Silver nanoparticle uptake in the human lung assessed through in-vitro and in-silico methods.

Silver nanoparticles (AgNP) are commonly used in medical, cosmetics, clothing, and industrial applications for their antibacterial and catalytic properties. As AgNP become more prevalent, the doses to which humans are exposed may increase and pose health risks, particularly through incidental inhalation. This exposure was evaluated through in-vitro methods simulating lung fluids and lung epithelium, and through computational fluid dynamics (CFD) methods of AgNP transport. A high-dose scenario simulated a short-term inhalation of 10 µg AgNP/m3, based on an exposure limit recommended by the National Institute of Occupational Safety and Health for the case of a health-care worker who handles AgNP-infused wound dressings, and regularly wears AgNP-imbedded clothing. Bioaccessibility tests were followed by a Parallel Artificial Membrane Permeability Assay (PAMPA) and supported by CFD models of the lung alveoli, membrane, pores, and blood capillaries. Results indicate that such exposure produces an average and maximum AgNP flux of approximately 4.7 × 10-21 and 6.5 × 10-19 mol m-2·s-1 through lung tissue, respectively, yielding a blood-silver accumulation of 0.46-64 mg per year, which may exceed the lowest adverse effect level of 25 mg for an adult male. Results from in-silico simulations were consistent with values estimated in vitro (within an order of magnitude), which suggest that CFD models may be used effectively to predict silver exposure from inhaled AgNP. Although the average short-term exposure concentrations are 3 orders of magnitude smaller than the reported threshold for mammalian cytotoxicity effects (observed at 5000 ppb), cumulative effects resulting from constant exposure to AgNP may pose risks to human health in the long-term, with predicted bioaccumulation reaching potential toxic effects after only five months of exposure, based on maximum flux.

Splice variant PRKC-ζ(-PrC) is a novel biomarker of human prostate cancer.

BACKGROUND: Previously, using gene-knockdown techniques together with genome expression array analysis, we showed the gene protein Kinase C (PKC)-zeta (PRKCZ) to mediate the malignant phenotype of human prostate cancer. However, according to NCBI, the gene has undergone several major iterations. Therefore, to understand the relationship between its structure and biological activities, we have analysed its expressed sequence in prostate cancer cell lines and tissues. METHODS: Transcriptome-walking and targeted PCR were used to sequence the mRNA transcribed from PRKCZ. Hydropathy analysis was employed to analyse the hypothetical protein sequence subsequently translated and to identify an appropriate epitope to generate a specific monoclonal antibody. RESULTS: A novel sequence was identified within the 3'-terminal domain of human PRKCZ that, in prostate cancer cell lines and tissues, is expressed during transcription and thereafter translated into protein (designated PKC-ζ(-PrC)) independent of conventional PKC-ζ(-a). The monoclonal antibody detected expression of this 96 kD protein only within malignant prostatic epithelium. INTERPRETATION: Transcription and translation of this gene sequence, including previous intronic sequences, generates a novel specific biomarker of human prostate cancer. The presence of catalytic domains characteristic of classic PKC-ß and atypical PKC-ι within PKC-ζ(-PrC) provides a potential mechanism for this PRKCZ variant to modulate the malignant prostatic phenotype out-with normal cell-regulatory control.

Characterization of susceptibility and carrier status of burbot, Lota lota (L.), to IHNV, IPNV, Flavobacterium psychrophilum, Aeromonas salmonicida and Renibacterium salmoninarum.

In this study, susceptibility and potential carrier status of burbot, Lota lota, were assessed for five important fish pathogens. Burbot demonstrated susceptibility and elevated mortality following challenge with infectious haematopoietic necrosis virus (IHNV) by immersion and to Aeromonas salmonicida by intraperitoneal (i.p.) injection. IHNV persisted in fish for at least 28 days, whereas A. salmonicida was not re-isolated beyond 17 days post-challenge. In contrast, burbot appeared refractory to Flavobacterium psychrophilum following intramuscular (i.m.) injection and to infectious pancreatic necrosis virus (IPNV) by immersion. However, i.p injection of IPNV resulted in re-isolation of virus from fish for the duration of the 28 day challenge. Renibacterium salmoninarum appeared to induce an asymptomatic carrier state in burbot following i.p. injection, but overt manifestation of disease was not apparent. Viable bacteria persisted in fish for at least 41 days, and bacterial DNA isolated by diagnostic polymerase chain reaction was detected from burbot kidney tissue 90 days after initial exposure. This study is the first to investigate susceptibility of burbot to selected fish pathogens, and this information will aid in efforts to culture and manage this species.

Irish Aid

Irish Aid is the Government of Ireland’s programme of assistance to developing countries.Ireland has had an official development assistance programme since 1974. It has grown steadily over the years from modest beginnings to its current size (total ODA in 2008 is estimated to be €899 million).Ireland’s development cooperation policy is an integral part of Ireland’s wider foreign policy. Our aid philosophy is rooted in our foreign policy, in particular its objectives of peace and justice. Our development cooperation policy and programme reflect our longstanding commitment to human rights and fairness in international relations and are inseparable from Irish foreign policy as a whole.

Debriefing after failed paediatric resuscitation: a survey of current UK practice.

OBJECTIVES: Debriefing is a form of psychological "first aid" with origins in the military. It moved into the spotlight in 1983, when Mitchell described the technique of critical incident stress debriefing. To date little work has been carried out relating to the effectiveness of debriefing hospital staff after critical incidents. The aim of this study was to survey current UK practice in order to develop some "best practice" guidelines. METHODS: This study was a descriptive evaluation based on a structured questionnaire survey of 180 lead paediatric and emergency medicine consultants and nurses, selected from 50 UK trusts. Questions collected data about trust policy and events and also about individuals' personal experience of debrief. Free text comments were analyzed using the framework method described for qualitative data. RESULTS: Overall, the response rate was 80%. 62% said a debrief would occur most of the time. 85% reported that the main aim was to resolve both medical and psychological and emotional issues. Nearly all involve both doctors and nurses (88%); in over half (62%) other healthcare workers would be invited, eg, paramedics, students. Sessions are usually led by someone who was involved in the resuscitation attempt (76%). This was a doctor in 80%, but only 18% of responders said that a specifically trained person had led the session. Individuals' psychological issues would be discussed further on a one-to-one basis and the person directed to appropriate agencies. Any strategic working problems highlighted would be discussed with a senior member of staff and resolved via clinical governance pathways. CONCLUSIONS: Little is currently known about the benefits of debriefing hospital staff after critical incidents such as failed resuscitation. Debriefing is, however, widely practised and the results of this study have been used to formulate some best practice guidelines while awaiting evidence from further studies.

Evaluation of lethal and non-lethal sampling methods for the detection of white sturgeon iridovirus infection in white sturgeon, Acipenser transmontanus (Richardson).

Pectoral fin tissue of white sturgeon was investigated as a potential non-lethal sample source for the detection of white sturgeon iridovirus (WSIV) infection. Histopathology and polymerase chain reaction (PCR) results using fin tissue were compared with the standard lethal histopathology sampling method that utilizes head tissue. Tissues for each of the three sampling methods were collected weekly for 8 weeks from individual sturgeon undergoing an experimental cohabitation challenge with fish infected with the Abernathy isolate of WSIV. Non-lethal fin histopathological evaluation did not reveal infection during the first 3 weeks of sampling, while non-lethal PCR and the lethal method were variable. However, all three sampling methods were equally capable of identifying infection from 4 to 8 weeks post-exposure. Of the survivors tested, all were negative by PCR and the lethal method, and only one fish was identified as being positive by non-lethal fin histopathology. In another experiment, all three sampling methods were applied to asymptomatic WSIV carriers in a case study conducted at the Kootenai Tribal Sturgeon Conservation Hatchery. Results showed that both lethal and non-lethal fin histopathology were equally effective in detecting infection, but PCR was unable to identify this strain of WSIV. Depending on the virus isolate, these results suggest that non-lethal sampling of fin tissue (histopathology or PCR) is comparable with the lethal sampling method at identifying WSIV infection once infection is established, and under certain circumstances may provide an alternative to lethal sampling.

Emergency department investigation of deep vein thrombosis.

OBJECTIVES: To apply a previously validated clinical model for predicting pre-test probability of deep vein thrombosis (DVT) to patients attending an emergency department with symptoms suggestive of DVT and assess its reproducibility in the patient population. To measure the diagnostic value of the SimpliRED D-dimer assay in effectively excluding DVT. METHOD: Prospective study between March 1999 and October 2000 of adult patients attending with suspected DVT. Patients were assessed using Wells' clinical prediction tool and risk stratified. SimpliRED D-dimer estimations were then performed and compression ultrasonography arranged. The pre-test probabilities of DVT in the low, moderate, and high risk groups of Wells' original cohort were compared with the authors' figures and the sensitivity, specificity, and predictive values of the SimpliRED assay calculated for the patient population. RESULTS: Application of Wells' criteria to patients in the department permitted stratification into high, moderate, and low risk groups (prevalence of DVT 58.3%, 8.9%, and 1.5% respectively). SimpliRED D-dimer assay sensitivity was 63.4% with specificity of 74.8%, with a likelihood ratio of 2.52 for a positive test and 0.49 for a negative test. CONCLUSIONS: Clinical risk stratification allowed patients to be categorised into high, moderate, and low risk groups, albeit with less discriminatory power than originally described by Wells. The low sensitivity of the SimpliRED D-dimer assay when used routinely in a busy emergency department raises substantial doubt over the use of this test to rule out DVT, even in low risk patients.

Open label tissue plasminogen activator for stroke: the Oregon experience.

BACKGROUND: Tissue plasminogen activator (t-PA) is the first effective treatment for stroke. This study sought to explore the outcome of patients treated with t-PA in the community after approval of its use in the treatment of stroke in June, 1996. METHODS: All patients with acute stroke within the 6-hospital Oregon Stroke Center network were screened for potential t-PA treatment. Baseline and 24-hour outcome assessments were performed with the use of the National Institutes of Health Stroke Scale (NIHSS) and computed tomography (CT); 3-month outcome was evaluated by using the Modified Rankin scale. RESULTS: Thirty-three patients who met the criteria for t-PA therapy were treated within 3 hours of symptom onset. All but 2 strokes were in the anterior circulation; 48.5% were cardioembolic. The NIHSS scores at 24 hours after administration of t-PA (mean, 14.7) showed modest gains from baseline NIHSS scores (mean, 16.6). Twelve patients (36%) had minimal or no deficits at 3 months. Three patients (9%), all of whom had baseline NIHSS scores of 20 or more, had symptomatic intracranial hemorrhages, 2 of which were fatal (6%). CONCLUSION: This study shows the feasibility of treating acute stroke with t-PA in the community. The percentage of fully recovered patients at 3 months mirrored those in the National Institute of Neurologic Disorders and Stroke (NINDS) trial.

Subtle neurological deficits and psychopathological findings in substance-abusing homeless and non-homeless veterans.

This study evaluated the hypothesis that homeless individuals would display higher levels of neurological deficits than non-homeless individuals, particularly in frontal lobe or executive functions. Eighteen acutely homeless, 15 chronically homeless, and 20 non-homeless individuals admitted to an inpatient psychiatric service received a battery of neurological and psychosocial measures. In comparison to non-homeless subjects with comparable levels of psychopathology, homeless individuals showed higher levels of hostility, prior criminal activity, and family history of psychiatric illness, but lower levels of depression. A positive relationship between hostility and neurological soft signs was observed among chronically homeless subjects. These results suggest that a substantial subset of nonpsychotic homeless veterans suffers from "occult" neurological deficits.

HIV/AIDS risk in heterosexual college students. A review of a decade of literature.

Empirical studies dealing with the psychosocial correlates of HIV risk among heterosexual college students are reviewed, including findings related to such theoretical variables as HIV/AIDS-related knowledge, personal and partner's attitudes toward condom use, perceived susceptibility, communication with sex partners, and sexual self-efficacy. Although college students are highly knowledgeable about basic HIV/AIDS facts, they retain some misperceptions about disease transmission. They hold neutral-to-negative hedonistic and practical attitudes about using condoms: those who have engaged in risky behavior accurately perceive their greater susceptibility to infection and experience anxiety regarding transmission of HIV infection. Heterosexual college students communicate infrequently with their partners about safer sex, but they often agree to a partner's suggestion that they use condoms. Higher levels of sexual self-efficacy among college students have been associated with a lower risk for HIV transmission. Limitations and clinical implications of the findings and recommendations for future interventions are discussed.

HIV risk correlates among non-injection cocaine dependent men in treatment.

Guided by the AIDS Risk Reduction Model (ARRM), psychosocial correlates of HIV risk behavior were examined among noninjection cocaine dependent, heterosexual men (NI-CD-HM) in treatment. Subjects (N = 111) completed a structured interview to measure ARRM mediating variables and HIV risk behaviors. The results indicated that greater perceived susceptibility to contracting HIV, lower sexual self-efficacy, higher lifetime incidence of sexually transmitted diseases, and being under the influence of alcohol or other drugs during sex predicted having more sexual partners in the month prior to admission. Despite adequate knowledge of safer sex guidelines, subjects remained misinformed regarding certain aspects of HIV transmission. Men who perceived that their partners viewed condoms more positively and who exchanged drugs for sex were more likely to use condoms, yet condom use skills were typically inadequate to ensure effective prevention. These results suggest that HIV prevention interventions among NI-CD-HM should focus on improving knowledge, enhancing beliefs in the capacity to enact safer sex behaviors for preventing HIV and other STDs, building relevant skills (e.g., condom use, open sexual communication between partners), and emphasizing psychoactive substance abstinence. Couple interventions, in which partners actually rehearse safer sex negotiations, may be particularly effective in this regard.

G protein-mediated neuronal DNA fragmentation induced by familial Alzheimer's disease-associated mutants of APP.

Missense mutations in the 695-amino acid form of the amyloid precursor protein (APP695) cosegregate with disease phenotype in families with dominantly inherited Alzheimer's disease. These mutations convert valine at position 642 to isoleucine, phenylalanine, or glycine. Expression of these mutant proteins, but not of normal APP695, was shown to induce nucleosomal DNA fragmentation in neuronal cells. Induction of DNA fragmentation required the cytoplasmic domain of the mutants and appeared to be mediated by heterotrimeric guanosine triphosphate-binding proteins (G proteins).

The effect of damage of the brachium of the superior colliculus in neonatal and adult hamsters and the use of peripheral nerve to restore retinocollicular projections.

Using horseradish peroxidase (HRP) tracing technique, we were able to confirm the critical age in hamsters as reported previously (SO et al., 1981). Thus, following transection of the retinal fibers at the brachium of the superior colliculus (BSC) on postnatal-day 4 (P4) or later, no retinocollicular projections were observed in the adult stage. However, the retinal fibers were observed to reinnervate the superior colliculus (SC) if the BSC was cut on P3 or earlier. Physiological recording showed a close to normal retinocollicular map following a BSC damage on P0. Although retinal fibers did not reinnervate the SC following a BSC cut on or after P4, they could be observed to grow along a membrane over the damaged site. Bridging the site of BSC damage in adult hamsters using a segment of peripheral nerve (PN), retinal fibers labelled with WGA-HRP were observed to reinnervate the SC along the PN graft and visual evoked responses could be recorded in the SC showing the PN graft is effective in restoring damaged central visual pathways in adult mammals.

Policing pubs: what happens to crime?

The aim of this study was to test the effect of heightened police enforcement of the NSW Liquor and Registered Clubs Acts on overall criminal offences and, specifically, the number of assaults. Ten police patrols were included in the study. Five of these patrols were allocated to the experimental condition and five were allocated to the control condition. Beat police in the experimental controls conducted frequent but random visits to predesignated licensed premises over a 2-month period. Police in the control patrols maintained their normal duties. Numbers of offences in the experimental and control patrols were then compared for 2 months before the intervention, for the 2-month intervention phase and for 2 months post-intervention. Results of the study indicated a significant increase in the number of offences in the experimental patrols during the intervention phase. Reasons for this increase are discussed.