Spontaneous mode non-invasive ventilation fails to treat respiratory failure in a patient with Multi-mincore disease: a case report

The increased morbidity and mortality resulting from respiratory failure in patients with neuromuscular disorders and/or kyphoscoliosis can be reversed with non-invasive ventilation. Spontaneous mode bilevel pressure ventilation is preferred to other modes of ventilation, due to relative ease of use, but may not be suitable for all patients. We report a 27-year old woman with Multi-minicore disease whose respiratory failure was refractory to spontaneous mode bilevel pressure ventilation. When we altered settings and provided mandatory inspiratory rise time and respiratory rate, it augmented her respiratory efforts and improved ventilation. Our case report describes the benefit of individualising non-invasive ventilation in the management of respiratory failure due to neuromuscular weakness and kyphoscoliosis

Muc5b Is the Major Polymeric Mucin in Mucus from Thoroughbred Horses With and Without Airway Mucus Accumulation

Mucus accumulation is a feature of inflammatory airway disease in the horse and has been associated with reduced performance in racehorses. In this study, we have analysed the two major airways gel-forming mucins Muc5b and Muc5ac in respect of their site of synthesis, their biochemical properties, and their amounts in mucus from healthy horses and from horses with signs of airway mucus accumulation. Polyclonal antisera directed against equine Muc5b and Muc5ac were raised and characterised. Immunohistochemical staining of normal equine trachea showed that Muc5ac and Muc5b are produced by cells in the submucosal glands, as well as surface epithelial goblet cells. Western blotting after agarose gel electrophoresis of airway mucus from healthy horses, and horses with mucus accumulation, was used to determine the amounts of these two mucins in tracheal wash samples. The results showed that in healthy horses Muc5b was the predominant mucin with small amounts of Muc5ac. The amounts of Muc5b and Muc5ac were both dramatically increased in samples collected from horses with high mucus scores as determined visually at the time of endoscopy and that this increase also correlated with increase number of bacteria present in the sample. The change in amount of Muc5b and Muc5ac indicates that Muc5b remains the most abundant mucin in mucus. In summary, we have developed mucin specific polyclonal antibodies, which have allowed us to show that there is a significant increase in Muc5b and Muc5ac in mucus accumulated in equine airways and these increases correlated with the numbers of bacteria

An Approximate Bayesian Estimator Suggests Strong, Recurrent Selective Sweeps in Drosophila

The recurrent fixation of newly arising, beneficial mutations in a species reduces levels of linked neutral variability. Models positing frequent weakly beneficial substitutions or, alternatively, rare, strongly selected substitutions predict similar average effects on linked neutral variability, if the product of the rate and strength of selection is held constant. We propose an approximate Bayesian (ABC) polymorphism-based estimator that can be used to distinguish between these models, and apply it to multi-locus data from Drosophila melanogaster. We investigate the extent to which inference about the strength of selection is sensitive to assumptions about the underlying distributions of the rates of substitution and recombination, the strength of selection, heterogeneity in mutation rate, as well as the population's demographic history. We show that assuming fixed values of selection parameters in estimation leads to overestimates of the strength of selection and underestimates of the rate. We estimate parameters for an African population of D. melanogaster (ŝ∼2E−03, ) and compare these to previous estimates. Finally, we show that surveying larger genomic regions is expected to lend much more discriminatory power to the approach. It will thus be of great interest to apply this method to emerging whole-genome polymorphism data sets in many taxa

Balancing Selection at the Tomato RCR3 Guardee Gene Family Maintains Variation in Strength of Pathogen Defense

Coevolution between hosts and pathogens is thought to occur between interacting molecules of both species. This results in the maintenance of genetic diversity at pathogen antigens (or so-called effectors) and host resistance genes such as the major histocompatibility complex (MHC) in mammals or resistance (R) genes in plants. In plant-pathogen interactions, the current paradigm posits that a specific defense response is activated upon recognition of pathogen effectors via interaction with their corresponding R proteins. According to the''Guard-Hypothesis,'' R proteins (the ``guards'') can sense modification of target molecules in the host (the ``guardees'') by pathogen effectors and subsequently trigger the defense response. Multiple studies have reported high genetic diversity at R genes maintained by balancing selection. In contrast, little is known about the evolutionary mechanisms shaping the guardee, which may be subject to contrasting evolutionary forces. Here we show that the evolution of the guardee RCR3 is characterized by gene duplication, frequent gene conversion, and balancing selection in the wild tomato species Solanum peruvianum. Investigating the functional characteristics of 54 natural variants through in vitro and in planta assays, we detected differences in recognition of the pathogen effector through interaction with the guardee, as well as substantial variation in the strength of the defense response. This variation is maintained by balancing selection at each copy of the RCR3 gene. Our analyses pinpoint three amino acid polymorphisms with key functional consequences for the coevolution between the guardee (RCR3) and its guard (Cf-2). We conclude that, in addition to coevolution at the ``guardee-effector'' interface for pathogen recognition, natural selection acts on the ``guard-guardee'' interface. Guardee evolution may be governed by a counterbalance between improved activation in the presence and prevention of auto-immune responses in the absence of the corresponding pathogen

Redox proteomics of the inflammatory secretome identifies a common set of redoxins and other glutathionylated proteins released in inflammation, influenza virus infection and oxidative stress

Protein cysteines can form transient disulfides with glutathione (GSH), resulting in the production of glutathionylated proteins, and this process is regarded as a mechanism by which the redox state of the cell can regulate protein function. Most studies on redox regulation of immunity have focused on intracellular proteins. In this study we have used redox proteomics to identify those proteins released in glutathionylated form by macrophages stimulated with lipopolysaccharide (LPS) after pre-loading the cells with biotinylated GSH. Of the several proteins identified in the redox secretome, we have selected a number for validation. Proteomic analysis indicated that LPS stimulated the release of peroxiredoxin (PRDX) 1, PRDX2, vimentin (VIM), profilin1 (PFN1) and thioredoxin 1 (TXN1). For PRDX1 and TXN1, we were able to confirm that the released protein is glutathionylated. PRDX1, PRDX2 and TXN1 were also released by the human pulmonary epithelial cell line, A549, infected with influenza virus. The release of the proteins identified was inhibited by the anti-inflammatory glucocorticoid, dexamethasone (DEX), which also inhibited tumor necrosis factor (TNF)-α release, and by thiol antioxidants (N-butanoyl GSH derivative, GSH-C4, and N-acetylcysteine (NAC), which did not affect TNF-α production. The proteins identified could be useful as biomarkers of oxidative stress associated with inflammation, and further studies will be required to investigate if the extracellular forms of these proteins has immunoregulatory functions

Predictors of delayed culture conversion among Ugandan patients.

BACKGROUND: Estimates of month-2 culture conversion, a proxy indicator of tuberculosis (TB) treatment efficacy in phase-2 trials can vary by culture-type and geographically with lower rates reported among African sites. The sub-study aimed at comparing TB detection rates of different culture media, within and across rifampicin-based regimens (R10, 15 and 20 mg/Kg) over a 6-month treatment follow-up period, and to establish predictors of month-2 culture non-conversion among HIV-negative TB patients enrolled at RIFATOX trial site in Uganda. METHODS: Unlike in other Rifatox Trial sites, it is only in Uganda were Lowenstein-Jensen (LJ) and Mycobacteria growth indicator tube (MGIT) were used throughout 6-months for treatment monitoring. Conversion rates were compared at month-2, 4 and 6 across cultures and treatment-type. Binomial regression analysis performed for predictors of month-2 non-conversion. RESULTS: Of the 100 enrolled patients, 45% had converted based on combined LJ and MGIT by month-2, with no significant differences across treatment arms, p = 0.721. LJ exhibited higher conversion rates than MGIT at month-2 (58.4% vs 56.0%, p = 0.0707) and month-4 (98.9% vs 88.4%, p = 0.0391) respectively, more so within the high-dose rifampicin arms. All patients had converted by month-6. Time-to-TB detection (TTD) on MGIT and social service jobs independently predict month-2 non-conversion. CONCLUSION: The month-2 culture conversion used in phase 2 clinical trials as surrogate marker of treatment efficacy is influenced by the culture method used for monitoring mycobacterial response to TB treatment. Therefore, multi-centric TB therapeutic trials using early efficacy endpoint should use the same culture method across sites. The Time-to-detection of MTB on MGIT prior to treatment and working in Social service jobs bear an increased risk of culture non-conversion at month-2. TRIAL REGISTRATION: ISRCTN ISRCTN55670677 . Registered 09th November 2010. Retrospectively registered

Functional characterization of the complement receptor type 1 and its circulating ligands in patients with schizophrenia

<p>Abstract</p> <p>Background</p> <p>Whereas the complement system alterations contribute to schizophrenia, complement receptors and regulators are little studied. We investigated complement receptor type 1 (CR1) expression on blood cells, the levels of circulating immune complexes (CIC) containing ligands of CR1, C1q complement protein and fragments of C3 complement protein (C1q-CIC, C3d-CIC), and CR1 C5507G functional polymorphism in schizophrenia patients and controls.</p> <p>Results</p> <p>We found an increased C1q-CIC level and CR1 expression on blood cells, elevated number of CR1 positive erythrocytes and reduced number of CR1 positive lymphocytes and monocytes in patients compared to controls. No difference in the levels of C3d-CIC between groups was observed. Higher CR1 expression on erythrocytes in CC genotype versus CG+GG for both groups was detected, whereas no difference was observed for other cell populations. Our results indicated that schizophrenia is associated with the increased CR1 expression and C1q-CIC level.</p> <p>Conclusions</p> <p>Our study for the first time indicated that schizophrenia is associated with the increased CR1 expression and C1q-CIC level. Further studies in other ethnic groups are needed to replicate these findings.</p

Why Do African Elephants (Loxodonta africana) Simulate Oestrus? An Analysis of Longitudinal Data

Female African elephants signal oestrus via chemicals in their urine, but they also exhibit characteristic changes to their posture, gait and behaviour when sexually receptive. Free-ranging females visually signal receptivity by holding their heads and tails high, walking with an exaggerated gait, and displaying increased tactile behaviour towards males. Parous females occasionally exhibit these visual signals at times when they are thought not to be cycling and without attracting interest from musth males. Using demographic and behavioural records spanning a continuous 28-year period, we investigated the occurrence of this “simulated” oestrus behaviour. We show that parous females in the Amboseli elephant population do simulate receptive oestrus behaviours, and this false oestrus occurs disproportionately in the presence of naïve female kin who are observed coming into oestrus for the first time. We compare several alternative hypotheses for the occurrence of this simulation: 1) false oestrus has no functional purpose (e.g., it merely results from abnormal hormonal changes); 2) false oestrus increases the reproductive success of the simulating female, by inducing sexual receptivity; and 3) false oestrus increases the inclusive fitness of the simulating female, either by increasing the access of related females to suitable males, or by encouraging appropriate oestrus behaviours from female relatives who are not responding correctly to males. Although the observed data do not fully conform to the predictions of any of these hypotheses, we rule out the first two, and tentatively suggest that parous females most likely exhibit false oestrus behaviours in order to demonstrate to naïve relatives at whom to direct their behaviour

Observations of bedforms on a dissipative macrotidal beach

NERC NE/H004262/1 and NE/H02543X/1 DRIB

Knowledge, attitude and practice of women in Campinas, São Paulo, Brazil with respect to physical exercise in pregnancy: a descriptive study

<p>Abstract</p> <p>Background</p> <p>Pregnancy is a good time to develop healthy lifestyle habits including regular exercise and good nutrition. Programs of physical exercise for pregnant women have been recommended; however, there are few references on this subject in the literature. The objective of this study was to evaluate the knowledge, attitude and practice of pregnant women with respect to appropriate physical exercise during pregnancy, and also to investigate why some women do not exercise during pregnancy.</p> <p>Methods</p> <p>A descriptive study was conducted in which 161 women of 18 to 45 years of age were interviewed in the third trimester of pregnancy. These women were receiving prenatal care at National Health Service (SUS) primary healthcare units and had no pathologies for which physical exercise would constitute a risk. The women were selected at an ultrasonography clinic accredited to the SUS in Campinas, São Paulo. A previously elaborated knowledge, attitude and practice (KAP) questionnaire was used to collect data, which were then stored in an Epinfo database. Statistical analysis was conducted using Pearson's chi-square test and Fisher's exact test to evaluate the association between the study variables (p < 0.05).</p> <p>Results</p> <p>Almost two-thirds (65.6%) of the women were sufficiently informed about the practice of physical exercise during pregnancy and the vast majority (93.8%) was in favor of it. Nevertheless, only just over 20% of the women in this sample exercised adequately. Significant associations were found between an adequate knowledge of physical exercise during pregnancy and education level (p = 0.0014) and between the adequate practice of physical exercise during pregnancy and having had fewer pregnancies (p = 0.0001). Lack of time and feeling tired and uncomfortable were the principal reasons given by the women for not exercising.</p> <p>Conclusion</p> <p>These results suggest that women's knowledge concerning the practice of physical exercise during pregnancy is reasonable and their attitude is favorable; however, relatively few actually exercise during pregnancy.</p