Polyurethanes (PU) are multifunctional polymers, used in automotive industry, in coatings, rigid and flexible foams, and also in biomimetic materials. In the same way as all plastic waste, the ...incorrect disposal of these materials leads to the accumulation of polyurethanes in the environment. To reduce the amount of waste as well as add value to degradation products, bioremediation methods have been studied for waste management of PU. Enzymes of the hydrolases class have been experimentally tested for enzymatic degradation of PU, with very promising results. In this work, two enzymes that can degrade polyurethanes were studied by molecular dynamics simulations: a protease and an esterase, both from
Pseudomonas
. From molecular dynamics simulations analysis, it was observed the stability of the structures, both in the simulations of the free enzymes and in the simulations of the complexes with a PU monomer. Hydrogen bonds were formed with the monomer and the enzymes throughout the simulation time, and the interaction free energy was found to be strongly negative, pointing to strong interactions in both cases.
Monoamine oxidase (MAO) catalyzes the oxidative deamination of biogenic and exogenous amines and its inhibitors have therapeutic value for several conditions including affective disorders, stroke, ...neurodegenerative diseases and aging. The discovery of 2,3,6-trimethyl-1,4-naphthoquinone (TMN) as a nonselective and reversible inhibitor of MAO, has suggested 1,4-naphthoquinone (1,4-NQ) as a potential scaffold for designing new MAO inhibitors. Combining molecular modeling tools and biochemical assays we evaluate the kinetic and molecular details of the inhibition of human MAO by 1,4-NQ, comparing it with TMN and menadione. Menadione (2-methyl-1,4-naphthoquinone) is a multitarget drug that acts as a precursor of vitamin K and an inducer of mitochondrial permeability transition. Herein we show that MAO-B was inhibited competitively by 1,4-NQ (Ki=1.4μM) whereas MAO-A was inhibited by non-competitive mechanism (Ki=7.7μM). Contrasting with TMN and 1,4-NQ, menadione exhibited a 60-fold selectivity for MAO-B (Ki=0.4μM) in comparison with MAO-A (Ki=26μM), which makes it as selective as rasagiline. Fluorescence and molecular modeling data indicated that these inhibitors interact with the flavin moiety at the active site of the enzyme. Additionally, docking studies suggest the phenyl side groups of Tyr407 and Tyr444 (for MAO-A) or Tyr398 and Tyr435 (for MAO-B) play an important role in the interaction of the enzyme with 1,4-NQ scaffold through forces of dispersion as verified for menadione, TMN and 1,4-NQ. Taken together, our findings reveal the molecular details of MAO inhibition by 1,4-NQ scaffold and show for the first time that menadione acts as a competitive and reversible inhibitor of human MAO.
Background
In North America and Europe, return‐to‐work (RTW) rates vary among breast cancer (BC) survivors, from 24% to 66% and from 53% to 82% at 6 and 36 months after diagnosis, respectively. To ...date, there is a lack of data on RTW rates after BC diagnosis in Latin America. Therefore, the primary objectives of this study were to define RTW rates at 12 and 24 months after BC diagnosis and to identify the factors associated with RTW in this population.
Methods
In total, 125 employed women from a single institution with newly diagnosed BC were interviewed by telephone at 6, 12, and 24 months after diagnosis. Those who had inoperable or metastatic disease were excluded.
Results
Overall, RTW rates were 30.3% and 60.4% at 12 and 24 months after BC diagnosis, respectively. Most women reported that they received support from their employer, but only 29.1% reported having been offered work adjustments. In multivariate analysis, the factors associated with positive RTW outcomes included higher household income (odds ratio OR, 17.76; 95% confidence interval CI, 3.33‐94.75; P = .001), breast‐conserving surgery (OR, 9.77; 95% CI, 2.03‐47.05; P = .004), and work adjustments (OR, 37.62; 95% CI, 2.03‐47.05; P = .004). The factors associated with negative RTW outcomes included adjuvant endocrine therapy (OR, 0.11; 95% CI, 0.02‐0.74; P = .023), and depression diagnosed after BC (OR, 0.07; 95% CI, 0.01‐0.63; P = .017).
Conclusions
RTW rates in the current study were lower than those observed in developed countries but similar to the rates among low‐income Americans. Workplace adjustments, higher income, breast‐conserving surgery, endocrine therapy, and depression after BC played an important role in the RTW decision.
After a diagnosis of breast cancer, return‐to‐work rates among Latin Americans appear to be lower than those observed in developed countries but similar to those in low‐income North Americans. Workplace adjustments, higher household income, breast‐conserving surgery, endocrine therapy, and depression after diagnosis play important roles in the decision to return to work.
Breast cancer (BC) is the most common type of cancer in premenopausal women with germline TP53 pathogenic variants (mTP53) (Li Fraumeni syndrome - LFS). However, little is known about the BC ...prognosis in these patients. This study analyzed the BC-related oncologic outcomes of patients with LFS.
We evaluated a cohort of LFS patients with BC in comparison with a control cohort of BC patients with no pathogenic variant in a hereditary cancer panel. The primary endpoint was recurrence-free survival (RFS). Due to the risk of second malignancies in LFS, only locoregional and distant recurrences were considered events for RFS. Secondary endpoints included rates of contralateral BC, overall survival (OS), and breast cancer-specific survival (BCSS).
Forty-one patients were evaluated in the mTP53 group and 82 in the control group. Median age at BC diagnosis was 40 and 41 years, respectively. The mTP53 group received less adjuvant radiotherapy than the control group (63.4% vs 93.9%, P < 0.001). Other relevant baseline characteristics and treatment received were similar between groups. 5y-RFS rates were 79.4% in the mTP53 versus 93.6% in the control group (HR 2.43, 95%CI 0.74–8.01, P = 0.143); and were not impacted by the use of adjuvant radiotherapy. 5y-BCSS rates were 92.2% and 98.6%, respectively (HR 1.87, IC95% 0.25–13.48, P = 0.534).
Our results showed no statistically significant difference in BC-related RFS and BCSS between patients with mTP53 and a control group with no pathogenic variant. Larger multicentric studies are warranted to confirm these results.
•Women with Li Fraumeni syndrome (LFS) have a high risk of breast cancer (BC).•BC in LFS is frequently estrogen receptor-positive and HER2-positive.•Nevertheless, little is known about BC behavior and prognosis in these patients.•We evaluated BC-related outcomes in LFS, including recurrence-free survival (RFS).•5-year RFS was 79% in the LFS group and 93% in a matched control group (P = 0.143).
Abstract Campomanesia xanthocarpa (Mart.) O. Berg is a South American fruit tree species with important ecological and medicinal properties, which remnants are currently found mainly in isolated ...forest fragments. In this study, SSR markers from three different genomic origins (gene-linked, nuclear neutral, and organellar) were used to evaluate the patterns of genetic diversity, fine-scale spatial genetic structure and historical gene flow in fragmented forest formations of C. xanthocarpa from the Atlantic Forest in southern Brazil. Our results show that the forest fragments present moderate to high levels of genetic diversity in comparison to species presenting similar life traits, although a trend opposite to expected was observed concerning gene-linked and neutral SSR markers. The fine-scale spatial genetic structure revealed different patterns in short and large distance classes, with a distinct influence of gene-linked and neutral markers in driving the genetic structure in each distance class. The presence of an isolation-by-adaptation pattern implies the need for maintenance of the current remnants to assure the conservation of the private alleles. Finally, as the genetic diversity is found predominantly within forest fragments, programs of seed collection and/or genetic rescue should prioritize a larger number of individuals within each fragment, to increase the sampled diversity.
Sport specific movements coming along with characteristic plantar pressure distribution and a fatigue of muscles result in an increasing postural sway and therefore lead to a decrease in balance ...control. Although single soccer specific movements were expatiated with respect to these parameters, no information is available for a complete training session. The objective of the present observational study was to analyze the direct influence of soccer training on postural stability and gait patterns and whether or not these outcomes were altered by age. One hundred and eighteen experienced soccer players participated in the study and were divided into two groups. Group 1 contained 64 soccer players (age 13.31±0.66 years) and Group 2 contains 54 ones (age 16.74±0.73 years). Postural stability, static plantar pressure distribution and dynamic foot loading patterns were measured. Our results showed that the soccer training session, as well as the age, has relevant influence on postural stability, while the age only (excluding the training) has an influence on static plantar pressure distribution. The parameters of dynamic assessment seem therefore to be affected by age, training and a combination of both. Training and young age correlate with a decreased postural stability; they lead to a significant increase of peak pressure in the previously most loaded areas, and, after reaching a certain age and magnitude of absolute values, to a change in terminal stance and preswing phase of the roll-over. Moreover, younger players show an inhomogenous static plantar pressure distribution which might be the result of the decreased postural control in the young age.
Topical antimicrobial drugs are indicated for limited superficial pyodermitis treatment, although they are largely used as self-prescribed medication for a variety of inflammatory dermatoses, ...including atopic dermatitis. Monitoring bacterial susceptibility to these drugs is difficult, given the paucity of laboratory standardization.
To evaluate the prevalence of Staphylococcus aureus topical antimicrobial drug resistance in atopic dermatitis patients.
We conducted a cross-sectional study of children and adults diagnosed with atopic dermatitis and S. aureus colonization. We used miscellaneous literature reported breakpoints to define S. aureus resistance to mupirocin, fusidic acid, gentamicin, neomycin and bacitracin.
A total of 91 patients were included and 100 S. aureus isolates were analyzed. All strains were methicillin-susceptible S. aureus. We found a low prevalence of mupirocin and fusidic acid resistance (1.1% and 5.9%, respectively), but high levels of neomycin and bacitracin resistance (42.6% and 100%, respectively). Fusidic acid resistance was associated with more severe atopic dermatitis, demonstrated by higher EASI scores (median 17.8 vs 5.7, p=.009). Our results also corroborate the literature on the absence of cross-resistance between the aminoglycosides neomycin and gentamicin.
Our data, in a southern Brazilian sample of AD patients, revealed a low prevalence of mupirocin and fusidic acid resistance of S. aureus atopic eczema colonizer strains. However, for neomycin and bacitracin, which are commonly used topical antimicrobial drugs in Brazil, high levels of resistance were identified. Further restrictions on the use of these antimicrobials seem necessary to keep resistance as low as possible.
Repetitive genomic elements were prospected in
Campomanesia xanthocarpa
, aiming to characterize these elements in a non-model plant species and to develop species-specific microsatellite markers. ...Approximately 4.12% of the partial genome of
C. xanthocarpa
is composed of repetitive elements, being retrotransposons the most widely represented. A total of nine polymorphic microsatellite markers were obtained: four nuclear-neutral, two nuclear EST, two plastidial and one mitochondrial. Levels of population genetic diversity of four natural populations of
C. xanthocarpa
were characterized using these markers. In addition, the cross-species amplification of the microsatellite markers was tested in seven species of tribe Myrteae (Myrtaceae). The characterized microsatellite markers revealed low to moderate levels of genetic diversity (expected heterozygosity range: 0.33–0.57; observed heterozygosity: 0.26–0.74 and number of alleles: 2.25–4.25). Cross-species amplification was successful for all loci, except Cxant76. These nine markers will contribute for studies on genetic diversity, gene flow, plant selection and breeding of this species, towards the conservation of natural populations, as well as its commercial use.
Metronomic therapy has been gaining importance in the neoadjuvant setting of breast cancer treatment. Its clinical benefits may involve antiangiogenic machinery. Cancer cells induce angiogenesis to ...support tumor growth by secreting factors, such as vascular endothelial growth factor (VEGF). In breast cancer, Trastuzumab (TZM) based treatment is of key importance and is believed to reduce diameter and volume of blood vessels as well as vascular permeability. Here in we investigated serum levels of angiogenic factors VEGF and MCSF in patients receiving metronomic neoadjuvant therapy with or without TZM. We observed in HER2+ cohort stable levels of MCSF through treatment, whereas VEGF trend was of decreasing levels. In HER2- cohort we observed increasing levels of MCSF and VEGF trend. Overall, HER2+ patients had better pathological response to treatment. These findings suggest that angiogenic pathway may be involved in TZM anti-tumoral effect in the neoadjuvant setting.
PDF
