Staphylococcus aureus forms biofilms, a structure that protects bacterial cells, conferring more resistance to difficult treatment. Synthetic peptides surge as an alternative to overcome the biofilm ...of multidrug-resistant pathogens. Mo-CBP
3
-PepI, when combined with Ciprofloxacin, reduced preformed S. aureus biofilm by 50% at low concentrations (0.2 and 6.2 μg. mL
−1
, respectively). The goal of this study was to evaluate the proteomic profile of biofilms after treatment with the Mo-CBP
3
-PepI combined with ciprofloxacin. Here, proteomic analysis confirmed with more depth previously described mechanisms and revealed changes in the accumulation of proteins related to DNA and protein metabolism, cell wall biosynthesis, redox metabolism, quorum sensing, and biofilm formation. Some proteins related to DNA and protein metabolism were reduced, while other proteins, like redox system proteins, disappeared in Ciprofloxacin+Mo-CBP
3
-PepI treatment. Our results indicated a synergistic effect of these two molecules with several mechanisms against S. aureus biofilm and opened new doors for combined treatments with other drugs.
Millions of people died during the COVID-19 pandemic, but the vast majority of infected individuals survived. Now, some consequences of the disease, known as long COVID, are been revealed. Although ...the respiratory system is the target of Sars-CoV-2, COVID-19 can influence other parts of the body, including bone. The aim of this work was to investigate the impact of acute coronavirus infection in bone metabolism.
We evaluated RANKL/OPG levels in serum samples of patients with and without acute COVID-19. In vitro, the effects of coronavirus in osteoclasts and osteoblasts were investigated. In vivo, we evaluated the bone phenotype in a BSL2 mouse model of SARS-like disease induced by murine coronavirus (MHV-3).
Patients with acute COVID-19 presented decreased OPG and increased RANKL/OPG ratio in the serum versus healthy individuals. In vitro, MHV-3 infected macrophages and osteoclasts, increasing their differentiation and TNF release. Oppositely, osteoblasts were not infected. In vivo, MHV-3 lung infection triggered bone resorption in the femur of mice, increasing the number of osteoclasts at 3dpi and decreasing at 5dpi. Indeed, apoptotic-caspase-3+ cells have been detected in the femur after infection as well as viral RNA. RANKL/OPG ratio and TNF levels also increased in the femur after infection. Accordingly, the bone phenotype of TNFRp55−/− mice infected with MHV-3 showed no signs of bone resorption or increase in the number of osteoclasts.
Coronavirus induces an osteoporotic phenotype in mice dependent on TNF and on macrophage/osteoclast infection.
Metformin is the most prescribed drug for DM2, but its site and mechanism of action are still not well established. Here, we investigated the effects of metformin on basolateral intestinal glucose ...uptake (BIGU), and its consequences on hepatic glucose production (HGP). In diabetic patients and mice, the primary site of metformin action was the gut, increasing BIGU, evaluated through PET-CT. In mice and CaCo2 cells, this increase in BIGU resulted from an increase in GLUT1 and GLUT2, secondary to ATF4 and AMPK. In hyperglycemia, metformin increased the lactate (reducing pH and bicarbonate in portal vein) and acetate production in the gut, modulating liver pyruvate carboxylase, MPC1/2, and FBP1, establishing a gut-liver crosstalk that reduces HGP. In normoglycemia, metformin-induced increases in BIGU is accompanied by hypoglycemia in the portal vein, generating a counter-regulatory mechanism that avoids reductions or even increases HGP. In summary, metformin increases BIGU and through gut-liver crosstalk influences HGP.
Background & Aims:
Proinflammatory interleukin (IL)-1 gene polymorphisms associated with high levels of IL-1β activity increase the risk for hypochlorhydria and distal gastric carcinoma. The aim of ...this study was to evaluate whether carriers of these polymorphic genes are protected against gastroesophageal reflux disease (GERD).
TNFA-308 polymorphisms were also studied.
Methods:
We prospectively evaluated 385 patients without gastric cancer and peptic ulcer. Of these patients, 383 (98 with GERD and 285 controls) were successfully genotyped for all cytokines studied. The
cagA status of
Helicobacter pylori isolates was determined by polymerase chain reaction (PCR).
IL1B-511/-31,
IL1RN, and
TNFA-308 polymorphisms were genotyped by PCR, PCR/restriction fragment length polymorphism, or PCR/confronting 2-pair primers. Histologic gastritis was assessed according to the updated Sydney system. The role of the proinflammatory cytokine genotypes in the genesis of GERD was evaluated before and after stratification by
H. pylori status in logistic regression models controlling for confounding factors.
Results:
IL1B-31 (a near-complete linkage disequilibrium between polymorphism at -31 and -511 was found) and
IL1RN∗2 allele polymorphisms were associated with GERD. After stratification, in the group of
H. pylori-positive patients,
cagA-positive status,
IL1B-31 polymorphic alleles,
IL1RN∗2 alleles, and the degree of corpus gastritis were negatively associated with GERD. In the
H. pylori-negative group,
IL1B-31C/C genotype was inversely associated with GERD even after adjustment for age and sex.
Conclusions:
This study provides evidence supporting the independent protective role of
cagA-positive
H. pylori status and
IL1B and
ILRN allele polymorphisms against GERD.
The impact of nanotechnology on the exponential growth of several research areas, particularly nanomedicine, is undeniable. The ability to deliver active molecules to the desired site could ...significantly improve the efficiency of medical treatments. One of the nanocarriers developed which has drawn researchers’ attention are cubosomes, which are nanosized dispersions of lipid bicontinuous cubic phases in water, consisting of a lipidic interior and aqueous domains folded in a cubic lattice. They stand out due to their ability to incorporate hydrophobic, hydrophilic, and amphiphilic compounds, their tortuous internal configuration that provides a sustained release, and the capacity to protect and safely deliver molecules. Several approaches can be taken to prepare this structure, as well as different lipids like monoolein or phytantriol. This review paper describes the different methods to prepare nanocarriers. As it is known, the physicochemical properties of nanocarriers are very important, as they influence their pharmacokinetics and their ability to incorporate and deliver active molecules. Therefore, an extensive characterization is essential to obtain the desired effect. As a result, we have extensively described the most common techniques to characterize cubosomes, particularly nanocarriers. The exceptional properties of the cubosomes make them suitable to be used in several applications in the biomedical field, from cancer therapeutics to imaging, which will be described. Taking in consideration the outstanding properties of cubosomes, their application in several research fields is envisaged.
Neuromyelitis Optica With Onset in Childhood and Adolescence Fragoso, Yara Dadalti, MD, MSc, PhD; Ferreira, Maria L.B., MD; Oliveira, Enedina M.L., MD, PhD ...
Pediatric neurology,
2014, January 2014, 2014-Jan, 2014-01-00, 20140101, Letnik:
50, Številka:
1
Journal Article
Recenzirano
Abstract Background Neuromyelitis optica with onset before the age of 18 years is a relatively rare, yet potentially devastating condition. The objective of the present study was to contribute to the ...study of early-onset neuromyelitis optica with a case series. Patients Data were collected from medical records of Brazilian neurologists caring for patients with neuromyelitis optica occurring in childhood and adolescence. Results Twenty-nine patients with neuromyelitis optica occurring before the age of 18 years and fulfilling the diagnostic criteria were identified. The average age at disease onset was 13 years and the patients had had an average disease duration of 6 years. The expanded disability scale score at the latest consultation was, on average, 4.7, and one patient had died from the disease. The 29 patients had had an average 4.5 relapses during the disease, accounting for 0.75 relapses per year, irrespective of the medication used. All patients were using one or more of the following medications: azathioprine, prednisone, immunoglobulin, and glatiramer acetate. Conclusions Neuromyelitis optica with onset in childhood and adolescence is a poorly understood condition that is often disabling and difficult to manage.
Midterm effects of bariatric surgery on patients with obesity and hypertension remain uncertain.
To determine the 3-year effects of Roux-en-Y gastric bypass (RYGB) on blood pressure (BP) compared ...with medical therapy (MT) alone.
Randomized clinical trial. (ClinicalTrials.gov: NCT01784848).
Investigator-initiated study at Heart Hospital (HCor), São Paulo, Brazil.
Patients with hypertension receiving at least 2 medications at maximum doses or more than 2 medications at moderate doses and with a body mass index (BMI) between 30.0 and 39.9 kg/m
were randomly assigned (1:1 ratio).
RYGB plus MT or MT alone.
The primary outcome was at least a 30% reduction in total number of antihypertensive medications while maintaining BP less than 140/90 mm Hg. Key secondary outcomes were number of antihypertensive medications, hypertension remission, and BP control according to current guidelines (<130/80 mm Hg).
Among 100 patients (76% female; mean BMI, 36.9 kg/m
SD, 2.7), 88% from the RYGB group and 80% from the MT group completed follow-up. At 3 years, the primary outcome occurred in 73% of patients from the RYGB group compared with 11% of patients from the MT group (relative risk, 6.52 95% CI, 2.50 to 17.03;
0.001). Of the randomly assigned participants, 35% and 31% from the RYGB group and 2% and 0% from the MT group achieved BP less than 140/90 mm Hg and less than 130/80 mm Hg without medications, respectively. Median (interquartile range) number of medications in the RYGB and MT groups at 3 years was 1 (0 to 2) and 3 (2.8 to 4), respectively (
0.001). Total weight loss was 27.8% and -0.1% in the RYGB and MT groups, respectively. In the RYGB group, 13 patients developed hypovitaminosis B
and 2 patients required reoperation.
Single-center, nonblinded trial.
RYGB is an effective strategy for midterm BP control and hypertension remission, with fewer medications required in patients with hypertension and obesity.
Ethicon, represented in Brazil by Johnson & Johnson do Brasil.
The Caatinga biome, characterized by its dynamic vegetation due to climate and land use changes, experiences varied environmental responses during the dry and rainy seasons. This research aims to ...dissect the complexity of surface radiation fluxes, vapor pressure, and air and soil temperatures across three distinct vegetation densities within the Caatinga: recovering, degraded, and preserved. Utilizing data from Moderate Resolution Imaging Spectroradiometer/Enhanced Vegetation Index products to analyze these densities offers a novel lens through which to view the biome's reaction to climatic shifts. Our findings unveiled specific patterns of solar and longwave radiation fluxes that correlate with key climatic variables like air temperature and surface albedo. This investigation not only addresses a critical gap in our knowledge of a globally significant but underexplored biome, but it also advances our comprehension of how vegetation density influences radiation fluxes in arid settings. Insights from this study are vital for forecasting and mitigating the ecological and climatic impacts of land cover transformations in semiarid regions worldwide. Significantly, the degraded site displayed nearly double the solar radiation reflection (138 Wm−2) compared to the recovering site (68 Wm−2), underscoring the role of vegetation density in modulating local climate conditions, despite atmospheric consistency across the study sites.
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•The Caatinga biome covers the world's most densely populated dry region.•The study observes radiation fluxes over different vegetation densities.•Recovering and degraded vegetation had higher incoming solar radiation.•Preserved Caatinga areas emitted the most intense longwave radiation.•Degraded Caatinga showed the highest surface albedo values.
The production of conductive and organic devices from a 3D printer represents a promising strategy for several areas. In particular, the synthesis of polypyrrole-coated acrylonitrile butadiene ...styrene (ABS) composites can be considered an important step to produce conductive supports for 3D printing. Herein, it is reported the production of ABS samples through the additive manufacturing process (3D printing) accordingly to the Fused Deposition Modeling (FDM) method. The hydrophilic behavior was controlled by the surface treatment using air plasma for the following step of coating with polypyrrole (PPy) via an in situ polymerization, using two different oxidants: ferric chloride (FeCl3.6H2O) and ammonium persulfate (APS). The chemical, optical, surface, and electrical properties of these materials were characterized through Fourier Transform infrared spectroscopy (FTIR), contact angle measurements, cyclic voltammetry, Scanning Electron Microscopy (SEM), 4-probe electrical measurement, and mechanical tensile testing. The ABS/PPy (FeCl3) composite exhibited a low electrical contact resistance and better performance for applications that require electrodes with a good conductance level.
It remains uncertain whether acetylcysteine prevents contrast-induced acute kidney injury.
We randomly assigned 2308 patients undergoing an intravascular angiographic procedure with at least 1 risk ...factor for contrast-induced acute kidney injury (age >70 years, renal failure, diabetes mellitus, heart failure, or hypotension) to acetylcysteine 1200 mg or placebo. The study drugs were administered orally twice daily for 2 doses before and 2 doses after the procedure. The allocation was concealed (central Web-based randomization). All analysis followed the intention-to-treat principle. The incidence of contrast-induced acute kidney injury (primary end point) was 12.7% in the acetylcysteine group and 12.7% in the control group (relative risk, 1.00; 95% confidence interval, 0.81 to 1.25; P=0.97). A combined end point of mortality or need for dialysis at 30 days was also similar in both groups (2.2% and 2.3%, respectively; hazard ratio, 0.97; 95% confidence interval, 0.56 to 1.69; P=0.92). Consistent effects were observed in all subgroups analyzed, including those with renal impairment.
In this large randomized trial, we found that acetylcysteine does not reduce the risk of contrast-induced acute kidney injury or other clinically relevant outcomes in at-risk patients undergoing coronary and peripheral vascular angiography.
http://www.clinicaltrials.gov. Unique identifier: NCT00736866.
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