The Vascularization Pattern of the Colon and Surgical Decision in Esophageal Reconstruction with Colon. A Selective SMA and IMA Arteriographic Study

Rezumat Pattern-ul de vascularizaåie al colonului aei decizia chirurgicalã în reconstrucåia esofagianã cu colon -studiu arteriografic selectiv al AMS aei AMI Introducere: Indiferent de tehnica reconstructivã, conceptele de fundamentare din reconstrucåia visceralã au ca baza principalã suportul vascular necesar pentru grefonul de substituåie. Particularitãåile vasculare individuale pot înclina sau chiar obliga chirurgul la o anumitã opåiune cãtre unul sau altul dintre procedee. De aceea, vascularizaåia este, fãrã îndoialã, factorul care dominã mobilizarea colonului pentru reconstrucåia esofagianã. Material aei metodã: Studiul nostru arteriografic aei-a propus o investigaåie asupra tiparului vascular al celor douã surse principale ce participã prin vasele emergente la irigarea arterialã a colonului: a. mezentericã superioarã (AMS) respectiv a. mezentericã inferioarã (AMI). Nu am avut în vedere selectarea pacienåilor dupã un anumit criteriu dupã cum nu am realizat nici o excludere dintr-un anumit considerent. Lotul de studiu a constat din 49 de pacienåi care s-au prezentat în clinicã pentru o tehnicã reconstructivã, toåi aparåinând perioadei 2000-2010. În intervalul 1981-2012, au fost efectuate 187 de tehnici reconstructive pentru o indicaåie postcausticã. Din totalul de 49 de pacienåi, 11 bolnavi suferiserã intervenåii chirurgicale abdominale majore iar dintre aceaetia, 5 cu tentative nereuaeite de reconstrucåie. Rezultate: Din cei 49 de pacienåi la care s-a efectuat explorarea, arteriografia a evidenåiat o situaåie favorabilã reconstrucåiei la 31 dintre aceştia. La ceilalåi 18 pacienåi au fost identificate anomalii ori distribuåii atipice, 5 ale AMS respectiv 13 ale AMI. Decizia operatorie a fost ajustatã la 22 de bolnavi. Un lucru important de semnalat dpdv predictiv asupra viscerul de mobilizat: nu am avut necroze de grefon la pacienåii cu examinare arteriograficã preoperatorie. Concluzii: Dictate de necesitatea unei bune mobilizãri, ligaturile arteriale trebuie adaptate şi modificate în funcåie de particularitãåile de distribuåie vascularã, astfel încât sã se menåinã un flux sangvin suficient în arcada marginalã pânã la nivelul secåiunilor colice şi, implicit, în arterele drepte din vecinãtatea acestora. main grounds the mandatory vascular support for the graft replacement. Individual vascular particularities can influence or even oblige the surgeon to choose a certain procedure. This is why the vascularization is beyond doubt the dominant factor in mobilizing the colon for reconstruction. Material and method: Our arteriographic study entails an investigation upon the vascularization pattern of the two main sources that participate in the arterial irrigation of the colon via the emerging vessels: superior mesenteric artery (SMA) and inferior mesenteric artery (IMA). We did not consider certain patients upon a specific criterion; also, we did not exclude any patients due to various reasons. We took into account 49 patients as study group, all of them having registered into the clinic for a reconstructive technique, throughout the years from 2000 to 2010. From 1981 to 2012 there have been 187 reconstructive techniques performed due to post caustic pathology. From a total of 49 patients, 11 had suffered major abdominal surgeries, 5 of which had had unsuccessful reconstructive attempts. Results: Out of the 49 patients on whom we have performed the exploration, arteriography showed a favorable situation for reconstruction in 31 of them. In the other 18 patients anomalies or atypical distributions were identified, in 5 of the SMA and in 13 of the IMA, respectively. Operative decision was modified in 22 patients. One important thing to note from the point of view of the segment to be moved: we had no graft necrosis in patients with preoperative arteriographic examination. Conclusions: Due to the need for good mobilization, arterial ligations should be adjusted and modified depending on the particular vascular distribution, to maintain a sufficient blood flow in the marginal artery, in order to reach the colic sections and the straight arteries near them. Abbreviations: SMA -superior mesenteric artery; IMAinferior mesenteric artery; ICa -ileocolic artery; RCa -right colic artery; MCa -middle colic artery; LCa -left colic artery; LC acc.a -left accessory colic artery (or middle left colic artery); ILCa -inferior left colic artery; S trunk -sigmoidian trunk; Sa -sigmoidian artery; SRa -superior rectal arter

Moments of spectral functions: Monte Carlo evaluation and verification

The subject of the present study is the Monte Carlo path-integral evaluation of the moments of spectral functions. Such moments can be computed by formal differentiation of certain estimating functionals that are infinitely-differentiable against time whenever the potential function is arbitrarily smooth. Here, I demonstrate that the numerical differentiation of the estimating functionals can be more successfully implemented by means of pseudospectral methods (e.g., exact differentiation of a Chebyshev polynomial interpolant), which utilize information from the entire interval $(-\beta \hbar / 2, \beta \hbar/2)$. The algorithmic detail that leads to robust numerical approximations is the fact that the path integral action and not the actual estimating functional are interpolated. Although the resulting approximation to the estimating functional is non-linear, the derivatives can be computed from it in a fast and stable way by contour integration in the complex plane, with the help of the Cauchy integral formula (e.g., by Lyness' method). An interesting aspect of the present development is that Hamburger's conditions for a finite sequence of numbers to be a moment sequence provide the necessary and sufficient criteria for the computed data to be compatible with the existence of an inversion algorithm. Finally, the issue of appearance of the sign problem in the computation of moments, albeit in a milder form than for other quantities, is addressed.Comment: 13 pages, 2 figure

Fast Convergence of Path Integrals for Many-body Systems

We generalize a recently developed method for accelerated Monte Carlo calculation of path integrals to the physically relevant case of generic many-body systems. This is done by developing an analytic procedure for constructing a hierarchy of effective actions leading to improvements in convergence of $N$-fold discretized many-body path integral expressions from 1/N to $1/N^p$ for generic $p$. In this paper we present explicit solutions within this hierarchy up to level $p=5$. Using this we calculate the low lying energy levels of a two particle model with quartic interactions for several values of coupling and demonstrate agreement with analytical results governing the increase in efficiency of the new method. The applicability of the developed scheme is further extended to the calculation of energy expectation values through the construction of associated energy estimators exhibiting the same speedup in convergence.Comment: 20 pages, 6 figures, 1 tabl

Pro-inflammatory endothelial cell dysfunction is associated with intersectin-1s down-regulation

<p>Abstract</p> <p>Background</p> <p>The response of lung microvascular endothelial cells (ECs) to lipopolysaccharide (LPS) is central to the pathogenesis of lung injury. It is dual in nature, with one facet that is pro-inflammatory and another that is cyto-protective. In previous work, overexpression of the anti-apoptotic Bcl-X_L rescued ECs from apoptosis triggered by siRNA knockdown of intersectin-1s (ITSN-1s), a pro-survival protein crucial for ECs function. Here we further characterized the cyto-protective EC response to LPS and pro-inflammatory dysfunction.</p> <p>Methods and Results</p> <p>Electron microscopy (EM) analyses of LPS-exposed ECs revealed an activated/dysfunctional phenotype, while a biotin assay for caveolae internalization followed by biochemical quantification indicated that LPS causes a 40% inhibition in biotin uptake compared to controls. Quantitative PCR and Western blotting were used to evaluate the mRNA and protein expression, respectively, for several regulatory proteins of intrinsic apoptosis, including ITSN-1s. The decrease in ITSN-1s mRNA and protein expression were countered by Bcl-X_L and survivin upregulation, as well as Bim downregulation, events thought to protect ECs from impending apoptosis. Absence of apoptosis was confirmed by TUNEL and lack of cytochrome c (cyt c) efflux from mitochondria. Moreover, LPS exposure caused induction and activation of inducible nitric oxide synthase (iNOS) and a mitochondrial variant (mtNOS), as well as augmented mitochondrial NO production as measured by an oxidation oxyhemoglobin (oxyHb) assay applied on mitochondrial-enriched fractions prepared from LPS-exposed ECs. Interestingly, expression of myc-ITSN-1s rescued caveolae endocytosis and reversed induction of iNOS expression.</p> <p>Conclusion</p> <p>Our results suggest that ITSN-1s deficiency is relevant for the pro-inflammatory ECs dysfunction induced by LPS.</p

Membrane Cholesterol Regulates Lysosome-Plasma Membrane Fusion Events and Modulates Trypanosoma cruzi Invasion of Host Cells

Trypanosoma cruzi, is the etiological agent of a neglected tropical malady known as Chagas' disease, which affects about 8 million people in Latin America. 30–40% of affected individuals develop a symptomatic chronic infection, with cardiomyopathy being the most prevalent condition. T. cruzi utilizes an interesting strategy for entering cells: T. cruzi enhances intracellular calcium levels, which in turn trigger the exocytosis of lysosomal contents. Lysosomes then donate their membrane for the formation of the parasitophorous vacuole. Membrane rafts, cholesterol-enriched microdomains in the host cell plasma membrane, have also been implicated in T. cruzi invasion process. Since both plasma membrane and lysosomes collaborate in parasite invasion, we decided to study the importance of these membrane domains for lysosomal recruitment and fusion during T. cruzi invasion into host cells. Our results show that drug dependent depletion of plasma membrane cholesterol changes raft organization and induces excessive lysosome exocytosis in the earlier stages of treatment, leading to a depletion of lysosomes near the cell cortex, which in turn compromises T. cruzi invasion. Based on these results, we propose that cholesterol depletion leads to unregulated exocytic events of pre-docked lysosomes, reducing lysosome availability at the cell cortex and consequently compromising T. cruzi infection

Impaired leukocyte influx in cervix of postterm women not responding to prostaglandin priming

<p>Abstract</p> <p>Background</p> <p>Prolonged pregnancies are associated with increased rate of maternal and fetal complications. Post term women could be divided into at least two subgroups, one where parturition is possible to induce by prostaglandins and one where it is not. Our aim was to study parameters in cervical biopsies in women with spontaneous delivery at term (controls) and compare to those that are successfully induced post term (responders), and those that are not induced (non-responders), by local prostaglandin treatment.</p> <p>Methods</p> <p>Stromal parameters examined in this study were the accumulation of leukocytes (CD45, CD68), mRNAs and/or proteins for the extracellular matrix degrading enzymes (matrix metalloproteinase (MMP)-2, MMP-8 and MMP-9), their inhibitors (tissue inhibitor of MMP (TIMP)-1 and TIMP-2), interleukin-8 (IL-8), the platelet activating factor-receptor (PAF-R), syndecan-1 and estrogen binding receptors (estrogen receptor (ER)α, ERβ and G-coupled protein receptor (GPR) 30) as well as the proliferation marker Ki-67.</p> <p>Results</p> <p>The influx of leukocytes as assessed by CD45 was strongest in the responders, thereafter in the controls and significantly lower in the non-responders. IL-8, PAF-R and MMP-9, all predominantly expressed in leukocytes, showed significantly reduced immunostaining in the group of non-responders, while ERα and GPR30 were more abundant in the non-responders, as compared to the controls.</p> <p>Conclusion</p> <p>The impaired leukocyte influx, as reflected by the reduced number of CD45 positive cells as well as decreased immunostaining of IL-8, PAF-R and MMP-9 in the non-responders, could be one explanation of the failed ripening of the cervix in post term women. If the decreased leukocyte influx is a primary explanation to absent ripening or secondary, as a result of other factors, is yet to be established.</p

Neurogenic inflammation after traumatic brain injury and its potentiation of classical inflammation

Background: The neuroinflammatory response following traumatic brain injury (TBI) is known to be a key secondary injury factor that can drive ongoing neuronal injury. Despite this, treatments that have targeted aspects of the inflammatory pathway have not shown significant efficacy in clinical trials. Main body: We suggest that this may be because classical inflammation only represents part of the story, with activation of neurogenic inflammation potentially one of the key initiating inflammatory events following TBI. Indeed, evidence suggests that the transient receptor potential cation channels (TRP channels), TRPV1 and TRPA1, are polymodal receptors that are activated by a variety of stimuli associated with TBI, including mechanical shear stress, leading to the release of neuropeptides such as substance P (SP). SP augments many aspects of the classical inflammatory response via activation of microglia and astrocytes, degranulation of mast cells, and promoting leukocyte migration. Furthermore, SP may initiate the earliest changes seen in blood-brain barrier (BBB) permeability, namely the increased transcellular transport of plasma proteins via activation of caveolae. This is in line with reports that alterations in transcellular transport are seen first following TBI, prior to decreases in expression of tight-junction proteins such as claudin-5 and occludin. Indeed, the receptor for SP, the tachykinin NK1 receptor, is found in caveolae and its activation following TBI may allow influx of albumin and other plasma proteins which directly augment the inflammatory response by activating astrocytes and microglia. Conclusions: As such, the neurogenic inflammatory response can exacerbate classical inflammation via a positive feedback loop, with classical inflammatory mediators such as bradykinin and prostaglandins then further stimulating TRP receptors. Accordingly, complete inhibition of neuroinflammation following TBI may require the inhibition of both classical and neurogenic inflammatory pathways.Frances Corrigan, Kimberley A. Mander, Anna V. Leonard and Robert Vin

Postoperative outcomes in oesophagectomy with trainee involvement

BACKGROUND: The complexity of oesophageal surgery and the significant risk of morbidity necessitates that oesophagectomy is predominantly performed by a consultant surgeon, or a senior trainee under their supervision. The aim of this study was to determine the impact of trainee involvement in oesophagectomy on postoperative outcomes in an international multicentre setting. METHODS: Data from the multicentre Oesophago-Gastric Anastomosis Study Group (OGAA) cohort study were analysed, which comprised prospectively collected data from patients undergoing oesophagectomy for oesophageal cancer between April 2018 and December 2018. Procedures were grouped by the level of trainee involvement, and univariable and multivariable analyses were performed to compare patient outcomes across groups. RESULTS: Of 2232 oesophagectomies from 137 centres in 41 countries, trainees were involved in 29.1 per cent of them (n = 650), performing only the abdominal phase in 230, only the chest and/or neck phases in 130, and all phases in 315 procedures. For procedures with a chest anastomosis, those with trainee involvement had similar 90-day mortality, complication and reoperation rates to consultant-performed oesophagectomies (P = 0.451, P = 0.318, and P = 0.382, respectively), while anastomotic leak rates were significantly lower in the trainee groups (P = 0.030). Procedures with a neck anastomosis had equivalent complication, anastomotic leak, and reoperation rates (P = 0.150, P = 0.430, and P = 0.632, respectively) in trainee-involved versus consultant-performed oesophagectomies, with significantly lower 90-day mortality in the trainee groups (P = 0.005). CONCLUSION: Trainee involvement was not found to be associated with significantly inferior postoperative outcomes for selected patients undergoing oesophagectomy. The results support continued supervised trainee involvement in oesophageal cancer surgery