Retroviral PBS-segment sequence and structure: Orchestrating early and late replication events.

An essential regulatory hub for retroviral replication events, the 5' untranslated region (UTR) encodes an ensemble of cis-acting replication elements that overlap in a logical manner to carry out divergent RNA activities in cells and in virions. The primer binding site (PBS) and primer activation sequence initiate the reverse transcription process in virions, yet overlap with structural elements that regulate expression of the complex viral proteome. PBS-segment also encompasses the attachment site for Integrase to cut and paste the 3' long terminal repeat into the host chromosome to form the provirus and purine residues necessary to execute the precise stoichiometry of genome-length transcripts and spliced viral RNAs. Recent genetic mapping, cofactor affinity experiments, NMR and SAXS have elucidated that the HIV-1 PBS-segment folds into a three-way junction structure. The three-way junction structure is recognized by the host's nuclear RNA helicase A/DHX9 (RHA). RHA tethers host trimethyl guanosine synthase 1 to the Rev/Rev responsive element (RRE)-containing RNAs for m7-guanosine Cap hyper methylation that bolsters virion infectivity significantly. The HIV-1 trimethylated (TMG) Cap licenses specialized translation of virion proteins under conditions that repress translation of the regulatory proteins. Clearly host-adaption and RNA shapeshifting comprise the fundamental basis for PBS-segment orchestrating both reverse transcription of virion RNA and the nuclear modification of m7G-Cap for biphasic translation of the complex viral proteome. These recent observations, which have exposed even greater complexity of retroviral RNA biology than previously established, are the impetus for this article. Basic research to fully comprehend the marriage of PBS-segment structures and host RNA binding proteins that carry out retroviral early and late replication events is likely to expose an immutable virus-specific therapeutic target to attenuate retrovirus proliferation.

Peri-procedural antithrombotic management: time to burn the bridge?

Emerging evidence suggests the use of peri-procedural bridging during interruptions in warfarin therapy increases bleed risk without reducing thromboembolic events. We implemented a peri-procedural anticoagulant management risk assessment tool in a single, outpatient anticoagulation clinic within an academic teaching institution. In this retrospective, pre-post observational study, we evaluated adults who required an interruption in warfarin therapy for an invasive procedure. The primary outcome was the proportion of patients who received bridging prior to and following implementation of the tool. Secondary outcomes included major bleeding, clinically relevant non-major bleeding, thromboembolic events, and other surgical complications within 30 days of the index procedure. In total, 149 patients were included. Bridging was recommended in 60% of the pre-intervention group and in 39.3% of the post-intervention group (p = 0.012). There were no significant differences in the secondary outcomes between the groups. However, patients who received bridging had numerically more bleeding events than patients who did not (12.3 vs. 3.9%, p = 0.102), and patients who received therapeutic dose bridging had more bleeding events than those who received modified dose bridging (10.9 vs. 1.4%, p = 0.466). Following implementation of the tool, there was a statistically significant decrease in the number of patients who received bridging without an increase in thromboembolic events. There were numerically higher rates of bleeding in those who received bridging. Additional research is needed to evaluate efficacy and safety of prophylactic versus treatment dose bridging and how implementation of peri-procedural antithrombotic tools reflecting the emerging evidence will affect patient outcomes, satisfaction and healthcare costs.

Pilot study of musculoskeletal pain in ophthalmologists following participation in a fifteen-minute online Iyengar yoga program.

Purpose: To evaluate the prevalence of musculoskeletal (MSK) complaints in ophthalmologists and to assess whether participation in an online Iyengar yoga video program improves the baseline pain scores and awareness of proper posture in the clinic and operating room. Methods: Ophthalmologists were recruited from online professional forums for this nonrandomized, prospective study. A pre-intervention survey, including demographics, office and procedure volumes, wellness activities, and baseline MSK pain scores, was completed. A fifteen-minute instructional video focusing on simple yoga poses for the neck, shoulder, and lower back created by one of the authors, who is both an ophthalmologist and a certified Iyengar yoga teacher, was provided to participants to complete three times weekly for a total of 4 weeks. A post-intervention survey collecting MSK pain scores and information about ergonomics and compliance was completed. Results: Fifty ophthalmologists completed the pre-intervention survey, of whom 49 (98%) reported at least 1 episode of MSK discomfort in the preceding year. Of those, discomfort was cervical in 36 (72%), in the shoulder(s) in 15 (29%), thoracic spinal in 23 (46%), lumbar spinal in 23 (46%), and centered in the wrist, hand, or finger in 22 (44%). Of the 50 ophthalmologists, 22 submitted the post-intervention surveys. The post-intervention pain scores were decreased compared to baseline for cervical spine (P < 0.01), shoulder (P < 0.01), thoracic spine (P < 0.01), lumbar spine (P < 0.01) and wrist, hand, or finger (P < 0.01). 20 respondents (91%) reported improved awareness of their posture in the clinic and operating room, and 19 (86%) felt that this awareness would decrease their MSK symptoms. Conclusions: Among our small group of survey respondents, a fifteen-minute Iyengar yoga video program specifically designed for ophthalmologists reduced MSK pain and improving awareness of proper ergonomics for practicing ophthalmologists.

Efectos de la ilegitimidad sobre el primer año de vida / Effects of ilegitimacy upon children in thein first year of life

Se estudió la evolución del primer año de vida de 80 hijos de madres solteras, 73 hijos de convivientes y 75 de madres casadas, que se controlaron en el consultorio Dr. Carlos Avendaño de la comuna de Pudahuel de Santiago, durante los años l980 y 1981. Los niños no presentaron diferencia en cuanto a tipo de parto ni peso de nacimiento; difirieron, en cambio, en su distribución por número de orden con una proporción significativamente mayor de primogénitos en el grupo de madres solteras. Las madres solteras, con edad promedio de 20,3 años, eran más jóvenes que las casadas y convivientes. Cuarenta y cuatro por ciento de los niños iniciaron sus controles de salud en los primeros 10 días de vida, sin diferencias por estado civil materno, pero la asistencia a controles de salud fue menos satisfactoria en los hijos de madres solteras y convivientes que en los de casadas (p < 0,05). La duración de la lactancia natural y el progreso pondoestatural fueron similares en los tres grupos, pero la incidencia de desnutrición muestra una tendencia marcada, aunque no claramente significativa, a ser mayor en los hijos de madres solteras. El estado civil no influyó en la frecuencia de consultas nuevas por enfermedades respiratorias y los hijos de solteras tuvieron una cifra ligeramente mayor de consultas por síndrome diarreico agudo

Características socieconómicas de la madre soltera no conviviente en un área periférica de Santiago / Socioeconomic aspects of single mothers without cohabitation in a peripheric area of Santiago

A través de una encuesta aplicada entre Noviembre de 1982 y Enero de 1983, se estudiaron las características socieconómicas y aspectos de la esfera afectiva de 100 madres solteras, sin convivencia marital y con hijos menores de 2 años en control en el Consultorio Dr. Carlos Avendaño (Servicio de Salud Metropolitano Occidente). Los principales resultados fueron: El 34% de las madres era menor de 20 años (mediana de edad: 21,7 años). Un 89% tenía entre 5§ año básico y enseñanza media. El 24% tenía más de un hijo, de diferente padre en 17 casos. Un 43% de los niños no estaba reconocido legalmente por sus padres, quienes hacían aporte económico sólo en un 36%, mientras las madres lo hacían en un 27%. Las viviendas no disponían de agua potable intradomiciliaria y conexión al alcantarillado en un 16% de los casos (1 de cada 6). El 92% de las encuestadas vivía con su familia (71% con los padres), siendo ésta la principal fuente de recursos económicos. La relación afectiva con el hijo fue calificada como regular o mala en un 3%. Un 60% de las madres no tenía lazos afectivos con el padre del menor y un 4% ya había formado pareja con otro individuo. El 76% no deseaba un nuevo embarazo, sin embargo sólo un tercio de ellas (22 casos) estaba usando algún método anticonceptivo