Objectives The targeted disruption of biofilms in chronic wounds is an important treatment strategy and the subject of intense research. In the present study, an in vitro model of chronic wound ...biofilms was developed to assess the efficacy of antimicrobial treatments for use in the wound environment. Methods Using chronic wound isolates, assays of bacterial coaggregation established that aerobic and anaerobic wound bacteria were able to coaggregate and form biofilms. A constant depth film fermenter (CDFF) was used to develop wound biofilms in vitro, which were analysed using light microscopy and scanning electron microscopy. The susceptibility of bacteria within these biofilms was examined in response to the most frequently prescribed ‘chronic wound’ antibiotics and a series of iodine- and silver-containing commercial antimicrobial products and lactoferrin. Results Defined biofilms were rapidly established within 1–2 days. Antibiotic treatment demonstrated that mixed Pseudomonas and Staphylococcus biofilms were not affected by ciprofloxacin (5 mg/L) or flucloxacillin (15 mg/L), even at concentrations equivalent to twice the observed peak serum levels. The results contrasted with the ability of povidone–iodine (1%) to disrupt the wound biofilm; an effect that was particularly pronounced in the dressing testing where iodine-based dressings completely disrupted established 7 day biofilms. In contrast, only two of six silver-containing dressings exhibited any effect on 3 day biofilms, with no effect on 7 day biofilms. Conclusions This wound model emphasizes the potential role of the biofilm phenotype in the observed resistance to antibiotic therapies that may occur in chronic wounds in vivo.
The origin of albuminuria remains controversial owing to difficulties in quantifying the actual amount of albumin filtered by the kidney. Here we use fluorescently labeled albumin, together with the ...powerful technique of intravital 2-photon microscopy to show that renal albumin filtration in non-proteinuric rats is ~50 times greater than previously measured and is followed by rapid endocytosis into proximal tubule cells (PTCs). The endocytosed albumin appears to undergo transcytosis in large vesicles (500nm in diameter), identified by immunogold staining of endogenous albumin by electron microscopy, to the basolateral membrane where the albumin is disgorged back to the peritubular blood supply. In nephrotic rats, the rate of uptake of albumin by the proximal tubule (PT) is decreased. This is consistent with reduced expression of clathrin, megalin, and vacuolar H+-ATPase A subunit, proteins that are critical components of the PT endocytotic machinery. These findings strongly support the paradigm-shifting concept that the glomerular filter normally leaks albumin at nephrotic levels. Albuminuria does not occur as this filtered albumin load is avidly bound and retrieved by PTCs. Dysfunction of this retrieval pathway leads to albuminuria. Thus, restoration of the defective endocytotic and processing function of PT epithelial cells might represent an effective strategy to limit urinary albumin loss, at least in some types of nephrotic syndrome.
Objectives
Although much research examining youth psychopathology from an ecological family systems theoretical framework has highlighted negative or pathological parental characteristics, it is ...important to identify and explore beneficial parent characteristics, such as mindful attention and awareness, that may be related to youth mental health. Dispositional mindfulness has been related, in cross-sectional research, to higher levels of mindful parenting, which impacts positive and negative parenting and, in turn, offspring internalizing and externalizing symptoms. The current study expands this work by examining associations among caregiver dispositional mindful attention, mindful parenting, parenting behaviors, and youth psychopathology in a short-term longitudinal model and by testing potential moderators.
Methods
A sample of 564 parents (60% mothers) of children between the ages of 3 and 17 reported on their dispositional mindful attention, mindful parenting, positive and negative parenting practices, and their youth’s internalizing and externalizing symptoms at 4 time points over a 12-month period.
Results
The structural equation model indicated that higher levels of baseline caregiver dispositional mindful attention were related to higher levels of mindful parenting at 4 months. Higher levels of mindful parenting were associated with higher levels of positive parenting and lower levels of negative parenting practices at 8 months. Finally, lower levels of negative parenting practices were related to lower levels of internalizing and externalizing symptoms at 12 months. Moderator analyses suggested that all prospective associations in the model were equivalent for mothers and fathers, boys and girls, and children and adolescents.
Conclusions
Findings shed light on the importance of considering caregiver dispositional mindful attention as it relates to parenting behaviors and youth mental health.
We have measured parity-violating asymmetries in elastic electron-proton scattering over the range of momentum transfers 0.12 < or =Q2 < or =1.0 GeV2. These asymmetries, arising from interference of ...the electromagnetic and neutral weak interactions, are sensitive to strange-quark contributions to the currents of the proton. The measurements were made at Jefferson Laboratory using a toroidal spectrometer to detect the recoiling protons from a liquid hydrogen target. The results indicate nonzero, Q2 dependent, strange-quark contributions and provide new information beyond that obtained in previous experiments.
ONJ has been increasingly suspected to be a potential complication of bisphosphonate therapy in recent years. Thus, the ASBMR leadership appointed a multidisciplinary task force to address key ...questions related to case definition, epidemiology, risk factors, diagnostic imaging, clinical management, and future areas for research related to the disorder. This report summarizes the findings and recommendations of the task force.
Introduction: The increasing recognition that use of bisphosphonates may be associated with osteonecrosis of the jaw (ONJ) led the leadership of the American Society for Bone and Mineral Research (ASBMR) to appoint a task force to address a number of key questions related to this disorder.
Materials and Methods: A multidisciplinary expert group reviewed all pertinent published data on bisphosphonate‐associated ONJ. Food and Drug Administration drug adverse event reports were also reviewed.
Results and Conclusions: A case definition was developed so that subsequent studies could report on the same condition. The task force defined ONJ as the presence of exposed bone in the maxillofacial region that did not heal within 8 wk after identification by a health care provider. Based on review of both published and unpublished data, the risk of ONJ associated with oral bisphosphonate therapy for osteoporosis seems to be low, estimated between 1 in 10,000 and <1 in 100,000 patient‐treatment years. However, the task force recognized that information on incidence of ONJ is rapidly evolving and that the true incidence may be higher. The risk of ONJ in patients with cancer treated with high doses of intravenous bisphosphonates is clearly higher, in the range of 1–10 per 100 patients (depending on duration of therapy). In the future, improved diagnostic imaging modalities, such as optical coherence tomography or MRI combined with contrast agents and the manipulation of image planes, may identify patients at preclinical or early stages of the disease. Management is largely supportive. A research agenda aimed at filling the considerable gaps in knowledge regarding this disorder was also outlined.
Urban tuberculosis (TB) clinic, Nashville, Tennessee, USA.
Chest radiographs (CXRs) help in the diagnosis of pulmonary TB, but may be normal. Mycobacterium tuberculosis in culture is diagnostic of ...TB, but cultures are not routinely obtained in resource-poor settings. We examined rates and risk factors for pulmonary TB associated with normal CXR.
An observational cohort study was performed among all respiratory culture-positive TB cases referred to the Nashville Health Department from October 1992 to July 2003. Clinical factors, demographics and underlying medical conditions were assessed.
Of 601 study patients, 53 (9%) had normal CXRs: 31/138 (22%) were human immunodeficiency virus (HIV) infected and 22/463 (5%) were non-HIV-infected/unknown (P<0.001). Among HIV-infected patients, normal CXR was more likely in persons with renal failure (13% vs. 3%, P=0.048). Among non-HIV-infected/unknown patients, normal CXR was more likely in those who were asymptomatic at presentation (32% vs. 13%, P=0.022). In multivariable logistic regression analysis, HIV infection was associated with an increased risk of normal CXR (odds ratio OR 6.61, P<0.0001); factors associated with reduced risk were dyspnea (OR 0.24, P=0.026), positive sputum smear (OR 0.45, P=0.028) and cough (OR 0.48, P=0.038).
The rate of normal CXR among persons with culture-confirmed pulmonary TB was high. Respiratory specimen cultures should be obtained in TB suspects with a normal CXR, particularly HIV-infected persons.
We investigated the validity and reliability of diagnoses made by eight neuropathologists who used the preliminary NINDS neuropathologic diagnostic criteria for progressive supranuclear palsy (PSP) ...and related disorders. The specific disorders were typical, atypical, and combined PSP, postencephalitic parkinsonism, corticobasal ganglionic degeneration, and Pickʼs disease. These disorders were chosen because of the difficulties in their neuropathologic differentiation. We assessed validity by measuring sensitivity and positive predictive value. Reliability was evaluated by measuring pairwise and group agreement. From a total of 62 histologic cases, each neuropathologist independently classified 16 to 19 cases for the pairwise analysis and 5 to 6 cases for the group analysis. The neuropathologists were unaware of the study design, unfamiliar with the assigned cases, and initially had no clinical information about the cases. Our results showed that with routine sampling and staining methods, neuropathologic examination alone was not fully adequate for differentiating the disorders. The main difficulties were discriminating the subtypes of PSP and separating postencephalitic parkinsonism from PSP. Corticobasal ganglionic degeneration and Pickʼs disease were less difficult to distinguish from PSP. The addition of minimal clinical information contributed to the accuracy of the diagnosis. On the basis of results obtained, we propose clinicopathologic diagnostic criteria to improve on the NINDS criteria
Aim We examined relationships between breeding bird distribution of 10 forest songbirds in the Great Lakes Basin, large-scale climate and the distribution of land cover types as estimated by advanced ...very high resolution radiometer (AVHRR) and multi-spectral scanner (MSS) land cover classifications. Our objective was to examine the ability of regional climate, AVHRR (1 km resolution) land cover and MSS (200 m resolution) land cover to predict the distribution of breeding forest birds at the scale of the Great Lakes Basin and at the resolution of Breeding Bird Atlas data (5-10 km2). Specifically we addressed the following questions. (1) How well do AVHRR or MSS classifications capture the variation in distribution of bird species? (2) Is one land cover classification more useful than the other for predicting distribution? (3) How do models based on climate compare with models based on land cover? (4) Can the combination of both climate and land cover improve the predictive ability of these models. Location Modelling was conducted over the area of the Great Lakes Basin including parts of Ontario, Canada and parts of Illinois, Indiana, Michigan, New York, Ohio, Pennsylvania Wisconsin, and Minnesota, USA. Methods We conducted single variable logistic regression with the forest classes of AVHRR and MSS land cover using evidence of breeding as the response variable. We conducted multiple logistic regression with stepwise selection to select models from five sets of explanatory variables (AVHRR, MSS, climate, AVHRR + climate, MSS + climate). Results Generally, species were related to both AVHRR and MSS land cover types in the direction expected based on the known local habitat use of the species. Neither land cover classification appeared to produce consistently more intuitive results. Good models were generated using each of the explanatory data sets examined here. And at least one but usually all five variable sets produced acceptable or excellent models for each species. Main conclusions Both climate and large scale land cover were effective predictors of the distribution of the 10 forest bird species examined here. Models generated from these data had good classification accuracy of independent validation data. Good models were produced from all explanatory data sets or combinations suggesting that the distribution of climate, AVHRR land cover, and MSS land cover all captured similar variance in the distribution of the birds. It is difficult to separate the effects of climate and vegetation on the species' distributions at this scale.
Background: Angiogenesis, the formation of new vessels from the existing vasculature, is a critical process during early development as well as in a number of disease processes. Tie2 (also known as ...Tek) is an endothelium-specific receptor tyrosine kinase involved in both angiogenesis and vasculature maintenance.
Results: We have determined the crystal structure of the Tie2 kinase domain to 2.2 Å resolution. The structure contains the catalytic core, the kinase insert domain (KID), and the C-terminal tail. The overall fold is similar to that observed in other serine/threonine and tyrosine kinase structures; however, several unique features distinguish the Tie2 structure from those of other kinases. The Tie2 nucleotide binding loop is in an inhibitory conformation, which is not seen in other kinase structures, while its activation loop adopts an “activated-like” conformation in the absence of phosphorylation. Tyr-897, located in the N-terminal domain, may negatively regulate the activity of Tie2 by preventing dimerization of the kinase domains or by recruiting phosphatases when it is phosphorylated.
Conclusion: Regulation of the kinase activity of Tie2 is a complex process. Conformational changes in the nucleotide binding loop, activation loop, C helix, and the C-terminal tail are required for ATP and substrate binding.
We have measured the beam-normal single-spin asymmetry in elastic scattering of transversely polarized 3 GeV electrons from unpolarized protons at Q2=0.15, 0.25 (GeV/c)2. The results are inconsistent ...with calculations solely using the elastic nucleon intermediate state and generally agree with calculations with significant inelastic hadronic intermediate state contributions. A(n) provides a direct probe of the imaginary component of the 2gamma exchange amplitude, the complete description of which is important in the interpretation of data from precision electron-scattering experiments.
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