Construction of recombinant adenovirus expression vector of avian reovirus σC protein and its effect on proliferation of hepatocellular carcinoma cells / 中国生物制品学杂志

@#Objective To construct the recombinant adenovirus vector pAd-σC for the expression of avian reovirus(ARV)aC protein and to detect its effects on the proliferation of hepatocellular carcinoma cells,in order to build up a basis for the development of novel anti-tumor vaccines.Methods The recombinant shuttle vector pShuttle-σC was constructed by PCR amplification of ARV σC gene,and then transformed into competent BJ5183 cells containing the adenovirus vector pAdessy-1.The recombi-nant adenovirus vector pAd-σC was obtained by homologous recombination,and the virus was packaged in HEK293 cells.The virus titer was measured by TCID_(50),the expression of σC protein was determined by Western blot and ELISA,and the effect of virus on the proliferation of human hepatocellular carcinoma cells SMMC7721 was detected by CCK-8 assay.Results The recombinant shuttle vector pShuttle-σC was confirmed to be constructed correctly by double enzyme digestion and sequen-cing,and the recombinant adenovirus vector pAd-σC was constructed correctly as identified by colony PCR.σC protein was successfully expressed in hepatocellular carcinoma cells SMMC7721.The recombinant adenovirus Ad-σC had a titer of 10~(7.5)/0.1 mL,which inhibited the proliferation of hepatocellular carcinoma cells SMMC7721.Conclusion The recombinant adenovirus vector pAd-trC containing ARV σC gene was successfully constructed,and its inhibitory effect on tumor cell proliferation was preliminarily analyzed,which lays a foundation for revealing the molecular mechanism of ARV oncolytic effect and further developing novel anti-tumor biological preparation.

Adolescents infectés par le VIH au cours de la transition des soins pédiatriques aux soins pour adultes dans un hôpital de référence à Abidjan (Côte d'Ivoire). Etudes des caractéristiques cliniques / Hiv-infected adolescents during the transition from paediatric to adult care in a referral hospital in abidjan (cote d'ivoire). Clinical characteristics study

Les adolescents vivant avec le VIH ont de moins bons résultats que les adultes en matière de soins, en particulier lors de la transition entre les soins pédiatriques et les soins aux adultes. L' Objectif était de décrire les particularités socio familiales, cliniques, para cliniques et thérapeutiques des adolescents au cours de cette phase charnière de leur prise en charge. Méthodes. Il s'agissait d'une étude rétrospective à visée descriptive qui s'est déroulé du 1er au 31 mars 2020 (1 mois) sur la cohorte d'enfants vivant avec le VIH suivi au CHU de Cocody (Abidjan) de novembre 2005 à mars 2020 (15 ans). Résultats. Trente-huit adolescents en phase de transition ont été inclus. L'âge moyen était de 17 ans avec des extrêmes de 15 et 20 ans. Le sex ratio était de 1,37. La majorité des enfants étaient scolarisé (81,57%) avec un retard scolaire chez plus de la moitié (58%). Près de la moitié des cas était orphelin d'un ou des 2 parents (47,4%). Les conditions socioéconomiques étaient modestes ou défavorable (73,7%). Près de la moitié des adolescents était suivi depuis plus de 10 ans (42%). Un surpoids a été retrouvé dans 21% des cas. On notait un échec immunologique dans 10,5% des cas et un échec virologique dans un tiers des cas (31,6%). L'observance était moyenne ou mauvaise chez près de la moitié des adolescents (44,7%). La majorité des adolescents (94,7%) n'avait jamais eu de contact avec un médecin d'adulte. Conclusion. La transition des soins pédiatriques aux soins pour adulte est un processus au cours duquel l'adolescent est confronté à des diffi cultés socio familiale et scolaire, a l'inobservance avec échec thérapeutique qui doit être repéré de façon précoce. Le succès de cette étape nécessite également le rapprochement entre pédiatres et médecins d'adultes pour une prise en charge optimal des patients.

A BRD4 PROTAC nanodrug for glioma therapy via the intervention of tumor cells proliferation, apoptosis and M2 macrophages polarization

Glioma is a primary aggressive brain tumor with high recurrence rate. The poor efficiency of chemotherapeutic drugs crossing the blood‒brain barrier (BBB) is well-known as one of the main challenges for anti-glioma therapy. Moreover, massive infiltrated tumor-associated macrophages (TAMs) in glioma further thwart the drug efficacy. Herein, a therapeutic nanosystem (SPP-ARV-825) is constructed by incorporating the BRD4-degrading proteolytic targeting chimera (PROTAC) ARV-825 into the complex micelle (SPP) composed of substance P (SP) peptide-modified poly(ethylene glycol)-poly(d,l-lactic acid)(SP-PEG-PDLLA) and methoxy poly(ethylene glycol)-poly(d,l-lactic acid) (mPEG-PDLLA, PP), which could penetrate BBB and target brain tumor. Subsequently, released drug engenders antitumor effect via attenuating cells proliferation, inducing cells apoptosis and suppressing M2 macrophages polarization through the inhibition of IRF4 promoter transcription and phosphorylation of STAT6, STAT3 and AKT. Taken together, our work demonstrates the versatile role and therapeutic efficacy of SPP-ARV-825 micelle against glioma, which may provide a novel strategy for glioma therapy in future.

Exploration of Mechanism of Guben Qingyuan Prescription Combined with Androgen Deprivation Therapy Against Castration-resistant Prostate Cancer from AR/AR-V7 Signaling Pathway / 中国实验方剂学杂志

Objective:To explore the efficacy and mechanism of Guben Qingyuan prescription combined with androgen deprivation therapy （ADT） in the treatment of castration-resistant prostate cancer （CRPC）. Method:A CRPC-bearing mouse model was established. When the tumor volume reached about 100 mm³， 50 CRPC-bearing BALB/c nude mice were randomly divided into the model group， ADT group， and ADT+low-， medium-， high-dose Guben Qingyuan prescription groups， with 10 mice in each group. After grouping， it was ensured that there was no statistically significant difference in tumor volume between groups. The mice in the model group was treated with the same amount of normal saline （10 mL·kg^-1） by gavage， twice a day， while those in the other groups were provided with bicalutamide （5 mg·kg^-1） for intragastric administration， once a day， and then with goserelin （0.36 mg·kg^-1） for intraperitoneal injection on the 10th day. On the basis of ADT， the ones in the ADT+Guben Qingyuan prescription groups further received Guben Qingyuan prescription at the low （2.5 g·kg^-1）， medium （25 g·kg^-1）， and high doses （50 g·kg^-1） by gavage， twice a day. After 25 days of continuous administration， the tumor tissue was harvested for recording the tumor growth and calculating the tumor inhibition rate. The mRNA and protein expression levels of androgen receptor （AR）， androgen receptor splice variant-7 （AR-V7）， and prostate-specific antigen （PSA） were detected by real-time polymerase chain reaction （Real-time PCR） and Western blot assay. Result:The tumor inhibition rates of the ADT+low-， medium-， and high-dose Guben Qingyuan prescription groups were 27.95%， 46.71%， and 44.46%， respectively， and the inhibition rates in the ADT+medium- and high-dose Guben Qingyuan prescription groups were significantly increased as compared with that in the ADT group （<italic>P</italic><0.05）. As revealed by comparison with the ADT group， Guben Qingyuan prescription at the medium and high doses significantly down-regulated the mRNA and protein expression levels of AR， AR-V7， and PSA （<italic>P</italic><0.05）. Conclusion:Guben Qingyuan prescription combined with ADT is efficient in controlling the tumor growth in CRPC-bearing mice， which is related to the regulation of AR/AR-V7 signaling pathway.

Outcomes of HIV-Exposed infants enrolled in the Prevention of Mother to Child Transmission of HIV (PMTCT) program in Philippine General Hospital: An 8-year retrospective study

Background@#Our country has the fastest growing number of HIV cases in the Asia-Pacific region with a 203% increase from 2010 to 2018. MTCT represents 6% of infections in children and interventions such as the PMTCT program are essential to help reduce new infant infections. @*Objective@#To determine the outcomes of HIV-exposed infants born in PGH from 2010 to 2018 enrolled in the PMTCT program. To analyze the association of maternal and neonatal clinicodemographic factors to MTCT of HIV.@*Methods@#A retrospective cohort study using data collected from medical records of HIV exposed infants enrolled in the program. @*Results@#Out of 117 mother-infant pairs, only 70 met the eligibility criteria. Maternal factors showed that majority have: timely antenatal visit (56/70), maternal HIV diagnosis (70/70) and ART initiation (67/70) prior to delivery, triple lifelong maternal ART (69/70), CD4 >200 prior to delivery (52/70) and cesarean delivery (67/70). Amongst the infant factors-early infant prophylaxis (60/62), >4weeks prophylaxis duration (62/70) and replacement feeding (62/70) were noted in the majority. 2/70 infants were HIV positive. Mortality rate was 1.4% and 50% for HIV infected infants. Overall LTFU rate was 33.3%. Logistic regression showed that maternal co-infection with Hepatitis B(p=0.0275) was a possible determinant of MTCT. Infant HIV prophylaxis duration of >4 weeks had higher survival proportion(p=.0001). @*Conclusion@#The HIV MTCT rate was 2.86% upon implementation of our PMTCT program, meeting the <5% goal of WHO, suggesting that the program was an effective health intervention strategy. The high LTFU rate though should be considered in the evaluation of the program effectiveness.

Caracterización clínico-epidemiológico de pacientes perinatalmente expuestos al VIH en el Hospital Nacional Mario Catarino Rivas / Clinical-epidemiological characterization of perinatally exposed HIV patients. Mario Catarino Rivas National Hospital

Antecedentes: En los países con escasos recursos, la infección por VIH infantil tiene dimensiones alarmantes. Más del 90% de los niños que viven con VIH en los países en desarrollo se infectaron por transmisión de madre a hijo durante el embarazo, parto o lactancia. Con el fin de reducir el número de niños infectados por el VIH, se ha enfatizado en los programas de prevención de la transmisión vertical, encontrándose una reducción de la transmisión del virus, actualmente menos del 1% en niños de bajo riesgo. Objetivo: Caracterizar clínica y epidemiológicamente a los pacientes perinatalmente expuestos al VIH atendidos en el Hospital Nacional Mario Catarino Rivas enero 2018 - junio del 2019. Pacientes y Métodos: Estudio cuantitativo, observacional, descriptivo; se realizó la revisión de 42 expedientes clínicos, se aplicó un cuestionario de 23 preguntas abiertas y cerradas, evaluando variables clínicas y epidemiológicas. Resultados: el 85% de las madres conocían el diagnostico de ser VIH positivo, 66% diagnosticadas previo al embarazo, 80% en tratamiento con ARV, 26% con carga viral no detectable, 78% finalizo su embarazo vía cesárea, 53% fueron categorizados como alto riesgo, 85% recibió terapia ARV por 4 semanas, incidencia de VIH fue de 4.7%, 2 de los 42 pacientes,19% están perdidos en seguimiento, 88% recibió profilaxis con TMP-SMX.Conclusiones: El diagnóstico precoz de VIH en la infancia mediante la realización de pruebas vi * Médico Residente tercer año de Pediatría, UNAH-VS. ** Médico Pediatra, Servicio de Atención Integral, HNMCR. *** Médico Pediatra, Servicio de Atención Integral, HNMCR. Dirigir correspondencia a: damavibau_723@hotmail.com Recibido: 20 de Diciembre 2019 Aprovado:15 de marzo 2020 favorece al inicio temprano de tratamiento antirretroviral con un pronóstico de vida más favorable...(AU)

Circulating tumor cells and their role in prostate cancer / 亚洲男科学杂志(英文版)

Circulating tumor cells (CTC) have become an important biomarker in patients with advanced prostate cancer. CTC count has been demonstrated to be a prognostic factor for overall survival in patients with metastatic castration-resistant prostate cancer (mCRPC). In localized prostate cancer, a clear correlation between CTC counts and clinicopathological risk parameters and outcome has not been observed. Currently, the focus of research is shifting from CTC enumeration towards molecular characterization of CTC leading to the discovery of markers predicting treatment response. The role of androgen receptor splice variants expressed by CTC as markers of resistance to abiraterone and enzalutamide has been assessed by various studies. The identification of CTC markers predicting treatment response represents a key step to guide the selection of treatment (e.g., abiraterone/enzalutamide vs taxanes), particularly in patients with mCRPC. As an alternative to CTC, the analysis of circulating tumor DNA has been shown to enable a noninvasive disease characterization having high potential to promote precision oncology.

Battle of the sexes: Contrasting roles of testis-specific protein Y-encoded (TSPY) and TSPX in human oncogenesis / 亚洲男科学杂志(英文版)

The Y-located testis-specific protein Y-encoded (TSPY) and its X-homologue TSPX originated from the same ancestral gene, but act as a proto-oncogene and a tumor suppressor gene, respectively. TSPY has specialized in male-specific functions, while TSPX has assumed the functions of the ancestral gene. Both TSPY and TSPX harbor a conserved SET/NAP domain, but are divergent at flanking structures. Specifically, TSPX contains a C-terminal acidic domain, absent in TSPY. They possess contrasting properties, in which TSPY and TSPX, respectively, accelerate and arrest cell proliferation, stimulate and inhibit cyclin B-CDK1 phosphorylation activities, have no effect and promote proteosomal degradation of the viral HBx oncoprotein, and exacerbate and repress androgen receptor (AR) and constitutively active AR variant, such as AR-V7, gene transactivation. The inhibitory domain has been mapped to the carboxyl acidic domain in TSPX, truncation of which results in an abbreviated TSPX exerting positive actions as TSPY. Transposition of the acidic domain to the C-terminus of TSPY results in an inhibitory protein as intact TSPX. Hence, genomic mutations/aberrant splicing events could generate TSPX proteins with truncated acidic domain and oncogenic properties as those for TSPY. Further, TSPY is upregulated by AR and AR-V7 in ligand-dependent and ligand-independent manners, respectively, suggesting the existence of a positive feedback loop between a Y-located proto-oncogene and male sex hormone/receptors, thereby amplifying the respective male oncogenic actions in human cancers and diseases. TSPX counteracts such positive feedback loop. Hence, TSPY and TSPX are homologues on the sex chromosomes that function at the two extremes of the human oncogenic spectrum.

Battle of the sexes: contrasting roles of testis-specific protein Y-encoded (TSPY) and TSPX in human oncogenesis / 亚洲男科学杂志(英文版)

The Y-located testis-specific protein Y-encoded (TSPY) and its X-homologue TSPX originated from the same ancestral gene, but act as a proto-oncogene and a tumor suppressor gene, respectively. TSPY has specialized in male-specific functions, while TSPX has assumed the functions of the ancestral gene. Both TSPY and TSPX harbor a conserved SET/NAP domain, but are divergent at flanking structures. Specifically, TSPX contains a C-terminal acidic domain, absent in TSPY. They possess contrasting properties, in which TSPY and TSPX, respectively, accelerate and arrest cell proliferation, stimulate and inhibit cyclin B-CDK1 phosphorylation activities, have no effect and promote proteosomal degradation of the viral HBx oncoprotein, and exacerbate and repress androgen receptor (AR) and constitutively active AR variant, such as AR-V7, gene transactivation. The inhibitory domain has been mapped to the carboxyl acidic domain in TSPX, truncation of which results in an abbreviated TSPX exerting positive actions as TSPY. Transposition of the acidic domain to the C-terminus of TSPY results in an inhibitory protein as intact TSPX. Hence, genomic mutations/aberrant splicing events could generate TSPX proteins with truncated acidic domain and oncogenic properties as those for TSPY. Further, TSPY is upregulated by AR and AR-V7 in ligand-dependent and ligand-independent manners, respectively, suggesting the existence of a positive feedback loop between a Y-located proto-oncogene and male sex hormone/receptors, thereby amplifying the respective male oncogenic actions in human cancers and diseases. TSPX counteracts such positive feedback loop. Hence, TSPY and TSPX are homologues on the sex chromosomes that function at the two extremes of the human oncogenic spectrum.

Role of Androgen Receptor in Prostate Cancer: A Review

Androgen receptor (AR) is a steroid receptor transcriptional factor for testosterone and dihydrotestosterone consisting of four main domains, the N-terminal domain, DNA-binding domain, hinge region, and ligand-binding domain. AR plays pivotal roles in prostate cancer, especially castration-resistant prostate cancer (CRPC). Androgen deprivation therapy can suppress hormone-naïve prostate cancer, but prostate cancer changes AR and adapts to survive under castration levels of androgen. These mechanisms include AR point mutations, AR overexpression, changes of androgen biosynthesis, constitutively active AR splice variants without ligand binding, and changes of androgen cofactors. Studies of AR in CRPC revealed that AR was still active in CRPC, and it remains as a potential target to treat CRPC. Enzalutamide is a second-generation antiandrogen effective in patients with CRPC before and after taxane-based chemotherapy. However, CRPC is still incurable and can develop drug resistance. Understanding the mechanisms of this resistance can enable new-generation therapies for CRPC. Several promising new AR-targeted therapies have been developed. Apalutamide is a new Food and Drug Administration-approved androgen agonist binding to the ligand-binding domain, and clinical trials of other new AR-targeted agents binding to the ligand-binding domain or N-terminal domain are underway. This review focuses on the functions of AR in prostate cancer and the development of CRPC and promising new agents against CRPC.

Correlations between clinical features and CD4 cell count in HIV patients with tuberculosis

Background: The correlation between tuberculosis and HIV is evident from the higher incidents of tuberculosis estimated 5-8% per year among HIV infected person with lesser CD4cell count. The high seroprevalence with tuberculosis in occurrence among AIDS patients.Methods: 100 HIV positive patients with tuberculosis who were admitted to medicine department and who visited to ARTS center were taken up for study for period of two years from December 2014 to 2016. Type of study is a observational comparative cross sectional study The investigation for HIV and TB were done as per NACO and WHO recommendation ELISA test CD4 cell counts AFB staining chest X-ray FNAC Mountoux test pleural fluid analysis Ascitic fluid analysis CSF fluid analysis USG of thorax CT scan of thorax.Results: It is seen that the maximum number of patients belong to the age group 31-40 years male 40 (40%) and female 4(4%) the common occupation in the study group was driver 36 (36%) the common constitutional symptom was weight loss physical examination reveal underweight (BMI <16-18.5) 54 (54%) among the study extra-pulmonary TB 63 (63%) X-ray chest finding pleural effusion found in 21% of patients CD4 cell counts 200-500 /µl was seen maximum number of patients.Conclusions: The CD4cell counts is important investigation in HIV and TB patients it is main investigation to know prognosis of HIV also important for initiation of ARV drugs.it is evident from this study the decrease the CD4cell counts there is increase the incidence of tuberculosis.

The study of CUDC-101 inhibits the expression of AR-V7 in castration-resistant prostate cancer cells / 中华泌尿外科杂志

Objective To solve the problem of castration resistant prostate cancer (castrationresistant prostate cancer,CRPC) the problem of drug resistance by studing the expression of the CUDC-101 inhibitor of castration resistant prostate cancer androgen receptor splice variant 7.Methods In this study,the expression of AR-V7 protein in prostate cancer cell lines PC-3,VCaP,22Rv1,LNCap was detected by imnmunoblotting between April 2015 and April 2016,and the highest expression level of cell lines was selected follow-up experiments.Through the cell proliferation and activity experiments,the epigenetic inhibitors:histone deacetylase inhibitor CUDC-101,histone methylation inhibitor DZNeP,DNA methylation inhibitor gemcitabine,histone acetyltransferase inhibitor MG149 to select an inhibitor that reduces the expression of AR-V7 protein in CRPC cells.22Rv1 cells were treated with 30 nmol and 300 nmol of CUDC101 and 1,10 and 20 μmol of Enzalutamide (MDV3100),respectively,and their inhibitory effects on the growth of 22Rv1 cells were examined.Results The results of immunoblotting showed that AR-V7 protein was only expressed in CRPC cell line 22Rv1 and negative in non-CRPC cell line.The expression of AR-V7 in 22Rv1 cells treated with CUDC-101 was significantly lower than that of negative control.While other inhibitors had no effect on the expression of AR-V7.In the cell proliferation and activity assay,the inhibitory rates of 30 nmol CUDC-101 and 1,10 and 20 μmol MDV3100 were 10％,35％ and 45％,respectively,higher than that of MDV3100 alone.28％ and 42％,the difference was statistically significant (P ＜ 0.05).The inhibitory rates of 300 nmol CUDC-101 and MDV3100 were 30％,60％ and 65％,respectively,which were significantly higher than those of MDV3100 alone (P ＜ 0.05).Conclusions CUDC-101 can inhibit the castration resistant prostate cancer androgen receptor splice variant 7 expression,and solved the resistance problem of CRPC.

Development of AR-V7 as a putative treatment selection marker for metastatic castration-resistant prostate cancer / 亚洲男科学杂志(英文版)

Prostate cancer cells demonstrate a remarkable "addiction" to androgen receptor (AR) signaling in all stages of disease progression. As such, suppression of AR signaling remains the therapeutic goal in systemic treatment of prostate cancer. A number of molecular alterations arise in patients treated with AR-directed therapies. These molecular alterations may indicate the emergence of treatment resistance and may be targeted for the development of novel agents for prostate cancer. The presence of functional androgen receptor splice variants may represent a potential explanation for resistance to abiraterone and enzalutamide, newer AR-directed agents developed to treat metastatic castration-resistant prostate cancer (mCRPC). In the last 8 years, many androgen receptor splice variants have been identified and characterized. Among these, androgen receptor splice variant-7 (AR-V7) has been investigated extensively. In AR-V7, the entire COOH-terminal ligand-binding domain of the canonical AR is truncated and replaced with a variant-specific peptide of 16 amino acids. Functionally, AR-V7 is capable of mediating constitutive nuclear localization and androgen receptor signaling in the absence of androgens, or in the presence of enzalutamide. In this review, we will focus on clinical translational studies involving detection/measurement of AR-V7. Methods have been developed to detect AR-V7 in clinical mCRPC specimens. AR-V7 can be reliably measured in both tissue and circulating tumor cells derived from mCRPC patients, making it possible to conduct both cross-sectional and longitudinal clinical correlative studies. Current evidence derived from studies focusing on detection of AR-V7 in mCRPC support its potential clinical utility as a treatment selection marker.

A study of compliance of animal bite victims to 4 dose intradermal schedule of anti-rabies vaccine and factors affecting it.

Background: Rabies is 100% fatal disease, but it is prevented by use of potent Anti-Rabies Vaccine (ARV). Noncompliance to vaccination schedule is one of the reasons for high number of deaths among animal bite victims. The present study is an attempt to reveal compliance of animal bite victims to 4 dose intradermal (id) schedule of Anti-Rabies Vaccine (ARV) schedule and socio-demographic factors with it. Methods: This cross sectional study was conducted at ARV centre of government medical college, Akola, Maharashtra state of India, from 1st January 2014 to 31st December 2014. Records of all animal bite victims were studied and data regarding their compliance for completion of vaccination schedule and sociodemographic and animal related factors was analyzed. Results: Out of these 3658 victims of animal bite, 1566 (42.81%) completed ARV schedule and remaining 2092 (57.91%) failed in it. Out of those who completed the schedule, 1484 (94.76%) didn’t delayed any dose and rest 82 (5.24%) delayed one or more doses. With respect to the completion to of id ARV schedule, no significant association was observed with gender, age, place of residence and economic status of victims. But significantly higher proportion of category II bite (63.85%) and unprovoked bite (69.44%) patients exhibited poor compliance for adherence of vaccination schedule than that of category III bite (56.42%) and provoked bite (33.16%) patients respectively. Conclusions: Poor compliance to ARV vaccination, among more than half of animal bite victims, is a serious concern in id schedule.

Evaluación de resistencia genotípica del VIH-1 en pacientes con fallo virológico de Guatemala / Evaluation of genotypic resistance of HIV-1 in patients with virologic failure Guatemala

La resistencia a la terapia antirretroviral (TARV) es un factor determinante para el fallo virológico en pacientes con VIH. El objetivo de este estudio fue identificar los patrones genotípicos de resistencia en pacientes con fallo virológico. Fueron incluidos pacientes de las diferentes unidades de atención integral de VIH en Guatemala, de quienes se sospechaba resistencia y que necesitaban cambios en la TARV por fallo virológico, se requirió haber evaluado la adherencia y una carga viral ≥1,000 copias/ml. La información clínica y demográfica fue recolectada a través de la forma de solicitud. El análisis de resistencia se realizó a través de la metodología TRUGENE® HIV-1. La muestra se restringió a 25 pacientes por motivos de accesibilidad. El 68% de las muestras analizadas presentaron resistencia; por familia de ARV la resistencia fue de 88.2% para ITINN, 70.5% para ITIAN y 17.6% para IP. Se identificaron 79 mutaciones entre el grupo de estudio, el 46.8% de fueron asociadas a ITINN, 76.6% a ITIAN y 26.6% a IP. Para ITIAN las mutaciones más frecuentes fueron la M184V 43%, M184I 14% y K219E 10%; el 23.8% fueron mutaciones TAMs. Para ITINN fueron la V179D 16%, K103N 14%, G190A 14% y Y181C 14%. Para los IP la mutación más frecuente fue la M36I con 29%. La resistencia identificada en este grupo, fue menor a lo reportado en otros países latinoamericanos; sin embargo es similar a lo reportado por OMS en países con bajo o medio ingreso económico.

ARV drug resistance is one of the leading causes of virologic failure among HIV patients on HAART. Theobjective of this study was to determine genotypic resistance profiles among HIV patients on virologic failure. Patients from one HIV clinic in Guatemala on whom ARV drug resistance was suspected and needed a change in their ARV regimen due to virologic failure were included. In order to perform the genotype, the patient had to demonstrate good adherence to therapy and a confirmed viral load ≥1,000 copies/ml. Demographics andclinical data were collected through the resistance-testing questionnaire. The TRUGENE® HIV-1 methodology was used for resistance analysis. The patient sample was restricted to 25 patients due to accessibility, 68% presented resistance to at least one ARV drug. By ARV class, 88.2% presented resistance to NNRTIs, 70.5% to NRTIs and 17.6% to IPs. We found 79 mutations among the samples analyzed. Of the mutations found, 46.8% were associated with NNRTI resistance, 76.6% to NRTI resistance and the remainder 26.6% to PI resistance. The most frequent NRTI associated mutations were M184V 43%, M184I 14% and K219E 10%; 23.8% were TAM. The NNRTI associated mutations were V179D 16%, K103N 14%, G190A 14% and Y181C 14%. For the PI the most frequent mutation was M36I with 29%. The resistance found in this study was lower to that reported in other Latin American studies, however, it is similar to what is reported by WHO in low and middle income countries.

Knowledge assessment about risk prevention of rabies amongst doctors in AIIMS, Jodhpur.

Background: Rabies still continues to be a public health problem in India and to protect our citizens from this menace; medical professionals have to be well equipped to tackle it more efficiently. The paper aims to assess the knowledge of residents and faculty in newly established AIIMS regarding risk prevention of rabies. Methods: A cross sectional study using a structured questionnaire on rabies was done at AIIMS Jodhpur amongst the doctors and the data was compiled in Microsoft excel 2010 were further analysed using SPSS version 21. Results: Out of the total sixty respondents, faculty constituted 38.3%, and junior residents and senior residents 28.3% and 33.3% respectively. Nearly 72% responded correctly regarding post exposure prophylaxis (PEP) i.e. 5 dose regimen of intramuscular administration of Anti Rabies Vaccine (ARV) and 56.7% doctors were unaware about the current recommendation of intradermal (ID) route. Rabies immunoglobulin (RIG) or Anti-Rabies Serum (ARS) against Rabies infection used in Class III bites was known to only 45% of the total doctors. Conclusion: The study reveals that there is a scope of improvement in important areas related to the knowledge of doctors in AIIMS regarding animal bites which needs to be upgraded time to time through continuing medical education in order to follow the standard protocol and guidelines at the apex institute.

Clinical and Laboratory Profile of ARV Naive HIV Infected Children in the Era of Highly Active Anti-retroviral Therapy in Enugu, South-East Nigeria.

Background: HIV/AIDS is one of the most dynamic epidemic infectious diseases. An estimated 1000 children are newly infected with HIV every day, most of them in sub-Saharan Africa. They often present with various clinical and laboratory manifestations that complicates their management. Objectives: To determine the baseline clinical and laboratory features of HIV-infected children presenting at the University of Nigeria Teaching Hospital (UNTH) Ituku/Ozalla. Methods: Clinical and laboratory data were collected from HIV infected children seen at the Pediatric HIV Clinic of UNTH between July 1st 2010 and June 30th 2012. Clinical and immunological staging of the patients were done using the WHO criteria and data analysis was with SPSS version19. Results: Two hundred and ten children were enrolled into the study. The most common route of HIV infection was vertical transmission (95.2%). Common presenting clinical and laboratory data were: anaemia (92.9%), cough (76.2%), fever (63.3%), popular rash (62.9%) and poor weight gain (61.0%). Thirty-four children (16.2%) each had severe and moderate acute malnutrition while 92 children (43.8%) were stunted. Tuberculosis, hepatitis B and C co-infections were seen in 32.4%, 1.9% and 3.3% of the children respectively. Most of the patients had either a WHO clinical stage III (42.4%) or II (39.0%) disease. Severe immunosuppression based on CD4% or count was seen in more than half of the patients (59.1%). Conclusions: Anaemia was the most common clinical/laboratory finding; followed by cough. Although our patients were likely to present with WHO clinical 2 or stage 3 disease, severe immunological suppression was common.

Risk Factors for First-line Antiretroviral Treatment Failure in HIV-1 Infected Children Attending Jos University Teaching Hospital, Jos, North Central Nigeria.

Aim: To determine risk factors for first-line antiretroviral treatment failure in HIV-1 infected children attending Jos University Teaching Hospital, Jos. Study Design: Retrospective cohort study. Place and Duration of Study: Paediatric HIV clinic at the Jos University Teaching Hospital, Jos, between February 2006 and December 2010. Methodology: Data on demographic, clinical and laboratory variables for 580 HIV-1 infected children aged 2 months to 15 years on antiretroviral therapy (ART) were analysed. A comparison of the data on children with and without treatment failure was made. Variables associated with treatment failure in a univariate analysis were then fit in a multivariate logistic model to determine the factors that were associated with treatment failure. Results: The rate of treatment failure among the children was 18.8%. Previous antiretroviral drugs (ARV) exposure for treatment, not receiving cotrimoxazole prophylaxis before commencement of ART and having severe immune suppression at HIV diagnosis were the factors independently associated with treatment failure. Children with previous ARV exposure for treatment were 4 times more likely to fail treatment compared to those without previous exposure (AOR=4.20 (1.93-9.15); p <0.001). Children who did not receive cotrimoxazole prophylaxis were twice more likely to develop treatment failure compared to those who did (AOR=2.26 (1.06-4.79); p=0.03) and children with severe immune suppression at HIV diagnosis were twice more likely to develop treatment failure compared to those without severe immune suppression (AOR=2.34 (1.47-3.72); p<0.001). Conclusion: HIV-infected children with previous ARV exposure for treatment and severe immune suppression should be monitored closely and given frequent adherence counseling to minimize the risk of treatment failure. Cotrimoxazole prophylaxis should be encouraged in HIV-infected children while they await commencement of ART, which may improve ART adherence and thus reduce the risk of treatment failure.

The occurrence of orthoreovirus, rotavirus and chicken anemia virus in chickens of the poultry industry in Minas Gerais, Brazil / Ocorrência de orthoreovirus, rotavirus e vírus da anemia das galinhas em frangos de corte da indústria avícola de Minas Gerais

Fifty-four fecal samples taken from broiler chickens from 1 to 45 days of age, and of pullets from 10 to 13 weeks of age, original from eight different poultry regions in the state of Minas Gerais, Brazil, were collected from March 2008 to January 2010 for avian Orthoreovirus (ARV) and avian Rotavirus (AvRV) analyses. For the assay of ARV, RNA was immediately extracted (Trizolâ) and transcribed into cDNA for assaying in a nested-PCR with ARV-specific primers. For AvRV, polyacrylamide gel electrophoresis (PAGE) was performed with RNA extracts obtained by phenol-chloroform extraction. CAV was additionally investigated through a nested-PCR of thymus and spleen. Results found 5.55% positive for ARV and 9.25% for AvRV. Also, CAV and ARV genomes were detected in co-infection, in a highly prostrated and claudicating chicken flock. No ARV or AvRV infections were detected in pullets. Material of a clinically affected flock was inoculated into SPF embryos, resulting in embryonic hemorrhage, whitish foci in the chorio-allantoic membrane and death. Sequencing of ARV amplicons and isolate cDNA grouped local strains with the ARV S1133 strain, historically used in live vaccines, suggesting the continued circulation of this vaccine virus strain in intensive poultry regions. Detection rates for ARV and AvRV, as well as the presence of CAV, were additionally indicative of failing biosecurity strategies for the intensive poultry regions examined.

Avaliou-se a ocorrência de Orthoreovirus (ARV) e Rotavirus (AvRV) aviários na avicultura industrial de Minas Gerais. Foram colhidas cinquenta e quatro amostras de fezes de frangos de corte entre um e 45 dias e de frangas de postura de 10 a 13 semanas de idade. Para análise de ARV, o RNA foi imediatamente extraído (Trizol), transcrito em cDNA e avaliado em uma PCR com oligonucleotídeos iniciadores específicos para ARV. Para a investigação de AvRV, os extratos de RNA foram obtidos por fenol-clorofórmio e submetidos à eletroforese em gel de poliacrilamida. Todas as amostras foram também avaliadas para o DNA do vírus da anemia das galinhas (CAV) em uma nested-PCR específica. Em frangos de corte, a positividade encontrada para ARV foi de 5,55% e para AvRV de 9,25%. CAV foi detectado em coinfecção em um plantel com refugagem, claudicação e prostração. Nenhuma amostra de poedeiras foi positiva para ARV ou AvRV. Material de plantel com sinais clínicos foi purificado e inoculado em ovos SPF embrionados, sendo obtidas lesões hemorrágicas e focos brancos na membrana cório-alantóide. O sequenciamento dos produtos de PCR e de embrião agrupou os isolados de ARV com a estirpe S1133, historicamente usada como vacina viva. Os resultados sugerem a continuada circulação da infecção por estirpes assemelhadas a ARV S1133 nas regiões de avicultura industrial. Os índices de detecção de ARV, AvRV e CAV indicam que a intensificação nas regiões produtoras tem resultado em falhas de biosseguridade.

Optimizing adherence to antiretroviral therapy.

HIV has now become a manageable chronic disease. However, the treatment outcomes may get hampered by suboptimal adherence to ART. Adherence optimization is a concrete reality in the wake of ‘universal access’ and it is imperative to learn lessons from various studies and programmes. This review examines current literature on ART scale up, treatment outcomes of the large scale programmes and the role of adherence therein. Social, behavioural, biological and programme related factors arise in the context of ART adherence optimization. While emphasis is laid on adherence, retention of patients under the care umbrella emerges as a major challenge. An in-depth understanding of patients’ health seeking behaviour and health care delivery system may be useful in improving adherence and retention of patients in care continuum and programme. A theoretical framework to address the barriers and facilitators has been articulated to identify problematic areas in order to intervene with specific strategies. Empirically tested objective adherence measurement tools and approaches to assess adherence in clinical/ programme settings are required. Strengthening of ART programmes would include appropriate policies for manpower and task sharing, integrating traditional health sector, innovations in counselling and community support. Implications for the use of theoretical model to guide research, clinical practice, community involvement and policy as part of a human rights approach to HIV disease is suggested.