Molecular Endoscopy and in vivo Imaging in Inflammatory Bowel Diseases.
Studies in recent years have shown that standard imaging modalities such as endoscopy, ultrasonography or MRI are essential for assessment of gut inflammation in patients with inflammatory bowel diseases (IBDs). In addition, endoscopy plays a pivotal role in the analysis of mucosal healing in these disorders. However, these techniques do not allow a detailed analysis of the molecular pathways driving gut inflammation in IBD patients. Here, we discuss the role of new techniques for the molecular imaging of gut inflammation in IBD with special reference to the prediction of responses to therapy using antibodies to tumor necrosis factor (anti-TNF). Key Messages: Several in vivo imaging studies have been performed in IBD patients before and after anti-TNF therapy. In one study, (99m)Technetium-labeled annexin V was given to patients with active Crohn's disease before and after anti-TNF therapy with infliximab. Subsequently, single-photon emission CT (SPECT) was performed to study the effect of anti-TNF treatment on apoptosis in the intestine during active colitis. This study showed enrichment of technetium signals in the gut of patients who responded to anti-TNF therapy. The findings suggested that anti-TNF treatment induces T-cell apoptosis in vivo and that SPECT imaging can be used for prediction of response to anti-TNF therapy. In another study, fluorescent anti-TNF antibodies (fluorescent adalimumab) were chosen for molecular imaging during confocal laser endomicroscopy in patients with active Crohn's disease. This study revealed that an increase of membrane-bound TNF expressing mucosal immune cells predicts response to subsequent adalimumab therapy. Molecular in vivo imaging is an exciting new field in patients with IBD. It is expected that this field will allow new insights into the pathophysiology of IBD and may be used for personalized medicine in the future.


Recovery from exercise-induced desaturation in the paraspinal muscles in idiopathic scoliosis.
A study using near-infrared light spectroscopy to measure recovery from exercise-induced desaturation in the paraspinal muscles of patients with idiopathic scoliosis. To measure oxygenation of the paraspinal muscles and obtain differences between the convex and concave sides. Authors of previous studies have reported that some patients experience pain on the convex side of the paraspinal muscles. The muscles on the convex side are more stretched and stressed than those on the concave side. The current authors investigated the degree of stress by measuring oxygenation and blood volume changes. Paraspinal muscle spectral properties at L3 were investigated using near-infrared light spectroscopy. Thirty-six patients (8 men and 28 women) underwent this procedure. To assess a level of peripheral adaptations to exercise, the half-time of Oxyhemoglobin/Myoglobin recovery was measured, which indicates the recovery from energy deficit after exercise. The average half-time recovery on the convex side was 3.38 seconds (range, 1.5-5.5 seconds), whereas that on the concave side was 1.51 seconds (range, 0.7-4.0 seconds). The average difference between the convex side and the concave side was 1.87 seconds (range, 0.9-3.5 seconds). Half-time recovery on the convex side in the patients with idiopathic scoliosis was slower than that in healthy adults (P < 0.05). Half-time recovery on the concave side in such patients was faster than that on the convex side (P < 0.01). The authors consider half-time recovery an indication of back muscle stress.


Cobalt bis(dicarbollide) derivatives: solubilization and self-assembly suppression.
Cobalt bis(dicarbollide) derivatives are promising therapeutic agents however their utilization is complicated due to their low solubility and self-assembling in water. Earlier we have shown that their solubility can be increased by using of suitable biocompatible excipients--carriers of pharmaceutically active compounds. Expected mechanism of solubilization was disassembling of self-assemblies and complexation of unimers. Newly our results of time-dependent light scattering study correct this presumption. Poor solubility of all derivatives can be easily improved by using various excipients, however only heptakis(2,6-di-O-methyl)-β-cyclodextrin displays ability to disassemble self-assemblies of all derivatives and suppress their self-assembling. Surprisingly, the other excipients participate on formation of mixed assemblies of derivative/excipient complex or cover assemblies to make them more soluble without decreasing their size.


Compartmental analyses of plasma n-3 essential fatty acids among male and female smokers and nonsmokers.
The effects of cigarette smoking on n-3 essential FA metabolism were studied in male and female subjects by fitting the concentration-time curves of the d(5)-labeled plasma fatty acids (FAs) originating from a dose of d(5)-18:3n-3 to a compartmental model of n-3 FA metabolism. For 3 weeks, female (smokers, n = 5; nonsmokers, n = 5) and male (smokers, n = 5; nonsmokers, n = 5) subjects subsisted on a beef-based diet. Beginning in the third week, subjects received a dose of d(5)-18:3n-3 ethyl ester (1 g). Plasma FAs were analyzed using gas chromatography (GC) and GC-mass spectrometry, and the kinetic rate parameters were determined from the concentration-time curves for d(5)-18:3n-3, d(5)-20:5n-3, d(5)-22:5n-3, and d(5)-22:6n-3. Women smokers had a 2-fold greater percent of dose in plasma (5.8% vs. 2.9%; P < 0.01) and a higher fractional rate constant coefficient for formation of d(5)-22:6n-3 from d(5)-22:5n-3 (0.03 h(-1) vs. 0.01 h(-1); P < 0.01), compared with nonsmokers. Male smokers had elevated total plasma n-3 FAs, more-rapid turnover of 18:3n-3 (13.3 mg/day(-1) vs. 4.3 mg/day(-1); P < 0.001), a disappearance rate of d(5)-20:5n-3 that was both delayed and slower (0.001 h(-1) vs. 0.012 h(-1); P < 0.05), and a percentage of d(5)-20:5n-3 directed into formation of d(5)-22:5n-3 (99% vs. 61%; P < 0.03) that was greater compared with nonsmokers. Smoking increased the bioavailability of n-3 FAs from plasma, accelerated the fractional synthetic rates, and heightened the percent formation of some long-chain n-3 PUFAs in men and women.


Cardiac resynchronization therapy: a review of CRT-D versus CRT-P.
Current evidence-based guidelines recommend an implantable cardioverter-defibrillator for the primary prevention of sudden cardiac death in selected patients with impaired left ventricular function, and cardiac resynchronization therapy for improvement of symptoms and survival in selected patients with impaired left ventricular function and abnormal ventricular conduction. Many patients may be eligible for both treatments, but it does not necessarily follow that such patients would obtain additional benefit from the combined treatment over one treatment alone. A simple pragmatic approach would be to use resynchronisation therapy, in order to reduce symptoms and extend life in patients with New York Heart Association class III or IV heart failure, with the addition of an implantable cardioverter-defibrillator left to clinical judgment on an individual basis when additional indications exist. When such an addition is contemplated the hypothesized incremental benefits in survival would need to be balanced by the possible increase in morbidity owing to, for example, inappropriate shocks.


Characteristics of Takayasu Arteritis Patients with Severe Ischemic Events.
Takayasu arteritis (TAK) is a rare large vessel vasculitis with a high risk of developing severe ischemic events (SIE). Outcomes for TAK patients with SIE are poorly understood. We aim to describe the characteristics of TAK patients experiencing SIE. All TAK patients with at least one follow-up visit seen between 1988 and 2015 were included from 3 academic centres in Ontario, Canada. Diagnosis was based on American College of Rheumatology (ACR) criteria, physician opinion and vascular imaging. SIE were defined as cerebrovascular accident (CVA), acute coronary syndrome (ACS), ischemic cardiomyopathy, ischemic blindness and/or ischemic bowel or limb requiring surgery. Of the 52 TAK patients included in the study, 51 (98%) were female and 22 (42%) were of European descent. The mean age was 31 (standard deviation [SD] 12) at the time of diagnosis and the follow-up time was 6 (SD 5) years. Fifteen (29%) experienced a SIE: 5 CVA, 5 ACS, 1 ischemic cardiomyopathy and 4 limb ischemia. 13/15 (87%) SIE occurred at or before diagnosis. Patients with SIE were more likely than those without SIE to be started on corticosteroids combined with immunosuppressants (p=0.03) and anti-platelet agents (p=0.0003). Outcomes including disease activity and damage scores were similar between patients with and without SIE. SIE are common in patients with TAK and occur early in the disease. With aggressive treatment, patients with SIE had a favourable prognosis.


Growth factors alter neonatal type II alveolar epithelial cell proliferation.
The type II alveolar epithelial cell plays a critical role in the repair of lung injury by repopulating the entire damaged alveolar epithelium. We report our studies of the effects of known growth factors on the in vitro proliferation of isolated neonatal rabbit type II cells. Transforming growth factor-alpha (TGF-alpha) and epidermal growth factor (EGF) increased [3H]thymidine incorporation, cell number, and labeling index above control. Transforming growth factor-beta (TGF-beta) decreased [3H]thymidine incorporation, cell number, and labeling index compared with control. When added simultaneously, TGF-beta blocked the stimulatory effect of TGF-alpha or EGF. If TGF-alpha is added before TGF-beta, the ability of TGF-beta to block the mitogenic effect of TGF-alpha was diminished the later in time TGF-beta was added. If TGF-beta was added first, later addition of TGF-alpha had no effect. The current work demonstrates that specific growth factors, including some known to be produced by other lung cells, alter the proliferation in vitro of isolated neonatal rabbit type II alveolar epithelial cells.


Irritant dermatitis from diallylglycol carbonate monomer in the optical industry: clinical and experimental studies of cutaneous tolerance and chemical investigations.
The diallylglycol carbonate monomer causes dermatitis due to irritation in the optical industry. Cutaneous intolerance may effect as many as 70% of the exposed persons employed. Almost all control subjects who where patch-tested showed irritation at a 2% concentration. The histological effects were an acute oedema with inflammation of the papillary dermis, and diapedesis of neutrophil polymorphonuclear leukocytes. Experiments on animals confirmed the irritant nature of the product; in the rabbit, a single application produced irritation, but to a lesser degree than in humans. Tests for possible sensitizing effects in the guinea pig have given negative results. Chemical analysis of the monomer revealed the presence of diallyl carbonate and acrolein. Allyl alcohol was detected in only one case. Patch tests were carried out in a group of control subjects with acrolein, diallyl carbonate and allyl alcohol. The histological appearance of the lesions caused by acrolein was quite different from that due to diallyglycol carbonate. It is probable that the irritant is the diallylglycol carbonate monomer itself.


Frazione polifenolica del bergamotto per il trattamento della sindrome metabolica nella schizofrenia: uno studio pilota.
Introduzione. La frazione polifenolica del bergamotto (BPF) ha dimostrato di possedere buona efficacia nel trattamento dei pazienti affetti da sindrome metabolica (SM) e pertanto potrebbe rappresentare una strategia promettente nel trattamento degli effetti collaterali indotti da antipsicotici di seconda generazione (SGA) in soggetti schizofrenici in trattamento con tali farmaci. Materiali e metodi. A 15 pazienti schizofrenici in trattamento stabilizzato con SGA e 15 soggetti di controllo non affetti da patologie psichiatriche, che presentavano valori ematici di colesterolo totale compresi tra 200 e 239 mg/dl, è stato somministrato un integratore contenente BPF (1000 mg) per un periodo di 60 giorni. A tutti i soggetti all'inizio e alla fine del trattamento sono state eseguite la misurazione dell'indice di massa corporea (BMI) e una serie di esami ematochimici per la valutazione degli aspetti metabolici (colesterolo totale, LDL, HDL, trigliceridi, glicemia). Risultati. In entrambi i gruppi si è evidenziata una riduzione significativa del BMI (BMI T0 vs Tfinale (media±DS)= schizofrenici: 34,5±5,7 vs 33,9±5,4, p=,041; controlli: 28,1±4,5 vs 27,3±4,1, p=,016 - BMIcambiamento schizofrenici vs controlli (media±DS)= -0,59±0.7 vs -0,72±0,8, p=,378); colesterolo totale e LDL risultano invece essere diminuiti esclusivamente nel gruppo di controllo (colesterolo totalecambiamento schizofrenici vs controlli (media±DS)= 8,2±31,5 vs -35,1±31,1, p=,003; LDLcambiamento schizofrenici vs controlli (media±DS)= 14,1±29,4 vs -9±38,9, p=,014). Discussione. La differenza di efficacia dei BPF sulla dislipidemia tra i soggetti schizofrenici e il gruppo di controllo potrebbe essere spiegata dai diversi meccanismi patogenetici che sono alla base delle alterazioni metaboliche nei soggetti in trattamento con SGA e nei pazienti che non assumono questa classe di farmaci. Conclusioni. Ulteriori studi si rendono necessari al fine di valutare in questa categoria di soggetti i possibili effetti sulla dislipidemia di dosi maggiori di BPF.


[Corynebacterium acnes osteitis. A case in a child].
The authors report a case of Corynebacterium acnes osteitis in an 11 year old girl, involving the upper of the right tibia. The lesion resembled a malignant tumour radiologically and tuberculosis histologically. Scintigraphy revealed involvement of the seventh right rib. 3 months treatment with Pristinamycin resulted in cure.


[Photoemission characteristic of transmission-mode extended blue GaAs photocathodes].
Based on the theoretical models of computing the photocathode optical performance, quantum yield and integral sensitivity, the photoemission characteristics of the domestic and ITT's transmission-mode extended blue GaAs photocathodes, namely the cathode optical properties and performance parameters, were respectively investigated. The compared results show that the integral sensitivity of the domestic transmission-mode extended blue photocathode has achieved 2,100 microA x lm(-1), still falling behind the ITT's integral sensitivity of 2,750 μA x m(-1). The reasons for the difference in quantum yield curves are that, on one hand, the thickness of GaAlAs window-layer and the Al mole fraction play a critical role in the short-wavelength response, especially in the extended blue region. On the other hand, the cathode performance parameters such as electron diffusion length and back interface recombination velocity work on the long-wavelength and short-wavelength response. All these factors are subject to the backwardness of basic industrial manufacturing level.


Comparison of the effects of felodipine and cilazapril on exercise performance in patients with mild to moderate hypertension. A crossover study.
This double-blind crossover study was designed to compare the effects of felodipine and cilazapril on exercise performance in hypertensive patients. After a 2-week placebo run-in period, 40 patients with mild to moderate hypertension were randomized into two parallel groups to receive either felodipine (10 mg) or cilazapril (5 mg) for 4 weeks. After another 2-week washout period, treatments were then crossed over for a further 4-week study period. All patients were given an extensive rest and exercise evaluation at the end of the placebo period. Extensive rest and exercise evaluations were repeated after a 4-week treatment period and again after the second washout period and after the second 4-week treatment period. Before each exercise test, epinephrine, norepinephrine and dopamine plasma levels and plasma renin activity were measured. Two groups were similar at baseline for systolic and diastolic blood pressure and heart rate as well as for laboratory and hormonal variables and duration of exercise test. At the end of treatment diastolic blood pressure was significantly reduced in the felodipine group (p = 0.019). Duration of exercise test was longer than at baseline (p = 0.031) in the felodipine group. Plasma dopamine levels were significantly increased in the cilazapril group. Plasma renin activity significantly increased in the felodipine group. In conclusion, our data show that the two drugs have the same effectiveness in resting conditions but that felodipine is more effective in lowering maximum exercise diastolic blood pressure and in improving exercise time with an double product increase (not significant); it has no statistically significant effect on maximal exercise systolic blood pressure.


Emissions from unvented kerosene heaters.
Vapor-phase polynuclear aromatic hydrocarbon (PAH) emissions from unvented kerosene heaters were measured. During normal heater operations, tri- and tetra-cyclic PAHs were observed, whereas penta-, hexa- and hepta-cyclic PAHs were not observed. The convective-type heaters had significantly less PAH emissions than the radiant-type heaters. Emissions of particulate soot were also measured. The soot did not contain PAH. A two-compartment model is presented and used to simulate heater operation in a home. Certain simulated PAH levels are similar to that measured in the ambient air of large cities.


Spectrum of spontaneous and 2,4,6-trinitrotoluene (TNT)-induced mutations in Salmonella typhimurium strains with different nitroreductase and O-acetyltransferase activities.
Spontaneous and 2,4,6-trinitrotoluene (TNT)-induced mutation spectra were determined at the hisD3052 allele of Salmonella typhimurium strains TA98, YG1021 (nitroreductase-overproducing) and YG1024 (O-acetyltransferase-overproducing). In TA98, 55% (11/20) of the spontaneous reversions and 95% (19/20) of reversions in TNT-treated plates were deletions of two bases at the same site (-2 hotspot deletions), whereas the respective figures were 65% (13/20) and 80% (16/20) in YG1021, and 75% (15/20) and 95% (19/20) in YG1024. Other mutations observed in the TNT treatment were complex frameshifts consisting of either a -2 hotspot deletion and a base substitution, or a +1 addition and base substitution at the stop codon. In addition, different kinds of deletions were recovered in the spontaneous spectra. The elevated enzymatic activities of strains, YG1021 and YG1024, resulting in enhanced mutagenicity of TNT, did not seem to have an effect on the spectrum of TNT-induced mutations. However, the YG strains, which also have a higher spontaneous revertant yield than the parental strain TA98, seemed to differ from TA98 in their spontaneous spectra. The increase consisted of revertants containing the -2 hotspot deletion, possibly indicating elevated activation of exogenous or endogenous premutagens by the higher enzyme activities of the YG strains.


[Preliminary observation on feeding preference of Oncomelania for Sedum sarmentosum].
As a result of screening, we discovered that Sedum sarmentosum Bunge was most preferred among 317 kinds of snail food. Both adult and young snails readily eat S. sarmentosum as evidenced by laboratory observation and dissection of the snails. In aquarium, more snails were attracted by S. sarmentosum than by Chinese cabbage and Chlorella suspension. On water surface, S. sarmentosum curtains attracted adult snails 2.1-3.7 times and immature snails 2.3-4.1 times more than rice straw curtains.


Ultrasonic aid in transvenous instrumental dilatation for patients with membranous stenosis of the hepatic portion of the inferior vena cava.
We report two cases of a membranous stenosis of the hepatic portion of the inferior vena cava. Membranotomy was performed with a specially designed instrument similar to a Tubbs' dilator following balloon membranotomy. During the procedures, ultrasonographic observations were made and this technique was confirmed to be effective for proper placing of a balloon and a dilator in the stenotic portion. Follow-up evaluation of the procedures was also feasible with this ultrasonic aid.


BRAF inhibitor resistance mechanisms in metastatic melanoma: spectrum and clinical impact.
Multiple BRAF inhibitor resistance mechanisms have been described, however, their relative frequency, clinical correlates, and effect on subsequent therapy have not been assessed in patients with metastatic melanoma. Fifty-nine BRAF(V600)-mutant melanoma metastases from patients treated with dabrafenib or vemurafenib were analyzed. The genetic profile of resistance mechanisms and tumor signaling pathway activity was correlated with clinicopathologic features and therapeutic outcomes. Resistance mechanisms were identified in 58% progressing tumors and BRAF alterations were common. Gene expression analysis revealed that mitogen-activated protein kinase (MAPK) activity remained inhibited in 21% of resistant tumors, and the outcomes of patients with these tumors were poor. Resistance mechanisms also occurred in pretreatment biopsies and heterogeneity of resistance mechanisms occurred within patients and within tumors. There were no responses to subsequent targeted therapy, even when a progressing tumor had a resistance mechanism predicted to be responsive. Selecting sequential drugs based on the molecular characteristics of a single progressing biopsy is unlikely to provide improved responses, and first-line therapies targeting multiple pathways will be required.


A novel mutation in the connexin 29 gene may contribute to nonsyndromic hearing loss.
Connexins (Cxs) are homologous four-transmembrane domain proteins and constitute the major components of gap junctions. Among a cohort of patients with nonsyndromic hearing loss, we recently identified a novel missense mutation, E269D, in the GJC3 gene encoding connexin 29 (Cx29), as being causally related to hearing loss. The functional alteration of Cx29 caused by the mutant GJC3 gene, however, remains unknown. This study compared the intracellular distribution and assembly of mutant Cx29 (Cx29E269D) with that of the wild-type Cx29 (Cx29WT) in HeLa cells and the effect the mutant protein had on those cells. Cx29TW showed continuous staining along apposed cell membranes in the fluorescent localization assay. In contrast, the p.E269D missense mutation resulted in accumulation of the Cx29 mutant protein in the endoplasmic reticulum (ER) rather than in the cytoplasmic membrane. Co-expression of Cx29WT and Cx29E269D proteins by a bi-directional tet-on expression system demonstrated that the heteromeric connexon accumulated in the cytoplasm, thereby impairing the formation of the gap junction. Based on these findings, we suggest that Cx29E269D has a dominant negative effect on the formation and function of the gap junction. These results provide a novel molecular explanation for the role Cx29 plays in the development of hearing loss.


Power spectral analysis of heart rate variability during positive pressure pneumoperitoneum: the significance of increased cardiac sympathetic expression.
Positive pressure pneumoperitoneum (PPP) effects on the autonomic nervous system (ANS) might be of clinical importance, as imbalance in the autonomic cardiac control might lead to serious consequences. Fifteen healthy patients undergoing elective laparoscopic cholecystectomy were analyzed for cardiac autonomic nervous activity by spectral heart rate variability, during awake state, before and after intubation, during CO2 PPP (14 mmHg), and after CO2 evacuation. The very low, low, high and very high frequency (VLF, LF, HF, VHF respectively) bands of the spectral density of the heart rate variability (HRV) and their normalized values, as well as the LF/HF ratio, were obtained from the power spectra of R-R intervals, using the fast-Fourier transformation algorithm. Using Friedman's nonparametric test, only the difference between the power of LF during anesthesia (median 30.74) and the middle of PPP (median 195.66) was found to be significant (p<0.012). Such change was recorded in 14 patients (p = 0.001, sign test). Increased LF power reflects sympathetic cardiac activation. As the LF range accounts for regulation of blood pressure and baroreflex, several mechanisms may explain this activation. This in turn may predispose patients who suffer from cardiac disease to higher risk of developing ventricular arrhythmias, besides the possible adverse hemodynamic consequences of PPP.


DNA from natural sources in design of functional devices.
The role of DNA as structuring or templating agent has become more significant with the development of nanobiotechnology. Although short single and double stranded DNA have extensively been used as immobilization tool, as a template for nanoparticle preparation and in design of various devices such as nanomotors and biosensors, DNA from natural sources has an advantage of being abundant, cheap and readily available. Therefore, it is not surprising that there is a huge interest in making the use of natural DNA properties for both nano- and micro-applications. In this review we attempt to give an overview of the up to date applications of natural DNA, either from viral, marine or mammalian sources, in design of functional devices. This article is meant to be a starting point and a guide to the platforms in which natural DNA is employed such as DNA origami, optoelectronic devices and organic catalysis.


Intra-articular osteoid osteoma.
Osteoid osteomas located within the capsule of a joint are uncommon and present challenging diagnostic difficulties. Twelve patients with an intra-articular osteoid osteoma were studied retrospectively to determine the spectrum of clinical and radiological findings. The features differ significantly from the well known classical hallmarks of the extra-articular lesion. The symptoms are non-specific with pain similar to other common joint disorders and the response to salicylate less precise. On plain radiography intra-articular lesions are difficult to identify, lacking the florid periosteal new bone and intense perifocal sclerotic reaction. A detectable focal lesion is commonly absent with considerable delay between the onset of symptoms and radiological detection of the tumour nidus. Bone scintigraphy and computed tomography (CT) are essential for an accurate and early diagnosis. These imaging techniques reveal abnormalities in bone and cartilage growth, new bone formation and sclerosis distant from the tumour on either side of the joint, and disruption of the articular surface. Radiological follow up after surgery shows that these changes can be reversible, especially when the diagnosis is made early.


Third-ventricular infusion of neuropeptide Y suppresses luteinizing hormone secretion in ovariectomized rhesus macaques.
Neuropeptide Y (NPY) has been shown to modulate gonadotropin secretion in an estrogen-dependent manner in the rat and rabbit, and to act centrally in these species to alter GnRH release. The present study examined the ability of centrally administered NPY to affect LH secretion in the primate. Human NPY (hNPY) was administered into the third cerebroventricle of unanesthetized, freely moving, ovariectomized (OVX), or estradiol (E2)-treated OVX rhesus monkeys. LH was measured in blood samples collected remotely at 10-min intervals throughout the experiments. An extensive range of NPY doses was tested in a preliminary study in which OVX monkeys received a 3-h control infusion of Krebs Ringer phosphate buffer (KRP) followed immediately by a 3-h infusion of hNPY (0.1-50 micrograms/h). Only doses greater than or equal to 5 micrograms/h produced a consistent and marked suppression of LH (5 micrograms/h; 35.1 +/- 7.2% reduction, P less than 0.05, n = 4). A longer duration study was performed to better characterize changes in LH pulse frequency and amplitude produced by hNPY treatment. We administered 5 micrograms/h and 15 micrograms/h to OVX (n = 5) and E2-treated OVX (n = 4) monkeys according to the following protocol: 8 h control KRP/8-h hNPY/6-h recovery KRP. In OVX monkeys, LH was suppressed after 2 to 3 h of peptide infusion (P less than 0.01); LH secretion returned to normal after treatment. Both doses of hNPY suppressed mean LH by approximately 55% (P less than 0.05) and LH pulse frequency by approximately 69% (P less than 0.025). LH pulse amplitude was unaffected. In E2-treated OVX monkeys, neither dose of hNPY affected mean LH or LH pulse amplitude. LH pulse frequency was suppressed by approximately 65% (P less than 0.05) during 15-micrograms/h treatment. Because centrally administered hNPY reduced LH pulse frequency and thereby mean LH levels, our results support a central, neural action of NPY to affect the GnRH/LH secretory system. The ability of estrogen feedback to alter the response to NPY treatment supports a physiological role for NPY in controlling reproduction in the primate.


Pain and depression in caregivers affected their perception of pain in stroke patients.
Informal caregivers often serve as proxy raters of Health-Related Quality of Life (HRQL) when patients cannot report on their own behalf. Caregiver depression has been associated with bias in proxy ratings, but few studies have examined the role of caregiver pain. The aim of this study was to determine if caregiver depressive symptoms and/or pain systematically affected patient-proxy agreement on patient HRQL after stroke. Secondary data analysis of 95 stroke patients and their caregivers (dyads) at 6 months poststroke. Caregiver depressive symptoms were measured by Center for Epidemiologic Studies Depression Rating Scale, and pain was measured using EQ-5D. Using multivariate regression, we examined the effect of caregiver depressive symptoms and pain on patient-proxy difference scores on Health Utilities Index 3 (HUI3) attributes and Short Form-36 domains of vitality and social functioning. Caregiver depressive symptoms and pain were associated with significant differences in patient-proxy scores on HUI3 pain (P<0.05). Depressed caregivers underestimated pain experienced by patients, and caregivers with pain overestimated patient pain. Additionally, an interaction between caregiver depressive symptoms and pain was identified. Presence of pain and depressive symptoms in caregivers can significantly affect perceptions of pain in stroke patients. Results suggest that caregivers with pain and/or depression may provide more biased proxy assessments of pain.


Versican: a novel modulator of hepatic fibrosis.
Little is known about the deposition and turnover of proteoglycans in liver fibrosis, despite their abundance in the extracellular matrix. Versican plays diverse roles in modulating cell behavior in other fibroproliferative diseases, but remains poorly described in the liver. Hepatic fibrosis was induced by carbon tetrachloride treatment of C57BL/6 mice over 4 weeks followed by recovery over a 28-day period. Primary mouse hepatic stellate cells (HSCs) were activated in culture and versican was transiently knocked down in human (LX2) and mouse HSCs. Expression of versican, A Disintegrin-like and Metalloproteinase with Thrombospondin-1 motifs (ADAMTS)-1, -4, -5, -8, -9, -15, and -20, and markers of fibrogenesis were studied using immunohistochemistry, real-time quantitative PCR, and western blotting. Immunohistochemistry showed increased expression of versican in cirrhotic human livers and the mouse model of fibrosis. Carbon tetrachloride treatment led to significant increases in versican expression and the proteoglycanases ADAMTS-5, -9, -15, and -20, alongside TNF-α, α-smooth muscle actin (α-SMA), collagen-1, and TGF-β expression. During recovery, expression of many of these genes returned to control levels. However, expression of ADAMTS-5, -8, -9, and -15 showed delayed increases in expression at 28 days of recovery, which corresponded with decreases in versican V0 and V1 cleavage products (G1-DPEAAE(1401) and G1-DPEAAE(441)). Activation of primary HSCs in vitro significantly increased versican, α-SMA, and collagen-1 expression. Transient knockdown of versican in HSCs led to decreases in markers of fibrogenesis and reduced cell proliferation, without inducing apoptosis. Versican expression increases during HSC activation and liver fibrosis, and proteolytic processing occurs during the resolution of fibrosis. Knockdown studies in vitro suggest a possible role of versican in modulating hepatic fibrogenesis.


Association between site of lesion and driving performance after ischemic stroke.
Stroke presents with heterogeneous recovery periods, severity, and manifestation of deficits, all of which may adversely impact fitness-to-drive. Little is known about the association between site of lesion and driving performance after stroke. To investigate the association between site of stroke lesion and driving performance. Seventy-three participants (age = 56 ± 11 years; 66 men) underwent a detailed battery of visual, cognitive, and on-road tests to determine fitness-to-drive at about 10 months after ischemic stroke. Associations between stroke location and driving performance were calculated using rank biserial (r rb) correlation coefficients. Correlations were considered weak below 0.10, moderate between 0.10 and 0.49, and strong above 0.50. Wilcoxon rank sum tests were employed to discern differences in on-road driving performance between participants whose performance was of concern to the driving assessor and those who exhibited no major difficulties on the road. In all, 28 (38%) out of the 73 participants exhibited major difficulties on the road. Those who showed difficulties on the road performed worse in all driving skills (P < 0.05). Correlation analysis showed moderate to strong correlations between site of lesion and performance in several visual, cognitive and on-road tests. Lesions in the parietal lobe showed correlations ranging between 0.23 and 0.25 with driving skills including vehicle control and speed adaptations. Lesions in the occipital lobes correlated strongly with visual field (r rb = 0.53) and moderately with visual neglect (r rb = 0.28). Our results suggest that cortical lesions in the parietal and occipital lobes are associated with driving deficits after stroke. Further advances in our understanding of the neural correlates of driving performance may provide prognostic markers of fitness-to-drive and lead to early, targeted rehabilitation.


Diagnosis, treatment and outcome of pneumonia in the acquired immune deficiency syndrome.
Fibreoptic bronchoscopy was performed in 43 of 52 consecutive patients with opportunistic pneumonia in the acquired immune deficiency syndrome (AIDS). The 15 patients in whom a likely pathogen was not found by bronchoscopy (including the nine not having the procedure) were treated for Pneumocystis carinii pneumonia (PCP) alone and all responded. In 11 of these a diagnosis of AIDS was confirmed because of an alternative opportunistic infection within 6 months. PCP was confirmed in 38 of the 52 patients and cytomegalovirus (CMV) was isolated from 15 patients. The lower the partial pressure of arterial oxygen (PaO2) on admission the more likely was a pathogen to be found by bronchoscopy. The admission PaO2 while the patient was breathing room air was the single most reliable prognostic indicator. The mean PaO2 for survivors was 9.6 kPa and 6.7 kPa for non-survivors (P less than 0.01 Student's t-test), with 50% mortality for patients with a PaO2 of less than 8 kPa on admission. Temperature and pulse rate were sensitive indicators of response to treatment, obviating the need for frequent arterial gas measurements and chest radiography. Our findings suggest that although fibreoptic bronchoscopy contributed little to the treatment and final outcome of the infection, it identified the causative pathogen in most patients.


Apoptotic induction by pinobanksin and some of its ester derivatives from Sonoran propolis in a B-cell lymphoma cell line.
Propolis is a resinous substance produced by honeybees (Apis mellifera) from the selective collection of exudates and bud secretions from several plants. In previous works, we reported the antiproliferative activity of Sonoran propolis (SP) on cancer cells; in addition we suggested the induction of apoptosis after treatment with SP due to the presence of morphological changes and a characteristic DNA fragmentation pattern. Herein, in this study we demonstrated that the antiproliferative effect of SP is induced through apoptosis in a B-cell lymphoma cancer cell line, M12.C3.F6, by an annexin V-FITC/Propidium iodide double labeling. This apoptotic effect of SP resulted to be mediated by modulations in the loss of mitochondrial membrane potential (ΔΨm) and through activation of caspases signaling pathway (3, 8 and 9). Afterward, in order to characterize the chemical constituents of SP that induce apoptosis in cancer cells, an HPLC-PDA-ESI-MS/MS method followed by a preparative isolation procedure and NMR spectroscopy analysis have been used. Eighteen flavonoids, commonly described in propolis from temperate regions, were characterized. Chrysin, pinocembrin, pinobanksin and its ester derivatives are the main constituents of SP and some of them have never been reported in SP. In addition, two esters of pinobanksin (8 and 13) are described by first time in propolis samples in general. The antiproliferative activity on M12.C3.F6 cells through apoptosis induction was exhibited by pinobanksin (4), pinobanksin-3-O-propanoate (14), pinobanksin-3-O-butyrate (16), pinobanksin-3-O-pentanoate (17), and the already reported galangin (11), chrysin (9) and CAPE. To our knowledge this is the first report of bioactivity of pinobanksin and some of its ester derivatives as apoptosis inducers. Further studies are needed to advance in the understanding of the molecular basis of apoptosis induction by SP and its constituents, as well as the structure-activity relationship of them.


The integrin ligand c(RGDf(NMe)Nal) reduces neointimal hyperplasia in a polymer-free drug-eluting stent system.
The use of highly active and selective integrin ligands in combination with stent implantation is emerging as a promising alternative to the release of classical immunosuppressive drugs by current drug-eluting stents (DES), which has been associated with delayed vascular healing and late stent thrombosis. Herein we present the development and biological evaluation of the integrin ligand c(RGDf(NMe)Nal) as a potent anti-proliferative molecule that targets coronary artery smooth muscle cells (CASMCs). This peptide showed an antagonistic activity for αvβ3 and αvβ5 in the low-nanomolar range, and selectivity against the platelet receptor αIIbβ3. In vitro, it efficiently inhibited the proliferation of CASMCs, displaying higher potency than the anti-tumor drug candidate cilengitide. This peptide was then loaded into a polymer-free bare metal stent (BMS), and its release studied at different time points. Up to seven days of elution, the peptide-coated stents retained high anti-proliferative activity toward CASMCs. Finally, the peptide was examined in vivo in a polymer-free DES system in a rabbit iliac artery model. After 28 days of implantation, histopathological analysis revealed that the peptide clearly decreased neointimal growth and improved vessel healing and re-endothelialization compared with the FDA-approved Cypher DES. Our study shows that this type of lipophilic integrin ligand, when eluted from a polymer-free stent system, has the potential to successfully decrease in-stent restenosis in the absence of delayed vascular healing.


[Cryotherapy as an alternative intervention to surgical excision in the management of cancer of the rectum].
For the time being, traditional surgery is still the best technique for rectal cancer. Alternative procedures such as cryosurgery prove valid in the case of inoperable subjects in poor general conditions, in aged patients or in the presence of widespread metastases. In the near future, cryosurgery is sure to meet with interesting developments.


Clustering requires modified methyl-accepting sites in low-abundance but not high-abundance chemoreceptors of Escherichia coli.
Chemotaxis signalling complexes of Escherichia coli, composed of chemoreceptors, CheA and CheW, form clusters located predominantly at cell poles. As the only kind of receptor in a cell, high-abundance receptors are polar and clustered whereas low-abundance chemoreceptors are polar but largely unclustered. We found that clustering was a function of the cytoplasmic, carboxyl-terminal domain and that effective clustering was conferred on low-abundance receptors by addition of the approximately 20-residue sequence from the carboxyl terminus of either high-abundance receptor. These sequences are different but share a carboxyl-terminal pentapeptide that enhances adaptational covalent modification and allows a physiological balance between modified and unmodified methyl-accepting sites, implying that receptor modification might influence clustering. Thus we investigated directly effects of modification state on chemoreceptor clustering. As the sole receptor type in a cell, low-abundance receptors were clustered only if modified, but high-abundance receptors were clustered independent of extent of modification. This difference could mean that the two receptor types are fundamentally different or that they are poised at different positions in the same conformational equilibrium. Notably, no receptor perturbation we tested altered a predominant location at cell poles, emphasizing a distinction between determinants of clustering and polar localization.


Incidence of and factors related to late complications in conformal and conventional radiation treatment of cancer of the prostate.
The fundament hypothesis of conformal radiation therapy is that tumor control can be increased by using conformal treatment techniques that allow a higher tumor dose while maintaining an acceptable level of complications. To test this hypothesis, it is necessary first to estimate the incidence of morbidity for both standard and conformal fields. In this study, we examine factors that influence the incidence of late Grade 3 and 4 morbidity in patients treated with conformal and standard radiation treatment for prostate cancer. Six hundred sixteen consecutive patients treated with conformal or standard techniques between 1986 and 1994 to doses greater than 65 Gy and with more than 3 months follow-up were analyzed. No patients treated with prostatectomies were included in the analysis. The conformal technique includes special immobilization by a cast, careful identification of the target volume in three dimensions, localization of the inferior border of the prostate using a retrograde urethrogram, and individually shaped portals that conform to the Planning Target Volume (PTV). Multivariate analysis using a proportional hazards model compares differences in the incidence of Radiation Therapy Oncology Group/European Organization for Research and Center Treatment (RTOG/EORTC) Grade 3 and 4 late gastrointestinal (GI) and genitourinary (GU) morbidity by technique, T-stage, grade, age, hormonal treatment, irradiated volume, dose, and comorbid conditions. Grade 3 rectal bleeding was defined as requiring three or more cautery procedures. The overall actuarial incidence of genitourinary (GU) toxicities at 5 years was 3.4%, with the crude incidence being six cases in 616 patients satisfying the selection criteria; for gastrointestinal (GI) toxicities, the overall actuarial incidence was 2.7%, with the crude incidence being 13 cases out of 616 patients. The average time to complication for our patients was 12.8 months for GI toxicity and 32.9 months for GU toxicity (p < 0.001). No factors were found that were predictive for GU morbidity. The only factors significantly related to incidence of late GI morbidity on multivariate analysis of our data were dose and age. The central axis dose was a more significant variable than the dose prescribed to the Treated Volume. Age was negatively correlated with late GI morbidity, with older patients having a reduced incidence of toxicity. The median tolerance dose for GI complications was estimated to be 92.8 Gy, and the dose for 10% incidence was estimated to be 80.2 Gy. Treating the pelvis to 45 Gy did not increase the incidence of late morbidity. Late GI and GU toxicities were not correlated. The conformal technique has been associated with fewer acute Grade 2 toxicities (6). The use of conformal fields did not decrease the incidence of late GI morbidity; however, patients with this technique invariably had higher doses. Because of the dose response for this complication and the correlation between the dose and the use of conformal fields, one would not expect to demonstrate an advantage to conformal fields in this data set. On the other hand, no dose effect was observed for late GU morbidity. In this case, there appears to be an advantage for conformal treatment that has not reached statistical significance because the follow-up time is shorter than for the patients treated with conventional fields and the latency for GU morbidity is long.


Identification of placental transforming growth factor-beta and bikunin metabolites as contaminants of pharmaceutical human chorionic gonadotrophin preparations by proteomic techniques.
A contaminant protein complex found in pharmaceutical urinary human chorionic gonadotrophin preparations is reported to have anti-human immunodeficiency virus-associated Kaposi's sarcoma activity. The aim of this study was to isolate and characterize this protein complex by proteomic approaches. Size exclusion chromatography was used in the isolation of these human chorionic gonadotrophin-associated fragments. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis showed the presence of a protein complex that dissociated into two protein bands under reducing conditions. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry of this complex showed three polypeptides at approximately 6.2, 11.4, and 15.8 kDa. Peptide mass mapping and N-terminal amino acid sequencing identified two polypeptides as metabolites of placental transforming growth factor-beta (11.4 kDa) and bikunin (15.8 kDa). Subsequent matrix-assisted laser desorption/ionization time-of-flight mass spectrometric analysis of the anti-human immunodeficiency virus-associated Kaposi's sarcoma active preparations CG-10 (Sigma), Pregnyl (Organon), and Profasi (Serono) revealed the presence of metabolites of placental transforming growth factor-beta in all three; no other non-human chorionic gonadotrophin-related protein species were observed in these preparations. Our findings present evidence that urinary human chorionic gonadotrophin preparations are contaminated with metabolites of placental transforming growth factor-beta, which may have transforming growth factor-beta agonist actions, and metabolites of bikunin, which is a protease inhibitor. In combination these molecules may be responsible for the anti-human immunodeficiency virus-associated Kaposi's sarcoma activity demonstrated for these urinary human chorionic gonadotrophin preparations.


Insoluble nonstarch polysaccharides in diets for weaned piglets.
To examine the effect of inclusion insoluble nonstarch polysaccharides (iNSP) in weaned diets on postweaning piglet performance, intestinal activity, and microbial composition 2 experiments were designed. In Exp. 1, 180 piglets were weaned at 28 d of age and divided over 3 treatments: positive control (PC; highly digestible protein), negative control (NC; standard cereal-based diet), and an experimental diet {iNSP; standard + 15% iNSP [wheat straw and oat (Avena sativa) hull]}. Diets were fed during 14 d after weaning. The ADFI, ADG, and G:F were determined. The inclusion of iNSP increased (P < 0.001) ADFI and G:F during days 0 to 14 after weaning and increased the ADG (P = 0.008) during days 0 to 7 after weaning compared with the NC diet. In Exp. 2, 36 piglets were fed the same diets as in Exp. 1. On days 5 and 14 after weaning, 18 piglets were euthanized to determine enzyme activity, intestinal morphology, and microbial population in the ileum and colon and organ weight. The iNSP diet reduced the concentration of Escherichia coli bacteria in the ileum (P = 0.021) and in the colon (P = 0.002) digesta and tended to increase (P = 0.060) the amylase activity. The iNSP diet stimulated the physical adaptation of the gastrointestinal tract because stomach weight as percentage of BW was heavier (P = 0.004) than for the NC diet. In conclusion, the consumption of diets with higher iNSP content in the early weaning period affects the microbial colonization without reducing enzyme activity or animal performance compared with a standard weaned pig diet.


Pulse transit time and blood pressure during cardiopulmonary exercise tests.
Pulse transit time (PTT), the interval between ventricular electrical activity and peripheral pulse wave, is assumed to be a surrogate marker for blood pressure (BP) changes. The objective of this study was to analyze PTT and its relation to BP during cardiopulmonary exercise tests (CPET). In 20 patients (mean age 51+/-18.4 years), ECG and finger-photoplethysmography were continuously recorded during routine CPETs. PTT was calculated for each R-wave in the ECG and the steepest slope of the corresponding upstroke in the plethysmogram. For each subject, linear and non-linear regression models were used to assess the relation between PTT and upper-arm oscillometric BP in 9 predefined measuring points including measurements at rest, during exercise and during recovery. Mean systolic BP (sBP) and PTT at rest were 128 mm Hg and 366 ms respectively, 197 mm Hg and 289 ms under maximum exercise, and 128 mm Hg and 371 ms during recovery. Linear regression showed a significant, strong negative correlation between PTT and sBP. The correlation between PTT and diastolic BP was rather weak. Bland-Altman plots of sBP values estimated by the regression functions revealed slightly better limits of agreements for the non-linear model (-10.9 to 10.9 mm Hg) than for the linear model (-13.2 to 13.1 mm Hg). These results indicate that PTT is a good potential surrogate measure for sBP during exercise and could easily be implemented in CPET as an additional parameter of cardiovascular reactivity. A non-linear approach might be more effective in estimating BP than linear regression.


Adaptive support ventilation.
Adaptive support ventilation (ASV) is a newer form of closed-loop ventilation control available on the Galileo ventilator (Hamilton Medical). ASV provides automated selection of initial ventilator parameters based on measurements of patient lung mechanics and breathing effort. After initiation, ASV will "titrate" ventilator output (mandatory breath rate, tidal volume, inspiratory pressure, inspiratory time, and I to E ratio) to maintain a calculated optimal breathing pattern that ensures delivery of a clinician selected minute ventilation target. ASV may be thought of as an "electronic" ventilator management protocol that may improve the safety and efficacy of mechanical ventilation. Additional clinical investigations regarding the effect of ASV on outcome, ventilator days, and so forth are forthcoming.


[Spinal cord metastasis of a glioblastoma].
Two years after surgery followed by chemotherapy and radiotherapy of a temporal glioblastoma, a 51 year-old woman presented pluriradicular symptoms ascribed to compression of the left part of the cauda equina. The second operation confirmed the metastatic nature of the compression, and histological investigation proved the similarity of the neoplastic tissues taken from the medullary and cerebral regions. The authors stress the rarity of the clinical forms of medullary metastases of glioblastomas. The factors conducive to this fluid effusion are trauma and ventricular effraction by the original tumour. Neither screening nor prophylactic irradiation seem necessary in view of the low frequency of these metastases.


Timing or Dosing of Intravenous Proton Pump Inhibitors in Acute Upper Gastrointestinal Bleeding Has Low Impact on Costs.
High-dose intravenous proton pump inhibitors (PPIs) post endoscopy are recommended in non-variceal upper gastrointestinal bleeding (UGIB), as they improve outcomes of patients with high-risk lesions. Determine the budget impact of using different PPI regimens in treating non-variceal UGIB, including pre- and post-endoscopic use, continuous infusion (high dose), and intermittent bolus (twice daily) dosing. A budget impact analysis using a decision model informed with data from the literature adopting a US third party payer's perspective with a 30-day time horizon was used to determine the total cost per patient (US$2014) presenting with acute UGIB. The base-case employing high-dose pre- and post-endoscopic IV PPI was compared with using only post-endoscopic PPI. For each, continuous or intermittent dosing regimens were assessed with associated incremental costs. Deterministic and probabilistic sensitivity analyses were performed. The overall cost per patient is $11,399 when high-dose IV PPIs are initiated before endoscopy. The incremental costs are all inferior in alternate-case scenarios: $106 less if only post-endoscopic high-dose IVs are used; with intermittent IV bolus dosing, the savings are $223 if used both pre and post endoscopy and $191 if only administered post endoscopy. Subgroup analysis suggests cost savings in patients with clean-base ulcers who are discharged early after endoscopy. Results are robust to sensitivity analysis. The incremental costs of using different IV PPI regimens are modest compared with total per patient costs.


[Prevention and treatment of infectious diseases in diabetic patients].
The bidirectional relationship between infectious diseases and diabetes is well-known. On the one hand, diabetes patients are at a higher risk of presenting with infectious diseases, possibly with more severity, and on the other hand, infectious diseases impair metabolic control in patients with diabetes. Population ageing arises partly due to an increased survival rate in chronic diseases, of which diabetes is amongst them. Improving infectious disease prevention could reduce complications arising from the former diseases, consequences of decompensated diabetes condition (morbidity, incapacity, hospital admissions, healthcare costs, and mortality rates) and result in improved quality of life in patients with diabetes. The current review presents the treatment of infectious diseases in patients with diabetes and the dealing with immuno-preventable diseases with the currently advised vaccinations.


A Late Triassic dinosauromorph assemblage from New Mexico and the rise of dinosaurs.
It has generally been thought that the first dinosaurs quickly replaced more archaic Late Triassic faunas, either by outcompeting them or when the more archaic faunas suddenly became extinct. Fossils from the Hayden Quarry, in the Upper Triassic Chinle Formation of New Mexico, and an analysis of other regional Upper Triassic assemblages instead imply that the transition was gradual. Some dinosaur relatives preserved in this Chinle assemblage belong to groups previously known only from the Middle and lowermost Upper Triassic outside North America. Thus, the transition may have extended for 15 to 20 million years and was probably diachronous at different paleolatitudes.


New hopane triterpenes and antioxidant constituents from Potentilla fulgens.
Phytochemical investigation of the aerial parts of Potentilla fulgens L. led to the isolation of two new triterpenes, potentene A (1) and potentene B (2). In addition, three known compounds afzelchin-4alpha --> 8"-catechin (3), epiafzelchin (4) and rutin (5) were isolated. The structures of all these compounds were elucidated by extensive spectroscopic and chemical evidence. Compounds 3, 4, and 5 exhibited significant 1,1,diphenyl-2-picrylhydrazyl radical scavenging activity, with IC50 values of 1.21, 2.88 and 5.20 mg/mL, respectively; the known standard antioxidant, vitamin C, had a value of 0.44 mg/mL.


Preliminary evidence of an adolescent HIV/AIDS peer education program.
Adolescent peer education has been found to be an effective method to improve adolescents' knowledge and positive health behaviors. The purpose of this study was to determine the extent to which a peer education program was effective in changing adolescents' HIV/AIDS knowledge, risk behavior intentions, and confidence to engage in safe sex. The results showed that there was a significant difference in HIV knowledge between the peer education group and the traditionally educated group, with the peer group demonstrating greater knowledge. There was no significant difference in confidence to engage in safe sex between the two groups, but students in the intervention group were more likely to engage in safe sex than students in the traditionally educated group. Nurses can provide leadership in the development, implementation, and evaluation of peer education in adolescent health.


Distance between the esophageal tumor and the aorta measured by using the contrast-enhanced attenuation on computed tomography for predicting this tumor invading aorta.
Despite remarkable advances in diagnostic modalities, preoperative assessment of the local tumor extent in esophageal cancer is still very difficult. The aim of this study was to evaluate the predictive value of the computed tomography (CT) attenuation value between the tumor and the aorta for esophageal cancer. Consecutive CT values were determined between the center of the tumor and the center of the aorta. The distance between the intersection of the average CT attenuation value of the tumor using the lower CT attenuation value of the inclusion tissues (T-A distance) was determined. The minimal CT attenuation value and the overall circumference of contact area (Picus' angle) were also determined. This study included 101 patients suspected of having a tumor invading the adventitia and evaluated the capacity of these parameters for predicting the aortic invasion. The T-A distance in patients who were diagnosed without aortic invasion was significantly longer than patients who were pathologically confirmed to have invasion to the aortic wall [pT4(Ao)] (P < 0.05). The minimal CT attenuation value in patients without aortic invasion was significantly lower than pT4(Ao) patients (P < 0.05), although such a difference was not observed for the Picus' angle. The T-A distance (1.3 mm >) is the most reliable feature for predicting the aortic invasion, according to the results of the area under the receiver operating characteristic curve. The assessment of the T-A distance is simple and objective, and it can help prevent unnecessary surgery in patients with inoperable tumors.


Morbidity related to transmandibular distraction osteogenesis for patients with developmental deformities.
The aim of this retrospective observational case series study was to determine the morbidity of transmandibular Distraction Osteogenesis (DO) using a bone-borne distraction device to adapt the surgical protocol and improve hardware design. The treatment of 23 consecutive, non-syndromic patients who underwent transverse mandibular DO after a midline symphyseal osteotomy with the TransMandibular Distractor (TMD ) was evaluated. The follow-up period lasted at least 1 year after the end of the contention period. Treatments were analysed according to the morphological and functional Success Criteria (SC) for Craniofacial Distraction Osteogenesis (CFDO) for patients with developmental dentofacial malformations established by the steering group of European Collaboration on Cranial Facial Anomalies (EUROCRAN). Appropriate distraction was obtained in 22 of the 23 patients. One patient had irreversible dentition damage, consisting of an inadvertent apical section. All other SC for CFDO were fulfilled 100% at 1 year follow-up. Seven patients suffered from short-term local infections during different phases of treatment. Two patients suffered subluxation of a central incisor that healed uneventfully. Local discomfort due to delayed union (in three patients) and trauma to the lower lip (one patient) were also observed. The main problems were high local infection rates and damage to an apex that required a root filling, as well as patient discomfort due to delayed union and/or the bulkiness of the TMD device. Based on the results of this morbidity study, modifications are recommended for both the surgical protocol and the TMD device hardware.


Quantification of the preexisting CD4 T-cell repertoire specific for human erythropoietin reveals its immunogenicity potential.
Antibody-mediated pure red cell aplasia is a rare but serious event resulting from the induction of neutralizing erythropoietin (Epo)-specific antibodies provoked by treatment with recombinant Epo. Because of the crucial role of CD4 T cells in humoral response, we have quantified the number of Epo-specific CD4 T cells in the blood of normal donors by in vitro stimulation. An important repertoire of preexisting Epo-specific T cells was observed in almost half of the donors, comparable with that of non-self-proteins. This observation suggests that, at the steady state, endogenous Epo weakly contributes to tolerance induction and may be ignored by the immune system. As a result, circulating Epo-specific CD4 T cells could be prone to be activated by altered batches of Epo, providing them with costimulatory signals. Our data also highlight the relevance of T-cell assays performed with normal donors to evaluate the potential immunogenicity of therapeutic proteins.


Ester and related derivatives of ring N-pentafluorobenzylated 5-hydroxymethyluracil. Hydrolytic stability, mass spectral properties, and trace detection by gas chromatography-electron-capture detection, gas chromatography-electron-capture negative ion mass spectrometry, and moving-belt liquid chromatography-electron-capture negative ion mass spectrometry.
One consequence of radiation damage to DNA is the conversion of thymine to 5-hydroxymethyluracil (HMU). In order to sensitively detect this DNA adduct by gas chromatography (GC) or high-performance liquid chromatography (HPLC) with electron-capture detection techniques, it is necessary to derivatize it. This study was designed to select an optimum ester derivative of the aliphatic hydroxyl group on HMU. N1, N3-Bis(pentafluorobenzyl)-HMU was formed as a parent derivative, and from this a series of esters. Also O-pentafluorobenzyl and O-tetrafluorobenzyl ether derivatives were prepared. Of the esters the pivalyl derivative was the best choice because it formed easily, was relatively stable to aqueous hydrolysis (t 1/2 = 9.8 days at pH 11.5, 24 degrees C) and gave a response at fmol levels by GC and LC comparable to that of the ethers. Unanticipated was a good response as well for the parent derivative, a free hydroxyl compound, by GC and LC at this level. The work also demonstrates a high performance by LC-electron-capture negative ion mass spectrometry with a belt interface for the trace detection of derivatives of this type.


Ancillary services for individuals living with HIV/AIDS.
Providing comprehensive care to those living with HIV/AIDS remains a daunting task. Access to early HIV medical care helps to delay an AIDS diagnosis, and ancillary services can help meet the non-medical needs of HIV-positive individuals, which can ultimately impact their ability to access medical care. Some research has been done measuring ancillary service provision and primary care entry and retention; however, due to the lack of a comprehensive system of care, it has been difficult to determine the true impact of ancillary service usage and health outcomes. Additional qualitative research examining ancillary service usage, health outcomes, and quality of life needs to be done to develop a standard model of appropriate and comprehensive HIV care.


Intermittent catheterization for post-operative urine retention.
This article describes a small study that looked at the safety and effectiveness of intermittent catheterization in managing post-operative urine retention on a gynecological ward.


Reduction of cis,trans,cis-[PtCl2(OCOCH3)2(NH3)2] by aqueous extracts of cancer cells.
Pt(IV) complexes must be reduced to kill cancer cells. While reduction rates correlate with reduction potentials, we wanted to check if the rates of reduction depend on the cell line used. The reduction of cis,trans,cis-[PtCl2(OCOCH3)2(NH3)2] by extracts of three cell lines was measured, and the rates follow the order A2780cisR > A2780 > HT-29. The reduction is not carried out by the low molecular weight (MW) antioxidants but primarily by cellular components with MW > 3000.


The minimum surface fibrinogen concentration necessary for platelet activation on dimethyldichlorosilane-coated glass.
Albumin and fibrinogen were competitively adsorbed onto dimethyldichlorosilane-coated glass (DDS-glass) and platelet activation was examined as a function of the surface fibrinogen concentration. The weight ratio of albumin to fibrinogen in the adsorption solution was varied from 10 to 700. Platelet activation was quantitated by the area and circularity of spread platelets. When the DDS-glass was coated with albumin alone, platelets were only contact adherent and could not spread at all. After competitive adsorption of fibrinogen and albumin, however, platelets were able to spread on the surface. Platelet activation increased linearly as the surface fibrinogen concentration increased up to 0.02 micrograms/cm2. Platelets were able to activate fully if the surface fibrinogen concentration was 0.02 micrograms/cm2 or higher, even though the surface was dominated by albumin. It appears that platelets can activate fully as long as only a small fraction (2-15%) of the surface is covered with tightly bound fibrinogen.


The fruitless effort of growing a fruitless tree: Early morpho-orthographic and morpho-semantic effects in sentence reading.
In this eye-tracking study, we investigated how semantics inform morphological analysis at the early stages of visual word identification in sentence reading. We exploited a feature of several derived Italian words, that is, that they can be read in a "morphologically transparent" way or in a "morphologically opaque" way according to the sentence context to which they belong. This way, each target word was embedded in a sentence eliciting either its transparent or opaque interpretation. We analyzed whether the effect of stem frequency changes according to whether the (very same) word is read as a genuine derivation (transparent context) versus as a pseudoderived word (opaque context). Analysis of the first fixation durations revealed a stem-word frequency effect in both opaque and transparent contexts, thus showing that stems were accessed whether or not they contributed to word meaning, that is, word decomposition is indeed blind to semantics. However, while the stem-word frequency effect was facilitatory in the transparent context, it was inhibitory in the opaque context, thus showing an early involvement of semantic representations. This pattern of data is revealed by words with short suffixes. These results indicate that derived and pseudoderived words are segmented into their constituent morphemes also in natural reading; however, this blind-to-semantics process activates morpheme representations that are semantically connoted.


Protection of rat primary hippocampal cultures from A beta cytotoxicity by pro-inflammatory molecules is mediated by astrocytes.
The brain of Alzheimer's disease patients shows abundant dystrophic neurites in close proximity to fibrillar beta-amyloid (A beta) plaques, and activated glial cells. We evaluated the influence of pro-inflammatory molecules (LPS + IFN-gamma) on A beta(1-42) neurotoxicity. 2 microM A beta(1-42) induced apoptosis of hippocampal cells and LPS + IFN-gamma reduced the apoptosis induced by A beta. However, LPS + IFN-gamma prevented apoptosis only in hippocampal cultures containing astrocytes. Also, LPS + IFN-gamma induced the secretion of TGF beta, a cytokine having neuroprotective effects, only in hippocampal cultures that contained astrocytes. Astrocytes had a regulatory effect over microglial and neuronal responses to A beta. The results suggest that LPS + IFN-gamma, traditionally considered as pro-apoptotic, reduced apoptosis induced by A beta through the activation of neuroprotective mechanisms mediated by astrocytes. We propose that astrocytes are pivotal in the modulation of inflammation of the CNS. The impairment of the regulatory functions performed by activated astrocytes could represent an important pathogenic mechanism for neurodegenerative diseases.


Mutational evidence that the VPg is involved in the replication and not the movement of Pea enation mosaic virus-1.
Pea enation mosaic disease is caused by an obligatory association between the enamovirus Pea enation mosaic virus-1 (PEMV-1) and the umbravirus Pea enation mosaic virus-2 (PEMV-2). Encapsidated RNAs 1 and 2 are covalently linked to a 3138 Da VPg encoded by the RNA of PEMV-1. To determine the role of the VPg in the pathogenicity of PEMV (PEMV-1+PEMV-2), the infectivity of clones with mutations in key amino acids in the VPg was evaluated in protoplasts and in plants. Using quantitative, real-time RT-PCR, we concluded that the inability of certain mutants to infect plants was due to their replicative (and not their movement) incompetence. Mutant clones that produced delayed and less severe infections accumulated 10- to 100-fold less RNA-1 compared to WT-RNA-1 both in plants and in protoplasts. The RNAs of clones that produced WT-like infections accumulated to levels similar to those of WT-PEMV. Also, we demonstrate that the severity of symptoms produced by WT-PEMV is proportional to the amount of RNA-1 that accumulates in infected plants and seems to be independent of the amount of RNA-2. A dual role for the VPg in the pathogenicity of PEMV is proposed.


Hypoplastic left heart syndrome repair. Preventing complications.
Hypoplastic left heart syndrome presents a special challenge for the neonatal/pediatric critical care nurse. The nurse plays a vital role in preventing the complications that may arise from the syndrome itself or the surgical repair. Here, the authors describe how to prevent complications following first stage palliation of hypoplastic left heart syndrome.


Pharmacologic myocardial perfusion stress tests. Adenosine thallium stress test.
Thallium-201 myocardial perfusion scintigraphy assists in detecting coronary artery disease and assessing the significance of known stenoses. An adenosine infusion protocol is discussed in conjunction with presentation of results obtained in a community hospital setting. Primary indications for pharmacologic stress maneuvers include: Evaluation of patients unable or unwilling to exercise to adequate levels of workload and patients undergoing preoperative evaluation (particularly in patients undergoing vascular surgery). Experience in a community hospital setting attests to the safety of this pharmacologic protocol while showing a diagnostic accuracy similar to results reported in peer review literature. The method has been readily received by referring internists and cardiologists and is associated with a 21% increase in nuclear myocardial perfusion stress tests during the first six months of 1991.


Correction to: KrioBlastTM as a New Technology of Hyper-fast Cryopreservation of Cells and Tissues. Part II. 2. Kinetic Vitrification of Human Pluripotent Stem Cells and Spermatozoa.
The title of the article should be «KrioBlastTM as a New Technology of Hyper-fast Cryopreservation of Cells and Tissues. Part II. 2. Kinetic Vitrification of Human Pluripotent Stem Cells and Spermatozoa».


[Treatment of inveterate unilateral dislocations of the mandible by open repositioning of the condyle and meniscectomy].
A new method for treating inveterate forms of mandibular luxation is described, after a brief review of conventional therapeutic procedures. The route of approach chosen provides wide exposure of the temporo-mandibular joint, the endoarticular approach ensuring protection of pericondylar venous plexuses and of the internal mammary artery by allowing section of the external pterygoid tendon and the performance of a juxta-cervical capsulotomy. Excellent results were obtained in two patients with unilateral inveterate dislocation of the mandible operated upon using this procedure.


Functional reorganization of adult cat somatosensory cortex is dependent on NMDA receptors.
We studied effects of selective blockade of N-methyl-D-aspartate (NMDA) receptors in the primary somatosensory cortex (SI) of the adult cat on reorganization of cortical maps after selective deafferentation. About two weeks after hindlimb deafferentation, cortical loci representing the 'trunk' seemingly expanded and 'migrated' into areas originally devoted to the 'hindlimb'. Selective blockade of NMDA receptors of the SI cells by continuous infusion of 2-amino-5-phosphonovalerate (APV) into the cortex disrupted such change. The APV treatment also depressed responses of SI cells to natural sensory stimulation, but left no long-lasting side effects. The results suggest that the processes of map reorganization take place within the SI and involve mechanisms dependent on NMDA-receptor-mediated activity.


Discovery of a new subclass of α-conotoxins in the venom of Conus australis.
Cone snails (Conus sp.) are poisonous animals that can be found in all oceans where they developed a venomous strategy to prey or to defend. The venom of these species contains an undeniable source of unique and potent pharmacologically active compounds. Their peptide compounds, called conotoxins, are not only interesting for the development of new pharmaceutical ligands, but they are also useful for studying their broad spectrum of targets. One conotoxin family in particular, the α-conotoxins, acts on nicotinic acetylcholine receptors (nAChRs) which dysfunctions play important roles in pathologies such as epilepsy, myasthenic syndromes, schizophrenia, Parkinson's disease and Alzheimer's disease. Here we define a new subclass of the α-conotoxin family. We purified the venom of a yet unexplored cone snail species, i.e. Conus australis, and we isolated a 16-amino acid peptide named α-conotoxin AusIA. The peptide has the typical α-conotoxin CC-Xm-C-Xn-C framework, but both loops (m/n) contain 5 amino acids, which has never been described before. Using conventional electrophysiology we investigated the response of synthetically made globular (I-III, II-IV) and ribbon (I-IV, II-III) AusIA to different nicotinic acetylcholine receptors. The α7 nAChR was the only receptor found to be blocked with a similar potency by both peptide-configurations. This suggests that both α5/5 conotoxin isomers might be present in the venom gland of C. australis. NMR spectroscopy showed that no secondary structures define the peptides' three-dimensional topology. Moreover, the ribbon configuration, which is generally considered to be non-native, is more stable than the globular isomer. Accordingly, our findings show relevancy concerning the α-conotoxin classification which might be helpful in the design of novel therapeutic compounds.


[Surgical treatment of aortic root aneurysm associating with infectious endocarditis].
From 1979 to 1989, aortic root aneurysms were encountered in 6 of the 30 patients who underwent surgical treatment for infectious endocarditis. Four patients underwent aortic valve replacement and direct or patch closure of the orifice of aortic root aneurysm. In additional 2 patients with infected aneurysm of right coronary sinus of Valsalva rupturing into the right ventricle, the aneurysm and infected tissue in the right ventricular outflow tract were completely resected and the defect of aortic sinus and VSD were closed with double Teflon fabric patches. All patients survived postoperatively, however, one patients died 1.5 months after the operation probably due to rupture of mycotic aneurysm of cerebral artery. Another late death seemed to be concerned with recurrent aortic root aneurysm, in which case direct closure of aneurysm had been performed. We believe that even if the aneurysm seems to be small, its orifice should be closed with the use of a fabric patch to prevent recurrent aneurysm formation.


Nephrotoxicity and hepatotoxicity in calves apparently caused by experimental feeding with Narthecium ossifragum.
Seven calves were fed a mixture of bog plants containing 15 g (wet matter) Narthecium ossifragum per kg live weight for two consecutive days. Their serum creatinine, urea and magnesium concentrations increased, whereas the serum calcium concentration decreased. Histopathological examination of the kidneys of the 5 calves that were killed revealed tubular epithelial cell degeneration and necrosis. There were signs of liver dysfunction in all the calves including increased aspartate aminotransferase (ASAT), glutamate dehydrogenase (GLDH) and gamma-glutamyltransferase activities. All the calves refused to ingest N. ossifragum after 2 days feeding, and their appetite for hay and concentrate was also reduced. It can be concluded that N. ossifragum is nephrotoxic and hepatotoxic to calves.


Recent results from clinical trials using SERMs to reduce the risk of breast cancer.
Selective estrogen receptor modulators (SERMs) are used for the treatment of invasive breast cancer. Chemoprevention is the use of specific natural or synthetic chemical agents to reverse, suppress, or prevent the progression of premalignant lesions to invasive carcinoma. The finding of a decrease in contralateral breast cancer incidence following tamoxifen administration for adjuvant therapy led to its use in breast cancer prevention. Four large trials have used tamoxifen, the prototypical SERM, as a breast cancer chemopreventive agent with differing results. In the National Surgical Adjuvant Breast and Bowel Project's (NSABP) Breast Cancer Prevention Trial (BCPT), tamoxifen reduced the risk of invasive breast cancer by 49%. Tamoxifen also reduced the incidence of benign breast disease as well as the number of breast biopsies in the treated women. Three other randomized prevention trials comparing tamoxifen with placebo have been reported and show a reduction in breast cancer incidence of 38%. Serum levels of estrone sulfate and testosterone are significantly associated with breast cancer risk, and estradiol appears to be more strongly associated with breast cancer in high-risk women. Raloxifene is comparable to tamoxifen in its ability to reduce the risk of breast cancer in postmenopausal, high-risk women and has fewer side effects, as shown in the study of tamoxifen and raloxifene. Several ongoing and planned studies will evaluate the ability of aromatase inhibitors to reduce the risk of breast cancer in women at increased risk.


Interferon-gamma independently activates the MHC class I antigen processing pathway and diminishes glucose responsiveness in pancreatic beta-cell lines.
The mouse pancreatic beta TC3 and beta TC6-F7 cell lines were used to characterize the effects of interferon-gamma (IFN-y) on beta-cell phenotype and function. Initially, intracellular and secreted insulin were compared in glucose-stimulated cells over time. A significant reduction in insulin content and secretion was observed on a per-cell basis in glucose-stimulated beta TC3 and beta TC6-F7 cells after 12 h of exposure to IFN-gamma. The steadystate level of pre-proinsulin mRNA expression was not affected by IFN-gamma. Thus, we postulate that IFN-gamma's inhibitory actions occur after transcription of pre-proinsulin genes. Time-course analysis of IFN-gamma-regulated mRNA expression of the two intra-MHC-encoded subunits of the proteasome (low-molecular-mass polypeptide [Lmp]-2 and Lmp-7) revealed a correlation between their induction and the inhibitory effects of IFN-gamma on glucose-stimulated insulin production. Increased expression of Lmp-2 and Lmp-7 mRNA was accompanied by a corresponding induction of LMP2 and LMP7 protein expression. Subsequently, major histocompatibility complex (MHC) class I cell-surface expression was significantly increased in IFN-gamma-treated beta TC3 and beta TC6-F7 cells. Exposure of IFN-gamma-treated beta-cells to a peptide aldehyde inhibitor of the proteasome (MG132) significantly attenuated MHC class I cell-surface expression but did not prevent the negative effects of IFN-gamma on glucose responsiveness. Enhanced expression of the MHC class I antigen processing and presentation pathway and diminished insulin production appear to be distinct pathological alterations in beta-cells exposed to the insulitic cytokine IFN-gamma.


Gene discovery in rheumatoid arthritis highlights the CD40/NF-kappaB signaling pathway in disease pathogenesis.
During the past several years, substantial progress has been made in the identification of genetic variants that predispose to rheumatoid arthritis (RA) and other autoimmune disorders. Progress in this area has been facilitated by the availability of new technology that allows for a much more comprehensive screen of the genome than was possible before, in conjunction with large samples of RA patients with well-characterized disease. Recent RA genetic studies have identified genes with important functions related to intracellular signaling mechanisms, transcription factors, cytokines, membrane receptors, costimulatory molecules, and enzymes. In particular, recent discoveries highlight the importance of the CD40/NF-kappaB signaling pathway in RA, based on genetic association with several genes relevant to this pathway, including CD40, TRAF1, TNFAIP3, and REL. Progress in the identification of genes that contribute to RA is proceeding at a very rapid pace. These genetic discoveries shed light on underlying disease mechanisms in RA and provide targets for the development of novel diagnostic and therapeutic tools for future use in this chronic inflammatory disorder.


High melamine migration in daily-use melamine-made tableware.
Melamine is commonly used to manufacture tableware, and this could be one of the important exposure sources in humans. The study aims to measure melamine migrated from different material-made tableware by the most sensitive technique of liquid chromatography-tandem mass spectrometry (LC-MS/MS). The test samples were filled with pre-warmed designated-temperature (from room temperature (∼20 °C), 30 °C, 40 °C, 50 °C, 60 °C, 70 °C, 80 °C, to 90 °C) simulant (either distilled water or 3% acetic acid) up to 20 ml and immersed in a water bath at that designated temperature for 15 or 30 minutes (min). High melamine migration levels, ranging from 6.97 to 19.03 μg/ml, can be measured from all melamine-made samples containing 20 ml 3% acetic acid in water bath of 90 °C for 30 min, whereas melamine cannot be detectable in all other material-made samples in the same condition. In addition, the cheaper the melamine-made tableware samples, the higher the melamine migration levels. The migration of melamine amount is dependent on different temperatures, contact times, simulant, and prices of tableware. Since tableware is used in daily life, it is prudent to cautiously select materials that contain foodstuffs.


Transjugular intrahepatic portosystemic shunt (TIPS); review of initial experience at Aga Khan University Hospital.
To retrospectively assess the therapeutic effectiveness and safety of transjugular intrahepafic portosystemic shunt (TIPS) in patients with portal hypertension related complications. Over a period of 7.5 years 19 patients (10 males and 9 females, age range 25-69 years) were referred for TIPS at our radiology department. Thirteen patients suffered from liver cirrhosis while 6 had Budd Chiari syndrome. All patients were evaluated with colour doppler ultrasonography and cross sectional imaging. Shunt procedures were performed under sedation or general anaesthesia through internal jugular approach. Metallic self expandable uncovered stents were placed in 15 patients and covered stent in 1 patient. Follow up of patency was evaluated with ultrasound in majority and by venography in some patients. Safety of the procedure and clinical outcome were analyzed. Indications of procedure included variceal bleeding (n=8), ascites (n=4), ascites and bleeding (n=1) and Budd-Chiari syndrome (n=6). Technical success rate was 84.21%. Complication rate was 10.53%. Three days mortality was 15.79%. Mean primary shunt patency was 306.62 +/- 533 days. During follow-up stent occlusion occurred in 5 patients (31.25%). Four of these patients underwent successful reintervention. Recurrence of symptoms occurred in 68.75% patients. TIPS is useful for management of complications of portal hypertension that are refractory to pharmacological and endoscopic treatment, however shunt stenosis or occlusion may cause recurrence of symptoms. Repeated interventions are often required to maintain shunt patency.


Evaluation of an instrument to assess the needs of men diagnosed with prostate carcinoma: an assessment of the validity and reliability of a self-administered questionnaire developed to measure the needs experienced by men diagnosed with prostate carcinoma.
This study was conducted to evaluate a self-administered questionnaire developed to measure the needs experienced by men diagnosed with prostate carcinoma (the Prostate Cancer Needs Questionnaire [PCNQv1.1]). The PCNQv1.1 was constructed in two parts. Part 1 measures the needs at diagnosis and initial treatment and Part 2 measures current needs. A random sample of 650 men diagnosed with prostate carcinoma who were being treated by a urologist of the Hunter Urology Group in Newcastle, New South Wales, Australia, were invited to participate in the study. They were sent by post the self-administered PCNQv1.1. Completed questionnaires were received from 385 men. Information provided on 100 additional men was considered ineligible. The principal components method of factor analysis with varimax orthogonal rotation identified eight factors with eigenvalues greater than 1, which accounted for 61.7% of the variance in Part 1 of the PCNQv1.1. Likewise, six factors were identified in Part 2, which accounted for 63.5% of the variance. Internal reliability coefficients (Cronbach alpha) were adequate for identified factors with values ranging from 0.70 to 0.88 for Part 1 and from 0.71 to 0.87 for Part 2. Test-retest reliability was acceptable with intraclass correlation coefficients ranging from 0.61 to 0.78 for Part 1 and from 0.60 to 0.82 for Part 2. These results suggest that the PCNQv1.1 is a valid and reliable instrument to assess the needs experienced by men diagnosed with prostate carcinoma.


Yersinia pestis autoagglutination factor is a component of the type six secretion system.
Autoagglutination (AA) is a protective phenotypic trait facilitating survival of bacteria in hostile environments and in the host during infection. Autoagglutination factors (AFs) that possess self-associating ability are currently characterized in many Gram-negative bacteria, but Yersinia pestis AFs are still a matter of debate. Previously, we have shown that AF of Hms(-) strain Y. pestis EV76 is a complex of the 17,485-kDa protein and a low-molecular-weight component with siderophore activity. Here, we identified the protein moiety of AF and examined its role in AA of Hms(+) and Hms(-)Y. pestis strains. Using MALDI-TOF MS of trypsin-hydrolyzed AF, we unambiguously identified the protein as YPO0502, which belongs to a family of Hcp-proteins forming pilus-like structures of the type six secretion system (T6SS). To address the role of YPO0502 in AA, we cloned ypo0502 in E. coli, overexpressed it in Y. pestis and constructed its knock-out mutant in Y. pestis. However, all these approaches failed: YPO0502 was not secreted in E. coli, formed inclusion bodies when overexpressed in Y. pestis, and could probably be compensated by other Hcp-like proteins in Y. pestis. In contrast, downregulation of ypo0502 expression by its antisense RNA supported the contribution of YPO0502 in AA of Hms(+) and Hms(-)Y. pestis strains. The results of the present study indicate that the Hcp-like component of T6SS encoded by ypo502 is involved in Y. pestis AA and suggest that at least one (ypo0499-0516) of the 6 T6SS clusters of Y. pestis is involved in bacterial interaction.


Magnetic resonance imaging in prostate cancer detection and management: a systematic review.
The aim of our work was to evaluate the role of multi-parametric magnetic resonance imaging (mpMRI) in detection and management of prostate cancer (PC); specifically investigating the efficacy of mpMRI-based biopsy techniques in terms of diagnostic yield of significant prostate neoplasm and the improved management of patients who choose conservative treatments or active surveillance. A systematic and critical analysis through Medline, Embase, Scopus and Web of Science databases was carried out in March 2016, following the PRISMA ("Preferred Reporting Items for Systematic Reviews and Meta-Analyses") statement. The search was conducted using the following key words: "MRI/TRUS-fusion biopsy," "PIRADS," "prostate cancer," "magnetic resonance imaging (MRI)," "multiparametric MRI (mpMRI)," "systematic prostate biopsy (SB)," "targeted prostate biopsy (TPB)." English language articles were reviewed for inclusion ability. Sixty-six studies were selected in order to evaluate the characteristics and limitations of traditional sample biopsy, the role of mpMRI in detection of PC, specifically the increased degree of diagnostic accuracy of targeted prostate biopsy compared to systematic biopsy (12 cores), and to transperineal saturation biopsies with trans-rectal ultrasound (TRUS) only. MpMRI can detect index lesions in approximately 90% of cases when compared to prostatectomy specimen. The diagnostic performance of biparametric MRI (T2w + DWI) is not inferior to mpMRI, offering valid options to diminish cost- and time-consumption. Since approximately 10% of significant lesions are still MRI-invisible, systematic cores biopsy seem to still be necessary. The analysis of the different techniques shows that in-bore MRI-guided biopsy and MRI/TRUS-fusion-guided biopsy are superior in detection of significant PC compared to visual estimation alone. MpMRI proved to be very effective in active surveillance, as it prevents underdetection of significant PC and it assesses low-risk disease accurately. In higher-risk disease, presurgical MRI may change the clinically-based surgical plan in up to a third of cases. Targeted prostate biopsy, guided by mpMRI, is able to improve diagnostic accuracy and to reduce the detection of insignificant PC. Since the negative predictive value (NPV) of mpMRI is still imperfect, systematic cores biopsy should not be omitted for optimal staging of disease. A process of a progressive and periodic evolution in the detection and radiological classification of prostate lesions (such as PIRADS), is still needed in patients in active surveillance and in radical prostatectomy planning.


Management of cardiogenic shock complicating acute myocardial infarction: The Henry Ford Hospital experience and review of the literature.
Cardiogenic shock complicating acute myocardial infarction (MI) carries a high mortality which in some series prior to 1980 exceeded 80%. Neither the use of inotropic and vasopressor agents nor intraaortic balloon counterpulsation was found to improve survival in this group of patients. Intravenous thrombolytic agents improve survival in patients with acute MI, but their role in cardiogenic shock is unknown. Reports of the use of surgical and mechanical interventions in patients with severe left ventricular dysfunction were examined to determine if there was any benefit to be derived from restoring blood flow to ischemic areas of the myocardium. It was found that urgent placement of intraaortic balloon counterpulsation followed by coronary bypass surgery may improve survival rates and successful coronary angioplasty also appeared to benefit patients with cardiogenic shock. Similar improvement in survival has been reported after successful coronary reperfusion. In surgical series with predominantly nonmechanical causes of shock, survival has varied from 40% to 88%. Data from our five-year experience in the management of MI patients with cardiogenic shock suggest that coronary revascularization with coronary angioplasty or bypass surgery improves survival in patients with cardiogenic shock especially when performed within 24 hours of the onset of shock.


Are one-stop shops acceptable? Community perspectives on one-stop shop models of sexual health service provision in the UK.
Traditionally, genitourinary medicine (GUM) and contraceptive services have been provided separately. Providing these services on one site, as a one-stop shop, has been suggested as a way of improving access to care. There is little evidence about the acceptability of such an approach. We aimed to assess acceptability of different one-stop shop models (a young people's, an all ages (mainstream) and a general practice service) of sexual health provision among different community groups. Between April and December 2005, 19 semi-structured interviews and 14 focus groups were conducted with young heterosexual men (n = 48), men who have sex with men (MSM; n = 46) and minority ethnic men and women (n = 28) across England. Knowledge of one-stop shops was limited. The concept was acceptable to participants (except MSM), although there was variation as to the preferred model. Young men and African individuals described distrust of general practice confidentiality, preferring young people's or mainstream models, respectively. South Asians associated stigma with GUM, preferring instead a general practice one-stop shop. Regardless of model, respondents expressed preference for one provider/one session to provide GUM and contraceptive care. In terms of acceptability there can be no blue print one-stop shop model. Local assessments should determine whether a one-stop shop would have public health benefit and if so how best one should be set up to maximise access. To accommodate client preference for one provider/session for their sexual health needs it may be that the development of "integrated training" for providers across clinical specialties is a more realistic way forward.


New microsurgical breast reconstruction using free paraumbilical perforator adiposal flaps.
Pedicled transverse rectus abdominis musculocutaneous (TRAM) flaps have generally been used for bilateral breast losses. The major disadvantages of this method are the total or partial loss of the rectus abdominis muscles and various resulting postoperative complications, such as abdominal bulging and lumbar pain. With the recent development of perforator flaps and supermicrosurgery with anastomosis of 0.5-mm caliber vessels, these serious complications can be overcome with a paraumbilical perforator adiposal flap, without sacrificing the rectus abdominis muscle. The breasts of a 57-year-old woman who had undergone a bilateral subcutaneous mastectomy, including silicone prostheses, were repaired simultaneously with this new method using free paraumbilical perforator adiposal flaps. This new method of breast augmentation with a vascularized adiposal flap and without any muscle component is minimally invasive; its advantages are the preservation of the rectus abdominis muscles and the short time elevation for the adiposal flap.


Revisiting the duty of care of the nonprofit director.
The current corporate responsibility environment has prompted interested stakeholders, including legislators and state charity law officials, to more closely evaluate what constitutes the proper exercise of the "duty of care" by the director of a nonprofit corporation. The authors review recent developments affecting duty-of-care obligations and conclude that corporate responsibility and related concepts are likely to require directors to give greater consideration to the exercise of their "oversight" obligations as subsumed within the duty of care. The Article identifies a number of recent instances in which state charity law officials and other third parties have raised issues associated with the proper exercise of directors' oversight obligation, and concludes that directors of nonprofits will require greater counseling on their duty-of-care obligations in order to reduce their liability profile in an increasingly contentious environment.


[September 11, 2001: experiencing post-traumatic stress disorder].
This article searches for a broader knowledge on the Post-Traumatic Stress Disorder (PTSD) after the author has experienced the tragedy occurred in September 2001 in New York. The article aims at reporting this life experience after the terrorist attacks by relating it to the PTSD as well as trying to interpret and to understand the event from the point of view of this personal experience. Thus, it is possible to contribute to the care of the clients who look for support and comfort after trauma experience and to help them with more knowledge by getting resources to face it and helping them in the search for both an integrated performance and well being.


[Myocardial scintigraphy with thallium-201 for evaluation of the patency of aorto-coronary bypasses in multiple vessel disease and multiple bypasses (author's transl)].
The reliability of myocardial scintigraphy with thallium-201 in evaluating the patency of aorto-coronary bypasses was examined. In addition to coronary angiography and ventriculography in 16 patients (42 stenosed vessels, 36 bypasses of which 22 were patent) quantitative myocardial scintigraphy was performed after maximum exercise and at rest, pre- and postoperatively. In general, 12 patients with postoperatively improved angina showed an improvement in their scintigram. The analysis of myocardial areas with a bypass showed a decrease of thallium uptake at rest in 39%, regardless of patency occlusion of the bypass. In 85% of these regions an increased thallium uptake was seen after exercise, again independent of the function of the bypass. The data show that myocardial scintigraphy with thallium-201 cannot be utilized in patients with multiple vessel disease and multiple bypasses to evaluate the patency of a particular bypass, but a general assessment is possible, whether myocardial perfusion has improved.