Comparative study of meningitis dynamics across nine African countries: a global perspective

Background  

Meningococcal meningitis (MM) represents an important public health problem especially in the "meningitis belt" in Africa. Although seasonality of epidemics is well known with outbreaks usually starting in the dry season, pluri-annual cycles are still less understood and even studied. In this context, we aimed at study MM cases time series across 9 sahelo-sudanian countries to detect pluri-annual periodicity and determine or not synchrony between dynamics. This global and comparative approach allows a better understanding of MM evolution in time and space in the long-term.     

Changes in socioeconomic inequalities in cancer mortality rates among French men between 1968 and 1996

Objectives. We investigated changes in socioeconomic inequalities in cancer mortality rates among men in France between 1968 and 1996.Methods. We used a representative sample of 1% of the French population and studied 4 periods (1968–1974, 1975–1981, 1982–1988, and 1990–1996). Causes of death were obtained by direct linkage with the French national death registry. The socioeconomic position of men aged 35 to 59 years was measured by using the occupational class reported at the time of the census at the beginning of each period. Analyses were conducted for all cancers and specifically for lung, upper aerodigestive tract, esophageal, colorectal, and other cancers.Results. In all analyses, we observed socioeconomic inequalities during the 4 periods considered; the inequalities increased between the first and the last period. Most of the total increase occurred between 1968 and 1981, and inequalities remained stable thereafter. Inequalities were larger when men out of the labor force were included in the analysis. The strongest increase in socioeconomic inequalities over time was observed for upper aerodigestive tract cancer.Conclusions. Although cancer mortality rates have decreased, substantial socioeconomic inequalities in cancer mortality among men remain.Changes over time in socioeconomic inequalities in mortality rates by cause of death among men have been examined principally in northern Europe, the United States, and the United Kingdom.1^–7 In France, changes over time in socioeconomic inequalities in cause-specific mortality rates have not been examined extensively,8^,9 and little is known regarding cancer mortality rates. The study of cancer mortality rates is of special interest in France because cancer rather than cardiovascular disease is the leading cause of premature mortality (before the age of 65 years). A comparative study found that cancer mortality contributed to approximately 40% of socioeconomic inequalities in total mortality in France, Italy, and Switzerland, compared with fewer than 20% in the United Kingdom and northern Europe.10 A comparative study including Italy, the United Kingdom, and northern European countries and focusing on time trends in socioeconomic inequalities in mortality rates found that trends in socioeconomic inequalities in cardiovascular mortality rates accounted for a large part of the change in the socioeconomic inequalities in all-cause mortality rates in all countries except Italy.11In addition, mortality rates by cancer site have been investigated in a few studies, but none of them have included data for France. Most of them have considered lung cancer2^–4^,6^,7^,12 and less often colorectal cancers separately.6^,12 Few results are available on prostate6 and stomach cancer.4For lung cancer mortality rates, socioeconomic inequalities are observed in all countries; in France, large inequalities are also observed for non–lung cancer mortality rates.10 This is principally attributable to upper aerodigestive tract (UADT) cancers, which in France are both frequent and unequally distributed among social classes.13The situation in France is specific with regard to cancer mortality rates, with large socioeconomic inequalities in lung cancer and non–lung cancer mortality rates. Investigating changes in socioeconomic inequalities in cancer mortality rates by cancer site in this context may provide leads to identify factors associated with cancer incidence and survival, as well as to formulate prevention strategies.We describe changes in socioeconomic inequalities in cancer mortality among French men between 1968 and 1996.     

Progressive dilation of the diameter of the aortic root in adults with a bicuspid aortic valve

BACKGROUND: To determine the rate of progression of dilation of the aortic root in adults with a bicuspid aortic valve. METHODS: We reviewed retrospectively the transthoracic echocardiograms of 50 adults with a bicuspid aortic valve. Each patient had had at least two examinations made 12 months apart. Measurements were taken at four levels: at the basal attachment of the leaflets of the valve within the left ventricular outflow tract, at the widest point of the sinuses of Valsalva, at the sinutubular junction, and in the ascending aorta 1 cm beyond the sinutubular junction. RESULTS: Progressive dilation occurred at all levels, ranging from 0.3 mm/yr at the basal attachment within the left ventricular outflow tract to 1.0 mm/yr, 1 cm beyond sinutubular junction. These rates of dilation were greater than the reported rate of 0.8 mm per decade in the normal population. The rate of dilation found in the ascending aorta 1 cm beyond the sinutubular junction was significantly greater than at the other sites (p = 0.005). The 21 patients with baseline measurements greater than 34 mm had a significantly higher rate of progression (p = 0.007). Sex, age, and the degree of valvar obstruction or regurgitation did not significantly influence the rate of progression of dilation. CONCLUSION: There is a significantly higher rate of dilation of the aortic root in adults with a bicuspid aortic valve when compared to the normal population. Periodic evaluation of the ascending aorta is essential in these patients, even after replacement of the aortic valve. Other imaging modalities should be considered if the region beyond the sinutubular junction is not well visualized by transthoracic echocardiography.     

Expression of leukemia inhibitory factor (LIF) and its receptor gp190 in human liver and in cultured human liver myofibroblasts. Cloning of new isoforms of LIF mRNA

BACKGROUND: The cytokine leukemia inhibitory factor (LIF) mediates its biological effects through binding to its high affinity receptor made of the low-affinity LIF receptor subunit gp190 (LIF-R) and the gp130 subunit. LIF exerts several important effects in the liver, however, data on liver expression of LIF are scarce. The aim of this study was to examine the expression of LIF and LIF-R in human liver. RESULTS: LIF expression, analyzed by immunohistochemistry, was barely detectable in normal liver but was strong within cirrhotic fibrous septa and was found in spindle-shaped cells compatible with myofibroblasts. Accordingly, cultured human liver myofibroblasts expressed high levels of LIF as shown by ELISA and Northern blot. Biological assay demonstrated that myofibroblast-derived LIF was fully active. RT-PCR showed expression of the LIF-D and M isoforms, and also of low levels of new variants of LIF-D and LIF-M resulting from deletion of exon 2 through alternative splicing. LIF receptor expression was detected mainly as a continuous sinusoidal staining that was enhanced in cirrhotic liver, suggestive of endothelial cell and/or hepatocyte labeling. Immunohistochemistry, flow cytometry and STAT-3 phosphorylation assays did not provide evidence for LIF receptor expression by myofibroblasts themselves. LIF secretion by cultured myofibroblasts was down regulated by the addition of interleukin-4. CONCLUSIONS: We show for the first time the expression of LIF in human liver myofibroblasts, as well as of two new isoforms of LIF mRNA. Expression of LIF by myofibroblasts and of its receptor by adjacent cells suggests a potential LIF paracrine loop in human liver that may play a role in the regulation of intra-hepatic inflammation.     

Unprecedented heat-related deaths during the 2003 heat wave in Paris: consequences on emergency departments

In August 2003, France sustained an unprecedented heat wave that resulted in 14,800 excess deaths. The consequences were maximal in the Paris area. The Assistance Publique–H?pitaux de Paris reported more than 2600 excess emergency department visits, 1900 excess hospital admissions, and 475 excess deaths despite a rapid organization. Indeed, simple preventice measures before hospital admissions are only able to reduce mortality which mostly occurred at home and in nursing homes.     

Lexical learning of the English language: a PET study in healthy French subjects

To investigate the neural correlates of word learning in adults, 10 right-handed French subjects who had learned English without mastering it performed an English and a French naming task during two PET sessions, one before (PET1) and the second after (PET2) a 4-week lexical training in English. Behavioral performance was collected during the two PET exams and 2 months after (T3). At T2, performance on English naming increased in all subjects; this improvement persisted at T3, with no correlation between English performance at T2 and T3. Cerebral activation during French naming mainly showed a left frontal temporal network. The pattern specifically associated with English lexical learning included, in addition to the anterior cingulate cortex involved in attentional processing and BAs 4/6 reflecting speech output, the right cerebellum and the left insular cortex that are linked to speech gesture learning, and the right medial temporal regions, likely to reflect the involvement of episodic memory during verbal learning. Correlations between English T2/T1 performance and English T2/T1 rCBF changes reinforced the hypothesis of intervention of episodic memory since they interested right frontal, hippocampal, and lateral temporal regions. 'Predictive' correlations between English T3/T2 performance and English T2/T1 rCBF changes showed, in good reminders, increased activities in the left posterior superior temporal sulcus and middle temporal cortex probably related to efficient semantic storage of learned words.     

Prognostic value of the pulmonary dead-space fraction during the first 6 days of acute respiratory distress syndrome

BACKGROUND: The ratio of pulmonary dead space to tidal volume (VD/VT) in acute respiratory distress syndrome (ARDS) is reported to be between 0.35 and 0.55. However, VD/VT has seldom been measured with consideration to the evolving pathophysiology of ARDS. METHODS: We made serial VD/VT measurements with 59 patients who required mechanical ventilation for > or = 6 days. We measured VD/VT within 24 h of the point at which the patient met the American-European Consensus Conference criteria for ARDS, and we repeated the VD/VT measurement on ARDS days 2, 3, and 6 with a bedside metabolic monitor during volume-regulated ventilation. We analyzed the changes in VD/VT over the 6-day period to determine whether VD/VT has a significant association with mortality. RESULTS: VD/VT was significantly higher in nonsurvivors on day 1 (0.61 +/- 0.09 vs 0.54 +/- 0.08, p < 0.05), day 2 (0.63 +/- 0.09 vs 0.53 +/- 0.09, p < 0.001), day 3 (0.64 +/- 0.09 vs 0.53 +/- 0.09, p < 0.001), and day 6 (0.66 +/- 0.09 vs 0.51 +/- 0.08, p < 0.001). CONCLUSION: In ARDS a sustained VD/VT elevation is characteristic of nonsurvivors, so dead-space measurements made beyond the first 24 hours may have prognostic value.     

DC-SIGN-mediated infectious synapse formation enhances X4 HIV-1 transmission from dendritic cells to T cells

Dendritic cells (DCs) are essential for the early events of human immunodeficiency virus (HIV) infection. Model systems of HIV sexual transmission have shown that DCs expressing the DC-specific C-type lectin DC-SIGN capture and internalize HIV at mucosal surfaces and efficiently transfer HIV to CD4+ T cells in lymph nodes, where viral replication occurs. Upon DC-T cell clustering, internalized HIV accumulates on the DC side at the contact zone (infectious synapse), between DCs and T cells, whereas HIV receptors and coreceptors are enriched on the T cell side. Viral concentration at the infectious synapse may explain, at least in part, why DC transmission of HIV to T cells is so efficient.Here, we have investigated the role of DC-SIGN on primary DCs in X4 HIV-1 capture and transmission using small interfering RNA-expressing lentiviral vectors to specifically knockdown DC-SIGN. We demonstrate that DC-SIGN- DCs internalize X4 HIV-1 as well as DC-SIGN+ DCs, although binding of virions is reduced. Strikingly, DC-SIGN knockdown in DCs selectively impairs infectious synapse formation between DCs and resting CD4+ T cells, but does not prevent the formation of DC-T cells conjugates.Our results demonstrate that DC-SIGN is required downstream from viral capture for the formation of the infectious synapse between DCs and T cells. These findings provide a novel explanation for the role of DC-SIGN in the transfer and enhancement of HIV infection from DCs to T cells, a crucial step for HIV transmission and pathogenesis.