Acute lower limb compartment syndrome after Cesarean section: a case report

Abstract: Introduction Acute compartment syndrome of the lower limb is a rare but severe intra- and post-partum complication. Prompt diagnosis is essential to avoid permanent functional restriction or even the loss of the affected limb. Clinical signs and symptoms might be nonspecific, especially in the early stages; therefore, knowledge of predisposing risk factors can be helpful. Case presentation We present the case of a 32-year-old Caucasian woman with acute post-partum compartment syndrome. Conclusion: Acute compartment syndrome is an important differential diagnosis for the sudden onset of intra- or post-partum lower-limb pain. Predisposing factors for the manifestation of acute compartment syndrome in an obstetric environment are augmented intra-partum blood loss, prolonged hypotensive episodes and the use of oxytocin to support or induce labor because of its vasoconstrictive properties. Treatment is prompt surgical decompression by performing fasciotomy in any affected muscular compartments

Genetic variation in genes regulating skeletal muscle regeneration and tissue remodelling associated with weight loss in chronic obstructive pulmonary disease

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is the third leading cause of death globally. COPD patients with cachexia or weight loss have increased risk of death independent of body mass index (BMI) and lung function. We tested the hypothesis genetic variation is associated with weight loss in COPD using a genome-wide association study approach. METHODS: Participants with COPD (N = 4308) from three studies (COPDGene, ECLIPSE, and SPIROMICS) were analysed. Discovery analyses were performed in COPDGene with replication in SPIROMICS and ECLIPSE. In COPDGene, weight loss was defined as self-reported unintentional weight loss > 5% in the past year or low BMI (BMI < 20 kg/m2). In ECLIPSE and SPIROMICS, weight loss was calculated using available longitudinal visits. Stratified analyses were performed among African American (AA) and Non-Hispanic White (NHW) participants with COPD. Single variant and gene-based analyses were performed adjusting for confounders. Fine mapping was performed using a Bayesian approach integrating genetic association results with linkage disequilibrium and functional annotation. Significant gene networks were identified by integrating genetic regions associated with weight loss with skeletal muscle protein–protein interaction (PPI) data. RESULTS: At the single variant level, only the rs35368512 variant, intergenic to GRXCR1 and LINC02383, was associated with weight loss (odds ratio = 3.6, 95% confidence interval = 2.3–5.6, P = 3.2 × 10−8) among AA COPD participants in COPDGene. At the gene level in COPDGene, EFNA2 and BAIAP2 were significantly associated with weight loss in AA and NHW COPD participants, respectively. The EFNA2 association replicated among AA from SPIROMICS (P = 0.0014), whereas the BAIAP2 association replicated in NHW from ECLIPSE (P = 0.025). The EFNA2 gene encodes the membrane-bound protein ephrin-A2 involved in the regulation of developmental processes and adult tissue homeostasis such as skeletal muscle. The BAIAP2 gene encodes the insulin-responsive protein of mass 53 kD (IRSp53), a negative regulator of myogenic differentiation. Integration of the gene-based findings participants with PPI data revealed networks of genes involved in pathways such as Rho and synapse signalling. CONCLUSIONS: The EFNA2 and BAIAP2 genes were significantly associated with weight loss in COPD participants. Collectively, the integrative network analyses indicated genetic variation associated with weight loss in COPD may influence skeletal muscle regeneration and tissue remodelling

Terrestrial water load and groundwater fluctuation in the Bengal Basin

Groundwater-level fluctuations represent hydraulic responses to changes in groundwater storage due to aquifer recharge and drainage as well as to changes in stress that include water mass loading and unloading above the aquifer surface. The latter ‘poroelastic’ response of confined aquifers is a well-established phenomenon which has been demonstrated in diverse hydrogeological environments but is frequently ignored in assessments of groundwater resources. Here we present high-frequency groundwater measurements over a twelve-month period from the tropical, fluvio-deltaic Bengal Aquifer System (BAS), the largest aquifer in south Asia. The groundwater level fluctuations are dominated by the aquifer poroelastic response to changes in terrestrial water loading by processes acting over periods ranging from hours to months; the effects of groundwater flow are subordinate. Our measurements represent the first direct, quantitative identification of loading effects on groundwater levels in the BAS. Our analysis highlights the potential limitations of hydrogeological analyses which ignore loading effects in this environment. We also demonstrate the potential for employing poroelastic responses in the BAS and across other tropical fluvio-deltaic regions as a direct, in-situ measure of changes in terrestrial water storage to complement analyses from the Gravity and Climate Experiment (GRACE) mission but at much higher resolution

Production of electrospun fast-dissolving drug delivery systems with therapeutic eutectic systems encapsulated in gelatin

Fast-dissolving delivery systems (FDDS) have received increasing attention in the last years. Oral drug delivery is still the preferred route for the administration of pharmaceutical ingredients. Nevertheless, some patients, e.g. children or elderly people, have difficulties in swallowing solid tablets. In this work, gelatin membranes were produced by electrospinning, containing an encapsulated therapeutic deep-eutectic solvent (THEDES) composed by choline chloride/mandelic acid, in a 1:2 molar ratio. A gelatin solution (30% w/ v) with 2% (v/v) of THEDES was used to produce electrospun fibers and the experimental parameters were optimized. Due to the high surface area of polymer fibers, this type of construct has wide applicability. With no cytotoxicity effect, and showing a fast-dissolving release profile in PBS, the gelatin fibers with encapsulated THEDES seem to have promising applications in the development of new drug delivery systems.The research leading to these results has received funding from Fundação para a Ciência e a Tecnologia (FCT) through the projects ENIGMA - PTDC/EQU-EPR/ 121491/2010 and UID/CTM/50025/2013, LAQVREQUIMTE: UID/QUI/50006/2013, UCIBIO-REQUIMTE: UID/Multi/04378/2013 (co-financed by the ERDF under the PT2020 Partnership Agreement [POCI-01-0145-FEDER- 007728]) and by FEDER through the COMPETE 2020 Programme. Marta Martins is grateful for financial support from FCT through the grant BIM/PTDC/EQUEPR/121491/ 2010/ENIGMA. This research has also received funding from the European Union Seventh Framework Programme (FP7/ 2007-2013) under grant agreement number REGPOTCT2012-316331-POLARIS and from the project BNovel smart and biomimetic materials for innovative regenerative medicine approaches^ RL1 - ABMR - NORTE-01-0124- FEDER-000016) co-financed by North Portugal Regional Operational Programme (ON.2 – O Novo Norte), under the National Strategic Reference Framework (NSRF), through the European Regional Development Fund (ERDF).info:eu-repo/semantics/publishedVersio

Evaluation of the Edinburgh Post Natal Depression Scale using Rasch analysis

BACKGROUND: The Edinburgh Postnatal Depression Scale (EPDS) is a 10 item self-rating post-natal depression scale which has seen widespread use in epidemiological and clinical studies. Concern has been raised over the validity of the EPDS as a single summed scale, with suggestions that it measures two separate aspects, one of depressive feelings, the other of anxiety. METHODS: As part of a larger cross-sectional study conducted in Melbourne, Australia, a community sample (324 women, ranging in age from 18 to 44 years: mean = 32 yrs, SD = 4.6), was obtained by inviting primiparous women to participate voluntarily in this study. Data from the EPDS were fitted to the Rasch measurement model and tested for appropriate category ordering, for item bias through Differential Item Functioning (DIF) analysis, and for unidimensionality through tests of the assumption of local independence. RESULTS: Rasch analysis of the data from the ten item scale initially demonstrated a lack of fit to the model with a significant Item-Trait Interaction total chi-square (chi Square = 82.8, df = 40; p < .001). Removal of two items (items 7 and 8) resulted in a non-significant Item-Trait Interaction total chi-square with a residual mean value for items of -0.467 with a standard deviation of 0.850, showing fit to the model. No DIF existed in the final 8-item scale (EPDS-8) and all items showed fit to model expectations. Principal Components Analysis of the residuals supported the local independence assumption, and unidimensionality of the revised EPDS-8 scale. Revised cut points were identified for EPDS-8 to maintain the case identification of the original scale. CONCLUSION: The results of this study suggest that EPDS, in its original 10 item form, is not a viable scale for the unidimensional measurement of depression. Rasch analysis suggests that a revised eight item version (EPDS-8) would provide a more psychometrically robust scale. The revised cut points of 7/8 and 9/10 for the EPDS-8 show high levels of agreement with the original case identification for the EPDS-10

Continental mass change from GRACE over 2002-2011 and its impact on sea level

Present-day continental mass variation as observed by space gravimetry reveals secular mass decline and accumulation. Whereas the former contributes to sea-level rise, the latter results in sea-level fall. As such, consideration of mass accumulation (rather than focussing solely on mass loss) is important for reliable overall estimates of sea-level change. Using data from the Gravity Recovery And Climate Experiment satellite mission, we quantify mass-change trends in 19 continental areas that exhibit a dominant signal. The integrated mass change within these regions is representative of the variation over the whole land areas. During the integer 9-year period of May 2002 to April 2011, GIA-adjusted mass gain and mass loss in these areas contributed, on average, to −(0.7 ± 0.4) mm/year of sea-level fall and + (1.8 ± 0.2) mm/year of sea-level rise; the net effect was + (1.1 ± 0.6) mm/year. Ice melting over Greenland, Iceland, Svalbard, the Canadian Arctic archipelago, Antarctica, Alaska and Patagonia was responsible for + (1.4±0.2) mm/year of the total balance. Hence, land-water mass accumulation compensated about 20 % of the impact of ice-melt water influx to the oceans. In order to assess the impact of geocentre motion, we converted geocentre coordinates derived from satellite laser ranging (SLR) to degree-one geopotential coefficients. We found geocentre motion to introduce small biases to mass-change and sea-level change estimates; its overall effect is + (0.1 ± 0.1) mm/year. This value, however, should be taken with care owing to questionable reliability of secular trends in SLR-derived geocentre coordinates

Antihyperlipidemic and antiperoxidative effect of Diasulin, a polyherbal formulation in alloxan induced hyperglycemic rats

BACKGROUND: This study was undertaken to investigation the effect of Diasulin, a poly herbal drug composed of ethanolic extract of ten medicinal plants on blood glucose, plasma insulin, tissue lipid profile, and lipidperoxidation in alloxan induced diabetes. METHODS: Ethanolic extract of Diasulin a, poly herbal drug was administered orally (200 mg/kg body weight) for 30 days. The different doses of Diasulin on blood glucose and plasma insulin in diabetic rats were studied and the levels of lipid peroxides [TBARS, and Hydroperoxide] and tissue lipids [cholesterol, triglyceride, phospholipides and free fatty acids] were also estimated in alloxan induced diabetic rats. The effects were compared with glibenclamide. RESULT: Treatment with Diasulin and glibenclamide resulted in a significant reduction of blood glucose and increase in plasma insulin. Diasulin also resulted in a significant decrease in tissue lipids and lipid peroxide formation. The effect produced by Diasulin was comparable with that of glibenclamide. CONCLUSION: The decreased lipid peroxides and tissue lipids clearly showed the antihyperlipidemic and antiperoxidative effect of Diasulin apart from its antidiabetic effect

HIF-1 activation induces doxorubicin resistance in MCF7 3-D spheroids via P-glycoprotein expression: a potential model of the chemo-resistance of invasive micropapillary carcinoma of the breast

BACKGROUND: Invasive micropapillary carcinoma (IMPC) of the breast is a distinct and aggressive variant of luminal type B breast cancer that does not respond to neoadjuvant chemotherapy. It is characterized by small pseudopapillary clusters of cancer cells with inverted cell polarity. To investigate whether hypoxia-inducible factor-1 (HIF-1) activation may be related to the drug resistance described in this tumor, we used MCF7 cancer cells cultured as 3-D spheroids, which morphologically simulate IMPC cell clusters. METHODS: HIF-1 activation was measured by EMSA and ELISA in MCF7 3-D spheroids and MCF7 monolayers. Binding of HIF-1α to MDR-1 gene promoter and modulation of P-glycoprotein (Pgp) expression was evaluated by ChIP assay and FACS analysis, respectively. Intracellular doxorubicin retention was measured by spectrofluorimetric assay and drug cytotoxicity by annexin V-FITC measurement and caspase activity assay. RESULTS: In MCF7 3-D spheroids HIF-1 was activated and recruited to participate to the transcriptional activity of MDR-1 gene, coding for Pgp. In addition, Pgp expression on the surface of cells obtained from 3-D spheroids was increased. MCF7 3-D spheroids accumulate less doxorubicin and are less sensitive to its cytotoxic effects than MCF7 cells cultured as monolayer. Finally, HIF-1α inhibition either by incubating cells with 3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole (a widely used HIF-1α inhibitor) or by transfecting cells with specific siRNA for HIF-1α significantly decreased the expression of Pgp on the surface of cells and increased the intracellular doxorubicin accumulation in MCF7 3-D spheroids. CONCLUSIONS: MCF7 breast cancer cells cultured as 3-D spheroids are resistant to doxorubicin and this resistance is associated with an increased Pgp expression in the plasma membrane via activation of HIF-1. The same mechanism may be suggested for IMPC drug resistance

Enzyme sequestration as a tuning point in controlling response dynamics of signalling networks

Signalling networks result from combinatorial interactions among many enzymes and scaffolding proteins. These complex systems generate response dynamics that are often essential for correct decision-making in cells. Uncovering biochemical design principles that underpin such response dynamics is a prerequisite to understand evolved signalling networks and to design synthetic ones. Here, we use in silico evolution to explore the possible biochemical design space for signalling networks displaying ultrasensitive and adaptive response dynamics. By running evolutionary simulations mimicking different biochemical scenarios, we find that enzyme sequestration emerges as a key mechanism for enabling such dynamics. Inspired by these findings, and to test the role of sequestration, we design a generic, minimalist model of a signalling cycle, featuring two enzymes and a single scaffolding protein. We show that this simple system is capable of displaying both ultrasensitive and adaptive response dynamics. Furthermore, we find that tuning the concentration or kinetics of the sequestering protein can shift system dynamics between these two response types. These empirical results suggest that enzyme sequestration through scaffolding proteins is exploited by evolution to generate diverse response dynamics in signalling networks and could provide an engineering point in synthetic biology applications

Caspase involvement in autophagy

Caspases are a family of cysteine proteases widely known as the principal mediators of the apoptotic cell death response, but considerably less so as the contributors to the regulation of pathways outside cellular demise. In regards to autophagy, the modulatory roles of caspases have only recently begun to be adequately described. In contrast to apoptosis, autophagy promotes cell survival by providing energy and nutrients through the lysosomal degradation of cytoplasmic constituents. Under basal conditions autophagy and apoptosis cross-regulate each other through an elaborate network of interconnections which also includes the interplay between autophagyrelated proteins (ATGs) and caspases. In this review we focus on the effects of this crosstalk at the cellular level, as we aim to concentrate the main observations from research conducted so far on the fine-tuning of autophagy by caspases. Several members of this protease-family have been found to directly interact with key ATGs involved in different tiers across the autophagic cascade. Therefore, we firstly outline the core mechanism of macroautophagy in brief. In an effort to emphasize the importance of the intricate cross-regulation of ATGs and caspases, we also present examples drawn from Drosophila and plant models regarding the contribution of autophagy to apoptotic cell death during normal development