Glioblastoma multiforme is one of the most prevalent and malignant forms of central nervous system tumors. The treatment of glioblastoma remains a great challenge due to its location in the ...intracranial space and the presence of the blood⁻brain tumor barrier. There is an urgent need to develop novel therapy approaches for this tumor, to improve the clinical outcomes, and to reduce the rate of recurrence and adverse effects associated with present options. The formulation of therapeutic agents in nanostructures is one of the most promising approaches to treat glioblastoma due to the increased availability at the target site, and the possibility to co-deliver a range of drugs and diagnostic agents. Moreover, the local administration of nanostructures presents significant additional advantages, since it overcomes blood⁻brain barrier penetration issues to reach higher concentrations of therapeutic agents in the tumor area with minimal side effects. In this paper, we aim to review the attempts to develop nanostructures as local drug delivery systems able to deliver multiple agents for both therapeutic and diagnostic functions for the management of glioblastoma.
Hyaluronic acid (HA) and gelatin (Gel) are major components of the extracellular matrix of different tissues, and thus are largely appealing for the construction of hybrid hydrogels to combine the ...favorable characteristics of each biopolymer, such as the gel adhesiveness of Gel and the better mechanical strength of HA, respectively. However, despite previous studies conducted so far, the relationship between composition and scaffold structure and physico-chemical properties has not been completely and systematically established. In this work, pure and hybrid hydrogels of methacroyl-modified HA (HAMA) and Gel (GelMA) were prepared by UV photopolymerization and an extensive characterization was done to elucidate such correlations. Methacrylation degrees of ca. 40% and 11% for GelMA and HAMA, respectively, were obtained, which allows to improve the hydrogels’ mechanical properties. Hybrid GelMA/HAMA hydrogels were stiffer, with elastic modulus up to ca. 30 kPa, and porous (up to 91%) compared with pure GelMA ones at similar GelMA concentrations thanks to the interaction between HAMA and GelMA chains in the polymeric matrix. The progressive presence of HAMA gave rise to scaffolds with more disorganized, stiffer, and less porous structures owing to the net increase of mass in the hydrogel compositions. HAMA also made hybrid hydrogels more swellable and resistant to collagenase biodegradation. Hence, the suitable choice of polymeric composition allows to regulate the hydrogels´ physical properties to look for the most optimal characteristics required for the intended tissue engineering application.
Abstract
We report the discovery of a new ultra-faint stellar system found near the Magellanic Clouds in the DECam Local Volume Exploration Survey. This new system, DELVE J0155−6815 (DELVE 2), is ...located at a heliocentric distance of
D
⊙
= 71 ± 4 kpc, which places it at a 3D physical separation of 12 ± 3 kpc from the center of the Small Magellanic Cloud and
from the center of the Large Magellanic Cloud (LMC). DELVE 2 is identified as a resolved overdensity of old (
τ
> 13.3 Gyr) and metal-poor (
dex) stars with a projected half-light radius of
and an absolute magnitude of
. The size and luminosity of DELVE 2 are consistent with both the population of recently discovered ultra-faint globular clusters and the smallest ultra-faint dwarf galaxies. However, its photometrically derived age and metallicity would place it among the oldest and most metal-poor globular clusters in the Magellanic system. In the absence of spectroscopic measurements of the system’s metallicity dispersion and internal kinematics, we are unable to conclusively classify this system at this time. DELVE 2 is detected in
Gaia
DR2 with a clear proper-motion signal, with multiple blue horizontal-branch stars near the centroid of the system with proper motions consistent with the systemic mean. We measure the system proper motion to be
=
mas yr
−1
. We compare the spatial position and proper motion of DELVE 2 with simulations of the accreted satellite population of the LMC and find that it is very likely to be associated with the LMC.
Water resources contaminated with wastewater are an important source for the dissemination of enteric viruses with an impact on the health of the population. The aim of the study was to assess the ...viral contamination of freshwater from a dam in Argentina by using infectious enterovirus detection, viral RNA amplification, and a genetic characterization of five enteric viruses associated with diarrhea and hepatitis. Enterovirus infectivity (iEV) was evaluated by cell culture and direct immunofluorescence. The detection of the viral genome of rotavirus (RV), human astrovirus (HAstV), norovirus (NoV), hepatitis A virus (HAV), and hepatitis E virus (HEV) was performed by reverse transcriptase PCR (RT-PCR). A total of 48 water samples from 4 monitoring points on the body of the dam from January to December 2012 and 66 water samples from 3 tourist beaches on the edge of the dam from October 2013 to October 2015 were collected monthly. During the first period, the overall viral frequency detection was 52.1% for group A RV, 50% for HAstV, 60.4% for NoV, 22.9% for HAV, 2.1% for HEV, and 64.6% for iEV. The overall frequency detection for the second sampling was 18.2% for RV and HAstV, 31.8% for NoV, 7.57% for HEV, and 66.7% for iEV. There was no detection of HAV during this period. The genotypes and genogroups detected through the study correlated with the most common genomic variants associated with human gastrointestinal and hepatitis illnesses. The results obtained could alert the health systems and environmental sanitation to make decisions for viral control and prevention in our environment.
The study shows the impact of anthropic contamination of one of the most important tourist water resources in Argentina. This course of recreational water would be a favorable scenario for infection, as well as a reservoir for the enteric viruses, creating a risk for the population exposed to these waters. The results obtained could alert the health systems and environmental sanitation to make decisions for the control and prevention of viral diseases in this environment.
Immune-related adverse events (irAEs) typically occur within 4 months of starting anti-programmed cell death protein 1 (PD-1)-based therapy anti-PD-1 ± anti-cytotoxic T-lymphocyte-associated protein ...4 (CTLA4), but delayed irAEs (onset >12 months after commencement) can also occur. This study describes the incidence, nature and management of delayed irAEs in patients receiving anti-PD-1-based immunotherapy.
Patients with delayed irAEs from 20 centres were studied. The incidence of delayed irAEs was estimated as a proportion of melanoma patients treated with anti-PD-1-based therapy and surviving >1 year. Onset, clinical features, management and outcomes of irAEs were examined.
One hundred and eighteen patients developed a total of 140 delayed irAEs (20 after initial combination with anti-CTLA4), with an estimated incidence of 5.3% (95% confidence interval 4.0-6.9, 53/999 patients at sites with available data). The median onset of delayed irAE was 16 months (range 12-53 months). Eighty-seven patients (74%) were on anti-PD-1 at irAE onset, 15 patients (12%) were <3 months from the last dose and 16 patients (14%) were >3 months from the last dose of anti-PD-1. The most common delayed irAEs were colitis, rash and pneumonitis; 55 of all irAEs (39%) were ≥grade 3. Steroids were required in 80 patients (68%), as well as an additional immunosuppressive agent in 27 patients (23%). There were two irAE-related deaths: encephalitis with onset during anti-PD-1 and a multiple-organ irAE with onset 11 months after ceasing anti-PD-1. Early irAEs (<12 months) had also occurred in 69 patients (58%), affecting a different organ from the delayed irAE in 59 patients (86%).
Delayed irAEs occur in a small but relevant subset of patients. Delayed irAEs are often different from previous irAEs, may be high grade and can lead to death. They mostly occur in patients still receiving anti-PD-1. The risk of delayed irAE should be considered when deciding the duration of treatment in responding patients. However, patients who stop treatment may also rarely develop delayed irAE.
•The incidence of delayed irAEs >12 months after commencing anti-PD-1 was 5.3%.•Delayed irAEs occurred in 118 patients; these were often high grade (39% G3+) including two delayed irAE-related deaths.•Delayed irAEs were often difficult to manage; 68% required steroids and 23% required an additional immunosuppressive agent.•Most occurred during anti-PD-1 therapy (74%), but delayed irAEs were also reported up to 26 months after stopping anti-PD-1.
One of the most common respiratory chronic diseases is asthma, with 5–16 % of world prevalence. In chronic disease, prevention, diagnosis, management, and palliation are the strategies for a care ...model; the patient-self management is fundamental with the so-called therapeutic education (TE) to train the patient in the necessary skills. The challenge of TE grows when the patient is a child or a person with special needs, even more in public health care in low- and middle-income countries. This is a problematic human situation, that needs soft system thinking. In this research, the analytic hierarchy process was used to determine the perceived importance of the factors that affect children's asthma health care in a public health institution in Mexico. The soft systems methodology (SSM) was applied to learn about the disease self-management, in order to obtain activities models and an action plan. According to AHP, human resources and education were percived as the most important among the factors that affect children health care within the institution. The perceived importance of two main subfactors (human resources training and TE) was around 34 %, which emphasizes the need to generate strategies for the improvement of the education of patients and health care providers. In MSS, the rich vision, the CATWOE, the root definition, and an activities model were proposed, including the application of an instructional design methodology (ADDIE) for the development of learning objects of asthma for children. Desirable and feasible actions and recommendations include the update of the national clinical practice guides, the use of control measures such as the Asthma Control Test, and a daily asthma diary to register the daily status of the breathing capacity, the drug administration, and the potential trigger events. The proposed model can be used as part of a systemic patient-and-family centered approach for chronic care model (CCM), particularly in diseases unsuitable for prevention interventions.
The impact of vectorial magnetic field effects on electrical conductivity and nonlinear optical transmittance exhibited by multi-wall carbon nanotubes was studied. The samples were synthetized by an ...aerosol pyrolysis processing route in a thin film form. Optical signals in a two-wave mixing configuration allowed us to identify two orthogonal directions of propagation for a magnetic field travelling through the nanomaterials studied. A selective modification in optical absorption was considered to be induced by magnetic perturbations in the sample. Standard optical Kerr gate measurements were carried out for exploring the third order nonlinear optical behavior of the film. A capacitive effect influenced by optical and magnetic excitations was distinguished to be characteristic of the sample. Magneto-quantum conductivity sensitive to the direction of an external magnetic field interacting with the tubes was analyzed. Magnetically-induced changes in electronic band parameters seem to be the main responsible for the optical and electrical modulation observed in the nanostructures. Immediate applications for developing magneto-optical and magneto-electrical functions can be contemplated.
Neuroendocrine neoplasms represent an uncommon disease with an increasing incidence. Thanks to improvements in diagnostic and therapeutic methods, metastases previously considered uncommon, such as ...bone metastases, or even very rare, such as brain, orbital and cardiac metastases, are more frequently found in daily practice. Due to the great heterogeneity of these neoplasms, there is a lack of high-quality evidence on the management of patients with these types of metastases. The aim of this review is to provide the current state of the art, reviewing neuroendocrine neoplasm specific studies and useful information from other tumor types and to propose a treatment recommendation with algorithms to consider in daily clinical practice.
•Bone metastases are considered a poor prognosis factor in context of advanced disease.•Bone metastases complications with bone-targeted agents and good multimodality treatment.•Brain, cardiac and orbital metastases are rare. Radiotherapy is preferred in orbital and brain metastases.•Prospective clinical trials focusing on bone and brain metastases-related outcomes in patients with neuroendocrine tumours are needed.•Studies focused on primary prevention and selection of high risk patients of skeletal-related events with bone-targeted agents are needed.
The resilience of forests to drought events has become a major natural resource sustainability concern, especially in response to climate change. Yet, little is known about the legacy effects of ...repeated droughts, and tree species ability to respond across environmental gradients. In this study, we used a tree‐ring database (121 sites) to evaluate the overall resilience of tree species to drought events in the last century. We investigated how climate and geography affected the response at the species level. We evaluated temporal trends of resilience using a predictive mixed linear modeling approach. We found that pointer years (e.g., tree growth reduction) occurred during 11.3% of the 20th century, with an average decrease in tree growth of 66% compared to the previous period. The occurrence of pointer years was associated with negative values of the Standardized Precipitation Index (SPI, 81.6%) and Palmer Drought Severity Index (PDSI, 77.3%). Tree species differed in their resilience capacity, however, species inhabiting xeric conditions were less resistant but with higher recovery rates (e.g., Abies concolor, Pinus lambertiana, and Pinus jeffreyi). On average, tree species needed 2.7 years to recover from drought events, with extreme cases requiring more than a decade to reach pre‐drought tree growth rates. The main abiotic factor related to resilience was precipitation, confirming that some tree species are better adapted to resist the effects of droughts. We found a temporal variation for all tree resilience indices (scaled to 100), with a decreasing resistance (−0.56 by decade) and resilience (−0.22 by decade), but with a higher recovery (+1.72 by decade) and relative resilience rate (+0.33 by decade). Our results emphasize the importance of time series of forest resilience, particularly by distinguishing the species‐level response in the context of legacy of droughts, which are likely to become more frequent and intense under a changing climate.
Drought has become a major threat to the vitality of forests. The study looks into the legacy effect of repeated droughts on the resilience capacity using a pooled national tree‐ring database. Years with pointer events (e.g., tree growth reduction) occurred during 11.3% of the 20th century, with an average decrease in tree growth of 66% compared to the previous period. Tree species differed in their resilience capacity; yet, species inhabiting xeric conditions were less resistant but with higher recovery rates. Precipitation was related to the trees' resilience. Furthermore, a temporal variation in resilience indices was observed.
The study identified insecticidal effects from the cinnamon and clove essential oils in Tenebrio molitor L. (Coleoptera: Tenebrionidae). The lethal concentrations (LC50 and LC90), lethal time, and ...repellent effect on larvae, pupae, and adults of T. molitor after exposure to six concentrations of each essential oil and toxic compounds were evaluated. The chemical composition of the cinnamon oil was also determined and primary compounds were eugenol (10.19%), trans-3-caren-2-ol (9.92%), benzyl benzoate (9.68%), caryophyllene (9.05%), eugenyl acetate (7.47%), α-phellandrene (7.18%), and α-pinene (6.92%). In clove essential oil, the primary compounds were eugenol (26.64%), caryophyllene (23.73%), caryophyllene oxide (17.74%), 2-propenoic acid (11.84%), α-humulene (10.48%), γ-cadinene (4.85%), and humulene oxide (4.69%). Cinnamon and clove essential oils were toxic to T. molitor. In toxic chemical compounds, eugenol have stronger contact toxicity in larvae, pupae, and adult than caryophyllene oxide, followed by α-pinene, α-phellandrene, and α-humulene. In general, the two essential oils were toxic and repellent to adult T. molitor. Cinnamon and clove essential oils and their compounds caused higher mortality and repellency on T. molitor and, therefore, have the potential for integrated management programs of this insect.
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