term prognosis for many patients remains poor. We describe a patient in whom direct intralesional injections of bleomycin successfully palliated severe recurrent epistaxis for almost 2 years without the need for adjuvant therapy.


Strength, fracture toughness and microstructure of a selection of all-ceramic materials. Part I. Pressable and alumina glass-infiltrated ceramics.
The present study, divided into two parts, aimed to compare the strength, fracture toughness and microstructure of a range of all-ceramic materials. In part I, three hot-pressed glass-ceramics (IPS-Empress, Empress 2 and a new experimental ceramic) and alumina glass-infiltrated ceramics (In-Ceram Alumina), processed by both slip casting and dry pressing, were compared. Tensile strength was appraised on 10 bar-shaped specimens (20 x 4 x 1.2 mm3) for each material with the three-point bending method; the fracture toughness was measured from 20 specimens (20 x 4 x 2 mm3), by using the indentation strength technique. Data were compared with ANOVA and the Sheffé post hoc test (p = 0.05). The volume fraction of each phase, the dimensions and shapes of the grains, porosity and the crack patterns were investigated using SEM. The average and standard deviation in strength (MPa) and fracture toughness (MPa m(1/2)) were: IPS-Empress 106(17)1, 1.2(0.14)1; Empress 2 306(29)2, 2.9(0.51)2, new experimental ceramic 303(49)2, 3.0(0.65)2, In-Ceram Alumina dry-pressed 440(50)2, 3.6(0.26)2, In-Ceram Alumina slip 594(52)3, 4.4(0.48)3. Values with the same superscript number showed no significant statistical difference. Microscopy revealed the relationship between the glass matrix and the crystalline phase and the characteristics of the latter were correlated to the strengthening and toughening mechanisms of these glass-ceramics. The mechanical properties and microstructure of core materials have been advocated as crucial to the clinical long-term performance of all-ceramic dental restorations. This investigation provides the clinician with data regarding strength, fracture toughness and microstructure of a broad range of current materials.


Purification and structural characterization of an α-glucosidase inhibitory polysaccharide from apricot (Armeniaca sibirica L. Lam.) pulp.
In this study, the crude polysaccharide (APPS) from the fruiting bodies of apricot (Armeniaca sibirica L. Lam.) was isolated and fractionated by ultrafiltration and Sephadex G-75 gel chromatography. The hypoglycemic activities of all fractions were determined by α-glucosidase inhibitory activity in vitro. The fraction APPS1-2 showed the best activity with an IC50 of 6.06 mg/mL. The properties and chemical compositions of this fraction were analyzed with high-performance liquid chromatography, gel permeation chromatography-eighteen angle laser light scattering instrument, UV spectroscopy, infrared spectroscopy, and NMR spectroscopy ((1)H). The results demonstrated that APPS1-2 was a neutral glycoconjugate with a molecular weight of 25.93 kDa. It comprised rhamnose, glucose, mannose, and galactose, with a relative molar ratio of 1.34:2.01:0.48:0.35. The backbone of APPS1-2 may consist of rhamnose and glucose, but its branches may consist of mannose and galactose. The IR and UV spectrum of APPS1-2 revealed the typical characteristics of heteropolysaccharide. (1)H NMR spectrum showed that APPS1-2 contained α-configurations.


Ultrastructural findings in incontinentia pigmenti.
From their ultrastructural study of incontinenti pigmenti, the authors confirm that in this condition there is no pigmentary anomaly, but that pigmentation is the last step of a still unknown process. At birth those who are affected display an intracellular edema which leads to the formation of a vesocobulla. In all 3 stages, the epidermis shows dyskeratotic cells and a transient pigmentary discharge.


Engineering antimicrobial peptides with improved antimicrobial and hemolytic activities.
The rapid rise of antibiotic resistance in pathogens becomes a serious and growing threat to medicine and public health. Naturally occurring antimicrobial peptides (AMPs) are an important line of defense in the immune system against invading bacteria and microbial infection. In this work, we present a combined computational and experimental study of the biological activity and membrane interaction of the computationally designed Bac2A-based peptide library. We used the MARTINI coarse-grained molecular dynamics with adaptive biasing force method and the umbrella sampling technique to investigate the translocation of a total of 91 peptides with different amino acid substitutions through a mixed anionic POPE/POPG (3:1) bilayer and a neutral POPC bilayer, which mimic the bacterial inner membrane and the human red blood cell (hRBC) membrane, respectively. Potential of mean force (PMF, free energy profile) was obtained to measure the free energy barrier required to transfer the peptides from the bulk water phase to the water-membrane interface and to the bilayer interior. Different PMF profiles can indeed identify different membrane insertion scenarios by mapping out peptide-lipid energy landscapes, which are correlated with antimicrobial activity and hemolytic activity. Computationally designed peptides were further tested experimentally for their antimicrobial and hemolytic activities using bacteria growth inhibition assay and hemolysis assay. Comparison of PMF data with cell assay results reveals a good correlation of the peptides between predictive transmembrane activity and antimicrobial/hemolytic activity. Moreover, the most active mutants with the balanced substitutions of positively charged Arg and hydrophobic Trp residues at specific positions were discovered to achieve the improved antimicrobial activity while minimizing red blood cell lysis. Such substitutions provide more effective and cooperative interactions to distinguish the peptide interaction with different lipid bilayers. This work provides a useful computational tool to better understand the mechanism and energetics of membrane insertion of AMPs and to rationally design more effective AMPs.


Pharmacological characterization of AR-M1000390 at human delta opioid receptors.
We investigated the pharmacological properties of a newly synthesised delta agonist AR-M1000390, derived from SNC-80 ((+)-4-[(alpha R)-alpha-((2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl]-N,N-diethyl-benzamide), in the neuroblastoma cell line SK-N-BE expressing only human delta-opioid receptors. Binding and functional experiments showed a weak affinity (K(i) = 106 +/- 34 nM) correlated with a weak potency (EC(50) = 111 +/- 31 nM) to inhibit the forskolin-stimulated cAMP accumulation. Sustained activation of opioid receptors in the presence of the maximal inhibitory concentration of AR-M1000390 produced a rapid and strong desensitization. In order to examine the contribution of internalization and down-regulation in the desensitization processes, binding and functional experiments were conducted in the presence or in the absence of hypertonic sucrose solution to block clathrin-dependent opioid receptor endocytosis. We observed both the inability of AR-M1000390 to down-regulate opioid receptors and the absence of any effect of sucrose on desensitization. The lack of delta-opioid receptor internalization by AR-M1000390 was further corroborated by confocal microscopy using antibodies directed either against the endogenous delta-opioid receptors or the FLAG-tagged delta-opioid receptors stably expressed in the SK-N-BE cells. These data suggest that uncoupling rather than internalization is responsible for delta-opioid receptors desensitization by AR-M1000390.


Impact of symptoms and aging attribution on emotions and coping.
Two experimental studies and a large field study were designed to examine how symptom severity, symptom duration, symptom ambiguity, and the association of symptoms with aging affected emotional responses and coping with illness threats. In Study 1, 280 respondents from the surrounding community reported the emotional and coping responses they would manifest to scenarios that varied the severity, duration, and ambiguity (i.e., labeled vs. unlabeled) of a common set of symptoms. Severity had more of an impact on coping strategies than did duration or illness label; severe symptoms elicited stronger emotional upset and a higher incidence of both self-care behaviors and seeking of medical care. Symptoms of longer duration also resulted in increased seeking of medical care. Responses of the 334 adults participating in Study 2 replicated and extended these findings: A closed-ended item asking participants whether the symptoms could be attributed to aging showed that attribution of symptoms to aging increased with age, was more frequent for mild symptoms, and was associated with reduced emotional response to symptoms and a tendency to delay seeking treatment. Participants in the field study (168 patients seeking medical care for a variety of symptoms) completed interviews tracing symptom processing and emotional and coping reactions. The results provided evidence for the external validity of the scenario studies, as the attribution of symptoms to aging was greater for older than younger patients and resulted in a significant tendency to delay seeking medical care. Results of these studies suggest that symptom experience and symptom interpretation must be considered in the study of coping responses to illness threats.


[The effect of norfloxacin on the luminol-dependent chemiluminescence and adhesion of leukocytes].
The in vitro effect of norfloxacin on the luminol-dependent chemiluminescence and adherence of polymorphonuclear leukocytes of guinea pigs was studied with the use of a wide range of the drug concentrations from 0.1 to 100 micrograms/ml under two different conditions, i.e. during the cell incubation in the presence of norfloxacin various concentrations and after the cell washing to remove the drug. In a concentration of 1 microgram/ml norfloxacin stimulated the zymosan-induced chemiluminescence. When the drug was used in a concentration of 10 micrograms/ml, the stimulating effect was less pronounced. In a concentration of 100 mu/ml norfloxacin significantly inhibited the leukocyte chemiluminescence. In concentrations of 0.1 to 100 micrograms/ml norfloxacin had no effect on the leukocyte adherence to the plastic surface covered by albumin.


[Polycystic disease of the kidneys and pregnancy (author's transl)].
A summary of pregnancy-developments of patients with polycystic disease of the kidneys is presented. The polycystic disease of the kidneys is a chronic progessive affection which takes both the kidneys in almost every case. The development of this disease can be divided in four stages. During the first, asymptomatic stage there is no disturbance of the pregnancy. In the second stage at the beginning of the decrease of the kidney-function therapy in pregnancy consists in confinement to bed and usual kidney-disease-diet. When complications as chronic recurrent pyelonephritis and hypertension rise and the final stage -- renal failure -- is achieved the pregnancy has to be finished as quick as possible in the early pregnancy by interruption and in the late pregnancy by sectio cesarian. Both methods should be followed by sterilisation of the patient.


Prenatal course and pregnancy outcome of fetuses with a transient nuchal translucency.
This study was designed to correlate fetuses in a normal prenatal population who exhibited transient nuchal translucency (NT) with both prenatal course and pregnancy outcome. The fetuses with abnormal NT were followed by ultrasonography at 1-2-week intervals during their prenatal course. Fetuses with NT who exhibited no detectable congenital malformations were defined as the NTO group; fetuses with abnormal NT and structural malformations but no chromosomal abnormalities were placed in the SM group; and fetuses with abnormal NT, structural malformations, and chromosomal abnormalities were categorized as the CA group. The groups were compared by: maternal age, weeks of gestation by ultrasound and the NT value at the initial exam, the maximum NT value, and the duration of abnormal NT. During the study period, 92 fetuses with abnormal NT were found, monochorionic twins excluded. Of the 92 fetuses, 80 were in the NTO group, 10 were in the SM group, and two were in the CA group. The maternal age and the gestational weeks at the initial diagnosis were not significantly different in the NTO and the SM groups. However, the NT value at the initial diagnosis, maximum NT value, and the duration of abnormal NT were significantly greater in the SM group than those values in the NTO group. Fetuses with transient nuchal translucency commonly had structural malformations, particularly fetuses with significant and large persistent NT.


Evaluating the Incidence, Cause, and Risk Factors for Unplanned 30-Day Readmission and Emergency Department/General Practitioner Visit After Short-Stay Thyroidectomy.
Unplanned 30-day readmission and emergency department (ED)/general practitioner (GP) visit after thyroidectomy are important healthcare quality measures and may reduce any cost savings from performing it as a short-stay (<24-h admission) procedure. Our study aimed to examine the incidence, cause, and risk factors for unplanned 30-day readmissions and ED/GP visits together following short-stay thyroidectomy. One-thousand and four patients who underwent short-stay thyroidectomy were reviewed. A territory-wide electronic medical record system was used to capture all unplanned readmissions and ED/GP visits within 30 days of thyroidectomy. Actual date and reason for readmission or ED/GP visit were recorded. Other preoperative and perioperative variables were collected prospectively. Of the 80 (8.0 %) unplanned readmissions and ED/GP visits, 38 (47.5 %) were readmissions and 42 (52.5 %) were ED/GP visits only. The three most common causes of unplanned readmission and ED/GP visit were symptomatic hypocalcemia (n = 20, 25.0 %), upper respiratory symptoms (n = 15, 18.8 %), and wound complaints (n = 8, 10.0 %). However, in the multivariate analysis, only American Society of Anesthesiologists (ASA) class III (β coefficient = 0.981, odds ratio 2.586 (95 % CI 1.353-4.943), p = 0.004) and renal insufficiency (RI) (β coefficient = 1.062, odds ratio 2.892 (95 % CI 1.109-7.544), p = 0.030) were independent risk factors for unplanned 30-day readmission and ED/GP visit. The overall incidence of unplanned 30-day ED/GP visit after thyroidectomy was 8.0 % with approximately half requiring readmission. The most common cause for unplanned ED/GP visit was symptomatic hypocalcemia (25.0 %), and it was attributed to patient non-compliance to prescribed supplements. ASA class III and RI were significant independent risk factors for unplanned 30-day readmission and ED/GP visit.


Effect of executive functioning on perceived needs in chronic schizophrenia.
Recent approaches to needs assessment involve patients in this process; however, little is known of the effects of mental illness on patients' ability to assess their own needs. The needs of 26 subjects with schizophrenia were assessed over 22 domains by patients and staff, using the Camberwell Assessment of Need Short Appraisal Schedule (CANSAS). Patients' executive functioning was assessed using the Wisconsin Card Sorting Test (WCST). Mean discrepancies between ratings by staff and by patients were compared across executive functioning; results showed no effect of executive functioning on the discrepancy between staff and patient ratings. Higher executive functioning was associated with more met needs. Multivariate analysis showed higher executive functioning associated with more needs in some but not all areas. Results suggest that patients with schizophrenia and impaired executive functioning can validly estimate their needs. Better executive functioning may be associated with the ability to get one's needs met, increased awareness of needs, better ability to communicate needs, or more needs in certain areas. Need is shown to be a complex variable, and not simply an index of functioning. Hospitals and clinics must ensure that patients' views find full expression in ratings. Needs ratings and rehabilitation status should be viewed in the light of neuropsychological functioning.


A role for metallothionein in the pathogenesis of diabetes and its cardiovascular complications.
It has been suspected for a long time that zinc has a role in various aspects of diabetes, but specific molecular targets of zinc remained largely elusive. Recent discoveries of associations between diabetes and polymorphisms in human genes now suggest that proteins that control the cellular availability of zinc ions are involved. One protein is the zinc transporter ZnT-8 that supplies pancreatic beta-cells with zinc. The other is metallothionein 1A, a member of a protein family that links zinc and redox metabolism. Changes in the availability of zinc ions modulate insulin signaling and redox processes. Both zinc and metallothionein protect cells against the redox stress that occurs in diabetes and contributes to its progression towards diabetic complications, including heart disease.


Helicobacter pylori FlhB processing-deficient variants affect flagellar assembly but not flagellar gene expression.
Regulation of the Helicobacter pylori flagellar gene cascade involves the transcription factors sigma(54) (RpoN), employed for expression of genes required midway through flagellar assembly, and sigma(28) (FliA), required for expression of late genes. Previous studies revealed that mutations in genes encoding components of the flagellar protein export apparatus block expression of the H. pylori RpoN and FliA regulons. FlhB is a membrane-bound component of the export apparatus that possesses a large cytoplasmic domain (FlhB(C)). The hook length control protein FliK interacts with FlhB(C) to modulate the substrate specificity of the export apparatus. FlhB(C) undergoes autocleavage as part of the switch in substrate specificity. Consistent with previous reports, deletion of flhB in H. pylori interfered with expression of RpoN-dependent reporter genes, while deletion of fliK stimulated expression of these reporter genes. In the DeltaflhB mutant, disrupting fliK did not restore expression of RpoN-dependent reporter genes, suggesting that the inhibitory effect of the DeltaflhB mutation is not due to the inability to export FliK. Amino acid substitutions (N265A and P266G) at the putative autocleavage site of H. pylori FlhB prevented processing of FlhB and export of filament-type substrates. The FlhB variants supported wild-type expression of RpoN- and FliA-dependent reporter genes. In the strain producing FlhB(N265A), expression of RpoN- and FliA-dependent reporter genes was inhibited when fliK was disrupted. In contrast, expression of these reporter genes was unaffected or slightly stimulated when fliK was disrupted in the strain producing FlhB(P266G). H. pylori HP1575 (FlhX) shares homology with the C-terminal portion of FlhB(C) (FlhB(CC)) and can substitute for FlhB(CC) in flagellar assembly. Disrupting flhX inhibited expression of a flaB reporter gene in the wild-type but not in the DeltafliK mutant or strains producing FlhB variants, suggesting a role for FlhX or FlhB(CC) in normal expression of the RpoN regulon. Taken together, these data indicate that the mechanism by which the flagellar protein export apparatus exerts control over the H. pylori RpoN regulon is complex and involves more than simply switching substrate specificity of the flagellar protein export apparatus.


Elevated susceptibility of the p53 knockout mouse esophagus to methyl-N-amylnitrosamine carcinogenesis.
Mutations of the p53 tumor suppressor gene constitute one of the most frequent molecular changes in a wide variety of human cancers, including those in the esophagus. Mice deficient in p53 have recently attracted attention for their potential to identify chemical genotoxins. In this study we investigated the susceptibility of p53 nullizygous (-/-), heterozygous (+/-) and wild-type (+/+) mice to methyl-N-amylnitrosamine (MNAN), which specifically induces esophageal tumors in mice and rats. The p53 (+/-) and (+/+) mice were treated with 5 or 15 p.p.m. MNAN in their drinking water for 8 weeks then maintained without further treatment for an additional 7 or 17 weeks, being killed at experimental weeks 15 or 25. An additional group of p53 (-/-) mice were given 5 p.p.m. MNAN for 8 weeks and killed at week 15. At 15 weeks in the 5 p.p.m. groups, squamous cell carcinomas (SCCs) were observed in 10/12 (83.3%) p53 (-/-) and 1/15 (6.7%) p53 (+/-) mice, but in none of the p53 (+/+) mice. In the animals receiving 15 p.p.m., 2/14 (14.3%) p53 (+/-) and 1/11 (9.1%) p53 (+/+) mice developed SCCs. At 25 weeks, the incidence of SCCs was 7/16 (43.8%) and 8/14 (57.1%) in p53 (+/-) mice and 1/13 (7.7%) and 2/10 (20.0%) in p53 (+/+) mice at 5 and 15 p.p.m., respectively. Of the SCCs examined by PCR-single strand conformation polymorphism analysis, 61% (14/23) from p53 (+/-) and 50% (6/12) from p53 (+/+) mice demonstrated mutations in the p53 gene (exons 5-8). These results indicate the order of susceptibility to MNAN-induced esophageal tumorigenesis to be as follows: nullizygotes (-/-) > heterozygotes (+/-) > wild-type (+/+), and provide strong evidence of involvement of p53 mutations in the development of esophageal SCCs.


The Spirit Is Willing, But the Flesh is Weak: Why Young People Drink More Than Intended on Weekend Nights-An Event-Level Study.
Heavy alcohol use is common among young adults on weekend nights and is assumed to be intentional. However, little is known about the extent to which heavy consumption is planned prior to the onset of drinking and what factors contribute to drinking more than intended. This study investigates drinking intentions at the beginning of an evening and individual and situational factors associated with a subsequent consumption over the course of multiple nights. Using a smartphone application, 176 young people aged 16 to 25 (mean age = 19.1; 49% women) completed questionnaires on drinking intentions, consumption, and drinking environments before, during, and after multiple Friday and Saturday nights (n = 757). Multilevel regressions were used to investigate individual-level and night-level factors associated with previous drinking intentions and subsequent deviations from intentions. Participants intended to consume 2.5 drinks (SD = 2.8) per night yet consumed 3.8 drinks (SD = 3.9) on average. Drinking intentions were higher among those who frequently went out at night and engaged in more frequent predrinking. Participants drank more than intended on 361 nights (47.7%). For both genders, the number of drinks consumed before 8 pm, attending multiple locations, and being with larger groups of friends contributed to higher consumption than intended at the individual and the night levels. Heavier consumption than intended also occurred when drinking away from home for men and when going to nightclubs for women. Making young adults aware of the tendency to drink more than intended, particularly when drinking begins early in the evening, moves from location to location, and includes large groups of friends, may be a fruitful prevention target. Structural measures, including responsible beverage service, may also help in preventing excessive drinking at multiple locations.


Sigmoid resection for diverticular disease - to ligate or to preserve the inferior mesenteric artery? Results of a systematic review and meta-analysis.
In colorectal cancer, ligation of the inferior mesenteric artery (IMA) is a standard surgical approach. In contrast, ligation of the IMA is not mandatory during treatment of diverticular disease. The object of this meta-analysis was to assess if preservation of the IMA reduces the risk of anastomotic leakage. A search was performed up to August 2018 using the following electronic databases: MEDLINE/PubMed, ISI Web of Knowledge and Scopus. The measures of treatment effect utilized risk ratios for dichotomous variables with calculation of the 95% CI. Data analysis was performed using the meta-analysis software Review Manager 5.3. Eight studies met the inclusion criteria and were included in the meta-analysis: two randomized controlled trials (RCTs) and six non-RCTs with 2190 patients (IMA preservation 1353, ligation 837). The rate of anastomotic leakage was higher in the IMA ligation group (6%) than the IMA preservation group (2.4%), but this difference was not statistically significant [risk ratio (RR) 0.59, 95% CI 0.26-1.33, I2 = 55%]. The conversion to laparotomy was significantly lower in the IMA ligation group (5.1%) than in the IMA preservation group (9%) (RR 1.74, 95% CI 1.14-2.65, I2 = 0%). Regarding the other outcomes (anastomotic bleeding, bowel injury and splenic damage), no significant differences between the two techniques were observed. This meta-analysis failed to demonstrate a statistically significant difference in the anastomotic leakage rate when comparing IMA preservation with IMA ligation. Thus, to date there is insufficient evidence to recommend the IMA-preserving technique as mandatory in resection for left-sided colonic diverticular disease.


Meta-analysis of probiotics for the prevention of antibiotic associated diarrhea and the treatment of Clostridium difficile disease.
Antibiotic-associated diarrhea (AAD) is a common complication of most antibiotics and Clostridium difficile disease (CDD), which also is incited by antibiotics, is a leading cause of nosocomial outbreaks of diarrhea and colitis. The use of probiotics for these two related diseases remains controversial. To compare the efficacy of probiotics for the prevention of AAD and the treatment of CDD based on the published randomized, controlled clinical trials. PubMed, Medline, Google Scholar, NIH registry of clinical trials, metaRegister, and Cochrane Central Register of Controlled Trials were searched from 1977 to 2005, unrestricted by language. Secondary searches of reference lists, authors, reviews, commentaries, associated diseases, books, and meeting abstracts. Trials were included in which specific probiotics given to either prevent or treat the diseases of interest. Trials were required to be randomized, controlled, blinded efficacy trials in humans published in peer-reviewed journals. Trials that were excluded were pre-clinical, safety, Phase 1 studies in volunteers, reviews, duplicate reports, trials of unspecified probiotics, trials of prebiotics, not the disease being studied, or inconsistent outcome measures. Thirty-one of 180 screened studies (totally 3,164 subjects) met the inclusion and exclusion criteria. One reviewer identified studies and abstracted data on sample size, population characteristics, treatments, and outcomes. From 25 randomized controlled trials (RCTs), probiotics significantly reduced the relative risk of AAD (RR = 0.43, 95% CI 0.31, 0.58, p < 0.001). From six randomized trials, probiotics had significant efficacy for CDD (RR = 0.59, 95% CI 0.41, 0.85, p = 0.005). A variety of different types of probiotics show promise as effective therapies for these two diseases. Using meta-analyses, three types of probiotics (Saccharomyces boulardii, Lactobacillus rhamnosus GG, and probiotic mixtures) significantly reduced the development of antibiotic-associated diarrhea. Only S. boulardii was effective for CDD.


Mutagenicity and mutation spectra of 2-acetylaminofluorene at frameshift and base-substitution alleles in four DNA repair backgrounds of Salmonella.
We used colony probe hybridization procedures to determine the mutations in approximately 600 revertants of the -1 frameshift allele hisD3052 and approximately 200 revertants of the base-substitution allele hisG46 of Salmonella typhimurium induced by 2-acetylaminofluorene (2-AAF) in the presence of Aroclor-induced rat liver S9. 2-AAF was primarily a frameshift mutagen, exhibiting 5 times more frameshift than base-substitution activity. The only frameshift mutation 2-AAF induced at the hisD3052 allele was a hotspot (-2) deletion within the sequence CGCGCGCG. The addition of the pKM101 plasmid had a small effect on the mutagenic potency of 2-AAF at this allele in a uvr+ background and no effect on the mutation spectra in either a uvr+ or uvr- background. The small amount of base-substitution activity exhibited by 2-AAF at the hisG46 allele required the presence of both the pKM101 plasmid and the uvrB mutation. The base substitutions were G.C-->T.A transversions (86%) and G.C-->A.T transitions (14%), and 85% of the substitutions were at the second position of the CCC target of the hisG46 allele; the remainder were at the first position. We propose that the hotspot frameshift may be initiated by N-acetyl-2-aminofluorene adducts located at the C(8) position of any of the guanines except the first one in the CGCGCGCG hotspot sequence. The mutation might then result from correct incorporation of cytosine opposite the adducted guanine, followed by a 2-base slippage according to our recently proposed correct-incorporation/slippage model. The hotspot mutation may also result from a 2-AAF-induced B- to Z-DNA transition at the repeating GpC site as well as by the action of enzymes involved in DNA metabolism, such as DNA resolvases or topoisomerases, on DNA structures that have been distorted by 2-AAF adducts. The small amount of 2-AAF-induced base-substitution activity may be due to mispairing of adenine opposite the minor aminofluorene adduct at the C(8) position of guanine.


Are healthcare professionals really prepared to deal with information-empowered citizens?
The new Global Information Society increasingly incorporates electronic tools in every walk of life. The e-communication revolution should not be welcomed just because it exists, but rather taken as a possible catalyst to better performance, however that is perceived. Healthcare practitioners must harness the good will & motivation of citizens to play proactive parts in the health & lifestyle management for themselves, their families & their communities. Citizens must recognise that they do not become 'experts' overnight & must work with professional practitioners to the benefit of health status per se. There are still a number of substantial challenges to be faced & a need for considerable parallel & collective development if we (professionals & public) are to contribute effectively together in healthcare in the future.


A novel serine protease overexpressed in the hair follicles of nude mice.
We have studied changes in gene expression between normal and nude mouse skin. Using the method of representational difference analysis, a cDNA encoding a novel serine protease designated BSSP was cloned. Our results show that in skin this gene is predominantly expressed in the sebaceous gland of the hair follicle and in the distal part of the outer root sheath. Thus, BSSP is the first serine protease known to be expressed in the sebaceous gland. In nude mouse skin, this gene is overexpressed.


Long-term voluntary ethanol consumption affects neither spatial nor passive avoidance learning, nor hippocampal acetylcholine release in alcohol-preferring rats.
Long-term ethanol consumption in humans and laboratory animals is associated with morphological and functional alterations of brain structures involved in cognitive processes. In the present experiments, we assessed whether voluntary long-term consumption of ethanol by alcohol-preferring (sP) rats under free choice condition with water (also) caused alterations in memory performance and hippocampal acetylcholine (ACh) release in vivo. A group of sP rats were offered a 10% v/v ethanol solution in a free choice with water for 36 weeks; controls had only tap water available. After withdrawal of ethanol, rats were tested in one trial passive avoidance test and thereafter were trained in a food-reinforced radial arm maze task for 12 days. One day after the last session in the radial-arm maze, rats were implanted with a microdialysis probe in the dorsal hippocampus and dialysate concentrations of ACh were measured. No significant differences were observed between sP drinking and control rats in retention latencies in the passive avoidance test, in radial arm-maze performance or in basal levels of hippocampal ACh release. These results show that long-term ethanol consumption by sP rats is not associated with cognitive impairments or with alterations in the hippocampal cholinergic function. To the extent that chronic ethanol intoxication can be considered a causal factor in the development of memory and neurochemical alterations, these results suggest that sP rats self-regulate ethanol consumption so as to avoid intoxication. These findings may challenge the notion that sP rat lines can be considered a valid model of human alcoholism.