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[Mental prognosis in scaphocephaly].

BACKGROUND: The mental prognosis of scaphocephaly remains a controversial issue, and surgery is performed for functional or aesthetical reasons without clear evidence in the literature of which is the most important. PATIENTS AND METHODS: Three hundred and ninety six children with scaphocephaly were prospectively studied to analyse the correlation between age, intracranial pressure (ICP) and mental outcome. Before any treatment, the intracranial pressure was recorded (systematically during the first period of the study); the mental level was evaluated at first consultation and after a mean five-year follow-up. The mental evolution was compared whether the child was operated or not. RESULTS: The mental outcome of the patients was good in most of the cases whether or not they had been operated. There were significantly more normal patients in the scaphocephalies seen before one year of age at first consultation (P < 0.001) than in those seen after one year of age. There were significantly more abnormally high intracranial pressure cases in the group of patients who were seen later than one year of age (P = 0.0015). There were more retarded patients in the group with increased ICP, but the difference was not significant (P = 0.17). There was no correlations between ICP and final IQ neither in operated nor in non-operated patients. Conversely, a correlation was found between the early and late psychometric assessments in all patients. CONCLUSIONS: The main predictive factor of mental outcome appears to be the initial developmental level. Since the mental level was worse in the older children, and since the surgery does not influence the functional outcome when the initial mental level is low, we can conclude that the indication to perform surgery in scaphocephaly is sometimes not only a cosmetic problem.

Child Development↗

[Plasma-derived products: therapeutic biological products].

The status of proprietary medicinal product has been conferred upon plasma derived products (PDP) by the European Community in its directive issued on the 14 of June 1989. This directive requires each Member State to comply with the current regulations applicable to medicinal products related to production, control and registration of PDP. A different evolution characterized the American regulation in which PDP have been classified as biological products, submitted to a particular regulation since 1992. These different conceptions led the authors to systematically review the specificities of PDP in comparison to classical medicinal products: plasmatic raw material, production of active ingredients and manufacturing of products in the same facility, divergent production of several products from a single starting material, infection risks and variability characterizing biological products, registration and distribution. The analysis of complementary regulation issued to adapt the pharmaceutical principles to the PDP shows that it does not provide all the expected answers to the specificities of the PDP. This shows the advantages that could be expected by giving a status of biological therapeutic product to the PDP. This could above all allow to federate qualified people and data in order to take into account more accurate and more immediate information about risks which may arise in very dispersed fields. This could also serve as a reminder of the ethical principles attached to the preparation of products coming from a human source.

Biological Products↗

Endoscopic transgastric abdominal exploration and organ resection: initial experience in a porcine model.

BACKGROUND & AIMS: The evolution of flexible endoscopes and endoscopic devices has recently enabled per-oral transgastric abdominal exploration in animal models. This study was undertaken to assess the ability to systematically identify abdominopelvic organs and to determine the feasibility of organ resection via the transgastric route. METHODS: Female Yorkshire pigs were used for the study. Under general anesthesia, a gastroscope was used to place a sterile overtube into the esophagus. After antibacterial lavage, the gastric wall was incised, and a sterile dual-channel endoscope was advanced into the peritoneal cavity. Endoscopic abdominal exploration was then methodically performed in 9 animals with oophorectomy and partial hysterectomy in 6 animals. The gastric incision was closed with endoclips. Of the animals that underwent organ resection, 3 were sacrificed immediately after surgery, and the subsequent 3 survived. RESULTS: The peritoneal cavity was accessed uneventfully, and the stomach, liver, small bowel, colon, urinary bladder, uterus, fallopian tubes, and ovaries were able to be evaluated in all cases. The gallbladder could be visualized in only 5 of the 9 animals, and retroperitoneal structures could not be consistently identified. Oophorectomy with partial hysterectomy was performed in 6 animals. The 3 animals in the survival group did well for 24 hours without sequelae. CONCLUSIONS: This study shows the ability of endoscopic transgastric peritoneal exploration to successfully identify most abdominopelvic organs and demonstrates the technical feasibility of transgastric organ resection.

Abdomen↗

Differences in prevalence, intensity of infection and parasite-specific antibody levels do not predict different age-infection profiles.

Acquired immunity is believed to influence the age-infection profile of Schistosoma infections. We compared antibody responses against Schistosoma mansoni adult worm antigen (AWA) and soluble egg antigen (SEA) in 164 residents of two communities with different levels of infection. IgG, IgA, IgM, IgE, and IgG subclass 1 to 4 antibodies were determined by ELISA. Seventy-five of the subjects were from Harbu, an area with a prevalence of 39% and an intensity of infection of 116 eggs per gram of stool (EPG), whereas 89 subjects were from Bati, with a prevalence of 66% and intensity of infection of 256 EPG. In both communities the prevalence and the intensity of infection were highest in the age group 10-14 years, although both were significantly higher in Bati than in Harbu. Mean levels of AWA-specific IgA, IgM, IgG, IgG1 and IgG2, and of SEA-specific IgG, IgM, IgG2 and IgG3 were significantly higher in Bati than in Harbu. However, mean levels of IgE against worm and egg antigens were significantly higher in Harbu than in Bati. Significant differences were detected in the levels of IgA, IgE, IgG, IgM, IgG1 and IgG2 against AWA, and in IgE, IgM, IgG2 and IgG3 against SEA according to the place of residence. The levels of anti-AWA IgG, IgG1 and IgG2 and anti-SEA IgG, IgG1 and IgG4 were significantly associated with the intensity of infection. Anti-AWA IgM levels were associated with age, whereas sex and age had interacting effects on the levels of AWA-specific IgG1 and SEA-specific IgG and IgM. Antibody responses exhibited different age-related patterns in the two communities. This may indicate that differences in history of exposure influence the evolution of immune responses. However, the study did not support the view that differences in antibody levels between communities subject to different levels of infection result in a systematic deviation in age-infection profile (the "peak shift").

Adolescent↗

Directed evolution of enzymes for product chemistry.

This review discusses the achievements of directed evolution of enzymes relevant to natural and unnatural product chemistry focusing on the period 1998-2004, citing 156 references. A few selected papers published before 1998 are also cited for their fundamental relevance, together with additional reviews covering other aspects of directed evolution applied to closely related topics. An overview of the latest methods applied in directed evolution is given in the introduction, together with a range of approaches for the selection of variants of enzymes with desired catalytic properties. All classes of enzymes are systematically covered.

Catalysis↗

[Gamma knife radiosurgery for the treatment of severe epilepsy].

The Gamma Knife radiosurgery is a neurosurgical approach having now demonstrated well its efficiency, its low morbidity and its comfort in the treatment of numerous neurosurgical disorders. These advantages of this type of intervention make it a method of great interest in functional neurosurgery and quite particularly in surgery of epilepsy. French experience is a pionner one in this domain. If for several years the positive evolution of the epilepsy associated to brain lesions had been noticed after the Gamma Knife radiosurgical treatment, the use of this approach in surgery of the epilepsy is systematically estimated since 1993. Data are today available concerning the surgical treatment of the epilepsies originating in temporomesiale area without occupying process, epilepsies associated to hypothalamic hamartomas and epilepsies associated to cavernous angiomas or to low grade gliomas. The quality of the epileptological result obtained in these various indications associated to a very reduced morbidity lets suppose that the Gamma Knife radiosurgery could indeed have tomorrow a place within the sample group of surgical approaches dedicated to the treatment of severe epilepsies. However, a larger number of treated patients and a more prolonged follow-up remains necessary to estimate in a more definitive way this approach.

Brain Diseases↗

The species selectivity of chemically distinct tachykinin nonpeptide antagonists is dependent on common divergent residues of the rat and human neurokinin-1 receptors.

During evolution mutations have occurred in peptide receptors that are neutral with respect to binding of the natural peptide ligand but frequently affect the binding of nonpeptide antagonists. By systematically introducing the nonconserved residues from the human neurokinin (NK)-1 receptor into the corresponding rat receptor we have attempted to localize the structural elements that are responsible for 15-76-fold higher affinity of three tachykinin nonpeptide antagonists for the human receptor, compared with the corresponding rat receptor. Surprisingly, exchange of the four divergent residues located around the previously located apparent binding site for CP 96,345 and FK 888 at the top of transmembrane segment (TM) V and VI, either alone or as a group, did not affect the binding of these nonpeptide compounds. However, substitution of Ser290 in TM VII of the rat receptor with isoleucine present in the human receptor increased the affinity for FK 888 20-fold and that for CP 96345 6-fold, corresponding to an affinity that was only about 4-fold less than the affinity for the human NK-1 receptor. Full human-like affinity for FK 888 and CP 96,345 could be conveyed to the rat receptor by the combined substitution of Ser290 in TM VII to isoleucine and Leu116 in TM III to valine. The NK-2 receptor-selective compound SR 48,968 was found to bind with low affinity to the human NK-1 receptor but with 15-fold even lower affinity to the rat receptor. Substitution of residue 290, which is situated within the previously located binding site for this compound, could completely account for this difference. These data demonstrate that the species selectivities of the nonpeptide antagonists CP 96345, FK 888, and SR 48,968, independently of clear differences in their chemical structures and modes of discovery, have a similar structural basis, being dependent on two divergent residues that apparently are not involved in peptide agonist binding.

Amino Acid Sequence↗

Synonymous and nonsynonymous substitutions in mammalian genes and the nearly neutral theory.

The nearly neutral theory of molecular evolution predicts larger generation-time effects for synonymous than for nonsynonymous substitutions. This prediction is tested using the sequences of 49 single-copy genes by calculating the average and variance of synonymous and nonsynonymous substitutions in mammalian star phylogenies (rodentia, artiodactyla, and primates). The average pattern of the 49 genes supports the prediction of the nearly neutral theory, with some notable exceptions. The nearly neutral theory also predicts that the variance of the evolutionary rate is larger than the value predicted by the completely neutral theory. This prediction is tested by examining the dispersion index (ratio of the variance to the mean), which is positively correlated with the average substitution number. After weighting by the lineage effects, this correlation almost disappears for nonsynonymous substitutions, but not quite so for synonymous substitutions. After weighting, the dispersion indices of both synonymous and nonsynonymous substitutions still exceed values expected under the simple Poisson process. The results indicate that both the systematic bias in evolutionary rate among the lineages and the episodic type of rate variation are contributing to the large variance. The former is more significant to synonymous substitutions than to nonsynonymous substitutions. Isochore evolution may be similar to synonymous substitutions. The rate and pattern found here are consistent with the nearly neutral theory, such that the relative contributions of drift and selection differ between the two types of substitutions. The results are also consistent with Gillespie's episodic selection theory.

Animals↗

Molecular evolution of the actin family.

Members of the actin family have well-characterized cytoskeletal functions, but actin and actin-related proteins (ARPs) have also been implicated in nuclear activities. Previous analyses of the actin family have identified four conserved subfamilies, but many actin-related proteins (ARPs) do not fall into these groups. A new systematic phylogenetic analysis reveals that at least eight ARP subfamilies are conserved from humans to yeast, indicating that these ARPs are part of the core set of eukaryotic proteins. Members of at least three subfamilies appear to be involved in chromatin remodeling, suggesting that ARPs play ancient, fundamental roles in this nuclear process.

Actins↗

Evolution of the human immunodeficiency virus epidemic among patients attending sexually transmitted disease clinics: a decade of experience.

Since human immunodeficiency virus (HIV) is predominantly sexually transmitted, serologic surveys for HIV infection in sexually transmitted disease (STD) clinics provide sentinel observations regarding HIV epidemiology. Over the past decade, 17,207 systematically collected sera from patients attending Baltimore STD clinics were analyzed. From 1979 through 1989, HIV seroprevalence rose from 0.23% to 5.35%, increasing significantly in both men and women (P less than .001). Due to a marked increase in HIV infection among women during the mid-1980s, the male-to-female ratio of HIV infection declined from 16:1 in 1979-1982 to 1.0 in 1988-1989. HIV seroprevalence increased significantly (P less than .001) in all age groups, with the greatest increase among teenagers, rising from 0.18% in 1979-1983 to 2.1% in 1987-1989 (P less than .001). Although HIV seroprevalence was higher among whites than blacks during the early 1980s, it increased in blacks subsequently (P less than .001), eventually resulting in a greater rate among black than white clinic patients (P less than .01). These data reflect the evolution of the HIV epidemic in US inner cities. HIV prevalence has increased greater than 20-fold, with recent increases being most marked among women, teenagers, and blacks. Additional resources will undoubtedly be required to support further intensive behavioral and educational programs targeted at adolescents and inner-city minorities.

Adolescent↗

Evolutionary psychology of spatial representations in the hominidae.

Comparatively little is known about the inherited primate background underlying human cognition, the human cognitive "wild-type." Yet it is possible to trace the evolution of human cognitive abilities and tendencies by contrasting the skills of our nearest cousins, not just chimpanzees, but all the extant great apes, thus showing what we are likely to have inherited from the common ancestor. By looking at human infants early in cognitive development, we can also obtain insights into native cognitive biases in our species. Here, we focus on spatial memory, a central cognitive domain. We show, first, that all nonhuman great apes and 1-year-old human infants exhibit a preference for place over feature strategies for spatial memory. This suggests the common ancestor of all great apes had the same preference. We then examine 3-year-old human children and find that this preference reverses. Thus, the continuity between our species and the other great apes is masked early in human ontogeny. These findings, based on both phylogenetic and ontogenetic contrasts, open up the prospect of a systematic evolutionary psychology resting upon the cladistics of cognitive preferences.

Animals↗

Evolution of encounter group methods in therapeutic communities for substance abusers.

Some literature indicates an evolution in the concept underlying therapeutic communities (TC, for substance abusers), where encounter group methods evolved from harsh confrontation to dialogue and discussion. The literally transcribed proceedings of two similar encounter groups, held at a 20-year interval, were systematically analyzed on four main variables: direction of communication sequences and associated behavior, emotions, and attitudes of all participants (staff members and "older" and "newer" residents). In general, "toward" and "back" messages are relatively more balanced in the "new" encounter (2000) as compared with the "old" encounter (1980). Furthermore, associated behavior in the "new" encounter is found to be more supportive, whereas ventilated emotions are more negative than in the "old" encounter. The number of communication units within the "old" and "new" encounter, characterizing a positive or negative attitude, seems to have remained stable over the years. These findings support the reported evolution in encounter groups, where the focus has moved from mutual confrontation toward balanced and respectful dialogue.

Attitude to Health↗

Amplification of the ancient murine Lx family of long interspersed repeated DNA occurred during the murine radiation.

We identified and characterized the relics of an ancient rodent L1 family, referred to as Lx, which was extensively amplified at the time of the murine radiation about 12 million years ago, and which we showed was ancestral to the modern L1 families in rat and mouse. Here we have extended our analysis of the Lx amplification by examining more murine and nonmurine species for Lx sequences using both blot hybridization and the polymerase chain reaction for a total of 36 species. In addition we have determined the relative copy number and sequence divergence, or age, of Lx elements in representative murine genera. Our results show that while Lx sequences are confined to murine genera, the extent of the amplification was different in the different murine lineages, indicating that the amplification of Lx did not precede, but was coincident with, the murine radiation. The implications of our findings for the evolutionary dynamics of L1 families and the utility of ancestral amplification events for systematics are discussed.

Animals↗

Genetics of susceptibility to human infectious disease.

Before Robert Koch's work in the late nineteenth century, diseases such as tuberculosis and leprosy were widely believed to be inherited disorders. Heritability of susceptibility to several infectious diseases has been confirmed by studies in the twentieth century. Infectious diseases, old and new, continue to be an important cause of mortality worldwide. A greater understanding of disease processes is needed if more effective therapies and more useful vaccines are to be produced. As part of this effort, developments in genetics have allowed a more systematic study of the impact that the human genome and infectious disease have on each other.

Biological Evolution↗

The aquatic budding bacterium Blastobacter denitrificans is a nitrogen-fixing symbiont of Aeschynomene indica.

Blastobacter spp. are freshwater bacteria that form rosette structures by cellular attachment to a common base. Comparative analyses of ribosomal 16S rRNA gene and internally transcribed spacer region sequences indicated that B. denitrificans is a member of the alpha-subdivision of Proteobacteria. Among the alpha-Proteobacteria, B. denitrificans was related to a cluster of genera, including Rhodopseudomonas palustris, Afipia felis, Nitrobacter hamburgensis, and Bradyrhizobium spp. Although the precise phylogenetic relationships among these genera could not be established with a high degree of confidence, the sequences of B. denitrificans and several bradyrhizobial isolates from nodules of Aeschynomene indica were almost identical. Bradyrhizobia are bacteria that form nitrogen-fixing symbioses with legumes, including soybeans (Glycine max) and members of the genus Aeschynomene. From symbiotic infectiveness tests we demonstrated that the type strain for B. denitrificans, IFAM 1005, was capable of forming an effective nitrogen-fixing symbiosis with A. indica. Not only do these results reveal a previously unknown ecological adaptation of a relatively obscure aquatic bacterium, but they also demonstrate how evidence gathered from molecular systematic analyses can sometimes provide clues for predicting ecological behavior.

DNA, Ribosomal Spacer↗

Recent paleoanthropological excavations of in situ deposits at Makapansgat, South Africa--a first report.

The Makapansgat Limeworks is a significant Pliocene site both for its sample of 35 hominin fossils as well as its wealth of fossil fauna. The lithological and paleontological successions reveal local environmental changes that are important for understanding the context of hominin evolution in southern Africa. Yet most of the site's fossils were found in dumps left behind by quarry operations, and the paleoecological interpretations rest upon debatable assumptions about the original fossil provenience. We have recently initiated systematic paleoanthropological excavations at Makapansgat to recover well provenanced fossils in order to: 1) assess whether faunal successions are discernable in the Makapansgat sequence; 2) assist environmental interpretations of the site; 3) and potentially recover the oldest hominins in South Africa, roughly coincident with Australopithecus afarensis in East Africa. This paper presents a summary of our current paleoenvironmental research at the Limeworks and preliminary results of ongoing in situ excavations.

Animals↗

Transposable elements drive evolution and perturb gene expression in Brassica rapa and B. oleracea.

Transposable elements (TEs) significantly influence genomic diversity and gene regulation in plants. Brassica rapa and B. oleracea, with their distinct domestication histories, offer excellent models to explore TE dynamics. Here, we developed a refined TE classification method and systematically analyzed TEs across 12 B. rapa and B. oleracea genomes, identifying 1878 TE families. Approximately half (49.5%) of these TE families were shared between the two species, reflecting a common evolutionary origin, whereas species-specific expansions, particularly among long-terminal repeat (LTR) retrotransposons, underscore their roles in genomic differentiation. We notably characterized a heat-responsive Ty1-copia family (Copia0035) in B. oleracea roots, distinguished by low GC content and the absence of CG and CHG methylation motifs, sharing regulatory similarities with the Arabidopsis heat-induced ONSEN element. Syntenic analyses of gene-TE associations highlighted significant intraspecies TE insertion variability, with more accession-specific insertions in B. rapa and more conserved insertions, often associated with distinct morphotypes in B. oleracea. Gene ontology enrichment indicated TE involvement in developmental, reproductive, and stress response pathways. Transcriptome analysis across diverse accessions revealed that genes proximal to TEs, particularly those regulating floral development and flowering time, exhibit increased expression variability. These findings advance our understanding of TE-mediated genome evolution in Brassica species and underscore their potential utility in breeding and genome engineering strategies for crop improvement.

DNA Transposable Elements↗

The human olfactory subgenome: from sequence to structure and evolution.

Olfactory receptors (ORs) constitute the largest multigene family in multicellular organisms. Their evolutionary proliferation has been driven by the need to provide recognition capacity for millions of potential odorants with arbitrary chemical configurations. Human genome sequencing has provided a highly informative picture of the "olfactory subgenome", the repertoire of OR genes. We describe here an analysis of 224 human OR genes, a much larger number than hitherto systematically analyzed. These are derived by literature survey, data mining at 14 genomic clusters, and by an OR-targeted experimental sequencing strategy. The presented set contains at least 53% pseudogenes and is minimally divided into 11 gene families. One of these (no. 7) has undergone a particularly extensive expansion in primates. The analysis of this collection leads to insight into the origin of OR genes, suggesting a graded expansion through mammalian evolution. It also allows us to delineate a structural map of the respective proteins. A sequence database and analysis package is provided (http://bioinformatics.weizmann.ac.il/HORDE), which will be useful for analyzing human OR sequences genome-wide.

Amino Acid Sequence↗