Prevalence of anal high-risk human papillomavirus (HR-HPV) types in people living with HIV and a history of cancer.

This study aimed to describe the prevalence of high-risk human papillomavirus (HR-HPV) types in the anal canal in a cohort of people living with HIV (PLWHIV) with a history of malignancy. SETTING: Referral tertiary care hospital for adult patients with cancer. METHODS: We reviewed data of patients from the AIDS Cancer Clinic on antiretroviral therapy in chronic control who were consecutively referred for high-resolution anoscopy (HRA), where they underwent anal evaluation, collection of specimens for anal cytology and anal human papillomavirus (HPV) followed by HRA with directed biopsy if needed. RESULTS: A total of 155 patients were included; 149 (96.1%) were men, all of them men who have sex with men (MSM); the median age was 39 (IQR 32-47) years; 105 (67.7%) with Kaposi sarcoma, 40 (25.8%) with non-Hodgkin lymphoma and 10 (6.4%) with other neoplasms; only 7 (4.5%) had active cancer. The prevalence of HR-HPV infection was 89% (n=138) (95% CI 83-93) with at least one HR-HPV infection, and 62% (96) had coinfection with at least two types; the median HR-HPV types of coinfection were 3 (IQR 2-4). The number of patients infected with HPV 16 was 64 (41.3%, 95% CI 33.8-49.3), HPV 18 was 74 (47.7%, 95% CI 39.9-55.7) and with both 35 (22.6%). Some 59 patients (38%) had high-grade squamous intraepithelial lesions (HSIL) and 49 (31.6%) had low-grade squamous intraepithelial lesions (LSIL). The prevalence of HR-HPV and HSIL among patients aged ≤35 and >35 years was the same. CONCLUSIONS: In this cohort of PLWHIV with a history of malignancy we found a high prevalence of HR-HPV 16 and 18 and anal HSIL, even in persons aged ≤35 years. These data highlight the importance of anal cancer screening in PLWHIV and history of malignancy.

High-intensity ultrasound improves color and oxidative stability of beef from grain-fed and pasture-fed Nellore cattle.

This research aimed to evaluate the influence of high-intensity ultrasound (HIU) levels (control: 0; high: 747.79; ultra-high: 1344.17 Wcm-2) on pH, instrumental color (redness, R630/580, hue angle and chroma) and oxidative stability (lipid and protein oxidation) of Psoas major (PM) muscle from Nellore cattle raised in two feeding systems: grain and pasture. Using a structural equation modeling (SEM) approach, the relations (P > 0.05) between exogenous (HIU levels) and endogenous (pH, color, lipid and protein oxidation) variables were observed. In beef from grain-fed animals the pH was directly and negatively related to lipid oxidation (γ = -0.321), hue angle (γ = -0.847) and chroma (γ = -0.442) and protein oxidation (γ = -0.752). In PM from pasture-fed HIU exhibited a negative relation with lipid (γ = -0.144) and protein (γ = -0.743) oxidation, suggesting a possible positive influence on the oxidative stability of meat and a positive relation with redness (γ = 0.197) and R630/580 (γ = 0.379). The HIU positively influenced the color and oxidative stability of beef from Bos indicus cattle, and a synergistic effect of HIU and feeding system on beef from pasture-fed animals.

The usefulness of intraoperative consultation for the diagnosis of borderline ovarian tumors.

BACKGROUND: Borderline ovarian tumors (BTs) must be recognized during the surgery by intraoperative consultation (IOC) to guide surgical treatment; however, this diagnosis can be imprecise. Therefore, this study aimed to evaluate the diagnostic accuracy of IOC for the diagnosis of BT. METHODS: A retrospective cohort study was carried out including all women diagnosed with a pelvic tumor consecutively surgically treated from 2005 to 2015 with IOC. We calculated the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and likelihood ratios (LR) for the IOC and BTs. RESULTS: A total of 758 patients were enrolled, the median age was 44 years, the median tumor size was 11.8 cm, and the median CA-125 levels were 45.65 U/µL. After IOC, 458 (64.1%) cases were diagnosed as benign, 111 (14.7%) as BT, and 161 (21.2%) as malignant. The definitive diagnosis was a benign tumor in 448 (59.1%) cases, BT in 110 (14.5%), and 200 (26.4%) cases were malignant. The diagnostic accuracy of the IOC for BT diagnosis was 89.8% (sensitivity =65.5%, specificity =93.9%). The diagnosis performance of IOC for the diagnosis between BT and benign tumors (n=546) had a sensitivity of 69.9%, a specificity of 98.4%, and a diagnostic accuracy of 84%; meanwhile for the diagnosis between BT and malignant tumors (n=242) IOC had a sensitivity of 92.3%, a specificity of 81.7%, and a diagnostic accuracy of 87%. CONCLUSIONS: For practitioners, knowing the accuracy and limitations of the IOC for BT enables the better selection of cases to perform a complete staging surgery.

Prognostic significance of the mad1l1 1673 g:a polymorphism in ovarian adenocarcinomas

Abstract Background: Ovarian cancer is the most lethal gynecologic cancer. Although most patients respond adequately to the first-line therapy, up to 85% experience a recurrence of disease, which carries a poor prognosis. Mitotic arrest deficiency 1 is a protein that helps in the assembly of the mitotic spindle assembly checkpoint by preventing anaphase until all chromatids are properly aligned. A single-nucleotide polymorphism in the MAD1L1 gene is prevalent in patients with advanced epithelial ovarian cancer and alters the way in which it responds to chemotherapy. Objective: The objective of the study was to study the relationship between the rs1801368 polymorphism of MAD1L1 and prognosis of ovarian adenocarcinoma. Methods: A total of 118 patients in whom the MAD1L1 gene was sequenced were analyzed using descriptive and comparative statistics. Results: Patients carrying the wild-type genotype had a higher distribution of early-stage disease. Having a MAD1L1 polymorphic allele increased the risk of being non-sensitive to chemotherapy. The median disease-free survival for patients with the wild-type MAD1L1 was 46.93 months, compared to 10.4 months for patients with at least one polymorphic allele. Conclusions: The rs1801368 polymorphism of MAD1L1 gene worsens prognosis in patients with ovarian adenocarcinoma. Traditional therapy for ovarian cancer might not be optimal in patients carrying this polymorphism.

Prognostic Significance of the MAD1L1 1673 G: A Polymorphism in Ovarian Adenocarcinomas.

BACKGROUND: Ovarian cancer is the most lethal gynecologic cancer. Although most patients respond adequately to the first-line therapy, up to 85% experience a recurrence of disease, which carries a poor prognosis. Mitotic arrest deficiency 1 is a protein that helps in the assembly of the mitotic spindle assembly checkpoint by preventing anaphase until all chromatids are properly aligned. A single-nucleotide polymorphism in the MAD1L1 gene is prevalent in patients with advanced epithelial ovarian cancer and alters the way in which it responds to chemotherapy. OBJECTIVE: The objective of the study was to study the relationship between the rs1801368 polymorphism of MAD1L1 and prognosis of ovarian adenocarcinoma. METHODS: A total of 118 patients in whom the MAD1L1 gene was sequenced were analyzed using descriptive and comparative statistics. RESULTS: Patients carrying the wild-type genotype had a higher distribution of early-stage disease. Having a MAD1L1 polymorphic allele increased the risk of being non-sensitive to chemotherapy. The median disease-free survival for patients with the wild-type MAD1L1 was 46.93 months, compared to 10.4 months for patients with at least one polymorphic allele. CONCLUSIONS: The rs1801368 polymorphism of MAD1L1 gene worsens prognosis in patients with ovarian adenocarcinoma. Traditional therapy for ovarian cancer might not be optimal in patients carrying this polymorphism.

THERAPEUTIC USE OF HUMAN PAPILLOMAVIRUS VACCINES IN CERVICAL LESIONS.

Human papillomavirus (HPV) has been associated with the development of precancerous lesions of the cervix and cervical cancer (CC). Prophylactic HPV vaccination induces the development of a specific memory immune response that facilitates HPV elimination once the natural infection occurs. At present, in addition to the prophylactic vaccine, therapeutic vaccines are being developed and researched with the aim of inducing an immune response that allows the elimination of HPV-infected cells. The purpose of this study is to describe the current evidence on the use of therapeutic vaccines and their effect on cervical precancerous lesions, to establish recommendations on their clinical use. So far, the studies that have generated results have described a marginal beneficial effect of the prophylactic vaccine in the management of infection and pre-invasive lesions. Based on the evidence, continuing research on the efficacy and safety of therapeutic vaccines for the treatment of cervical intraepithelial lesions is recommended. The use of the HPV prophylactic vaccine as treatment for pre-existing lesions is not advised, but it is recommended to prevent new lesions.

Therapeutic use of human papillomavirus vaccines in cervical lesions

ABSTRACT Human papillomavirus (HPV) has been associated with the development of precancerous lesions of the cervix and cervical cancer (CC). Prophylactic HPV vaccination induces the development of a specific memory immune response that facilitates HPV elimination once the natural infection occurs. At present, in addition to the prophylactic vaccine, therapeutic vaccines are being developed and researched with the aim of inducing an immune response that allows the elimination of HPV-infected cells. The purpose of this study is to describe the current evidence on the use of therapeutic vaccines and their effect on cervical precancerous lesions, to establish recommendations on their clinical use. So far, the studies that have generated results have described a marginal beneficial effect of the prophylactic vaccine in the management of infection and pre-invasive lesions. Based on the evidence, continuing research on the efficacy and safety of therapeutic vaccines for the treatment of cervical intraepithelial lesions is recommended. The use of the HPV prophylactic vaccine as treatment for pre-existing lesions is not advised, but it is recommended to prevent new lesions.

Prognostic Significance of the MAD1L1 1673 G: A Polymorphism in Ovarian Adenocarcinomas.

BACKGROUND: Ovarian cancer is the most lethal gynecologic cancer. Although most patients respond adequately to the first-line therapy, up to 85% experience a recurrence of disease, which carries a poor prognosis. Mitotic arrest deficiency 1 is a protein that helps in the assembly of the mitotic spindle assembly checkpoint by preventing anaphase until all chromatids are properly aligned. A single-nucleotide polymorphism in the MAD1L1 gene is prevalent in patients with advanced epithelial ovarian cancer and alters the way in which it responds to chemotherapy. OBJECTIVE: The objective of the study was to study the relationship between the rs1801368 polymorphism of MAD1L1 and prognosis of ovarian adenocarcinoma. METHODS: A total of 118 patients in whom the MAD1L1 gene was sequenced were analyzed using descriptive and comparative statistics. RESULTS: Patients carrying the wild-type genotype had a higher distribution of early-stage disease. Having a MAD1L1 polymorphic allele increased the risk of being non-sensitive to chemotherapy. The median disease-free survival for patients with the wild-type MAD1L1 was 46.93 months, compared to 10.4 months for patients with at least one polymorphic allele. CONCLUSIONS: The rs1801368 polymorphism of MAD1L1 gene worsens prognosis in patients with ovarian adenocarcinoma. Traditional therapy for ovarian cancer might not be optimal in patients carrying this polymorphism.

Cytomorphological features of high-grade intraepithelial neoplasia/carcinoma of the cervix following chemoradiotherapy.

BACKGROUND: Cervicovaginal cytology as a follow-up study in women with a history of a cervical carcinoma treated with chemo-radiotherapy (CRT) plays an important role; however, the cytomorphological characteristics for the diagnosis of high-grade squamous intraepithelial lesions (H-SIL) in post-CRT patients have not been established. The aim of the study is to find the cytomorphological characteristics that support the diagnosis of H-SIL by conventional cytology in these patients. MATERIALS AND METHODS: This is a cross-sectional study from 2009 to 2015, which includes patients with a diagnosis of squamous cell carcinoma treated with CRT, who all have cervix cytology for follow-up and a later biopsy. RESULTS: We identified 82 cases, where the most frequent clinical stage was IIA1 to IIB with 26 cases (61.9%), the most common symptom was transvaginal bleeding (64.29%). The cytological characteristics that were statistically associated with the presence of a positive biopsy were the presence of a hemorrhagic background (45.2% vs. 12.5%, P = .007), high cellularity (45.2% vs. 15%, P < .001), disposition in groups/sheets (69% vs. 22.5%, P < .001), postradiotherapy changes at the background of the smear (73.8 vs. 50%, P < .001) and an increased nuclear/cytoplasmic ratio (100% vs. 22.5%, P < .001). CONCLUSIONS: In patients with CRT, the presence of specific features can help the diagnosis of H-SIL with excellent diagnostic performance.

[Resultados quirúrgicos de histerectomía radical laparoscópica en pacientes con cáncer de cérvix en etapa temprana: experiencia inicial en Instituto de Cáncer]. / Surgical outcomes of laparoscopic radical hysterectomy for patients with early cervical cancer: Initial experience in Cancer Institute.

ANTECEDENTES: La histerectomía radical abierta con linfadenectomía pélvica bilateral es el tratamiento estándar para el cáncer de cérvix uterino (CACU) en etapas temprana (1A2-1B1); la histerectomía radical por laparoscopia (HRL) es una opción segura y viable. OBJETIVO: Evaluar la seguridad y la factibilidad de la HRL en un centro hospitalario de atención de cáncer. MÉTODO: Estudio retrospectivo que incluyó 17 pacientes con CACU en etapa temprana intervenidas con HRL entre abril de 2013 y noviembre de 2016 en el Instituto Nacional de Cancerología de México. RESULTADOS: Las 17 pacientes se encontraban en etapa clínica IB1, en 10 (58.8%) fue subtipo epidermoide, en 4 (23.5%) adenocarcinoma y en 3 (17.6%) adenoescamoso. La media de edad fue de 42 ± 8 años. El tamaño del tumor fue de 2.3 ± 0.9 cm, y en el 94.1% los márgenes quirúrgicos estaban libres de enfermedad. El promedio de tiempo operatorio fue de 341 ± 65 minutos, con una pérdida sanguínea de 107 ± 64 ml, no requirieron trasfusión sanguínea y no hubo conversión a cirugía abierta. La media de estancia hospitalaria fue de 2.7 días (rango: 2-7 días). No se presentaron complicaciones intraoperatorias ni posoperatorias. CONCLUSIONES: La HRL es una alternativa segura y confiable para el tratamiento del CACU en etapa temprana. BACKGROUND: Open radical hysterectomy with bilateral pelvic lymphadenectomy is the standard treatment in early stages (1A2-1B1) of uterine cervical cancer (UCC); laparoscopic radical hysterectomy (LRH) is a safe and viable option. OBJECTIVE: To evaluate the safety and feasibility of LRH in a hospital cancer care center. METHOD: Retrospective study that included the first 17 patients with UCC in an early stage operated with LRH in the period from April 2013 to November 2016 at the National Cancer Institute of Mexico. RESULTS: The 17 patients were stage IB1 clinical, of which 10 (58.8%) was epidermoid subtype, 4 (23.5%) adenocarcinoma and 3 (17.6%) adenoescamoso. The mean age was 42 ± 8 years. The tumor size was 2.3 ± 0.9 cm, and in 94.1% the surgical margins were free of disease. The average operative time was 341 ± 65 minutes and blood loss of 107 ± 64 ml, no patient required blood transfusion and there was no case of conversion to open surgery. The average length of hospital stay was 2.7 days (range: 2-7 days). There were no intraoperative or postoperative complications. CONCLUSIONS: LRH is a safe and reliable alternative for the treatment of early stage UCC.

Single-cell sequencing unveils the lifestyle and CRISPR-based population history of Hydrotalea sp. in acid mine drainage.

Acid mine drainage (AMD) is characterized by an acid and metal-rich run-off that originates from mining systems. Despite having been studied for many decades, much remains unknown about the microbial community dynamics in AMD sites, especially during their early development, when the acidity is moderate. Here, we describe draft genome assemblies from single cells retrieved from an early-stage AMD sample. These cells belong to the genus Hydrotalea and are closely related to Hydrotalea flava. The phylogeny and average nucleotide identity analysis suggest that all single amplified genomes (SAGs) form two clades that may represent different strains. These cells have the genomic potential for denitrification, copper and other metal resistance. Two coexisting CRISPR-Cas loci were recovered across SAGs, and we observed heterogeneity in the population with regard to the spacer sequences, together with the loss of trailer-end spacers. Our results suggest that the genomes of Hydrotalea sp. strains studied here are adjusting to a quickly changing selective pressure at the microhabitat scale, and an important form of this selective pressure is infection by foreign DNA.

Color stability and lipid oxidation of broiler breast meat from animals raised on organic versus non-organic production systems.

The aim of the present research was to evaluate the influence of organic and non-organic production systems on color stability and lipid oxidation of broiler meat Pectoralis major (PM) stored under refrigeration (4°C) for 9 days. PM samples from organic (ORG) and non-organic (NORG) production systems were compared based on physicochemical analyses (instrumental color, myoglobin concentration, metmyoglobin reducing activity (MRA), pH, and lipid oxidation) performed in 4 different trials (n = 4). In general, NORG broilers demonstrated higher (P < 0.05) b* and lipid oxidation values than ORG, whereas ORG samples exhibited increased (P < 0.05) MRA, ratio of reflectance at 630 per 580 nanometers (R 630/580), and a* values. The lower color stability observed in NORG samples can be partly due to lipid oxidation. Therefore, the production system can affect color and lipid stability of broiler breast meat during storage.

Frequency of glutathione-S-transferase null-M1 and null-T1 genotypes among the Turabah population in Saudi Arabia.

Glutathione-S-transferases (GST) are key phase II detoxifying enzymes that play critical roles in protection against products of oxidative stress and against electrophiles. Glutathione S-transferase mu (GST-M1) and theta (GST-T1) are isoforms of glutathione transferase enzymes that participate in the metabolism of a wide range of chemicals. Deletion variants that are associated with a lack of enzyme function exist at both these loci. The frequencies of homozygous GSTM1 and GSTT1 deletion carriers are very high in most of the populations studied to date. The aim of this study was to investigate the frequencies of GSTM1 and GSTT1 genotypes among the Turabah population in Saudi Arabia in comparison with the data published for some other Arabic populations. The subjects consisted of 164 unrelated healthy individuals from the Turabah population. GST genotyping was performed by multiplex polymerase chain reaction-based methods. The GSTM1 deletion homozygosity was 56.1% and GSTT1 deletion homozygosity was 20.7%, while the GSTM1 and GSTT1 double-deletion homozygosity was 11.0%. Comparison with published data from Bahraini, Lebanese, and Tunisian populations demonstrated no significant difference for GSTM1 between these populations. The GSTT1 null-allele frequency was significantly lower than those for the Lebanese and Tunisian populations (P = 0.001) but similar to that for the Bahraini population (P = 0.099). Characterization of GST genetic polymorphisms in the Saudi population may aid in genetic studies on the association of GSTM1 and GSTT1 polymorphisms with disease risks and the pharmacogenetics of chemotherapy.

Randomized Phase II Study of Talc Versus Iodopovidone for the Prevention of Seroma Formation Following Modified Radical Mastectomy.

BACKGROUND: The most common complication following modified radical mastectomy is seroma formation. Numerous approaches have been attempted to prevent this complication, ranging from the use of chemical substances to mechanical means, and none of these have proven to be consistently reliable. AIM: The aim of this study was to evaluate the safety and efficacy of talc in preventing postoperative seromas compared with iodine and standard care. METHODS: Patients with breast cancer undergoing modified radical mastectomy were randomly assigned to one of three study groups: control, subcutaneous talc, or iodine application. The primary endpoint was frequency of seroma formation. Secondary outcomes included wound complications (surgical site infection, flap necrosis, and wound dehiscence), analgesic use, postoperative pain, total drain outputs, and drainage duration. RESULTS: Of the 86 patients randomized in the study, 80 were analyzed. After interim analysis, the iodine intervention was discontinued because of increased adverse outcomes (drainage duration and total amount of fluid drained). Talc failed to demonstrate that its application in subcutaneous breast tissue prevents seroma formation (19.4% for talc group vs. 23.3% for control group; p = 0.70). However, patients who developed seroma in the talc group had fewer aspirations per patient seroma and less volume drained when compared with the control group (88.2 ± 73 vs. 158.3 ± 90.5; p = 0.17). CONCLUSIONS: Subcutaneous talc application was safe in the short term, but there was not sufficient evidence to support its use for seroma prevention following modified radical mastectomy in patients with breast cancer.

[Risk factors of nontransmissible chronic diseases in students of medicine of Carabobo University. Venezuela. Year 2006]. / Factores de riesgo de enfermedades crónicas no ransmisibles en estudiantes de la carrera de Medicina. Universidad de Carabobo, Venezuela. Año 2006.

UNLABELLED: Generally, a student changes lifestyle when enters to the University, this can lead to different alimentary habits that could become as risk factors of nontransmissible chronic diseases (NTCD). OBJECTIVE: To evaluate the presence of risk factors of NTCD in students of medicine race in Carabobo University. METHODOLOGY: 120 people were evaluated, students of third to the sixth year of the medicine race, Carabobo University, year 2006. Family records, nutritional habits, alcohol and tobacco consumption were studied. Anthropometric measures, arterial pressure, glycemia and lipids sérics, were determined. RESULTS: Of evaluated students 68 they belonged to feminine sex and 52 masculine, age between 18 and 26 years old. The risk factor more frequent was the sedentary (72.49%), followed of alcoholic habits (68.3%) and smoking tobacco (34.16%). A 37.5% had high consumption of oils and fats, 58.3% starches and sugars. A 33.34% was overweight or obesity; 3.33% with high blood pressure and metabolic syndrome. The family antecedent predominant was high blood pressure (60%) and obesity (28.2%). CONCLUSION: In this student population risk factors for NTCD exist, which alerts on the necessity to restore plans of education and measures of primary prevention in order to diminish to future the appearance of NTCD in the students of the medicine race in Carabobo University.

[Overweight and associated pathologies in adult women]. / Exceso de peso y patologías asociadas en mujeres adultas.

UNLABELLED: Overweight and obesity represent an important public health problem in the world, including developed and underdeveloped countries, as contributing factors for non transmissible chronic illnesses in the adult, affecting both sexes, but especially to women. OBJECTIVE: To associate excess in weight to the presence of comorbidities in adult women. METHODOLOGY: 130 women, age 25 to 70 years with body mass index (BMI) > 25 kg/m(2) were assessed. Weight, height, arm, waist and hip circumferences, tricipital and subescapular skinfolds. BMI, waist/hip ratio (W/H ratio) and fatty area were determined. Presence of diabetes mellitus (DM); high blood pressure (HBP), dyslipidemia and arthropathy were assessed. Overweight and obesity were classified according to OMS criteria. Data was analyzed by SPSS version 11.0. RESULTS: 24,6% of women (n = 32) were overweight; 38,5% (n = 50) were obese I; 23,8% (n = 31) were obese II; and 13,1% (n = 17) had obesity III. Associated pathologies were present in 80,8% of the studied women: 46,9% (n = 61) with dyslipidemia; 42,3% (n = 55) with HBP; 33,1% (n = 43) with arthropaties; and 16,2% (n = 21) with DM. Overweight and obese I women showed a higher prevalence of dyslipidemia (56%) and (52%), respectively; while in Obese II and Obese III, 38,7% and 47,1% presented HBP respectively. There was a positive correlation (Spearman) among DM, HBP and dyslipidemia (p < 0,05) with age; and significant correlation (Pearson, p < 0,05) between W/H ratio and DM. CONCLUSION: There was a high prevalence of associated pathologies in the valued women, being the most frequent dyslipidemia, HBP and arthropathy, which are directly proportional with the age and the IC/C.

Closure of rRNA related gaps in the Chromobacterium violaceum genome with the PCR-assisted contig extension (PACE) protocol

In the finishing phase of the Chromobacterium violaceum genome project, the shotgun sequences were assembled into 57 contigs that were then organized into 19 scaffolds, using the information from shotgun and cosmid clones. Among the 38 ends resulting from the 19 scaffolds, 10 ended with sequences corresponding to rRNA genes (seven ended with the 5S rRNA gene and three ended with the 16S rRNA gene). The 28 non-ribosomal ends were extended using the PCR-assisted contig extension (PACE) methodology, which immediately closed 15 real gaps. We then applied PACE to the 16S rRNA gene containing ends, resulting in eight different sequences that were correctly assembled within the C. violaceum genome by combinatory PCR strategy, with primers derived from the non-repetitive genomic region flanking the 16S and 5S rRNA gene. An oriented combinatory PCR was used to correctly position the two versions (copy A and copy B, which differ by the presence or absence of a 100-bp insert); it revealed six copies corresponding to copy A, and two to copy B. We estimate that the use of PACE, followed by combinatory PCR, accelerated the finishing phase of the C. violaceum genome project by at least 40 per cent

Surgical outcome in mesial temporal sclerosis correlates with prion protein gene variant.

BACKGROUND: Mesial temporal lobe epilepsy related to hippocampal sclerosis (MTLE-HS) is the most common surgically remediable epileptic syndrome. Ablation of the cellular prion protein (PrP(c)) gene (PRNP) enhances neuronal excitability of the hippocampus in vitro and sensitivity to seizure in vivo, indicating that PrP(c) might be related to epilepsy. OBJECTIVE: To evaluate the genetic contribution of PRNP to MTLE-HS. METHODS: The PRNP coding sequence of DNA from peripheral blood cells of 100 consecutive patients with surgically treated MTLE-HS was compared to that from a group of healthy controls adjusted for sex, age, and ethnicity (n = 180). The presence of PRNP variant alleles was correlated with clinical and presurgical parameters as well as surgical outcome. RESULTS: A variant allele at position 171 (Asn-->Ser), absent in controls, was found in heterozygosis (Asn171Ser) in 23% of patients (p < 0.0001). The PRNP genotypes were not correlated with any clinical or presurgical data investigated. However, patients carrying the Asn171Ser variant had a five times higher chance of continuing to have seizures after temporal lobectomy (95% CI 1.65 to 17.33, p = 0.005) than those carrying the normal allele. At 18 months after surgery, 91.8% of patients with the normal allele at codon 171 were seizure free, in comparison to 68.2% of those carrying Asn171Ser (p = 0.005). CONCLUSIONS: The PRNP variant allele Asn171Ser is highly prevalent in patients with medically untreatable MTLE-HS and influences their surgical outcome. The results suggest that the PRNP variant allele at codon 171 (Asn171Ser) is associated with epileptogenesis in MTLE-HS.

Human semaphorin 6B [(HSA)SEMA6B], a novel human class 6 semaphorin gene: alternative splicing and all-trans-retinoic acid-dependent downregulation in glioblastoma cell lines.

We have identified a novel human gene related to the class 6 semaphorin family of axon guidance molecules, termed human semaphorin 6B or (HSA)SEMA6B. Two splicing variants of this gene were identified by RT-PCR: (HSA)SEMA6B.1 (short isoform) and (HSA)SEMA6B.2 (longer isoform). Computational analysis suggests that these isoforms correspond to putative secreted and transmembranous semaphorins, respectively. The levels of (HSA)SEMA6B expression were evaluated by Northern blot analysis in different tissues and in some pathological and pharmacological conditions. We observed that (HSA)SEMA6B is highly expressed in human brain and at lower levels in a variety of other tissues. Interestingly, the (HSA)SEMA6B transcript was downregulated in two different human glioblastoma cell lines (T98G and A172) upon prolonged treatment with all-trans-retinoic acid, an anti-tumor and differentiation-inducing agent.