Adaptive Gene Loss? Tracing Back the Pseudogenization of the Rabbit CCL8 Chemokine.

Studies of the process of pseudogenization have widened our understanding of adaptive evolutionary change. In Rabbit, an alteration at the second extra-cellular loop of the CCR5 chemokine receptor was found to be associated with the pseudogenization of one of its prime ligands, the chemokine CCL8. This relationship has raised questions about the existence of a causal link between both events, which would imply adaptive gene loss. This hypothesis is evaluated here by tracing back the history of the genetic modifications underlying the chemokine pseudogenization. The obtained data indicate that mutations at receptor and ligand genes occurred after the lineage split of New World Leporids versus Old World Leporids and prior to the generic split of the of Old World species studied, which occurred an estimated 8-9 million years ago. More important, they revealed the emergence, before this zoographical split, of a "slippery" nucleotide motif (CCCCGGG) at the 3' region of CCL8-exon2. Such motives are liable of generating +1G or -1G frameshifts, which could, however, be overcome by "translesion" synthesis or somatic reversion. The CCL8 pseudogenization in the Old World lineage was apparently initiated by three synapomorphic point mutations at the exon2-intron2 boundary which provide at short range premature terminating codons, independently of the reading frame imposed by the slippery motif. The presence of this motif in New World Leporids might allow verifying this scenario. The importance of CCL8-CCR5 signaling in parasite-host interaction would suggest that the CCL8 knock-out in Old World populations might be related to changes in pathogenic environment.

Out-of-hours endoscopy for non-variceal upper gastrointestinal bleeding.

BACKGROUND: Most countries lack a well-coordinated approach to out-of-hours endoscopy. Economic constraints and lack of resources have been identified as important barriers. OBJECTIVE: To assess the performance evaluation of an out-of-hours emergency endoscopy model of care. DESIGN: During a 3 year period (January 2010 to December 2012), data from consecutive outpatients (n = 332) with non-variceal acute upper gastrointestinal bleeding admitted or transferred to a single referral hospital were prospectively collected. RESULTS: 34% (n = 113) were direct admissions whereas 66% (n = 219) were transferred from other hospitals. Median time to upper endoscopy esophagogastroduodenoscopy (EGD) was 6 h and 7.7 h for direct admissions and transferred, respectively. EGD was performed within 24 h in 90% of the patients. Rebleeding, in-hospital mortality, 30 day mortality and need for surgery were respectively 9.8%, 5.8%, 7.4%, and 6.6% and were not significantly different between the two groups. Age, malignancy, and moderate to high clinical Rockall risk score were independent predictors of in-hospital mortality in both groups. Age remained as an important predictor of main outcomes in transferred patients, while comorbidities differed according to admission status and predictable outcomes. CONCLUSION: This gastroenterology emergency model improved access and equity to out-of-hours endoscopy in an effective, safe, and timely way, recognized by the rates and the homogeneity observed in the outcomes, between transferred patients and direct admissions.

Hepatitis B Virus Inactive Carriers: Which Follow-up Strategy?

INTRODUCTION: The natural history of patients with inactive hepatitis B virus (HBV) is still unclear, persisting doubts about the optimal management of these patients. AIM: To evaluate the long-term outcome in a cohort of hepatitis B inactive carriers. METHODS: We conducted a retrospective study in a cohort of 100 HBV inactive carriers (categorized after quarterly determinations of serum ALT and HBV DNA over one year) and analyzed the results of serial determinations of HBV DNA and alanine transaminase (ALT). The HBV DNA was quantified by Cobas TaqMan®. We used the Spearman's rank correlation coefficient to evaluate the correlation between the serum ALT and HBV DNA. RESULTS: We studied 100 HBV inactive carriers (53% females, mean age 48.7 ± 13.8 years, range 16-77 year). Vertical transmission was identified in 18%. The mean follow-up time was 4.6 ± 2.5 (2-13) years. Two patients had transient elevation of ALT (alcohol and drugs). We observed clearance of hepatitis B surface antigen (HBsAg) in four patients (4%) and biological and virological reactivation in 10% (from the 4th year of follow-up). Mild lesions were found in the 12 patients in whom liver biopsy was performed; genotypes A and D predominated. Viral load and serum ALT levels were unremarkable in 90% of the patients. There was no significant correlation (p > 0.05) between the values of ALT and HBV DNA throughout the follow-up. CONCLUSION: The management strategy, using both patterns of biochemical and virologic activity, seems adequate. The lack of correlation between the values of ALT and HBV DNA caveat its effectiveness and the stability of the levels of HBV DNA and ALT in most patients suggests that the prognosis of the inactive carriers, when defined accurately, is mostly benign. Further studies, including ones with new tests available, are needed to standardize and improve the management of this group of patients.

INTRODUÇÃO: A história natural dos portadores inactivos do vírus da hepatite B (VHB) é ainda pouco clara, persistindo dúvidas acerca da melhor estratégia de seguimento. OBJECTIVO: Avaliar o outcome num coorte de portadores inactivos VHB. MÉTODOS: Estudo retrospectivo num coorte de 100 portadores inactivos do VHB (categorizados após determinações seriadas trimestrais da ALT sérica e do ADN VHB durante 1 ano) através de doseamentos seriados anuais do ADN VHB e da ALT. O ADN do VHB foi quantificado através do Cobas TaqMan®. Utilizou-se o coeficiente de correlação estatística não paramétrico de Spearman para avaliar a existência de correlação entre os valores séricos da ALT e do ADN VHB. RESULTADOS: Dos 100 doentes incluídos, 53% são do sexo feminino; a idade média é de 48,7±13,8 (16-77) anos. A transmissão vertical foi identificada em 18%. A duração média do follow-up é de 4,6±2,5 (2-13) anos. Dois doentes apresentaram elevação transitória da ALT (álcool e fármacos). Observou-se clearance do AgHBs em 4 doentes (4%) e reactivação biológica e virológica em 10% (a partir do 4° ano de follow-up). Foi realizada biopsia hepática em 12 doentes que apresentavam lesões mínimas. Os genótipos A e D foram os mais comuns. A carga viral e os níveis séricos da ALT mantiveram-se estáveis na maioria dos doentes (90%). Não foi observada correlação significativa (p>0,05) entre os valores da ALT e do ADN do VHB, ao longo do follow-up. CONCLUSÕES: A estabilidade dos níveis do ADN do VHB e da ALT na maioria dos doentes e a ausência de correlação entre os valores da ALT e do ADN do VHB ressalvam a eficácia desta estratégia de follow-up e sugerem que o prognóstico dos portadores inactivos, quando definidos com rigor, é sobretudo benigno. São necessários mais estudos, com novos e promissores métodos, para optimizar e uniformizar a abordagem deste grupo de doentes.