Leukocyte infiltration plays an active role in controlling tumor development. In the early stages of carcinogenesis, T cells counteract tumor growth. However, in advanced stages, cancer cells and ...infiltrating stromal components interfere with the immune control and instruct immune cells to support, rather than counteract, tumor malignancy, via cell-cell contact or soluble mediators. In particular, metabolites are emerging as active players in driving immunosuppression. Here we demonstrate that in a prostate cancer model lactate released by glycolytic cancer-associated fibroblasts (CAFs) acts on CD4
T cells, shaping T-cell polarization. In particular, CAFs exposure (i) reduces the percentage of the antitumoral Th1 subset, inducing a lactate-dependent, SIRT1-mediated deacetylation/degradation of T-bet transcription factor; (ii) increases T
cells, driving naive T cells polarization, through a lactate-based NF-kB activation and FoxP3 expression. In turn, this metabolic-based CAF-immunomodulated environment exerts a pro-invasive effect on prostate cancer cells, by activating a previously unexplored miR21/TLR8 axis that sustains cancer malignancy.
Introduction. Daily evaluation of mechanically ventilated (MV) patients is essential for successful extubation. Proper withdrawal prevents complications and reduces the cost of hospitalization in the ...intensive care unit (ICU). Diaphragm ultrasonography (DUS) has emerged as a potential instrument for determining whether a patient is ready to be extubated. This study compared the efficacy rate of extubation using a standard withdrawal protocol and DUS in patients with MV. Methods. A randomized, parallel, single-blind, controlled study was conducted on ICU patients undergoing MV. Patients were randomly assigned to either the control (conventional weaning protocol) group or intervention (DUS-guided weaning) group in a 1 : 1 ratio. The primary outcome measure was the rate of reintubation and hospital mortality. Results. Forty patients were randomized to the trial. The mean age of the sample was 70 years, representing an older population. The extubation success rate was 90% in both groups. There was no reintubation in the first 48 hours and only two reintubations in both groups between the second and seventh days. The hospital mortality risk in patients with acute kidney injury was positively correlated with age and the need for hemodialysis. Discussion. This study demonstrates the usefulness of DUS measurement protocols for withdrawing MV. The rate of reintubation was low for both cessation methods. As a parameter, the diaphragm thickness fraction comprehensively evaluates the diaphragm function. The results demonstrate that DUS has the potential to serve as a noninvasive tool for guiding extubation decisions. In conclusion, using DUS in patients with respiratory failure revealed no difference in reintubation rates or mortality compared with the conventional method. Future research should concentrate on larger, multicentered, randomized trials employing a multimodal strategy that combines diaphragmatic parameters with traditional clinical withdrawal indices.
Two randomized, open-label, noninferiority phase 3 trials compared the prolyl hydroxylase inhibitor vadadustat with darbepoetin alfa in patients with incident or prevalent chronic kidney disease who ...were undergoing dialysis. Vadadustat was noninferior to darbepoetin alfa with respect to cardiovascular safety and correction and maintenance of hemoglobin concentrations.
Vancomycin (VCM) is a tricyclic glycopeptide antibiotic produced by Streptococcus orientalis. Widely used in hospitals, it is indicated to fight severe infections caused by Gram-positive bacteria, ...especially with the advent of MRSA (methicillin-resistant Staphylococcus aureus), penicillin-resistant pneumococci among others. Furthermore, it is indicated for the treatment of patients allergic to penicillins and cephalosporins. Dose recommendations, dilution rates and types of infusion are controversial and also result in toxic effects. Aim of this paper was to perform a literature review showing the therapeutic and adverse effects of vancomycin.
This is a literature review of recent articles published on MEDLINE and SciELO databases in English, Portuguese and Spanish.
The main adverse effects of vancomycin are: hypotension, phlebitis, nephrotoxicity, ototoxicity, hypersensitivity reactions, red man syndrome, neutropenia, chills, fever, interstitial nephritis.
The use of vancomycin is still very common; however, inadequate doses and prolonged therapy pose a risk of increasing minimum inhibitory concentrations (MICs), resulting in subtherapeutic levels, treatment failures and toxicity. Therefore, further studies should be conducted to optimize the administration of vancomycin, monitoring treatments from the beginning in order to ensure a safe and effective use of the drug.
Chronic kidney disease (CKD) is highly prevalent worldwide. Patients with CKD on hemodialysis are more likely to present behavioral changes and worse quality of life as a result of their routine and ...complications. They also have higher levels of cytokines. The aim of this study is to assess the relationship between the inflammatory profile and quality of life measured by KDOQL-SF36 in hemodialysis outpatients. Patients older than 21 years of age and on routine hemodialysis for at least 6 months with treatment on a regular weekly basis were included and their anthropometric parameters and serum inflammatory markers were evaluated. Thirty patients consented to participate. Homocysteine (Hcy) levels were correlated with worse glomerular filtration rate (GFR; P=0.003) and creatinine (P=0.002). IL-6 was not correlated with worse nutritional status taking into account body mass index (BMI; kg/m2; P=0.83). On the other hand, TNF-alpha was positively correlated with albumin (P=0.008), nutritional status by BMI (P=0.04), and nutritional status by arm circumference area (P=0.04). IL-6 was correlated with activity limitation (P=0.02) and Hcy with work status (P=0.04). Hcy was correlated with nutritional status and inflammatory markers. In this population, the majority of the sections in KDOQL-SF36 were not correlated with cytokines levels.
Community-acquired pneumonia (CAP) is amongst the leading causes of death worldwide. As inflammatory markers, cytokines can predict outcomes, if interpreted together with clinical data and scoring ...systems such as CURB-65, CRB, and Acute Physiology and Chronic Health Evaluation II (APACHE II). The aim of this study was to determine the impact of inflammatory biomarkers on the early mortality of hospitalized CAP patients. Twenty-seven CAP patients needing hospitalization were enrolled for the study and samples of interleukin-1 (IL-1) and interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), C-reactive protein (CRP), and homocystein were collected at the time of admission (day 1) as well as on the seventh day of the treatment. There was a significant reduction in the levels of IL-6 between the first and the second collections. Median IL-6 values decreased from 24 pg/mL (day 1) to 8 pg/mL (day 7) (P=0.016). The median levels of TNF-α were higher in patients: i) with acute kidney injury (AKI) (P=0.045), ii) requiring mechanical ventilation (P=0.040), iii) with short hospital stays (P=0.009), iv) admitted to the intensive care unit (ICU) (P=0.040), v) who died early (P=0.003), and vi) with worse CRB scores (P=0.013). In summary, IL-6 and TNF-α levels were associated with early mortality of CAP patients. Longer admission levels demonstrated greater likelihood of early death and overall mortality, necessity of mechanical ventilation, and AKI.
Irisin is a muscle-secreted protein released into the circulation by cleavage of fibronectin type III domain containing protein 5(FNDC5). Since its discovery in 2012, it has been the subject of many ...researches due to its physiological role. It is believed that understanding irisin's function may be the key to comprehend many diseases and their development. The aim of this study is to perform a systematic review in order to establish whether there is an association of irisin's levels with obesity, diabetes mellitus, non-alcoholic steatohepatitis, chronic kidney disease and cancer in terms of prognosis.
The articles that support these findings were selected from Medline using the keyword "irisin" and filtered with "humans only". The selected articles were in English and with abstract.
Higher baseline irisin concentrations are associated with greater reductions in glycemia and insulinemia after weight loss in obese subjects. Besides, it was observed that macrovascular disease, a complication of diabetes, was developed when there were lower levels of irisin. In addition, although not statistically significant, high levels of irisin were associated with portal inflammation and severity of histological lesions. Its concentrations decreased with increasing chronic kidney disease stage, and they were not only independently and positively predicted by renal function and insulin resistance but also associated with sarcopenia and carotid atherosclerosis in patients undergoing peritoneal dialysis. Regarding cancer, irisin reduced the proliferation, viability and migration of malignant breast cells. Finally, it is also related to bone health once its concentration is associated with previous osteoporotic fractures.
In every condition studied, irisin's concentrations were related to the development of the disease.
Between the ever-increasing availability of surveillance evidence and expert-based forensic facial comparison being considered admissible in court, confirming its validity is paramount. Facial ...comparison is most commonly conducted using morphological analysis (MA), a largely untested feature-based approach. This study aimed at validating the current recommended practice of MA in both standardised and suboptimal surveillance samples. Face pools of 175 South African males were compiled with a series of facial photographs, using images from the Wits Face Database. The first 75 face pools consisted of wildtype (unstandardised) high-quality target photographs, while the remaining 100 face pools consisted of suboptimal closed-circuit television (CCTV) target images. Target images were compared to high-quality standardised photographs. Face pools were analysed using the Facial Identification Scientific Working Group’s guidelines and feature list. Confusion matrices were used to determine the performance of MA in each cohort. MA was found highly accurate (chance-corrected accuracy (CCA): 99.1%) and reliable (κ = 0.921) in the photographic sample and less accurate (CCA: 82.6%) and reliable (κ = 0.743), in the CCTV sample. Higher false-positive and false-negative rates were noted for the CCTV sample, with the majority of errors resulting in false-negative outcomes. The decreased performance in the CCTV sample was attributed to various factors including image quality, angle of recording and lighting. Other studies testing facial comparison identified lower accuracies and reliability across various conditions. Better performance was found here and in other studies that included some form of facial feature list, reinforcing the importance of using a systematic facial feature list.
Abstract Geometric morphometrics (GMM) have been applied to understand morphological variation in biological structures. However, research studying cortical bone through geometric histomorphometrics ...(GHMM) is scarce. This research aims to develop a landmark‐based GHMM protocol to depict osteonal shape variation in the femoral diaphysis, exploring the role of age and biomechanics in bone microstructure. Proximal, midshaft, and distal anatomical segments from the femoral diaphysis of six individuals were assessed, with 864 secondary intact osteons from eight periosteal sampling areas being manually landmarked. Observer error was tested using Procrustes ANOVA. Average osteonal shape and anatomical segment‐specific variation were explored using principal component analysis. Osteon shape differences between segments were examined using canonical variate analysis (CVA). Sex differences were assessed through Procrustes ANOVA and discriminant function analysis (DFA). The impact of osteonal size on osteonal shape was investigated. High repeatability and reproducibility in osteon shape landmarking were reported. The average osteon shape captured was an elliptical structure, with PC1 reflecting more circular osteons. Significant differences in osteon shape were observed between proximal and distal segments according to CVA. Osteon shape differed between males and females, with DFA showing 52% cross‐validation accuracies. No effect of size on shape was reported. Osteonal shape variation observed in this study might be explained by the elderly nature of the sample as well as biomechanical and physiological mechanisms playing different roles along the femoral diaphysis. Although a larger sample is needed to corroborate these findings, this study contributes to the best of our knowledge on human microanatomy, proposing a novel GHMM approach.
•Forensic facial comparison is frequently used in South Africa and worldwide.•Here we outline the scope of practice and training in South Africa.•We propose new levels for assessment of ...agreement.•The reliability of facial comparisons should be addressed in future research.
Forensic facial comparison (FFC) is a scientific technique used to link suspects to a crime scene based on the analysis of photos or video recordings from that scene. While basic guidelines on practice and training are provided by the Facial Identification Scientific Working Group, details of how these are applied across the world are scarce. FFC is frequently used in South Africa, with more than 700 comparisons conducted in the last two years alone. In this paper the standards of practice are outlined, with new proposed levels of agreement/conclusions. We outline three levels of training that were established, with training in facial anatomy, terminology, principles of image comparison, image science, facial recognition and computer skills being aimed at developing general competency. Training in generating court charts and understanding court case proceedings are being specifically developed for the South African context. Various shortcomings still exist, specifically with regard to knowledge of the reliability of the technique. These need to be addressed in future research.
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