Background Rates of Adverse Pregnancy Outcomes for Assessing the Safety of Maternal Vaccine Trials in Sub-Saharan Africa

Background

Maternal immunization has gained traction as a strategy to diminish maternal and young infant mortality attributable to infectious diseases. Background rates of adverse pregnancy outcomes are crucial to interpret results of clinical trials in Sub-Saharan Africa.

Methods

We developed a mathematical model that calculates a clinical trial''s expected number of neonatal and maternal deaths at an interim safety assessment based on the person-time observed during different risk windows. This model was compared to crude multiplication of the maternal mortality ratio and neonatal mortality rate by the number of live births. Systematic reviews of severe acute maternal morbidity (SAMM), low birth weight (LBW), prematurity, and major congenital malformations (MCM) in Sub-Saharan African countries were also performed.

Findings

Accounting for the person-time observed during different risk periods yields lower, more conservative estimates of expected maternal and neonatal deaths, particularly at an interim safety evaluation soon after a large number of deliveries. Median incidence of SAMM in 16 reports was 40.7 (IQR: 10.6–73.3) per 1,000 total births, and the most common causes were hemorrhage (34%), dystocia (22%), and severe hypertensive disorders of pregnancy (22%). Proportions of liveborn infants who were LBW (median 13.3%, IQR: 9.9–16.4) or premature (median 15.4%, IQR: 10.6–19.1) were similar across geographic region, study design, and institutional setting. The median incidence of MCM per 1,000 live births was 14.4 (IQR: 5.5–17.6), with the musculoskeletal system comprising 30%.

Interpretation

Some clinical trials assessing whether maternal immunization can improve pregnancy and young infant outcomes in the developing world have made ethics-based decisions not to use a pure placebo control. Consequently, reliable background rates of adverse pregnancy outcomes are necessary to distinguish between vaccine benefits and safety concerns. Local studies that quantify population-based background rates of adverse pregnancy outcomes will improve safety assessment of interventions during pregnancy.     

Synthesis of RGD amphiphilic cyclic peptide as fibrinogen or fibronectin antagonist

Summary This paper investigates the effect of the incorporation of a diazaethylene glycol derivative (Deg,2) into a cyclic peptide containing the tripeptide sequence Arg-Gly-Asp (RGD). This motif is a common structural element of many integrin ligands. The synthesis of cyclo-(Arg-Gly-Asp-Deg) (7) has been accomplished in solution using standard peptide chemistry. The intent was to improve the bioavailability of this new RGD cyclic peptide, which is shown to interact with α_IIbβ₃ or α₅β₁ receptors. A preliminary step for the conformational study of peptide7 was done in DMSO-d ₆ using nuclear magnetic resonance spectroscopy techniques.     

The novel flightless-I gene brings together two gene families, actin- binding proteins related to gelsolin and leucine-rich-repeat proteins involved in Ras signal transduction

The Drosophila melanogaster gene flightless-I, involved in gastrulation and muscle degeneration, has Caenorhabditis elegans and human homologues. In these highly conserved genes, two previously known gene families have been brought together, families encoding the actin- binding proteins related to gelsolin and the leucine-rich-repeat (LRR) group of proteins involved in protein-protein interactions. Both these gene families exhibit characteristics of molecular changes involving replication slippage and exon shuffling. Phylogenetic analyses of 19 amino acid sequences of 6 related protein types indicate that actin- associated proteins related to gelsolin are monophyletic to a common ancestor and include flightless proteins. Conversely, comparison of 24 amino acid sequences of LRR proteins including the flightless proteins indicates that flightless proteins are members of a structurally related subgroup. Included in the flightless cluster are human and mouse rsp-1 proteins involved in suppressing v-Ras transformation of cells and the membrane-associated yeast (Saccharomyces cerevisae) adenylate cyclase whose analogous LRRs are required for interaction with Ras proteins. There is a strong possibility that ligands for this group could be related and that flightless may have a similar role in Ras signal transduction. It is hypothesized that an ancestral monomeric gelsolin precursor protein has undergone at least four independent gene reorganization events to account for the structural diversity of the extant family of gelsolin-related proteins and that gene duplication and exon shuffling events occurred prior to or at the beginning of multicellular life, resulting in the evolution of some members of the family soon after the appearance of actin-type proteins.      

Une nouvelle fonction pour la transferrine exprimée par le testicule

In men, oligozoospermia corresponds with a low level of transferrin in semen. Transferrin appears to be a relevant indicator of gonadal function. Transferrin expression in normal testes is perfectly controlled. Transferrin contributes to iron transport. However, recent results show the existence of a dimeric form, which acts as a powerful regulator of phagocytosis of residual bodies by Sertoli cells. A disturbance of this new highlighted function may account for some forms of oligozoospermia.     

Aspects cliniques, biologiques et thérapeutiques de la cryptorchidie diagnostiquée à l’âge adulte: analyse d’une série de 69 cas

Objective

To report the clinical, biological and therapeutic features of adult cryptorchidism and to determine whether orchidopexy at adulthood may improve male fertility.

Material and methods

We retrospectively studied the clinical pattern, biological and therapeutic features of 69 men aged of more than 18 years admitted for cryptorchidism at the urological department of Aristide-Le-Dantec teaching hospital between January 1999 and December 2007.

Results

The mean age of our patients was 31.04 ± 8.4 years. In the majority of cases, cryptorchidism was diagnosed in a context of infertility (38 cases), scrotum vacancy (21 cases) and testicular cancer (six cases). Cryptorchidism was unilateral in 69.5% and bilateral in 30.4% of cases. Semen analyses were done for 60 patients and showed azoospermia in 46.6%, oligozoospermia in 38.3% and a normal sperm count in 15% of cases. In all bilateral cryptorchidism cases, semen analyses showed azoospermia. At surgery, the undescended testis was found in 66 cases (95.6%) and orchidopexy was the most done surgical procedure. Seven patients (without testicular cancer) underwent unilateral orchiectomy and histology of specimens showed sertoli-cell-only syndrome with no spermatogenesis in all cases. The histological type of testicular cancer was seminoma (three cases) and embryonic carcinoma (three cases). In azoospermic men (28 cases) no induction of spermatogenesis was achieved after orchidopexy. In infertile patients, the improvement of sperm count was seen in three patients with unilateral cryptorchidism. Three patients with unilateral crytorchidism achieved pregnancy (pregnancy rate of 7.8%).

Conclusion

Orchidopexy for adult cryptorcidism had little impact in male fertility. Because of the risk of testicular cancer, orchidectomy was recommended as treatment of unilateral cryptorchidism. But with the recent development of TESE, orchidopexy appears as a reasonable treatment of adult cryptorchidism.     

Diatoms of Dindifelou fall (upper Basin of the Gambia River,Senegal): floristic inventory

The Dindifelou fall, located in south‐eastern Senegal, receives its water from discharging springs located in Dande plate‐land. These waters form, at the foot of the cliff, a pond that drains into the Thiokoye, a tributary of the Gambia River. The water quality of the pond and the stream is very good based on physicochemical analyses. Around the pond region, a microclimate characterized by a higher humidity and a lower temperature compared with the surrounding area is present. Diatoms study is carried out in different habitat types associated with this fall. The samples were taken by scraping the surface of rocks and rinsing fern leaves with sparkling water. Dande plate‐land is made of Upper Proterozoic sandstones whose gravity accumulations litter the bottom of the pond and the stream. This study allowed us to inventory 61 species and varieties of diatoms belonging to 28 genera. The most represented genera are Achnanthidium (ten species), Eunotia and Pinnularia (eight species each). Twelve species and varieties are reported for the first time in Senegambia including five of the genera Achnanthidium. The microflora is dominated by Achnantidium minutissimum and Achnanthidium catenatum, followed by Ulnaria ulna and various species of the genera Eunotia and Brachysira. Aerial habitats are more diversified here than the epilithic samples.     

Rapid Increase of Pneumococcal Resistance to β-Lactam and Other Antibiotics in Isolates from the Respiratory Tract (Nagasaki,Japan: 1975–1994)

The susceptibility of 101 pneumococcal isolates from the respiratory tract during 1991–1994 was examined and compared with the susceptibility of isolates over the period of 1975–1990. A rapid increase of resistance was seen not only to penicillin but also other antimicrobial agents. During 1991–1994, 38% of all the isolates were resistant to penicillin. The rates of resistance during this period were 16–23% for three newer cephalosporins, 18% for imipenem, 69% for tetracycline, 31% for erythromycin, 20% for chloramphenicol and 9% for clindamycin. The use of antibiotics within one month prior to pneumococcal isolation was correlated with penicillin resistance (P < 0.05). Serotyping of the isolates by antiserum revealed differences in predominant types between penicillin-resistant (19F, 23F, 4) and -susceptible isolates (15, 4, 11A). Our data suggests that anti-pneumococcal antibiotics should be carefully chosen on the basis of susceptibility tests.     

Rates and patterns of mitochondrial DNA sequence evolution in fringilline finches (fringilla spp.) and the greenfinch (Carduelis chloris)

Rates and patterns of evolution in partial sequences of five mitochondrial genes (cytochrome b, ATPase 6, NADH dehydrogenase subunit 5, tRNA(Glu), and the control region) were compared among taxa in the passerine bird genera Fringilla and Carduelis. Rates of divergence do not vary significantly among genes, even in comparisons with the control region. Rate variation among lineages is significant only for the control region and NADH dehydrogenase subunit 5, and patterns of variation are consistent with the expectations of neutral theory. Base composition is biased in all genes but is stationary among lineages, and there is evidence for directional mutation pressure only in the control region. Despite these similarities, patterns of substitution differ among genes, consistent with alternative regimes of selective constraint. Rates of nonsynonymous substitution are higher in NADH dehydrogenase subunit 5 than in other protein-coding genes, and transitions exist in elevated proportions relative to transversions. Transitions appear to accumulate linearly with time in tRNA(Glu), and despite exhibiting the highest overall rate of divergence among species, there are no transversional changes in this gene. Finally, for resolving phylogenetic relationships among Fringilla taxa, the combined protein-coding data are broadly similar to those of the control region in terms of phylogenetic informativeness and statistical support.      

Magnesium-induced inner membrane aggregation in heart mitochondria: prevention and reversal by carboxyatractyloside and bongkrekic acid

Mg(2+) at an optimal concentration of 2mM (ph 6.5) induces large increases (up to 30 percent) in the optical density of bovine heart mitochondria incubated under conditions of low ionic strength (< approx. 0.01). The increases are associated with aggregation (sticking together) of the inner membranes and are little affected by changes in the energy status of the mitochondria. Virtually all of a number of other polyvalent cations tested and Ag(+) induce increases in mitochondrial optical density similar to those induced by Mg(2+), their approximate order of concentration effectiveness in respect to Mg(2+) being: La(3+) > Pb(2+) = Cu(2+) > Cd(2+) > Zn(2+) > Ag(+) > Mn(2+) > Ca(2+) > Mg(2+). With the exception of Mg(2+), all of these cations appear to induce swelling of the mitochondria concomitant with inner membrane aggregation. The inhibitors of the adenine nucleotide transport reaction carboxyatratyloside and bongkrekic acid are capable of preventing and reversing Mg(2+)-induced aggregation at the same low concentration required for complete inhibition of phosphorylating respiration, suggesting that they inhibit the aggregation by binding to the adenine nucleotide carrier. The findings are interpreted to indicate (a) that the inner mitochondrial membrane is normally prevented from aggregating by virtue of its net negative outer surface change, (b) that the cations induce the membrane to aggregate by binding at its outer surface, decreasing the net negative charge, and (c) that carboxyatractyloside and bongkrekic acid inhibit the aggregation by binding to the outer surface of the membrane, increasing the net negative charge.     

Mesophilic and thermophilic methane fermentation ofEuphorbia tirucalli

Summary Methanization ofEuphorbia tirucalli was determined under mesophilic and moderate thermophilic conditions. Three different plant pre-treatments were tested: ground, coarse chopped and dried and ground material. The batch digesters were fed at 5% dilution of dried matter. During a 35 days test, the best daily yield (0.78 l/l/d) was obtained with the chopped raw material under moderate thermophilic conditions.

---

Fermentation méthanique mésophile et thermophiled'Euphorbia tirucalli

Résumé La méthanisation d'Euphorbiatirucalli a été réalisée en conditions mésophile et modérément thermophile. Trois différents pré-traitements de cette plante ont été testés: simple fragmentation, broyat, séchage puis broyage. Les digesteurs ont été alimentés avec 5% de matière sèche en batch. Lors d'une expérimentation de 35 jours, le meilleur rendement (0,78 l/l/j) a été obtenu avec les fragments de plante en condition thermophile modérée.