Chronic dermatomycoses of the foot as risk factors for acute bacterial cellulitis of the leg: A case-control study

Objective: To assess the role of foot dermatomycosis ( tinea pedis and onychomycosis) and other candidate risk factors in the development of acute bacterial cellulitis of the leg. Methods: A case-control study, including 243 patients ( cases) with acute bacterial cellulitis of the leg and 467 controls, 2 per case, individually matched for gender, age (+/-5 years), hospital and admission date (+/-2 months). Results: Overall, mycology-proven foot dermatomycosis was a significant risk factor for acute bacterial cellulitis (odds ratio, OR: 2.4; p < 0.001), as were tinea pedis interdigitalis (OR: 3.2; p < 0.001), tinea pedis plantaris (OR: 1.7; p = 0.005) and onychomycosis (OR: 2.2; p < 0.001) individually. Other risk factors included: disruption of the cutaneous barrier, history of bacterial cellulitis, chronic venous insufficiency and leg oedema. Conclusions: Tinea pedis and onychomycosis were found to be significant risk factors for acute bacterial cellulitis of the leg that are readily amenable to treatment with effective pharmacological therapy. Copyright (C) 2004 S. Karger AG, Basel

Tumor-Induced IL-6 Reprograms Host Metabolism to Suppress Anti-tumor Immunity

In patients with cancer, the wasting syndrome, cachexia, is associated with caloric deficiency. Here, we describe tumor-induced alterations of the host metabolic response to caloric deficiency that cause intratumoral immune suppression. In pre-cachectic mice with transplanted colorectal cancer or autochthonous pancreatic ductal adenocarcinoma (PDA), we find that IL-6 reduces the hepatic ketogenic potential through suppression of PPARalpha, the transcriptional master regulator of ketogenesis. When these mice are challenged with caloric deficiency, the resulting relative hypoketonemia triggers a marked rise in glucocorticoid levels. Multiple intratumoral immune pathways are suppressed by this hormonal stress response. Moreover, administering corticosterone to elevate plasma corticosterone to a level that is lower than that occurring in cachectic mice abolishes the response of mouse PDA to an immunotherapy that has advanced to clinical trials. Therefore, tumor-induced IL-6 impairs the ketogenic response to reduced caloric intake, resulting in a systemic metabolic stress response that blocks anti-cancer immunotherapy.We also thank the University of Cambridge, Cancer Research UK, the CRUK Cambridge Institute Core Facilities, and Hutchison Whampoa Limited. This work was also supported by the Lustgarten Foundation for Pancreatic Cancer Research, the Ludwig Institute for Cancer Research, the NIHR Biomedical Research Centre, and the Cambridge ECMC. T.R.F. was supported by the Rosetrees Trust and the Cambridge School of Clinical Medicine’s MB/PhD Programme, T.J. was supported by the Wellcome Trust Translational Medicine and Therapeutics Programme and the University of Cambridge Department of Oncology (RJAG/076), C.M.C. was supported by the Cambridge University Hospitals NHS Foundation Trust, E.W.R. was supported by the CRI Irvington Postdoctoral Fellowship Program, and A.P.C. was supported by the Medical Research Council (MRC) Metabolic Diseases Unit (MRC_MC_UU_12012/1). D.T.F. is a Distinguished Scholar of the Lustgarten Foundation

Urbanization and seasonality strengthens the CO2 capacity of the Red River Delta, Vietnam

Tropical rivers are dynamic CO2 sources. Regional patterns in the partial pressure of CO2 (pCO2) and relationships with other a/biotic factors in densely populated and rapidly developing river delta regions of Southeast Asia are still poorly constrained. Over one year, at 21 sites across the river system in the Red River Delta (RRD), Vietnam, we calculated pCO2 levels from temperature, pH, and total alkalinity and inter-linkages between pCO2 and phytoplankton, water chemistry and seasonality were then assessed. The smaller, more urbanized, and polluted Day River had an annual median pCO2 of 5000 ± 3300 µatm and the larger Red River of 2675 ± 2271 µatm. pCO2 was 1.6 and 3.2 times higher during the dry season in the Day and Red rivers respectively than the rainy season. Elevated pCO2 levels in the Day River during the dry season were also 2.4-fold higher than the median value (2811 ± 3577 µatm) of calculated and direct pCO2 measurements in >20 sub/tropical rivers. By further categorizing the river data into Hanoi City vs. other less urban-populated provinces, we found significantly higher nutrients, organic matter content, and riverine cyanobacteria during the dry season in the Day River across Hanoi City. Forward selection also identified riverine cyanobacteria and river discharge as the main predictors explaining pCO2 variation in the RRD. After accounting for the shared effects (14%), river discharge alone significantly explained 12% of the pCO2 variation, cyanobacteria uniquely a further 21%, while 53% of the pCO2 variance was unexplained by either. We show that the urbanization of rivers deltas could result in increased sources of riverine pCO2, water pollution, and harmful cyanobacterial blooms. Such risks could be mitigated through water management to increase water flows in problem areas during the dry season

Methodological considerations in the assessment of direct and indirect costs of back pain: A systematic scoping review

Background Back pain is a common and costly health problem worldwide. There is yet a lack of consistent methodologies to estimate the economic burden of back pain to society. Objective To systematically evaluate the methodologies used in the published cost of illness (COI) literature for estimating the direct and indirect costs attributed to back pain, and to present a summary of the estimated cost burden. Methods Six electronic databases were searched to identify COI studies of back pain published in English up to February 2021. A total of 1,588 abstracts were screened, and 55 full-text studies were subsequently reviewed. After applying the inclusion criteria, 45 studies pertaining to the direct and indirect costs of back pain were analysed. Results The studies reported data on 15 industrialised countries. The national cost estimates of back pain in 2015 USD ranged from $259 million ($29.1 per capita) in Sweden to $71.6 billion ($868.4 per capita) in Germany. There was high heterogeneity among the studies in terms of the methodologies used for analysis and the resulting costs reported. Most of the studies assessed costs from a societal perspective (n = 29). The magnitude and accuracy of the reported costs were influenced by the case definition of back pain, the source of data used, the cost components included and the analysis method. Among the studies that provided both direct and indirect cost estimates (n = 15), indirect costs resulting from lost or reduced work productivity far outweighed the direct costs. Conclusion Back pain imposes substantial economic burden on society. This review demonstrated that existing published COI studies of back pain used heterogeneous approaches reflecting a lack of consensus on methodology. A standardised methodological approach is required to increase credibility of the findings of COI studies and improve comparison of estimates across studies

Structure and Dynamics of the EGF Receptor as Revealed by Experiments and Simulations and Its Relevance to Non-Small Cell Lung Cancer

The epidermal growth factor receptor (EGFR) is historically the prototypical receptor tyrosine kinase, being the first cloned and the first where the importance of ligand-induced dimer activation was ascertained. However, many years of structure determination has shown that EGFR is not completely understood. One challenge is that the many structure fragments stored at the PDB only provide a partial view because full-length proteins are flexible entities and dynamics play a key role in their functionality. Another challenge is the shortage of high-resolution data on functionally important higher-order complexes. Still, the interest in the structure/function relationships of EGFR remains unabated because of the crucial role played by oncogenic EGFR mutants in driving non-small cell lung cancer (NSCLC). Despite targeted therapies against EGFR setting a milestone in the treatment of this disease, ubiquitous drug resistance inevitably emerges after one year or so of treatment. The magnitude of the challenge has inspired novel strategies. Among these, the combination of multi-disciplinary experiments and molecular dynamic (MD) simulations have been pivotal in revealing the basic nature of EGFR monomers, dimers and multimers, and the structure-function relationships that underpin the mechanisms by which EGFR dysregulation contributes to the onset of NSCLC and resistance to treatment

Safety and efficacy of fluticasone propionate in the topical treatment of skin diseases

Fluticasone propionate - the first carbothioate corticosteroid - has been classified as a potent anti-inflammatory drug for dermatological use. It is available as 0.05% cream and 0.005% ointment formulations for the acute and maintenance treatment of patients with dermatological disorders such as atopic dermatitis, psoriasis and vitiligo. This glucocorticoid is characterized by high lipophilicity, high glucocorticoid receptor binding and activation, and a rapid metabolic turnover in skin. Although skin blanching following fluticasone propionate exceeds that of corticosteroids of medium strength, several clinical trials demonstrate a low potential for cutaneous and systemic side-effects, even in difficult-to-treat areas like the face, the eyelids and intertriginous areas. Even among paediatric patients with atopic dermatitis, fluticasone propionate proved to be safe and effective. These pharmacological and clinical properties are reflected by the high therapeutic index of this glucocorticoid

Fermion correlators in non-abelian holographic superconductors

We consider fermion correlators in non-abelian holographic superconductors. The spectral function of the fermions exhibits several interesting features such as support in displaced Dirac cones and an asymmetric distribution of normal modes. These features are compared to similar ones observed in angle resolved photoemission experiments on high T_c superconductors. Along the way we elucidate some properties of p-wave superconductors in AdS_4 and discuss the construction of SO(4) superconductors.Comment: 49 pages, 11 figure

Ecological Meltdown in the Firth of Clyde, Scotland: Two Centuries of Change in a Coastal Marine Ecosystem

BACKGROUND: The Firth of Clyde is a large inlet of the sea that extends over 100 km into Scotland\u27s west coast. METHODS: We compiled detailed fisheries landings data for this area and combined them with historical accounts to build a picture of change due to fishing activity over the last 200 years. FINDINGS: In the early 19th century, prior to the onset of industrial fishing, the Firth of Clyde supported diverse and productive fisheries for species such as herring (Clupea harengus, Clupeidae), cod (Gadus morhua, Gadidae), haddock (Melanogrammus aeglefinus, Gadidae), turbot (Psetta maxima, Scophthalmidae) and flounder (Platichthys flesus, Pleuronectidae). The 19th century saw increased demand for fish, which encouraged more indiscriminate methods of fishing such as bottom trawling. During the 1880s, fish landings began to decline, and upon the recommendation of local fishers and scientists, the Firth of Clyde was closed to large trawling vessels in 1889. This closure remained in place until 1962 when bottom trawling for Norway lobster (Nephrops norvegicus, Nephropidae) was approved in areas more than three nautical miles from the coast. During the 1960s and 1970s, landings of bottomfish increased as trawling intensified. The trawl closure within three nautical miles of the coast was repealed in 1984 under pressure from the industry. Thereafter, bottomfish landings went into terminal decline, with all species collapsing to zero or near zero landings by the early 21st century. Herring fisheries collapsed in the 1970s as more efficient mid-water trawls and fish finders were introduced, while a fishery for mid-water saithe (Pollachius virens, Gadidae) underwent a boom and bust shortly after discovery in the late 1960s. The only commercial fisheries that remain today are for Nephrops and scallops (Pecten maximus, Pectinidae). SIGNIFICANCE: The Firth of Clyde is a marine ecosystem nearing the endpoint of overfishing, a time when no species remain that are capable of sustaining commercial catches. The evidence suggests that trawl closures helped maintain productive fisheries through the mid-20th century, and their reopening precipitated collapse of bottomfish stocks. We argue that continued intensive bottom trawling for Nephrops with fine mesh nets will prevent the recovery of other species. This once diverse and highly productive environment will only be restored if trawl closures or other protected areas are re-introduced. The Firth of Clyde represents at a small scale a process that is occurring ocean-wide today, and its experience serves as a warning to others