Cord blood neutropenia is an independent predictor of early sepsis.

OBJECTIVE: The significance of cord blood neutropenia as a screening tool for early-onset sepsis (EOS) is unclear. The objectives were to define reference values for cord blood neutrophil count and to determine the sensitivity and positive likelihood ratio of cord neutropenia for the detection of EOS. STUDY DESIGN: This retrospective observational cohort study included all mother-infant pairs with deliveries between 2009 and 2014 for whom cord neutrophil counts were routinely done. EOS cases were identified by interrogation of electronic charts. Maternal and perinatal factors were assessed to determine reference values of cord neutrophil. The diagnostic value of neutropenia for detecting EOS was assessed. A nested case-control design was used to measure the value of neutropenia in the detection of EOS in comparison with other risk factors. RESULTS: A total of 8,590 mother-infant pairs were included. We identified 84 sepsis cases. The neutrophil count was strongly associated with gestational age. Neutropenia adjusted for gestational age was strongly associated with EOS and had good specificity but poor sensitivity. The addition of neutropenia to other EOS risk factors increased sensitivity without decreasing specificity. CONCLUSION: Cord blood neutropenia was significantly associated with EOS and the addition of cord neutropenia to current EOS risk factors increased the detection rate of EOS.

Environmental contaminants and human health in the Canadian Arctic.

The third Canadian Arctic Human Health Assessment conducted under the Canadian Northern Contaminants Program (NCP), in association with the circumpolar Arctic Monitoring and Assessment Programme (AMAP), addresses concerns about possible adverse health effects in individuals exposed to environmental contaminants through a diet containing country foods. The objectives here are to: 1) provide data on changes in human contaminant concentrations and exposure among Canadian Arctic peoples; 2) identify new contaminants of concern; 3) discuss possible health effects; 4) outline risk communication about contaminants in country food; and 5) identify knowledge gaps for future contaminant research and monitoring. The nutritional and cultural benefits of country foods are substantial; however, some dietary studies suggest declines in the amount of country foods being consumed. Significant declines were found for most contaminants in maternal blood over the last 10 years within all three Arctic regions studied. Inuit continue to have the highest levels of almost all persistent organic pollutants (POPs) and metals among the ethnic groups studied. A greater proportion of people in the East exceed Health Canada's guidelines for PCBs and mercury, although the proportion of mothers exceeding these guidelines has decreased since the previous assessment. Further monitoring and research are required to assess trends and health effects of emerging contaminants. Infant development studies have shown possible subtle effects of prenatal exposure to heavy metals and some POPs on immune system function and neurodevelopment. New data suggest important beneficial effects on brain development for Inuit infants from some country food nutrients. The most successful risk communication processes balance the risks and benefits of a diet of country food through input from a variety of regional experts and the community, to incorporate the many socio-cultural and economic factors to arrive at a risk management decision that will be the most beneficial in Arctic communities.

Cancer incidence and mortality rates in Bermuda / Incidencia del cáncer y tasas de mortalidad en Bermuda

OBJECTIVE: To describe cancer and mortality rates in Bermuda and to compare such rates to those of the United States of America (USA). METHODS: Age-adjusted race-specific cancer incidence rates for Bermuda were calculated using the Bermuda Cancer Registry. These rates were then compared to USA cancer rates published by the National Cancer Institute. RESULTS: Overall age-adjusted incidence rate was 495 cases per 100 000for Blacks and 527 cases per 100 000 for Whites. Incident cases were more frequent among men than women in both races. For Blacks, the highest incidences were prostate for men and breast for women, followed by colon/rectum and lung cancer. For Whites, if we exclude benign skin cancers, the picture was similar with the notable exception of lung cancer being more frequent than colon/rectum in White males. When Bermuda's rates were compared to those of the USA, overall cancer rates were similar in both countries. Rates in Bermuda were higher for cancer of the mouth, ovarian cancer (Black women), melanoma (Whites), colorectal cancer (White women) and breast cancer (White women). Lung and colorectal cancers were less frequent in Bermuda s Black population. CONCLUSION: Further epidemiological studies are needed to identify potential risk factors that could contribute to these differences. Screening and prevention strategies could be adjusted accordingly.

OBJETIVO: Describir las tasas de cáncer y mortalidad en la Bermudas y comparar estas tasas con las de los Estados Unidos de América (EE. UU.). MÉTODOS: Las tasas de incidencia de cáncer específicas por raza y ajustadas por edad en Bermuda, se calcularon usando el Registro de Cáncer de Bermuda. Estas tasas fueron comparadas con las tasas de cáncer en los EE. UU. publicadas por el Instituto Nacional del Cáncer. RESULTADOS: La tasa general de incidencia ajustada por edad fue de 495 casos por 100 000 negros y 527 casos por 100 000 blancos. Los casos incidentes fueron más frecuentes entre los hombres que entre las mujeres en ambas razas. En el caso de los negros, las incidencias más altas estuvieron en la próstata para los hombres y en las mamas para las mujeres, seguidas por el cáncer de colon y recto, y el cáncer de pulmón. En el caso de los blancos, si se excluyen los cánceres benignos de la piel, el cuadro fue similar con la excepción notable de que el cáncer pulmonar fue más frecuente que el cáncer de colon y recto en los varones blancos. Cuando las tasas de Bermudas se compararon con las de EE.UU., las tasas generales de cáncer resultaron ser similares en ambos países. Las tasas en Bermuda fueron más altas para el cáncer de la boca, el cáncer ovárico (mujeres negras), el melanoma (blancos), el cáncer del colorectal (mujeres blancas), y el cáncer de mamas (mujeres blancas). Los cánceres de pulmón y colorectal fueron menos frecuentes en la población negra de Bermudas. CONCLUSIÓN: Se necesita continuar los estudios epidemiológicos a fin de identificar los factores de riesgo potenciales que podrían contribuir a estas diferencias. Las estrategias de pesquisaje y prevención podrían ajustarse en consecuencia con ello.

Cancer incidence and mortality rates in Bermuda.

OBJECTIVE: To describe cancer and mortality rates in Bermuda and to compare such rates to those of the United States of America (U.S.A.). METHODS: Age-adjusted race-specific cancer incidence rates for Bermuda were calculated using the Bermuda Cancer Registry. These rates were then compared to U.S.A. cancer rates published by the National Cancer Institute. RESULTS: Overall age-adjusted incidence rate was 495 cases per 100,000 for Blacks and 527 cases per 100,000 for Whites. Incident cases were more frequent among men than women in both races. For Blacks, the highest incidences were prostate for men and breast for women, followed by colon/rectum and lung cancer. For Whites, if we exclude benign skin cancers, the picture was similar with the notable exception of lung cancer being more frequent than colon/rectum in White males. When Bermuda's rates were compared to those of the U.S.A., overall cancer rates were similar in both countries. Rates in Bermuda were higher for cancer of the mouth, ovarian cancer (Black women), melanoma (Whites), colorectal cancer (White women) and breast cancer (White women). Lung and colorectal cancers were less frequent in Bermuda's Black population. CONCLUSION: Further epidemiological studies are needed to identify potential risk factors that could contribute to these differences. Screening and prevention strategies could be adjusted accordingly.

Monitoring of umbilical cord blood lead levels and sources assessment among the Inuit.

Analyses completed on samples collected between 1993 and 1996 showed that about 7% of 475 Inuit newborns from northern Quebec (Canada) had a cord blood lead concentration equal to or greater than 0.48 micromol/l, an intervention level adopted by many governmental agencies. A comparison between the cord blood lead isotope ratios of Inuit and southern Quebec newborns showed that lead sources for these populations were different. Our investigation suggests that lead shots used for game hunting were an important source of lead exposure in the Inuit population. A cohort study conducted in three Inuit communities shows a significant decrease of cord blood lead concentrations after a public health intervention to reduce the use of lead shot. Lead shot ammunition can be a major and preventable source of human exposure to lead.

Microbiological and inflammatory factors associated with the development of pneumococcal pneumonia.

Pneumococcal pneumonia still is associated with a high mortality rate, despite appropriate antimicrobial therapy. Many gaps remain in the understanding of the pathogenesis of this deadly infection. The microbial and inflammatory events that characterize survival or death after intranasal inoculation of mice with an LD(50) inoculum of Streptococcus pneumoniae were investigated. Survival was associated with rapid bacterial clearance and low inflammation (surfactant and red blood cells in alveoli), but no neutrophil recruitment or lung tissue injury was noted. By contrast, death was preceded by strong bacterial growth that peaked 48 h after the infection and was associated with gradual increases in pulmonary levels of interleukin-6, macrophage inflammatory protein (MIP)-1alpha, MIP-2, monocyte chemoattractant protein-1, KC, and neutrophil recruitment. The injection of tumor necrosis factor-alpha or the addition of lipopolysaccharide or heat-killed S. pneumoniae to the inoculum enhanced early host response and survival. These observations may help develop appropriate markers of evolution of pneumonia, as well as new therapeutic strategies.

Efficacy of recombinant human granulocyte colony-stimulating factor in a murine model of pneumococcal pneumonia: effects of lung inflammation and timing of treatment.

The effect of recombinant human granulocyte colony-stimulating factor (rhG-CSF) in a murine model of pneumococcal pneumonia was examined. Intranasal inoculations were 10(7) cfu/mouse (high inoculum) and 5 x 10(4) cfu/mouse (low inoculum) of Streptococcus pneumoniae, which induced severe or mild lung inflammation, respectively. With the low inoculum, rhG-CSF significantly improved survival when initiated 24 h or 10 min before, but not when initiated 24 h after, infection. Pretreatment with rhG-CSF significantly increased myeloperoxidase (MPO) activity in lungs 8 h after the infection and increased circulating neutrophil count 24, 48, and 72 h after infection. In contrast, rhG-CSF did not improve survival of animals infected with the high inoculum and did not increase MPO activity or neutrophil count in blood over those of sham-treated controls. These data strongly suggest that the severe inflammatory response typically observed in pneumococcal pneumonia recruits a maximum number of neutrophils in the lungs and thus masks the beneficial effect of rhG-CSF.

Heterogeneous nuclear ribonucleoprotein A1 and UP1 protect mammalian telomeric repeats and modulate telomere replication in vitro.

The heterogeneous nuclear ribonucleoprotein A1 protein and a shortened derivative (UP1) promote telomere elongation in mammalian cells. To gain insights into the function of A1/UP1 in telomere biogenesis, we have investigated the binding properties of recombinant A1/UP1 and derivatives to single-stranded DNA oligonucleotides. Our results indicate that UP1 prefers to bind to DNA carrying single-stranded telomeric extensions at the 3' terminus. The RNA recognition motif 1 is sufficient for strong and specific binding to oligomers carrying vertebrate telomeric repeats. We find that the binding of A1/UP1 protects telomeric sequences against degradation by endo- and exonucleases. Moreover, A1/UP1 binding prevents extension by telomerase and terminal deoxynucleotidyltransferase and inhibits rNTP-dependent DNA synthesis in vitro. These observations are consistent with the hypothesis that A1/UP1 is a telomere end-binding protein that plays a role in the maintenance of long 3' overhangs.

Activation of muscarinic receptors during blockade of GABA(A)-mediated inhibition induces synchronous epileptiform activity in immature rat hippocampus.

We investigated the effects of the cholinergic agonist carbachol (25 microM) on the synaptic potentials recorded extracellularly and intracellularly from the CA3 area of immature hippocampal slices of the rat (postnatal days 10-20). In control conditions, carbachol reduced the amplitude of evoked synaptic responses (n=8) and did not induce any spontaneous synchronous activity (n=12); the depressant effect of carbachol was mimicked by acetylcholine (100 microM, in eserine 10 microM, n=5) and was reversed by the muscarinic antagonist atropine (1 microM, n=2). The GABA(A)-receptor antagonist bicuculline (10 microM) enhanced the amplitude and duration of the evoked synaptic responses and induced infrequent (0.016-0.045 Hz) spontaneous synchronous discharges in 23/37 of the slices. Application of carbachol in the presence of bicuculline reduced the amplitude of the evoked synaptic responses (n=21) and in addition induced synchronous discharges with rates of occurrence 0.075-0.225 Hz, in 64/68 slices. Both effects were mimicked by acetylcholine and eserine, and antagonized by atropine. The specific muscarinic antagonists pirenzepine (M1-type), tripitramine (M2-type), 4-diphenylacetoxy-N-methylpiperidine methiodide (M3-type) and tropicamide (M4-type) (all tested at 0.1-1 microM) reversibly reduced the frequency of synchronous carbachol-induced discharges. In addition, these discharges were reversibly blocked by high Ca2+ perfusion medium (7 mM CaCl2, n=4) and by the glutamate receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (10 microM, n=7). Synchronous epileptiform discharges were recorded from both CA1 and CA3 areas in intact slices (n=3), but only from CA3 following disruption of the CA1-CA3 synaptic connections (n=3). These experiments suggest that activation of muscarinic receptors during blockade of GABA(A)-mediated potentials, may enhance synchronous epileptiform activity in immature (postnatal days 10-20) hippocampus, through activation of local excitatory circuits and that endogenous acetylcholine may be sufficient to play this role.