Our goal was to assess the coagulation profile in the immediate postoperative time after major liver surgery and its association with the liver function. Our hypothesis is that a decreased synthesis ...of the coagulation factor levels reflects an impaired liver synthesis following hepatic resection and will be associated with poor outcomes. This is a prospective, observational study recruiting consecutive patients scheduled for major liver resection in a tertiary hospital. Coagulation profile was assessed by conventional assays, viscoelastic assays and coagulation factor levels preoperatively and, on postoperative days 1, 2 and 6. Factor VIII to protein C (FVIII/PC) ratio has been used as a surrogate marker of hemostatic imbalance. Liver function was measured with conventional and indocyanine green (ICG) clearance tests, which were obtained preoperatively and on postoperative days 1 and 2. Sixty patients were recruited and 51 were included in the study. There is a clear increase in FVIII/PC ratio after surgery, which was significantly associated with low liver function, being more pronounced beyond postoperative day 2 and in patients with poorer liver function ( P < 0.001). High FVIII/PC ratio values were significantly associated with higher postoperative morbidity, prolonged ICU and hospital stay and less survival ( P < 0.05). High FVIII/PC ratio on postoperative day 2 was found to be predictor of posthepatectomy liver failure (PHLF; area under the ROC curve = 0.8129). Early postoperative high FVIII/PC ratio values are associated with low liver function, PHLF and poorer outcomes in patients undergoing major hepatic resection.
Cancer cells utilize vitamin folate to fulfill their excessive demand for nucleotides and amino acids. Dihydrofolate reductase (DHFR), an enzyme involved in folate metabolism converts dihydrofolate ...into tetrahydrofolate, which is required for the de novo synthesis of purines, and certain amino acids. DHFR inhibitors are used as a chemotherapeutic agent. Cancer sequencing analysis has identified additional enzymes in folate metabolism that are dysregulated in cancer. Methylenetetrahydrofolate dehydrogenase 1 like (MTHFD1L), one such enzyme is overexpressed in bladder cancer. MTHFD1L is a mitochondrial enzyme involved in the folate cycle by catalyzing the reaction of formyl-tetrahydrofolate to formate and tetrahydrofolate (THF). THF is crucial for de novo purine and thymidylate synthesis and is also involved in the regeneration of methionine. Cancer cells rely on purines derived from the de novo pathway for the nucleotides whereas normal cells favor the salvage pathway. In this study we examined MTHFD1L expression in bladder cancer. By using publicly available cancer transcriptome data analysis web-portal UALCAN, we found overexpression of MTHFD1L in bladder cancer and expression was associated with overall survival. RT-PCR and immunoblot analysis confirmed the overexpression of MTHFD1L in muscle invasive bladder cancer tissues compared to normal urothelium. Furthermore, our investigations suggested a critical role for MTHFD1L in bladder cancer cell proliferation, colony formation and invasion. Thus, in this study, we show the significance of the folate metabolic enzyme MTHFD1L in aggressive bladder cancers and suggest that being an enzyme, MTHFD1L serves as a valuable therapeutic target.
Objective
To evaluate microbiological, histological, and ultrastructural characteristics of short‐term cryopreserved (STC) canine corneoscleral tissue (<1 year) and to compare it with long‐term ...cryopreserved (LTC) tissue (>6 years).
Animals studied
Thirty‐six healthy canine globes.
Procedure
After a decontamination protocol, globes were enucleated and stored at −20 °C. Corneoscleral tissue was evaluated at different periods: <1 year (20 eyes) and >6 years (12 eyes). Four eyes were used as controls. Microbiologic study included direct (blood, McConkey and Sabouraud agars) and enrichment (brain‐heart infusion broth) cultures. Cryopreservation artifacts were evaluated by hematoxylin‐eosin. Corneoscleral collagen organization and number of normal and dead keratocytes were established by transmission electron microscopy (TEM). Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) was also used for keratocyte characterization.
Results
Corneal microbial growth was observed in 25% of the direct STC cultures, and in 47.4% and 16.7% of the enriched STC and LTC cultures, respectively. Scleral STC direct cultures were 30% positive, while enrichment cultures were positive in 66.7% and 16.7% of the STC and LTC, respectively (P = 0.011). Cryopreservation artifacts were higher in LTC tissues (P < 0.001). Apoptotic keratocytes were predominant by TEM and TUNEL, in both STC and LTC. Minimal structural differences were detected in collagen organization between STC and LTC.
Conclusions
Cryopreservation of canine corneoscleral tissue seems to reduce bacterial contamination over time. Apoptosis is the main way of death of cryopreserved canine keratocytes. Based on the lack of significant structural differences between STC and LTC samples, these cryopreserved tissues could potentially be used for tectonic support for at least 8 years without structural or microbiological impediment.
The inappropriate and widespread use of conventional antibiotics for the treatment of infectious diseases has resulted in the emergence of resistant strains of pathogenic microorganisms, and this, in ...turn, has promoted the search for antibacterial metabolites with new mechanisms of action. The use of antivirulence agents, which focus on attenuating bacterial pathogenicity rather than affecting cell viability, represents an alternate and interesting approach for treating bacterial infections. Quorum sensing is one of the main targets of antivirulence agents, since it plays a fundamental role in the expression of virulence and resistance factors during the infection process. Considering that natural products represent a potentially important source of antivirulence agents, this review describes secondary metabolites from plants and microorganisms reported to inhibit quorum sensing, particularly over the opportunistic pathogen
Pseudomonas aeruginosa
, one of the most problematic human pathogens and one that, because of its intrinsic resistance to antibiotics, has been adopted as a model for the discovery of new antimicrobial agents.
Dogs cared for in a shelter are dewormed every three–four months, but they all become infected one–two months later by the soil-transmitted helminths (STHs) Toxocara canis, Toxascaris leonina, ...Trichuris vulpis, and Ancylostoma caninum. For the purpose of reducing their risk of infection by decreasing the survival of helminths’ infective stages in soil, chlamydospores of two parasiticide fungi, Mucor circinelloides (ovicide) and Duddingtonia flagrans (larvicide) were formulated as handmade edible gelatins and given three days per week for 17 months to 18 dogs (DRF, dogs receiving fungi); a second group was maintained without fungi (CD, control dogs). All individuals were dewormed at months 0, 3, 7, 10 and 13, and it was observed that the levels of helminths egg-output were reduced by 96–98% fourteen days after each treatment. Fecal egg counts of STHs were similar in both groups until the 6th–8th months, and then remained significantly lower in DRF than in CD (42–100% ascarids; 30–100% trichurids and ancylostomatids). According to the results, and considering that gelatin treats have always been fully accepted, it is concluded that this new formulation offers an efficient solution to decrease the risk of infection among dogs maintained in shelters, and is therefore recommended.
In this study, we investigated the effect of transcranial magnetic stimulation (TMS) on the ultrastructure of muscle fibers and satellite cells in rats with experimental autoimmune encephalomyelitis ...(EAE). EAE-induced animals were treated with TMS (60 Hz at 0.7 mT) for 2 hours in the morning, once a day, 5 days a week, for 3 weeks, starting on day 15 post-immunization. The rats were sacrificed on day 36 post-immunization, and the soleus muscles were evaluated by light microscopy and transmission electron microscopy. Findings were compared with a non-treated EAE group. Electron microscopy analysis showed the presence of degenerated mitochondria, autophagic vacuoles, and altered myofibrils in non-treated EAE group. This correlates with the presence of acid phosphatase activity in muscle fibers and core-targetoid lesions with desmin immunohistochemistry. Most myonuclei in the EAE group showed apoptotic features. In contrast, EAE induced-TMS treated animals had less ultrastructural changes in the mitochondria and the myofibrils, together with less frequent apoptotic nuclear features. Peripheral desmin+ protrusions, as a marker of active satellite cells, were significantly increased in TMS-treated group. This correlates ultrastructurally with the presence of active features in satellite cells in the TMS group. In conclusion, the attenuation of ultrastructural alterations in muscle fibers and activation response of satellite cells caused by EAE indicated that skeletal muscle had a regenerative response to TMS.
A method has been developed for the conversion of primary, secondary, and tertiary alcohols, and phenol, into the corresponding esters at room temperature. The method uses a titanium(III) species ...generated from a substoichiometric amount of titanocene dichloride together with manganese(0) as a reductant, as well as methylene diiodide. It involves a transesterification from an ethyl ester, or a reaction with an acyl chloride. A radical mechanism is proposed for these transformations.
A set of primary, secondary, and tertiary alcohols, and phenol, have been converted into the corresponding esters using a substoichiometric amount of bis(cyclopentadienyl)titanium(III) chloride in good yields and under mild reaction conditions.
Emerging youth movements to promote issues reflected in the United Nations Sustainable Development Goals (SDGs) are celebrated as critical for the future attainment of societal aims. We explore the ...possibility for institutions of higher education to serve as an intentional third space to engender the creation and mobilization of hybrid movements that intentionally engage youth internationally. This case study interrogates the YouthMappers digital humanitarian mapping model of student-led, faculty-mentored, globally-networked chapters through a global survey of 205 participating students from 32 countries. Results indicate the extent to which youth reflect on skill-development versus global citizenship, and how they understand the meanings of their actions for SDGs, locally and globally. Detected differences by gender, world region, and duration of participation are interpreted and validated with additional qualitative data. We conclude with observations about how universities can open enabling spaces for youth action on SDGs.
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