American Cancer Society guideline for the early detection of prostate cancer: update 2010.

In 2009, the American Cancer Society (ACS) Prostate Cancer Advisory Committee began the process of a complete update of recommendations for early prostate cancer detection. A series of systematic evidence reviews was conducted focusing on evidence related to the early detection of prostate cancer, test performance, harms of therapy for localized prostate cancer, and shared and informed decision making in prostate cancer screening. The results of the systematic reviews were evaluated by the ACS Prostate Cancer Advisory Committee, and deliberations about the evidence occurred at committee meetings and during conference calls. On the basis of the evidence and a consensus process, the Prostate Cancer Advisory Committee developed the guideline, and a writing committee drafted a guideline document that was circulated to the entire committee for review and revision. The document was then circulated to peer reviewers for feedback, and finally to the ACS Mission Outcomes Committee and the ACS Board of Directors for approval. The ACS recommends that asymptomatic men who have at least a 10-year life expectancy have an opportunity to make an informed decision with their health care provider about screening for prostate cancer after they receive information about the uncertainties, risks, and potential benefits associated with prostate cancer screening. Prostate cancer screening should not occur without an informed decision-making process. Men at average risk should receive this information beginning at age 50 years. Men in higher risk groups should receive this information before age 50 years. Men should either receive this information directly from their health care providers or be referred to reliable and culturally appropriate sources. Patient decision aids are helpful in preparing men to make a decision whether to be tested.

Early parenteral lipids and growth velocity in extremely-low-birth-weight infants.

BACKGROUND & AIMS: Whether early parenteral lipids improve postnatal growth of preterm neonates remains unclear. We aimed to assess the effects of parenteral lipids on growth velocity in extremely-low-birth-weight infants. METHODS: This retrospective cohort study included 121 extremely-low-birth-weight infants. The associations between parenteral lipids (cumulative intakes during the first week and delays in their introduction) and growth velocities (weight, head circumference and length) up to 28 days of life and to 36 weeks of corrected age were analysed using uni- and multivariate linear regression. RESULTS: Univariate analyses showed a significant positive association between the cumulative intakes of parenteral lipids during the first week and i) weight gain up to day 28; ii) weight gain up to 36 weeks of corrected age; iii) head circumference growth up to day 28. There was a negative correlation between the delay in parenteral lipid introduction and weight gain up to day 28. In multivariate analyses, the association between the cumulative intakes of parenteral lipids and weight gain up to 28 days was independent of gestational age at birth, birth weight, sex, smallness for gestational age, and enteral intakes (regression coefficient: 0.19; 95% CI: 0.01-0.38) and, up to 36 weeks, independent of gestational age, birth weight, sex, smallness for gestational age and parenteral glucose and amino acids (0.16; 95% CI: 0.04-0.27). CONCLUSIONS: Parenteral lipids during the first week were positively associated with weight gain in extremely-low-birth-weight infants and could improve early nutritional support of preterm neonates.

Safety of artemether-lumefantrine exposure in first trimester of pregnancy: an observational cohort.

BACKGROUND: There is limited data available regarding safety profile of artemisinins in early pregnancy. They are, therefore, not recommended by WHO as a first-line treatment for malaria in first trimester due to associated embryo-foetal toxicity in animal studies. The study assessed birth outcome among pregnant women inadvertently exposed to artemether-lumefantrine (AL) during first trimester in comparison to those of women exposed to other anti-malarial drugs or no drug at all during the same period of pregnancy. METHODS: Pregnant women with gestational age <20 weeks were recruited from Maternal Health clinics or from monthly house visits (demographic surveillance), and followed prospectively until delivery. RESULTS: 2167 pregnant women were recruited and 1783 (82.3%) completed the study until delivery. 319 (17.9%) used anti-malarials in first trimester, of whom 172 (53.9%) used (AL), 78 (24.4%) quinine, 66 (20.7%) sulphadoxine-pyrimethamine (SP) and 11 (3.4%) amodiaquine. Quinine exposure in first trimester was associated with an increased risk of miscarriage/stillbirth (OR 2.5; 1.3-5.1) and premature birth (OR 2.6; 1.3-5.3) as opposed to AL with (OR 1.4; 0.8-2.5) for miscarriage/stillbirth and (OR 0.9; 0.5-1.8) for preterm birth. Congenital anomalies were identified in 4 exposure groups namely AL only (1/164[0.6%]), quinine only (1/70[1.4%]), SP (2/66[3.0%]), and non-anti-malarial exposure group (19/1464[1.3%]). CONCLUSION: Exposure to AL in first trimester was more common than to any other anti-malarial drugs. Quinine exposure was associated with adverse pregnancy outcomes which was not the case following other anti-malarial intake. Since AL and quinine were used according to their availability rather than to disease severity, it is likely that the effect observed was related to the drug and not to the disease itself. Even with this caveat, a change of policy from quinine to AL for the treatment of uncomplicated malaria during the whole pregnancy period could be already envisaged.

Acute life-threatening extrinsic allergic alveolitis in a paint controller.

BACKGROUND: Occupational diisocyanate-induced extrinsic allergic alveolitis (EAA) is a rare and probably underestimated diagnosis. Two acute occupational EAA cases have been described in this context, but neither of them concerned hexamethylene diisocyanate (HDI) exposure. AIMS: To investigate the cause of a life-threatening EAA arising at work in a healthy 30-year-old female paint quality controller. METHODS: Occupational medical assessment, workplace evaluation, airborne and biological monitoring and immunodermatological tests. RESULTS: Diagnosis of EAA relied on congruent clinical and radiological information, confirmed occupational HDI exposure and positive IgG antibodies and patch tests. The patient worked in a small laboratory for 7 years, only occasionally using HDI-containing hardeners. While working with HDI for 6 h, she developed breathlessness, rapidly progressing to severe respiratory failure. Workplace HDI airborne exposure values ranged from undetectable levels to 4.25 p.p.b. Biological monitoring of urinary hexamethylene diamine in co-workers ranged from <1.0 to 15.4 μg/g creatinine. Patch tests 8 months later showed delayed skin reaction to HDI at 48 h. Subsequent skin biopsy showed spongiotic dermatitis with infiltration of CD4(+) and CD8(+) T cells. CONCLUSIONS: We believe this is the first reported case of acute life-threatening EAA following exposure to HDI. Low concentrations of airborne HDI and relatively high urinary hexamethylene diamine suggest significant skin absorption of HDI could have significantly contributed to the development of this acute occupational EAA.

Experience of meaning in life in bereaved informal caregivers of palliative care patients.

PURPOSE: Providing care for terminally ill family members places an enormous burden on informal caregivers. Meaning in life (MiL) may be a protective factor, but is jeopardised in caregiving and bereavement. This study evaluates the following questions: To what extent do bereaved informal caregivers of palliative care (PC) patients experience meaning in their lives? What differences emerge in carers compared to the general German population? How does MiL relate to well-being in former caregivers? METHODS: Eighty-four bereaved PC caregivers completed the Schedule for Meaning in Life Evaluation, the Brief Symptom Inventory, the WHOQOL-BREF, a single-item numerical rating scale of quality of life, and the Satisfaction with Life Scale. The experience of MiL of bereaved caregivers was compared to a representative population sample (n=977). RESULTS: The overall MiL fulfillment of bereaved caregivers (69 % female, age 55.5 ± 12.9 years) was significantly lower than in the general population (68.5 ± 19.2 vs. 83.3 ± 14, p<.001), as was the overall importance ascribed to their meaning framework (76.6 ± 13.6 vs. 85.6 ± 12.3, p< .001). PC caregivers are far more likely to list friends, leisure, nature/animals, and altruism. Higher MiL was correlated with better life satisfaction and quality of life. CONCLUSION: Coping with the loss of a loved one is associated with changes in MiL framework and considerably impairs a carer's experience of MiL fulfillment. Individual MiL is associated with well-being in PC caregivers during early bereavement. Specific interventions for carers targeted at meaning reconstruction during palliative care and bereavement are needed to help individuals regain a sense of meaning and purpose.

Circulatory adaptation to long-term high altitude exposure in Aymaras and Caucasians.

About 30 million people live above 2500 m in the Andean Mountains of South America. Among them are 5.5 million Aymaras, an ethnic group with its own language, living on the altiplano of Bolivia, Peru, and northern Chile at altitudes of up to 4400 m. In this high altitude region traces of human population go back for more than 2000 years with constant evolutionary pressure on its residents for genetic adaptation to high altitude. Aymaras as the assumed direct descendents of the ancient cultures living in this region were the focus of much research interest during the last decades and several distinctive adaptation patterns to life at high altitude have been described in this ethnic group. The aim of this article was to review the physiology and pathophysiology of circulatory adaptation and maladaptation to longtime altitude exposure in Aymaras and Caucasians.

Towards a consensus view on understanding nanomaterials hazards and managing exposure

The aim of this article is to present an overview of salient issues of exposure, characterisation and hazard assessment of nanomaterials as they emerged from the consensus-building of experts undertaken within the four year European Commission coordination project NanoImpactNet. The approach adopted is to consolidate and condense the findings and problem-identification in such a way as to identify knowledge-gaps and generate a set of interim recommendations of use to industry, regulators, research bodies and funders. The categories of recommendation arising from the consensual view address: significant gaps in vital factual knowledge of exposure, characterisation and hazards; the development, dissemination and standardisation of appropriate laboratory protocols; address a wide range of technical issues in establishing an adequate risk assessment platform; the more efficient and coordinated gathering of basic data; greater inter-organisational cooperation; regulatory harmonization; the wider use of the life-cycle approaches; and the wider involvement of all stakeholders in the discussion and solution-finding efforts for nanosafety.

Early diagenesis of bone and tooth apatite in fluvial and marine settings: Constraints from combined oxygen isotope, nitrogen and REE analysis

Fossil bones and teeth of Late Pleistocene terrestrial mammals from Rhine River gravels (RS) and the North Sea (NS), that have been exposed to chemically and isotopically distinct diagenetic fluids (fresh water versus seawater), were investigated to study the effects of early diagenesis on biogenic apatite. Changes in phosphate oxygen isotopic composition (delta O-18(PO4)), nitrogen content (wt.% N) and rare earth element (REE) concentrations were measured along profiles within bones that have not been completely fossilized, and in skeletal tissues (bone, dentine, enamel) with different susceptibilities to diagenetic alteration. Early diagenetic changes of elemental and isotopic compositions of apatite in fossil bone are related to the loss of the stabilizing collagen matrix. The REE concentration is negatively correlated with the nitrogen content, and therefore the amount of collagen provides a sensitive proxy for early diagenetic alteration. REE patterns of RS and NS bones indicate initial fossilization in a fresh water fluid with similar REE compositions. Bones from both settings have nearly collagen-free, REE-, U-, F- and Sr-enriched altered outer rims, while the collagen-bearing bone compacta in the central part often display early diagenetic pyrite void-fillings. However, NS bones exposed to Holocene seawater have outer rim delta O-18(PO4) values that are 1.1 to 2.6 parts per thousand higher compared to the central part of the same bones (delta O-18(PO4) = 18.2 +/- 0.9 parts per thousand, n = 19). Surprisingly, even the collagen-rich bone compacta with low REE contents and apatite crystallinity seems altered, as NS tooth enamel (delta O-18(PO4) =15.0 +/- 0.3 parts per thousand, n=4) has about 3%. lower delta O-18(PO4) values, values that are also similar to those of enamel from RS teeth. Therefore, REE concentration, N content and apatite crystallinity are in this case only poor proxies for the alteration of delta O-18(PO4) values. Seawater exposure of a few years up to 8 kyr can change the delta O-18(PO4) values of the bone apatite by > 3 parts per thousand. Therefore, bones fossilized in marine settings must be treated with caution for palaeoclimatic reconstructions. However, enamel seems to preserve pristine delta O-18(PO4) values on this time scale. Using species-specific calibrations for modern mammals, a mean delta O-18(H2O) value can be reconstructed for Late Pleistocene mammalian drinking water of around -9.2 +/- 0.5 parts per thousand, which is similar to that of Late Pleistocene groundwater from central Europe. (c) 2008 Elsevier B.V. All rights reserved.

Changing patterns of cancer incidence in the early- and late-HAART periods: the Swiss HIV Cohort Study.

BACKGROUND: The advent of highly active antiretroviral therapy (HAART) in 1996 led to a decrease in the incidence of Kaposi's sarcoma (KS) and non-Hodgkin's lymphoma (NHL), but not of other cancers, among people with HIV or AIDS (PWHA). It also led to marked increases in their life expectancy. METHODS: We conducted a record-linkage study between the Swiss HIV Cohort Study and nine Swiss cantonal cancer registries. In total, 9429 PWHA provided 20,615, 17,690, and 15,410 person-years in the pre-, early-, and late-HAART periods, respectively. Standardised incidence ratios in PWHA vs the general population, as well as age-standardised, and age-specific incidence rates were computed for different periods. RESULTS: Incidence of KS and NHL decreased by several fold between the pre- and early-HAART periods, and additionally declined from the early- to the late-HAART period. Incidence of cancers of the anus, liver, non-melanomatous skin, and Hodgkin's lymphoma increased in the early- compared with the pre-HAART period, but not during the late-HAART period. The incidence of all non-AIDS-defining cancers (NADCs) combined was similar in all periods, and approximately double that in the general population. CONCLUSIONS: Increases in the incidence of selected NADCs after the introduction of HAART were largely accounted for by the ageing of PWHA.

Passive immunization with neutralizing antibodies interrupts the mouse mammary tumor virus life cycle.

Mouse mammary tumor virus (MMTV) infects the host via mucosal surfaces and exploits the host immune system for systemic spread and chronic infection. We have tested a neutralizing rat monoclonal antibody specific for the retroviral envelope glycoprotein gp52 for its efficiency in preventing acute and chronic mucosal and systemic infection. The antibody completely inhibits the superantigen response and chronic viral infection following systemic or nasal infection. Surprisingly however, the antibody only partially inhibits the early infection of antigen-presenting cells in the draining lymph node. Despite this initially inefficient protection from infection, superantigen-specific B- and T-cell responses and systemic viral spread are abolished, leading to complete clearance of the retroviral infection and hence interruption of the viral life cycle. In conclusion, systemic neutralizing monoclonal antibodies can provide an efficient protection against chronic retroviral amplification and persistence.

Status Epilepticus Severity Score (STESS): a tool to orient early treatment strategy

BACKGROUND : Status epilepticus (SE) treatment ranges from small benzodiazepine doses to coma induction. For some SE subgroups, it is unclear how the risk of an aggressive therapeutic approach balances with outcome improvement. We recently developed a prognostic score (Status Epilepticus Severity Score, STESS), relying on four outcome predictors (age, history of seizures, seizure type and extent of consciousness impairment), determined before treatment institution. Our aim was to assess whether the score might have a role in the treatment strategy choice. METHODS : This cohort study involved adult patients in three centers. For each patient, the STESS was calculated before primary outcome assessment: survival vs. death at discharge. Its ability to predict survival was estimated through the negative predictive value for mortality (NPV). Stratified odds ratios (OR) for mortality were calculated considering coma induction as exposure; strata were defined by the STESS level. RESULTS : In the observed 154 patients, the STESS had an excellent negative predictive value (0.97). A favorable STESS was highly related to survival (P < 0.001), and to return to baseline clinical condition in survivors (P < 0.001). The combined Mantel-Haenszel OR for mortality in patients stratified after coma induction and their STESS was 1.5 (95 % CI: 0.59-3.83). CONCLUSION : The STESS reliably identifies SE patients who will survive. Early aggressive treatment could not be routinely warranted in patients with a favorable STESS, who will almost certainly survive their SE episode. A randomized trial using this score would be needed to confirm this hypothesis.

Transgenic reexpression of GLUT1 or GLUT2 in pancreatic beta cells rescues GLUT2-null mice from early death and restores normal glucose-stimulated insulin secretion.

GLUT2-null mice are hyperglycemic, hypoinsulinemic, hyperglucagonemic, and glycosuric and die within the first 3 weeks of life. Their endocrine pancreas shows a loss of first phase glucose-stimulated insulin secretion (GSIS) and inverse alpha to beta cell ratio. Here we show that reexpression by transgenesis of either GLUT1 or GLUT2 in the pancreatic beta cells of these mice allowed mouse survival and breeding. The rescued mice had normal-fed glycemia but fasted hypoglycemia, glycosuria, and an elevated glucagon to insulin ratio. Glucose tolerance was, however, normal. In vivo, insulin secretion assessed following hyperglycemic clamps was normal. In vitro, islet perifusion studies revealed that first phase of insulin secretion was restored as well by GLUT1 or GLUT2, and this was accompanied by normalization of the glucose utilization rate. The ratio of pancreatic insulin to glucagon and volume densities of alpha to beta cells were, however, not corrected. These data demonstrate that 1) reexpression of GLUT1 or GLUT2 in beta cells is sufficient to rescue GLUT2-null mice from lethality, 2) GLUT1 as well as GLUT2 can restore normal GSIS, 3) restoration of GSIS does not correct the abnormal composition of the endocrine pancreas. Thus, normal GSIS does not depend on transporter affinity but on the rate of uptake at stimulatory glucose concentrations.

Another way of thinking about ADHD: the predictive role of early attachment deprivation in adolescents' level of symptoms.

PURPOSE: Attention deficit and hyperactivity disorder (ADHD) is one of the most frequent disorders in childhood and adolescence. Both neurocognitive and environmental factors have been related to ADHD. The current study contributes to the documentation of the predictive relation between early attachment deprivation and ADHD. METHOD: Data were collected from 641 adopted adolescents (53.2 % girls) aged 11-16 years in five countries, using the DSM oriented scale for ADHD of the Child Behavior Checklist (CBCL) (Achenbach and Rescorla, Manual for the ASEBA school-age forms and profiles. University of Vermont, Research Center for Children, Youth and Families, Burlington, 2001). The influence of attachment deprivation on ADHD symptoms was initially tested taking into consideration several key variables that have been reported as influencing ADHD at the adoptee level (age, gender, length of time in the adoptive family, parents' educational level and marital status), and at the level of the country of origin and country of adoption (poverty, quality of health services and values). The analyses were computed using the multilevel modeling technique. RESULTS: The results showed that an increase in the level of ADHD symptoms was predicted by the duration of exposure to early attachment deprivation, estimated from the age of adoption, after controlling for the influence of adoptee and country variables. The effect of the age of adoption was also demonstrated to be specific to the level of ADHD symptoms in comparison to both the externalizing and internalizing behavior scales of the CBCL. CONCLUSION: Deprivation of stable and sensitive care in infancy may have long-lasting consequences for children's development.

Sources d'exposition aux phtalates dans une unité de soins néonatals [Phthalate exposure in the neonatal intensive care unit].

There are growing concerns on long-term health consequences, notably on fertility rates, of plasticizers such as phthalates. While di(2-ethylhexyl)phthalate (DEHP) is currently used in several medical devices, newborns in the neonatal intensive care unit are both more exposed and more vulnerable to DEHP. The objectives of this study were to identify, count, and describe possible sources of DEHP in a neonatal care unit. Our method consisted in the listing and the inspection of the information on packaging, complemented by contact with manufacturers when necessary. According to the results, 6% of all products and 10% of plastic products contained some DEHP; 71% of these involved respiratory support devices. A vast majority of the items showed no information on the content of DEHP. Further research is needed, particularly to determine the effects of such an early exposure and to study and develop safer alternatives.

Toxicokinetic modeling of folpet fungicide and its ring-biomarkers of exposure in humans.

A human in vivo toxicokinetic model was built to allow a better understanding of the toxicokinetics of folpet fungicide and its key ring biomarkers of exposure: phthalimide (PI), phthalamic acid (PAA) and phthalic acid (PA). Both PI and the sum of ring metabolites, expressed as PA equivalents (PAeq), may be used as biomarkers of exposure. The conceptual representation of the model was based on the analysis of the time course of these biomarkers in volunteers orally and dermally exposed to folpet. In the model, compartments were also used to represent the body burden of folpet and experimentally relevant PI, PAA and PA ring metabolites in blood and in key tissues as well as in excreta, hence urinary and feces. The time evolution of these biomarkers in each compartment of the model was then mathematically described by a system of coupled differential equations. The mathematical parameters of the model were then determined from best fits to the time courses of PI and PAeq in blood and urine of five volunteers administered orally 1 mg kg(-1) and dermally 10 mg kg(-1) of folpet. In the case of oral administration, the mean elimination half-life of PI from blood (through feces, urine or metabolism) was found to be 39.9 h as compared with 28.0 h for PAeq. In the case of a dermal application, mean elimination half-life of PI and PAeq was estimated to be 34.3 and 29.3 h, respectively. The average final fractions of administered dose recovered in urine as PI over the 0-96 h period were 0.030 and 0.002%, for oral and dermal exposure, respectively. Corresponding values for PAeq were 24.5 and 1.83%, respectively. Finally, the average clearance rate of PI from blood calculated from the oral and dermal data was 0.09 ± 0.03 and 0.13 ± 0.05 ml h(-1) while the volume of distribution was 4.30 ± 1.12 and 6.05 ± 2.22 l, respectively. It was not possible to obtain the corresponding values from PAeq data owing to the lack of blood time course data.