Up-regulated mitochondrial biogenesis associated with GH/IGF axis in the ovaries of muskrats (Ondatra zibethicus).

Mitochondria play a critical role in follicular development and ovulation, at least in part through the actions of growth hormone (GH)/insulin-like growth factor-1 (IGF-1) on mitochondrial biogenesis. This study aimed to identify seasonal alterations in the GH/IGF-1 system and mitochondrial biogenesis in muskrat (Ondatra zibethicus) ovaries. We utilized the muskrat, a typical seasonal breeder, to clarify the potential impact of the GH/IGF-1 system on mitochondrial biogenesis across different breeding seasons using immunohistochemistry, gene expression and high-throughput sequencing. Alterations in follicular development existed in muskrat ovaries between the breeding season (BS) and non-breeding season (NBS), accompanied by a striking decrease in circulating and ovarian GH and IGF-1 concentrations. GH, GHR, IGF-1, IGF-1R, and mitochondrial biogenesis markers were localized in the ovarian cells of muskrats during both seasons. In contrast, Gh, Ghr, Igf-1, Igf-1r, Ppargc1a, Ppargc1b, Tfam, and Nrf1/2 mRNA levels were higher in BS. The relative levels of GH and IGF-1 in circulation and ovaries were positively associated with mitochondrial biogenesis markers. Additionally, RNA-seq analysis demonstrated that differentially expressed genes might be associated with insulin and PI3K/Akt signaling pathways, as well as mitochondrial function-related pathways. These findings suggest that the intra-ovarian GH/IGF-1 system, which is associated with seasonal changes in mitochondrial biogenesis, is activated in muskrat ovaries in BS.

Durum Wheat at Risk in a Climate Change Scenario: The Carotenoid Content is Affected by Short Heat Waves.

Short heat waves (SHW), defined as periods of several consecutive days with high temperatures above the developmental optimum, will become more frequent due to climate change. The impact of SHW on yield and yield-related parameters has received considerable interest, but their effects on grain quality remain poorly understood. We employed a simulation approach to investigate the impact of SHW on durum wheat quality over a 7 day period, starting 1 week after anthesis. During the SHW treatment, carried out using portable polyethylene tents, the temperature in the treated plots increased by 10-15 °C during daily hours. The SHW treatment reduced the number of grains per spike, thousand kernel weight, and total carotenoid content in grains in stressed plants in comparison to control plants. However, no differences in the protein content or percentage of vitreous grains were observed. The behavior of individual carotenoids in response to SHW appears to differ, suggesting a differential change in the balance between ß,ε- and ß,ß-branches of the carotenoid biosynthetic pathway as a consequence of SHW-induced stress. The present study highlights the importance of developing efficient breeding strategies for reduced sensitivities to heat stress. Such strategies should not only prioritize yield but also encompass grain quality.

Pituitary Apoplexy: Comorbidities, Management and Outcomes. A Spanish Observational Multicenter Study.

BACKGROUND: Pituitary apoplexy (PA) is the paradigm of endocrine and neurosurgical emergency. OBJECTIVE: To evaluate the comorbidities, risk factors, clinical presentation, pituitary apoplexy score (PAS) and the outcomes of surgical vs. conservative management of PA in Spain. METHODS: Spanish multicenter, observational study of 301 patients with acute PA. Statistical analyses compared risk factors, clinical presentation and outcomes between the surgical and conservative treatment groups, adjusting for potential confounders. The prevalence of cardiovascular risk factors in patients with pituitary apoplexy was compared with the Spanish population and with patients with non-functioning pituitary adenomas. RESULTS: Median age was 59.3 years, 201 (66.8%) were men and non-functioning adenomas (77.9%) were the most common tumor type. The prevalence of diabetes (20.3% vs 13.9%, p<0.01), hypertension (48.8% vs 33.4%, p<0.01) and dyslipidemia (44.2% vs 23.3%, p<0.01), exceeded the Spanish age-adjusted population prevalence. Overall, 209 (69.4%) underwent surgery and 92 (30.6%) received conservative treatment. Surgical patients had larger tumors (26.2 vs 21.0 mm, p<0.01), chiasmal compression more frequently (77.2% vs 53.4%, p<0.01) and higher values of PAS. In the follow-up, while there were no statistically significant differences in anterior pituitary hormonal deficits between treatments, permanent vasopressin deficiency was more frequent after surgery (14.8% vs 3.3%, p<0.01). CONCLUSION: There is a high burden of cardiovascular risk factors among patients with PA suggesting that metabolic factors may play a potential role in the development of PA. This underscores the need for comprehensive management of these conditions in addition to treating the apoplexy itself in this population. Surgical management has a relevant place in PA approach mainly in patients with higher PAS. However, it leads permanent vasopressin deficit more frequently than conservative approach.

Irruption of Network Analysis to Explain Dietary, Psychological and Nutritional Patterns and Metabolic Health Status in Metabolically Healthy and Unhealthy Overweight and Obese University Students: Ecuadorian Case.

BACKGROUND: The association between dietary nutritional patterns, psychological factors, and metabolic health status has not been investigated in university students. There are studies that include numerous variables to test hypotheses from various theoretical bases, but due to their complexity, they have not been studied in combination. The scientific community recognizes the use of Gaussian graphical models (GGM) as a set of novel methods capable of addressing this. OBJECTIVE: To apply GGMs to derive specific networks for groups of healthy and unhealthy obese individuals that represent nutritional, psychological, and metabolic patterns in an Ecuadorian population. METHODOLOGY: This was a quantitative, non-experimental, cross-sectional, correlational study conducted on a sample of 230 obese/overweight university students, selected through a multi-stage random sampling method. To assess usual dietary intake, a Food Frequency Questionnaire (FFQ) was used; to evaluate psychological profiles (anxiety, depression, and stress), the DASS-21 scale was employed; blood pressure and anthropometric data were collected; and insulin levels, lipid profiles, and glucose levels were determined using fasting blood samples. The International Diabetes Federation (IDF) criteria were applied to identify metabolically healthy and unhealthy individuals. Statistical analysis relied on univariate methods (frequencies, measures of central tendency, and dispersion), and the relationships were analyzed through networks. The Mann-Whitney U test was used to analyze differences between groups. RESULTS: In metabolically unhealthy obese individuals, GGMs identified a primary network consisting of the influence of waist circumference on blood pressure and insulin levels. In the healthy obese group, a different network was identified, incorporating stress and anxiety variables that influenced blood pressure, anthropometry, and insulin levels. Other identified networks show the dynamics of obesity and the effect of waist circumference on triglycerides, anxiety, and riboflavin intake. CONCLUSIONS: GGMs are an exploratory method that can be used to construct networks that illustrate the behavior of obesity in the studied population. In the future, the identified networks could form the basis for updating obesity management protocols in Primary Care Units and supporting clinical interventions in Ecuador.

Occurrence of modified mycotoxins in Latin America: an up-to-date review.

The Latin America region has a considerable extent of varied climate conditions: from tropical, subtropical, and warm temperate to temperate. Among the surface territory, different agricultural products are produced, making them an important food source for human consumption. Fungal species commonly colonize those important agricultural products and often contaminate them with mycotoxins that have a major impact on health, welfare, and productivity. Nowadays, special attention is paid to modified mycotoxins, which are those that cannot be detected by conventional analytical methods. However, little data about their natural occurrence in food and feed is available, especially in Latin American countries, where, among all the countries in this region, only a few of them are working on this subject. Thus, the present review summarizes the published information available in order to determine the possible human exposure risk to these toxins.

Comparative effectiveness of perioperative physical activity in older adults with lung cancer and their family caregivers: design of a multicenter pragmatic randomized trial.

BACKGROUND: With a median age at diagnosis of 70, lung cancer remains a significant public health challenge for older Americans. Surgery is a key component in treating most patients with non-metastatic lung cancer. These patients experience postoperative pain, fatigue, loss of respiratory capacity, and decreased physical function. Data on quality of life (QOL) in older adults undergoing lung cancer surgery is limited, and few interventions are designed to target the needs of older adults and their family caregivers (FCGs). The primary aim of this comparative effectiveness trial is to determine whether telephone-based physical activity coaching before and after surgery will be more beneficial than physical activity self-monitoring alone for older adults and their FCGs. METHODS: In this multicenter comparative effectiveness trial, 382 older adults (≥ 65 years) with lung cancer and their FCGs will be recruited before surgery and randomized to either telephone-based physical activity coaching or physical activity self-monitoring alone. Participants allocated to the telephone-based coaching comparator will receive five telephone sessions with coaches (1 pre and 4 post surgery), an intervention resource manual, and a wristband pedometer. Participants in the self-monitoring only arm will receive American Society of Clinical Oncology (ASCO) physical activity information and wristband pedometers. All participants will be assessed at before surgery (baseline), at discharge, and at days 30, 60, and 180 post-discharge. The primary endpoint is the 6-minute walk test (6MWT) at 30 days post-discharge. Geriatric assessment, lower extremity function, self-reported physical function, self-efficacy, and QOL will also be assessed. DISCUSSION: The trial will determine whether this telephone-based physical activity coaching approach can enhance postoperative functional capacity and QOL outcomes for older adults with lung cancer and their FCGs. Trial results will provide critical findings to inform models of postoperative care for older adults with cancer and their FCGs. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT06196008.

Tailoring the pore structure of iron oxide core@stellate mesoporous silica shell nanocomposites: effects on MRI and magnetic hyperthermia properties and applicability to anti-cancer therapies.

Core-shell nanocomposites made of iron oxide core (IO NPs) coated with mesoporous silica (MS) shells are promising theranostic agents. While the core is being used as an efficient heating nanoagent under alternating magnetic field (AMF) and near infra-red (NIR) light and as a suitable contrast agent for magnetic resonance imaging (MRI), the MS shell is particularly relevant to ensure colloidal stability in a biological buffer and to transport a variety of therapeutics. However, a major challenge with such inorganic nanostructures is the design of adjustable silica structures, especially with tunable large pores which would be useful, for instance, for the delivery of large therapeutic biomolecule loading and further sustained release. Furthermore, the effect of tailoring a porous silica structure on the magneto- or photothermal dissipation still remains poorly investigated. In this work, we undertake an in-depth investigation of the growth of stellate mesoporous silica (STMS) shells around IO NPs cores and of their micro/mesoporous features respectively through time-lapse and in situ liquid phase transmission electron microscopy (LPTEM) and detailed nitrogen isotherm adsorption studies. We found here that the STMS shell features (thickness, pore size, surface area) can be finely tuned by simply controlling the sol-gel reaction time, affording a novel range of IO@STMS core@shell NPs. Finally, regarding the responses under alternating magnetic fields and NIR light which are evaluated as a function of the silica structure, IO@STMS NPs having a tunable silica shell structure are shown to be efficient as T2-weighted MRI agents and as heating agents for magneto- and photoinduced hyperthermia. Furthermore, such IO@STMS are found to display anti-cancer effects in pancreatic cancer cells under magnetic fields (both alternating and rotating).

Carbapenem-resistant Acinetobacter baumannii (CRAB): metabolic adaptation and transcriptional response to human urine (HU).

Carbapenem-resistant Acinetobacter baumannii (CRAB) is a major human pathogen and a research priority for developing new antimicrobial agents. CRAB is a causative agent of a variety of infections in different body sites. One of the manifestations is catheter-associated urinary tract infection, which exposes the bacteria to the host's urine, creating a particular environment. Exposure of two CRAB clinical isolates, AB5075 and AMA40, to human urine (HU) resulted in the differential expression levels of 264 and 455 genes, respectively, of which 112 were common to both strains. Genes within this group play roles in metabolic pathways such as phenylacetic acid (PAA) catabolism, the Hut system, the tricarboxylic acid (TCA) cycle, and other processes like quorum sensing and biofilm formation. These results indicate that the presence of HU induces numerous adaptive changes in gene expression of the infecting bacteria. These changes presumably help bacteria establish and thrive in the hostile conditions in the urinary tract. These analyses advance our understanding of CRAB's metabolic adaptations to human fluids, as well as expand knowledge on bacterial responses to distinct human fluids containing different concentrations of human serum albumin (HSA).

Hetero-antagonism of avibactam and sulbactam with cefiderocol in carbapenem-resistant Acinetobacter spp.

Cefiderocol, a siderophore-cephalosporine conjugate antibiotic, shows promise as a therapeutic option for carbapenem-resistant (CR) Acinetobacter infections. While resistance has already been reported in A. baumannii, combination therapies with avibactam or sulbactam reduce MICs of cefiderocol, extending its efficacy. However, careful consideration is necessary when using these combinations. In our experiments, exposure of A. baumannii and A. lwoffii to cefiderocol and sulbactam or avibactam led to the selection of cefiderocol-resistant strains. Three of those were subjected to whole genome sequencing and transcriptomic analysis. The strains all possessed synonymous and non-synonymous substitutions and short deletions. The most significant mutations affected efflux pumps, transcriptional regulators, and iron homeostasis genes. Transcriptomics showed significant alterations in expression levels of outer membrane proteins, iron homeostasis, and ß-lactamases, suggesting adaptive responses to selective pressure. This study underscores the importance of carefully assessing drug synergies, as they may inadvertently foster the selection of resistant variants and complicate the management of CR Acinetobacter infections.IMPORTANCEThe emergence of carbapenem-resistant Acinetobacter strains as a serious global health threat underscores the urgent need for effective treatment options. Although few drugs show promise against CR Acinetobacter infections, resistance to both drugs has been reported. In this study, the molecular characterization of spontaneous cefiderocol-resistant variants, a CR A. baumannii strain with antagonism to sulbactam, and an A. lwoffii strain with antagonism to avibactam, provides valuable insights into the mechanisms of resistance to cefiderocol. Some mechanisms observed are associated with mutations affecting efflux pumps, regulators, and iron homeostasis genes. These findings highlight the importance of understanding resistance mechanisms to optimize treatment options. They also emphasize the importance of early evaluation of drug synergies to address the challenges of antimicrobial resistance in Acinetobacter infections.

Discrepancy in opioid prescription patterns for Black or African American patients following lower extremity bypass surgery for chronic limb-threatening ischemia.

BACKGROUND: Disparity in the allocation of medical services and resources based on race is present within the health care industry today, including the prescription of postoperative analgesics. The purpose of this study was to evaluate the presence of race-based disparity in the prescription of postdischarge opioids after lower extremity bypass (LEB) surgery for chronic limb-threatening ischemia (CLTI). METHODS: Retrospective analysis was conducted on adult CLTI patients who underwent LEB from 2000 to 2023 in the TrinetX database. Patients were stratified into two groups based on race: White (group I) and black or African American (AA) (group II). Primary outcomes were defined as oral opioid prescriptions at 7 days and 30 days after discharge, and mortality at 1 year postoperatively. Secondary outcomes included length of stay and 30-day postoperative outcomes, including myocardial infarction, pulmonary embolism, cerebral vascular accident, deep vein thrombosis, acute kidney injury, major amputation, minor amputation, major adverse cardiac events, and major adverse limb events. Stratified analysis was conducted based on disease stage (rest pain vs lower extremity ulcer vs gangrene). Univariate analysis was performed via two-sample t test and χ2 test. Logistic regression was performed to estimate the association of Black or AA (vs White) race while controlling for pertinent preoperative potential confounders. RESULTS: There were 3345 patients who met the inclusion criteria. Group I included 2661 White patients and group II included 684 Black or AA patients. Group II patients were more likely to be younger, female, present with gangrene, and have a history of hypertension, diabetes, chronic kidney disease, or diabetic neuropathy. At both 7 and 30 days after discharge, the Black or AA cohort had significantly lower rates of opioid prescriptions (33.2% vs 42.5% and 35.8% vs 47.2%, respectively) (all P < .05). Stratification by indication showed that opioid prescription disparity persisted despite black or AA patients presenting at worse stages of disease both at 7 and 30 days after discharge (7 days: rest pain 43.4% vs 33.7% [P = .013], ulcer 41.4% vs 31.7% [P = .027], gangrene, 42.7% vs 33.6% [P = .006] and 30 days: rest pain 47.8% vs 37.1% [P = .007], ulcer 45.4% vs 33.5% [P = .007], gangrene, 48.2% vs 36.1% [P < .001]). Adjusted analysis confirmed that Black or AA race was associated with lower rates of 7- (adjusted odds ratio, 0.607; P = .001) and 30-day (adjusted odds ratio, 0.56; P = .001) postdischarge opioid prescriptions. CONCLUSIONS: Black or AA patients were less likely to receive postdischarge opioid prescriptions compared with their White counterparts at 7 and 30 days after LEB for CLTI.

Differential effect of training impure tacts versus pure tacts plus intraverbal on the emergence of new verbal operants: A conceptual and methodological study.

The aim of this research was to test the effect of training impure tact versus pure tact and intraverbals on the emergence of new verbal operants (impure tacts), thus establishing a conceptual and methodological differentiation on these operants. This was done by varying the training order of intraverbal or impure tact to analyze and confirm whether or not impure tact is the mere sum of pure tact plus intraverbal and therefore has different functions and consequences in learning. An experiment was conducted with 30 participants randomly assigned to three groups. In Group 1, pure tact plus intraverbal and then impure tact were trained. In Group 3 the training order of these operants was counterbalanced. Group 2 was the control group, training only pure tact plus intraverbal. After the training phases, the emergence of impure tacts was tested. The results of this research indicate that the training of impure tacts favors the emergence of new impure tacts to a greater extent than the training of pure tact plus intraverbal and that they therefore have different functions. It is also shown that variation in the order of presentation of the type of training influences the subsequent emergence of new operants (impure tacts), so that creating a previous history of learning in impure tacts favors emergence even when the intraverbal alone is subsequently trained. This has important implications at both conceptual and methodological levels as it would contribute to the development of more effective language training technologies.

Analysis of the Fungal Community Composition in Endemic Orchids with Terrestrial Habitat in Subtropical Regions.

Habenaria and Liparis are well-known orchid genera that grow in terrestrial habitats in the tropics, subtropics or temperate zones. Three species have been found in subtropical regions of China, inhabiting terrestrial to epiphytic habitats. This study focuses on three species, H. dentata (distributed in Asia), H. yachangensis, and L. gigantea. For H. yachangensis and L. gigantea, there is no information about the mycorrhizal community in these species. This study aims to conduct the fungal community screening of Chinese ground orchids from subtropical regions. We performed a comparative analysis of the fungal community among H. dentata, H. yachangensis, and L. gigantea, determining their ITS regions using NGS paired-end sequences. The results clarified the diversity and the predominance of fungal genera. Ascomycota was abundant compared to Basidiomycota or other fungi groups in all communities, with a high dominance in all populations, especially for L. gigantea. At different root spatial locations, the fungal community diversity and richness were higher in the soil than in the rhizosphere or inner root. However, the results suggest that L. gigantea has a different fungal community compared to Habenaria species. In this order, the subtropical terrestrial orchids have a different fungal network compared to the northern terrestrial orchids. Also, there is a high probability of co-existence and co-evolution of endophytic fungi in these terrestrial orchids, indicating the potential role of host plants in selecting an endophytic fungal community. Furthermore, our results highlight the need to elucidate the microbe interactions of these unique orchids for long-term purposes, such as isolating indigenous fungi for suitable inoculants for further orchid propagation, restoration, and conservation.

Interleukins IL33/ST2 and IL1-ß in Intrauterine Growth Restriction and Seropositivity of Anti-Toxoplasma gondii Antibodies.

Toxoplasma gondii (T. gondii) is the causal agent of toxoplasmosis. It may produce severe damage in immunocompromised individuals, as well as congenital infection and intrauterine growth restriction (IUGR). Previous reports have associated interleukin IL-33 with miscarriage, fetal damage, and premature delivery due to infections with various microorganisms. However, IL-33 has not been associated with congenital toxoplasmosis. The sST2 receptor has been reported in patients who have had recurrent miscarriages. On the other hand, IL-1ß was not found in acute Toxoplasma infection. Our aim was to analyze the associations between the serum levels of IL-33 and IL-1ß in IUGR and toxoplasmosis during pregnancy. Eighty-four serum samples from pregnant women who had undergone 26 weeks of gestation were grouped as follows: with anti-Toxoplasma antibodies, without anti-Toxoplasma antibodies, IUGR, and the control group. IgG and IgM anti-T. gondii antibodies, as well as IL-33, ST2, and IL-1ß, were determined using an ELISA assay. Statistical analyses were performed using the Pearson and Chi-square correlation coefficients, as well as the risk factors and Odds Ratios (ORs), with a confidence interval of 95% (CI 95). The results showed that 15/84 (17.8%) of cases were positive for IgG anti-Toxoplasma antibodies and 2/84 (2.38%) of cases were positive for IgM. A statistically significant difference was found between IUGR and IL-33 (p < 0.001), as well as between ST2 and IUGR (p < 0.001). In conclusion, IUGR was significantly associated with IL-33 and ST2 positivity based on the overall IUGR grade. No significant association was found between IUGR and the presence of anti-Toxoplasma antibodies. There was no association between IL-1ß and IUGR. More research is needed to strengthen the utility of IL-33 and ST2 as biomarkers of IUGR.

Catheter directed therapy in high-risk pulmonary embolism: Analysis of 9 cases. / Terapia dirigida por catéter en embolia pulmonar de alto riesgo: análisis de 9 casos.

BACKGROUND: Mechanical thrombectomy is a useful technique in patients with high-risk pulmonary embolism. It is indicated as an alternative to systemic fibrinolysis when it is contraindicated or as an adjuvant therapy when it fails. OBJECTIVE: To describe clinical characteristics, evolution and survival of patients with high-risk pulmonary embolism who have undergone mechanical thrombectomy. METHOD: Single-center retrospective descriptive study of consecutive patients who underwent mechanical thrombectomy. Demographic, clinical and survival variables were analyzed. RESULTS: 9 patients were included (56% men, 44% women). All patients had pulmonary artery pressure assessed using a Swan-Ganz catheter before thrombectomy. The median pulmonary artery pressure before the procedure was 46mmHg (51-38mmHg). Systemic fibrinolysis was also performed in 5 cases, in 2 of them in the setting of cardiorespiratory arrest, without hemorrhagic complications. No patient died during hospitalization. Survival one month after the procedure was 100%. CONCLUSIONS: In our series, mechanical thrombectomy is a useful technique as an alternative to systemic fibrinolysis or as an adjuvant therapy to it.

Competitive inhibition and mutualistic growth in co-infections: deciphering Staphylococcus aureus-Acinetobacter baumannii interaction dynamics.

Staphylococcus aureus (Sa) and Acinetobacter baumannii (Ab) are frequently co-isolated from polymicrobial infections that are severe and refractory to therapy. Here, we apply a combination of wet-lab experiments and in silico modeling to unveil the intricate nature of the Ab/Sa interaction using both, representative laboratory strains and strains co-isolated from clinical samples. This comprehensive methodology allowed uncovering Sa's capability to exert a partial interference on Ab by the expression of phenol-soluble modulins. In addition, we observed a cross-feeding mechanism by which Sa supports the growth of Ab by providing acetoin as an alternative carbon source. This study is the first to dissect the Ab/Sa interaction dynamics wherein competitive and cooperative strategies can intertwine. Through our findings, we illuminate the ecological mechanisms supporting their coexistence in the context of polymicrobial infections. Our research not only enriches our understanding but also opens doors to potential therapeutic avenues in managing these challenging infections.

Feasibility, acceptability, and appropriability of a national whole-school program for reducing school violence and improving school coexistence.

Introduction: The increase in school violence following the COVID-19 pandemic underscores the need for schools to adopt a multilevel whole-school approach. This study examines a national program designed by the Chilean Ministry of Education, in collaboration with universities, as part of the Ministry's Educational Reactivation Plan, aimed at improving school climate management across Chile. Methods: The "Learning to Live Together Program" (LLT) was implemented across all 16 regions of Chile, focusing on establishing school climate networks, providing direct intensive university technical assistance, and enhancing professional development and training. The feasibility, acceptability, and appropriability of the LLT program were assessed through a survey distributed to 1,561 staff members from 783 schools. Participants responded to a comprehensive set of instruments measuring acceptability, appropriability, feasibility, attitudes toward implementation, fidelity, and initial perceived results. Results: The results indicate high initial adoption rates and significant improvements in the assessed dimensions. The enhancement of school climate practices and strengthening school collaboration networks were of considerable relevance. Discussion: These findings support the efficacy of the multilevel whole-school approach as a viable strategy for Latin American countries, providing critical data for educational and governmental decision-making. Furthermore, this study provides evidence that these outcomes may be applicable to the implementation of similar policies in different contexts and countries.

Family Care in Members with COVID-19 Using Telenursing.

The COVID-19 pandemic has caused the infection and death of millions of people around the world. The Pan American Health Organization (PAHO) and the Center for Disease Control and Prevention have issued recommendations for caregivers of patients sent home with COVID-19, such as; the use of facemasks, hygiene at home, the use of the vaccine, among others. The purpose of the study was to determine the relationship between the level of support from information technologies (Whatsapp) with the level of knowledge to provide better care at home by family caregivers of people with COVID-19 by an educational program to 130 caregivers.

Structure-Activity Relationship of Pyrrolidine Pentamine Derivatives as Inhibitors of the Aminoglycoside 6'-N-Acetyltransferase Type Ib.

Resistance to amikacin and other major aminoglycosides is commonly due to enzymatic acetylation by the aminoglycoside 6'-N-acetyltransferase type I enzyme, of which type Ib [AAC(6')-Ib] is the most widespread among Gram-negative pathogens. Finding enzymatic inhibitors could be an effective way to overcome resistance and extend the useful life of amikacin. Small molecules possess multiple properties that make them attractive for drug development. Mixture-based combinatorial libraries and positional scanning strategy have led to the identification of a chemical scaffold, pyrrolidine pentamine, that, when substituted with the appropriate functionalities at five locations (R1-R5), inhibits AAC(6')-Ib-mediated inactivation of amikacin. Structure-activity relationship studies have shown that while truncations to the molecule result in loss of inhibitory activity, modifications of functionalities and stereochemistry have different effects on the inhibitory properties. In this study, we show that alterations at position R1 of the two most active compounds, 2700.001 and 2700.003, reduced inhibition levels, demonstrating the essential nature not only of the presence of an S-phenyl moiety at this location but also the distance to the scaffold. On the other hand, modifications on the R3, R4, and R5 positions had varied effects, demonstrating the potential for optimization. A correlation analysis between molecular docking values (ΔG) and the dose required for two-fold potentiation of the compounds described in this and the previous studies showed a significant correlation between ΔG values and inhibitory activity.