FORMULATION AND CHARACTERIZATION OF POLOXAMER 407 (R): THERMOREVERSIBLE GEL CONTAINING POLYMERIC MICROPARTICLES AND HYALURONIC ACID

The influence of the composition and preparation method on the sol-gel transition temperature (Tsol-gel) and rheological response of poloxamer-based formulations was determined. Manual and more complex mechanical stirring were found to provide similar results. In addition, a linear dependence of Tsol-gel on the poloxamer content was observed in the range of concentrations analyzed, and a Poloxamer 407® concentration of 18% was selected. The addition of hyaluronic acid did not lead to significant changes in the Tsol-gel values. In contrast, the addition of microparticles caused a reduction in Tsol-gel without a significant reduction in gel strength, and pseudoplastic characteristics were observed, indicating that a thermoreversible gel was obtained with a rheology suitable for application in the treatment of burn wounds

Conserved and species-specific transcriptional responses to daily programmed resistance exercise in rat and mouse

Mice are often used in gain or loss of function studies to understand how genes regulate metabolism and adaptation to exercise in skeletal muscle. Once-daily resistance training with electrical nerve stimulation produces hypertrophy of the dorsiflexors in rat, but not in mouse. Using implantable pulse generators, we assessed the acute transcriptional response (1-h post-exercise) after 2, 10, and 20 days of training in free-living mice and rats using identical nerve stimulation paradigms. RNA sequencing revealed strong concordance in the timecourse of many transcriptional responses in the tibialis anterior muscles of both species including responses related to “stress responses/immediate-early genes, and “collagen homeostasis,” “ribosomal subunits,” “autophagy,” and “focal adhesion.” However, pathways associated with energy metabolism including “carbon metabolism,” “oxidative phosphorylation,” “mitochondrial translation,” “propanoate metabolism,” and “valine, leucine, and isoleucine degradation” were oppositely regulated between species. These pathways were suppressed in the rat but upregulated in the mouse. Our transcriptional analysis suggests that although many pathways associated with growth show remarkable similarities between species, the absence of an actual growth response in the mouse may be because the mouse prioritizes energy metabolism, specifically the replenishment of fuel stores and intermediate metabolites

In vitro activation and enzyme kinetic analysis of recombinant midgut serine proteases from the Dengue vector mosquito Aedes aegypti

<p>Abstract</p> <p>Background</p> <p>The major Dengue virus vector <it>Aedes aegypti </it>requires nutrients obtained from blood meal proteins to complete the gonotrophic cycle. Although bioinformatic analyses of <it>Ae. aegypti </it>midgut serine proteases have provided evolutionary insights, very little is known about the biochemical activity of these digestive enzymes.</p> <p>Results</p> <p>We used peptide specific antibodies to show that midgut serine proteases are expressed as zymogen precursors, which are cleaved to the mature form after blood feeding. Since midgut protein levels are insufficient to purify active proteases directly from blood fed mosquitoes, we engineered recombinant proteins encoding a heterologous enterokinase cleavage site to permit generation of the bona fide mature form of four midgut serine proteases (AaET, AaLT, AaSPVI, AaSPVII) for enzyme kinetic analysis. Cleavage of the chromogenic trypsin substrate BApNA showed that AaET has a catalytic efficiency (k_cat/K_M) that is ~30 times higher than bovine trypsin, and ~2-3 times higher than AaSPVI and AaSPVII, however, AaLT does not cleave BApNA. To measure the enzyme activities of the mosquito midgut proteases using natural substrates, we developed a quantitative cleavage assay based on cleavage of albumin and hemoglobin proteins. These studies revealed that the recombinant AaLT enzyme was indeed catalytically active, and cleaved albumin and hemoglobin with equivalent efficiency to that of AaET, AaSPVI, and AaSPVII. Structural modeling of the AaLT and AaSPVI mature forms indicated that AaLT is most similar to serine collagenases, whereas AaSPVI appears to be a classic trypsin.</p> <p>Conclusions</p> <p>These data show that <it>in vitro </it>activation of recombinant serine proteases containing a heterologous enterokinase cleavage site can be used to investigate enzyme kinetics and substrate cleavage properties of biologically important mosquito proteases.</p

Returning home: forced conscription, reintegration, and mental health status of former abductees of the Lord's Resistance Army in northern Uganda

<p>Abstract</p> <p>Background</p> <p>Since the late 1980s, the Lord's Resistance Army (LRA), a spiritualist rebel group in northern Uganda, has killed and mutilated thousands of civilians and abducted an estimated 52,000 to 75,000 people to serve as soldiers, porters, and sex slaves for its commanders. This study examines the types of violence to which former abductees have been exposed and the extent to which these acts have affected their psychological well-being.</p> <p>Methods</p> <p>This is a cross-sectional study of 2,875 individuals selected through a multi-stage stratified cluster sampling design conducted in 8 districts of northern Uganda. Multivariate logistic regressions were performed with symptoms for Post-traumatic Stress Disorder (PTSD) and depression as the main outcome measures.</p> <p>Results</p> <p>One-third of the respondents (33%) self-reported having experienced abduction (49% among the Acholi, the largest tribal group in northern Uganda). Over half (56%) of all the respondents and over two-thirds of those who experienced abduction met the criteria for symptoms of post-traumatic stress disorder (PTSD). Multivariate analysis shows that several factors increased the risk of former LRA abductees developing symptoms of PTSD. These factors included gender (females were more susceptible than males), being a member of the Acholi ethnic group, participating in or witnessing a cumulative number of traumatic events, and encountering difficulties re-integrating into communities after abduction. Factors associated with increased risk of meeting criteria for symptoms of depression included older age of males at the time of abduction, lower score on social relationship scale, high incidence of general traumatic event exposure, high incidence of forced acts of violence, and problems reintegrating into communities after abduction.</p> <p>Conclusion</p> <p>Abduction and forced conscription of civilians has affected the psychological well-being of a significant number of northern Ugandans. The sources of psychological trauma are multiple, ranging from witnessing to being forced to commit violent acts, and compounded by prolonged exposure to violence, often for months or years. Community-based mental health care services and reintegration programs are needed to facilitate the reintegration of former abductees back into their communities.</p

PTSD, depression and anxiety among former abductees in Northern Uganda

<p>Abstract</p> <p>Background</p> <p>The population in Northern Uganda has been exposed to extreme levels of traumatic stress and thousands abducted forcibly became rebel combatants.</p> <p>Methods</p> <p>Using structured interviews, the prevalence and severity of posttraumatic stress disorder (PTSD), depression and anxiety was assessed in 72 former abducted adults, 62 of them being former child soldiers.</p> <p>Results</p> <p>As retrospective reports of exposure to traumatic stress increased, anxiety and PTSD occurrence increased (r = .45). 49% of respondents were diagnosed with PTSD, 70% presented with symptoms of depression, and 59% with those of anxiety. In a multiple linear regression analysis four factors could best explain the development of PTSD symptoms: male respondents (sex) living in an IDP-Camp (location) with a kinship murdered in the war (family members killed in the war) and having experienced a high number of traumatic events (number of traumatic events) were more likely to develop symptoms of PTSD than others. In disagreement to a simple dose-response-effect though, we also observed a negative correlation between the time spent with the rebels and the PTSD symptom level.</p> <p>Conclusions</p> <p>Former abductees continue to suffer from severe mental ill-health. Adaptation to the living condition of rebels, however, may lower trauma-related mental suffering.</p

Chromosome evolution in Cophomantini (Amphibia, Anura, Hylinae)

The hylid tribe Cophomantini is a diverse clade of Neotropical treefrogs composed of the genera Aplastodiscus, Boana, Bokermannohyla, Hyloscirtus, and Myersiohyla. The phylogenetic relationships of Cophomantini have been comprehensively reviewed in the literature, providing a suitable framework for the study of chromosome evolution. Employing different banding techniques, we studied the chromosomes of 25 species of Boana and 3 of Hyloscirtus; thus providing, for the first time, data for Hyloscirtus and for 15 species of Boana. Most species showed karyotypes with 2n = 2x = 24 chromosomes; some species of the B. albopunctata group have 2n = 2x = 22, and H. alytolylax has 2n = 2x = 20. Karyotypes are all bi-armed in most species presented, with the exception of H. larinopygion (FN = 46) and H. alytolylax (FN = 38), with karyotypes that have a single pair of small telocentric chromosomes. In most species of Boana, NORs are observed in a single pair of chromosomes, mostly in the small chromosomes, although in some species of the B. albopunctata, B. pulchella, and B. semilineata groups, this marker occurs on the larger pairs 8, 1, and 7, respectively. In Hyloscirtus, NOR position differs in the three studied species: H. alytolylax (4p), H. palmeri (4q), and H. larinopygion (1p). Heterochromatin is a variable marker that could provide valuable evidence, but it would be necesserary to understand the molecular composition of the C-bands that are observed in different species in order to test its putative homology. In H. alytolylax, a centromeric DAPI+ band was observed on one homologue of chromosome pair 2. The band was present in males but absent in females, providing evidence for an XX/XY sex determining system in this species. We review and discuss the importance of the different chromosome markers (NOR position, C-bands, and DAPI/CMA3 patterns) for their impact on the taxonomy and karyotype evolution in Cophomantini

Pooled analysis of WHO Surgical Safety Checklist use and mortality after emergency laparotomy

Background The World Health Organization (WHO) Surgical Safety Checklist has fostered safe practice for 10 years, yet its place in emergency surgery has not been assessed on a global scale. The aim of this study was to evaluate reported checklist use in emergency settings and examine the relationship with perioperative mortality in patients who had emergency laparotomy. Methods In two multinational cohort studies, adults undergoing emergency laparotomy were compared with those having elective gastrointestinal surgery. Relationships between reported checklist use and mortality were determined using multivariable logistic regression and bootstrapped simulation. Results Of 12 296 patients included from 76 countries, 4843 underwent emergency laparotomy. After adjusting for patient and disease factors, checklist use before emergency laparotomy was more common in countries with a high Human Development Index (HDI) (2455 of 2741, 89.6 per cent) compared with that in countries with a middle (753 of 1242, 60.6 per cent; odds ratio (OR) 0.17, 95 per cent c.i. 0.14 to 0.21, P <0001) or low (363 of 860, 422 per cent; OR 008, 007 to 010, P <0.001) HDI. Checklist use was less common in elective surgery than for emergency laparotomy in high-HDI countries (risk difference -94 (95 per cent c.i. -11.9 to -6.9) per cent; P <0001), but the relationship was reversed in low-HDI countries (+121 (+7.0 to +173) per cent; P <0001). In multivariable models, checklist use was associated with a lower 30-day perioperative mortality (OR 0.60, 0.50 to 073; P <0.001). The greatest absolute benefit was seen for emergency surgery in low- and middle-HDI countries. Conclusion Checklist use in emergency laparotomy was associated with a significantly lower perioperative mortality rate. Checklist use in low-HDI countries was half that in high-HDI countries.Peer reviewe