Decompressive Hemicraniectomy in a South American Population – Morbidity and Outcomes Analysis

Background

Malignant cerebral artery strokes have a poor prognosis, with nearly 80% of mortality in some series despite intensive care. After a large randomized trial, decompressive hemicraniectomy has been performed more often in stroke patients. Here, we describe patients in a tertiary teaching hospital in Brazil, emphasizing the impact of age on outcomes.

Methods

A retrospective cohort of patients, with malignant strokes which received a decompressive hemicraniectomy, from paper and electronic medical records, from January 2010 to December 2013 was divided into two groups according to age.

Results

The final analysis included 60 patients. The overall mortality was higher among patients older than 60 yrs (67% vs. 41%; p = 0.039), whose group also had a worse outcome (76% with mRS 5 or 6) at 90 days (OR 3.91 CI95% 1.30–11.74), whereas only 24% had mRS of 0–4 (p = 0.015). All patients who presented with sepsis died (p = 0.003). The incidence of pulmonary infection was very high in the elderly group (76%) with significant intergroup differences (p = 0.027, OR 8.32 CI95% 0.70–98.48).

Conclusions

Older patients present more commonly with infections, more disabilities and a higher mortality, highlighting very poor results in elderly population. These results should be proved with a South American trial, and if confirmed, it can impact on future decisions regarding decompressive craniectomy for acute ischemic stroke in our region.     

Major Histocompatibility Complex (MHC) class II sequence polymorphism in long-finned pilot whale (Globicephala melas) from the North Atlantic

Determining how intra-specific genetic diversity is apportioned among natural populations is essential for detecting local adaptation and identifying populations with inherently low levels of extant diversity which may become a conservation concern. Sequence polymorphism at two adaptive loci (MHC DRA and DQB) was investigated in long-finned pilot whales (Globicephala melas) from four regions in the North Atlantic and compared with previous data from New Zealand (South Pacific). Three alleles were resolved at each locus, with trans-species allele sharing and higher levels of non-synonymous to synonymous substitution, especially in the DQB locus. Overall nucleotide diversities of 0.49?±?0.38% and 4.60?±?2.39% were identified for the DRA and DQB loci, respectively, which are relatively low for MHC loci in the North Atlantic, but comparable to levels previously described in New Zealand (South Pacific). There were significant differences in allele frequencies within the North Atlantic and between the North Atlantic and New Zealand. Patterns of diversity and divergence are consistent with the long-term effects of balancing selection operating on the MHC loci, potentially mediated through the effects of host-parasite coevolution. Differences in allele frequency may reflect variation in pathogen communities, coupled with the effects of differential drift and gene flow.     

The Role of Community and Individuals in the Formation of Social Capital

Because social capital shapes many desirable socioeconomic outcomes, we ask what incentives drive private investments in social capital. We estimate the association between private investments in social capital (outcome variable) and the following explanatory variables: (a) individual-level variables from an optimal investment model, (b) spillovers from group social capital, (c) village income inequality, and (d) market openness. We draw on information from Tsimane’, a native Amazonian society of foragers and farmers in Bolivia, and equate social capital with gifts, help given, and communal labor offered by the household. Age bore an inverted U-shaped and income bore a positive association with social capital, but geographic mobility, wealth, and schooling bore no significant association with social capital. We found strong group-level associations even after instrumenting social capital; the association probably stems from strong kinship ties which tend to blur the line between the group and the individual. Village measures of social capital were positively and significantly associated with private investments in social capital. We found some evidence that village income inequality and market openness were negatively associated with private investments in social capital.     

Fetal bovine serum enables cardiac differentiation of human embryonic stem cells

During development, cardiac commitment within the mesoderm requires endoderm-secreted factors. Differentiation of embryonic stem cells into the three germ layers in vitro recapitulates developmental processes and can be influenced by supplements added to culture medium. Hence, we investigated the effect of fetal bovine serum (FBS) and KnockOut serum replacement (SR) on germ layers specification and cardiac differentiation of H1 human embryonic stem cells (hESC) within embryoid bodies (EB). At the time of EB formation, FBS triggered an increased apoptosis. As assessed by quantitative PCR on 4-, 10-, and 20-day-old EB, FBS promoted a faster down-regulation of pluripotency marker Oct4 and an increased expression of endodermal (Sox17, alpha-fetoprotein, AFP) and mesodermal genes (Brachyury, CSX). While neuronal and hematopoietic differentiation occurred in both supplements, spontaneously beating cardiomyocytes were only observed in FBS. Action potential (AP) morphology of hESC-derived cardiomyocytes indicated that ventricular cells were present only after 2 months of culture. However, quantification of myosin light chain 2 ventricular (mlc2v)-positive areas revealed that mlc2v-expressing cardiomyocytes could be detected already after 2 weeks of differentiation, but not in all beating clusters. In conclusion, FBS enabled cardiac differentiation of hESC, likely in an endodermal-dependent pathway. Among cardiac cells, ventricular cardiomyocytes differentiated over time, but not as the predominant cardiac cell subtype.     

Immunological and microbiological activity of Davilla elliptica St. Hill. (Dilleniaceae) against Mycobacterium tuberculosis

Mycobacterium tuberculosis is responsible for over 8 million cases of tuberculosis (TB) annually. Natural products may play important roles in the chemotherapy of TB. The immunological activity of Davilla elliptica chloroform extract (DECE) was evaluated in vitro by the determination of hydrogen peroxide (H2O2), nitric oxide (NO), and tumor necrosis factor-alpha (TNF-alpha) release in peritoneal macrophages cultures. DECE was also tested for its antimycobacterial activity against M. tuberculosis using the microplate alamar blue assay. DECE (50, 150, 250 microg/ml) stimulated the production of H2O2 (from 1,79 +/- 0,23 to 7,27 +/- 2,54; 15,02 +/- 2,86; 20,5 +/- 2,1 nmols) (means +/- SD), NO (from 2,64 +/- 1,02 to 25,59 +/- 2,29; 26,68 +/- 2,41; 29,45 +/- 5,87 micromols) (means +/- SD) and TNF-alpha (from 2,44 +/- 1,46 to 30,37 +/- 8,13; 38,68 +/- 1,59; 41,6 +/- 0,90 units/ml) (means +/- SD) in a dose-dependent manner and also showed a promising antimycobacterial activity with a minimum inhibitory concentration of 62,5 microg/ml. This plant may have therapeutic potential in the immunological and microbiological control of TB.     

Molecular basis for PP2A regulatory subunit B56alpha targeting in cardiomyocytes

Protein phosphatase 2A (PP2A) is a multifunctional protein phosphatase with critical roles in excitable cell signaling. In the heart, PP2A function is linked with modulation of beta-adrenergic signaling and has been suggested to regulate key ion channels and transporters including Na/Ca exchanger, ryanodine receptor, inositol 1,4,5-trisphosphate receptor, and Na/K ATPase. Although many of the functional roles and molecular targets for PP2A in heart are known, little is established regarding the cellular pathways that localize specific PP2A isoform activities to subcellular sites. We report that the PP2A regulatory subunit B56alpha is an in vivo binding partner for ankyrin-B, an adapter protein required for normal subcellular localization of the Na/Ca exchanger, Na/K ATPase, and inositol 1,4,5-trisphosphate receptor. Ankyrin-B and B56alpha are colocalized and coimmunoprecipitate in primary cardiomyocytes. Using multiple strategies, we identified the structural requirements on B56alpha for ankyrin-B association as a 13 residue motif in the B56alpha COOH terminus not present in other B56 family polypeptides. Finally, we report that reduced ankyrin-B expression in primary ankyrin-B(+/-) cardiomyocytes results in disorganized distribution of B56alpha that can be rescued by exogenous expression of ankyrin-B. These new data implicate ankyrin-B as a critical targeting component for PP2A in heart and identify a new class of signaling proteins targeted by ankyrin polypeptides.     

beta-Catenin regulates P-cadherin expression in mammary basal epithelial cells

P-cadherin expression is restricted to the basal layer of stratified epithelia including that of the mammary gland. Although evidence for an important role of P-cadherin in mammary morphogenesis and tumorigenesis is increasing, the mechanisms that regulate its expression are poorly understood. We show that in basal mammary epithelial cells, beta-catenin is associated with the P-cadherin promoter and activates its expression independently of LEF/TCF in a cell-type specific manner. Down-regulation of endogenous beta-catenin levels by RNA interference technique inhibited P-cadherin promoter activity. In vivo, in skin and mammary gland of mutant mice, activation of beta-catenin signalling correlates with up-regulation of P-cadherin expression. These data suggest that beta-catenin-dependent modulation of P-cadherin expression can contribute to the establishment of the basal phenotype.     

Characterization of stem cells from the murine adult mammary gland

The postnatal mammary morphogenesis comprises two steps, first, formation of a system of branching ducts at puberty and second, alveologenesis during pregnancy. The mammary epithelium is organized as a bilayer, composed of two cellular types, basal myoepithelial and luminal epithelial. The remarkable regenerative properties revealed in serial transplantation experiments suggest that the adult mammary epithelium harbors stem cells. Various strategies including analysis of DNA label-retaining cells, transgenic approach, and in vivo transplantation assay, have been used to isolate and characterize murine mammary stem and progenitor cells. Their molecular characteristics remain to be defined precisely but notable progress have been already made in the enrichment and identification of these cells. Current studies favor the hypothesis of a basal-type mammary stem cells expressing high levels of alpha 6, beta1 and beta 3 integrin chains, the major receptors of extracellular matrix proteins. Luminal-type progenitors may participate in the establishment of the bilayered alveolar epithelium during pregnancy.     

Superantigen natural affinity maturation revealed by the crystal structure of staphylococcal enterotoxin G and its binding to T-cell receptor Vbeta8.2

The illnesses associated with bacterial superantigens (SAgs) such as food poisoning and toxic shock syndrome, as well as the emerging threat of purpura fulminans and community-associated methicillin-resistant S. aureus producer of SAgs, emphasize the importance of a better characterization of SAg binding to their natural ligands, which would allow the development of drugs or biological reagents able to neutralize their action. SAgs are toxins that bind major histocompatibility complex class II molecules (MHC-II) and T-cell receptors (TCR), in a nonconventional manner, inducing T-cell activation that leads to production of cytokines such as tumor necrosis factor and interleukin-2, which may result in acute toxic shock. Previously, we cloned and expressed a new natural variant of staphylococcal enterotoxin G (SEG) and evaluated its ability to stimulate in vivo murine T-cell subpopulations. We found an early, strong, and widespread stimulation of mouse Vbeta8.2 T-cells when compared with other SAgs member of the SEB subfamily. In search for the reason of the strong mitogenic potency, we determined the SEG crystal structure by X-ray crystallography to 2.2 A resolution and analyzed SEG binding to mVbeta8.2 and MHC-II. Calorimetry and SPR analysis showed that SEG has an affinity for mVbeta8.2 40 to 100-fold higher than that reported for other members of SEB subfamily, and the highest reported for a wild type SAg-TCR couple. We also found that mutations introduced in mVbeta8.2 to produce a high affinity mutant for other members of the SEB subfamily do not greatly affect binding to SEG. Crystallographic analysis and docking into mVbeta8.2 in complex with SEB, SEC3, and SPEA showed that the deletions and substitution of key amino acids remodeled the putative surface of the mVbeta8.2 binding site without affecting the binding to MHC-II. This results in a SAg with improved binding to its natural ligands, which may confer a possible evolutionary advantage for bacterial strains expressing SEG.