Novel UL23 and UL30 substitutions in HSV1 and HSV2 viruses related to polymorphism or drug resistance.

Data on herpes simplex virus (HSV) polymorphism as well as acyclovir (ACV) and foscarnet (FOS) resistance mutations are not exhaustive and may hinder accurate diagnosis by next-generation sequencing (NGS). Here, we report novel UL23 and UL30 substitutions for HSV1 and HSV2 identified in immunocompromised patients treated for hematological malignancies during the last 6 years of HSV resistance surveillance at the University Hospital of Lyon. For HSV1, 35 novel UL23 substitutions and 52 novel UL30 substitutions were identified. For HSV2, 2 novel UL23 substitutions and 12 novel UL30 substitutions were identified. These results allow to complete the database of HSV1 and HSV2 substitutions, related either to polymorphism or to ACV and FOS resistance.

Unveiling the Ir single atoms as selective active species for the partial hydrogenation of butadiene by operando XAS.

Single-atom catalysts represent an intense topic of research due to their interesting catalytic properties for a wide range of reactions. Clarifying the nature of the active sites of single-atom catalysts under realistic working conditions is of paramount importance for the design of performant materials. We have prepared an Ir single-atom catalyst supported on a nitrogen-rich carbon substrate that has proven to exhibit substantial activity toward the hydrogenation of butadiene with nearly 100% selectivity to butenes even at full conversion. We evidence here, by quantitative operando X-ray absorption spectroscopy, that the initial Ir single atoms are coordinated with four light atoms i.e., Ir-X4 (X = C/N/O) with an oxidation state of +3.2. During pre-treatment under hydrogen flow at 250 °C, the Ir atom loses one neighbour (possibly oxygen) and partially reduces to an oxidation state of around +2.0. We clearly demonstrate that Ir-X3 (X = C/N/O) is an active species with very good stability under reactive conditions. Moreover, Ir single atoms remain isolated under a reducing atmosphere at a temperature as high as 400 °C.

Characterization of naturally occurring parainfluenza virus type 2 (hPIV-2) variants.

BACKGROUND: Human parainfluenza viruses (hPIV) are respiratory pathogens responsible for upper and lower respiratory tract infections. In most labs, the clinical diagnosis of hPIV is routinely done using techniques based on the detection of viral antigens such as immunofluorescence assay or/and viral isolation. STUDY DESIGN: Five hPIV-2 isolated from respiratory samples exhibited unusual phenotypic and antigenic characteristics. These isolates showed important syncytial cytopathic effect and failed to react with one specific monoclonal antibody. These variant strains were subsequently compared with hPIV-2 prototype strain by cellular and molecular techniques. RESULTS: Both variant and prototype strains showed similar growth kinetics. Observation of plaque formation and syncytia assay indicated a more important fusogenic activity for the variant strains. Sequencing of fusion (F) and hemagglutinin-neuraminidase (HN) genes showed differences between the "atypical" hPIV-2 isolates and the Greer hPIV-2 prototype strain. These differences were analyzed with molecular modelling and structure prediction soft wares. A potential new glycosylation site in HN, in addition to minor changes observed in the predicted structure for the variant strains could explain their antigenic variation. Genetic changes in the fusion peptide and the cleavage site of F could also explain the difference observed in the fusion activity. CONCLUSIONS: Continuous global viral surveillance is essential to monitor antigenic changes that may occur in nature particularly with regards to the implementation of diagnostic assays. The differences observed in F and HN between the prototype strain and clinical hPIV-2 variants could also provide new data for the analysis of Paramyxovirus fusion mechanisms and their pathogenesis.

Surveillance network for herpes simplex virus resistance to antiviral drugs: 3-year follow-up.

Herpes simplex virus (HSV) infections are very common in the general population and among immunocompromised patients. Acyclovir (ACV) is an effective treatment which is widely used. We deemed it essential to conduct a wide and coordinated survey of the emergence of ACV-resistant HSV strains. We have formed a network of 15 virology laboratories which have isolated and identified, between May 1999 and April 2002, HSV type 1 (HSV-1) and HSV-2 strains among hospitalized subjects. The sensitivity of each isolate to ACV was evaluated by a colorimetric test (C. Danve, F. Morfin, D. Thouvenot, and M. Aymard, J. Virol. Methods 105:207-217, 2002). During this study, 3900 isolated strains among 3357 patients were collected; 55% of the patients were immunocompetent. Only six immunocompetent patients excreted ACV-resistant HSV strains (0.32%), including one female patient not treated with ACV who was infected primary by an ACV-resistant strain. Among the 54 immunocompromised patients from whom ACV-resistant HSV strains were isolated (3.5%), the bone marrow transplantation patients showed the highest prevalence of resistance (10.9%), whereas among patients infected by human immunodeficiency virus, the prevalence was 4.2%. In 38% of the cases, the patients who excreted the ACV-resistant strains were treated with foscarnet (PFA), and 61% of them developed resistance to PFA. The collection of a large number of isolates enabled an evaluation of the prevalence of resistance of HSV strains to antiviral drugs to be made. This prevalence has remained stable over the last 10 years, as much among immunocompetent patients as among immunocompromised patients.

Resistant herpes simplex virus type 1 infection: an emerging concern after allogeneic stem cell transplantation.

Fourteen cases of severe acyclovir-resistant herpes simplex virus type 1 (HSV-1) infection, 7 of which showed resistance to foscarnet, were diagnosed among 196 allogeneic stem cell transplant recipients within a 29-month period. Recipients of unrelated stem cell transplants were at higher risk. All patients received foscarnet; 8 subsequently received cidofovir. Strains were initially foscarnet-resistant in 3 patients and secondarily so in 4 patients. In vitro resistance to acyclovir or foscarnet was associated with clinical failure of these drugs; however, in vitro susceptibility to foscarnet was associated with complete response in only 5 of 7 patients. No strain from any of the 7 patients was resistant in vitro to cidofovir; however, only 3 of 7 patients achieved complete response. Therefore, acyclovir- and/or foscarnet-resistant HSV-1 infections after allogeneic stem cell transplantation have become a concern; current strategies need to be reassessed and new strategies must be evaluated in this setting.

Reactivation of acyclovir-resistant thymidine kinase-deficient herpes simplex virus harbouring single base insertion within a 7 Gs homopolymer repeat of the thymidine kinase gene.

HSV infections are treated efficiently and prevented by acyclovir, although resistant strains have been reported. Resistance to acyclovir involves mainly mutations in the viral gene encoding thymidine kinase; mutations may lead to an altered or, more frequently, deficient TK. These acyclovir-resistant TK deficient strains are not able to reactivate from a latent infection in an experimental model, compared to TK positive strains. A case is reported of a bone marrow transplant child who developed HSV infection at 11 days post-transplantation. Acyclovir-resistant HSV 1 was isolated on day 19 post-transplantation. The patient was cured of his infection. A resistant virus was detected 20 months later that harboured the same TK gene mutation as the first resistant virus. This mutation is an insertion of one guanine in a homopolymer repeat of seven guanines located at codon 146 of TK. It has previously been reported and associated with the expression of a deficient TK activity and the ability to reactivate in mice. These results corroborate the clinical relevance of this mutation, which is associated with acyclovir-resistant recurrent infections in humans.

Genetic characterization of thymidine kinase from acyclovir-resistant and -susceptible herpes simplex virus type 1 isolated from bone marrow transplant recipients.

Emergence of acyclovir (Acy)-resistant herpes simplex virus (HSV) is a major concern in bone marrow transplant recipients. Phenotypic and genetic characterization of thymidine kinase (TK) was done for 7 Acy-susceptible and 11 Acy-resistant HSV-1 isolated from 11 patients. In total, 19 amino acid substitutions were detected that were not related to Acy resistance but to TK gene polymorphism, including 5 mutations that have not been previously reported. The Acy-resistant strain from 1 patient presented no TK gene mutation related to resistance. Five patients (45%) had isolates that harbored point mutations leading to amino acid substitutions that could be associated with Acy resistance. Of the 5 substitutions detected, 3 have not been previously reported (codons 51, 83, and 175). A nucleotide insertion or deletion was detected in resistant isolates from 5 patients (45%); these mutations are located in homopolymer repeats at codon 92 (1 subject) and at codon 146 (4 subjects).

Acyclovir-resistant varicella infection with atypical lesions in a non-HIV leukemic infant.

UNLABELLED: An HIV-negative infant presented with VZV primary infection during the maintenance therapy for megakaryoblastic leukaemia. The lesions were initially vesicular and necrotic but became verrucous and hyperkeratotic. A clinical resistance to acyclovir was suspected and confirmed by histologic and virologic studies. The patient was successfully treated by foscarnet. CONCLUSION: resistance of VZV to acyclovir may occur after a short treatment in a non-AIDS patient.

Lipoprotein(a) levels in children and adolescents with diabetes.

OBJECTIVE: To determine lipoprotein(a) in children and adolescents with IDDM and assess its relation with Lp(a) levels in their first degree relatives. RESEARCH DESIGN AND METHODS: In a cross-sectional study we included 141 IDDM patients, (58 male and 83 female) with mean ages 12.2 +/- 2.8 and 12.6 +/- 3.1 years, respectively. Patients with microalbuminuria, hepatopathy, thyroid dysfunction, infectious disease, acute decompensation or surgery three months prior to the study, were excluded. Clinical history, physical examination, blood chemistry, glycosilated hemoglobin, microalbuminuria and lipid profile including total cholesterol triglycerides, HDL-C, Apo A-I, Apo B and Lp(a) were determined. Parents and non-diabetic siblings were also studied when feasible. RESULTS: Mean plasma concentration of total cholesterol, HDL-C and Apo A-I were significantly higher in diabetic boys compared to their non-diabetic sibs. Mean Lp(a) plasma values and the prevalence of Lp(a) > 30 mg/dL were similar in the IDDM patients, their healthy sibs and parents. Hypercholesterolemia and hypertriglyceridemia were more frequent among the IDDM patients. No correlation was found between HbA1, and Lp(a) concentrations. However, a correlation was observed between Lp(a) plasma concentrations of parents and their diabetic and healthy offspring. CONCLUSION: Diabetes mellitus does not seem to affect Lp(a) levels. These data are consistent with a genetic regulation of Lp(a) plasma levels.

Tumor primario de células germinales del sistema nervioso central en pediatría: presentación de 14 casos / Primary tumor of germinal cells in pediatric central nervous system: presentation of 14 cases

De 200 casos de tumores primarios del sistema nervioso central, 14 (7 por ciento) resultaron tumores de células germinales, histológicamente 11 de ellos fueron germinomas, dos teratomas inmaduros con áreas de coroacarcinoma y tumor de senos endodérmicos (TI-C-TSE) y un teratoma maduro. Las manifestaciones clínicas iniciales fueron de tipo neuronal y endocrinológicas: hidrocefalia (57 por ciento) de campo visual (50 por ciento), ataxia y signos piramidales (43 por ciento), convulsiones (43 por ciento), paresias de pares craneános (36 por ciento), signo de Parinaud (21 por ciento), atrofia óptica 14 por ciento; hiperprolactinemia (43 por ciento), talla baja (43 por ciento), diabetes insípida (43 por ciento), pubertad precoz, hipotiroidismo e insuficiencia adrenal (7 por ciento) respectivamente. Las tomografías computarizadas de cráneo (TCC) evidenciaron el proceso tumoral en el 100 por ciento de los casos, contrastando con las radiografías simples de cráneo que sólo lo mostraron en el 36 por ciento de los casos. El tratamiento en todos fue cirugía y radioterapia sólo uno recibió quimioterapia, el TI-C.TSE con metástasis pulmonar. Concluimos que los germinomas deberán recibir radioterapia como tratamiento inicial. Es imprescindible la TCC, la búsqueda de células exfoliativas en líquido cefalorraquídeo y marcadores tumorales para el diagnóstico, así como las determinaciones hormonales necesarias

Hipofisectomia transesfenoidal. / Transphenoidal hypophysectomy

La hipofisectomia transesfenoidal a traves de un acceso oronasal a traves de la linea media fue introducida por Cushing en 1907.Guiot y Hardy introdujeron innovaciones tales como el uso de la fluoroscopia transoperatoria y del microscopio quirurgico.Se hizo hipofisectomia transesfenoidal con reseccion total del tumor y la glandula a 18 pacientes tratados en el Servicio de Neurocirugia del Hospital General del CM La Raza IMSS desde febrero de 1975 hasta junio de 1977. Hubo desaparicion de los sintomas de "hiperfuncionamiento" en estos pacientes y mejoria de la hemianopsia en el caso que tenia este defecto campimetrico. Todos los casos recibieron tratamiento hormonal de substitucion. Una paciente murio 36 horas despues de la operacion. En casos de "microadenomas" no debe hacerse reseccion total de la glandula, sino unicamente del tumor