A Note on the Density Wave Model of the Galaxy

In this paper the general gas dynamical equations have been solved in the wave form and the general dispersion relation has been deduced. This dispersion relation has been used with simplifying assumptions plausible for special regions of the Galaxy, and results obtained have been shown to be able to interpret some observed dynamical behaviours as well as the distributional property of the gas in those special regions. For example, the analysis has yielded the interpretation of (a) the absence of any wave-pattern in the central region of the Galaxy, (b) the largescale deviation of the gas from the galactic plane in the outer regions of the Galaxy and (c) probably, the large-scale outflow of gas in the central region, as well as the large outward motion of the 3kpc arm. The analysis further indicates that in the solar neighbourhood the rotation curve of the Galaxy may possess a local maximum

Prediction of multiple infections after severe burn trauma: a prospective cohort study.

OBJECTIVE: To develop predictive models for early triage of burn patients based on hypersusceptibility to repeated infections. BACKGROUND: Infection remains a major cause of mortality and morbidity after severe trauma, demanding new strategies to combat infections. Models for infection prediction are lacking. METHODS: Secondary analysis of 459 burn patients (≥16 years old) with 20% or more total body surface area burns recruited from 6 US burn centers. We compared blood transcriptomes with a 180-hour cutoff on the injury-to-transcriptome interval of 47 patients (≤1 infection episode) to those of 66 hypersusceptible patients [multiple (≥2) infection episodes (MIE)]. We used LASSO regression to select biomarkers and multivariate logistic regression to built models, accuracy of which were assessed by area under receiver operating characteristic curve (AUROC) and cross-validation. RESULTS: Three predictive models were developed using covariates of (1) clinical characteristics; (2) expression profiles of 14 genomic probes; (3) combining (1) and (2). The genomic and clinical models were highly predictive of MIE status [AUROCGenomic = 0.946 (95% CI: 0.906-0.986); AUROCClinical = 0.864 (CI: 0.794-0.933); AUROCGenomic/AUROCClinical P = 0.044]. Combined model has an increased AUROCCombined of 0.967 (CI: 0.940-0.993) compared with the individual models (AUROCCombined/AUROCClinical P = 0.0069). Hypersusceptible patients show early alterations in immune-related signaling pathways, epigenetic modulation, and chromatin remodeling. CONCLUSIONS: Early triage of burn patients more susceptible to infections can be made using clinical characteristics and/or genomic signatures. Genomic signature suggests new insights into the pathophysiology of hypersusceptibility to infection may lead to novel potential therapeutic or prophylactic targets

A Small Volatile Bacterial Molecule Triggers Mitochondrial Dysfunction in Murine Skeletal Muscle

Mitochondria integrate distinct signals that reflect specific threats to the host, including infection, tissue damage, and metabolic dysfunction; and play a key role in insulin resistance. We have found that the Pseudomonas aeruginosa quorum sensing infochemical, 2-amino acetophenone (2-AA), produced during acute and chronic infection in human tissues, including in the lungs of cystic fibrosis (CF) patients, acts as an interkingdom immunomodulatory signal that facilitates pathogen persistence, and host tolerance to infection. Transcriptome results have led to the hypothesis that 2-AA causes further harm to the host by triggering mitochondrial dysfunction in skeletal muscle. As normal skeletal muscle function is essential to survival, and is compromised in many chronic illnesses, including infections and CF-associated muscle wasting, we here determine the global effects of 2-AA on skeletal muscle using high-resolution magic-angle-spinning (HRMAS), proton (1H) nuclear magnetic resonance (NMR) metabolomics, in vivo 31P NMR, whole-genome expression analysis and functional studies. Our results show that 2-AA when injected into mice, induced a biological signature of insulin resistance as determined by 1H NMR analysis-, and dramatically altered insulin signaling, glucose transport, and mitochondrial function. Genes including Glut4, IRS1, PPAR-γ, PGC1 and Sirt1 were downregulated, whereas uncoupling protein UCP3 was up-regulated, in accordance with mitochondrial dysfunction. Although 2-AA did not alter high-energy phosphates or pH by in vivo 31P NMR analysis, it significantly reduced the rate of ATP synthesis. This affect was corroborated by results demonstrating down-regulation of the expression of genes involved in energy production and muscle function, and was further validated by muscle function studies. Together, these results further demonstrate that 2-AA, acts as a mediator of interkingdom modulation, and likely effects insulin resistance associated with a molecular signature of mitochondrial dysfunction in skeletal muscle. Reduced energy production and mitochondrial dysfunctional may further favor infection, and be an important step in the establishment of chronic and persistent infections

Limiting damage during infection:lessons from infection tolerance for novel therapeutics

The distinction between pathogen elimination and damage limitation during infection is beginning to change perspectives on infectious disease control, and has recently led to the development of novel therapies that focus on reducing the illness caused by pathogens ("damage limitation") rather than reducing pathogen burdens directly ("pathogen elimination"). While beneficial at the individual host level, the population consequences of these interventions remain unclear. To address this issue, we present a simple conceptual framework for damage limitation during infection that distinguishes between therapies that are either host-centric (pro-tolerance) or pathogen-centric (anti-virulence). We then draw on recent developments from the evolutionary ecology of disease tolerance to highlight some potential epidemiological and evolutionary responses of pathogens to medical interventions that target the symptoms of infection. Just as pathogens are known to evolve in response to antimicrobial and vaccination therapies, we caution that claims of "evolution-proof" anti-virulence interventions may be premature, and further, that in infections where virulence and transmission are linked, reducing illness without reducing pathogen burden could have non-trivial epidemiological and evolutionary consequences that require careful examination

Pseudomonas aeruginosa Quorum Sensing Molecule Alters Skeletal Muscle Protein Homeostasis by Perturbing the Antioxidant Defense System

Pseudomonas aeruginosa, a bacterium that is resistant to treatment, causes serious acute, persistent, and relapsing infections in humans. There is increasing evidence that bacterial excreted small molecules play a critical role during infection. We have shown that a quorum sensing (QS)-regulated excreted small molecule, 2-AA, which is abundantly produced by P. aeruginosa, promotes persistent infections, dampens host inflammation, and triggers mitochondrial dysfunction in skeletal muscle. QS is a cell-to-cell communication system utilized by bacteria to promote collective behaviors. The significance of our study in identifying a mechanism that leads to skeletal muscle dysfunction, via the action of a QS molecule, is that it may open new avenues in the control of muscle loss as a result of infection and sepsis. Given that QS is a common characteristic of prokaryotes, it is possible that 2-AA-like molecules promoting similar effects may exist in other pathogens.Skeletal muscle function is compromised in many illnesses, including chronic infections. The Pseudomonas aeruginosa quorum sensing (QS) signal, 2-amino acetophenone (2-AA), is produced during acute and chronic infections and excreted in human tissues, including the lungs of cystic fibrosis patients. We have shown that 2-AA facilitates pathogen persistence, likely via its ability to promote the formation of bacterial persister cells, and that it acts as an interkingdom immunomodulatory signal that epigenetically reprograms innate immune functions. Moreover, 2-AA compromises muscle contractility and impacts the expression of genes involved in reactive oxygen species (ROS) homeostasis in skeletal muscle and in mitochondrial functions. Here, we elucidate the molecular mechanisms of 2-AA’s impairment of skeletal muscle function and ROS homeostasis. Murine in vivo and differentiated C2C12 myotube cell studies showed that 2-AA promotes ROS generation in skeletal muscle via the modulation of xanthine oxidase (XO) activity, NAD(P)H oxidase2 (NOX2) protein level, and the activity of antioxidant enzymes. ROS accumulation triggers the activity of AMP-activated protein kinase (AMPK), likely upstream of the observed locations of induction of ubiquitin ligases Muscle RING Finger 1 (MuRF1) and Muscle Atrophy F-box (MAFbx), and induces autophagy-related proteins. The protein-level perturbation in skeletal muscle of silent mating type information regulation 2 homolog 1 (SIRT1), peroxisome proliferator-activated receptor gamma coactivator 1 (PGC-1), and uncoupling protein 3 (UCP3) is rescued by the antioxidant N-acetyl-l-cysteine (NAC). Together, these results unveil a novel form of action of a QS bacterial molecule and provide molecular insights into the 2-AA-mediated skeletal muscle dysfunction caused by P. aeruginosa

Femoral shaft fractures in children: traction and spica casting (conservative treatment) versus closed titanium elastic nailing: A clinical study at Eastern India

Background: Femoral fractures are among the most common fractures of long bones. The management of paediatric femoral fractures depends primarily on the age of the child although the bone age and size of a child may determine the choice of treatment. Multiple traumas may necessitate rapid stabilization of femoral shaft fractures to facilitate overall care. Not many years ago, traction and casting were standard treatment for all femoral shaft fractures in children, and femoral fractures ranked high in duration of hospitalization for a single diagnosis. The aim of my study was to compare the results of conservative treatment and closed intra-medullary titanium elastic nailing in cases of fractures shaft femur in children. Materials & Methods: The patients with fractures shaft of femur attending either emergency or outdoor and also patients referred from peripheral hospitals were selected. We included the patient of 5 year to 10 year with closed fractures shaft of femur in children including Gustillo type I fractures. We excluded patients with an active infection, Gustillo type II and type III open fractures of shaft femur, pathological fractures, and abnormal medullary cavity. Out of the 42 patients, 23 were treated by intra-medullary titanium elastic nailing and 19 were treated by surface traction for three weeks followed by one and a half hip spica. After titanium elastic nailing, physical therapy with touchdown weight-bearing was begun as soon as the patient was comfortable, generally around 3weeks. Gentle knee exercises and quadriceps strengthening were begun. Full weight-bearing generally was given by 8 weeks. In conservatively managed group the cast was used until six to eight weeks after the injury. After the cast has been removed, management included skin care and physical therapy with touchdown weight-bearing was begun. Ambulation was accomplished with weight bearing as tolerated. The patients were evaluated at the regular interval of 2, 4, 6 & 8 weekly and after that every month. Results: In the patients treated with titanium elastic nailing the results were excellent in 16 (69.5%) patient, successful in 6 (26%) patient, and poor in 1(4.5%) patient. In the patient treated with traction and spica cast the results were excellent in 11 (58%) patients, successful in 6 (31.5%) and poor in 2 (10.5%) patients. Compared with the children treated with traction and a cast, those treated with titanium elastic nails had significantly shorter hospitalization period(p<0.0001), mean 8.5 days in operated group compared to mean 26 days in conservatively treated group. The time taken for full weight bearing was also significantly less in patient treated with titanium elastic nailing (p<0.0001); mean 9.1 weeks in operated group compared to 11.5 weeks in conservatively treated group. Conclusion: We conclude that closed pediatric femoral shaft fractures within the ages of 5-10 years can be treated successfully by any methods of traction followed by spica cast or intramedullary titanium elastic nailing. However, because of shorter immobilization period and earlier ambulation, we recommend internal fixation with titanium elastic nailing as the better choice to treat this fracture in school aged children

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Not AvailableThe objective of this study was to develop a simple and quick DNA extraction procedure for rapid diagnosis of sex of chicken and its embryos using multiplex polymerase chain reaction (PCR). Using alkaline method of DNA extraction from whole blood and feather bulb of adults, and tissue samples from embryos, the present study demonstrated that identification of sex by multiplex PCR protocol is simplest, safer, faster and inexpensive. Multiplex PCR was used to amplify W chromosome specific 481-bp fragment in female and 256bp fragment of 18S ribosomal gene in both male and female chicken. DNA samples were prepared by conventional phenol-chloroform-iso-amyl alcohol (PCI) method, modified PCI method, wizard genomic DNA purification kit and a simple alkaline method from blood samples and feather bulbs of adults and tissue samples of embryos. The protocol successfully identified sex of embryos and White Leghorn (Exotic), indigenous and Vanaraja (Hybrid of exotic and indigenous) varieties of chicken. Sequence comparison of W chromosome specific PCR products amplified from these three varieties showed no difference among them.SER

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Not AvailableA simple and rapid multiplex polymerase chain reaction (PCR) was developed for quick diagnosis of sex of duck and duck embryos. W chromosome specific DNA sequence was selected and primers were designed to amplify 335 bp fragment from female sex while 16s ribosomal sequence was selected to design primers to amplify 468 bp PCR products both in male and female sex as an internal control. Nucleotide sequences of W chromosome specific DNA fragments of Khaki Campbell and Indian Runner breeds of duck were found to be identical both in size and sequences, The study concluded that the protocol was successful in precisely identifying the gender of ducklings belonging to both Indian Runner and Khaki Campbell breeds of ducks and duck embryosSER