Gene expression profiling unveils the temporal dynamics of CIGB-300-regulated transcriptome in AML cell lines.

BACKGROUND: Protein kinase CK2 activity is implicated in the pathogenesis of various hematological malignancies like Acute Myeloid Leukemia (AML) that remains challenging concerning treatment. This kinase has emerged as an attractive molecular target in therapeutic. Antitumoral peptide CIGB-300 blocks CK2 phospho-acceptor sites on their substrates but it also binds to CK2α catalytic subunit. Previous proteomic and phosphoproteomic experiments showed molecular and cellular processes with relevance for the peptide action in diverse AML backgrounds but earlier transcriptional level events might also support the CIGB-300 anti-leukemic effect. Here we used a Clariom S HT assay for gene expression profiling to study the molecular events supporting the anti-leukemic effect of CIGB-300 peptide on HL-60 and OCI-AML3 cell lines. RESULTS: We found 183 and 802 genes appeared significantly modulated in HL-60 cells at 30 min and 3 h of incubation with CIGB-300 for p < 0.01 and FC > = │1.5│, respectively; while 221 and 332 genes appeared modulated in OCI-AML3 cells. Importantly, functional enrichment analysis evidenced that genes and transcription factors related to apoptosis, cell cycle, leukocyte differentiation, signaling by cytokines/interleukins, and NF-kB, TNF signaling pathways were significantly represented in AML cells transcriptomic profiles. The influence of CIGB-300 on these biological processes and pathways is dependent on the cellular background, in the first place, and treatment duration. Of note, the impact of the peptide on NF-kB signaling was corroborated by the quantification of selected NF-kB target genes, as well as the measurement of p50 binding activity and soluble TNF-α induction. Quantification of CSF1/M-CSF and CDKN1A/P21 by qPCR supports peptide effects on differentiation and cell cycle. CONCLUSIONS: We explored for the first time the temporal dynamics of the gene expression profile regulated by CIGB-300 which, along with the antiproliferative mechanism, can stimulate immune responses by increasing immunomodulatory cytokines. We provided fresh molecular clues concerning the antiproliferative effect of CIGB-300 in two relevant AML backgrounds.

Postmortem Findings in Patient with Guillain-Barré Syndrome and Zika Virus Infection.

Postmortem examination results of a patient with Guillain-Barré syndrome and confirmed Zika virus infection revealed demyelination of the sciatic and cranial IV nerves, providing evidence of the acute demyelinating inflammatory polyneuropathy Guillain-Barré syndrome variant. Lack of evidence of Zika virus in nervous tissue suggests that pathophysiology was antibody mediated without neurotropism.

Targeting of Protein Kinase CK2 Elicits Antiviral Activity on Bovine Coronavirus Infection.

Coronaviruses constitute a global threat to the human population; therefore, effective pan-coronavirus antiviral drugs are required to tackle future re-emerging virus outbreaks. Protein kinase CK2 has been suggested as a promising therapeutic target in COVID-19 owing to the in vitro antiviral activity observed after both pharmacologic and genetic inhibition of the enzyme. Here, we explored the putative antiviral effect of the anti-CK2 peptide CIGB-325 on bovine coronavirus (BCoV) infection using different in vitro viral infected cell-based assays. The impact of the peptide on viral mRNA and protein levels was determined by qRT-PCR and Western blot, respectively. Finally, pull-down experiments followed by Western blot and/or mass spectrometry analysis were performed to identify CIGB-325-interacting proteins. We found that CIGB-325 inhibited both the cytopathic effect and the number of plaque-forming units. Accordingly, intracellular viral protein levels were clearly reduced after treatment of BCoV-infected cells, with CIGB-325 determined by immunocytochemistry. Pull-down assay data revealed the physical interaction of CIGB-325 with viral nucleocapsid (N) protein and a group of bona fide CK2 cellular substrates. Our findings evidence in vitro antiviral activity of CIGB-325 against bovine coronavirus as well as some molecular clues that might support such effect. Altogether, data provided here strengthen the rationale of inhibiting CK2 to treat betacoronavirus infections.

CIGB-300-Regulated Proteome Reveals Common and Tailored Response Patterns of AML Cells to CK2 Inhibition.

Protein kinase CK2 is a highly pleiotropic and ubiquitously expressed Ser/Thr kinase with instrumental roles in normal and pathological states, including neoplastic phenotype in solid tumor and hematological malignancies. In line with previous reports, CK2 has been suggested as an attractive prognostic marker and molecular target in acute myeloid leukemia (AML), a blood malignant disorder that remains as an unmet medical need. Accordingly, this work investigates the complex landscape of molecular and cellular perturbations supporting the antileukemic effect exerted by CK2 inhibition in AML cells. To identify and functionally characterize the proteomic profile differentially modulated by the CK2 peptide-based inhibitor CIGB-300, we carried out LC-MS/MS and bioinformatic analysis in human cell lines representing two differentiation stages and major AML subtypes. Using this approach, 109 and 129 proteins were identified as significantly modulated in HL-60 and OCI-AML3 cells, respectively. In both proteomic profiles, proteins related to apoptotic cell death, cell cycle progression, and transcriptional/translational processes appeared represented, in agreement with previous results showing the impact of CIGB-300 in AML cell proliferation and viability. Of note, a group of proteins involved in intracellular redox homeostasis was specifically identified in HL-60 cell-regulated proteome, and flow cytometric analysis also confirmed a differential effect of CIGB-300 over reactive oxygen species (ROS) production in AML cells. Thus, oxidative stress might play a relevant role on CIGB-300-induced apoptosis in HL-60 but not in OCI-AML3 cells. Importantly, these findings provide first-hand insights concerning the CIGB-300 antileukemic effect and draw attention to the existence of both common and tailored response patterns triggered by CK2 inhibition in different AML backgrounds, a phenomenon of particular relevance with regard to the pharmacologic blockade of CK2 and personalized medicine.

CIGB-300 Anticancer Peptide Differentially Interacts with CK2 Subunits and Regulates Specific Signaling Mediators in a Highly Sensitive Large Cell Lung Carcinoma Cell Model.

Large cell lung carcinoma (LCLC) is one form of NSCLC that spreads more aggressively than some other forms, and it represents an unmet medical need. Here, we investigated for the first time the effect of the anti-CK2 CIGB-300 peptide in NCI-H460 cells as an LCLC model. NCI-H460 cells were highly sensitive toward CIGB-300 cytotoxicity, reaching a peak of apoptosis at 6 h. Moreover, CIGB-300 slightly impaired the cell cycle of NCI-H460 cells. The CIGB-300 interactomics profile revealed in more than 300 proteins that many of them participated in biological processes relevant in cancer. Interrogation of the CK2 subunits targeting by CIGB-300 indicated the higher binding of the peptide to the CK2α' catalytic subunit by in vivo pull-down assays plus immunoblotting analysis and confocal microscopy. The down-regulation of both phosphorylation and protein levels of the ribonuclear protein S6 (RPS6) was observed 48 h post treatment. Altogether, we have found that NCI-H460 cells are the most CIGB-300-sensitive solid tumor cell line described so far, and also, the findings we provide here uncover novel features linked to CK2 targeting by the CIGB-300 anticancer peptide.

Phosphoproteomic Landscape of AML Cells Treated with the ATP-Competitive CK2 Inhibitor CX-4945.

Casein kinase 2 (CK2) regulates a plethora of proteins with pivotal roles in solid and hematological neoplasia. Particularly, in acute myeloid leukemia (AML) CK2 has been pointed as an attractive therapeutic target and prognostic marker. Here, we explored the impact of CK2 inhibition over the phosphoproteome of two cell lines representing major AML subtypes. Quantitative phosphoproteomic analysis was conducted to evaluate changes in phosphorylation levels after incubation with the ATP-competitive CK2 inhibitor CX-4945. Functional enrichment, network analysis, and database mining were performed to identify biological processes, signaling pathways, and CK2 substrates that are responsive to CX-4945. A total of 273 and 1310 phosphopeptides were found differentially modulated in HL-60 and OCI-AML3 cells, respectively. Despite regulated phosphopeptides belong to proteins involved in multiple biological processes and signaling pathways, most of these perturbations can be explain by direct CK2 inhibition rather than off-target effects. Furthermore, CK2 substrates regulated by CX-4945 are mainly related to mRNA processing, translation, DNA repair, and cell cycle. Overall, we evidenced that CK2 inhibitor CX-4945 impinge on mediators of signaling pathways and biological processes essential for primary AML cells survival and chemosensitivity, reinforcing the rationale behind the pharmacologic blockade of protein kinase CK2 for AML targeted therapy.

Targeting of Protein Kinase CK2 in Acute Myeloid Leukemia Cells Using the Clinical-Grade Synthetic-Peptide CIGB-300.

Protein kinase CK2 has emerged as an attractive therapeutic target in acute myeloid leukemia (AML), an advent that becomes particularly relevant since the treatment of this hematological neoplasia remains challenging. Here we explored for the first time the effect of the clinical-grade peptide-based CK2 inhibitor CIGB-300 on AML cells proliferation and viability. CIGB-300 internalization and subcellular distribution were also studied, and the role of B23/nucleophosmin 1 (NPM1), a major target for the peptide in solid tumors, was addressed by knock-down in model cell lines. Finally, pull-down experiments and phosphoproteomic analysis were performed to study CIGB-interacting proteins and identify the array of CK2 substrates differentially modulated after treatment with the peptide. Importantly, CIGB-300 elicited a potent anti-proliferative and proapoptotic effect in AML cells, with more than 80% of peptide transduced cells within three minutes. Unlike solid tumor cells, NPM1 did not appear to be a major target for CIGB-300 in AML cells. However, in vivo pull-down experiments and phosphoproteomic analysis evidenced that CIGB-300 targeted the CK2α catalytic subunit, different ribosomal proteins, and inhibited the phosphorylation of a common CK2 substrates array among both AML backgrounds. Remarkably, our results not only provide cellular and molecular insights unveiling the complexity of the CIGB-300 anti-leukemic effect in AML cells but also reinforce the rationale behind the pharmacologic blockade of protein kinase CK2 for AML-targeted therapy.

Treatment with an Anti-CK2 Synthetic Peptide Improves Clinical Response in COVID-19 Patients with Pneumonia. A Randomized and Controlled Clinical Trial.

The instrumental role of CK2 in the SARS-CoV-2 infection has pointed out this protein kinase as promising therapeutic target in COVID-19. Anti-SARS-CoV-2 activity has been reported by CK2 inhibitors in vitro; however, no anti-CK2 clinical approach has been investigated in COVID-19. This trial aimed to explore the safety and putative clinical benefit of CIGB-325, an anti-CK2 peptide previously assessed in cancer patients. A monocentric, controlled, and therapeutic exploratory trial of intravenous CIGB-325 in adults hospitalized with COVID-19 was performed. Twenty patients were randomly assigned to receive CIGB-325 (2.5 mg/kg/day during 5-consecutive days) plus standard-of-care (10 patients) or standard-of-care alone (10 patients). Adverse events were classified by the WHO Adverse Reaction Terminology. Parametric and nonparametric statistical analyses were performed according to the type of variable. Considering the small sample size, differences between groups were estimated by Bayesian analysis. CIGB-325 induced transient mild and/or moderate adverse events such as pruritus, flushing, and rash in some patients. Both therapeutic regimens were similar with respect to SARS-CoV-2 clearance in nasopharynx swabs over time. However, CIGB-325 significantly reduced the median number of pulmonary lesions (9.5 to 5.5, p = 0.042) at day 7 and the proportion of patients with such an effect was also higher according to Bayesian analysis (pDif > 0; 0.951). Also, CIGB-325 significantly reduced the CPK (p = 0.007) and LDH (p = 0.028) plasma levels at day 7. Our preliminary findings suggest that this anti-CK2 clinical approach could be combined with standard-of-care in COVID-19 in larger studies.

Development of diagnostic criteria for serious non-AIDS events in HIV clinical trials.

PURPOSE: Serious non-AIDS (SNA) diseases are important causes of morbidity and mortality in the HAART era. We describe development of standard criteria for 12 SNA events for Endpoint Review Committee (ERC) use in START, a multicenter international HIV clinical trial. METHODS: SNA definitions were developed based upon the following: (1) criteria from a previous trial (SMART), (2) review of published literature, (3) an iterative consultation and review process with the ERC and other content experts, and (4) evaluation of draft SNA criteria using retrospectively collected reports in another trial (ESPRIT). RESULTS: Final criteria are presented for acute myocardial infarction, congestive heart failure, coronary artery disease requiring drug treatment, coronary revascularization, decompensated liver disease, deep vein thrombosis, diabetes mellitus, end-stage renal disease, non-AIDS cancer, peripheral arterial disease, pulmonary embolism, and stroke. Of 563 potential SNA events reported in ESPRIT and reviewed by an ERC, 72% met "confirmed" and 13% "probable" criteria. Twenty-eight percent of cases initially reviewed by the ERC required follow-up discussion (adjudication) before a final decision was reached. CONCLUSION: HIV clinical trials that include SNA diseases as clinical outcomes should have standardized SNA definitions to optimize event reporting and validation and should have review by an experienced ERC with opportunities for adjudication.

Viral load and CD4+ cell count as risk factors for prolonged QT interval in HIV-infected subjects: a cohort-nested case-control study in an outpatient population.

BACKGROUND: QTc interval prolongation is a serious ECG finding which has frequently been reported in HIV-infected patients, but associated risk factors have not been determined in this population. METHODS: Data were collected from the charts of a cohort of 135 consecutive HIV-infected patients from our HIV outpatient clinic. The cohort was divided into two groups, patients with prolonged QTc and those with normal QTc interval. Multiple variables and potential risk factors were analyzed, including the CD4+ cell count and viral load (VL), which were assessed on the same day or within several days of the initial ECG. RESULTS: 23 patients were found to have prolonged QTc (17%). No significant difference in baseline characteristics was observed between the groups; however, statistically significant differences were observed with regard to the CD4+ cell count and VL. CONCLUSION: A low CD4 cell count and a high VL may be risk factors potentially related to QT prolongation in HIV patients in the outpatient setting.

Kodamaea ohmeri fungemia in an immunocompetent patient treated with micafungin: case report and review of the literature.

Kodamaea (Pichia) ohmeri is an unusual yeast-form fungus that has recently been identified as an important etiology of fungemia, endocarditis, cellulitis, funguria and peritonitis in immunocompromised patients. We report a case of K. ohmeri fungemia in a 34-year-old hospitalized patient with thrombophlebitis. The patient was admitted to the hospital for evaluation and management of an acquired tracheo-esophageal fistula secondary to an impacted denture. Fever developed on hospital day 22, and physical exam revealed right arm superficial thrombophlebitis at the site of the peripheral venous catheter that was confirmed by Doppler ultrasound. The peripheral vein was removed and blood cultures from hospital day 22 and 23 grew yeast species. The yeast was subsequently identified to be K. ohmeri by Vitek II and API20C and was confirmed by 18S rRNA gene sequencing. The fungemia and right arm phlebitis was successfully treated with a 2-week course of micafungin therapy. This is the first case of K. ohmeri fungemia in a patient that was successfully treated with micafungin.

Determination of the underlying cause of death in three multicenter international HIV clinical trials.

PURPOSE: Describe processes and challenges for an Endpoint Review Committee (ERC) in determining and adjudicating underlying causes of death in HIV clinical trials. METHOD: Three randomized HIV trials (two evaluating interleukin-2 and one treatment interruption) enrolled 11,593 persons from 36 countries during 1999-2008. Three ERC members independently reviewed each death report and supporting source documentation to assign underlying cause of death; differences of opinion were adjudicated. RESULTS: Of 453 deaths reported through January 14, 2008, underlying causes were as follows: 10% AIDS-defining diseases, 21% non-AIDS malignancies, 9% cardiac diseases, 9% liver disease, 8% non-AIDS-defining infections, 5% suicides, 5% other traumatic events/accidents, 4% drug overdoses/acute intoxications, 11% other causes, and 18% unknown. Major reasons for unknown classification were inadequate clinical information or supporting documentation to determine cause of death. Half (51%) of deaths reviewed by the ERC required follow-up adjudication; consensus was eventually always reached. CONCLUSION: ERCs can successfully provide blinded, independent, and systematic determinations of underlying cause of death in HIV clinical trials. Committees should include those familiar with AIDS and non-AIDS-defining diseases and have processes for adjudicating differences of opinion. Training for local investigators and procedure manuals should emphasize obtaining maximum possible documentation and follow-up information on all trial deaths.

Bienestar y salud ocupacional de profesores universitarios en la formación investigativa mediante el teletrabajo / Well-being and occupational health of university professors in research training through teleworking i: en

Introducción: La COVID-19 provocó cambios laborales e influyó en el comportamiento de los docentes universitarios. Objetivo: Describir el bienestar y la salud ocupacional de profesores universitarios en la formación investigativa mediante el teletrabajo. Métodos: Se realizó un análisis sistemático mediante la metodología PRISMA que incluyó todo el año 2022 y los primeros meses del 2023. Con los artículos incluidos se aplicó la herramienta de búsqueda bibliográfica en línea Litmaps. Asimismo, se empleó un cuestionario y posteriormente la escala de Likert. El instrumento se validó con el coeficiente alfa de Cronbach y se consideró la prueba t de una muestra para probar como hipótesis descriptiva si el bienestar y la salud ocupacional desde la formación investigativa en docentes universitarios mediante el teletrabajo eran satisfactorios. Resultados: En el estudio, 41,2 % de los artículos de revisión e investigación seleccionados con la metodología PRISMA correspondieron al año 2022; sin embargo, el 50,0 % de los artículos semillas fueron del 2023, donde su análisis mapa indicó que no hubo citas de correspondencias. En cuanto al resultado de la valoración con la escala de Likert y luego con la prueba de hipótesis, se obtuvo insatisfacción en los profesores respecto a la formación investigativa mediante el teletrabajo. Conclusiones: Existió insatisfacción respecto al bienestar y la salud ocupacional para la formación investigativa desde el teletrabajo porque los docentes universitarios consideraban que las condiciones laborales no fueron favorables.

Introduction: COVID-19 caused job changes and influenced the behavior of university professors. Objective: To describe well-being and occupational health in research training of university professors through teleworking. Methods: A systematic analysis was carried out using the PRISMA methodology that included the entire year 2022 and the first months of 2023. The online bibliographic search tool Litmaps was applied to the included articles. Likewise, a questionnaire was used and subsequently the Likert scale. The instrument was validated with Cronbach's alpha coefficient and the one-sample T-test was considered as a descriptive hypothesis whether well-being and occupational health from research training in university professors through teleworking were satisfactory. Results: In the study, 41.2% of the review and research articles selected with the PRISMA methodology corresponded to the year 2022; however, 50.0% of the seed articles were from 2023, where their map analysis indicated that there were no citations of correspondences. Regarding the result of the assessment with the Likert scale and then with the hypothesis test, dissatisfaction was obtained among professors concerning research training through teleworking. Conclusions: There was dissatisfaction regarding well-being and occupational health for research training through teleworking because university professors considered that working conditions were not favorable.

Formación investigativa de docentes universitarios para el aprendizaje sincrónico durante la covid-19 / Investigative training of university professors for the synchronous learning during covid-19 i:en

Introducción: Las capacitaciones permanentes durante la pandemia posibilitaron el aprendizaje en la educación superior. Objetivo: Describir la formación investigativa y la función pedagógica en docentes universitarios desde la complejidad psicosocial del aprendizaje sincrónico durante la covid-19. Métodos: Se efectuó un estudio desde julio del 2020 hasta febrero del 2022 en la Universidad Nacional San Luis Gonzaga de Ica, en Perú. La formación investigativa consistió en 2 modalidades: talleres de formación y cursos de posgrado, y se registró la participación de las áreas académicas de ciencias de la salud, ingenierías y letras y humanidades. Se describió mediante un dendrograma la función pedagógica entre dos grupos de profesores (con asistencia permanente o no). Resultados: En los talleres de formación, 52,0 % de los asistentes correspondió al área académica de ciencias de la salud, 35,0 % a letras y humanidades y 13,0 % a ingenierías; mientras la participación activa fue de 22,2 % en ingeniería, 8,9 % en ciencias de la salud y 4,1 % en letras y humanidades. En cambio, el porcentaje para los cursos de posgrado fue de 41,0 en ciencias de la salud, 30,0 en letras y humanidades y 29,0 en ingenierías, con participación activa de 6, 4 y 3 docentes, respectivamente. No hubo diferencias significativas en la evaluación interna entre los cursos de posgrado (p<0,00915). Conclusiones: La asistencia fue menor en los cursos de posgrado al ser más riguroso el proceso de aprendizaje; sin embargo, fue mayor la participación activa. Existió mayor similitud en la función pedagógica cuando la asistencia fue permanente.

Introduction: Ongoing trainings during the covid-19 pandemic enabled learning in higher education. Objective: To describe the investigative training and pedagogical function in university professors from the psychological complexity of synchronous learning during covid-19. Methods: A study was carried out from July, 2020 to February, 2022, at San Luis Gonzaga National University in Ica, Peru. The investigative training consisted of two modalities: training workshops and postgraduates courses. Participation was recorded in the academic areas of health sciences, engineering and arts and humanities. A dendrogram was used to describe the pedagogical function between two groups of university professors (those who had permanent attendance and those who did not). Results: In the training workshops, 52.0% of the participants corresponded to the academic area of health sciences, 35.0% to arts and humanities and 13.0% to engineering; while active participation was 22.2% in engineering, 8.9% in health sciences and 4.1% in arts and humanities. On the other hand, the percentage for graduate courses was 41.0 in health sciences, 30.0 in arts and humanities, and 29.0 in engineering, with active participation of 6, 4 and 3 professors, respectively. There were no significant differences in the internal evaluation between the postgraduate courses (p<0.00915). The dendrogram indicated greater similarity in university professors with permanent attendance. Conclusions: There was lower attendance in postgraduates courses as the learning process was more rigorous and demanding; however, active participation was higher. There was greater similarity in the pedagogical function when attendance was permanent.

Habilidades digitales y tecnoestrés en docentes universitarios mayores de 60 años / Digital skills and technostress in university professors aged 60 years and over i: en

Introducción: Las limitaciones en el uso de las tecnologías en los docentes de la educación superior conducen al aislamiento social y la exclusión e impiden demostrar las competencias profesionales. Objetivo: Describir las habilidades digitales en docentes universitarios adultos mayores y su relación con el tecnoestrés. Métodos: Se realizó un estudio cualitativo, de mayo a noviembre del 2022, de 19 docentes en las edades de 60 y más años de la Universidad Nacional San Luis Gonzaga de Ica, en Perú. Para ello, se desarrolló un taller de capacitación y se evaluó la comprensión de 6 herramientas teórico-prácticas de la categoría docente en el proceso de enseñanza-aprendizaje a través de la ejecución de actividades (cuestionario, chat y tareas) en la plataforma virtual Moodle. Asimismo, se orientó marcar los criterios de identificación de la investigación formativa y, para la calificación, se establecieron 3 intervalos de puntuación. Se aplicó una encuesta fundamentada en la demostración de las habilidades digitales y el estado emocional en relación con la tecnología. Resultados: El valor promedio de la calificación fue 14,73±0,42 y se obtuvieron los siguientes porcentajes para cada intervalo de puntuación: I) 57,9; II) 31,6 y III) 10,5. Igualmente, 73,7 % requirió asistencia técnica para interactuar con la enseñanza virtual, mientras que 84,2 % se agobió con el uso de la tecnología. Existió correlación (p=0,0256) entre la puntuación asignada en las habilidades digitales y el tecnoestrés. Conclusiones: Los docentes universitarios mayores de 60 años mostraron deficiencias en las habilidades digitales, lo cual condujo a la aparición de tecnoestrés.

Introduction: Limitations in the use of technologies in higher education professors lead to social isolation and exclusion and prevent the demonstration of professional skills. Objective: Describe digital skills in elderly university professors and their relationship with technostress. Methods: A qualitative study was carried out, from May to November, 2022, of 19 professors aged 60 years and over from San Luis Gonzaga National University in Ica, Peru. To this purpose, a training workshop was developed and the understanding of 6 theoretical-practical tools of teaching category in the teaching learning process was evaluated through the implementation of activities (questionnaire, chat and tasks) on the online platform Moodle. Likewise, the aim was to mark the identification criteria of training research and, for grading, 3 scoring intervals were established. A survey was applied based on the demonstration of digital skills and the emotional state concerning technology. Results: The mean value of score was 14.73±0.42 and the following percentages were obtained for each score interval: I) 57.9; II) 31.6 and III) 10.5. Also, 73.7% required technical assistance to interact with virtual teaching, while 84.2% were overwhelmed with the use of technology. There was a correlation (p=0.0256) between the score assigned in digital skills and technostress. Conclusions: University professors over 60 years of age showed deficiencies in the digital skills, which led to the appearance of technostress.

Prevalence of GB virus type C in urban Americans infected with human immunodeficiency virus type 1.

GBV-C virus infection has been linked to improved clinical outcome in HIV-1 co-infected individuals. The epidemiology of GBV-C has, thus far, been limited to the gay male, HIV+ population. Here we describe the prevalence of antibodies against GBV-C envelope glycoprotein E2 and GBV-C viremia in an HIV+ inner city population. This study group is predominantly African-American; 41% of the participants are women. The major risk factor for HIV infection is intravenous drug use. Overall, 56% of the study population had evidence of current or past infection with GBV-C. GBV-C exposure was not associated with hepatitis C virus infection. The group of participants, who had GBV-C viremia and anti-E2 antibodies, had high percentage of patients with an undetectable HIV-1 viral load. These data provide increased insight into the prevalence of GBV-C co-infection in the HIV epidemic in this understudied population.

Comparison of prognostic importance of latest CD4+ cell count and HIV RNA levels in patients with advanced HIV infection on highly active antiretroviral therapy.

UNLABELLED: The comparative prognostic importance of latest plasma HIV RNA levels (viral loads) and CD4+ cell counts among patients prescribed highly active antiretroviral therapy (HAART) has not been well characterized. METHOD: We assessed the prognostic value of latest CD4+ cell counts and latest viral loads for progression to AIDS or death and explored their interaction among 432 HIV-infected persons with advanced HIV who were prescribed a protease inhibitor (PI) as their first HAART regimen. RESULTS: Pre-HAART median CD4+ cell count and viral load were 41 cells/mm3 and 126,331 copies/mL, respectively. After 12 months of HAART, the median CD4+ cell count was 154 cells/mm3; 39% of patients had a viral load of 400 copies/mL or lower. Over a median follow-up of 33 months, 109 (25%) of the 432 patients experienced an AIDS event or died. The hazard ratio for AIDS or death for those with latest CD4+ cell count <50 cells/mm3 versus > or =200 cells/mm3 was 13.9 (95% CI 6.5 to 29.7) without adjustment for latest viral load measurements and 9.5 (95% CI 4.0 to 22.5) after adjustment for latest viral load. In contrast, the hazard ratio for AIDS or death for those with viral load > or =100,000 versus <400 copies/mL was 4.2 (95% CI 2.3 to 7.7) without adjustment for latest CD4+ level and 1.2 (95% CI 0.6 to 2.4) with adjustment for latest CD4+ cell count. CONCLUSION: We conclude that when latest CD4+ cell count and viral load are considered separately, both are significantly related to AIDS or death; when these markers are jointly considered, the association of viral load with AIDS or death is substantially diminished. Latest CD4+ levels are more strongly related to AIDS or death than latest viral load levels in patients on HAART.

Prevalence and characteristics of hepatitis C virus coinfection in a human immunodeficiency virus clinical trials group: the Terry Beirn Community Programs for Clinical Research on AIDS.

The baseline prevalence of hepatitis C virus (HCV) and human immunodeficiency virus (HIV) coinfection among 2705 patients enrolled in HIV clinical trials in the Community Programs for Clinical Research on AIDS (CPCRA) was 16.6%. For men, multivariate logistic regression showed that the baseline prevalence of HIV-HCV coinfection was positively associated with history of injection drug use, older age, antiretroviral therapy naive status, African American or Latino ethnicity, and no history of having sex with men. No association was found with baseline CD4+ cell count or HIV RNA level. The prevalence of HCV coinfection in a diverse HIV clinical trials cohort provides additional information about risk behaviors and demographic factors that can be used in the analysis of clinical and virologic outcomes.

A randomized clinical trial comparing nelfinavir and ritonavir in patients with advanced HIV disease (CPCRA 042/CTN 102).

PURPOSE: To compare the long-term clinical efficacy and toxicity of initial strategies of nelfinavir (NFV) or ritonavir (RTV) in patients with CD4+ cells below 200/mm3. METHOD: This was an open-label randomized multicenter trial (CPCRA, CTN). Patients were naïve to protease inhibitor use except for hard gel saquinavir. Patients who were intolerant to their assigned therapy were allowed to switch arms (later RTV-intolerant patients could switch to indinavir). The primary objective was to compare the regimens for AIDS-defining conditions and death (AIDS/death) using intent-to-treat analysis. Hazard ratios (HR) for NFV and RTV were estimated using Cox's proportional hazards models. Kaplan-Meier life table summaries were also used to compare the two groups. RESULTS: There were 775 patients who were randomized beginning in January 1997 and followed through December 2001. At entry, mean CD4+ cell count was 58 cells/mm3 and HIV RNA level averaged 4.9 log copies/mL. After a median follow-up of 52 months, rates of AIDS/death were 12.7 and 11.0 per 100 person years for the NFV and RTV groups, respectively (HR=1.16; 95% CI, 0.92-1.46; p=.21). Discontinuations occurred earlier in the RTV group (p=.0001). CONCLUSION: There are moderate differences in efficacy and large differences in tolerability between a strategy of initial NFV or RTV in patients with advanced disease. Finding the right balance between potency and tolerability remains a challenge.

Modeling of Equivalent Effective Temperature and its possible incidence on larval density of Anopheles mosquitoes (Diptera: Culicidae) in Villa Clara province, Cuba / Modelación de la Temperatura Efectiva Equivalente y posible incidencia en la densidad larval de mosquitos Anopheles (Diptera: Culicidae) en la provincia Villa Clara, Cuba

AbstractThe wind chill or Equivalent Effective Temperature (EET) is the thermic sensation that a person feels when being exposed to a certain combination of temperature from the air, relative humidity and wind velocity. The objective of this investigation was directed to determine the possible incidence of the EET upon the larval density of Anopheles mosquitoes in Villa Clara province, Cuba. The Climatological data were compiled from the Yabú station in Santa Clara, and a total of 5 370 measurements were included in a database every three hours, using the aggregate function of the Statistical Package of Social Science software version 13 (SPSS), from January 1st, 2011 to September 30th, 2013. A long term forecast (1 year of advance) was made to obtain EET and the Anopheles larval density in the locality of Santo Domingo was modelled. These entomological data were taken at the same time but monthly, so the EET data were converted to monthly scale to be correlated with the monthly data of the larval density. The result was a 97.1 % of variance with a standard error (SE) of 3.57 °C for the model of the EET with a year of anticipation; therefore, the tendency in time was significant. The modeling also included the Anopheles larval density of mosquitoes in Santo Domingo, Villa Clara province, observing an increase of the EET, while the Anopheles mosquito larvae also increased. The most important variables in the model were the EET that were back in 1, 2, 3, 4, 7, 16, 24, 40 for the previous year; that is to say 2 920, 2 921, and so on, which explained a strong contagion among the data. EET correlation compared with itself in previous year was high; therefore, it may be used as a predictable variable. The anophelinic density in Santo Domingo explained the 66 % of the variance, with a SE of 0.66 larvae.m-2. The tendency of the Anopheles larval density was to diminish. In conclusion, EET has an important impact in larval density of Anopheles with EET increase associated with larval density decrease.

ResumenLa Temperatura Efectiva Equivalente (TEE) es la sensación térmica que siente una persona frente a una determinada combinación de temperatura del aire, humedad relativa y velocidad del viento. El objetivo de la investigación fue determinar la posible incidencia de la TEE sobre la densidad larval de mosquitos del género Anopheles en la provincia Villa Clara, Cuba. Una base de datos recogió medidas climatológicos cada tres horas durante el periodo comprendido entre el 1 de enero 2011 hasta el 30 de septiembre 2013, proveyendo un total de 5 370 medidas de la estación Yabú de Santa Clara. Se realizó un pronóstico a largo plazo (1 año) para obtener la TEE y se modeló la densidad larvaria total de mosquitos en la localidad de Santo Domingo. Los datos entomológicos fueron recogidos en el mismo lapso temporal pero con una periodicidad mensual, por lo que los datos de TEE fueron convertidos a escala mensual para poder ser empleados con los datos de densidad larvaria. Para la modelación se utilizó la Metodología de Regresión Objetiva Regresiva que explicó el 97.1 % de varianza con un error estándar (SE) de 3.57 ºC para el modelo de TEE con un año de antelación; la tendencia en el tiempo fue significativa al aumento. Además, al modelar la densidad larvaria anofelínica en el municipio Santo Domingo, se observó que a medida que aumenta la TEE, disminuye la densidad larval anofelínica. La variable más importante en el modelo fue la TEE regresada en 1, 2, 3, 4, 7, 16, 24, 40, pero del año anterior, es decir 2 920, 2 921, y así sucesivamente, explicando un contagio muy fuerte entre los datos. Ello fue debido a que la correlación de TEE con ella misma en años anteriores fue alta, por lo que puede ser utilizada como variable predictora. El modelo de densidad larval anofelínica en Santo Domingo explicó el 66 % de la varianza, con un SE de 0.06 larvas/m2. La tendencia de la DLA fue a la disminución. En conclusión, la TEE tuvo una incidencia directamente proporcional en la densidad larval anofelínica, ya que a medida que aumentaba este indicador, disminuyó la densidad larval anofelínica.