Bilateral methachronous testicular germ cell tumor and testicular microlithiasis in a child: Genetic analysis and insights. A case report.

OBJECTIVES: To report our experience with a case of a child with bilateral testicular micro-lithiasis (TML) who developed bilateral metachronous testicular germ cell tumor (TGCT) and determine the most appropriate follow-up and care management in children with testicular micro calcifications in regards to the theoretical risk of testicular cancer. CASE REPORT: A 12 year-old boy was diagnosed with TGCT and TML. Ten years after complete remission, he presented with a recurrence on the contralateral testis. Genetic screening was performed on both resected and the patient's karyotype was analyzed. RESULTS: Blood karyotype was normal. Aberrations were found in the tumor karyotype. CGH array showed alterations in chromosome arm 12p. DISCUSSION: TML is frequently associated with testicular malignancy in adults: in 16.9% of cases the normal contralateral testicle develops TML in TGCT. Recent works of literature find no relationship between TML and cancer in general, but in patients with additional risks, the relationship becomes stronger. Some authors suggest that environmental components and genetics are determinant factors. This is highly suspected in our reported case. It would seem that TML is not a precancerous lesion per se, but rather a marker of an at-risk situation. Long term evolution is uncertain and regular self-palpation that starts before puberty is the only way to ensure proper screening and monitoring. CONCLUSION: TML have been suspected to be a sign of testicular dysgenesis syndrome, which yields a risk of developing TGCT in case of noxious associations. In patients with a history of TGCT contralateral TML is alarming and aggressive surgical management should be discussed. Therapeutic education of these patients on self-palpation is the best way to ensure proper follow-up.

Xq28 duplication including MECP2 in six unreported affected females: what can we learn for diagnosis and genetic counselling?

Duplication of the Xq28 region, involving MECP2 (dupMECP2), has been primarily described in males with severe developmental delay, spasticity, epilepsy, stereotyped movements and recurrent infections. Carrier mothers are usually asymptomatic with an extremely skewed X chromosome inactivation (XCI) pattern. We report a series of six novel symptomatic females carrying a de novo interstitial dupMECP2, and review the 14 symptomatic females reported to date, with the aim to further delineate their phenotype and give clues for genetic counselling. One patient was adopted and among the other 19 patients, seven (37%) had inherited their duplication from their mother, including three mildly (XCI: 70/30, 63/37, 100/0 in blood and random in saliva), one moderately (XCI: random) and three severely (XCI: uninformative and 88/12) affected patients. After combining our data with data from the literature, we could not show a correlation between XCI in the blood or duplication size and the severity of the phenotype, or explain the presence of a phenotype in these females. These findings confirm that an abnormal phenotype, even severe, can be a rare event in females born to asymptomatic carrier mothers, making genetic counselling difficult in couples at risk in terms of prognosis, in particular in prenatal cases.

Role of angiogenesis-related genes in cleft lip/palate: review of the literature.

OBJECTIVES: Cleft lip and cleft palate (CLP) are the most common congenital craniofacial anomalies. They have a multifactorial etiology and result from an incomplete fusion of the facial buds. Two main mechanisms, acting alone or interacting with each other, were evidenced in this fusion defect responsible for CLP: defective tissue development and/or defective apoptosis in normal or defective tissues. The objective of this work was to study the implication and role of angiogenesis-related genes in the etiology of CL/P. METHODS: Our methodological approach included a systematic and thorough analysis of the genes involved in CL/P (syndromic and non-syndromic forms) including previously identified genes but also genes that could potentially be angiogenesis-related (OMIM, Pub Med).We studied the interactions of these different genes and their relationships with potential environmental factors. RESULTS: TGFß, FGA, PDGFc, PDGFRa, FGF, FGFR1, FGFR2 growth factors as well as MMP and TIMP2 proteolytic enzymes are involved in the genesis of CLP (P>L). Furthermore, 18 genes involved in CLP also interact with angiogenesis-related genes. DISCUSSION: Even if the main angiogenesis-related genes involved in CLP formation are genes participating in several biological activities and their implication might not be always related to angiogenesis defects, they nevertheless remain an undeniably important research pathway. Furthermore, their interactions with environmental factors make them good candidates in the field of CLP prevention.

Reproducibility and relative validity of a brief quantitative food frequency questionnaire for assessing fruit and vegetable intakes in North-African women.

BACKGROUND: In the context of a rapidly increasing prevalence of noncommunicable diseases, fruit and vegetables could play a key preventive role. To date, there is no rapid assessment tool available for measuring the fruit and vegetable intakes of North-African women. The present study aimed to investigate the reproducibility and relative validity of an eight-item quantitative food frequency questionnaire that measures the fruit and vegetable intakes (FV-FFQ) of Moroccan women. METHODS: During a 1-week period, 100 women, living in the city of Rabat, Morocco (aged 20-49 years) completed the short FV-FFQ twice: once at baseline (FV-FFQ1) and once at the end of the study (FV-FFQ2). In the mean time, participants completed three 24-h dietary recalls. All questionnaires were administered by interviewers. Reproducibility was assessed by computing Spearman's correlation coefficients, intraclass correlation (ICC) coefficients and kappa statistics. Relative validity was assessed by computing Wilcoxon signed-rank tests and Spearman's correlation coefficients, as well as by performing Bland-Altman plots. RESULTS: In terms of reproducibility, Spearman's correlation coefficient was 0.56; ICC coefficient was 0.68; and weighted kappa was 0.35. In terms of relative validity, compared with the three 24-h recalls, the FV-FFQ slightly underestimated mean fruit and vegetable intakes (-10.9%; P = 0.006); Spearman's correlation coefficient was 0.69; at the individual level, intakes measured by the FV-FFQ were between 0.39 and 2.19 times those measured by the 24-h recalls. CONCLUSIONS: The brief eight-item FV-FFQ is a reliable and relatively valid tool for measuring mean fruit and vegetable intakes at the population level, although this is not the case at the individual level.

Microdeletions including YWHAE in the Miller-Dieker syndrome region on chromosome 17p13.3 result in facial dysmorphisms, growth restriction, and cognitive impairment.

BACKGROUND: Deletions in the 17p13.3 region are associated with abnormal neuronal migration. Point mutations or deletion copy number variants of the PAFAH1B1 gene in this genomic region cause lissencephaly, whereas extended deletions involving both PAFAH1B1 and YWHAE result in Miller-Dieker syndrome characterised by facial dysmorphisms and a more severe grade of lissencephaly. The phenotypic consequences of YWHAE deletion without deletion of PAFAH1B1 have not been studied systematically. METHODS: We performed a detailed clinical and molecular characterization of five patients with deletions involving YWHAE but not PAFAH1B1, two with deletion including PAFAH1B1 but not YWHAE, and one with deletion of YWHAE and mosaic for deletion of PAFAH1B1. RESULTS: Three deletions were terminal whereas five were interstitial. Patients with deletions including YWHAE but not PAFAH1B1 presented with significant growth restriction, cognitive impairment, shared craniofacial features, and variable structural abnormalities of the brain. Growth restriction was not observed in one patient with deletion of YWHAE and TUSC5, implying that other genes in the region may have a role in regulation of growth with CRK being the most likely candidate. Using array based comparative genomic hybridisation and long range polymerase chain reaction, we have delineated the breakpoints of these nonrecurrent deletions and show that the interstitial genomic rearrangements are likely generated by diverse mechanisms, including the recently described Fork Stalling and Template Switching (FoSTeS)/Microhomology Mediated Break Induced Replication (MMBIR). CONCLUSIONS: Microdeletions of chromosome 17p13.3 involving YWHAE present with growth restriction, craniofacial dysmorphisms, structural abnormalities of brain and cognitive impairment. The interstitial deletions are mediated by diverse molecular mechanisms.

The crystal structure of CD8 in complex with YTS156.7.7 Fab and interaction with other CD8 antibodies define the binding mode of CD8 alphabeta to MHC class I.

The CD8alphabeta heterodimer interacts with class I pMHC on antigen-presenting cells as a co-receptor for TCR-mediated activation of cytotoxic T cells. To characterize this immunologically important interaction, we used monoclonal antibodies (mAbs) specific to either CD8alpha or CD8beta to probe the mechanism of CD8alphabeta binding to pMHCI. The YTS156.7 mAb inhibits this interaction and blocks T cell activation. To elucidate the molecular basis for this inhibition, the crystal structure of the CD8alphabeta immunoglobulin-like ectodomains were determined in complex with mAb YTS156.7 Fab at 2.7 A resolution. The YTS156.7 epitope on CD8beta was identified and implies that residues in the CDR1 and CDR2-equivalent loops of CD8beta are occluded upon binding to class I pMHC. To further characterize the pMHCI/CD8alphabeta interaction, binding of class I tetramers to CD8alphabeta on the surface of T cells was assessed in the presence of anti-CD8 mAbs. In contrast to YTS156.7, mAb YTS105.18, which is specific for CD8alpha, does not inhibit binding of CD8alphabeta to class I tetramers, indicating the YTS105.18 epitope is not occluded in the pMHCI/CD8alphabeta complex. Together, these data indicate a model for the pMHCI/CD8alphabeta interaction similar to that observed for CD8alphaalpha in the CD8alphaalpha/pMHCI complex, but in which CD8alpha occupies the lower orientation (membrane proximal to the antigen presenting cell), and CD8beta occupies the upper position (membrane distal). The implication of this molecular assembly for the function of CD8alphabeta in T cell activation is discussed.

[Analysis of 1697 cases of childhood malaria treated using intra-rectal Quinimax (QIR) in the Tilaberi health district in Niger]. / Analyse de 1697 cas de paludisme de l'enfant traité par Quinimax intra-rectal (QIR) dans le district sanitaire de Tilaberi au Niger.

Management of malaria attacks with vomiting or other complications in rural areas of Africa raises the often insurmountable challenge of transferring patients to medical centers better equipped than health dispensaries providing initial care. In addition intramuscular quinine can lead to complications. Since intrarectal administration of quinine could help to resolve these problems, it should be included in the therapeutic algorithm. The purpose of this study was to validate the safety, acceptability, tolerance, and efficacy of Intra-Rectal Quinimax (QIR) for treatment of children (0 to 10 years) in the rural Tilaberi region of Niger where malaria is endemic. Of the 3012 children enrolled in the study, a total of 1697 benefited from treatment with treatment using QIR. Thirty-five percent of the cases treated involved complicated malaria attacks. Use of QIR caused no problem in terms of safety or acceptability. Duration of surveillance following treatment using QIR in children is particularly important to prevent early evacuation of the product that was observed in 16% of cases. No short-term side effects were observed. Contraindications for QIR were observed in 10% of the patients enrolled in the study. Success and mortality rates were not statistically different after intrarectal and intramuscular administration. A survey to evaluate the skill of care providers was carried out at the onset of the study. The presentation and functionality of the QIR kit was validated by care providers.

CD4+ T-cell responses to Epstein-Barr virus (EBV) latent-cycle antigens and the recognition of EBV-transformed lymphoblastoid cell lines.

There is considerable interest in the potential of Epstein-Barr virus (EBV) latent antigen-specific CD4+ T cells to act as direct effectors controlling EBV-induced B lymphoproliferations. Such activity would require direct CD4+ T-cell recognition of latently infected cells through epitopes derived from endogenously expressed viral proteins and presented on the target cell surface in association with HLA class II molecules. It is therefore important to know how often these conditions are met. Here we provide CD4+ epitope maps for four EBV nuclear antigens, EBNA1, -2, -3A, and -3C, and establish CD4+ T-cell clones against 12 representative epitopes. For each epitope we identify the relevant HLA class II restricting allele and determine the efficiency with which epitope-specific effectors recognize the autologous EBV-transformed B-lymphoblastoid cell line (LCL). The level of recognition measured by gamma interferon release was consistent among clones to the same epitope but varied between epitopes, with values ranging from 0 to 35% of the maximum seen against the epitope peptide-loaded LCL. These epitope-specific differences, also apparent in short-term cytotoxicity and longer-term outgrowth assays on LCL targets, did not relate to the identity of the source antigen and could not be explained by the different functional avidities of the CD4+ clones; rather, they appeared to reflect different levels of epitope display at the LCL surface. Thus, while CD4+ T-cell responses are detectable against many epitopes in EBV latent proteins, only a minority of these responses are likely to have therapeutic potential as effectors directly recognizing latently infected target cells.

Perceptions of healthy and desirable body size in urban Senegalese women.

OBJECTIVE: To examine the cultural ideals for body size held by urban Senegalese women; to determine the body size that women associate with health; and to estimate the change in prevalence of female obesity in an urban neighbourhood of Dakar. DESIGN: Cross-sectional, population-based study in the subject's home, using a structured interviewer-administered questionnaire, conducted in the same Dakar neighbourhood as that of a previous survey conducted in 1996. SUBJECTS: A total of 301 randomly selected women, aged 20-50 y, living in a specific Dakar neighbourhood, Senegal. MEASUREMENTS: A total of 32 items concerning body satisfaction, social status, health and individual attributes to associate with one of six photographic silhouettes; body mass index (BMI), waist circumference, waist-to-hip ratio by anthropometry; and measures of economic status. RESULTS: In all, 26.6% of women were overweight (BMI 25-29.9 kg/m2) and 18.6% were obese (BMI > or =30 kg/m2) compared with 22.4 and 8.0% respectively in 1996. Overweight was the most socially desirable body size, although obesity itself was seen as undesirable, associated with greediness and the development of diabetes and heart disease. Lay definitions of overweight and normal weight differed substantially from health definitions, as one-third of the sample saw the 'overweight' category as normal. Over a third of women with BMI > or =25 kg/m2 wanted to gain more weight. CONCLUSION: There has been a sharp rise in the prevalence of obesity in Senegalese women living in a Dakar neighbourhood over the last 7 y. In general, overweight body sizes (but not obese) were seen in a positive light. The finding that the term 'overweight' made little sense to these Senegalese women could have important implications for developing public health policies.

The marking of livestock in traditional pastoral societies.

The marking of animals has been practised in all pastoral systems since time immemorial. Using a series of examples representative of the major pastoral civilisations of the world, the author presents the techniques used (branding and ear incisions, either separately or in combination). In the light of the characteristics common to pastoral societies, the following points are analysed: a) the manner in which the marks used by these societies have been conserved or modified in the course of vertical (inherited) or lateral changes of ownership b) the content and meaning of the messages conveyed by the marks c) the various functions of the marks, namely: collective or individual identification, establishment of rights, protection against theft. In conclusion, the mark of the lineage is seen as symbolic of the founding pact of the pastoral system, uniting a community of humans, a community of animals and a territory. Traditional livestock marking systems are generally not used for health purposes. Moreover, the characteristics of these traditional systems are not compatible with the requirements of modern traceability. Nevertheless, these systems could be adapted, as is the case for the marking of the reindeer herds of the Lapps in Norway, which has been given legal value and has been made mandatory.

[Trajectory types of health status during the life of the dairy cow]. / Types de trajectoire du statut sanitaire au cours de la carrière des vaches laitières.

This paper presents a first approach of the health over the whole life-cycle of dairy cows, a scale which is intended to define a trajectory. Trajectories are defined as the chain of health profiles on the lactation scale, which are characterized by major disorders: foul of the foot; lameness; arthritis; calving disorders; mastitis; digestive and metabolic disorders; and no disorders. A few examples of trajectories are discussed for life-cycles lasting 4 lactations.

[Feeding, pathology and productivity of the dairy cow: interrelations during the course of lactation]. / Alimentation, pathologie et productivité de la vache laitière: interrelations à l'échelle de la carrière.

The influence of winter feeding (hay versus grass silage-based diets, supplemented with a high or low level of concentrate) and disease on the longevity of 136 Friesian or Montbeliarde dairy cows was studied in a long-term experiment spanning 6 consecutive years. Breed had no great effect on longevity. The longevity of cows given a silage diet with a low level of supplementation was lower than that of cows given any one of the other diets (2.5 lactation/cycle versus 3.2-3.5). Cows that developed frequent lameness during the 1st lactation had a shorter period of productivity (-1.1 lactation/cycle) than comparable healthy animals. Among the different pathological lactation profiles, only the profile "healthy lactation" recurs from one lactation to the next (41% of the cases). In particular, lameness (which is very recurrent during a single lactation) is not recurrent from one lactation to the next. The characteristics of the 1st lactation cycle (disease, milk production, reproduction) appeared to be determinant for the productive future of the animals. On average, milk production and live-weight increased by 352 and 24 kg respectively between the 1st and 2nd lactation and by 270 and 27 kg between the 2nd and 3rd lactation. Cows given a hay diet (with a low or high level of supplementation) or a silage diet with a high level of supplementation showed a greater increase in production between the 1st and 3rd lactation (+ 752 kg) than those given a silage diet with a low level of supplementation (+ 359 kg). Over 3 lactations, the cumulative effects of the type of winter feeding can become marked: differences in milk production can attain up to 2770 kg between a hay/high concentrate and a silage/low concentrate diet. These results question the validity of conclusions drawn from experiments conducted over 1 winter or 1 lactation cycle only.

[Characterization of the pathology of lactating cows based on the level of lactation. Principal factors in the variation and typing of pathologic profiles of lactation]. / Caractérisation de la pathologie de la vache laitière à l'échelle de la lactation. Principaux facteurs de variation et typologie des profils pathologiques de lactation.

The health disturbances investigated were observed during a long-term trial (six years) conducted at an experimental station located at 1,100 m elevation. The study dealt with 487 lactations involving 190 cows of the Montbéliarde and French Friesian breeds, which produced on average 4,200 kg milk per lactation. The disturbances concerned 59% of monitored lactations, with a mean incidence of 2.1 disturbances per lactation. Lameness and mastitis accounted respectively for 52 and 24% of the clinical affections. Pathology was significantly influenced by breed, basic diet (hay or grass silage), concentrate quantities, lactation rank and year. The authors describe a method permitting an independent analysis of the effects of lactation stage and of season on mastitis and lameness frequency, by limiting the biases due to grouping of calvings and to culling. The study of lactations affected by several pathological disturbances shows that the different types of affections recorded are mutually independent but that successive occurrences of the same affection are not. On the basis of these results, the authors have proposed to globally characterize the "pathological profiles" of lactations.

[Pathology and productivity of the lactating cow: interrelations based on the level of lactation]. / Pathologie et productivité de la vache laitière: interrelations à l'échelle de la lactation.

The effects of sanitary problems in dairy herds on milk production have been determined using 595 cases of health problems noted in Friesian and Montbeliarde cows in a long-term feeding trial, covering over 487 lactations. Relationships between each sanitary condition and lactation characteristics were established. On a short-term basis (5 weeks), the greater milk losses were first due to lameness at turnout (56 kg) and second to winter mastitis (24 kg); the effects of lameness lasted beyond the 5th week depending on when the problem was first detected. Over the whole lactation cycle, the highest milk losses resulted from recurrent lameness: 640 kg loss for cows presenting a lameness at least three times, versus 20 kg for those presenting only one lameness. The frequency of recurrent lameness was three times higher in Friesian than in Montbeliarde cows and four times higher with grass silage-based diets as compared with hay diets. Four main types of lactation cycles were characterized on the basis of the cows' level of production, their health status, their reproduction performances and their culling rate. Cumulative differences in any of those characteristics accounted for up to a 1 800 kg difference in milk production.