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BACKGROUND: The world has suffered immeasurably during the COVID-19 pandemic. Increased distress and mental and medical health concerns are collateral consequences to the disease itself. The Genes to Mental Health (G2MH) Network consortium sought to understand how individuals affected by the rare copy number variations of 22q11.2 deletion and duplication syndrome, associated with neurodevelopmental/neuropsychiatric conditions, were coping. The article focuses on worry and disruptions in medical care caused by the pandemic. METHODS: The University of Pennsylvania COVID-19 Stressor List and care disruption questions were circulated by 22 advocacy groups in English and 11 other languages. RESULTS: A total of 512 people from 23 countries completed the survey; most were caregivers of affected individuals. Worry about family members acquiring COVID-19 had the highest average endorsed worry, whilst currently having COVID-19 had the lowest rated worry. Total COVID-19 worries were higher in individuals completing the survey towards the end of the study (later pandemic wave); 36% (n = 186) of the sample reported a significant effect on health due to care interruption during the pandemic; 44% of individuals (n = 111) receiving care for their genetic syndrome in a hospital setting reported delaying appointments due to COVID-19 fears; 12% (n = 59) of the sample reported disruptions to treatments; and of those reporting no current disruptions, 59% (n = 269) worried about future disruptions if the pandemic continued. Higher levels of care disruptions were related to higher COVID-19 worries (Ps < 0.005). Minimal differences by respondent type or copy number variation type emerged. CONCLUSIONS: Widespread medical care disruptions and pandemic-related worries were reported by individuals with 22q11.2 syndrome and their family members. Reported worries were broadly consistent with research results from prior reports in the general population. The long-term effects of COVID-19 worries, interruptions to care and hospital avoidance require further study.
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COVID-19 , Variaciones en el Número de Copia de ADN , Cuidadores , Cromosomas , Humanos , PandemiasRESUMEN
SARS-CoV-2 infection, named COVID-19, can lead to a dysregulated immune response and abnormal coagulation responsible for a viral sepsis. In this review, we specify physiopathological mechanisms of each phase of COVID-19 - viral, immune and pro-thrombotic - notably because they involve different treatment. Finally, we specify the physiopathological mechanisms of organ injury.
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Betacoronavirus , Infecciones por Coronavirus , Pandemias , Neumonía Viral , Animales , Betacoronavirus/genética , Betacoronavirus/inmunología , Betacoronavirus/ultraestructura , COVID-19 , Infecciones por Coronavirus/complicaciones , Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/inmunología , Infecciones por Coronavirus/terapia , Citocinas/metabolismo , Humanos , Inmunización , Inmunomodulación , Especificidad de Órganos , Neumonía Viral/complicaciones , Neumonía Viral/epidemiología , Neumonía Viral/inmunología , Neumonía Viral/terapia , SARS-CoV-2 , Trombosis/prevención & control , Trombosis/virología , Tropismo Viral , Internalización del Virus , Replicación Viral/fisiología , Zoonosis/virologíaRESUMEN
Volume-phonon-polaritons (VPP's) propagating at a light-in-vacuum-like speed are identified in the wurtzite-type Zn0.74Mg0.26Se mixed crystal by near-forward Raman scattering. Their detection is selective to both the laser energy and the laser polarization, depending on whether the ordinary (n0) or extraordinary (ne) refractive index is addressed. Yet, no significant linear birefringence (n0 [Formula: see text] ne) is observed by ellipsometry. The current access to ultrafast VPP's is attributed to the quasi-resonant Raman probing of an anomalous dispersion of n0 due to impurity levels created deep in the optical band gap by oriented structural defects. The resonance conditions are evidenced by a dramatic enhancement of the Raman signals due to the polar modes. Hence, this work reveals a capacity for the lattice defects' engineering to "accelerate" the VPP's of a mixed crystal up to light-in-vacuum-like speeds. This is attractive for ultrafast signal processing in the terahertz range. On the fundamental side we provide an insight into the VPP's created by alloying ultimately close to the center of the Brillouin zone.
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The original version of this Article omitted the author Dr Mathias Chamaillard from the l'Institut de Pasteur, Lille, France. This has been corrected in both the PDF and HTML versions of the Article.
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BACKGROUND: HIV-1 viral load testing is now recommended by the World Health Organization for every patient receiving antiretroviral therapy (ART). OBJECTIVES: The objective of this study is to evaluate the performance of commercial assays for their ability to quantify HIV-1 strains currently circulating in France. STUDY DESIGN: The performances of the Generic HIV-RNA assay from Biocentric were compared to those of the Roche CAP/CTM v1.5, Roche CAP/CTM v2.0 and Abbott m2000 RealTime HIV-1 assays. A total of 1885 HIV-1 plasma samples were tested, including 684 samples from patients included in the ANRS-Primo Cohort. RESULTS: We found a good concordance of quantification between the Roche v2.0 and the Biocentric assays, both of which were superior to the Roche v1.5 assay. We show moderate agreement between techniques; however, CRF02_AG strains and undetermined viruses were underestimated when quantified with the Roche CAP/CTM v2.0. In contrast, a comparison of the Biocentric and Abbott assay results showed strong agreement between assays, indicating that both are well suited for quantification of CRF02_AG strains. Moreover, a 2% underestimation of the B subtypes was observed with the Biocentric assay. CONCLUSIONS: These results have implications for viral load monitoring in Western Africa, where CRF02_AG strains are highly prevalent. Closer epidemiological surveillance and evaluation of commercial assays are still necessary to better evaluate the impact of the genetic evolution of circulating viruses on HIV-RNA quantification in the regions most affected by the HIV-1 epidemic.
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Técnicas de Laboratorio Clínico/métodos , Infecciones por VIH/diagnóstico , VIH-1/clasificación , ARN Viral/sangre , Carga Viral/métodos , Estudios de Cohortes , Francia , Infecciones por VIH/virología , Seropositividad para VIH/diagnóstico , Humanos , Tamizaje Masivo , ARN Viral/genética , Sensibilidad y EspecificidadRESUMEN
Background: Atazanavir is a PI widely used as a third agent in combination ART. We aimed to determine the prevalence and the patterns of resistance in PI-naive patients failing on an atazanavir-based regimen. Methods: We analysed patients failing on an atazanavir-containing regimen used as a first line of PI therapy. We compared the sequences of reverse transcriptase and protease before the introduction of atazanavir and at failure [two consecutive viral loads (VLs) >50 copies/mL]. Resistance was defined according to the 2014 Agence Nationale de Recherche sur le SIDA et les Hépatites Virales (ANRS) algorithm. Results: Among the 113 patients, atazanavir was used in the first regimen in 71 (62.8%) patients and in the first line of a PI-based regimen in 42 (37.2%). Atazanavir was boosted with ritonavir in 95 (84.1%) patients and combined with tenofovir/emtricitabine or lamivudine (n = 81) and abacavir/lamivudine or emtricitabine (n = 22). At failure, median VL was 3.05 log10 copies/mL and the median CD4+ T cell count was 436 cells/mm3. The median time on atazanavir was 21.2 months. At failure, viruses were considered resistant to atazanavir in four patients (3.5%) with the selection of the following major atazanavir-associated mutations: I50L (n = 1), I84V (n = 2) and N88S (n = 1). Other emergent PI mutations were L10V, G16E, K20I/R, L33F, M36I/L, M46I/L, G48V, F53L, I54L, D60E, I62V, A71T/V, V82I/T, L90M and I93L/M. Emergent NRTI substitutions were detected in 21 patients: M41L (n = 2), D67N (n = 3), K70R (n = 1), L74I/V (n = 3), M184V/I (n = 16), L210W (n = 1), T215Y/F (n = 3) and K219Q/E (n = 2). Conclusions: Resistance to atazanavir is rare in patients failing the first line of an atazanavir-based regimen according to the ANRS. Emergent NRTI resistance-associated mutations were reported in 18% of patients.
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Sulfato de Atazanavir/uso terapéutico , Farmacorresistencia Viral/genética , Infecciones por VIH/tratamiento farmacológico , Inhibidores de la Proteasa del VIH/uso terapéutico , VIH-1/genética , Adulto , Didesoxinucleósidos , Combinación de Medicamentos , Emtricitabina/uso terapéutico , VIH-1/efectos de los fármacos , Humanos , Lamivudine , Masculino , Persona de Mediana Edad , Mutación , Estudios Retrospectivos , Tenofovir/uso terapéutico , Insuficiencia del Tratamiento , Carga ViralRESUMEN
Upon oral infection with Toxoplasma gondii cysts (76 K strain) tachyzoites are released into the intestinal lumen and cross the epithelial barrier causing damage and acute intestinal inflammation in C57BL/6 (B6) mice. Here we investigated the role of microbiota and IL-22 in T.gondii-induced small intestinal inflammation. Oral T.gondii infection in B6 mice causes inflammation with IFNγ and IL-22 production. In IL-22-deficient mice, T.gondii infection augments the Th1 driven inflammation. Deficiency in either IL-22bp, the soluble IL-22 receptor or Reg3γ, an IL-22-dependent antimicrobial lectin/peptide, did not reduce inflammation. Under germ-free conditions, T.gondii-induced inflammation was reduced in correlation with parasite load. But intestinal inflammation is still present in germ-free mice, at low level, in the lamina propria, independently of IL-22 expression. Exacerbated intestinal inflammation driven by absence of IL-22 appears to be independent of IL-22 deficiency associated-dysbiosis as similar inflammation was observed after fecal transplantation of IL-22-/- or WT microbiota to germ-free-WT mice. Our results suggest cooperation between parasite and intestinal microbiota in small intestine inflammation development and endogenous IL-22 seems to exert a protective role independently of its effect on the microbiota. In conclusion, IL-22 participates in T.gondii induced acute small intestinal inflammation independently of microbiota and Reg3γ.
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Microbioma Gastrointestinal/inmunología , Inflamación/inmunología , Interleucinas/metabolismo , Intestinos/inmunología , Toxoplasma/fisiología , Toxoplasmosis/inmunología , Animales , Células Cultivadas , Progresión de la Enfermedad , Interleucinas/genética , Intestinos/parasitología , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Proteínas Asociadas a Pancreatitis/genética , Proteínas Asociadas a Pancreatitis/metabolismo , Carga de Parásitos , Receptores de Interleucina/genética , Receptores de Interleucina/metabolismo , Interleucina-22RESUMEN
Background: Surveillance of HIV-1 resistance in treated patients with a detectable viral load (VL) is important to monitor, in order to assess the risk of spread of resistant viruses and to determine the proportion of patients who need new antiretroviral drugs with minimal cross-resistance. Methods: The HIV-1 protease and reverse transcriptase (RT) and integrase genes were sequenced in plasma samples from 782 consecutive patients on failing antiretroviral regimens, seen in 37 specialized centres in 2014. The genotyping results were interpreted using the ANRS v24 algorithm. Prevalence rates were compared with those obtained during a similar survey conducted in 2009. Results: The protease and RT sequences were obtained in 566 patients, and the integrase sequence in 382 patients. Sequencing was successful in 60%, 78%, 78% and 87% of patients with VLs of 51-200, 201-500, 501-1000 and >1000â copies/mL, respectively. Resistance to at least one antiretroviral drug was detected in 56.3% of samples. Respectively, 3.9%, 8.7%, 1.5% and 3.4% of patients harboured viruses that were resistant to any NRTI, NNRTI, PI and integrase inhibitor (INI). Resistance rates were lower in 2014 than in 2009. Resistance was detected in 48.5% of samples from patients with a VL between 51 and 200â copies/mL. Conclusion: In France in 2014, 90.0% of patients in AIDS care centres were receiving antiretroviral drugs and 12.0% of them had VLs >50 copies/mL. Therefore, this study suggests that 6.7% of treated patients in France might transmit resistant strains. Resistance testing may be warranted in all treated patients with VL > 50â copies/mL.
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Fármacos Anti-VIH/uso terapéutico , Farmacorresistencia Viral Múltiple , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/virología , VIH-1/efectos de los fármacos , Carga Viral , Adulto , Terapia Antirretroviral Altamente Activa , Femenino , Francia , Genes Virales , Genotipo , Infecciones por VIH/sangre , Integrasa de VIH/sangre , Integrasa de VIH/genética , Proteasa del VIH/sangre , Proteasa del VIH/genética , Transcriptasa Inversa del VIH/sangre , Transcriptasa Inversa del VIH/genética , VIH-1/genética , Humanos , Masculino , Persona de Mediana Edad , ARN Viral/sangre , Inhibidores de la Transcriptasa Inversa/uso terapéutico , Análisis de Secuencia de ADN , Insuficiencia del TratamientoRESUMEN
Copy number variants (CNVs) are major contributors to genomic imbalance disorders. Phenotyping of 137 unrelated deletion and reciprocal duplication carriers of the distal 16p11.2 220 kb BP2-BP3 interval showed that these rearrangements are associated with autism spectrum disorders and mirror phenotypes of obesity/underweight and macrocephaly/microcephaly. Such phenotypes were previously associated with rearrangements of the non-overlapping proximal 16p11.2 600 kb BP4-BP5 interval. These two CNV-prone regions at 16p11.2 are reciprocally engaged in complex chromatin looping, as successfully confirmed by 4C-seq, fluorescence in situ hybridization and Hi-C, as well as coordinated expression and regulation of encompassed genes. We observed that genes differentially expressed in 16p11.2 BP4-BP5 CNV carriers are concomitantly modified in their chromatin interactions, suggesting that disruption of chromatin interplays could participate in the observed phenotypes. We also identified cis- and trans-acting chromatin contacts to other genomic regions previously associated with analogous phenotypes. For example, we uncovered that individuals with reciprocal rearrangements of the trans-contacted 2p15 locus similarly display mirror phenotypes on head circumference and weight. Our results indicate that chromosomal contacts' maps could uncover functionally and clinically related genes.
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Trastorno Autístico/genética , Mapeo Cromosómico/métodos , Cromosomas Humanos Par 16/fisiología , Obesidad/genética , Adolescente , Adulto , Anciano , Trastorno del Espectro Autista/genética , Índice de Masa Corporal , Niño , Preescolar , Cromatina/metabolismo , Cromatina/fisiología , Deleción Cromosómica , Duplicación Cromosómica , Cromosomas Humanos Par 16/genética , Variaciones en el Número de Copia de ADN/genética , Femenino , Humanos , Hibridación Fluorescente in Situ , Lactante , Discapacidad Intelectual/genética , Masculino , Megalencefalia/genética , Microcefalia/genética , Persona de Mediana Edad , FenotipoRESUMEN
BACKGROUND: The 600 kb BP4-BP5 copy number variants (CNVs) at the 16p11.2 locus have been associated with a range of neurodevelopmental conditions including autism spectrum disorders and schizophrenia. The number of genomic copies in this region is inversely correlated with body mass index (BMI): the deletion is associated with a highly penetrant form of obesity (present in 50% of carriers by the age of 7 years and in 70% of adults), and the duplication with being underweight. Mechanisms underlying this energy imbalance remain unknown. OBJECTIVE: This study aims to investigate eating behavior, cognitive traits and their relationships with BMI in carriers of 16p11.2 CNVs. METHODS: We assessed individuals carrying a 16p11.2 deletion or duplication and their intrafamilial controls using food-related behavior questionnaires and cognitive measures. We also compared these carriers with cohorts of individuals presenting with obesity, binge eating disorder or bulimia. RESULTS: Response to satiety is gene dosage-dependent in pediatric CNV carriers. Altered satiety response is present in young deletion carriers before the onset of obesity. It remains altered in adolescent carriers and correlates with obesity. Adult deletion carriers exhibit eating behavior similar to that seen in a cohort of obesity without eating disorders such as bulimia or binge eating. None of the cognitive measures are associated with eating behavior or BMI. CONCLUSIONS: These findings suggest that abnormal satiety response is a strong contributor to the energy imbalance in 16p11.2 CNV carriers, and, akin to other genetic forms of obesity, altered satiety responsiveness in children precedes the increase in BMI observed later in adolescence.
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Trastorno Autístico/genética , Trastorno Autístico/fisiopatología , Trastornos de los Cromosomas/genética , Trastornos de los Cromosomas/fisiopatología , Cromosomas Humanos Par 16/genética , Discapacidad Intelectual/genética , Discapacidad Intelectual/fisiopatología , Obesidad/genética , Saciedad , Adulto , Trastorno Autístico/complicaciones , Índice de Masa Corporal , Estudios de Casos y Controles , Niño , Deleción Cromosómica , Trastornos de los Cromosomas/complicaciones , Disfunción Cognitiva/etiología , Disfunción Cognitiva/genética , Disfunción Cognitiva/fisiopatología , Variaciones en el Número de Copia de ADN/genética , Metabolismo Energético/genética , Metabolismo Energético/fisiología , Función Ejecutiva , Conducta Alimentaria/fisiología , Femenino , Predisposición Genética a la Enfermedad , Humanos , Discapacidad Intelectual/complicaciones , Masculino , Obesidad/etiología , Obesidad/fisiopatología , Fenotipo , Eliminación de Secuencia/genética , SuizaAsunto(s)
Displasia Broncopulmonar/fisiopatología , Displasia Broncopulmonar/terapia , Antibacterianos/uso terapéutico , Cafeína/uso terapéutico , Estimulantes del Sistema Nervioso Central/uso terapéutico , Femenino , Glucocorticoides/uso terapéutico , Humanos , Recién Nacido , Terapia por Inhalación de Oxígeno , Embarazo , Atención Prenatal , Surfactantes Pulmonares/uso terapéuticoRESUMEN
Anatomical structures and mechanisms linking genes to neuropsychiatric disorders are not deciphered. Reciprocal copy number variants at the 16p11.2 BP4-BP5 locus offer a unique opportunity to study the intermediate phenotypes in carriers at high risk for autism spectrum disorder (ASD) or schizophrenia (SZ). We investigated the variation in brain anatomy in 16p11.2 deletion and duplication carriers. Beyond gene dosage effects on global brain metrics, we show that the number of genomic copies negatively correlated to the gray matter volume and white matter tissue properties in cortico-subcortical regions implicated in reward, language and social cognition. Despite the near absence of ASD or SZ diagnoses in our 16p11.2 cohort, the pattern of brain anatomy changes in carriers spatially overlaps with the well-established structural abnormalities in ASD and SZ. Using measures of peripheral mRNA levels, we confirm our genomic copy number findings. This combined molecular, neuroimaging and clinical approach, applied to larger datasets, will help interpret the relative contributions of genes to neuropsychiatric conditions by measuring their effect on local brain anatomy.
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Trastorno Autístico/genética , Encéfalo/patología , Cromosomas Humanos Par 16/genética , Variaciones en el Número de Copia de ADN/genética , Obesidad/genética , Esquizofrenia/genética , Adolescente , Adulto , Antropometría , Proteínas de Arabidopsis/metabolismo , Trastorno Autístico/patología , Índice de Masa Corporal , Mapeo Encefálico , Niño , Femenino , Dosificación de Gen , Estudios de Asociación Genética , Humanos , Transferasas Intramoleculares/metabolismo , Masculino , Persona de Mediana Edad , Obesidad/patología , Fenotipo , Escalas de Valoración Psiquiátrica , Esquizofrenia/patología , Adulto JovenRESUMEN
The formation of large assemblies on the Si(111)-B surface is discussed with the help of STM simulations and DFT calculations. Although highly regular assemblies of DTB10B along the Si row direction are observed, the existence of two herringbone isomers introduces a lower periodicity within the 2D molecular network. The formation of herringbone units is explained by weak intermolecular interactions while the 1D assembling depends mainly on the interactions of the C10 side chains with the Si(111)-B surface.
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INTRODUCTION: Normal pressure hydrocephalus (NPH) was described by Adams et al. (1965). The common clinical presentation is the triad: gait disturbance, cognitive decline and urinary incontinence. Although these symptoms are suggestive, they are not specific to diagnosis. The improvement of symptoms after high-volume lumbar puncture (hVLP) could be a strong criterion for diagnosis. We tried to determine a specific pattern of dynamic walking and posture parameters in NPH. Additionally, we tried to specify the evolution of these criteria after hVLP and to determine predictive values of ventriculoperitoneal shunting (VPS) efficiency. PATIENTS AND METHODS: Sixty-four patients were followed during seven years from January 2002 to June 2009. We identified three periods: before (S1), after hVLP (S2) and after VPS (S3). The following criteria concerned walking and posture parameters: walking parameters were speed, step length and step rhythm; posture parameters were statokinesigram total length and surface, length according to the surface (LFS), average value of equilibration for lateral movements (Xmoyen), anteroposterior movements (Ymoyen), total movement length in lateral axis (longX) and anteroposterior axis (longY). RESULTS: Among the 64 patients included, 22 had VPS and 16 were investigated in S3. All kinematic criteria are decreased in S1 compared with normal values. hVLP improved these criteria significantly (S2). Among posture parameters, only total length and surface of statokinesigram showed improvement in S1, but no improvement in S2. A gain in speed greater or equal to 0.15m/s between S1 and S2 predicted the efficacy of VPS with a positive predictive value (PPV) of 87.1% and a negative predictive value (NPV) of 69.7% (area under the ROC curve [AUC]: 0.86). CONCLUSION: Kinematic walking parameters are the most disruptive and are partially improved after hVLP. These parameters could be an interesting test for selecting candidates for VPS. These data have to be confirmed in a larger cohort.
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Hidrocéfalo Normotenso/diagnóstico , Postura/fisiología , Punción Espinal , Caminata/fisiología , Adulto , Anciano , Anciano de 80 o más Años , Área Bajo la Curva , Fenómenos Biomecánicos , Estudios de Cohortes , Femenino , Humanos , Hidrocéfalo Normotenso/fisiopatología , Hidrocéfalo Normotenso/terapia , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Curva ROC , Resultado del Tratamiento , Derivación VentriculoperitonealRESUMEN
The non-classical class I major histocompatibility complex molecules human leucocyte antigen (HLA)-G have been shown to play a role in HIV persistence, but no data are available on the expression of the soluble forms HLA-G5 and sHLA-G1 in HIV-infected patients with and without opportunistic infections. The soluble HLA-G isoform was measured with an enzyme-linked immunosorbent assay (ELISA) method in plasma from 94 subjects: 31 HIV-1-seropositive, 17 with visceral leishmaniasis (VL), seven with both VL and HIV-1 infection and 39 healthy HIV-seronegative subjects. Between groups, the frequency of sHLA-G positivity was statistically different: 81% of HIV-infected patients were positive, as were 57% of HIV-Leishmania infantum co-infected patients, 35% of HIV-seronegative patients with VL and 3% of healthy controls. Levels of the soluble forms of the immunomodulatory molecules HLA-G are elevated during HIV infection. In HIV-Leishmania co-infected patients, sHLA-G secretion could contribute to the tolerogenic environment and to Leishmania immune evasion.
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Infecciones por VIH/inmunología , VIH-1 , Antígenos HLA/sangre , Antígenos de Histocompatibilidad Clase I/sangre , Leishmaniasis Visceral/inmunología , Infecciones Oportunistas Relacionadas con el SIDA/inmunología , Adulto , Niño , Ensayo de Inmunoadsorción Enzimática/métodos , Antígenos HLA-G , Humanos , Tolerancia Inmunológica , SolubilidadRESUMEN
Some studies (mostly retrospective) have pointed to an increasing frequency (up to 60%) of herpes simplex virus type 1 (HSV-1) in genital herpes (GH), but they were biased towards severe or atypical cases. We wished to evaluate the frequency of HSV-1 in patients attending our clinic for both first and recurrent episodes of GH. All patients (men and women) with genital lesions compatible with GH were included in a prospective study between May 1999 and April 2002. For all patients a standardized questionnaire, clinical examination, MRC5 culture (Dade Behring), polymerase chain reaction (PCR)-herpes consensus (Argène Biosoft) in case of negative culture and type-specific herpes serology HSV-1 and HSV-2 (Elisa Eurobio) were obtained. Predictive factors associated with HSV-1 and HSV-2 GH were studied by uni- and multivariable analyses. In all, 255 patients had a positive culture (n = 216) or PCR (n = 39). A total of 248 patients had typable herpes (148 men and 100 women). Median age was 33 (27-43); 20% had anal herpes; 48% had clinically recurrent lesions; 21% were HIV +; 20% of men were homosexual; 77% practised oral sex. In all, 36 were HSV-1 (14.5%): more in women, 25/100 (25%), than in men, 11/148 (7.5%) (odds ratio [OR]: 4 [1.8-9.1], P = 0.008). HSV-1 accounted for 23% of cases of first clinical episodes (women: 31.5%; men: 14.7%) (P = 0.02) and 6% of clinically recurrent episodes (women: 15%; men: 1.2%) (OR: 3.8 [1.6-9.1], P = 0.0033). Serological study was done in 239: primary infection was disclosed in 33 (HSV-1: 61%), HSV-2 non-primary first episode in 22 and recurrence in 184 (HSV-1: 8%). In all, 37% of recurrent episodes presented as a first clinical episode. HSV-1 was linked in men with homosexuality (P<0.01) and anilingus (P<0.01), in women with younger age (P<0.01), more sexual intercourses (P<0.0001) and more oral sex (P<0.001). Although HSV-1 is frequent in first clinical (23%) and primary (61%) episodes of GH, recurrent GH remains mostly due to HSV-2 (94%).
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Instituciones de Atención Ambulatoria , Anticuerpos Antivirales/sangre , Herpes Genital/epidemiología , Herpesvirus Humano 1/aislamiento & purificación , Herpesvirus Humano 2/aislamiento & purificación , Enfermedades de Transmisión Sexual/prevención & control , Adulto , Femenino , Herpes Genital/virología , Herpesvirus Humano 1/genética , Herpesvirus Humano 1/inmunología , Herpesvirus Humano 2/genética , Herpesvirus Humano 2/inmunología , Humanos , Masculino , Paris , Reacción en Cadena de la Polimerasa , Prevalencia , Estudios ProspectivosRESUMEN
OBJECTIVES: To assess the antiviral response to optimized therapy following genotypic resistance testing and to identify factors associated with virological response in HIV-1-infected patients failing antiretroviral therapy. METHODS: A prospective cohort study was conducted in 344 HIV-1-infected patients who underwent genotypic resistance testing because of virological failure. Virological response was defined as a plasma HIV RNA level below 200 HIV-1 RNA copies/mL or a drop of plasma viral load from baseline of more than 1 log10. A multivariate logistic regression analysis was performed to identify factors associated with virological response. RESULTS: The median age of the patients was 40 years, with a male to female ratio of 4:1. Fifty-one per cent of patients had received the three major classes of antiretrovirals and the median duration of previous antiretroviral therapy was 4.6 years. At baseline, the median plasma HIV RNA level was 4.4 log10 copies/mL and the median CD4 cell count was 274 cells/microL. At 3 months, 55% of patients (188 of 344) had a virological response, which was sustained at 6 months (53%). Predictors of virological response were exposure to two or fewer protease inhibitors [odds ratio (OR) 1.8; P=0.046], and use in optimized therapy of a new class of antiretrovirals (OR 2.9; P=0.006), of more than two new drugs (OR 3.0; P<0.0001), of abacavir (OR 1.9; P=0.03), or of lopinavir/ritonavir (OR 3.7; P=0.0002). CONCLUSIONS: A high proportion of patients achieved a short-term virological response in this cohort study. Patients with the least experience of protease inhibitor treatment and in whom a new class of antiretroviral, more than two new drugs, abacavir or lopinavir/ritonavir was used in optimized therapy had the best virological outcome.
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Antivirales/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/virología , VIH-1 , Adulto , Terapia Antirretroviral Altamente Activa , Recuento de Linfocito CD4 , Didesoxinucleósidos/uso terapéutico , Esquema de Medicación , Farmacorresistencia Viral Múltiple , Quimioterapia Combinada , Femenino , Infecciones por VIH/inmunología , Inhibidores de la Proteasa del VIH/uso terapéutico , VIH-1/genética , Humanos , Lopinavir , Masculino , Estudios Prospectivos , Pirimidinonas/uso terapéutico , ARN Viral/sangre , Ritonavir/uso terapéutico , Insuficiencia del TratamientoRESUMEN
PATIENTS AND METHODS: We studied prospectively the feasibility of post exposure prophylaxis against HIV in 93 subjects consulting after sexual exposure at STD Center of Hopital Saint-Louis. Among the 93 subjects, 76 were men (45 homosexual) and 17 women. RESULTS: Delay to consultation was 38 h. Among sexual exposure 90 p. 100 were anal or vaginal intercourse and 10 p. 100 oral intercourse. Fifty percent were unprotected. Seventy-five percent of source subject HIV status was unknown, but controlled negative in 14 p. 100 of cases. Three subjects were infected initially. Seventy-two subjects were treated, with triple regimen, for 30 days without severe adverse event. Twenty-five percent were lost to follow up before the end of treatment, only 54 controlled their serology after the end of treatment (after 1 month: 70 p. 100, after 2 months: 51 p. 100 and after 4-6 months: 13 p. 100). DISCUSSION: This study underlines the difficulty in obtaining clinical and serological control after post exposure prophylaxis, even in a STD Department involved in prevention and counseling.
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Fármacos Anti-VIH/uso terapéutico , Infecciones por VIH/prevención & control , Infecciones por VIH/transmisión , Indinavir/uso terapéutico , Lamivudine/uso terapéutico , Nelfinavir/uso terapéutico , Conducta Sexual , Zidovudina/uso terapéutico , Serodiagnóstico del SIDA , Quimioterapia Combinada , Estudios de Factibilidad , Femenino , Infecciones por VIH/sangre , Infecciones por VIH/diagnóstico , Infecciones por VIH/epidemiología , Humanos , Masculino , Paris/epidemiología , Estudios Prospectivos , Conducta Sexual/estadística & datos numéricos , Factores de Tiempo , Resultado del TratamientoRESUMEN
To compare the effectiveness and predictive value of radiologic studies with fine-needle aspiration biopsy (FNAB) in correctly diagnosing thyroid lesions, we reviewed the medical records of 441 patients who had been treated surgically for thyroid disease from 1987 through 1999. We compared the results of thyroid scintigraphy, ultrasound, and FNAB with findings on final surgical pathology. The data were analyzed according to the chi-squared (chi 2) test. Of 189 thyroid scintigraphy scans that showed a hypofunctional (cold) nodule, 52 (27.5%) were found to be cancerous, and of 35 hyperfunctional (hot) nodules, two (5.7%) were malignant (sensitivity = 91%; specificity = 19%; accuracy = 38%; chi 2 = 7.67; p = 0.006). Of 66 ultrasounds that detected a solid or a mixed solid-cystic mass, 16(24.2%) were cancerous, while none of the eight sonograms that showed a purely cystic lesion was malignant (sensitivity = 100%; specificity = 14%; accuracy = 32%; chi 2 = 2.47; p = 0.116 [not statistically significant]). Of the 119 patients whose FNABs were diagnostic, 55 biopsies revealed follicular cells. Of the remaining 64 biopsies, cancer was correctly predicted in 35 of 44 patients (79.5%) and benign disease was correctly diagnosed in 18 of 20 patients (90.0%) (sensitivity = 95%; specificity = 67%; accuracy = 83%; chi 2 = 27.3; p = 0.00). We conclude that in the evaluation of thyroid lesions, FNAB is superior to imaging studies, which yield a relatively high rate of false-positive results.