A Novel Nomogram to Identify Candidates for Extended Pelvic Lymph Node Dissection Among Patients with Clinically Localized Prostate Cancer Diagnosed with Magnetic Resonance Imaging-targeted and Systematic Biopsies

Background

Available models for predicting lymph node invasion (LNI) in prostate cancer (PCa) patients undergoing radical prostatectomy (RP) might not be applicable to men diagnosed via magnetic resonance imaging (MRI)-targeted biopsies.

Profilin-mediated food-induced allergic reactions are associated with oral epithelial remodeling

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Adult trkB Signaling in Parvalbumin Interneurons is Essential to Prefrontal Network Dynamics

Inhibitory interneurons expressing parvalbumin (PV) are central to cortical network dynamics, generation of γ oscillations, and cognition. Dysfunction of PV interneurons disrupts cortical information processing and cognitive behavior. Brain-derived neurotrophic factor (BDNF)/tyrosine receptor kinase B (trkB) signaling regulates the maturation of cortical PV interneurons but is also implicated in their adult multidimensional functions. Using a novel viral strategy for cell-type-specific and spatially restricted expression of a dominant-negative trkB (trkB.DN), we show that BDNF/trkB signaling is essential to the integrity and maintenance of prefrontal PV interneurons in adult male and female mice. Reduced BDNF/trkB signaling in PV interneurons in the medial prefrontal cortex (mPFC) resulted in deficient PV inhibition and increased baseline local field potential (LFP) activity in a broad frequency band. The altered network activity was particularly pronounced during increased activation of the prefrontal network and was associated with changed dynamics of local excitatory neurons, as well as decreased modulation of the LFP, abnormalities that appeared to generalize across stimuli and brain states. In addition, our findings link reduced BDNF/trkB signaling in prefrontal PV interneurons to increased aggression. Together our investigations demonstrate that BDNF/trkB signaling in PV interneurons in the adult mPFC is essential to local network dynamics and cognitive behavior. Our data provide direct support for the suggested association between decreased trkB signaling, deficient PV inhibition, and altered prefrontal circuitry.SIGNIFICANCE STATEMENT Brain-derived neurotrophic factor (BDNF)/tyrosine receptor kinase B (trkB) signaling promotes the maturation of inhibitory parvalbumin (PV) interneurons, neurons central to local cortical dynamics, γ rhythms, and cognition. Here, we used a novel viral approach for reduced BDNF/trkB signaling in PV interneurons in the medial prefrontal cortex (mPFC) to establish the role of BDNF/trkB signaling in adult prefrontal network activities. Reduced BDNF/trkB signaling caused pronounced morphologic alterations, reduced PV inhibition, and deficient prefrontal network dynamics. The altered network activity appeared to manifest across stimuli and brain states and was associated with aberrant local field potential (LFP) activities and increased aggression. The results demonstrate that adult BDNF/trkB signaling is essential to PV inhibition and prefrontal circuit function and directly links BDNF/trkB signaling to network integrity in the adult brain.     

Long-term outcome after early repair of iatrogenic bile duct injury. A national Danish multicentre study

Background

The aim of this retrospective study was to evaluate the peri-operative and long-term outcome after early repair with a hepaticojejunostomy (HJ).

Methods

Between 1995 and 2010, a nationwide, retrospective multi-centre study was conducted. All iatrogenic bile duct injury (BDI) sustained during a cholecystectomy and repaired with HJ in the five Hepato-Pancreatico-Biliary centres in Denmark were included.

Results

In total, 139 patients had an HJ repair. The median time from the BDI to reconstruction was 5 days. A concomitant vascular injury was identified in 26 cases (19%). Post-operative morbidity was 36% and mortality was 4%. Forty-two patients (30%) had a stricture of the HJ. The median follow-up time without stricture was 102 months. Nineteen out of the 42 patients with post-reconstruction biliary strictures had a re-HJ. Twenty-three patients were managed with percutaneous transhepatic cholangiography and dilation. The overall success rate of re-establishing the biliodigestive flow approached 93%. No association was found between timing of repair, concomitant vascular injury, level of injury and stricture formation.

Conclusion

In this national, unselected and consecutive cohort of patients with BDI repaired by early HJ we found a considerable risk of long-term complications (e.g. 30% stricture rate) and mortality in both the short- and the long-term perspective.     

Decreased plasminogen activator inhibitor and tissue metalloproteinase inhibitor expression may promote increased metalloproteinase activity with increasing duration of human atrial fibrillation

Introduction: Atrial fibrosis has been shown to concur with the persistence of atrial fibrillation (AF) and is only incompletely reversible, thus counteracting attempts to restore and maintain sinus rhythm (SR). Besides the angiotensin system, the matrix metalloproteinases (MMP) play a major role in the pathogenesis of fibrosis. Thus, the present study investigated changes of the MMP system during the development of human AF.
Methods and Results: Right atrial appendages of 146 patients were excised during heart surgery and grouped according to rhythm (SR vs AF) and AF duration. Hydroxyproline as a surrogate for collagen content and morphometrically determined collagen content increased significantly from SR (14.3 ± 7.7%) to chronic permanent AF (CAF) of 6–24 months (21.2 ± 9.2%, P = 0.02), and CAF of > 60 months (25.3 ± 4.7%, P < 0.01). From SR to paroxysmal and chronic persistent AF (CPAF) and to CAF MMP-2 and MMP-9 activity rose, while their mRNA and protein levels were not altered significantly. Plasminogen activator inhibitor (PAI), an inhibitor of a potent activator of many MMPs, was significantly decreased with increasing duration of AF. In parallel, the mRNA levels of the tissue inhibitors of MMPs TIMP-1 and -2 decreased significantly.
Conclusion: Human atrial fibrogenesis is enhanced with increasing duration of AF: a longer AF duration is associated with elevated atrial interstitial MMP activity, but decreased PAI and TIMP expression.     

Increased postoperative peritoneal adhesion formation after the treatment of experimental peritonitis with chlorhexidine

Background and aims Chlorhexidine is known as a substance that produces adhesions. However, in an experimental model of peritoneal injury, lavage with chlorhexidine and saline solutions produced a similar number of adhesions. This study was designed to test the hypothesis that chlorhexidine gluconate 0.05% solution used for the treatment of peritonitis increases formation of postoperative peritoneal adhesions as compared to standard lavage with saline solution.Material and methods Forty Wistar rats were randomly allocated to gastric or faecal peritonitis groups. In each group rats were further randomly subdivided into saline or chlorhexidine peritoneal lavage groups. After 30 days the rats were killed and intraperitoneal adhesions were evaluated by adhesion score and grading.Results Adhesion scores were statistically significantly different between saline and chlorhexidine groups in both gastric and faecal peritonitis models. In the faecal peritonitis chlorhexidine group a 20% small bowel intussusception rate was observed, while there were no such complications in the other study groups. The conglomerate of organs formed by dense adhesions was present in 60% of cases when gastric peritonitis was lavaged by chlorhexidine and in only 10% when saline solution was used (P<0.05). Neither chlorhexidine nor saline solutions have caused such dense adhesions in faecal peritonitis.Conclusion Peritoneal lavage with chlorhexidine gluconate 0.05% solution in the treatment of experimental peritonitis results in increased adhesion formation.     

Network Asynchrony Underlying Increased Broadband Gamma Power

Synchronous activity of cortical inhibitory interneurons expressing parvalbumin (PV) underlies expression of cortical γ rhythms. Paradoxically, deficient PV inhibition is associated with increased broadband γ power in the local field potential. Increased baseline broadband γ is also a prominent characteristic in schizophrenia and a hallmark of network alterations induced by NMDAR antagonists, such as ketamine. Whether enhanced broadband γ is a true rhythm, and if so, whether rhythmic PV inhibition is involved or not, is debated. Asynchronous and increased firing activities are thought to contribute to broadband power increases spanning the γ band. Using male and female mice lacking NMDAR activity specifically in PV neurons to model deficient PV inhibition, we here show that neuronal activity with decreased synchronicity is associated with increased prefrontal broadband γ power. Specifically, reduced spike time precision and spectral leakage of spiking activity because of higher firing rates (spike “contamination”) affect the broadband γ band. Desynchronization was evident at multiple time scales, with reduced spike entrainment to the local field potential, reduced cross-frequency coupling, and fragmentation of brain states. Local application of S(+)-ketamine in (control) mice with intact NMDAR activity in PV neurons triggered network desynchronization and enhanced broadband γ power. However, our investigations suggest that disparate mechanisms underlie increased broadband γ power caused by genetic alteration of PV interneurons and ketamine-induced power increases in broadband γ. Our study confirms that enhanced broadband γ power can arise from asynchronous activities and demonstrates that long-term deficiency of PV inhibition can be a contributor.SIGNIFICANCE STATEMENT Brain oscillations are fundamental to the coordination of neuronal activity across neurons and structures. γ oscillations (30-80 Hz) have received particular attention through their association with perceptual and cognitive processes. Synchronous activity of inhibitory parvalbumin (PV) interneurons generates cortical γ oscillation, but, paradoxically, PV neuron deficiency is associated with increases in γ oscillations. We here reconcile this conundrum and show how deficient PV inhibition can lead to increased and asynchronous excitatory firing, contaminating the local field potential and manifesting as increased γ power. Thus, increased γ power does not always reflect a genuine rhythm. Further, we show that ketamine-induced γ increases are caused by separate network mechanisms.     

Electroless Platinum Deposition Using Co3+/Co2+ Redox Couple as a Reducing Agent

In the present work, the kinetics of electroless deposition of Pt, using a cobalt ion redox system (Co³⁺/Co²⁺) as a reducing agent, has been investigated. The deposition rate of Pt depends on the pH, concentration of reactants, and temperature. The deaeration and bubbling of the plating solution with argon play an essential role. It was found that 0.11 mg cm⁻² of Pt films could be deposited on the surface of a roughed glass sheet in one hour without replenishing the solution. Additional data have been obtained on the grounds of electrochemical quartz crystal microbalance experiments. The bubbling (agitation) of the electroless Pt plating solution with argon during the deposition of Pt results in a higher deposition rate and is ca. 3 µg cm⁻² min⁻¹. The Pt deposition rate is far less, and is as low as 0.14 µg cm⁻² min⁻¹ when the electroless Pt plating solution is not bubbled with argon during the deposition of Pt.     

Metabolomics in pancreatic cancer biomarkers research

Pancreatic cancer is one of the worst prognoses of all malignancies. More than 40,000 deaths a year from this disease are observed in European Union alone. The only possibly curative treatment of pancreatic cancer is surgery, yet only 15–20% of patients have operable disease and even patients, which go through surgery and adjuvant chemotherapy, survival is less than 30%. The sensitive and specific biomarkers which could be used for the advance of early diagnostics are needed and constantly researched. Metabolomics is a technology which analyzes the concentrations of low-molecular-weight metabolites (the metabolome) has lately effectively developed due to the improvements in analytical technology. Metabolome analysis can be a one of the useful approaches for the biomarker discovery and disease diagnosis. Here we discuss recent discoveries in the field of pancreatic cancer metabolomics as well as the most promising biomarkers for diagnostics, prognosis and prediction.