ABSTRACT
The development of efficient methods for dereplication has been critical in the re-emergence of the research in natural products as a source of drug leads. Current dereplication workflows rapidly identify already known bioactive secondary metabolites in the early stages of any drug discovery screening campaign based on natural extracts or enriched fractions. Two main factors have driven the evolution of natural products dereplication over the last decades. First, the availability of both commercial and public large databases of natural products containing the key annotations against which the biological and chemical data derived from the studied sample are searched for. Second, the considerable improvement achieved in analytical technologies (including instrumentation and software tools) employed to obtain robust and precise chemical information (particularly spectroscopic signatures) on the compounds present in the bioactive natural product samples. This chapter describes the main methods of dereplication, which rely on the combined use of large natural product databases and spectral libraries, alongside the information obtained from chromatographic, UV-Vis, MS, and NMR spectroscopic analyses of the samples of interest.
Subject(s)
Biological Products , Biological Products/chemistry , Databases, Factual , Drug Discovery/methods , Molecular Structure , Magnetic Resonance SpectroscopyABSTRACT
Background: The aim of the study was to evaluate the 12-month cumulative probability of treatment discontinuation (TD) in people with human immunodeficiency virus (HIV; PWH) and a long exposure to antiretroviral therapy (ART) switching to long-acting cabotegravir and rilpivirine (CAB/RPV). Methods: SCohoLART is a single-center, prospective, cohort study designed to collect both samples and clinical data from PWH with virological suppression who switched to bimonthly long-acting CAB/RPV. TD occurred at switch to another regimen for any reason including virological failure (VF); VF was defined as HIV RNA levels ≥50 copies/mL at 2 consecutive measurements or a single HIV RNA level ≥1000 copies/mL. Results were reported as median (interquartile range [IQR]) or frequency (percentage). Cumulative probabilities of TD were estimated using Kaplan-Meier curves. Results: We evaluated 514 participants; 467 (90.9%) were male, and their median age (IQR) was 49 (40-56) years. At the time of switching, the median time from HIV diagnosis and the median duration of ART were 14.0 (IQR, 8.8-20.5) and 11.4 (7.9-17.4) years, respectively; before starting CAB/RPV, the median number of antiretroviral regimens was 3 (2-4). During a median study follow-up (IQR) of 13.1 (9.1-15.5) months, 52 PWH (10.1%) experienced TD, including 4 (0.8%) for VF. The 12-month cumulative probability of TD was 11% (95% confidence interval, 8%-14%). The main cause of TD was injection site reaction (15 participants [28.8%]). Conclusions: The 1-year cumulative probability of TD with long-acting CAB/RPV was quite low in this cohort of people with a median exposure to ART of 10 years, in whom injection site reaction was the leading cause of TD. VFs were rare during study follow-up.
ABSTRACT
This article presents two cross-sectional studies that group the most relevant (and potential) factors contemplated in the bystander literature on Intimate Partner Violence Against Women, (IPVAW). We analyzed their relationship with the intention to respond to hypothetical scenarios with specific helping behaviors based on the witnesses' gender, political ideology and on the bystander effect (study 1). We also studied them as predictors of helping behaviors (study 2). In total, 1,563 Spanish people participated in study 1 and 755 Spanish people in study 2. Participants had to study an IPVAW vignette (with a single bystander or multiple bystanders) and a control scenario (a robbery with a woman as victim or a man) and assess the perceived severity of the situation, the perceived responsibility of the victim and the aggressor(s), the personal perceived responsibility of the bystander and the intention to perform 8 helping behaviors. They also fulfilled a social desirability scale (study 1 and 2), the Inventory of Distorted Thoughts about Women and Violence and the Scale on Gender Ideology (study 2). Women tend to assess the IPVAW scenario in a way that favors displaying active helping behaviors to a greater extent than men. An individual's political opinion has also shown to affect the assessment and, to a lesser extent, the intention to help an IPVAW victim. The bystander effect only takes place when negative attitudes are present. When analyzing the interaction between the type of violence (gender versus non-gender-based violence) and the above-mentioned variables, the results tend to confirm previous studies. Regarding the predictors of the helping behaviors, perceived personal responsibility is key, together with victim blaming attitudes or the perceived severity of the situation. This study expands the knowledge on bystander behaviors in IPVAW contexts and offers elements to work on awareness campaigns.
Subject(s)
Helping Behavior , Intimate Partner Violence , Humans , Female , Intimate Partner Violence/psychology , Adult , Spain , Male , Middle Aged , Cross-Sectional Studies , Young Adult , Crime Victims/psychology , Adolescent , Surveys and QuestionnairesABSTRACT
Bioprospecting the secondary metabolism of underexplored Actinomycetota taxa is a prolific route to uncover novel chemistry. In this work, we report the isolation, structure elucidation, and bioactivity screening of cellulamides A and B (1 and 2), two novel linear peptides obtained from the culture of the macroalga-associated Cellulosimicrobium funkei CT-R177. The host of this microorganism, the Chlorophyta Codium tomentosum, was collected in the northern Portuguese coast and, in the scope of a bioprospecting study focused on its associated actinobacterial community, strain CT-R177 was isolated, taxonomically identified, and screened for the production of antimicrobial and anticancer compounds. Dereplication of a crude extract of this strain using LC-HRMS(/MS) analysis unveiled a putative novel natural product, cellulamide A (1), that was isolated following mass spectrometry-guided fractionation. An additional analog, cellulamide B (2) was obtained during the chromatographic process and chemically characterized. The chemical structures of the novel linear peptides, including their absolute configurations, were elucidated using a combination of HRMS, 1D/2D NMR spectroscopy, and Marfey's analysis. Cellulamide A (1) was subjected to a set of bioactivity screenings, but no significant biological activity was observed. The cellulamides represent the first family of natural products reported from the Actinomycetota genus Cellulosimicrobium, showcasing not only the potential of less-explored taxa but also of host-associated marine strains for novel chemistry discovery.
Subject(s)
Peptides , Humans , Peptides/chemistry , Peptides/pharmacology , Peptides/isolation & purification , Actinobacteria/chemistry , Actinobacteria/metabolism , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/isolation & purification , Aquatic Organisms , Biological Products/pharmacology , Biological Products/chemistry , Biological Products/isolation & purification , Cell Line, Tumor , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/isolation & purificationABSTRACT
Several states are considering competitive procurement to help shape Medicaid managed care markets. In New York state, the focus of our study, regulators propose contracts that reward quality improvement and simplify state administration by rewarding plans that operate across several of the state's 62 counties. This case analysis uses novel regulatory data from New York state, obtained via public records request, to examine incentives underlying Medicaid markets and help inform contracting design. The data report plan enrollment by county and plan spending across administrative activities for all 16 Medicaid plans in New York state for 2018. We examine the counties in which plans operate, profitability, and administrative resource allocation. We compare outcomes by tertile of plan profitability, measured as net income per member-month. Plan profitability ranged widely, with the most profitable plan realizing nearly $30 per member-month while the least profitable 5 plans realized net negative earnings. Operational differences across plan profitability emerged most clearly in administrative spending. The most profitable plans reported greater spending on salaries overall and for executive management, and taxes, while the least profitable plans spent more on operational functions including utilization management/ quality improvement, claims processing, and informational systems. We observe modest differences in county rurality and little in geographic breadth. Procurement design that rewards capacity-building in key administrative functions might impact market evolution, given that on average, highly profitable firms spent less on these activities in New York's Medicaid managed care market in 2018.
Subject(s)
Managed Care Programs , Medicaid , Managed Care Programs/economics , Managed Care Programs/organization & administration , New York , Medicaid/economics , United States , Humans , MotivationABSTRACT
Pancreatic cancer (PC) shows a high fatality rate that can only be faced with a combination of surgery and chemotherapy or palliative treatment in the case of advanced patients. Besides, PC tumors are enriched with subpopulations of cancer stem cells (CSCs) that are resistant to the existing chemotherapeutic agents, which raises an important need for the identification of new drugs. To fill this gap, we have tested the anti-tumoral activity of microbial extracts, which chemical diversity offers a broad spectrum of potential new bioactive compounds. Extracts derived from the fungus Onychocola sp. CF-107644 were assayed via high throughput screening followed by bioassay-guided fractionation and resulted in the identification and isolation of six benzophenone derivatives with antitumoral activity: onychocolones A-F (#1-6). The structures of the compounds were established by spectroscopic methods, including ESI-TOF MS, 1D and 2D NMR analyses and X-ray diffraction. Compounds #1-4 significantly inhibited the growth of the pancreas tumoral cell lines, with low-micromolar Median Effective Doses (ED50s). Compound #1 (onychocolone A) was prioritized for further profiling due to its pro-apoptotic effect, which was further validated on 3D spheroids and pancreatic CSCs. Protein expression assays showed that the effect was mechanistically linked to the inhibition of MEK onco-signaling pathway. The efficacy of onychocolone A was also demonstrated in vivo by the reduction of tumor growth in a pancreatic xenograft mouse model generated by CSCs. Altogether, the data support that onychocolone A is a promising new small molecule for hit-to-lead development of a new treatment for PC.
Subject(s)
Antineoplastic Agents , Neoplastic Stem Cells , Pancreatic Neoplasms , Signal Transduction , Pancreatic Neoplasms/drug therapy , Pancreatic Neoplasms/pathology , Animals , Humans , Neoplastic Stem Cells/drug effects , Neoplastic Stem Cells/pathology , Neoplastic Stem Cells/metabolism , Cell Line, Tumor , Signal Transduction/drug effects , Mice , Antineoplastic Agents/pharmacology , Benzophenones/pharmacology , Benzophenones/chemistry , Xenograft Model Antitumor Assays , Ascomycota/chemistry , Mice, Nude , Cell Proliferation/drug effectsABSTRACT
Purpose: Total knee arthroplasty is a common procedure due to increased life expectancy and ageing populations, necessitating implants with long-term efficacy. After some initial designs, the third-generation modular posterior-stabilised NexGen® prosthesis aimed to enhance kinematics and reduce complications. This study evaluates the long-term outcomes, survivorship, revision rates and complications of this implant. With promising results observed up to 15 years in previous studies, this investigation aims to assess the implant's performance over extended follow-up periods, aiding in optimal implant selection for improved patient outcomes. Methods: We carried out a retrospective study on 263 total knee arthroplasties performed in our centre between 1998 and 2002. Statistical analysis of complications was performed and study of survival using the Kaplan-Meier method and competing risk analysis were calculated. Description of reinterventions and complications were also included. Results: Results show a 20-year prosthesis survival rate of 90.8% for revision due to any reason, with an estimated survival of 92.3% considering competitive events. Estimated survivorship at 20 years is 98% for aseptic loosening as the end point, and an estimation of 98.80% considering competitive events. Twenty revisions were performed, with 10 cases due to infection and 10 for noninfectious reasons and three of them due to aseptic loosening. Radiographic analysis revealed radiolucent lines, but no clinical evidence of loosening was observed in these cases. Conclusion: This study offers survivorship data from longer follow-up periods, what is difficult to find in the reported literature and showed excellent results of this implant in terms of survivorship and low rates of revision in our cohort. Level of Evidence: Level IV.
ABSTRACT
Macromolecular scaffolds are rapidly emerging in catalysis owing to the ability to control catalyst placement at precise locations. This spatial proximity allows for enhanced catalyst activity that may not be observed using small molecules. Herein, we describe a triphenylpyrylium (TPT)-based visible-light active single-chain polymer nanoparticle (SCNP) that facilitates the radical cation [4 + 2]-cycloaddition. We find that the catalytic activity is highly dependent on the styrylarene comonomer used, wherein it can act as a redox mediator under confinement, increasing the catalytic turnover (TON) by up to 30 times in comparison to free TPT in solution. Mechanistic studies indicate that TPT excited states are quenched by the acene, with the resultant radical cation formed from naphthalene-based SCNPs able to proceed in oxidizing the dienophile in the elementary step of the reaction, while leading to near quantitative yields of the cycloadduct. The TPT-SCNP demonstrates enhanced photocatalyst efficiency compared to molecular TPT, and is able to be recycled and reused in three iterations of the reaction prior to decreased performance from photobleaching. Our results overall suggest that the confined nature of the SCNP and spatial proximity of acene-based pendants enforces their participation as cocatalytic redox mediators that impart enhanced photoredox catalysis under confinement.
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Background and Purpose: The aims of this study are as follows: to adapt and validate the psychometric properties of the Spanish version of the Practice Environment Scale of the Nursing Work Index (PES-NWI) adapted to the nursing home environment across seven Spanish-speaking countries and to cross-culturally adapt the Scale of the Nursing Work Index with nurses from seven countries. Methods: Adaptation process and psychometric validation of the instrument included translation and back-translation, content validity, test-retest reliability, internal consistency, and construct validity. Results: A total of 134 nursing homes belonging to the same religious order were randomly selected from seven Spanish-speaking countries with a sample of 378 nurses. The exploratory factor analysis explained a five-factor structure (56% of the explained variance) with adequate goodness-of-fit indices in the final factor solution. Conclusions: The validation process indicates that the Spanish language version of the PES-NWI with five factors and 31 items, for long-term care facilities for the elderly, is valid and reliable in its current version and can be used to measure the environment of nurses working in clinical practice in Spanish-speaking nursing homes.
ABSTRACT
Piperazic acid is a cyclic nonproteinogenic amino acid that contains a hydrazine N-N bond formed by a piperazate synthase (KtzT-like). This amino acid, found in bioactive natural products synthesized by non-ribosomal peptide synthetases (NRPSs), confers conformational constraint to peptides, an important feature for their biological activities. Genome mining of Streptomyces strains has been revealed as a strategy to identify biosynthetic gene clusters (BGCs) for potentially active compounds. Moreover, the isolation of new strains from underexplored habitats or associated with other organisms has allowed to uncover new BGCs for unknown compounds. The in-house "Carlos Sialer (CS)" strain collection consists of seventy-one Streptomyces strains isolated from the cuticle of leaf-cutting ants of the tribe Attini. Genomes from twelve of these strains have been sequenced and mined using bioinformatics tools, highlighting their potential to encode secondary metabolites. In this work, we have screened in silico those genomes, using KtzT as a hook to identify BGCs encoding piperazic acid-containing compounds. This resulted in uncovering the new BGC dpn in Streptomyces sp. CS113, which encodes the biosynthesis of the hybrid polyketide-depsipeptide diperamycin. Analysis of the diperamycin polyketide synthase (PKS) and NRPS reveals their functional similarity to those from the aurantimycin A biosynthetic pathway. Experimental proof linking the dpn BGC to its encoded compound was achieved by determining the growth conditions for the expression of the cluster and by inactivating the NRPS encoding gene dpnS2 and the piperazate synthase gene dpnZ. The identity of diperamycin was confirmed by High-Resolution Mass Spectrometry (HRMS) and Nuclear Magnetic Resonance (NMR) and by analysis of the domain composition of modules from the DpnP PKS and DpnS NRPS. The identification of the dpn BGC expands the number of BGCs that have been confirmed to encode the relatively scarcely represented BGCs for depsipeptides of the azinothricin family of compounds and will facilitate the generation of new-to-nature analogues by combinatorial biosynthesis.
Subject(s)
Depsipeptides , Pyridazines , Streptomyces , Streptomyces/genetics , Streptomyces/metabolism , Antimicrobial Cationic Peptides/metabolism , Polyketide Synthases/genetics , Polyketide Synthases/metabolism , Multigene Family , Depsipeptides/genetics , Depsipeptides/metabolism , Amino Acids/metabolismABSTRACT
OBJECTIVES: New drugs are required to treat neglected diseases caused by trypanosomatid parasites such as Leishmania, Trypanosoma brucei and Trypanosoma cruzi. An Achilles' heel of these parasites is their heme auxotrophy; they have an absolute dependence on scavenging this molecule from the host, and trypanosomatid HRG heme transporters (TrypHRG) play an important role in this process. As these proteins are essential for the parasites and have low similarity with their human orthologue, they have been proposed as attractive therapeutic targets. Here, we have developed two yeast-based assays that allow an inexpensive high-throughput screening of TrypHRG inhibitors within a cellular context. METHODS: We first assessed that Leishmania major, Leishmania donovani and T. brucei HRG proteins were heterologously expressed in the digestive vacuole membrane of a mutant heme auxotrophic yeast strain. Here, TrypHRG imports hemoglobinderived heme into the cytosol, allowing mutant yeast to grow in the presence of low hemoglobin concentrations and promoting the activity of hemeproteins such as catalase, which was used as a reporter of cytosolic heme levels. RESULTS: In the presence of a TrypHRG inhibitor, both catalase activity (test 1) and yeast growth (test 2) were diminished, being easily monitored. The assays were then tested on a pilot scale for HTS purposes using a collection of repurposing drugs and food antioxidants. Some of the TrypHRG inhibitors identified in yeast presented strong trypanocidal and leishmanicidal activity in the submicromolar range, proving the potential of this approach. CONCLUSIONS: Cumulatively, it was shown that the inhibition bioassays developed were robust and applicable to large-scale HTS.
Subject(s)
Leishmania , Saccharomyces cerevisiae , Humans , Saccharomyces cerevisiae/genetics , Catalase , Biological Assay , HemeABSTRACT
Protozoan parasites are responsible for dramatic, neglected diseases. The automatic determination of intracellular parasite burden from fluorescence microscopy images is a challenging problem. Recent advances in deep learning are transforming this process, however, high-performance algorithms have not been developed. The limitations in image acquisition, especially for intracellular parasites, make this process complex. For this reason, traditional image-processing methods are not easily transferred between different datasets and segmentation-based strategies do not have a high performance. Here, we propose a novel method FiCRoN, based on fully convolutional regression networks (FCRNs), as a promising new tool for estimating intracellular parasite burden. This estimation requires three values, intracellular parasites, infected cells and uninfected cells. FiCRoN solves this problem as multi-task learning: counting by regression at two scales, a smaller one for intracellular parasites and a larger one for host cells. It does not use segmentation or detection, resulting in a higher generalization of counting tasks and, therefore, a decrease in error propagation. Linear regression reveals an excellent correlation coefficient between manual and automatic methods. FiCRoN is an innovative freedom-respecting image analysis software based on deep learning, designed to provide a fast and accurate quantification of parasite burden, also potentially useful as a single-cell counter.
Subject(s)
Deep Learning , Parasites , Humans , Animals , Algorithms , Software , Microscopy, Fluorescence , Image Processing, Computer-Assisted/methodsABSTRACT
Mpox has caused a global outbreak since May 2022, particularly affecting people belonging to key populations, but cases among healthcare providers have been reported. The aim of this work is to present the experience of the Infectious Diseases Unit of San Raffaele Scientific Institute, Milan, Italy with respect to infection control and prevention of mpox occupational transmission. Between May-November 2022, 140 individuals were diagnosed with mpox and six required hospitalization. Overall, 12 medical doctors and 22 nurses provided care to people with mpox. A hospital policy aimed at controlling viral transmission was implemented in May 2022. Protective equipment was used for all healthcare providers. One accidental puncture occurred with a scalpel contaminated with blood from a mpox viremic individual (mpox plasma cycle threshold = 36); no mpox related symptoms were observed and mpox testing ruled out transmission. Six months following exposure, neutralizing antibodies were not detectable, ruling out contagion. Overall, we observed no mpox transmission among healthcare workers, despite the number of visits and procedures performed, including bodily-fluids sampling, and even following puncture with contaminated blood. Hospital preparedness for the management of new infectious disease outbreaks, with rapid implementation of policies aimed at controlling infection, is paramount to avoid occupational transmission.
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Long-distance "thru-hiking" has extraordinary physical demands and has become increasingly popular. This report describes a man (55 y) who thru-hiked the Pacific Crest Trail in 2021 and was at risk of developing the relative energy deficiency in sport (RED-S) syndrome. Hiking distance was 3767 km over 128 d. Eighty-eight days (69%) were full days of hiking, covering 38±8 km/d (mean±SD) in 7.9±1.6 h/d. Exercise energy expenditure above rest (heart rate vs indirect calorimetry regression method) was 2834±1518 kcal/d, total energy expenditure was 5702±1323 kcal/d, and energy intake was 4141 kcal/d. Body mass decreased by 9%, and fat mass (dual-energy X-ray absorptiometry) decreased by 46%. Energy availability (energy intake minus exercise energy expenditure) was 19.3 kcal/d/kg fat-free mass, indicating low energy availability (defined as <30 kcal/d/kg). Dual-energy X-ray absorptiometry-measured spine bone mineral density (BMD) decreased by 8.6%, with little to no decrease in total hip (-1.0%) and femoral neck (-1.5%) BMD. Total cholesterol, low-density lipoprotein cholesterol, and triglycerides increased by 24, 39, and 57%, respectively. Within 8 mo after the hike, BMD and serum lipids nearly or fully returned to baseline. No changes in high-density lipoprotein cholesterol, glycemia, or blood pressure were observed. According to guidelines, these observations are consistent with a moderate risk of RED-S, and a medical evaluation and treatment plan are advisable in order to avoid clinical manifestations (eg, stress fractures, anemia, psychological disturbances). To minimize RED-S risk, it may be prudent for thru-hikers to optimize energy availability by moderating daily hiking distances and/or increasing food intake.
Subject(s)
Bone Density , Relative Energy Deficiency in Sport , Male , Humans , Bone Density/physiology , Energy Intake , Absorptiometry, Photon , Energy Metabolism , CholesterolABSTRACT
Malaria control demands the development of a wide range of complementary strategies. We describe the properties of a naturally occurring, non-genetically modified symbiotic bacterium, Delftia tsuruhatensis TC1, which was isolated from mosquitoes incapable of sustaining the development of Plasmodium falciparum parasites. D. tsuruhatensis TC1 inhibits early stages of Plasmodium development and subsequent transmission by the Anopheles mosquito through secretion of a small-molecule inhibitor. We have identified this inhibitor to be the hydrophobic molecule harmane. We also found that, on mosquito contact, harmane penetrates the cuticle, inhibiting Plasmodium development. D. tsuruhatensis TC1 stably populates the mosquito gut, does not impose a fitness cost on the mosquito, and inhibits Plasmodium development for the mosquito's life. Contained field studies in Burkina Faso and modeling showed that D. tsuruhatensis TC1 has the potential to complement mosquito-targeted malaria transmission control.
Subject(s)
Anopheles , Delftia , Host-Parasite Interactions , Malaria, Falciparum , Plasmodium falciparum , Animals , Anopheles/microbiology , Malaria, Falciparum/microbiology , Malaria, Falciparum/prevention & control , Malaria, Falciparum/transmission , Plasmodium falciparum/microbiology , Plasmodium falciparum/physiology , Delftia/physiology , Symbiosis , HumansABSTRACT
Medicaid Fraud Control Units investigate and prosecute acts of financial fraud and patient abuse within the program. Prior to the expansion of Medicaid under the Affordable Care Act (ACA), federal government MFCU expenditures totaled half a percent of Medicaid expenditures. Following the enrollment of 12 million adults into the Medicaid program under the ACA, expenditures for these units are now less than pre-ACA levels, as a share of program expenses. We use data for states' fraud enforcement efforts in the period 2010-2018 and a difference-in-differences design that exploits states' decision to expand Medicaid under the ACA. States that did expand Medicaid increased their fraud investigations, compared to states that did not expand. Further, civil recoveries and excluded individuals increased after the Medicaid expansion. We find evidence that increases in program scale, in terms of enrollment and utilization, reverted to the mean, facilitating the identification of outlier provider behavior.
Subject(s)
Medicaid , Patient Protection and Affordable Care Act , Adult , United States , Humans , Health ExpendituresABSTRACT
Genome mining using standard bioinformatics tools has allowed for the uncovering of hidden biosynthesis gene clusters for specialized metabolites in Streptomyces genomes. In this work, we have used an alternative approach consisting in seeking "Streptomyces Antibiotic Regulatory Proteins" (SARP) encoding genes and analyzing their surrounding DNA region to unearth cryptic gene clusters that cannot be identified using standard bioinformatics tools. This strategy has allowed the unveiling of the new ahb cluster in Streptomyces argillaceus, which had not been retrieved before using antiSMASH. The ahb cluster is highly preserved in other Streptomyces strains, which suggests a role for their encoding compounds in specific environmental conditions. By combining overexpression of three regulatory genes and generation of different mutants, we were able to activate the ahb cluster, and to identify and chemically characterize the encoded compounds that we have named ahbamycins (AHBs). These constitute a new family of metabolites derived from 3-amino-4-hydroxybenzoate (3,4-AHBA) known for having antibiotic and antitumor activity. Additionally, by overexpressing three genes of the cluster (ahbH, ahbI, and ahbL2) for the synthesis and activation of 3,4-AHBA, a new hybrid compound, AHB18, was identified which had been produced from a metabolic crosstalk between the AHB and the argimycin P pathways. The identification of this new BGC opens the possibility to generate new compounds by combinatorial biosynthesis.
Subject(s)
Anti-Bacterial Agents , Streptomyces , Anti-Bacterial Agents/chemistry , Transcription Factors/metabolism , Multigene Family , Genes, Regulator , Streptomyces/genetics , Streptomyces/metabolism , Hydroxybenzoates/metabolismABSTRACT
Introduction: Violence against women (VAW) is a worldwide social and health problem of epidemic proportions. This violence is preventable, and bystander programs are one of the possible preventative strategies. The main purpose of this research was to develop a tool that, by applying a contrastive methodology for its application in different forms of violence (forms of gender-based violence, such as intimate partner VAW, sexual harassment at work, and street harassment, and common violence, such as a robbery), would allow measuring the probability of occurrence of bystander response in the face of these types of violence with good evidence of content validity. Method: Firstly (Study 1), an initial version of a measure tool, the Questionnaire of Intention to Help in VAW Cases (QIHVC), was developed; secondly (Study 2), a Delphi (modified) study was carried out to obtain valid, content-based evidence; and finally (Study 3), a pilot study was carried out to evaluate the appropriate functioning of the QIHVC and, if required, to make any necessary adjustments. Results and discussion: The main result is the development of a set of case scenarios and a questionnaire related to its content which constitutes the QIHVC and, in its initial approximation, seems to constitute an adequate and sensible tool to capture the differences between the characterizations of common violence and VAW and in the possible response of bystanders in the face of such violence.