ALBERT

Description: Over the years, the increasing acquisition of antibiotic resistance genes has led to the emergence of highly resistant bacterial strains and the loss of standard antibiotics’ efficacy, including β-lactam/β-lactamase inhibitor combinations and the last line carbapenems. Klebsiella pneumoniae is considered one of the major exponents of a group of multidrug-resistant ESKAPE pathogens responsible for serious healthcare-associated infections. In this study, we proved the antimicrobial activity of two analogues of Temporin L against twenty carbapenemase-producing K. pneumoniae clinical isolates. According to the antibiotic susceptibility assay, all the K. pneumoniae strains were resistant to at least one other class of antibiotics, in addition to beta-lactams. Peptides 1B and C showed activity on all test strains, but the lipidated analogue C expressed the greater antimicrobial properties, with MIC values ranging from 6.25 to 25 µM. Furthermore, the peptide C showed bactericidal activity at MIC values. The results clearly highlight the great potential of antimicrobial peptides both as a new treatment option for difficult-to-treat infections and as a new strategy of drug-resistance control.

Description: Purpose: Historically, studies suggested that intraoperative hypothermia (IH) could result in significant resource consumption, but more recent studies have found the opposite. The purpose of this study is to estimate the value of active warming devices for IH prevention based on synthesized evidence. Methods: A cost-benefit analysis was conducted using the effect of active warming versus passive warming devices for intraoperative hypothermia from a meta-analysis. The item-based aggregated treatment cost approach was adopted to estimate the cost of each adverse event, which was then weighted to calculate the total cost of IH. Results: IH was associated with higher risks of bleeding, surgical site infection, and shivering compared with normothermia. The cost of one case of IH was $363.80, and the use of active warming devices might save $152.80. Extra investment in active warming (e.g., $291.00) might only be cost-beneficial when the minimum willingness-to-pay is $150.00. Conclusions: Synthesized evidence showed that the cost of IH might be overestimated. Furthermore, the value of using active warming devices remains uncertain because the willingness to pay may vary between decision-makers. As not enough awareness of hypothermia prevention in some countries, further research into the clinical use of active warming devices during major surgeries is warranted.

Description: Potato is the fourth staple crop in China after wheat, maize and rice. The agro-pastoral ecotone (APE) in North China is a main region for potato production. However, potato yield has been seriously constrained by water shortages because of low precipitation and highly variable precipitation patterns during the growing season in this area. In this study, the Agricultural Production Systems Simulator (APSIM) model was used to simulate potato water-limited yield and historical years were divided into different water-temperature year types to optimize the optimal planting period (OPP) and cultivar of potato. The results showed that the potato yield varied in different water-temperature year types. Fast-developing cultivar Favorita could obtain the highest yield in most places and water-temperature year types due to its relatively short length of tuber formation stage. In this study, we suggest changing the planting date according to the water-temperature year type, which offers a new way to adapt to a highly variable climate. However, our method should be adopted carefully because we only considered climate factors; other agronomic management practices (adjusting planting density, plastic film mulch, conservation tillage etc.) also have a great effect on planting date and cultivar selection, which should be further investigated in the future.

Description: Cardiovascular diseases are currently among the leading causes of morbidity and mortality in many developed countries. They are distinguished by chronic and latent development, a course with stages of worsening of symptoms and a period of improvement, and a constant potential threat to life. One of the most important disorders in cardiovascular disease is ischemic stroke. The causes of ischemic stroke can be divided into non-modifiable and modifiable causes. One treatment modality from a neurological point of view is acetylsalicylic acid (ASA), which blocks cyclooxygenase and, thus, thromboxane synthesis. The legitimacy of its administration does not raise any doubts in the case of the acute phase of stroke in patients in whom thrombolytic treatment cannot be initiated. The measurement of thromboxane B2 (TxB2) in serum (a stable metabolic product of TxA2) is the only test that measures the effect of aspirin on the activity of COX-1 in platelets. Measurement of thromboxane B2 may be a potential biomarker of vascular disease risk in patients treated with aspirin. The aim of this study is to present the role of thromboxane B2 in ischemic stroke and to present effective therapies for the treatment of ischemic stroke. Scientific articles from the PubMed database were used for the work, which were selected on the basis of a search for “thromboxane and stroke”. Subsequently, a restriction was introduced for works older than 10 years, those concerning animals, and those without full text access. Ultimately, 58 articles were selected. It was shown that a high concentration of TXB2 may be a risk factor for ischemic stroke or ischemic heart disease. However, there is insufficient evidence to suggest that thromboxane could be used in clinical practice as a marker of ischemic stroke. The inclusion of ASA in the prevention of stroke has a beneficial effect that is associated with the effect on thromboxane. However, its insufficient power in 25% or even 50% of the population should be taken into account. An alternative and/or additional therapy could be a selective antagonist of the thromboxane receptor. Thromboxane A2 production is inhibited by estrogen; therefore, the risk of CVD after the menopause and among men is higher. More research is needed in this area.

Description: Catharanthus roseus is a well-known traditional herbal medicine for the treatment of cancer, hypertension, scald, and sore in China. Phytochemical investigation on the twigs and leaves of this species led to the isolation of two new monoterpene indole alkaloids, catharanosines A (1) and B (2), and six known analogues (3–8). Structures of 1 and 2 were established by 1H-, 13C- and 2D-NMR, and HREIMS data. The absolute configuration of 1 was confirmed by single-crystal X-ray diffraction analysis. Compound 2 represented an unprecedented aspidosperma-type alkaloid with a 2-piperidinyl moiety at C-10. Compounds 6–8 exhibited remarkable Cav3.1 low voltage-gated calcium channel (LVGCC) inhibitory activity with IC50 values of 11.83 ± 1.02, 14.3 ± 1.20, and 14.54 ± 0.99 μM, respectively.

Description: The long non-coding RNA (lncRNA) MALAT1 acts as an oncogene. RNA interference (RNAi) is an effective method to control the expression of specific genes and can be used for the treatment of tumors, but an effective and safe carrier system is a significant obstacle to gene therapy. Herein, we explored the possibility of constructing an in situ bio-responsive self-assembled fluorescent gold-short hairpin RNA nanocomplex (Au–shRNA NCs) delivery system by co-incubating gold and MALAT1-shRNA for precise hepatocellular carcinoma (HCC) imaging and treatment. Due to the characteristics of the cancer microenvironment, Au–shRNA NCs self-assembled in HCC cells (HepG2) but did not occur in control cells (L02) under the same conditions. The in situ bio-responsive self-assembled Au–shRNA NCs delivery system can realize cancer cell bioimaging and promote cell uptake and endosomal escape mechanism, thereby realizing effective transfection. They effectively silenced target gene MALAT1, and with the downregulation of MALAT1, we found that several molecules involved in autophagic flux were also regulated. In vitro and tumor-bearing mouse model experiments demonstrated that the as-prepared fluorescent Au–shRNA NCs can readily realize tumor bioimaging and effectively silence the target gene MALAT1, and those autophagy-related pathway molecules were significantly downregulated, thereby exerting a tumor suppressor efficiency. This raises the possibility of realizing accurate multi-scale bio-imaging from the molecular-level with targeted gene-recognition to cancer cell imaging as well as in vivo tumor tissue imaging for the simultaneous precise cancer therapy.

Description: RNA activation (RNAa) is a mechanism whereby RNA oligos complementary to genomic sequences around the promoter region of genes increase the transcription output of their target gene. Small activating RNA (saRNA) mediate RNAa through interaction with protein co-factors to facilitate RNA polymerase II activity and nucleosome remodeling. As saRNA are small, versatile and safe, they represent a new class of therapeutics that can rescue the downregulation of critical genes in disease settings. This review highlights our current understanding of saRNA biology and describes various examples of how saRNA are successfully used to treat various oncological, neurological and monogenic diseases. MTL-CEBPA, a first-in-class compound that reverses CEBPA downregulation in oncogenic processes using CEBPA-51 saRNA has entered clinical trial for the treatment of hepatocellular carcinoma (HCC). Preclinical models demonstrate that MTL-CEBPA reverses the immunosuppressive effects of myeloid cells and allows for the synergistic enhancement of other anticancer drugs. Encouraging results led to the initiation of a clinical trial combining MTL-CEBPA with a PD-1 inhibitor for treatment of solid tumors.

Description: The first step in the infection of fungal pathogens in humans is the adhesion of the pathogen to host tissue cells or abiotic surfaces such as catheters and implants. One of the main players involved in this are the expressed cell wall adhesins. Here, we review the Flo adhesin family and their involvement in the adhesion of these yeasts during human infections. Firstly, we redefined the Flo adhesin family based on the domain architectures that are present in the Flo adhesins and their functions, and set up a new classification of Flo adhesins. Next, the structure, function, and adhesion mechanisms of the Flo adhesins whose structure has been solved are discussed in detail. Finally, we identified from Pfam database datamining yeasts that could express Flo adhesins and are encountered in human infections and their adhesin architectures. These yeasts are discussed in relation to their adhesion characteristics and involvement in infections.

Description: Limited therapeutic tools and an overwhelming clinical demand are the major limiting factors in pediatric obesity management. The optimal protocol, environment, body mass index (BMI) change targets and duration of obesity-oriented interventions remain to be elucidated. Aims: We aimed to characterize the singularities of follow-up, anthropometric and metabolic evolution of a large cohort of pediatric patients with obesity in a specialized university hospital outpatient obesity unit. Patients and methods: Follow-up duration (up to seven years), attrition rate and anthropometric and metabolic evolution of 1300 children and adolescents with obesity were studied. An individualized analysis was conducted in patients attaining a high level of weight loss (over 1.5 BMI-SDS (standard deviation score) and/or 10% of initial weight; n = 252; 19.4%) as well as in “metabolically healthy” patients (n = 505; 38.8%). Results: Attrition rate was high during the early stages (11.2% prior to and 32.5% right after their initial metabolic evaluation). Mean follow-up time was 1.59 ± 1.60 years (7% of patients fulfilled 7 years). The highest BMI reduction occurred in the first year (−1.11 ± 0.89 SDS, p 〈 0.001 in 72.5% of patients). At the end of the follow-up, improvements in glucose and lipid metabolism parameters were observed (both p 〈 0.05), that were highest in patients with the greatest weight reduction (all p 〈 0.01), independent of the time spent to achieve weight loss. The pubertal growth spurt negatively correlated with obesity severity (r = −0.38; p 〈 0.01) but patients attaining adult height exceeded their predicted adult height (n = 308, +1.6 ± 5.4 cm; p 〈 0.001). “Metabolically healthy” patients, but with insulin resistance, had higher blood pressure, glucose, uric acid and triglyceride levels than those without insulin resistance (all p 〈 0.05). Preservation of the “metabolically healthy” status was associated with BMI improvement. Conclusions: Behavioral management of children with obesity can be effective and does not impair growth but is highly conditioned by high attrition. The best results regarding BMI reduction and metabolic improvement are achieved in the first year of intervention and can be preserved if follow-up is retained.

Description: Wireless technologies are increasingly relevant in different activities and lines of the economy, as well as in the daily life of people and companies. The advent of fifth generation networks (5G) implies a promising synergy with the Internet of Things (IoT), allowing for more automations in production processes and an increase in the efficiency of information transmission, managing to improve the efficiency in decision-making through tools such as big data and artificial intelligence. This article presents a description of the 5G implementation process in Colombia, as well as a revision of opportunities when combining with IoT in featured sectors of the departmental development plans, such as agriculture, tourism, health, the environment, and industry. Results shows that the startup of 5G in Colombia has been a slow process, but there are comparisons with similar procedures in other developed countries. Additionally, we present examples of 5G and IoT applications which can be promoted in Colombia, aimed at improving the quality of life of their habitants and promoting economic development.