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A Clinical Review of Diabetic Foot Infections.
Chastain CA, Klopfenstein N, Serezani CH, Aronoff DM
(2019) Clin Podiatr Med Surg 36: 381-395
MeSH Terms: Anti-Bacterial Agents, Debridement, Diabetic Foot, Drug Resistance, Microbial, Humans, Infectious Disease Medicine, Osteomyelitis, Risk Factors, Wound Healing
Show Abstract · Added March 18, 2020
"Diabetic foot infections (DFIs) are a common cause of morbidity and mortality. This article summarizes current knowledge regarding DFI epidemiology, disease pathogenesis, and the impact of antimicrobial resistance among DFI. An evidence-based approach to clinical assessment, diagnosing osteomyelitis, as well as medical and surgical treatment is discussed, including a review of empiric and directed antibiotic treatment recommendations. The current state and needs of the clinical literature are identified throughout, with a discussion of the supporting role of infectious diseases specialists as well as future directions of the field."
Copyright © 2019 Elsevier Inc. All rights reserved.
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Existence of a Colonizing Staphylococcus aureus Strain Isolated in Diabetic Foot Ulcers.
Messad N, Prajsnar TK, Lina G, O'Callaghan D, Foster SJ, Renshaw SA, Skaar EP, Bes M, Dunyach-Remy C, Vandenesch F, Sotto A, Lavigne JP
(2015) Diabetes 64: 2991-5
MeSH Terms: Animals, Diabetic Foot, Humans, Staphylococcal Infections, Staphylococcus aureus, Virulence, Zebrafish
Show Abstract · Added February 8, 2016
Staphylococcus aureus is an opportunistic bacterium capable of causing a wide range of severe diseases when it gains access to underlying tissues. Paradoxically, S. aureus is a common inhabitant of the skin microflora and colonizes the nares and other human mucosa. The purpose of this study was to determine the genetic basis for the differences in the pathogenic versus colonizing potential of S. aureus isolated from diabetic foot ulcers (DFUs). By performing optical map comparisons of a collection of S. aureus strains isolated from DFUs, we brought to light a prophage present in noninfecting bacteria. The phage, namely ROSA-like, was localized in a hotspot region ΦNM2 near the locus isd, the iron surface determinant system. The integrated phage significantly reduces the virulence of the strain and increases the biofilm formation. DFUs seem to be a specific niche of this colonizing strain. The ROSA-like phage represents the first description of a mobile element present mainly in S. aureus isolated from DFUs, which modulates the relationship of the bacteria with its human host. This phage appears to attenuate bacterial virulence and promote colonization.
© 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.
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7 MeSH Terms
Phosphorylation-dependent derepression by the response regulator HnoC in the Shewanella oneidensis nitric oxide signaling network.
Plate L, Marletta MA
(2013) Proc Natl Acad Sci U S A 110: E4648-57
MeSH Terms: Bacterial Proteins, Biofilms, DNA Footprinting, Electrophoretic Mobility Shift Assay, Microarray Analysis, Models, Biological, Nitric Oxide, Phosphorylation, Regulatory Elements, Transcriptional, Shewanella, Signal Transduction
Show Abstract · Added March 3, 2020
Nitric oxide (NO) is an important signaling molecule that regulates diverse physiological processes in all domains of life. In many gammaproteobacteria, NO controls behavioral responses through a complex signaling network involving heme-nitric oxide/oxygen binding (H-NOX) domains as selective NO sensors. In Shewanella oneidensis, H-NOX-mediated NO sensing increases biofilm formation, which is thought to serve as a protective mechanism against NO cytotoxicity. The H-NOX/NO-responsive (hno) signaling network involves H-NOX-dependent control of HnoK autophosphorylation and phosphotransfer from HnoK to three response regulators. Two of these response regulators, HnoB and HnoD, regulate cyclic-di-GMP levels and influence biofilm formation. However, the role of the third response regulator in the signaling network, HnoC, has not been determined. Here we describe a role for HnoC as a transcriptional repressor for the signaling genes in the hno network. The genes controlled by HnoC were identified by microarray analysis, and its function as a repressor was confirmed in vivo. HnoC belongs to an uncharacterized family of DNA-binding response regulators. Binding of HnoC to its promoter targets was characterized in vitro, revealing an unprecedented regulation mechanism, which further extends the functional capabilities of DNA-binding response regulators. In the unphosphorylated state HnoC forms a tetramer, which tightly binds to an inverted-repeat target sequence overlapping with the promoter regions. Phosphorylation of HnoC induces dissociation of the response regulator tetramer and detachment of subunits from the promoter DNA, which subsequently leads to transcriptional derepression.
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Blood pressure and left ventricular hypertrophy during American-style football participation.
Weiner RB, Wang F, Isaacs SK, Malhotra R, Berkstresser B, Kim JH, Hutter AM, Picard MH, Wang TJ, Baggish AL
(2013) Circulation 128: 524-31
MeSH Terms: Adolescent, Athletes, Blood Pressure, Blood Pressure Determination, Football, Humans, Hypertension, Hypertrophy, Left Ventricular, Longitudinal Studies, Male, Physical Endurance, Prospective Studies, Students, United States, Universities, Young Adult
Show Abstract · Added April 15, 2014
BACKGROUND - Hypertension, a strong determinant of cardiovascular disease risk, has been documented among elite, professional American-style football (ASF) players. The risk of increased blood pressure (BP) and early adulthood hypertension among the substantially larger population of collegiate ASF athletes is not known.
METHODS AND RESULTS - We conducted a prospective, longitudinal study to examine BP, the incidence of hypertension, and left ventricular remodeling among collegiate ASF athletes. Resting BP and left ventricular structure were assessed before and after a single season of competitive ASF participation in 6 consecutive groups of first-year university athletes (n=113). ASF participation was associated with significant increases in systolic BP (116±8 versus 125±13 mm Hg; P<0.001) and diastolic BP (64±8 mm Hg versus 66±10 mm Hg; P<0.001). At the postseason assessment, the majority of athletes met criteria for Joint National Commission (seventh report) prehypertension (53 of 113, 47%) or stage 1 hypertension (16 of 113, 14%). Among measured characteristics, lineman field position, intraseason weight gain, and family history of hypertension were the strongest independent predictors of postseason BP. Among linemen, there was a significant increase in the prevalence of concentric left ventricular hypertrophy (2 of 64 [3%] versus 20 of 64 [31%]; P<0.001) and change in left ventricular mass correlated with intraseason change in systolic BP (R=0.46, P<0.001).
CONCLUSIONS - Collegiate ASF athletes may be at risk for clinically relevant increases in BP and the development of hypertension. Enhanced surveillance and carefully selected interventions may represent important opportunities to improve later-life cardiovascular health outcomes in this population.
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16 MeSH Terms
Skin toxicity and efficacy of sunitinib and sorafenib in metastatic renal cell carcinoma: a national registry-based study.
Poprach A, Pavlik T, Melichar B, Puzanov I, Dusek L, Bortlicek Z, Vyzula R, Abrahamova J, Buchler T, Czech Renal Cancer Cooperative Group
(2012) Ann Oncol 23: 3137-3143
MeSH Terms: Aged, Angiogenesis Inhibitors, Antineoplastic Agents, Carcinoma, Renal Cell, Disease-Free Survival, Exanthema, Female, Hand-Foot Syndrome, Humans, Indoles, Kidney Neoplasms, Male, Middle Aged, Neoplasm Metastasis, Niacinamide, Phenylurea Compounds, Protein Kinase Inhibitors, Pyrroles, Registries, Retrospective Studies, Skin, Sorafenib, Sunitinib, Treatment Outcome
Show Abstract · Added March 5, 2014
BACKGROUND - A retrospective, registry-based analysis to assess the outcomes of metastatic renal cell cancer (mRCC) patients treated with sunitinib and sorafenib who developed dermatologic adverse events was performed.
PATIENTS AND METHODS - Data on mRCC patients treated with sunitinib or sorafenib were obtained from the Czech Clinical Registry of Renal Cell Cancer Patients. Outcomes of patients who developed hand-foot syndrome (HFS) of any grade and/or grade 3/4 rash during the treatment were compared with patients without HFS and no, mild, or moderate rash.
RESULTS - The cohort included 705 patients treated with sunitinib and 365 patients treated with sorafenib. For sunitinib, the median overall survival (OS) was 43.0 months versus 31.0 months (P = 0.027) and median progression-free survival (PFS) 20.8 months versus 11.1 months (P = 0.007) for patients with versus without dermatologic toxicity, respectively. For sorafenib, the median OS and PFS were 27.9 and 24.6 months (P = 0.244), and 12.2 and 8.8 months (P = 0.050), respectively. In multivariable Cox regression, the skin toxicity was significantly associated with longer OS in the sunitinib cohort.
CONCLUSION - The presence of skin toxicity is associated with improved OS and PFS in patients with mRCC treated with sunitinib.
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24 MeSH Terms
Epigenetic priming of a pre-B cell-specific enhancer through binding of Sox2 and Foxd3 at the ESC stage.
Liber D, Domaschenz R, Holmqvist PH, Mazzarella L, Georgiou A, Leleu M, Fisher AG, Labosky PA, Dillon N
(2010) Cell Stem Cell 7: 114-26
MeSH Terms: Animals, Cell Line, Cells, Cultured, Chromatin Immunoprecipitation, DNA Footprinting, Embryonic Stem Cells, Enhancer Elements, Genetic, Epigenesis, Genetic, Forkhead Transcription Factors, Hemangioblasts, Immunoglobulin Light Chains, Surrogate, Mice, Oligonucleotide Array Sequence Analysis, Precursor Cells, B-Lymphoid, Protein Binding, Repressor Proteins, Reverse Transcriptase Polymerase Chain Reaction, SOXB1 Transcription Factors, SOXC Transcription Factors
Show Abstract · Added August 2, 2010
Modifications to the core histones are thought to contribute to ESC pluripotency by priming tissue-specific promoters and enhancers for later activation. However, it is unclear how these marks are targeted in ESCs and maintained during differentiation. Here, we show that the ESC factor Sox2 targets H3K4 methylation to monovalent and bivalent domains. In ESCs, Sox2 contributes to the formation of a monovalent mark at an enhancer in the pro/pre-B cell-specific lambda5-VpreB1 locus. Binding of Foxd3 suppresses intergenic transcription of the enhancer and surrounding sequences. In pro-B cells, enhancer activity is dependent on the Sox and Fox binding sites, and the enhancer is bound by Sox4, which is required for efficient expression of lambda5. Our results lead us to propose a factor relay model whereby ESC factors establish active epigenetic marks at tissue specific elements before being replaced by cell type-specific factors as cells differentiate.
Copyright (c) 2010 Elsevier Inc. All rights reserved.
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19 MeSH Terms
One-year surveillance of methicillin-resistant Staphylococcus aureus nasal colonization and skin and soft tissue infections in collegiate athletes.
Creech CB, Saye E, McKenna BD, Johnson BG, Jimenez N, Talbot TR, Bossung T, Gregory A, Edwards KM
(2010) Arch Pediatr Adolesc Med 164: 615-20
MeSH Terms: Adolescent, Adult, Athletes, Female, Football, Humans, Male, Methicillin-Resistant Staphylococcus aureus, Nose, Prospidium, Racquet Sports, Sports, Staphylococcal Infections, Staphylococcal Skin Infections
Show Abstract · Added February 3, 2014
OBJECTIVE - To determine the frequency and clinical importance of methicillin-resistant Staphylococcus aureus (MRSA) colonization in student athletes.
DESIGN - Prospective observational cohort study.
SETTING - A major university in the southeastern United States.
PARTICIPANTS - Student athletes participating in the men's football and women's lacrosse programs (N = 126). Main Exposure Monthly assessment of S aureus nasal colonization.
MAIN OUTCOME MEASURES - Trends in S aureus colonization over time and the occurrence of skin and soft tissue infections.
RESULTS - Methicillin-resistant S aureus nasal colonization varied significantly through the athletic season (4%-23%), peaking during times of highest athletic activity. This increase in colonization was not associated with the development of an outbreak of skin and soft tissue infections, and no single MRSA clone emerged as a dominant isolate.
CONCLUSIONS - During the athletic season, there is a considerable burden of MRSA colonization in student athletes; however, colonization alone appears to be insufficient to trigger an outbreak of staphylococcal infections. A combination of distinct molecular characteristics in the organism and specific host factors may govern the development of staphylococcal disease.
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14 MeSH Terms
Left-right differences on timed motor examination in children.
Roeder MB, Mahone EM, Gidley Larson J, Mostofsky SH, Cutting LE, Goldberg MC, Denckla MB
(2008) Child Neuropsychol 14: 249-62
MeSH Terms: Adolescent, Age Distribution, Child, Child Behavior, Child Development, Female, Fingers, Foot, Functional Laterality, Hand, Humans, Male, Motor Skills, Neuropsychological Tests, Practice, Psychological, Serial Learning, Sex Distribution, Time Factors
Show Abstract · Added May 27, 2014
Age-related change in the difference between left- and right-side speed on motor examination may be an important indicator of maturation. Cortical maturation and myelination of the corpus callosum are considered to be related to increased bilateral skill and speed on timed motor tasks. We compared left minus right foot, hand, and finger speed differences using the Revised Physical and Neurological Assessment for Subtle Signs (PANESS; Denckla, 1985); examining 130 typically developing right-handed children (65 boys, 65 girls) ages 7-14. Timed tasks included right and left sets of 20 toe taps, 10 toe-heel alternation sequences, 20 hand pats, 10 hand pronate-supinate sets, 20 finger taps, and 5 sequences of each finger-to-thumb apposition. For each individual, six difference scores between left- and right-sided speeded performances of timed motor tasks were analyzed. Left-right differences decreased significantly with age on toe tapping, heel-toe alternations, hand pronation-supination, finger repetition, and finger sequencing. There were significant gender effects for heel-toe sequences (boys showing a greater left-right difference than girls), and a significant interaction between age and gender for hand pronation-supination, such that the magnitude of the left-right difference was similar for younger, compared with older girls, while the difference was significantly larger for younger, compared to older boys. Speed of performing right and left timed motor tasks equalizes with development; for some tasks, the equalization occurs earlier in girls than in boys.
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18 MeSH Terms
Repression of Clostridium difficile toxin gene expression by CodY.
Dineen SS, Villapakkam AC, Nordman JT, Sonenshein AL
(2007) Mol Microbiol 66: 206-19
MeSH Terms: Bacterial Proteins, Bacterial Toxins, Clostridioides difficile, DNA Footprinting, DNA, Bacterial, Electrophoretic Mobility Shift Assay, Enterotoxins, Gene Deletion, Gene Expression Regulation, Bacterial, Mutagenesis, Insertional, Promoter Regions, Genetic, Protein Binding, RNA, Bacterial, RNA, Messenger, Repressor Proteins, Sigma Factor, Transcription, Genetic
Show Abstract · Added March 3, 2020
CodY, a global regulator of gene expression in low G + C Gram-positive bacteria, was found to repress toxin gene expression in Clostridium difficile. Inactivation of the codY gene resulted in derepression of all five genes of the C. difficile pathogenicity locus during exponential growth and stationary phase. CodY was found to bind with high affinity to a DNA fragment containing the promoter region of the tcdR gene, which encodes a sigma factor that permits RNA polymerase to recognize promoters of the two major toxin genes as well as its own promoter. CodY also bound, but with low affinity, to the toxin gene promoters, suggesting that the regulation of toxin gene expression by CodY occurs primarily through direct control of tcdR gene expression. Binding of CodY to the tcdR promoter region was enhanced in the presence of GTP and branched-chain amino acids, suggesting a link between nutrient limitation and the expression of C. difficile toxin genes.
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17 MeSH Terms
Molecular basis of the targeting of topoisomerase II-mediated DNA cleavage by VP16 derivatives conjugated to triplex-forming oligonucleotides.
Duca M, Guianvarc'h D, Oussedik K, Halby L, Garbesi A, Dauzonne D, Monneret C, Osheroff N, Giovannangeli C, Arimondo PB
(2006) Nucleic Acids Res 34: 1900-11
MeSH Terms: Antineoplastic Agents, Phytogenic, DNA, DNA Damage, DNA Footprinting, DNA Topoisomerases, Type II, Drug Delivery Systems, Enzyme Inhibitors, Etoposide, Humans, Oligodeoxyribonucleotides, Topoisomerase II Inhibitors
Show Abstract · Added March 5, 2014
Human topoisomerase II (topo II) is the cellular target for a number of widely used antitumor agents, such as etoposide (VP16). These agents 'poison' the enzyme and induce it to generate DNA breaks that are lethal to the cell. Topo II-targeted drugs show a limited sequence preference, triggering double-stranded breaks throughout the genome. Circumstantial evidence strongly suggests that some of these breaks induce chromosomal translocations that lead to specific types of leukaemia (called treatment-related or secondary leukaemia). Therefore, efforts are ongoing to decrease these secondary effects. An interesting option is to increase the sequence-specificity of topo II-targeted drugs by attaching them to triplex-forming oligonucleotides (TFO) that bind to DNA in a highly sequence-specific manner. Here five derivatives of VP16 were attached to TFOs. The active topo II poisons, once linked, induced cleavage 13-14 bp from the triplex end where the drug was attached. The use of triple-helical DNA structures offers an efficient strategy for targeting topo II-mediated cleavage to DNA specific sequences. Finally, drug-TFO conjugates are useful tools to investigate the mechanistic details of topo II poisoning.
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11 MeSH Terms