Tuberculosis among the indian population in São Gabriel da Cachoeira, Amazonas State, Brazil

This study describes the tuberculosis situation in S?o Gabriel da Cachoeira, Amazonas State, Brazil, from 1997 to 2002. The county, which has a predominantly Indian population, is a relevant tuberculosis area in Amazonas, since the infection rate is 2.4 to 4 times that of the overall State and national rates. The statistical analyses used to assess its association with age, gender, and clinical form showed differences in the endemic behavior, comparing the urban and rural incidence rates. Males had higher standardized incidence rates than females in both the urban and rural areas. The most heavily affected age group was greater than 50 years, but the rate among individuals under 15 years was above the overall national rate, in addition to presenting different severity levels in the rural sub-areas that were studied. The situation can be explained mainly by inequalities in access to health services, which paradoxically appear to show lower case-resolving capacity in urban areas of the county.     

Use of Ketofol for procedural sedation and analgesia in children with hematological diseases

Background: The aim of this study was to evaluate the effectiveness and safety of intravenous ketamine–propofol admixture (“ketofol”) in the same syringe for procedural sedation and analgesia in children undergoing bone marrow aspiration. Methods: This was a prospective, observational pilot study. Patients aged between 4 and 12 years requiring sedation for bone marrow aspiration were included. Ketofol (1 : 1 mixture of ketamine 10 mg/mL and propofol 10 mg/mL) was given intravenously in 0.5 mg/kg aliquots each with a 1‐min interval and titrated to reach sedation levels of 3 or 4 (Ramsay score). The primary outcome was patient satisfaction with the degree of sedation. Secondary outcomes included injection pain, total sedation time, recovery time, hemodynamic and respiratory parameters, and adverse events. Results: A total of 20 patients were enrolled in the study. The median total dose of ketofol administered was 1.25 mg/kg each of propofol and ketamine (95%CI 0.77–2 mg/kg). The median score on the visual analog scale was 0 (extremely comfortable) (0–1.5; 95%CI 0.2–2.2). Median recovery time was 23 min (20.5–28 min; 95%CI 17.1–51.2). The incidence of injection pain was 2/20. Two patients had transient diplopia and one child reported dreams. No patients had hypotension, vomiting or required airway intervention. Conclusion: Ketofol provided effective sedation, which was reflected in the high degree of satisfaction recorded by children requiring procedural sedation and analgesia for bone marrow aspiration. We also observed rapid recovery and no clinically significant complications. A large number of patients is required to evaluate and validate these findings.     

Spontaneous bacterial peritonitis caused by Streptococcus bovis: case report and review of the literature

Spontaneous bacterial peritonitis (SBP) is a frequent and severe complication that occurs in patient with cirrhosis and ascites. It occurs in 10% to 30% of patients admitted to hospital. The organisms that cause SBP are predominantly enteric. Escherichia coli is the most frequent recovered pathogen, and Gram-positive bacteria, mainly Staphylococcus spp., are being considered an emerging causative agent of SBP. Streptococcus bovis that may be found as part of the commensal bowel flora in about 10% of healthy adults constitute an uncommon cause of peritonitis that was first reported in 1994. We describe the first case of SBP at the University Hospital of Santa Maria (HUSM) caused by S. bovis, resistant to the antibiotics erythromycin and clindamycin (inducible clindamycin resistance detected by disk diffusion test using the D-zone test).     

Evolutionally dynamic L1 regulation in embryonic stem cells

Mobile elements are important evolutionary forces that challenge genomic integrity. Long interspersed element-1 (L1, also known as LINE-1) is the only autonomous transposon still active in the human genome. It displays an unusual pattern of evolution, with, at any given time, a single active L1 lineage amplifying to thousands of copies before getting replaced by a new lineage, likely under pressure of host restriction factors, which act notably by silencing L1 expression during early embryogenesis. Here, we demonstrate that in human embryonic stem (hES) cells, KAP1 (KRAB [Krüppel-associated box domain]-associated protein 1), the master cofactor of KRAB-containing zinc finger proteins (KRAB-ZFPs) previously implicated in the restriction of endogenous retroviruses, represses a discrete subset of L1 lineages predicted to have entered the ancestral genome between 26.8 million and 7.6 million years ago. In mice, we documented a similar chronologically conditioned pattern, albeit with a much contracted time scale. We could further identify an L1-binding KRAB-ZFP, suggesting that this rapidly evolving protein family is more globally responsible for L1 recognition. KAP1 knockdown in hES cells induced the expression of KAP1-bound L1 elements, but their younger, human-specific counterparts (L1Hs) were unaffected. Instead, they were stimulated by depleting DNA methyltransferases, consistent with recent evidence demonstrating that the PIWI–piRNA (PIWI-interacting RNA) pathway regulates L1Hs in hES cells. Altogether, these data indicate that the early embryonic control of L1 is an evolutionarily dynamic process and support a model in which newly emerged lineages are first suppressed by DNA methylation-inducing small RNA-based mechanisms before KAP1-recruiting protein repressors are selected.     

Fatal necrotic tracheitis by Aviadenovirus in captive Alagoas curassows (Pauxi mitu) extinct from the wild

Extinct from nature, captive young Alagoas curassows (Pauxi mitu) were found agonizing or dead with respiratory disease. Intranuclear inclusion bodies were found in the epithelia of the trachea, associated with marked necrotic tracheitis. An Aviadenovirus was isolated in chicken eggs and characterized genetically with 99% identity to the fowl Aviadenovirus A, as based on the hexon protein gene. This is the first report of respiratory disease caused by Aviadenovirus in any cracid species in Brazil, recommending for stricter biosecurity in the conservation premises.

RESEARCH HIGHLIGHTS

• Fatal tracheitis in curassows extinct from nature was associated with Aviadenovirus A.

• Seven-month-old Alagoas curassows (Aves: Cracidae) died with haemorrhagic tracheitis.

• Aviadenovirus A with 99% identity to fowl adenovirus 1 was detected in dead curassows.

• Fatal tracheitis by Aviadenovirus was described in Pauxi mitu (Aves: Cracidae).

     

Synthesis, biological evaluation, and molecular modeling of chalcone derivatives as potent inhibitors of Mycobacterium tuberculosis protein tyrosine phosphatases (PtpA and PtpB)

Tuberculosis (TB) is a major infectious disease caused by Mycobacterium tuberculosis (Mtb). According to the World Health Organization (WHO), about 1.8 million people die from TB and 10 million new cases are recorded each year. Recently, a new series of naphthylchalcones has been identified as inhibitors of Mtb protein tyrosine phosphatases (PTPs). In this work, 100 chalcones were designed, synthesized, and investigated for their inhibitory properties against MtbPtps. Structure-activity relationships (SAR) were developed, leading to the discovery of new potent inhibitors with IC(50) values in the low-micromolar range. Kinetic studies revealed competitive inhibition and high selectivity toward the Mtb enzymes. Molecular modeling investigations were carried out with the aim of revealing the most relevant structural requirements underlying the binding affinity and selectivity of this series of inhibitors as potential anti-TB drugs.