Phenotypic and molecular assessment of seven patients with 6p25 deletion syndrome: relevance to ocular dysgenesis and hearing impairment.

BACKGROUND: Thirty-nine patients have been described with deletions involving chromosome 6p25. However, relatively few of these deletions have had molecular characterization. Common phenotypes of 6p25 deletion syndrome patients include hydrocephalus, hearing loss, and ocular, craniofacial, skeletal, cardiac, and renal malformations. Molecular characterization of deletions can identify genes that are responsible for these phenotypes. METHODS: We report the clinical phenotype of seven patients with terminal deletions of chromosome 6p25 and compare them to previously reported patients. Molecular characterization of the deletions was performed using polymorphic marker analysis to determine the extents of the deletions in these seven 6p25 deletion syndrome patients. RESULTS: Our results, and previous data, show that ocular dysgenesis and hearing impairment are the two most highly penetrant phenotypes of the 6p25 deletion syndrome. While deletion of the forkhead box C1 gene (FOXC1) probably underlies the ocular dysgenesis, no gene in this region is known to be involved in hearing impairment. CONCLUSIONS: Ocular dysgenesis and hearing impairment are the two most common phenotypes of 6p25 deletion syndrome. We conclude that a locus for dominant hearing loss is present at 6p25 and that this locus is restricted to a region distal to D6S1617. Molecular characterization of more 6p25 deletion patients will aid in refinement of this locus and the identification of a gene involved in dominant hearing loss.

Subtelomeric 6p deletion: clinical and array-CGH characterization in two patients

We report on two patients with de novo subtelomeric terminal deletion of chromosome 6p. Patient 1 is an 8-month-old female born with normal growth parameters, typical facial features of 6pter deletion, bilateral corectopia, and protruding tongue. She has severe developmental delay, profound bilateral neurosensory deafness, poor visual contact, and hypsarrhythmia since the age of 6 months. Patient 2 is a 5-year-old male born with normal growth parameters and unilateral hip dysplasia; he has a characteristic facial phenotype, bilateral embryotoxon, and moderate mental retardation. Further characterization of the deletion, using high-resolution array comparative genomic hybridization (array-CGH; Agilent Human Genome kit 244 K), revealed that Patient 1 has a 8.1 Mb 6pter-6p24.3 deletion associated with a contiguous 5.8 Mb 6p24.3-6p24.1 duplication and Patient 2 a 5.7 Mb 6pter-6p25.1 deletion partially overlapping with that of Patient 1. Complementary FISH and array analysis showed that the inv del dup(6) in Patient 1 originated de novo. Our results demonstrate that simple rearrangements are often more complex than defined by standard techniques. We also discuss genotype-phenotype correlations including previously reported cases of deletion 6p.

Four novel Loci (19q13, 6q24, 12q24, and 5q14) influence the microcirculation in vivo.

There is increasing evidence that the microcirculation plays an important role in the pathogenesis of cardiovascular diseases. Changes in retinal vascular caliber reflect early microvascular disease and predict incident cardiovascular events. We performed a genome-wide association study to identify genetic variants associated with retinal vascular caliber. We analyzed data from four population-based discovery cohorts with 15,358 unrelated Caucasian individuals, who are members of the Cohort for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium, and replicated findings in four independent Caucasian cohorts (n  =  6,652). All participants had retinal photography and retinal arteriolar and venular caliber measured from computer software. In the discovery cohorts, 179 single nucleotide polymorphisms (SNP) spread across five loci were significantly associated (p<5.0×10(-8)) with retinal venular caliber, but none showed association with arteriolar caliber. Collectively, these five loci explain 1.0%-3.2% of the variation in retinal venular caliber. Four out of these five loci were confirmed in independent replication samples. In the combined analyses, the top SNPs at each locus were: rs2287921 (19q13; p  =  1.61×10(-25), within the RASIP1 locus), rs225717 (6q24; p = 1.25×10(-16), adjacent to the VTA1 and NMBR loci), rs10774625 (12q24; p  =  2.15×10(-13), in the region of ATXN2,SH2B3 and PTPN11 loci), and rs17421627 (5q14; p = 7.32×10(-16), adjacent to the MEF2C locus). In two independent samples, locus 12q24 was also associated with coronary heart disease and hypertension. Our population-based genome-wide association study demonstrates four novel loci associated with retinal venular caliber, an endophenotype of the microcirculation associated with clinical cardiovascular disease. These data provide further insights into the contribution and biological mechanisms of microcirculatory changes that underlie cardiovascular disease.

HHV-8 infection in patients with AIDS-related Kaposi's sarcoma in Brazil

The aims of the present study were to determine the prevalence of human herpesvirus type 8 (HHV-8) in HIV-positive Brazilian patients with (HIV+/KS+) and without Kaposi's sarcoma (HIV+/KS-) using PCR and immunofluorescence assays, to assess its association with KS disease, to evaluate the performance of these tests in detecting HHV-8 infection, and to investigate the association between anti-HHV-8 antibody titers, CD4 counts and staging of KS disease. Blood samples from 66 patients, 39 HIV+/KS+ and 27 HIV+/KS-, were analyzed for HHV-8 viremia in peripheral blood mononuclear cells by PCR and HHV-8 antigenemia for latent and lytic infection by immunofluorescence assay. Positive samples for latent nuclear HHV-8 antigen (LNA) antibodies were titrated out from 1/100 to 1/409,600 dilution. Clinical information was collected from medical records and risk behavior was assessed through an interview. HHV-8 DNA sequences were detected by PCR in 74.3% of KS+ patients and in 3.7% of KS- patients. Serological assays were similar in detecting anti-LNA antibodies and anti-lytic antigens in sera from KS+ patients (79.5%) and KS- patients (18.5%). HHV-8 was associated with KS whatever the method used, i.e., PCR (odds ratio (OR) = 7.4, 95% confidence interval (CI) = 2.16-25.61) or anti-LNA and anti-lytic antibodies (OR = 17.0, 95%CI = 4.91-59.14). Among KS+ patients, HHV-8 titration levels correlated positively with CD4 counts (rho 0.48, P = 0.02), but not with KS staging. HHV-8 is involved in the development of KS in different geographic areas worldwide, as it is in Brazil, where HHV-8 is more frequent among HIV+ patients. KS severity was associated with immunodeficiency, but no correlation was found between HHV-8 antibody titers and KS staging.

Privacidad e intimidad en las interacciones virtuales

El presente trabajo es una revisión de la literatura de investigación en Ciberpsicología centrada en las categorías de privacidad, intimidad, identidad y vulnerabilidad, y en la forma como estas se desarrollan en las redes sociales virtuales. Los principales hallazgos indicaron que son los jóvenes quienes dedican gran parte de su tiempo a interactuar en dichas redes, y a su vez, dado el manejo que les dan, tienen mayor exposición ante los posibles riesgos de estas, como el matoneo, las conductas auto lesivas, la explotación sexual y los trastornos de la alimentación. Se describen estos riesgos y se proponen posibles soluciones.

Recalled relationships with parents and perceptions of professional support in mothers of infants treated for cleft lip

This study examined whether individual differences in perception of the quality of professional support available at a time of stress may be associated with security of attachment. We developed a new measure of parents' perceptions of emotional and practical support provided by a wide range of professionals involved in the treatment of infants with cleft lip. it showed good internal reliability and stability over 4 months. Mothers of 102 infants with cleft lip, with or without cleft palate, completed the measure at 2 and 6 months, together with the Parental Bonding Instrument and the General Health Questionnaire. Mean scores reflecting how much they could trust or talk frankly, or share their worst fears, with professionals, and the extent to which they saw them as a source of useful information or practical help, were lower among mothers with recollections of low maternal care in childhood, or high control. This was the case at 2 and 6 months, and there were some indications of an increasing contribution of low maternal care from 2 to 6 months. The associations were not explained by current depression. Further research is needed to clarify the role of attachment processes in parents' responses to serious medical conditions in their children, and into the implications for the way professionals in paediatric services provide support.

Use of a LightCycler gyrA mutation assay for rapid identification of mutations conferring decreased susceptibility to ciprofloxacin in multiresistant Salmonella enterica serotype typhimurium DT104 isolates

A LightCycler-based PCR-hybridization gyrA mutation assay (GAMA) was developed to rapidly detect gyrA point mutations in multiresistant (MR) Salmonella enterica serotype Typhimurium DT104 with decreased susceptibility to ciprofloxacin (MIC, 0.25 to 1.0 mg/liter). Ninety-two isolates (49 human, 43 animal) were tested with three individual oligonucleotide probes directed against an Asp-87-to-Asn (GAC --> AAC) mutation, an Asp-87-to-Gly (GAC --> GGC) mutation, and a Ser-83-to-Phe (TCC --> TTC) mutation. Strains homologous to the probes could be distinguished from strains that had different mutations by their probe-target melting temperatures. Thirty-seven human and 30 animal isolates had an Asp-87-to-Asn substitution, 6 human and 6 animal isolates had a Ser-83-to-Phe substitution, and 5 human and 2 animal isolates had an Asp-87-to-Gly substitution. The remaining six strains all had mismatches with the three probes and therefore different gyrA mutations. The sequencing of gyrA from these six isolates showed that one human strain and two animal strains had an Asp-87-to-Tyr (GAC --> TAC) substitution and two animal strains had a Ser-83-to-Tyr (TCC --> TAC) substitution. One animal strain had no gyrA mutation, suggesting that this isolate had a different mechanism of resistance. Fifty-eight of the strains tested were indistinguishable by several different typing methods including antibiograms, pulsed-field gel gel electrophoresis, and plasmid profiling, although they could be further subdivided according to gyrA mutation. This study confirmed that MR DT104 with decreased susceptibility to ciprofloxacin from humans and food animals in England and Wales may have arisen independently against a background of clonal spread of MR DT104.

Epstein-Barr virus: clinical and epidemiological revisits and genetic basis of oncogenesis

Epstein-Barr virus (EBV) is classified as a member in the order herpesvirales, family herpesviridae, subfamily gammaherpesvirinae and the genus lymphocytovirus. The virus is an exclusively human pathogen and thus also termed as human herpesvirus 4 (HHV4). It was the first oncogenic virus recognized and has been incriminated in the causation of tumors of both lymphatic and epithelial nature. It was reported in some previous studies that 95% of the population worldwide are serologically positive to the virus. Clinically, EBV primary infection is almost silent, persisting as a life-long asymptomatic latent infection in B cells although it may be responsible for a transient clinical syndrome called infectious mononucleosis. Following reactivation of the virus from latency due to immunocompromised status, EBV was found to be associated with several tumors. EBV linked to oncogenesis as detected in lymphoid tumors such as Burkitt's lymphoma (BL), Hodgkin's disease (HD), post-transplant lymphoproliferative disorders (PTLD) and T-cell lymphomas (e.g. Peripheral T-cell lymphomas; PTCL and Anaplastic large cell lymphomas; ALCL). It is also linked to epithelial tumors such as nasopharyngeal carcinoma (NPC), gastric carcinomas and oral hairy leukoplakia (OHL). In vitro, EBV many studies have demonstrated its ability to transform B cells into lymphoblastoid cell lines (LCLs). Despite these malignancies showing different clinical and epidemiological patterns when studied, genetic studies have suggested that these EBV- associated transformations were characterized generally by low level of virus gene expression with only the latent virus proteins (LVPs) upregulated in both tumors and LCLs. In this review, we summarize some clinical and epidemiological features of EBV- associated tumors. We also discuss how EBV latent genes may lead to oncogenesis in the different clinical malignancies

Observations on the feeding habits of Lutzomyia longipalpis (Lutz & Neiva, 1912) (Diptera: Psychodidae: Phlebotominae) in Campo Grande, an endemic area of visceral leishmaniasis in Mato Grosso do Sul, Brazil

Sand flies were captured weekly with CDC light traps from December 2003 to November 2005 in three areas of Campo Grande, in the Brazilian state of Mato Grosso do Sul. These areas incorporated two patches of remnant forest and five houses. The blood meals of engorged female sand flies were identified using the avidin-biotin system of immunoenzymatic ELISA capture. Most (327/355) of the females analysed were Lutzomyia longipalpis, of which 66.4% reacted with human blood, 64.8% with that of birds and 8.9% with that of dogs. Females that had taken human blood predominated in the residential areas and two forest patches. The following combinations of blood were also detected for L. longipalpis in some of the samples analysed: bird + human (43.4%), bird + human + dog (6.1%). The combination bird + human + dog + pig was also found for Nyssomyia whitmani. Dogs and pigs appear to have little attractiveness for L. longipalpis. The results obtained demonstrate the eclecticism and high anthropophily of L. longipalpis and raise new questions with regard to the importance of dogs in VL epidemiology and the possible role of man as a source of infection for sand flies. (C) 2008 Elsevier B.V. All rights reserved.

Presença do papilomavirus humano em lesões malignas de mucosa oral

O objetivo deste estudo foi investigar a prevalência do papilomavírus humano 6/11 e 16/18 em pacientes, com lesões orais clínicamente diagnosticadas como leucoplasias, atendidas na Faculdade de Odontologia de Araraquara, UNESP, Brasil. Após a inclusão em parafina, os cortes corados com H&E, foram selecionadas 30 biópsias e separadas em 3 grupos: lesões sem displasia (n=10), lesões com diferentes graus de displasia (n=10) e carcinoma espinocelular invasivo(n=10). As lesões que apresentaram displasia epitelial foram classificadas de acordo com os critérios histopatológicos propostos por Van Der Waal. As lesões foram investigadas para a presença de HPV por hibridização in situ com sondas biotiniladas de amplo espectro, 6/11 e 16/18. HPV 16/18 foi detectado em 20% (n=2) das biópsias com displasia severa. A presença de HPV 16/18 em lesões malignas sugere sua importância como fator de risco na carcinogênese oral.

Antiviral activity of Bignoniaceae species occurring in the State of Minas Gerais (Brazil): part 1

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Profitability measures of dairy cows

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Effects of vaccination against reproductive diseases on reproductive performance of beef cows submitted to fixed-timed AI in Brazilian cow-calf operations

The objectives were to assess incidence of pregnancy losses, associate this outcome with immunization programs against reproductive diseases, and evaluate the effects of vaccination against bovine herpesvirus-1 (BoHV-1), bovine viral diarrhea virus (BVDV), and Leptospira spp., on reproductive efficiency of Brazilian cow-calf operations. In experiment 1, 7614 lactating Nelore cows from 18 ranches were assigned to the same estrus synchronization and fixed-time AI protocol (ESFTAI; Days -11 to 0). Pregnancy status was determined with transrectal ultrasonography on Days 30 and 120 after AI. Pregnancy loss was deemed to have occurred when cows were pregnant on Day 30 but nonpregnant on Day 120. Incidence of pregnancy loss across all ranches was 4.1%; pregnancy losses were detected (P < 0.10) in 14 ranches but not detected (P > 0.11) in four ranches. Pregnancy loss was lower (P ≤ 0.02) in ranches that vaccinated against BoHV-1, BVDV, and Leptospira spp. compared with ranches that did not vaccinate, or only vaccinated against Leptospira spp. In experiments 2 and 3, lactating Nelore cows (N = 1950 and 2793, respectively) from ranches that did not have a history of vaccinating against reproductive diseases (experiment 2), or only vaccinated against Leptospira spp. (experiment 3), were assigned to the same ESFTAI used in experiment 1. Within each ranch, cows received (VAC) or not (CON) vaccination against BoHV-1, BVDV, and Leptospira spp. at the beginning of the ESFTAI (Day -11) and 30 days after (Day 41) AI. In experiment 2, VAC cows had greater (P ≤ 0.05) pregnancy rates compared with CON on Days 30 and 120. In experiments 2 and 3, pregnancy loss was reduced (P ≤ 0.03) in primiparous VAC cows compared with CON cohorts. In experiment 4, 367 primiparous, lactating Nelore cows previously vaccinated against Leptospira spp. were assigned to the same ESFTAI used in experiment 1. Cows received VAC, or the same vaccine 30 days before (Day -41) and at the beginning (Day -11) of the ESFTAI (PREVAC). Pregnancy rates on Days 30 and 120 were greater (P ≤ 0.05) in PREVAC cows compared with VAC cows. In conclusion, pregnancy losses affected reproductive and overall efficiency of Brazilian cow-calf operations, and might be directly associated with BoHV-1, BVDV, and Leptospira spp. infections. Hence, vaccinating cows against these pathogens, particularly when both doses are administered before fixed-time AI, improved reproductive performance in Brazilian cow-calf systems. © 2013 Elsevier Inc.

Effects of vaccination against reproductive diseases on reproductive performance of lactating dairy cows submitted to AI

Four experiments evaluated the effects of vaccination against bovine herpesvirus-1 (BoHV-1), bovine viral diarrhea virus (BVDV), and Leptospira spp. on reproductive performance of lactating dairy cows without (experiments 1, 2, and 3) or with previous vaccination against these diseases (experiment 4). Cows were assigned to a fixed-time AI protocol (FTAI; d -11 to 0) in all experiments, as well as AI 12. h upon estrus detection in experiment 3. Pregnancy status was determined with transrectal ultrasonography on d 30 and 71 (d 60 for experiment 3) after AI. Pregnancy loss was considered in cows pregnant on d 30 but non-pregnant on the subsequent evaluation. In experiment 1, 853 cows received (VAC) or not (CON) vaccination against BoHV-1, BVDV, and Leptospira spp. at the beginning of the FTAI (d -11) and 30. d after AI. Pregnancy loss was reduced (P=0.03) in VAC cows compared with CON. In experiment 2, 287 cows received VAC or CON 30. d prior to (d -41) and at the beginning (d -11) of the FTAI. Pregnancy rates on d 30 and 71 were greater (P≤0.03) in VAC cows compared with CON. In experiment 3, 1680 cows with more than 28. d in milk were randomly assigned to receive VAC or CON with doses administered 14. d apart, and inseminated within 15-135. d after the second dose. Pregnancy rates on d 30 and 60 were greater (P≤0.02) in VAC cows compared with CON. In experiment 4, 820 cows received (REVAC) or not (CON) revaccination against BoHV-1, BVDV, and Leptospira spp. at the beginning of the FTAI protocol (d -11). Pregnancy rates and loss were similar (P≥0.54) between treatments. Hence, vaccinating naïve cows against BoHV-1, BVDV, and Leptospira spp. improved reproductive efficiency in dairy production systems, particularly when both doses were administered prior to AI. © 2013 Elsevier B.V.