In the framework of computer-aided diagnosis of eye diseases, retinal vessel segmentation based on line operators is proposed. A line detector, previously used in mammography, is applied to the green ...channel of the retinal image. It is based on the evaluation of the average grey level along lines of fixed length passing through the target pixel at different orientations. Two segmentation methods are considered. The first uses the basic line detector whose response is thresholded to obtain unsupervised pixel classification. As a further development, we employ two orthogonal line detectors along with the grey level of the target pixel to construct a feature vector for supervised classification using a support vector machine. The effectiveness of both methods is demonstrated through receiver operating characteristic analysis on two publicly available databases of color fundus images.
Chronic ulcers are an intractable problem in many patients and are associated with impaired quality of life and high health-care costs. In an attempt to improve outcome, our centre began cleansing ...wounds with a novel spray acidoxidising solution (Nexodyn) with unique physicochemical features, pH <3.0; oxidation reduction potential >1000mV; and free chlorine content (>95% HClO).
A retrospective analysis was conducted in patients with numerous comorbidities and an unsatisfactory response to standard therapy. The solution was administered for six weeks and the patients' clinical course evaluated using standard measures of wound healing, pain and bioburden.
We assessed 20 patients with a mean time since ulcer onset of 23.7 months. Complete resolution of the lesion was achieved in 25% of cases (p=0.005). In the group as a whole, wound size decreased significantly (11% mean reduction versus baseline; p=0.039). In the relatively short six-week observation period, significant reductions versus baseline were also observed in control of wound bioburden (p=0.005) and ulcer-related pain score (p<0.001). Furthermore, the wound bed preparation score suggests an improved wound microenvironment with better wound bed cleansing and the presence of granulation tissue. There were no adverse systemic effects of treatment nor adverse local effects in the wound bed or on healthy periwound skin.
Encouraging initial results in a population refractory to standard management provide evidence that this new product may make a helpful contribution to the care of chronic ulcers. The integration of this cleansing solution into standard care contributes to the modulation of local microenvironmental responses that inhibit physiological healing processes while also contributing to the reduction of bacterial load.
The occurrence of peritoneal carcinomatosis is a major cause of treatment failure in colorectal cancer and is considered incurable. However, new therapeutic approaches have been proposed, including ...cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (HIPEC). Although HIPEC has been effective in selected patients, it is not known how HIPEC prolongs a patient's lifespan. Here, we have demonstrated that HIPEC-treated tumor cells induce the activation of tumor-specific T cells and lead to vaccination against tumor cells in mice. We have established that this effect results from the HIPEC-mediated exposure of heat shock protein (HSP) 90 at the plasma membrane. Inhibition or blocking of HSP90, but not HSP70, prevented the HIPEC-mediated antitumoral vaccination. Our work raises the possibility that the HIPEC procedure not only kills tumor cells but also induces an efficient anticancer immune response, therefore opening new opportunities for cancer treatment.
Surface tension measurements are a central task in the study of surfaces and interfaces. For liquid metals, they are complicated by the high temperatures and the consequently high reactivity ...characterising these melts. In particular, oxidation of the liquid surface in combination with evaporation phenomena requires a stringent control of the experimental conditions, and an appropriate theoretical treatment. Recently, much progress has been made on both sides. In addition to improving the conventional sessile drop technique, new containerless methods have been developed for surface tension measurements. This paper reviews the experimental progress made in the last few years, and the theoretical framework required for modelling and understanding the relevant physico-chemical surface phenomena.
Most cancer cells exhibit increased glycolysis for generation of their energy supply. This specificity could be used to preferentially kill these cells. In this study, we identified the signaling ...pathway initiated by glycolysis inhibition that results in sensitization to death receptor (DR)-induced apoptosis. We showed, in several human cancer cell lines (such as Jurkat, HeLa, U937), that glucose removal or the use of nonmetabolizable form of glucose (2-deoxyglucose) dramatically enhances apoptosis induced by Fas or by tumor necrosis factor-related apoptosis-inducing ligand. This sensitization is controlled through the adenosine monophosphate (AMP)-activated protein kinase (AMPK), which is the central energy-sensing system of the cell. We established the fact that AMPK is activated upon glycolysis block resulting in mammalian target of rapamycin (mTOR) inhibition leading to Mcl-1 decrease, but no other Bcl-2 anti-apoptotic members. Interestingly, we determined that, upon glycolysis inhibition, the AMPK-mTOR pathway controlled Mcl-1 levels neither through transcriptional nor through posttranslational mechanism but rather by controlling its translation. Therefore, our results show a novel mechanism for the sensitization to DR-induced apoptosis linking glucose metabolism to Mcl-1 downexpression. In addition, this study provides a rationale for the combined use of DR ligands with AMPK activators or mTOR inhibitors in the treatment of human cancers.
Cellular metabolism influences life and death decisions. An emerging theme in cancer biology is that metabolic regulation is intricately linked to cancer progression. In part, this is due to the fact ...that proliferation is tightly regulated by availability of nutrients. Mitogenic signals promote nutrient uptake and synthesis of DNA, RNA, proteins and lipids. Therefore, it seems straight-forward that oncogenes, that often promote proliferation, also promote metabolic changes. In this review we summarize our current understanding of how 'metabolic transformation' is linked to oncogenic transformation, and why inhibition of metabolism may prove a cancer's 'Achilles' heel'. On one hand, mutation of metabolic enzymes and metabolic stress sensors confers synthetic lethality with inhibitors of metabolism. On the other hand, hyperactivation of oncogenic pathways makes tumors more susceptible to metabolic inhibition. Conversely, an adequate nutrient supply and active metabolism regulates Bcl-2 family proteins and inhibits susceptibility to apoptosis. Here, we provide an overview of the metabolic pathways that represent anti-cancer targets and the cell death pathways engaged by metabolic inhibitors. Additionally, we will detail the similarities between metabolism of cancer cells and metabolism of proliferating cells.
Analizar los resultados de la sustitución valvular aórtica (SVA) a través de esternotomía parcial superior (EPS).
Entre enero de 2011 y diciembre de 2016, 507 pacientes fueron sometidos a SVA simple, ...306 mediante esternotomía convencional media (ECM) y 201 por EPS. Se usó el índice de propensión para comparar los resultados de ambas técnicas en 201 pares de pacientes.
La edad media fue de 70±11,5 años, el 60% eran varones y el 58% tenían estenosis aórtica. El EuroSCORE II mediano fue del 1,58% (0,99-2,46). La mediana del tiempo de isquemia y circulación extracorpórea para EPS y ECM fue de 82min (72-92) y 102min (90-114) vs. 66min (55-75) y 87min (75-101), respectivamente (p<0,05). Los pacientes con ECM presentaron mayor sangrado postoperatorio y requerimiento de transfusión de hemoderivados que los pacientes con EPS (p<0,05). No hubo diferencias significativas en la incidencia de eventos adversos cardiovasculares y cerebrovasculares mayores en el postoperatorio entre ambos grupos. La mortalidad hospitalaria fue del 3,7% (p>0,05). La supervivencia a los 5 años fue del 83%. Tras la intervención quirúrgica el 96% de los pacientes estaban en clase funcional NYHA I o II y tenían una media de índice de salud EQ-5D® de 0,81 independientemente del grupo.
La SVA por EPS es una técnica segura con resultados a corto, mediano y largo plazo comparables a la ECM. Se asocia con menor sangrado y requerimientos de transfusión de hemoderivados en el postoperatorio; pero con un mayor tiempo de isquemia y de circulación extracorpórea.
To analyse the results of aortic valve replacement (AVR) through partial upper sternotomy (PUS).
Between January 2011 and December 2016, 507 patients underwent simple AVR: 306 through conventional median sternotomy (CMS) and 201 through PUS. The propensity score was used to compare the results of both techniques in 201 patient pairs.
The average age was 70±11.5 years. Sixty percent were men and 58% had aortic stenosis. The median EuroSCORE II was 1.58% (.99-2.46). The median time of ischaemia and extracorporeal circulation for PUS and CMS was 82 minutes (72-92) and 102 minutes (90-114), vs 66 minutes (55-75) and 87 minutes (75-101), respectively (P<.05). Patients with CMS presented with greater postoperative bleeding and need for blood product transfusion than patients with PUS (P<.05). There were no significant differences between the two groups in the incidence of major adverse cardiovascular and cerebrovascular events in the postoperative period. Hospital mortality rate was 3.7% (P>.05). Five-year survival rate was 83%. After surgery, 96% of the patients were in NYHA functional class I or II and had a mean EQ-5D® health index of .81, regardless of group.
AVR by PUS is a safe technique with short-, medium- and long-term results comparable to CMS. It is associated with less postoperative bleeding and need for blood product transfusion, but with a longer duration of ischaemia and extracorporeal circulation.
Deregulated expression of glycolytic enzymes contributes not only to the increased energy demands of transformed cells but also has non-glycolytic roles in tumors. However, the contribution of these ...non-glycolytic functions in tumor progression remains poorly defined. Here, we show that elevated expression of glyceraldehyde-3-phosphate dehydrogenase (GAPDH), but not of other glycolytic enzymes tested, increased aggressiveness and vascularization of non-Hodgkin's lymphoma. Elevated GAPDH expression was found to promote nuclear factor-κB (NF-κB) activation via binding to tumor necrosis factor receptor-associated factor-2 (TRAF2), enhancing the transcription and the activity of hypoxia-inducing factor-1α (HIF-1α). Consistent with this, inactive mutants of GAPDH failed to bind TRAF2, enhance HIF-1 activity or promote lymphomagenesis. Furthermore, elevated expression of gapdh mRNA in biopsies from diffuse large B-cell non-Hodgkin's lymphoma patients correlated with high levels of hif-1α, vegf-a, nfkbia mRNA and CD31 staining. Collectively, these data indicate that deregulated GAPDH expression promotes NF-κB-dependent induction of HIF-1α and has a key role in lymphoma vascularization and aggressiveness.
Veterinary pathologists commonly encounter lesions of blunt trauma. The development of lesions is affected by the object’s mass, velocity, size, shape, and angle of impact and by the plasticity and ...mobility of the impacted organ. Scrape, impact, and pattern abrasions cause localized epidermal loss and sometimes broken hairs and implanted foreign material. Contusions are best identified after reflecting the skin, and must be differentiated from coagulopathies and livor mortis. Lacerations—traumatic tissue tears—may have irregular margins, bridging by more resilient tissue, deviation of the wound tail, crushed hairs, and unilateral abrasion. Hanging or choking can cause circumferential cervical abrasions, contusions and rupture of hairs, hyoid bone fractures, and congestion of the head. Other special forms of blunt trauma include fractured nails, pressure sores, and dog bites. Ocular blunt trauma causes extraocular and intraocular hemorrhages, proptosis, or retinal detachment. The thoracic viscera are relatively protected from blunt trauma but may develop hemorrhages in intercostal muscles, rib fractures, pulmonary or cardiac contusions or lacerations with subsequent hemothorax, pneumothorax, or cardiac arrhythmia. The abdominal wall is resilient and moveable, yet the liver and spleen are susceptible to traumatic laceration or rupture. Whereas extravasation of blood can occur after death, evidence of vital injury includes leukocyte infiltration, erythrophagocytosis, hemosiderin, reparative lesions of fibroblast proliferation, myocyte regeneration in muscle, and callus formation in bone. Understanding these processes aids in the diagnosis of blunt force trauma including estimation of the age of resulting injuries.
The High-energy Particle Detector (HEPD) on board the China Seismo-Electromagnetic Satellite (CSES-01)-launched on 2018 February 2-is a light and compact payload suitable for measuring electrons ...(3-100 MeV), protons (30-250 MeV), and light nuclei (up to a few hundreds of MeV). The Sun-synchronous orbit and large acceptance allow HEPD to measure cosmic-ray particles near the 65° latitude limit for a fair amount of time per day. In this work, three semiannual galactic hydrogen energy spectra between ∼40 and 250 MeV are presented, including a comparison with theoretical spectra from HelMod, a 2D Monte Carlo model developed to simulate the solar modulation of cosmic rays throughout the heliosphere. To our knowledge, these are the first hydrogen energy spectra below 250 MeV measured at 1 au between 2018 and 2020.
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