Applications of Silver Nanoparticles in Patent Research.

BACKGROUND: Silver nanoparticles (AgNPs) have been widely applied in research and industrial fields, finding applications in nanomedicine, drug delivery, biomedical devices, electronics, the energy sector, and environmental protection. Patents provide information on the industrial viability of product technologies, and the number of patent documents provides an estimate of the evolution of a specific technological field. AIMS: The present work aims to describe the current trends in AgNPs patent applications. In addition, a retrospective study of published patents in Brazil is presented. METHODS: Analyses of AgNPs-related patents were conducted using the free platform for patent search Lens® in 2010-2019 and articles published in same period using the Scholar® base. The patent applications and their evolution over time, major depositors and holders, and the main technological areas associated with AgNP applications have been described. RESULTS: China and United States are the major patent applicants for nanotechnologies. The worldwide distribution of publications of journal articles shows that China, India, and the United States are the leading countries in the total number of articles published, in that order. CONCLUSION: Our study of patent applications and published articles confirmed the growing global increase in new technologies involving NPs and AgNPs, particularly in the biotechnology area, in the fields of medicine and agriculture.

Could Necroleachate Be the Cemetery's Sewage? A Panorama from Brazilian Legislation.

Cemeteries can be compared to landfills, as the leachate produced in these areas, also known as necroleachate, can be environmentally transported, polluting groundwater, surface water, and soil. In Brazil, to ensure no negative environmental impacts and public health risks, cemetery management is the responsibility of states and municipalities. In this context, this article aims to discuss Brazilian sanitary-environmental legislation concerning cemetery waste management. Only half of all Brazilian states have established sanitary-environmental cemetery legislation, and only 19 municipalities have specific laws. These laws, however, are broad and contain many gaps. Necroleachate care and control require both sanitary and environmental assessments to avoid environmental vulnerability and contamination risks for populations inhabiting surrounding areas. In this regard, new water analysis parameters in environmentally vulnerable areas should be established to control the population's drinking water quality, such as the detection of C. perfringens. Furthermore, the construction of vertical cemeteries instead of horizontal ones and the adoption of cremation procedures should also be considered. This assessment comprises a novel research framework, as no studies on the impact of Brazilian laws on environmental necroleachate contamination are available to date.

Effects of babassu nut oil on ischemia/reperfusion-induced leukocyte adhesion and macromolecular leakage in the microcirculation: observation in the hamster cheek pouch.

BACKGROUND: The babassu palm tree is native to Brazil and is most densely distributed in the Cocais region of the state of Maranhão, in northeastern Brazil. In addition to the industrial use of refined babassu oil, the milk, the unrefined oil and the nuts in natura are used by families from several communities of African descendants as one of the principal sources of food energy. The objective of this study was to evaluate the effects of babassu oil on microvascular permeability and leukocyte-endothelial interactions induced by ischemia/reperfusion using the hamster cheek pouch microcirculation as experimental model. METHODS: Twice a day for 14 days, male hamsters received unrefined babassu oil (0.02 ml/dose [BO-2 group], 0.06 ml/dose [BO-6 group], 0.18 ml/dose [BO-18 group]) or mineral oil (0.18 ml/dose [MO group]). Observations were made in the cheek pouch and macromolecular permeability increase induced by ischemia/reperfusion (I/R) or topical application of histamine, as well as leukocyte-endothelial interaction after I/R were evaluated. RESULTS: The mean value of I/R-induced microvascular leakage, determined during reperfusion, was significantly lower in the BO-6 and BO-18 groups than in the MO one (P < 0.001). In addition, histamine-induced increase of microvascular permeability was significantly less pronounced in BO groups compared to MO one. No significant differences among groups in terms of leukocyte adhesion, concentrations of tumor necrosis factor alpha, interleukin 1, and interleukin 6 were found. CONCLUSIONS: Our findings suggest that unrefined babassu oil reduced microvascular leakage and protected against histamine-induced effects in postcapillary venules and highlights that these almost unexploited nut and its oil might be secure sources of food energy.

Effects of replica running shoes upon external forces and muscle activity during running.

Twelve participants ran (9 km · h(-1)) to test two types of running shoes: replica and original shoes. Ground reaction force, plantar pressure and electromyographic activity were recorded. The shoes were tested randomly and on different days. Comparisons between the two experimental conditions were made by analysis of variance (ANOVA) test (P ≤ 0.05). The time to first peak, loading rate of the first peak and impulse of the first 75 ms of stance were significantly different between the shoes (P ≤ 0.05), revealing an increase of impact forces for the replica shoes. The peak plantar pressure values were significantly higher (P ≤ 0.05) when wearing replica shoes. During running, the contact area was significantly smaller (P ≤ 0.05) for the replica shoe. The electromyographic activity of the analysed muscles did not show changes between the two shoes in running. These findings suggest that the use of replica running shoes can increase the external load applied to the human body, but may not change the muscle activity pattern during locomotion. This new mechanical situation may increase the risk of injuries in these movements.

Aging effects of haptic input on postural control under a dual-task paradigm.

Postural control relies on three principal sensory systems: vision, vestibular and proprioceptive; that are affected by aging. When performing a cognitive task concomitantly with a motor task, those sensory impairments lead to even greater deleterious effects on balance. We aimed to study the effects of a sensory aid (a light touch) on a dual task paradigm and sought to understand the different responses on balance due to aging. Fifty healthy and highly physical active women were divided in two groups: young (N = 25, 24.2 ± 4.0 years) and older adults (N = 25, 67.3 ± 4.2 years). In a random and balanced order, all participants performed five tasks: Stroop test while seated (Seated); Stroop test while standing quiet (ST); Standing quiet (BL); Standing quiet with a haptic input (LT); and Stroop test with a haptic input while standing quiet (SL). In the Stroop test, older women committed more errors (50 vs 11 errors, p < 0.001) and had higher reaction time (1.001 ± 0.191 vs 0.699 ± 0.081 s, p < 0.001). The haptic input (LT) reduced all body sway parameters, in both groups, regardless the condition. This means that postural control under a dual task paradigm (ST) deleterious effect can be mitigated by a haptic input.

Methodology for a Comprehensive Health Impact Assessment in Water Supply and Sanitation Programmes for Brazil.

Based on the broader concept of health proposed by the Pan-American Health Organization/World Health Organization (PAHO/ WHO), 2018, and the absence in the literature of indices that translate the causal relationship between sanitation and health, a methodology for assessing the health impact of a water and sanitation programmes, known as a Health Impact Assessment (HIA), was developed, specifically in the Brazilian context, and focused on a school in the northeast of the country. Through exploratory and descriptive evidence, and using documentary research as a method, a retrospective survey was carried out from 2000 to 2022 using documents proposing evaluation methodologies. A single document was found to fit the research objective, which was used to develop the proposed HIA methodology. Development of the methodology consisted of two stages: definition of the health dimensions and selection of the indicators making up each dimension. The HIA methodology was then applied to a school in northeast Brazil to test its use, before a water-efficient management intervention was going to be used. The overall score of 46% indicated that there was room for improvement, which the new management approach could facilitate. This methodology is therefore proposed to be an instrument for the evaluation of public water and sanitation policies, thus assisting managers in the decision-making process and in guiding sanitation programs and plans.

Schinus terebinthifolius Leaf Lectin (SteLL) Reduces the Bacterial and Inflammatory Burden of Wounds Infected by Staphylococcus aureus Promoting Skin Repair.

Staphylococcus aureus is commonly found in wound infections where this pathogen impairs skin repair. The lectin isolated from leaves of Schinus terebinthifolius (named SteLL) has antimicrobial and antivirulence action against S. aureus. This study evaluated the effects of topical administration of SteLL on mice wounds infected by S. aureus. Seventy-two C57/BL6 mice (6−8 weeks old) were allocated into four groups: (i) uninfected wounds; (ii) infected wounds, (iii) infected wounds treated with 32 µg/mL SteLL solution; (iv) infected wounds treated with 64 µg/mL SteLL solution. The excisional wounds (64 mm2) were induced on the dorsum and infected by S. aureus 432170 (4.0 × 106 CFU/wound). The daily treatment started 1-day post-infection (dpi). The topical application of both SteLL concentrations significantly accelerated the healing of S. aureus-infected wounds until the 7th dpi, when compared to untreated infected lesions (reductions of 1.95−4.55-fold and 1.79−2.90-fold for SteLL at 32 µg/mL and 64 µg/mL, respectively). The SteLL-based treatment also amended the severity of wound infection and reduced the bacterial load (12-fold to 72-fold for 32 µg/mL, and 14-fold to 282-fold for 64 µg/mL). SteLL-treated wounds show higher collagen deposition and restoration of skin structure than other groups. The bacterial load and the levels of inflammatory markers (IL-6, MCP-1, TNF-α, and VEGF) were also reduced by both SteLL concentrations. These results corroborate the reported anti-infective properties of SteLL, making this lectin a lead candidate for developing alternative agents for the treatment of S. aureus-infected skin lesions.

Perception of impact is affected by stimulus intensity.

Perception of external loads may be a central topic to understand adjustments to the mechanical demands during movement. Nevertheless, the association between the perceived and the real load received is still controversial. This study aimed to correlate vertical ground reaction force (vGRF) to the perception of impact in different regimens of stimulus application. Ten physically active men performed drop jumps from four different heights (0.20, 0.40, 0.60 and 0.80 m). A force plate measured the vGRF, while perception of impact was evaluated through Borg's Ratings of Perceived Exertion. Higher values of maximum vGRF (Fy_max) and impulse of the first 50 ms (I_50), and reduced time to reach Fy_max indicate increased external forces as drop jump height raised. Perception of impact increased gradually with increasing jump height for I_50. Fy_max and I_50 showed moderate to strong correlations to perceived load for 70% and 90% of participants, respectively. Higher and different intensity of stimulus facilitated the perception of impact, presenting moderate to strong correlations to kinetic parameters related to external load during landing from drop jump. Perception of higher impacts could be used as a surrogate to monitor 'real' impacts and possibly also for managing impact-related injury risk.

First-trimester miscarriage: A histopathological classification proposal.

BACKGROUND: Histopathology of first-trimester abortion products may be useful in document an intrauterine pregnancy, identifying an important pathology affecting the mother or the embryo and diagnosing conditions that are likely to recur in future pregnancies or that explain the adverse fetal outcome. Relevant information provided by histology is essential to determine the cause and to guide the patients with early pregnancy failure. AIMS: Histopathological classification proposal in first-trimester miscarriage. METHODS: Published pathological criteria in first-trimester abortion specimens were collected, standardized and focused into a comprehensive diagnosis. The idea was to create a comprehensive classification related to major pathophysiological processes. Thus, the histological criteria were grouped into 7 categories: i. Changes suggesting aneuploidy (CSA) or metabolic storage disease; ii. Embryo anomaly (EA); iii. Multifactorial (MF) causes; iv. Maternal causes (MC); v. Gestational trophoblastic disease, such as hydatidiform mole (HM) and non neoplastic lesions and neoplasms; vi. Ectopic pregnancy; vii. Other. So, a 6-years retrospective study of first-trimester spontaneous miscarriage were reviewed. Two groups were created: i. Study group include specimens with pathological diagnosis; ii. Control group incorporate specimens with pathological diagnosis and additional genetic study in order to validate pathological criteria. RESULTS: Pathological criteria concordance between inter-observers was generally good, with an excellent correlation in EA and HM categories. Despite greater inter-observer disagreement in the CSA and MC categories the correlation with the genetic results was very positive. CONCLUSION: A standardized, reproducible and biologically comprehensive histopathological classification may improve fetal follow-up and couple's management.

Genotoxic effects of the antileishmanial drug Glucantime.

Leishmaniasis is caused by species of the protozoan parasite Leishmania. It is the third most important vector-borne disease and is widely distributed throughout the world. The World Health Organization recommends pentavalent antimonials as drugs of first choice in its treatment. Although Glucantime has traditionally been used to treat leishmaniasis, there are still many questions about its structure, mechanisms of action and ability to induce damage in DNA. In this study, the genotoxic activity of this drug was evaluated in vitro using human lymphocytes treated for 3 and 24 h (comet assay) and 48 h (apoptosis assay) with 3.25, 7.5 and 15 mg/ml of Glucantime, respectively, corresponding to 1.06, 2.12 and 4.25 mg/ml of pentavalent antimony. In the in vivo tests, Swiss mice received acute treatment with three doses (212.5, 425 and 850 mg/kg) of pentavalent antimony. All the treatments were administered intraperitoneally in the volumes of 0.1 ml/10 g of body weight, adapting human exposure to murine conditions. The animals were treated for 3 h in the comet assay using resident peritoneal exudate macrophages, for 24 h in the comet assay using peripheral blood leukocytes and for 24 h in the bone marrow erythrocyte micronucleus test. While no genotoxic effect was observed in the in vitro tests, the in vivo tests showed that Glucantime induces DNA damage. These findings indicate that Glucantime is a promutagenic compound that causes damage to DNA after reduction of pentavalent antimony (SbV) into the more toxic trivalent antimony (SbIII) in the antimonial drug meglumine antimoniate.

Human monocytes but not dendritic cells are killed by blocking of autocrine cyclooxygenase activity.

Dendritic cells (DCs), in peripheral tissues, derive mostly from blood precursors that differentiate into DCs under the influence of the local microenvironment. Monocytes constitute the main known DC precursors in blood and their infiltration into tissues is up-regulated during inflammation. During this process, the local production of mediators, like prostaglandins (PGs), influence significantly DC differentiation and function. In the present paper we show that treatment of blood adherent mononuclear cells with 10microM indomethacin, a dose achieved in human therapeutic settings, causes monocytes' progressive death but does not affect DCs viability or cell surface phenotype. This resistance of DCs was observed both for cells differentiated in vitro from blood monocytes and for a population with DCs characteristics already present in blood. This phenomenon could affect the local balance of antigen-presenting cells, influence the induction and pattern of immune responses developed under the treatment with non-steroidal anti-inflammatory drugs and, therefore, deserves further investigation.

The role of GSTA2 polymorphisms and haplotypes in breast cancer susceptibility: a case-control study in the Portuguese population.

Glutathione-S-transferases (GSTs) are a super-family of phase II metabolizing enzymes that catalyse the detoxification of a large range of endogenous and exogenous toxic compounds, playing an important role in protecting cells against damage, through glutathione conjugation with electrophilic substances. Polymorphic variation in these enzymes that affect its activity seems to be related to individual susceptibility to various human diseases, including cancer. Of the GST super-family, the alpha class GSTs have commonly been described as one of the most versatile class, since it is responsible for detoxification of compounds such as bilirubin, bile acids and penicillin, thyroid and steroid hormones, allowing its solubilization and storage in the liver. Among the alpha class, GSTA1 and GSTA2 isoforms are the most widely expressed in human tissues. Additionally, these enzymes can catalyse conjugation of the nitrogen mustard group of alkylating anticancer drugs, some heterocyclic amines and alpha,beta-unsaturated aldehydes. Since some risk factors for increased breast cancer risk could be related to high production of reactive oxygen species during the metabolism of estrogens by catechol estrogens, or to the exposure to genotoxic compounds, and some of these toxic compounds are usually metabolized by GSTA2, we carried out a hospital based case-control study in a Caucasian Portuguese population (291 breast cancer patients without familiar history of breast cancer and 547 controls matched for age, sex and ethnicity) in order to evaluate the potential modifying role of three non-synonymous polymorphisms in the GSTA2 gene (P110S Ex 5+56C>T;, rs2234951; S112T Ex5+63G>C, rs2180314 and E210A Ex7+83A>C, rs6577) on the individual susceptibility to breast cancer. Our data show that the studied polymorphisms are in strong linkage disequilibrium, but no association was observed between individual GSTA2 polymorphisms and haplotypes and individual susceptibility to breast cancer.

Thyroid Cancer: The Quest for Genetic Susceptibility Involving DNA Repair Genes.

The incidence of thyroid cancer (TC), particularly well-differentiated forms (DTC), has been rising and remains the highest among endocrine malignancies. Although ionizing radiation (IR) is well established on DTC aetiology, other environmental and genetic factors may also be involved. DNA repair single nucleotide polymorphisms (SNPs) could be among the former, helping in explaining the high incidence. To further clarify the role of DNA repair SNPs in DTC susceptibility, we analyzed 36 SNPs in 27 DNA repair genes in a population of 106 DTCs and corresponding controls with the aim of interpreting joint data from previously studied isolated SNPs in DNA repair genes. Significant associations with DTC susceptibility were observed for XRCC3 rs861539, XPC rs2228001, CCNH rs2230641, MSH6 rs1042821 and ERCC5 rs2227869 and for a haplotype block on chromosome 5q. From 595 SNP-SNP combinations tested and 114 showing relevance, 15 significant SNP combinations (p < 0.01) were detected on paired SNP analysis, most of which involving CCNH rs2230641 and mismatch repair variants. Overall, a gene-dosage effect between the number of risk genotypes and DTC predisposition was observed. In spite of the volume of data presented, new studies are sought to provide an interpretability of the role of SNPs in DNA repair genes and their combinations in DTC susceptibility.

Creatine supplementation can improve impact control in high-intensity interval training.

OBJECTIVES: This study aimed to investigate the effects of creatine (Cr) supplementation on biomechanical parameters related to shock attenuation during a session of high-intensity interval training (HIIT). METHODS: A single-blinded, placebo-controlled, crossover design was adopted to test eight male elite soccer players during HIIT sessions under two conditions: after placebo supplementation and after Cr supplementation. HIIT test sessions consisted of an intermittent test (five bouts of running) with a constant load applied until exhaustion was reached. The vertical component of ground reaction force and electromyography data were recorded by Gaitway and Lynx-EMG Systems, respectively. Heart rate, rated perceived exertion (Borg's Scale) and lactate concentration information were also obtained. RESULTS: Cr supplementation did not affect heart rate, rated perceived exertion, and lactate concentration. Decreased values of magnitude of the first peak of the vertical component of ground reaction force (17.2-24.2%) and impulse of the first 50 ms (Imp50; 34.3%) were observed for Cr, but higher values of time to reach the first peak were detected for Cr compared with placebo. Significant modifications in muscle activation were also observed, mainly in the pre-activation phase, and changes were observed in intermediary bouts. CONCLUSIONS: Cr supplementation has the potential to influence biomechanical parameters related to impact control during a single session of HIIT based on running. In particular, the findings of the current study indicate possible improvements in shock attenuation and a safer practice of HIIT under Cr supplementation.

Treatment Sequencing in a Chronic Lymphocytic Leukemia Patient with Central Nervous System Involvement.

Early-stage chronic lymphocytic leukemia (CLL) with neurologic involvement is a rare condition and should require a careful follow-up. Although no standard protocol exists for this condition, intrathecal chemotherapy, combined with systemic chemoimmunotherapy, has been used previously. This case describes the treatment of a patient with CLL and symptomatic compromise of the central nervous system. Our results suggest that a combination of chemotherapy, radiotherapy, and ibrutinib, administered sequentially over a 2-year period, led to a near-complete resolution of the cerebral spinal fluid neoplastic infiltration. Importantly, this response has been maintained with ibrutinib monotherapy for more than 12 months.

Atypical haematological presentation in a case of polycythaemia vera with a new variant mutation detected in exon 12: c.1605G>T (p.Met535Ile).

One of the major genetic insights into the pathogenesis of polycythaemia vera included the identification of the somatic point gain-of-function mutations in Janus kinase 2 gene-first JAK2V617F on exon 14, present in 95%-97% of the cases, and later on exon 12. In the literature, we can find some reported studies where different exon 12 mutations are identified. Unlike patients with JAK2V617F mutation in exon 14, the mutation at exon 12 is not usually associated with an increase in the three haematopoietic series (erythrocytosis, leucocytosis and thrombocytosis). It appears to be associated with a distinct syndrome, mostly characterised by isolated and more marked erythrocytosis, independently of the mutational variant. We report here the case of a patient who is JAK2exon 12 positive, presenting a novel mutation-c.1605G>T (p.Met535Ile)-associated with c.1612C>T (p.His538Tyr) mutation previously described, evidencing an atypical clinical phenotype.

Anti-arthritic properties of crude extract from Chenopodium ambrosioides L. leaves.

OBJECTIVES: To evaluate the effect of hydroalcoholic crude extract (HCE) from Chenopodium ambrosioides leaves on the development of type II collagen-induced arthritis (CIA) and on pro-inflammatory cytokine balance. METHODS: Collagen-induced arthritis was induced in DBA1/J mice. On the 21st day, the mice were treated orally with HCE or methotrexate, daily. Six weeks after beginning the treatment, the following measures were determined: lymphoid organs cell numbers, percentage of blood cells, IL-6, IFN-γ, TNF-α and IL-17 serum concentrations, activity of hepatic and kidney glutathione S-transferase, hepatic 7-ethoxyresorufin-O-deethylase activity, bone density and histopathology. KEY FINDINGS: Treatment of CIA mice with HCE 5 mg/kg (HCE5) reduced the percentage of neutrophils and macrophages and the number of bone marrow cells and increased the lymphocyte numbers and the inguinal lymph node cellularity. This treatment inhibited the serum concentration of IL-6 and TNF-α, which may be related to the preservation of bone density and to the slight thickening of periarticular tissues, with minimal fibrosis and fibroblast proliferation in the joints. The CIA group presented advanced articular erosion and synovial hyperplasia. Phytochemical analysis showed mainly flavonols. CONCLUSIONS: HCE5 presented anti-arthritic potential and reduced IL-6 and TNF-α, which participate directly in the development and maintenance of the inflammatory process in rheumatoid arthritis.

Anti-thrombotic effect of chronic oral treatment with Orbignya phalerata Mart.

Babassu is the popular name of Orbignya phalerata Mart. (Arecaceae). The mesocarp flour obtained from their fruits has been used in Brazil as medicine in the treatment of pains, constipation, obesity, leukemia, rheumatism, ulcerations, tumors, inflammations and venous diseases. The effect of the chronic oral treatment with aqueous extract of babassu mesocarp (500mg/kgday) on the number of platelets, the prothrombin time (PT), the activated partial thromboplastin time (aPTT), the nitric oxide (NO) production and the carrageenin-induced thrombosis was evaluated, using C57Bl/6 mice. The chronic oral treatment with babassu mesocarp induced an anti-thrombotic effect. There was a 88.9% reduction in the necrosis of the tail. This effect seems to be related to an increase in the ability of the macrophage to produce NO and to a slow coagulation process associated to an increase of 12.0 and 13.9% in PT and aPTT, respectively. However, the anti-thrombotic effect seems to be not related to alterations in the number of platelets. It is possible to conclude that the oral treatment with babassu mesocarp has a significant anti-thrombotic effect, which could justify the popular use of babassu mesocarp in the treatment of venous diseases. Meanwhile, this study suggests a potential use of babassu mesocarp as a prophylactic agent to avoid thrombosis events.

Prevalence of the Janus kinase 2 V617F mutation in Philadelphia-negative myeloproliferative neoplasms in a Portuguese population.

Myeloproliferative neoplasms (MPNs) result from the malignant transformation of a hematopoietic stem-cell (HSC), leading to abnormal amplification and proliferation of myeloid lineages. Identification of the Janus kinase 2 (JAK2) V617F mutation developed the knowledge of Philadelphia-negative (PN)-MPNs, contributing to and influencing the definition of the phenotype and prognostic impact. Considering the lack of Portuguese epidemiological data, the present study intends to characterize the prevalence of the JAK2 mutation in a PN-MPN versus a control Portuguese population. Caucasian Portuguese PN-MPN patients (n=133) and 281 matched control subjects were investigated. No significant differences were identified between the case and control groups concerning age distribution or smoking habits. Pathology distribution was as follows: 60.2% with essential thrombocythemia (ET), 29.3% with polycythemia vera (PV) and 10.5% with primary myelofibrosis (PMF). A total of 75.0% of patients were positive for the presence of the JAK2 V617F mutation. In addition, the prevalence of PV was 87.2%, ET was 73.4% and PMF was 50.0%. The JAK2 V617F mutation is observed in various MPN phenotypes, and has an increased incidence in ET patients and a decreased incidence in PV patients. These data may contribute to improving the knowledge of the pathophysiology of these disorders, and to a more rational and efficient selection of therapeutic strategies to be adopted, notably because most of the patients are JAK2 V617F negative.

Correction: 16 Weeks of Progressive Barefoot Running Training Changes Impact Force and Muscle Activation in Habitual Shod Runners.

[This corrects the article DOI: 10.1371/journal.pone.0167234.].