Asymptotically consistent numerical approximation of hemolysis

In a previous communication, we have proposed a numerical framework for the prediction of in vitro hemolysis indices in the preselection and optimization of medical devices. This numerical methodology is based on a novel interpretation of Giersiepen-Wurzinger blood damage correlation as a volume integration of a damage function over the computational domain. We now propose an improvement of this approach based on a hyperbolic equation of blood damage that is asymptotically consistent. Consequently, while the proposed correction has yet to be proven experimentally, it has the potential to numerically predict more realistic red blood cell destruction in the case of in vitro experiments. We also investigate the appropriate computation of the shear stress scalar of the damage fraction model. Finally, we assess the validity of this consistent approach with an analytical example and with some 3D examples.     

Targeting antibody responses to the membrane proximal external region of the envelope glycoprotein of human immunodeficiency virus

Although human immunodeficiency type 1 (HIV-1) infection induces strong antibody responses to the viral envelope glycoprotein (Env) only a few of these antibodies possess the capacity to neutralize a broad range of strains. The induction of such antibodies represents an important goal in the development of a preventive vaccine against the infection. Among the broadly neutralizing monoclonal antibodies discovered so far, three (2F5, Z13 and 4E10) target the short and hidden membrane proximal external region (MPER) of the gp41 transmembrane protein. Antibody responses to MPER are rarely observed in HIV-infected individuals or after immunization with Env immunogens. To initiate antibody responses to MPER in its membrane-embedded native conformation, we generated expression plasmids encoding the membrane-anchored ectodomain of gp41 with N-terminal deletions of various sizes. Following transfection of these plasmids, the MPER domains are displayed on the cell surface and incorporated into HIV virus like particles (VLP). Transfected cells displaying MPER mutants bound as efficiently to both 2F5 and 4E10 as cells transfected with a plasmid encoding full-length Env. Mice immunized with VLPs containing the MPER mutants produced MPER-specific antibodies, the levels of which could be increased by the trimerization of the displayed proteins as well as by a DNA prime-VLP boost immunization strategy. Although 2F5 competed for binding to MPER with antibodies in sera of some of the immunized mice, neutralizing activity could not be detected. Whether this is due to inefficient binding of the induced antibodies to MPER in the context of wild type Env or whether the overall MPER-specific antibody response induced by the MPER display mutants is too low to reveal neutralizing activity, remains to be determined.     

Identification and characterization of a melanocyte-specific novel 65-kDa peripheral membrane protein.

In order to study proteins of the melanosome, we developed a panel of antisera against various protein fractions of melanosomes from B16 melanoma cells. An antiserum raised against a Triton X-100 insoluble fraction of melanosomes recognized a 65-kDa protein in melanocytes from mice homozygous for the buff mutation, but not in their wild type counterparts. Further studies were conducted using a specific, second generation antiserum raised against the purified protein. The protein was also detected in melanocytes cultured from albino mice, but absent in cultured mouse cell lines not of melanocyte origin. Density gradient centrifugation of subcellular organelles and indirect immunofluorescent cell staining, indicated that the protein was associated with melanosomes and vesicles. The protein on intact organelles could be made soluble using sodium carbonate, and digested with proteases in the absence of detergent suggesting that it was a peripheral membrane protein localized on the cytosolic face of organelle membranes. Metabolic labelling of cells and N-glycosidase F digestion of cell extracts indicated that the protein was not N-glycosylated. Based on its intracellular localization and biochemical defects in the buff mouse, a potential role has been suggested for the 65-kDa protein in intracellular membrane trafficking.     

Unintended Pregnancies among Young Women Living in Urban Slums: Evidence from a Prospective Study in Nairobi City,Kenya

Background

Despite the significant proportion of young people residing in slum communities, little attention has been paid to the sexual and reproductive health (SRH) challenges they face during their transition to adulthood within this harsh environment. Little is known about the extent to which living in extreme environments, like slums, impact SRH outcomes, especially during this key developmental period. This paper aims to fill this research gap by examining the levels of and factors associated with unintended pregnancies among young women aged 15–22 in two informal settlements in Nairobi, Kenya.

Methods

We use data from two waves of a 3-year prospective survey that collected information from adolescents living in the two slums in 2007–2010. In total, 849 young women aged 15–22 were considered for analysis. We employed Cox and logistic regression models to investigate factors associated with timing of pregnancy experience and unintended pregnancy among adolescents who were sexually active by Wave 1 or Wave 2.

Findings

About two thirds of sexually experienced young women (69%) have ever been pregnant by Wave 2. For 41% of adolescents, the pregnancies were unintended, with 26% being mistimed and 15% unwanted. Multivariate analysis shows a significant association between a set of factors including age at first sex, schooling status, living arrangements and timing of pregnancy experience. In addition, marital status, schooling status, age at first sex and living arrangements are the only factors that are significantly associated with unintended pregnancy among the young women.

Conclusions

Overall, this study underscores the importance of looking at reproductive outcomes of early sexual initiation, the serious health risks early fertility entail, especially among out-of school girls, and sexual activity in general among young women living in slum settlements. This provides greater impetus for addressing reproductive behaviors among young women living in resource-poor settings such as slums.     

Epidemiology of yellow fever virus in humans,arthropods, and non-human primates in sub-Saharan Africa: A systematic review and meta-analysis

Yellow fever (YF) has re-emerged in the last two decades causing several outbreaks in endemic countries and spreading to new receptive regions. This changing epidemiology of YF creates new challenges for global public health efforts. Yellow fever is caused by the yellow fever virus (YFV) that circulates between humans, the mosquito vector, and non-human primates (NHP). In this systematic review and meta-analysis, we review and analyse data on the case fatality rate (CFR) and prevalence of YFV in humans, and on the prevalence of YFV in arthropods, and NHP in sub-Saharan Africa (SSA). We performed a comprehensive literature search in PubMed, Web of Science, African Journal Online, and African Index Medicus databases. We included studies reporting data on the CFR and/or prevalence of YFV. Extracted data was verified and analysed using the random effect meta-analysis. We conducted subgroup, sensitivity analysis, and publication bias analyses using the random effect meta-analysis while I² statistic was employed to determine heterogeneity. This review was registered with PROSPERO under the identification CRD42021242444. The final meta-analysis included 55 studies. The overall case fatality rate due to YFV was 31.1% (18.3–45.4) in humans and pooled prevalence of YFV infection was 9.4% (6.9–12.2) in humans. Only five studies in West and East Africa detected the YFV in mosquito species of the genus Aedes and in Anopheles funestus. In NHP, YFV antibodies were found only in members of the Cercopithecidae family. Our analysis provides evidence on the ongoing circulation of the YFV in humans, Aedes mosquitoes and NHP in SSA. These observations highlight the ongoing transmission of the YFV and its potential to cause large outbreaks in SSA. As such, strategies such as those proposed by the WHO’s Eliminate Yellow Fever Epidemics (EYE) initiative are urgently needed to control and prevent yellow fever outbreaks in SSA.     

Spatial patterns of light‐demanding tree species in the Yangambi rainforest (Democratic Republic of Congo)

Most Central African rainforests are characterized by a remarkable abundance of light‐demanding canopy species: long‐lived pioneers (LLP) and non‐pioneer light demanders (NPLD). A popular explanation is that these forests are still recovering from intense slash‐and‐burn farming activities, which abruptly ended in the 19th century. This “human disturbance” hypothesis has never been tested against spatial distribution patterns of these light demanders. Here, we focus on the 28 most abundant LLP and NPLD from 250 one‐ha plots distributed along eight parallel transects (~50 km) in the Yangambi forest. Four species of short‐lived pioneers (SLP) and a single abundant shade‐tolerant species (Gilbertiodendron dewevrei) were used as reference because they are known to be strongly aggregated in recently disturbed patches (SLP) or along watercourses (G. dewevrei). Results show that SLP species are strongly aggregated with clear spatial autocorrelation of their diameter. This confirms that they colonized the patch following a one‐time disturbance event. In contrast, LLP and NPLD species have random or weakly aggregated distribution, mostly without spatial autocorrelation of their diameter. This does not unambiguously confirm the “human disturbance” hypothesis. Alternatively, their abundance might be explained by their deciduousness, which gave them a competitive advantage during long‐term drying of the late Holocene. Additionally, a canonical correspondence analysis showed that the observed LLP and NPLD distributions are not explained by environmental variables, strongly contrasting with the results for the reference species G. dewevrei, which is clearly aggregated along watercourses. We conclude that the abundance of LLP and NPLD species in Yangambi cannot be unambiguously attributed to past human disturbances or environmental variables. An alternative explanation is that present‐day forest composition is a result of adaptation to late‐Holocene drying. However, results are inconclusive and additional data are needed to confirm this alternative hypothesis.     

Identification of citrullinated alpha-enolase as a candidate autoantigen in rheumatoid arthritis

Antibodies against citrullinated proteins are highly specific for rheumatoid arthritis (RA), but little is understood about their citrullinated target antigens. We have detected a candidate citrullinated protein by immunoblotting lysates of monocytic and granulocytic HL-60 cells treated with peptidylarginine deiminase. In an initial screen of serum samples from four patients with RA and one control, a protein of molecular mass 47 kDa from monocytic HL-60s reacted with sera from the patients, but not with the serum from the control. Only the citrullinated form of the protein was recognised. The antigen was identified by tandem mass spectrometry as alpha-enolase, and the positions of nine citrulline residues in the sequence were determined. Serum samples from 52 patients with RA and 40 healthy controls were tested for presence of antibodies against citrullinated and non-citrullinated alpha-enolase by immunoblotting of the purified antigens. Twenty-four sera from patients with RA (46%) reacted with citrullinated alpha-enolase, of which seven (13%) also recognised the non-citrullinated protein. Six samples from the controls (15%) reacted with both forms. Alpha-enolase was detected in the RA joint, where it co-localised with citrullinated proteins. The presence of antibody together with expression of antigen within the joint implicates citrullinated alpha-enolase as a candidate autoantigen that could drive the chronic inflammatory response in RA.     

Contrasted allometries between stem diameter,crown area,and tree height in five tropical biogeographic areas

Key message

Across five biogeographic areas, DBH-CA allometry was characterized by inter-site homogeneity and intra-site heterogeneity, whereas the reverse was observed for DBH-H allometry.

Abstract

Tree crowns play a central role in stand dynamics. Remotely sensed canopy images have been shown to allow inferring stand structure and biomass which suggests that allometric scaling between stems and crowns may be tight, although insufficiently investigated to date. Here, we report the first broad-scale assessment of stem vs. crown scaling exponents using measurements of bole diameter (DBH), total height (H), and crown area (CA) made on 4148 trees belonging to 538 species in five biogeographic areas across the wet tropics. Allometries were fitted with power functions using ordinary least-squares regressions on log-transformed data. The inter-site variability and intra-site (sub-canopy vs. canopy trees) variability of the allometries were evaluated by comparing the scaling exponents. Our results indicated that, in contrast to both DBH-H and H-CA allometries, DBH-CA allometry shows no significant inter-site variation. This fairly invariant scaling calls for increased effort in documenting crown sizes as part of tree morphology. Stability in DBH-CA allometry, indeed, suggests that some universal constraints are sufficiently pervasive to restrict the exponent variation to a narrow range. In addition, our results point to inverse changes in the scaling exponent of the DBH-CA vs. DBH-H allometries when shifting from sub-canopy to canopy trees, suggesting a change in carbon allocation when a tree reaches direct light. These results pave the way for further advances in our understanding of niche partitioning in tree species, tropical forest dynamics, and to estimate AGB in tropical forests from remotely sensed images.

     

Elevated total and isoenzyme forms of acid phosphatase in falciparum malaria

The activities of total serum acid phosphatase (E.C. 3.1.3.2) and of two of its isoenzymes, tartrate-resistant acid phosphatase and erythrocyte-specific acid phosphatase were measured in 109 adult male and female patients presenting acute falciparum malaria infection, and a normal, healthy control group comprised of 82 subjects. All the three forms of acid phosphatase were found to be significantly (p<0.05) higher during infection as compared to their activity in the control group. This result suggests that the measurement of acid phosphatase, particularly the erythrocyte isoenzyme, in serum could be potentially used as a biomarker of acute falciparum malaria infection.     

Viral Etiology of Respiratory Tract Infections in Children at the Pediatric Hospital in Ouagadougou (Burkina Faso)

Background

Acute respiratory infections (ARIs) are a major cause of morbidity and mortality in children in Africa. The circulation of viruses classically implicated in ARIs is poorly known in Burkina Faso. The aim of this study was to identify the respiratory viruses present in children admitted to or consulting at the pediatric hospital in Ouagadougou.

Methods

From July 2010 to July 2011, we tested nasal aspirates of 209 children with upper or lower respiratory infection for main respiratory viruses (respiratory syncytial virus (RSV), metapneumovirus, adenovirus, parainfluenza viruses 1, 2 and 3, influenza A, B and C, rhinovirus/enterovirus), by immunofluorescence locally in Ouagadougou, and by PCR in France. Bacteria have also been investigated in 97 samples.

Results

153 children (73.2%) carried at least one virus and 175 viruses were detected. Rhinoviruses/enteroviruses were most frequently detected (rhinovirus n = 88; enterovirus n = 38) and were found to circulate throughout the year. An epidemic of RSV infections (n = 25) was identified in September/October, followed by an epidemic of influenza virus (n = 13), mostly H1N1pdm09. This epidemic occurred during the period of the year in which nighttime temperatures and humidity were at their lowest. Other viruses tested were detected only sporadically. Twenty-two viral co-infections were observed. Bacteria were detected in 29/97 samples with 22 viral/bacterial co-infections.

Conclusions

This study, the first of its type in Burkina Faso, warrants further investigation to confirm the seasonality of RSV infection and to improve local diagnosis of influenza. The long-term objective is to optimize therapeutic management of infected children.