A rare study from the wintering grounds provides insight into the costs of malaria infection for migratory birds

Malaria parasites can have strong effects on the population dynamics and evolution of migratory bird species. In many species, parasite transmission occurs on the wintering grounds, but studies to determine the consequences of infection have taken place during the breeding season, when malaria parasites circulate at chronic levels. We examined the predictors of malarial infections for great reed warblers during the northern winter in Africa, where active parasite transmission is thought to occur and naïve individuals experience acute infections. Counter to expectations, we found that winter infection intensities were lower than those encountered on the breeding grounds. One potential explanation is that reduced immune function during breeding allows parasites to persist at higher chronic intensities. We found no relationships between the incidence or intensity of infection on condition (as measured by scaled mass index, plasma metabolites, and feather corticosterone), spring migration departure dates, or home range sizes. We also tested a prediction of the Hamilton–Zuk hypothesis and found that male ornament (song) quality was unrelated to parasitic infection status. Overall, our results provide the first evidence that long‐distance migrants captured on their wintering grounds are in the chronic stage of infection, and suggest that winter studies may fare no better than breeding studies at determining the costs of acute malarial infection for great reed warblers.This is the final version of the article. It first appeared from Wiley via http://dx.doi.org/10.1111/jav.0087

Incident venous thromboembolic events in the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER)

<p>Background: Venous thromboembolic events (VTE), including deep venous thrombosis and pulmonary embolism, are common in older age. It has been suggested that statins might reduce the risk of VTE however positive results from studies of middle aged subjects may not be generalisable to elderly people. We aimed to determine the effect of pravastatin on incident VTE in older people; we also studied the impact of clinical and plasma risk variables.</p> <p>Methods: This study was an analysis of incident VTE using data from the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER), a randomized, double-blind, placebo-controlled trial of pravastatin in men and women aged 70-82. Mean follow-up was 3.2 years. Risk for VTE was examined in non-warfarin treated pravastatin (n = 2834) and placebo (n = 2865) patients using a Cox's proportional hazard model, and the impact of other risk factors assessed in a multivariate forward stepwise regression analysis. Baseline clinical characteristics, blood biochemistry and hematology variables, plasma levels of lipids and lipoproteins, and plasma markers of inflammation and adiposity were compared. Plasma markers of thrombosis and hemostasis were assessed in a nested case (n = 48) control (n = 93) study where the cohort was those participants, not on warfarin, for whom data were available.</p> <p>Results: There were 28 definite cases (1.0%) of incident VTE in the pravastatin group recipients and 20 cases (0.70%) in placebo recipients. Pravastatin did not reduce VTE in PROSPER compared to placebo [unadjusted hazard ratio (95% confidence interval) 1.42 (0.80, 2.52) p = 0.23]. Higher body mass index (BMI) [1.09 (1.02, 1.15) p = 0.0075], country [Scotland vs Netherlands 4.26 (1.00, 18.21) p = 0.050 and Ireland vs Netherlands 6.16 (1.46, 26.00) p = 0.013], lower systolic blood pressure [1.35 (1.03, 1.75) p = 0.027] and lower baseline Mini Mental State Examination (MMSE) score [1.19 (1.01, 1.41) p = 0.034] were associated with an increased risk of VTE, however only BMI, country and systolic blood pressure remained significant on multivariate analysis. In a nested case control study of definite VTE, plasma Factor VIII levels were associated with VTE [1.52 (1.01, 2.28), p = 0.044]. However no other measure of thrombosis and haemostasis was associated with increased risk of VTE.</p> <p>Conclusions: Pravastatin does not prevent VTE in elderly people at risk of vascular disease. Blood markers of haemostasis and inflammation are not strongly predictive of VTE in older age however BMI, country and lower systolic blood pressure are independently associated with VTE risk.</p&gt

Severe postpartum sepsis with prolonged myocardial dysfunction: a case report

<p>Abstract</p> <p>Introduction</p> <p>Severe sepsis during pregnancy or in the postpartum period is a rare clinical event. In non obstetric surviving patients, the cardiovascular changes seen in sepsis and septic shock are fully reversible five to ten days after their onset. We report a case of septic myocardial dysfunction lasting longer than ten days. To the best of our knowledge, this is the first report of prolonged septic myocardial dysfunction in a parturient.</p> <p>Case presentation</p> <p>A 24 year old Hispanic woman with no previous medical history developed pyelonephritis and severe sepsis with prolonged myocardial dysfunction after a normal spontaneous vaginal delivery.</p> <p>Conclusions</p> <p>Septic myocardial dysfunction may be prolonged in parturients requiring longer term follow up and pharmacologic treatment.</p

Dark Matter from Minimal Flavor Violation

We consider theories of flavored dark matter, in which the dark matter particle is part of a multiplet transforming nontrivially under the flavor group of the Standard Model in a manner consistent with the principle of Minimal Flavor Violation (MFV). MFV automatically leads to the stability of the lightest state for a large number of flavor multiplets. If neutral, this particle is an excellent dark matter candidate. Furthermore, MFV implies specific patterns of mass splittings among the flavors of dark matter and governs the structure of the couplings between dark matter and ordinary particles, leading to a rich and predictive cosmology and phenomenology. We present an illustrative phenomenological study of an effective theory of a flavor SU(3)_Q triplet, gauge singlet scalar.Comment: 10 pages, 2 figures; v2: references added, minor changes to collider analysis, conclusions unchange

Purinergic signaling microenvironments: An introduction

The common theme of this introductory article and the minireviews that follow in this special issue is the concept of microenvironments within tissues and surrounding cells that would be ideal signaling venues for a biologically active purinergic ligand. Collectively, the editors/authors and the other contributing authors agree that nucleotides and nucleosides would be most potent within a confined system. A talented cadre of purinergics has been solicited to discuss purinergic signaling in his or her favorite microenvironment within a given organ or tissue. We are gratified by the large number of original articles that also have successfully navigated the peer review process and are part of this special issue. These concepts are not simply purinergic, but the idea of maximal potency in a tissue microenvironment and surrounding specialized cells within a tissue pertains to any autacoid or paracrine agonist

Diagnosis and treatment of musculoskeletal chest pain: design of a multi-purpose trial

<p>Abstract</p> <p>Background</p> <p>Acute chest pain is a major health problem all over the western world. Active approaches are directed towards diagnosis and treatment of potentially life threatening conditions, especially acute coronary syndrome/ischemic heart disease. However, according to the literature, chest pain may also be due to a variety of extra-cardiac disorders including dysfunction of muscles and joints of the chest wall or the cervical and thoracic part of the spine. The diagnostic approaches and treatment options for this group of patients are scarce and formal clinical studies addressing the effect of various treatments are lacking.</p> <p>Methods/Design</p> <p>We present an ongoing trial on the potential usefulness of chiropractic diagnosis and treatment in patients dismissed from an acute chest pain clinic without a diagnosis of acute coronary syndrome. The aims are to determine the proportion of patients in whom chest pain may be of musculoskeletal rather than cardiac origin and to investigate the decision process of a chiropractor in diagnosing these patients; further, to examine whether chiropractic treatment can reduce pain and improve physical function when compared to advice directed towards promoting self-management, and, finally, to estimate the cost-effectiveness of these procedures. This study will include 300 patients discharged from a university hospital acute chest pain clinic without a diagnosis of acute coronary syndrome or any other obvious cardiac or non-cardiac disease. After completion of the clinic's standard cardiovascular diagnostic procedures, trial patients will be examined according to a standardized protocol including a) a self-report questionnaire; b) a semi-structured interview; c) a general health examination; and d) a specific manual examination of the muscles and joints of the neck, thoracic spine, and thorax in order to determine whether the pain is likely to be of musculoskeletal origin. To describe the patients status with regards to ischemic heart disease, and to compare and indirectly validate the musculoskeletal diagnosis, myocardial perfusion scintigraphy is performed in all patients 2–4 weeks following discharge. Descriptive statistics including parametric and non-parametric methods will be applied in order to compare patients with and without musculoskeletal chest pain in relation to their scintigraphic findings. The decision making process of the chiropractor will be elucidated and reconstructed using the CART method. Out of the 300 patients 120 intended patients with suspected musculoskeletal chest pain will be randomized into one of two groups: a) a course of chiropractic treatment (therapy group) of up to ten treatment sessions focusing on high velocity, low amplitude manipulation of the cervical and thoracic spine, mobilisation, and soft tissue techniques. b) Advice promoting self-management and individual instructions focusing on posture and muscle stretch (advice group). Outcome measures are pain, physical function, overall health, self-perceived treatment effect, and cost-effectiveness.</p> <p>Discussion</p> <p>This study may potentially demonstrate that a chiropractor is able to identify a subset of patients suffering from chest pain predominantly of musculoskeletal origin among patients discharged from an acute chest pain clinic with no apparent cardiac condition. Furthermore knowledge about the benefits of manual treatment of patients with musculoskeletal chest pain will inform clinical decision and policy development in relation to clinical practice.</p> <p>Trial registration</p> <p>NCT00462241 and NCT00373828</p

A survey of failed post-retained restorations

Survival of endodontically treated, post-restored teeth depends on a multitude of factors, all of which are practically impossible to include in a randomized, controlled clinical study. The purpose of this survey was to characterize and analyze reported failures of post-retained restorations to identify factors critical to failure and to type of failure. A questionnaire was mailed to private practitioners in Denmark with a request to complete the questionnaire whenever a patient presented with a failed post-retained restoration. Information was gathered on factors related to the patient, the tooth, the restorative materials, and the techniques. Two-hundred and sixty questionnaires were collected from 171 practitioners over a 3-year period. Functioning time until failure varied between 3 months and 38 years. Mean survival time until failure was 11 years. Of the failed restorations, 61% had functioned for 10 years or less. Fracture of the tooth was the most common type of failure reported, followed by loosening of the post and fracture of the post. Tapered posts implied an increased risk of tooth fracture compared to loosening or fracture of the post, and the relative risk of tooth fracture increased with the functioning time until failure. Fracture of the post was more common among male than female patients. On the basis of this survey of failed post-retained restorations, it was concluded that tapered posts were associated with a higher risk of tooth fracture than were parallel-sided posts

Expression Screening of Fusion Partners from an E. coli Genome for Soluble Expression of Recombinant Proteins in a Cell-Free Protein Synthesis System

While access to soluble recombinant proteins is essential for a number of proteome studies, preparation of purified functional proteins is often limited by the protein solubility. In this study, potent solubility-enhancing fusion partners were screened from the repertoire of endogenous E. coli proteins. Based on the presumed correlation between the intracellular abundance and folding efficiency of proteins, PCR-amplified ORFs of a series of highly abundant E. coli proteins were fused with aggregation-prone heterologous proteins and then directly expressed for quantitative estimation of the expression efficiency of soluble translation products. Through two-step screening procedures involving the expression of 552 fusion constructs targeted against a series of cytokine proteins, we were able to discover a number of endogenous E. coli proteins that dramatically enhanced the soluble expression of the target proteins. This strategy of cell-free expression screening can be extended to quantitative, global analysis of genomic resources for various purposes.National Research Foundation of KoreaKorea (South). Ministry of Education, Science and Technology (MEST) (grant 2011K000841)Korea (South). Ministry of Education, Science and Technology (MEST) (grant 2011-0027901

Efficacy and adverse effects of intravenous lignocaine therapy in fibromyalgia syndrome

BACKGROUND: To investigate the effects of intravenous lignocaine infusions (IV lignocaine) in fibromyalgia. METHODS: Prospective study of the adverse effects of IV lignocaine in 106 patients with fibromyalgia; retrospective questionnaire study of the efficacy of IV lignocaine in 50 patients with fibromyalgia. RESULTS: Prospective study: Two major (pulmonary oedema and supraventricular tachycardia) and 42 minor side-effects were reported. None had long-term sequelae. The commonest was hypotension (17 cases). Retrospective study: Pain and a range of psychosocial measures (on single 11-point scales) improved significantly after treatment. There was no effect of the treatment on work status. The average duration of pain relief after the 6-day course of treatment was 11.5 ± 6.5 weeks. CONCLUSIONS: Intravenous lignocaine appears to be both safe and of benefit in improving pain and quality of life for patients with fibromyalgia. This needs to be confirmed in prospective randomised controlled trials

The novel Fh8 and H fusion partners for soluble protein expression in Escherichia coli : a comparison with the traditional gene fusion technology

The Escherichia coli host system is an advantageous choice for simple and inexpensive recombinant protein production but it still presents bottlenecks at expressing soluble proteins from other organisms. Several efforts have been taken to overcome E. coli limitations, including the use of fusion partners that improve protein expression and solubility. New fusion technologies are emerging to complement the traditional solutions. This work evaluates two novel fusion partners, the Fh8 tag (8 kDa) and the H tag (1 kDa), as solubility enhancing tags in E. coli and their comparison to commonly used fusion partners. A broad range comparison was conducted in a small-scale screening and subsequently scaled-up. Six difficult-to-express target proteins (RVS167, SPO14, YPK1, YPK2, Frutalin and CP12) were fused to eight fusion tags (His, Trx, GST, MBP, NusA, SUMO, H and Fh8). The resulting protein expression and solubility levels were evaluated by sodium dodecyl sulfate polyacrylamide gel electrophoresis before and after protein purification and after tag removal. The Fh8 partner improved protein expression and solubility as the well-known Trx, NusA or MBP fusion partners. The H partner did not function as a solubility tag. Cleaved proteins from Fh8 fusions were soluble and obtained in similar or higher amounts than proteins from the cleavage of other partners as Trx, NusA or MBP. The Fh8 fusion tag therefore acts as an effective solubility enhancer, and its low molecular weight potentially gives it an advantage over larger solubility tags by offering a more reliable assessment of the target protein solubility when expressed as a fusion protein.The financial support of the EMBL Heidelberg, Germany and Fundacao para a Ciencia e Tecnologia (FCT), Portugal, is acknowledged: the fellowship SFRH/BD/46482/2008 to Sofia J. Costa and the project PTDC/CVT/103081/2008. The authors wish to acknowledge Anne-Claude Gavin for providing four of the constructs for this study (RVS167, SPO14, YPK1, and YPK2) and Emmanuel Poilpre for the experimental help (both from the EMBL Heidelberg, Germany)