Comparison of explicit values clarification method (VCM), implicit VCM and no VCM decision aids for men considering prostate cancer screening: protocol of a randomized trial.

BACKGROUND: Screening with prostate-specific antigen (PSA) test for prostate cancer is considered a preference sensitive decision; meaning it does not only depend on what is best from a medical point of view, but also from a patient value standpoint. Decision aids are evidence-based tools which are shown to help people feel clearer about their values; therefore it has been advocated that decision aids should contain a specific values clarification method (VCM). VCMs may be either implicit or explicit, but the evidence concerning the best method is scarce. We aim to compare the perceived clarity of personal values in men considering PSA screening using decision aids with no VCM versus an implicit VCM versus an explicit VCM. METHODS: Male factory employees from an industrial facility in the Northern region of Portugal aged 50 to 69 years old will be randomly assigned to one of three decision aid groups used to support prostate cancer screening decisions: (i) decision aid with information only (control), (ii) decision aid with information plus an implicit VCM, (iii) decision aid with information plus an explicit VCM. Men will be allowed release time from work to attend a session at their workplace. After a brief oral presentation, those willing to participate in the study will fill the baseline questionnaire, plus a 5 point-Likert scale question about intentions to undergo screening, and will then receive the intervention materials to complete. We estimated a total sample size of 276 participants; with 92 in each group. The primary outcome will be the perceived clarity of personal values assessed by the Portuguese validated translation of the three subscales of the Decisional Conflict Scale. Secondary outcomes will be intention to be screened (before and after the intervention), the total score from the Decisional Conflict Scale and the self-report of having or not undergone screening at 6 months. DISCUSSION: This study will add to the body of evidence on the role of decision aids to support health preference-sensitive choices and provide further insight on the impact of different methods for eliciting people's values embedded within a decision aid. TRIAL REGISTRATION: NCT03988673 - clinicalTrials.gov (2019/06/17).

Self-reported cognitive function in a large international cohort of people with multiple sclerosis: associations with lifestyle and other factors.

BACKGROUND AND PURPOSE: We aimed to estimate the prevalence of perceived cognitive impairment (PCI) and explore its associations with lifestyle and disease characteristics in a large international cohort of people with multiple sclerosis (MS). METHODS: This study was a cross-sectional analysis. Participants rated their cognitive function over the preceding 4 weeks using four questions in a subscale within the Multiple Sclerosis Quality of Life questionnaire (MSQOL-54). These questions assessed perceived concentration, attention and memory by the patient and family/friends. Four definitions of PCI were derived, ranging from lowest to highest specificity. Associations with PCI were assessed by log-binomial regression. RESULTS: The prevalence of PCI in our sample ranged from 41.0% (95% confidence interval, 39.0-43.0) using the least-specific definition to 11.6% (95% confidence interval, 10.3-12.9) using the most specific definition. A number of factors were associated with PCI, increasing in magnitude as the definition specificity increased, including positive associations for smoking and body mass index, whereas physical activity, dietary quality and use of vitamin D/omega-3 supplements were inversely associated with PCI. CONCLUSIONS: Our study reports associations between healthy lifestyle behaviours and PCI in people with MS. Although reverse causality is a potential explanation for our findings, previous studies have shown comparable associations with healthy lifestyle and MS onset and progression. Subject to external validation, these results suggest benefits realized from a healthy lifestyle in people with MS.

Paravertebral block in paediatric abdominal surgery-a systematic review and meta-analysis of randomized trials.

The increased popularity of paravertebral block (PVB) can be attributed to its relative safety and comparable efficacy when compared with epidural analgesia. It has thus been recommended for open cholecystectomy and other less painful surgeries such as inguinal herniorraphy and appendectomy. We performed a systematic review of PVB in paediatric abdominal conditions to assess its clinical efficacy and side effects compared with other analgesic therapies.A search of Medline, Embase, and Web of Science and hand-searching references from inception date to May 2016 was done. Relevant studies were randomized clinical trials in patients 0-18 years old comparing PVB (single shot or continuous catheter) with any comparator and analgesic medication. Pain scores, rescue analgesia and adverse events were compared.The systematic reviews identified six trials enrolling 358 paediatric patients. PVB medications included bupivacaine, ropivacaine, lidocaine, and fentanyl. Surgical procedures included inguinal herniorraphy, cholecystectomy, and appendectomy. The standardized mean difference in early pain scores favoured PVB: 0.85 [95% confidence interval (CI) 0.12-1.58] at 4-6 h and 0.64 (95% CI 0.28-1.00) at 24 h. One study reported a reduced length of stay. Parental [odds ratio (OR) 5.12 (95% CI 2.59-10.1)] and surgeon [OR 6.05 (95% CI 2.25-16.3)] satisfaction were higher in those receiving a PVB. No major complications occurred with a PVB.PVB resulted in minimally improved pain scores for up to 24 h after surgery, reduced rescue analgesia requirements, and increased surgeon and parental satisfaction. PVB is a good alternative to caudal and ilioinguinal block in paediatric abdominal surgery.

Prion filament networks in [URE3] cells of Saccharomyces cerevisiae.

The [URE3] prion (infectious protein) of yeast is a self-propagating, altered form of Ure2p that cannot carry out its normal function in nitrogen regulation. Previous data have shown that Ure2p can form protease-resistant amyloid filaments in vitro, and that it is aggregated in cells carrying the [URE3] prion. Here we show by electron microscopy that [URE3] cells overexpressing Ure2p contain distinctive, filamentous networks in their cytoplasm, and demonstrate by immunolabeling that these networks contain Ure2p. In contrast, overexpressing wild-type cells show a variety of Ure2p distributions: usually, the protein is dispersed sparsely throughout the cytoplasm, although occasionally it is found in multiple small, focal aggregates. However, these distributions do not resemble the single, large networks seen in [URE3] cells, nor do the control cells exhibit cytoplasmic filaments. In [URE3] cell extracts, Ure2p is present in aggregates that are only partially solubilized by boiling in SDS and urea. In these aggregates, the NH(2)-terminal prion domain is inaccessible to antibodies, whereas the COOH-terminal nitrogen regulation domain is accessible. This finding is consistent with the proposal that the prion domains stack to form the filament backbone, which is surrounded by the COOH-terminal domains. These observations support and further specify the concept of the [URE3] prion as a self-propagating amyloid.

Prion domain initiation of amyloid formation in vitro from native Ure2p.

The [URE3] non-Mendelian genetic element of Saccharomyces cerevisiae is an infectious protein (prion) form of Ure2p, a regulator of nitrogen catabolism. Here, synthetic Ure2p1-65 were shown to polymerize to form filaments 40 to 45 angstroms in diameter with more than 60 percent beta sheet. Ure2p1-65 specifically induced full-length native Ure2p to copolymerize under conditions where native Ure2p alone did not polymerize. Like Ure2p in extracts of [URE3] strains, these 180- to 220-angstrom-diameter filaments were protease resistant. The Ure2p1-65-Ure2p cofilaments could seed polymerization of native Ure2p to form thicker, less regular filaments. All filaments stained with Congo Red to produce the green birefringence typical of amyloid. This self-propagating amyloid formation can explain the properties of [URE3].

Prions in Saccharomyces and Podospora spp.: protein-based inheritance.

Genetic evidence showed two non-Mendelian genetic elements of Saccharomyces cerevisiae, called [URE3] and [PSI], to be prions of Ure2p and Sup35p, respectively. [URE3] makes cells derepressed for nitrogen catabolism, while [PSI] elevates the efficiency of weak suppressor tRNAs. The same approach led to identification of the non-Mendelian element [Het-s] of the filamentous fungus Podospora anserina, as a prion of the het-s protein. The prion form of the het-s protein is required for heterokaryon incompatibility, a normal fungal function, suggesting that other normal cellular functions may be controlled by prions. [URE3] and [PSI] involve a self-propagating aggregation of Ure2p and Sup35p, respectively. In vitro, Ure2p and Sup35p form amyloid, a filamentous protein structure, high in beta-sheet with a characteristic green birefringent staining by the dye Congo Red. Amyloid deposits are a cardinal feature of Alzheimer's disease, non-insulin-dependent diabetes mellitus, the transmissible spongiform encephalopathies, and many other diseases. The prion domain of Ure2p consists of Asn-rich residues 1 to 80, but two nonoverlapping fragments of the molecule can, when overproduced, induce the de nova appearance of [URE3]. The prion domain of Sup35 consists of residues 1 to 114, also rich in Asn and Gln residues. While runs of Asn and Gln are important for [URE3] and [PSI], no such structures are found in PrP or the Het-s protein. Either elevated or depressed levels of the chaperone Hsp104 interfere with propagation of [PSI]. Both [URE3] and [PSI] are cured by growth of cells in millimolar guanidine HCl. [URE3] is also cured by overexpression of fragments of Ure2p or fusion proteins including parts of Ure2p.

Prions: Portable prion domains.

Self-propagating abnormal proteins, prions, have been identified in yeast; asparagine/glutamine-rich 'prion domains' within these proteins can inactivate the linked functional domains; new prion domains and reporters have been used to make 'synthetic prions', leading to discoveries of new natural prions.

Cross-species prediction of human survival probabilities for accelerated anthrax vaccine absorbed (AVA) regimens and the potential for vaccine and antibiotic dose sparing.

Anthrax vaccine adsorbed (AVA, BioThrax) was recently approved by the Food and Drug Administration (FDA) for a post-exposure prophylaxis (PEP) indication in adults 18-65years of age. The schedule is three doses administered subcutaneous (SC) at 2-week intervals (0, 2, and 4weeks), in conjunction with a 60-day course of antimicrobials. The Public Health Emergency Medical Countermeasures Enterprise (PHEMCE) developed an animal model to support assessment of a shortened antimicrobial PEP duration following Bacillus anthracis exposure. A nonhuman primate (NHP) study was completed to evaluate the efficacy of a two dose anthrax vaccine absorbed (AVA) schedule (0, 2weeks) aerosol challenged with high levels of B. anthracis spores at week4- the time point at which humans would receive the third vaccination of the approved PEP schedule. Here we use logistic regression models to combine the survival data from the NHP study along with serum anthrax lethal toxin neutralizing activity (TNA) and anti-PA IgG measured by enzyme linked immunosorbent assay (ELISA) data to perform a cross-species analysis to estimate survival probabilities in vaccinated human populations at this time interval (week4 of the PEP schedule). The bridging analysis demonstrated that high levels of NHP protection also yield high predicted probability of human survival just 2weeks after the second dose of vaccine with the full or half antigen dose regimen. The absolute difference in probability of human survival between the full and half antigen dose was estimated to be at most approximately 20%, indicating that more investigation of the half-antigen dose for vaccine dose sparing strategies may be warranted.

Evaluation of early immune response-survival relationship in cynomolgus macaques after Anthrax Vaccine Adsorbed vaccination and Bacillus anthracis spore challenge.

Anthrax Vaccine Adsorbed (AVA, BioThrax) is approved by the US Food and Drug Administration for post-exposure prophylaxis (PEP) of anthrax in adults. The PEP schedule is 3 subcutaneous (SC) doses (0, 14 and 28 days), in conjunction with a 60 day course of antimicrobials. The objectives of this study were to understand the onset of protection from AVA PEP vaccination and to assess the potential for shortening the duration of antimicrobial treatment (http://www.phe.gov/Preparedness/mcm/phemce/Documents/2014-phemce-sip.pdf). We determined the efficacy against inhalation anthrax in nonhuman primates (NHP) of the first two doses of the PEP schedule by infectious challenge at the time scheduled for receipt of the third PEP dose (Day 28). Forty-eight cynomolgus macaques were randomized to five groups and vaccinated with serial dilutions of AVA on Days 0 and 14. NHP were exposed to Bacillus anthracis Ames spores on Day 28 (target dose 200 LD50 equivalents). Anti-protective antigen (PA) IgG and toxin neutralizing antibody (TNA) responses to vaccination and in post-challenge survivors were determined. Post-challenge blood and selected tissue samples were assessed for B. anthracis at necropsy or end of study (Day 56). Pre-challenge humoral immune responses correlated with survival, which ranged from 24 to 100% survival depending on vaccination group. Surviving, vaccinated animals had elevated anti-PA IgG and TNA levels for the duration of the study, were abacteremic, exhibited no apparent signs of infection, and had no gross or microscopic lesions. However, survivors had residual spores in lung tissues. We conclude that the first two doses of the PEP schedule provide high levels of protection by the scheduled timing of the third dose. These data may also support consideration of a shorter duration PEP antimicrobial regimen.

X-ray absorption and resonance raman spectroscopy of human myeloperoxidase at neutral and acid pH.

Myeloperoxidase (MPO), an important enzyme in the oxygen-dependent host defense system of human polymorphonuclear leukocytes, utilizes hydrogen peroxide to catalyze the production of hypochlorous acid, an oxidizing bactericidal agent. While MPO shows significant sequence homology with other peroxidases and this homology is particularly striking among the active-site residues, MPO exhibits unusual spectral features and the unique ability to catalyze the oxidation of chloride ions. We have investigated the MPO active-site with X-ray absorption (XAS) and resonance Raman (RRS) spectroscopies at neutral pH and also at the physiological acidic pH (pH approximately 3) and have compared these results with those of horseradish peroxidase (HRP). At pH 7.5, XAS results show that the iron heme active site is 6-coordinate where the distal ligand is likely nitrogen or oxygen, but not sulfur. The heme is distorted compared to HRP, other peroxidases, and heme compounds, but at pH approximately 3, the distal ligand is lost and the heme is less distorted. RRS results under identical pH conditions show that the skeletal core-size sensitive modes and v3 are shifted to higher frequency at pH approximately 3 indicating a 6- to 5-coordination change of high spin ferric heme. In addition, a new band at 270 cm(-1) is observed at pH approximately 3 which is consistent with the loss of the sixth ligand. The higher symmetry of the heme at pH approximately 3 is reflected by a single v4 mode in the (RRS) spectrum. HRP also loses its loosely associated distal water at this pH, but little change in heme distortion is observed. This change suggests that loss of the distal ligand in MPO releases stress on the heme which may facilitate binding of chloride ion.

Epidemiology of capsular and surface polysaccharide in Staphylococcus aureus infections complicated by bacteraemia.

Staphylococcus aureus is a leading cause of serious hospital- and community-acquired infections. The discovery of serologically distinct capsular polysaccharides on the surface of clinical isolates has allowed the development of vaccines and passive protective immunity. We have studied patient characteristics, infection characteristics and the surface and capsular polysaccharide serotype distribution in patients with S. aureus infections complicated by bacteraemia admitted to VA hospitals in Maryland between 1995 and 2000. Nine hundred and ninety-three blood cultures from 331 patients were positive for S. aureus. Thirty-eight percent of patients had diabetes, 11% had end-stage renal failure, and 23% were injection drug users. Forty-two percent of infections were caused by methicillin-resistant strains (MRSA), and 60% were acquired during hospitalization. Serotyping of the first available isolate per patient (N=234 isolates) using polyclonal antibodies showed three major phenotypes--42%, type 8 (T8) capsule; 50%, type 5 (T5) capsule; and 8%, 336 polysaccharide. MRSA isolates were significantly more likely to be T5 than methicillin-susceptible isolates (66% vs. 39%, P<0.001). The proportion of T5 MRSA increased significantly (years 1-2: 41%; years 3-4: 65%; years 5-6: 90%, P<0.001). This large sample of patients with serious S. aureus infection confirms that capsular polysaccharides T5 and T8 cause most human infections, and together with serotype 336, account for nearly all those with bacteraemia.

Studies on substrate specificity of the hog liver flavin-containing monooxygenase. Anionic organic sulfur compounds.

The influence of anionic groups on interaction of nucleophilic sulfur compounds with the purified hog liver flavin-containing monooxygenase was evaluated from kinetic constants obtained with various dithiobenzoates, thiolbenzoates, and thiolalkylcarboxylic acids. All compounds tested bearing a single negative charge localized on sulfur were excellent substrates but derivatives with a carboxylic acid group one or two carbons removed from the heteroatom exhibited low or no substrate activity. The effect of a carboxylic acid group more distal from sulfur appeared to depend on steric factors that are not well defined. For instance, none of the carboxylic acids (C2-C8) bearing a single thiol on the terminal carbon were oxygenated at detectable rates, whereas dihydrolipoic acid appeared to be a substrate although the concentration required for half-maximal activity was quite high (approximately 2 mM). Lipoic acid was a much better substrate (Km = 0.12 mM), and kinetic constants obtained with lipoic acid analogues suggest that position of the negative charge relative to the dithiolane ring is critical, since increasing the length of the side chain increased the Km. None of the alicyclic disulfides or sulfides containing one or more carboxylic acid groups showed detectable substrate activity. However, the more lipophilic sulfur-containing fatty acids inhibited the enzyme which may mask their potential substrate activity.

Distress, personality, and mammography utilization among women with a family history of breast cancer.

The authors examined the impact of psychological distress and the personality construct of conscientiousness (as measured by the Neuroticism, Extraversion, and Openness-Five Factor Inventory) on mammography utilization among women who were at increased risk for breast cancer. Participants were 200 women who had at least 1 first degree relative with breast cancer. Overall, 80% of the participants had obtained a mammogram in the previous year. Analyses controlling for potential confounders (perceived risk, decisional balance, and physician recommendation for mammography), revealed that distress was negatively associated with mammography utilization among participants who were low in conscientiousness. Distress was not significantly related to mammography utilization among highly conscientious women. The results are discussed in terms of their implications regarding interventions designed to increase mammography utilization in this population.

Spousal negative responses to cancer patients: the role of social restriction, spouse mood, and relationship satisfaction.

This cross-sectional study examined perceptions of spousal negative behaviors in 219 cancer patients. A mediational model was proposed to explain why a spouse might respond negatively to an ill partner because of greater restriction on activities as functional impairment increases. A moderating effect of the spouse's marital satisfaction assessed 3 months before other study measures was also proposed. Results provided support for the proposed model. The relationship between increasing patient functional impairment and spousal negative behaviors was medicated by greater restriction in spouse activities, as well as spousal negative mood. A marginally significant moderating effect for marital satisfaction was found. Although these results must be replicated with a prospective study, the findings begin to shed light on why spouses might respond in negative ways to an ill partner.

Immunohistochemical detection of gastric mucin in normal and disease states.

At least seven human mucin genes have been described, which express glycoproteins MUC1-7 in various tissues. It has been shown that different mucins are expressed in various gastric disease states compared to the normal. In this study we used histochemical and immunohistochemical methods to determine the type and pattern of mucin in 54 patients with a variety of gastric conditions [i.e., normal controls, fetal stomachs, gastritis, low-grade dysplasia, intestinal metaplasia (associated with gastritis, benign ulcers, dysplasia, and cancer), early and advanced intestinal type adenocarcinoma, and diffuse adenocarcinoma]. We report for the first time the use of all seven MUC antibodies in the various conditions. Normal controls were immunoreactive for MUC4, 5, and 6 , and gastritis specimens showed similar results, although the latter showed more MUC1 immunoreactivity. Whereas early fetal stomach showed no MUC immunoreactivity, MUC4, 5, and 6 were present from the early second trimester onwards. There was no significant difference between dysplasia and intestinal metaplasia, both categories showing the presence of MUC2 and 3 predominantly. Early intestinal type adenocarcinomas did not show any mucins in the majority of cases. Advanced intestinal type adenocarcinomas showed immunoreactivity predominantly for MUC1, 5, and 6, as well as MUC2 in some cases. Diffuse adenocarcinomas showed strong positive MUC2 and 6 staining, and in some cases MUC5 and 7. In conclusion, we have shown different patterns of mucin immunoreactivity in various gastric disease states. Specimens with dysplasia, intestinal metaplasia, late intestinal type adenocarcinoma, and diffuse gastric cancer were characterized by increased diversity of mucin types, whereas early intestinal cancer showed loss of mucin immunoreactivity.

Experimental seizures in the frog (Rana pipiens).

We investigated the effects of chemical convulsants in the leopard frog. Systemic kainic acid (5-20 mg/kg) caused limbic-like seizures, with staring, catatonia, fasciculations, and severe motor seizures, which were almost always lethal. Intracerebral electroencephalographic (EEG) recordings showed spike or spike-and-wave patterns at 6-8 Hz that decreased in frequency and increased in amplitude, maximal at an electrode in the midline olfactory/telencephalic (OLF-M) region. With time, an interictal pattern of 100-200 microV periodic spikes developed, followed by diffuse suppression of all brain activity. Seizures induced by pentylenetetrazole (150-450 mg/kg) and bicuculline (5-10 mg/kg) were characterized by the abrupt onset of motor activity, which continued intermittently for several hours, followed by recovery. EEG recordings in animals treated with pentylenetetrazole showed rhythmic spike-and-wave bursts at 1.5-3 Hz that were maximal at OLF-M. Recordings from frogs treated with bicuculline showed repetitive 3-6 Hz spike-and-wave discharges maximal at OLF-M that were nearly constant in amplitude and at times became continuous. Strychnine (1-5 mg/kg) caused reversible seizures characterized by tonic extensions of the extremities, that seemed to originate in the spinal cord. Frogs with recurrent seizures from systemic cis-diamminedichloroplatinum II showed 4-8 Hz rhythmic spike-and-wave activity that gradually slowed in frequency and increased in amplitude. Thus, the frog's reactivity to convulsive agents is similar to that of mammals.

Strategies of social comparison among people with low self-esteem: self-protection and self-enhancement.

People with low self-esteem (LSE) seem to focus on self-protection; rather than trying to achieve gains for their self-esteem, they try to avoid losses. This research examined, in a social comparison context, the hypothesis that LSEs seek self-enhancement when they have an opportunity that is "safe," that is, carrying little risk of humiliation. Experiments 1 and 2 indicated that LSEs sought the most social comparisons after receiving success feedback, whereas high-self-esteem Ss (HSEs) sought the most comparisons after failure. Further results suggested that LSEs who succeeded were seizing a safe means of self-enhancement and that HSEs who failed were seeking to compensate for the failure. Also supporting this interpretation for LSEs was Experiment 3, in which LSEs who succeeded sought the most comparisons when such comparisons promised to be favorable. All three studies illustrate the value of a new measure of social comparison selection.

Evaluation of the insect parasitoids of Sirex noctilio (Hymenoptera: Siricidae) in Tasmania.

Sampling of Sirex noctilio F. and the insect parasitoids released in a forest of Pinus radiata D. Don near Hobart, Tasmania, has shown that the rhyssines, Megarhyssa nortoni (Cresson) and Rhyssa persuasoria (L.) were mainly responsible for reducing the level of the population of S. noctilio between 1965 and 1974. Parasitic nematodes were not present during this period. Key factor analysis indicates that in this forest the two species act as one delayed density-dependent factor, whereas Ibalia leucospoides Hochenw. is apparently density-independent, its ability to parasitize the host being regulated by conditions within the tree.

Weight reduction and fluid intake in an obese and fluid noncompliant ESRD patient.

This case study describes the application of a behavioral weight reduction program to an obese ESRD patient who was also fluid noncompliant. The major purpose of the study was to determine whether the behavioral weight reduction program could be successfully applied to a hemodialysis patient, and if so, what effect reduced caloric intake would have on fluid intake. Based on animal and human studies showing a strong relation between eating and drinking, it was expected that body weight reduction would be accompanied by reduced fluid intake. On the other hand, an alternative psychological hypothesis suggested that increased fluid intake might be substituted for reduced food intake. The results of the weight reduction program indicated that a successful weight reduction of 42 lbs was maintained over an 18-month follow-up period. However, fluid intake increased during periods when caloric intake was reduced. Overall, the results indicated that behavioral weight reduction programs can be successfully applied to weight reduction in obese hemodialysis patients but that ways to avoid increased fluid intake need to be carefully addressed by such programs.