bluuebunny/crossref_metadata_2025_split huggingface dataset:
Detection of lymphangiogenesis by near‐infrared fluorescence imaging and responses to VEGF‐C during healing in a mouse full‐dermis thickness wound model
Authors: Hall Mary A. , Robinson Holly , Chan Wenyaw , Sevick‐Muraca Eva M. 
Published: June 2013

AbstractNoninvasive, longitudinal near‐infrared fluorescence (NIRF) imaging was used to detect and quantify lymphangiogenesis following a full‐dermis thickness incision in the presence and absence of locally administered vascular endothelial growth factor‐C (VEGF‐C), a well‐known regulator of lymphangiogenesis. Peripheral cytokines/chemokines were also measured in treated and sham‐injected animals. Lymphangiogenesis was detected via NIRF imaging by day 7–8 and confirmed by intravital microscopy, while angiogenesis was observed by day 2–3 postincision (PI). All lymph vessel parameters quantified were significantly greater on wounded vs. nonwounded sides of mice. Lymph vessel parameters appeared larger on wounded sides of VEGF‐C– relative to NaCl‐treated mice, although differences were not significant. Interleukin‐1α and interleukin‐22 were significantly elevated at day 7 PI relative to respective preincision levels in VEGF‐C‐treated mice, and decreased by day 21 PI to levels nearing those measured preincision. For the majority of cytokines/chemokines measured, mean responses were significantly greater in VEGF‐C– vs. NaCl‐treated animals. Local VEGF‐C administration may stimulate lymphangiogenesis during tissue repair and regeneration via mediating systemic cytokine/chemokine levels. NIRF imaging can be utilized to detect lymphangiogenesis during wound healing, and offers a promising platform to complement current methods for monitoring wound status and studying the effects of growth factors on healing.
Role of salivary vascular endothelial growth factor (VEGF) in palatal mucosal wound healing
Authors: Keswani Sundeep G. , Balaji Swathi , Le Louis D. , Leung Alice , Parvadia Jignesh K. , Frischer Jason , Yamano Seiichi , Taichman Norton , Crombleholme Timothy M. 
Published: June 2013

AbstractThe mucosa of alimentary tract heals more rapidly than cutaneous wounds. The underlying mechanisms of this enhanced healing have not been completely elucidated. Constant exposure to salivary growth factors has been shown to play a critical role in mucosal homeostasis and tissue repair. Angiogenesis also has an essential role in successful wound repair. One of the main angiogenic growth factors, vascular endothelial growth factor (VEGF), has a pleiotropic role in tissue repair via neovascularization, reepithelialization, and regulation of extracellular matrix. We have previously reported a critical role for salivary VEGF in bowel adaptation after small bowel resection. We hypothesize that salivary VEGF is an essential stimulus for oral mucosal tissue repair, and use the murine palatal wound model to test our hypothesis. In a loss‐of‐function experiment, we removed the primary source of VEGF production through selective submandibular gland (SMG) sialoadenectomy in a murine model and observed the effects on wound closure and neovascularization. We then performed a selective loss‐of‐function experiment using the protein VEGF‐Trap to inhibit salivary VEGF. In a gain‐of‐function experiment, we supplemented oral VEGF following SMG sialoadenectomy. After SMG sialoadenectomy, there was significant reduction in salivary VEGF level, wound closure, and vessel density. Lower levels of salivary VEGF were correlated with impaired neovascularization and reepithelialization. The selective blockade of VEGF using VEGF‐Trap resulted in a similar impairment in wound healing and neovascularization. The sole supplementation of oral VEGF after SMG sialoadenectomy rescued the impaired wound healing phenotype and restored neovascularization to normal levels. These data show a novel role for salivary‐VEGF in mucosal wound healing, and provide a basis for the development of novel therapeutics aimed at augmenting wound repair of the oral mucosa, as well as wounds at other sites in the alimentary tract.
Adenylyl cyclase 6 mediates the action of cyclic AMP‐dependent secretagogues in mouse pancreatic exocrine cells via protein kinase A pathway activation
Authors: Sabbatini Maria E. , D’Alecy Louis , Lentz Stephen I. , Tang Tong , Williams John A. 
Published: June 2013

Key points
Cyclic AMP (cAMP), produced from ATP and the enzyme adenylyl cyclase (AC), plays an important role in the regulation of pancreatic exocrine cells.
We identified five AC isoforms in pancreatic exocrine cells. AC3, AC4, AC6 and AC9 are expressed in both pancreatic acini and duct fragments, whereas AC7 is expressed only in duct fragments.
In mice deficient in AC6, cAMP formation and protein kinase A activation were impaired. As a consequence, a reduction in amylase secretion and pancreatic fluid production was observed.
These results indicate that AC6 plays a regulatory role in pancreatic exocrine cells.
Abstract  Both secretin and vasoactive intestinal polypeptide (VIP) receptors are responsible for the activation of adenylyl cyclases (ACs), which increase intracellular cyclic AMP (cAMP) levels in the exocrine pancreas. There are nine membrane‐associated isoforms, each with its own pattern of expression and regulation. In this study we sought to establish which AC isoforms play a regulatory role in pancreatic exocrine cells. Using RT‐PCR, AC3, AC4, AC6, AC7 and AC9 were found to be expressed in the pancreas. AC3, AC4, AC6 and AC9 were expressed in both pancreatic acini and ducts, whereas AC7 was expressed only in pancreatic ducts. Based on known regulation by intracellular signals, selective inhibitors and stimulators were used to suggest which isoforms play an important role in the induction of cAMP formation. AC6 appeared to be an important isoform because protein kinase A (PKA), PKC and calcium all inhibited VIP‐induced cAMP formation, whereas calcineurin or calmodulin did not modify the response to VIP. Mice with genetically deleted AC6 were studied and showed reduced cAMP formation and PKA activation in both isolated pancreatic acini and duct fragments. The absence of AC6 reduced cAMP‐dependent secretagogue‐stimulated amylase secretion, and abolished fluid secretion in both in vivo and isolated duct fragments. In conclusion, several AC isoforms are expressed in pancreatic acini and ducts. AC6 mediates a significant part of pancreatic amylase and fluid secretion in response to secretin, VIP and forskolin through cAMP/PKA pathway activation.
Classification of frequency response areas in the inferior colliculus reveals continua not discrete classes
Authors: Palmer Alan R. , Shackleton Trevor M. , Sumner Christian J. , Zobay Oliver , Rees Adrian 
Published: June 2013

Key points
Neurons in the auditory midbrain, the inferior colliculus, are selectively sensitive to combinations of sound frequency and level as illustrated by their frequency/level receptive fields. Different receptive field shapes have been described, but we do not know if these represent discrete classes reflecting afferent inputs from individual sources, or a more complex pattern of integration.
In this study we used objective methods to analyse the receptive fields of over 2000 neurons in the guinea pig inferior colliculus.
Subjectively we identified seven different receptive field classes, but objectively these classes formed continua with many neurons having receptive field shapes intermediate to these extremes.
These findings are consistent with neurons receiving inhibitory inputs of different strength and frequency disposition but not consistent with neurons reflecting inputs only from individual brainstem nuclei.
These results are important for understanding the functional organisation of the inferior colliculus and its role in auditory processing.
Abstract  A differential response to sound frequency is a fundamental property of auditory neurons. Frequency analysis in the cochlea gives rise to V‐shaped tuning functions in auditory nerve fibres, but by the level of the inferior colliculus (IC), the midbrain nucleus of the auditory pathway, neuronal receptive fields display diverse shapes that reflect the interplay of excitation and inhibition. The origin and nature of these frequency receptive field types is still open to question. One proposed hypothesis is that the frequency response class of any given neuron in the IC is predominantly inherited from one of three major afferent pathways projecting to the IC, giving rise to three distinct receptive field classes. Here, we applied subjective classification, principal component analysis, cluster analysis, and other objective statistical measures, to a large population (2826) of frequency response areas from single neurons recorded in the IC of the anaesthetised guinea pig. Subjectively, we recognised seven frequency response classes (V‐shaped, non‐monotonic Vs, narrow, closed, tilt down, tilt up and double‐peaked), that were represented at all frequencies. We could identify similar classes using our objective classification tools. Importantly, however, many neurons exhibited properties intermediate between these classes, and none of the objective methods used here showed evidence of discrete response classes. Thus receptive field shapes in the IC form continua rather than discrete classes, a finding consistent with the integration of afferent inputs in the generation of frequency response areas. The frequency disposition of inhibition in the response areas of some neurons suggests that across‐frequency inputs originating at or below the level of the IC are involved in their generation.
Maintaining tumor targeting accuracy in real‐time motion compensation systems for respiration‐induced tumor motion
Authors: Malinowski Kathleen , McAvoy Thomas J. , George Rohini , Dieterich Sonja , D'Souza Warren D. 
Published: June 2013

Purpose:To determine how best to time respiratory surrogate‐based tumor motion model updates by comparing a novel technique based on external measurements alone to three direct measurement methods.Methods:Concurrently measured tumor and respiratory surrogate positions from 166 treatment fractions for lung or pancreas lesions were analyzed. Partial‐least‐squares regression models of tumor position from marker motion were created from the first six measurements in each dataset. Successive tumor localizations were obtained at a rate of once per minute on average. Model updates were timed according to four methods:never, respiratory surrogate‐based (when metrics based on respiratory surrogate measurements exceeded confidence limits), error‐based (when localization error ≥3 mm), and always (approximately once per minute).Results:Radial tumor displacement prediction errors (mean ± standard deviation) for the four schema described above were 2.4 ± 1.2, 1.9 ± 0.9, 1.9 ± 0.8, and 1.7 ± 0.8 mm, respectively. Thenever‐update error was significantly larger than errors of the other methods. Mean update counts over 20 min were 0, 4, 9, and 24, respectively.Conclusions:The same improvement in tumor localization accuracy could be achieved through any of the three update methods, but significantly fewer updates were required when therespiratory surrogate method was utilized. This study establishes the feasibility of timing image acquisitions for updating respiratory surrogate models without direct tumor localization.
Synergistic Activity of Colistin plus Rifampin against Colistin-Resistant KPC-Producing Klebsiella pneumoniae
Authors: Tascini Carlo , Tagliaferri Enrico , Giani Tommaso , Leonildi Alessandro , Flammini Sarah , Casini Beatrice , Lewis Russell , Ferranti Simone , Rossolini Gian Maria , Menichetti Francesco 
Published: June 2013

ABSTRACT

Infections caused by carbapenem-resistant KPC-producing
Klebsiella pneumoniae
are responsible for high rates of mortality and represent a major therapeutic challenge, especially when the isolates are also resistant to colistin. We used the checkerboard method to evaluate the synergistic activity of 10 antibiotic combinations against 13 colistin-resistant KPC-producing
K. pneumoniae
isolates (colistin MIC range of 8 to 128 mg/liter). Colistin plus rifampin was the only combination that demonstrated consistent synergistic bacteriostatic activity against 13/13 strains tested, reducing the colistin MIC below the susceptibility breakpoint (MIC ≤ 2 mg/liter) in 7/13 strains at rifampin concentrations ranging from 4 to 16 mg/liter. Bactericidal synergistic activity was also documented for 8/13 tested strains. Other antimicrobial combinations with carbapenems, gentamicin, and tigecycline showed variously synergistic results. Colistin plus rifampin also exhibited bacteriostatic synergistic activity against 4/4 colistin-susceptible KPC-producing
K. pneumoniae
isolates (colistin MIC range of 0.5 to 2 mg/liter) and 4/4 ertapenem-resistant extended-spectrum beta-lactamase (ESBL)-producing
K. pneumoniae
isolates (ertapenem MIC range of 16 to 32 mg/liter). Collectively, our data suggest that colistin plus rifampin is the most consistently synergistic combination against KPC-producing
K. pneumoniae
isolates, including colistin-resistant strains. Colistin-rifampin combinations may have a role in the treatment of multidrug-resistant
K. pneumoniae
and may possibly slow the selection of heteroresistant subpopulations during colistin therapy.
A Modified Zinc Acetate Gel, a Potential Nonantiretroviral Microbicide, Is Safe and Effective against Simian-Human Immunodeficiency Virus and Herpes Simplex Virus 2 Infection
In Vivo
Authors: Kenney Jessica , Rodríguez Aixa , Kizima Larisa , Seidor Samantha , Menon Radhika , Jean-Pierre Ninochka , Pugach Pavel , Levendosky Keith , Derby Nina , Gettie Agegnehu , Blanchard James , Piatak Michael , Lifson Jeffrey D. , Paglini Gabriela , Zydowsky Thomas M. , Robbiani Melissa , Fernández Romero José A. 
Published: June 2013

ABSTRACT

We previously showed that a prototype gel comprising zinc acetate (ZA) in carrageenan (CG) protected mice against vaginal and rectal herpes simplex virus 2 (HSV-2) challenge as well as macaques against vaginal simian-human immunodeficiency virus reverse transcriptase (SHIV-RT) challenge. In this work, we modified buffers and cosolvents to obtain a stable, nearly iso-osmolal formulation and evaluated its safety and efficacy against SHIV-RT and HSV-2.
In vitro
toxicity to lactobacilli and
Candida albicans
was determined. Macaques were given daily doses of ZA and CG (ZA/CG) or CG alone vaginally for 14 days and challenged with SHIV-RT 24 h later. Mice were challenged vaginally or rectally with HSV-2 immediately after a single gel treatment to measure efficacy or vaginally 12 h after daily gel treatment for 7 days to evaluate the gel's impact on susceptibility to HSV-2 infection. The modified ZA/CG neither affected the viability of lactobacilli or
C. albicans
nor enhanced vaginal HSV-2 infection after daily ZA/CG treatment. Vaginal SHIV-RT infection of macaques was reduced by 66% (
P
= 0.006) when macaques were challenged 24 h after the last dose of gel. We observed 60% to 80% uninfected mice after vaginal (
P
< 0.0001) and rectal (
P
= 0.008) high-dose HSV-2 challenge. The modified ZA/CG gel is safe and effective in animal models and represents a potential candidate to limit the transmission of HIV and HSV-2.
First Description of KPC-2-Producing Klebsiella oxytoca in Brazil
Authors: Almeida Anna C. S. , Cavalcanti Felipe L. S. , Martins Willames M. B. , Vilela Marinalda A. , Gales Ana C. , Morais Junior Marcos A. , Morais Márcia M. C. 
Published: June 2013

ABSTRACT

The present work reports the detection of the first case of nosocomial
Klebsiella oxytoca
producing class A carbapenemase KPC-2 in Brazil. The isolate KPN106 carried a 65-kb IncW-type plasmid that harbors the
bla
KPC
gene and Tn
4401
b. Moreover, we detected the presence of a class 1 integron containing a new allele,
arr-8
, followed by a 5′-truncated
dhfrIIIc
gene. In view of the recent results, we emphasize the high variability of the bacterial and genetic hosts of this resistance determinant.
Agglutinating Secretory IgA Preserves Intestinal Epithelial Cell Integrity during Apical Infection by Shigella flexneri
Authors: Mathias Amandine , Longet Stéphanie , Corthésy Blaise 
Published: June 2013

ABSTRACTShigella flexneri, by invading intestinal epithelial cells (IECs) and inducing inflammatory responses of the colonic mucosa, causes bacillary dysentery. Although M cells overlying Peyer's patches are commonly considered the primary site of entry ofS. flexneri, indirect evidence suggests that bacteria can also use IECs as a portal of entry to the lamina propria. Passive delivery of secretory IgA (SIgA), the major immunoglobulin secreted at mucosal surfaces, has been shown to protect rabbits from experimental shigellosis, but no information exists as to its molecular role in maintaining luminal epithelial integrity. We have established that the interaction of virulentS. flexneriwith the apical pole of a model intestinal epithelium consisting of polarized Caco-2 cell monolayers resulted in the progressive disruption of the tight junction network and actin depolymerization, eventually resulting in cell death. The lipopolysaccharide (LPS)-specific agglutinating SIgAC5 monoclonal antibody (MAb), but not monomeric IgAC5 or IgGC20 MAbs of the same specificity, achieved protective functions through combined mechanisms, including limitation of the interaction betweenS. flexneriand epithelial cells, maintenance of the tight junction seal, preservation of the cell morphology, reduction of NF-κB nuclear translocation, and inhibition of proinflammatory mediator secretion. Our results add to the understanding of the function of SIgA-mediated immune exclusion by identifying a mode of action whereby the formation of immune complexes translates into maintenance of the integrity of epithelial cells lining the mucosa. This novel mechanism of protection mediated by SIgA is important to extend the arsenal of effective strategies to fight againstS. flexnerimucosal invasion.
Role of Klebsiella pneumoniae Type 1 and Type 3 Fimbriae in Colonizing Silicone Tubes Implanted into the Bladders of Mice as a Model of Catheter-Associated Urinary Tract Infections
Authors: Murphy Caitlin N. , Mortensen Martin S. , Krogfelt Karen A. , Clegg Steven 
Published: June 2013

ABSTRACT

Catheter-associated urinary tract infections are biofilm-mediated infections that cause a significant economic and health burden in nosocomial environments. Using a newly developed murine model of this type of infection, we investigated the role of fimbriae in implant-associated urinary tract infections by the Gram-negative bacterium
Klebsiella pneumoniae
, which is a proficient biofilm former and a commonly isolated nosocomial pathogen. Studies have shown that type 1 and type 3 fimbriae are involved in attachment and biofilm formation
in vitro
, and these fimbrial types are suspected to be important virulence factors during infection. To test this hypothesis, the virulence of fimbrial mutants was assessed in independent challenges in which mouse bladders were inoculated with the wild type or a fimbrial mutant and in coinfection studies in which the wild type and fimbrial mutants were inoculated together to assess the results of a direct competition in the urinary tract. Using these experiments, we were able to show that both fimbrial types serve to enhance colonization and persistence. Additionally, a double mutant had an additive colonization defect under some conditions, indicating that both fimbrial types have unique roles in the attachment and persistence in the bladder and on the implant itself. All of these mutants were outcompeted by the wild type in coinfection experiments. Using these methods, we are able to show that type 1 and type 3 fimbriae are important colonization factors in the murine urinary tract when an implanted silicone tube is present.
Republished research: Facilitated physical activity as a treatment for depressed adults: randomised controlled trial
Authors: Chalder Melanie , Wiles Nicola J , Campbell John , Hollinghurst Sandra P , Haase Anne M , Taylor Adrian H , Fox Kenneth R , Costelloe Ceire , Searle Aidan , Baxter Helen , Winder Rachel , Wright Christine , Turner Katrina M , Calnan Michael , Lawlor Deborah A , Peters Tim J , Sharp Deborah J , Montgomery Alan A , Lewis Glyn 
Published: June 2013

Study questionDoes facilitated physical activity provide an effective treatment for adults with depression presenting in primary care?Summary answerAlthough trial participants receiving the physical activity intervention in addition to usual care reported increased physical activity compared with those receiving usual care alone, there was no evidence to suggest that the intervention brought about any improvement in depressive symptoms or reduction in antidepressant use.What is known and what this paper addsNumerous studies have reported the positive effects of physical activity, but most of the current evidence originates from small non-clinical samples using interventions that are not practicable in a healthcare setting. Our results indicate that offering patients a facilitated physical activity intervention is not an effective strategy for reducing symptoms of depression, although it increased self reported physical activity and sustained this effect over 12 months.
HYPERMOBILITY- A RISK FACTOR FOR RECURRENT SHOULDER DISLOCATIONS
Authors: Akhtar Muhammad Adeel , Jenkins Paul , Ashton Fiona , Robinson Christopher Michael 
Published: June 2013

BackgroundHypermobility is associated with increased risk of sporting injuries. This study was performed to assess the risk of recurrent shoulder dislocations in patients with hypermobility.MethodsProspective data was collected for 38 patients with primary shoulder dislocations between October 2008 and July 2009 including demographic details, contact sport played, hypermobility, family history of laxity and Benign Joint Hypermobility Syndrome (BJHS). Electronic records from emergency and orthopaedic departments were checked in January 2013 to confirm recurrent shoulder dislocation. Beighton score of 6 or above was used for hypermobility. Brighton criteria were used to diagnose BJHS.ResultsThe mean age was 25 years (range 15–55). There were 35 males and 3 females. twenty-two patients (58%) were involved in contact sports and most common sport played was rugby in twelve patients (55%). The mean Beighton score for these patients was 3.6 (range 0–9). Ten patients (26%) in this group had a Beighton score of 6 or more indicating hypermobility (Group A). twenty-eight patients (74%) had Beighton score less than 6 (Group B).The mean age for Group A (10 patients) was 26 years (range 15–55). There were 9 males and 1 female. Five patients were involved in contact sports. Six patients (60%) in this group had a recurrent shoulder dislocation. The mean Beighton score for these patients was 7.4 (range 6–9). Three patients (30%) had BJHS and six patients (60%) had a family history of laxity.The mean age for Group B (28 patients) was 25 years (range 15–44). There were 26 males and 2 females. Eleven patients (39%) were involved in contact sports. The mean Beighton score for these patients was 2 (range 0–5). One patient (3%) had BJHS and three patients (11%) had a family history of laxity. Eleven patients (39%) in this group had a recurrent shoulder dislocation.Discussion/ConclusionHypermobile patients had a higher incidence of recurrent shoulder dislocations (60% vs 39%). 30% patients fulfilled the Brighton criteria for BJHS and 60% had a family history of laxity. These factors should be assessed in patients after primary shoulder dislocation to decide appropriate rehabilitation and treatment plan to prevent recurrence.