Adaptation of clinical isolates of Klebsiella pneumoniae to the combination of niclosamide with the efflux pump inhibitor phenyl-arginine-ß-naphthylamide (PaßN): co-resistance to antimicrobials.

OBJECTIVES: To search for new means of combatting carbapenemase-producing strains of Klebsiella pneumoniae by repurposing the anti-helminth drug niclosamide as an antimicrobial agent and combining it with the efflux pump inhibitor (EPI) phenyl-arginine-ß-naphthylamide (PaßN). METHODS: Niclosamide and PaßN MICs were determined for six clinical K. pneumoniae isolates harbouring different carbapenemases by broth microdilution and chequerboard assays. Time-kill curves in the presence of each drug alone and in combination were conducted. The viability of bacterial cells in the presence of repetitive exposures at 8 h to the treatment at the same concentration of niclosamide and/or PaßN (adapted isolates) was determined. The acrAB-tolC genes and their regulators were sequenced and quantitative RT-PCR was performed to assess whether the acrA gene was overexpressed in adapted isolates compared with non-adapted isolates. Finally, the MICs of several antimicrobials were determined for the adapted isolates. RESULTS: Niclosamide and PaßN had synergistic effects on the six isolates in vitro, but adaptation appeared when the treatment was applied to the medium every 8 h, with an increase of 6- to 12-fold in the MIC of PaßN. Sequencing revealed different mutations in the regulators of the tripartite AcrAB-TolC efflux pump (ramR and acrR) that may be responsible for the overexpression of the efflux pump and the adaptation to this combination. Co-resistance to different antimicrobials confirmed the overexpression of the AcrAB-TolC efflux pump. CONCLUSIONS: Despite the synergistic effect that preliminary in vitro stages may suggest, the combinations of drugs and EPI may generate adapted phenotypes associated with antimicrobial resistance that must be taken into consideration.

Executive functions in deaf and hearing children: The mediating role of language skills in inhibitory control.

This study aimed to analyze one of the critical components of inhibitory control-the ability to suppress interference-in deaf and hearing children and to investigate the mediating role of language skills in this central component of executive functions. To this end, a cross-sectional study was carried out with 40 deaf children with and without cochlear implants (CIs) and 21 hearing children age 7-10 years. The ability to suppress interference was assessed with the children's version of the Attentional Network Test (child-ANT), and language skills were assessed with a computerized version of the Carolina Picture Vocabulary Test (CPVT), a receptive vocabulary test. As a measure of control of nonverbal cognitive abilities, we used the Test of Nonverbal Intelligence (TONI-2). The results showed that deaf children had lower nonverbal IQ than hearing children. In addition, deaf children, compared with hearing children and regardless of whether they used CIs, showed a lower range of receptive vocabulary and a poorer ability to suppress the interference of distractors in the child-ANT. Linear regression mediation analyses revealed that this more significant interference effect was mediated by receptive vocabulary level and not by hearing deprivation. These results are consistent with the hypothesis that language is one of the critical factors in the development of executive functions.

CRISPR-Cas Controls Cryptic Prophages.

The bacterial archetypal adaptive immune system, CRISPR-Cas, is thought to be repressed in the best-studied bacterium, Escherichia coli K-12. We show here that the E. coli CRISPR-Cas system is active and serves to inhibit its nine defective (i.e., cryptic) prophages. Specifically, compared to the wild-type strain, reducing the amounts of specific interfering RNAs (crRNA) decreases growth by 40%, increases cell death by 700%, and prevents persister cell resuscitation. Similar results were obtained by inactivating CRISPR-Cas by deleting the entire 13 spacer region (CRISPR array); hence, CRISPR-Cas serves to inhibit the remaining deleterious effects of these cryptic prophages, most likely through CRISPR array-derived crRNA binding to cryptic prophage mRNA rather than through cleavage of cryptic prophage DNA, i.e., self-targeting. Consistently, four of the 13 E. coli spacers contain complementary regions to the mRNA sequences of seven cryptic prophages, and inactivation of CRISPR-Cas increases the level of mRNA for lysis protein YdfD of cryptic prophage Qin and lysis protein RzoD of cryptic prophage DLP-12. In addition, lysis is clearly seen via transmission electron microscopy when the whole CRISPR-Cas array is deleted, and eliminating spacer #12, which encodes crRNA with complementary regions for DLP-12 (including rzoD), Rac, Qin (including ydfD), and CP4-57 cryptic prophages, also results in growth inhibition and cell lysis. Therefore, we report the novel results that (i) CRISPR-Cas is active in E. coli and (ii) CRISPR-Cas is used to tame cryptic prophages, likely through RNAi, i.e., unlike with active lysogens, active CRISPR-Cas and cryptic prophages may stably co-exist.

Enhanced Antibacterial Activity of Repurposed Mitomycin C and Imipenem in Combination with the Lytic Phage vB_KpnM-VAC13 against Clinical Isolates of Klebsiella pneumoniae.

Klebsiella pneumoniae is an opportunistic Gram-negative pathogen that employs different strategies (resistance and persistence) to counteract antibiotic treatments. This study aimed to search for new means of combatting imipenem-resistant and persister strains of K. pneumoniae by repurposing the anticancer drug mitomycin C as an antimicrobial agent and by combining the drug and the conventional antibiotic imipenem with the lytic phage vB_KpnM-VAC13. Several clinical K. pneumoniae isolates were characterized, and an imipenem-resistant isolate (harboring OXA-245 ß-lactamase) and a persister isolate were selected for study. The mitomycin C and imipenem MICs for both isolates were determined by the broth microdilution method. Time-kill curve data were obtained by optical density at 600 nm (OD600) measurement and CFU enumeration in the presence of each drug alone and with the phage. The frequency of occurrence of mutants resistant to each drug and the combinations was also calculated, and the efficacy of the combination treatments was evaluated using an in vivo infection model (Galleria mellonella). The lytic phage vB_KpnM-VAC13 and mitomycin C had synergistic effects on imipenem-resistant and persister isolates, both in vitro and in vivo. The phage-imipenem combination successfully killed the persisters but not the imipenem-resistant isolate harboring OXA-245 ß-lactamase. Interestingly, the combinations decreased the emergence of in vitro resistant mutants of both isolates. Combinations of the lytic phage vB_KpnM-VAC13 with mitomycin C and imipenem were effective against the persister K. pneumoniae isolate. The lytic phage-mitomycin C combination was also effective against imipenem-resistant K. pneumoniae strains harboring OXA-245 ß-lactamase.

Heavy metal solubilisation during the hydrothermal treatment of sludge.

The present study analyses the combined effects of temperature (from 160 to 200 °C), and, for the first time ever, type of atmosphere (oxidising or inert) and pressure (from 60 to 100 bar) on the solubilisation of heavy metals during the hydrothermal treatment of wet no-diluted sewage sludge. Results revealed that Cd, Pb, Al and Fe were hardly affected by neither the atmosphere nor temperature, remained almost completely in the solid phase during all the hydrothermal treatments tested; while Cr, Ni, Cu and Zn were partially solubilised, being this solubilisation favoured by the presence of an oxidising atmosphere. In contrast, initial dissolved Hg was partially precipitated under both types of atmosphere, although it was re-dissolved after 30 min under an inert atmosphere. Regarding the working conditions, the highest temperature (200 °C) caused the greatest metal immobilisation, whereas the range of pressures tested barely had any effect on it. Concerning the reaction time, the lowest concentration of metals in the liquid fraction of the hydrolysed sludge was obtained during the initial 30 min of treatment.

(p)ppGpp and Its Role in Bacterial Persistence: New Challenges.

Antibiotic failure not only is due to the development of resistance by pathogens but can also often be explained by persistence and tolerance. Persistence and tolerance can be included in the "persistent phenotype," with high relevance for clinics. Two of the most important molecular mechanisms involved in tolerance and persistence are toxin-antitoxin (TA) modules and signaling via guanosine pentaphosphate/tetraphosphate [(p)ppGpp], also known as "magic spot." (p)ppGpp is a very important stress alarmone which orchestrates the stringent response in bacteria; hence, (p)ppGpp is produced during amino acid or fatty acid starvation by proteins belonging to the RelA/SpoT homolog family (RSH). However, (p)ppGpp levels can also accumulate in response to a wide range of signals, including oxygen variation, pH downshift, osmotic shock, temperature shift, or even exposure to darkness. Furthermore, the stringent response is not only involved in responses to environmental stresses (starvation for carbon sources, fatty acids, and phosphates or heat shock), but it is also used in bacterial pathogenesis, host invasion, and antibiotic tolerance and persistence. Given the exhaustive and contradictory literature surrounding the role of (p)ppGpp in bacterial persistence, and with the aim of summarizing what is known so far about the magic spot in this bacterial stage, this review provides new insights into the link between the stringent response and persistence. Moreover, we review some of the innovative treatments that have (p)ppGpp as a target, which are in the spotlight of the scientific community as candidates for effective antipersistence agents.

Multiplex Real-Time PCR-shortTUB Assay for Detection of the Mycobacterium tuberculosis Complex in Smear-Negative Clinical Samples with Low Mycobacterial Loads.

Tuberculosis (TB) remains a major health problem worldwide. Control of TB requires rapid, accurate diagnosis of active disease. However, extrapulmonary TB is very difficult to diagnose because the clinical specimens have very low bacterial loads. Several molecular methods involving direct detection of the Mycobacterium tuberculosis complex (MTBC) have emerged in recent years. Real-time PCR amplification simultaneously combines the amplification and detection of candidate sequences by using fluorescent probes (mainly TaqMan or Molecular Beacons) in automated systems. The multiplex real-time PCR-short assay is performed using locked nucleic acid (LNA) probes (length, 8 to 9 nucleotides) in combination with CodUNG to detect multiple pathogens in clinical samples. In this study, we evaluated the performance of this novel multiplex assay for detecting the MTBC in comparison with that of the conventional culture-based method. The multiplex real-time PCR-shortTUB assay targets two genes, whiB3 (redox-responsive transcriptional regulator) and pstS1 (phosphate-specific transporter), yielding limits of detection (LOD) of 10 copies and 100 copies, respectively, and amplification efficiencies of 92% and 99.7%, respectively. A total of 94 extrapulmonary samples and pulmonary samples with low mycobacterial loads (all smear negative; 75 MTBC culture positive) were analyzed using the test, yielding an overall sensitivity of 88% and a specificity of 95%. For pleural fluid and tissues/biopsy specimens, the sensitivity was 83% and 85%, respectively. In summary, this technique could be implemented in routine clinical microbiology testing to reduce the overall turnaround time for MTBC detection and may therefore be a useful tool for the diagnosis of extrapulmonary tuberculosis and diagnosis using pulmonary samples with low mycobacterial loads.

Relationship between Tolerance and Persistence Mechanisms in Acinetobacter baumannii Strains with AbkAB Toxin-Antitoxin System.

The molecular mechanisms of tolerance and persistence associated with several compounds in Acinetobacter baumannii clinical isolates are unknown. Using transcriptomic and phenotypic studies, we found a link between mechanisms of bacterial tolerance to chlorhexidine and the development of persistence in the presence of imipenem in an A. baumannii strain belonging to clinical clone ST-2 (OXA-24 ß-lactamase and AbkAB toxin-antitoxin [TA] system carried in a plasmid). Interestingly, the strain A. baumannii ATCC 17978 (AbkAB TA system from plasmid) showed persistence in the presence of imipenem and chlorhexidine.

A Novel Battery to Assess "Cool" and "Hot" Executive Functions: Sensitivity to Age Differences in Middle Childhood.

The main goal of the current work was to assess the age sensitivity of a novel battery of cool and hot Executive Function (EF) tasks developed for the middle childhood period: the Executive Brain Battery (EBB). To this end, we carried out a first study in which the EBB was administered to six age groups ranging from 6 to 11. Additionally, in a second study, we compared children at the end of middle childhood (age 11 years) and adult performance in the EBB. Results showed that tasks included in the EBB were suitable for all age groups, with more age-related changes being found in cool than hot EF tasks. Moreover, at the end of middle childhood, children reach an adult-like performance in most of these cool and hot tasks. The present findings extend previous research suggesting that cool and hot EFs exhibit different patterns of age-related growth in middle childhood. Additionally, the EEB could become a useful tool for research on EFs during middle childhood that could be adapted for a wide range of populations.

Toxin/antitoxin systems induce persistence and work in concert with restriction/modification systems to inhibit phage.

IMPORTANCE: To date, there are no reports of phage infection-inducing persistence. Therefore, our results are important since we show for the first time that a phage-defense system, the MqsRAC toxin/antitoxin system, allows the host to survive infection by forming persister cells, rather than inducing cell suicide. Moreover, we demonstrate that the MqsRAC system works in concert with restriction/modification systems. These results imply that if phage therapy is to be successful, anti-persister compounds need to be administered along with phages.

Single-cell analysis reveals that cryptic prophage protease LfgB protects Escherichia coli during oxidative stress by cleaving antitoxin MqsA.

Although toxin/antitoxin (TA) systems are ubiquitous, beyond phage inhibition and mobile element stabilization, their role in host metabolism is obscure. One of the best-characterized TA systems is MqsR/MqsA of Escherichia coli, which has been linked previously to protecting gastrointestinal species during the stress it encounters from the bile salt deoxycholate as it colonizes humans. However, some recent whole-population studies have challenged the role of toxins such as MqsR in bacterial physiology since the mqsRA locus is induced over a hundred-fold during stress, but a phenotype was not found upon its deletion. Here, we investigate further the role of MqsR/MqsA by utilizing single cells and demonstrate that upon oxidative stress, the TA system MqsR/MqsA has a heterogeneous effect on the transcriptome of single cells. Furthermore, we discovered that MqsR activation leads to induction of the poorly characterized yfjXY ypjJ yfjZF operon of cryptic prophage CP4-57. Moreover, deletion of yfjY makes the cells sensitive to H2O2, acid, and heat stress, and this phenotype was complemented. Hence, we recommend yfjY be renamed to lfgB (less fatality gene B). Critically, MqsA represses lfgB by binding the operon promoter, and LfgB is a protease that degrades MqsA to derepress rpoS and facilitate the stress response. Therefore, the MqsR/MqsA TA system facilitates the stress response through cryptic phage protease LfgB.IMPORTANCEThe roles of toxin/antitoxin systems in cell physiology are few and include phage inhibition and stabilization of genetic elements; yet, to date, there are no single-transcriptome studies for toxin/antitoxin systems and few insights for prokaryotes from this novel technique. Therefore, our results with this technique are important since we discover and characterize a cryptic prophage protease that is regulated by the MqsR/MqsA toxin/antitoxin system in order to regulate the host response to oxidative stress.

Development of full-body rhythmic synchronization in middle childhood.

Rhythmic entrainment is a fundamental aspect of musical behavior, but the skills required to accurately synchronize movement to the beat seem to develop over many years. Motion capture studies of corporeal synchronization have shown immature abilities to lock in to the beat in children before age 5, and reliable synchronization ability in adults without musical training; yet there is a lack of data on full-body synchronization skills between early childhood and adulthood. To document typical rhythmic synchronization during middle childhood, we used a wireless motion capture device to measure period- and phase-locking of full body movement to rhythm and metronome stimuli in 6 to 11 year-old children in comparison with adult data. Results show a gradual improvement with age; however children's performance did not reach adult levels by age 12, suggesting that these skills continue to develop during adolescence. Our results suggest that in the absence of specific music training, full-body rhythmic entrainment skills improve gradually during middle childhood, and provide metrics for examining the continued maturation of these skills during adolescence.

Phages produce persisters.

Arguably, the greatest threat to bacteria is phages. It is often assumed that those bacteria that escape phage infection have mutated or utilized phage-defence systems; however, another possibility is that a subpopulation forms the dormant persister state in a manner similar to that demonstrated for bacterial cells undergoing nutritive, oxidative, and antibiotic stress. Persister cells do not undergo mutation and survive lethal conditions by ceasing growth transiently. Slower growth and dormancy play a key physiological role as they allow host phage defence systems more time to clear the phage infection. Here, we investigated how bacteria survive lytic phage infection by isolating surviving cells from the plaques of T2, T4, and lambda (cI mutant) virulent phages and sequencing their genomes. We found that bacteria in plaques can escape phage attack both by mutation (i.e. become resistant) and without mutation (i.e. become persistent). Specifically, whereas T4-resistant and lambda-resistant bacteria with over a 100,000-fold less sensitivity were isolated from plaques with obvious genetic mutations (e.g. causing mucoidy), cells were also found after T2 infection that undergo no significant mutation, retain wild-type phage sensitivity, and survive lethal doses of antibiotics. Corroborating this, adding T2 phage to persister cells resulted in 137,000-fold more survival compared to that of addition to exponentially growing cells. Furthermore, our results seem general in that phage treatments with Klebsiella pneumonia and Pseudomonas aeruginosa also generated persister cells. Hence, along with resistant strains, bacteria also form persister cells during phage infection.

Regulation of anti-phage defense mechanisms by using cinnamaldehyde as a quorum sensing inhibitor.

Background: Multidrug-resistant bacteria and the shortage of new antibiotics constitute a serious health problem. This problem has led to increased interest in the use of bacteriophages, which have great potential as antimicrobial agents but also carry the risk of inducing resistance. The objective of the present study was to minimize the development of phage resistance in Klebsiella pneumoniae strains by inhibiting quorum sensing (QS) and thus demonstrate the role of QS in regulating defense mechanisms. Results: Cinnamaldehyde (CAD) was added to K. pneumoniae cultures to inhibit QS and thus demonstrate the role of the signaling system in regulating the anti-phage defense mechanism. The QS inhibitory activity of CAD in K. pneumoniae was confirmed by a reduction in the quantitative expression of the lsrB gene (AI-2 pathway) and by proteomic analysis. The infection assays showed that the phage was able to infect a previously resistant K. pneumoniae strain in the cultures to which CAD was added. The results were confirmed using proteomic analysis. Thus, anti-phage defense-related proteins from different systems, such as cyclic oligonucleotide-based bacterial anti-phage signaling systems (CBASS), restriction-modification (R-M) systems, clustered regularly interspaced short palindromic repeat-Cas (CRISPR-Cas) system, and bacteriophage control infection (BCI), were present in the cultures with phage but not in the cultures with phage and CAD. When the QS and anti-phage defense systems were inhibited by the combined treatment, proteins related to phage infection and proliferation, such as the tail fiber protein, the cell division protein DamX, and the outer membrane channel protein TolC, were detected. Conclusion: Inhibition of QS reduces phage resistance in K. pneumoniae, resulting in the infection of a previously resistant strain by phage, with a significant increase in phage proliferation and a significant reduction in bacterial growth. QS inhibitors could be considered for therapeutic application by including them in phage cocktails or in phage-antibiotic combinations to enhance synergistic effects and reduce the emergence of antimicrobial resistance.

Improving phage therapy by evasion of phage resistance mechanisms.

Antibiotic failure is one of the most worrisome threats to global health. Among the new therapeutic efforts that are being explored, the use of bacteriophages (viruses that kill bacteria), also known as 'phages', is being extensively studied as a strategy to target bacterial pathogens. However, one of the main drawbacks of phage therapy is the plethora of defence mechanisms that bacteria use to defend themselves against phages. This review aims to summarize the therapeutic approaches that are being evaluated to overcome the bacterial defence systems, including the most innovative therapeutic approaches applied: circumvention of phage receptor mutations; modification of prophages; targeting of CRISPR-Cas systems and the biofilm matrix; engineering of safer and more efficacious phages; and inhibition of the anti-persister strategies used by bacteria.

Mitomycin C as an Anti-Persister Strategy against Klebsiella pneumoniae: Toxicity and Synergy Studies.

The combination of several therapeutic strategies is often seen as a good way to decrease resistance rates, since bacteria can more easily overcome single-drug treatments than multi-drug ones. This strategy is especially attractive when several targets and subpopulations are affected, as it is the case of Klebsiella pneumoniae persister cells, a subpopulation of bacteria able to transiently survive antibiotic exposures. This work aims to evaluate the potential of a repurposed anticancer drug, mitomycin C, combined with the K. pneumoniae lytic phage vB_KpnM-VAC13 in vitro and its safety in an in vivo murine model against two clinical isolates of this pathogen, one of them exhibiting an imipenem-persister phenotype. At the same time, we verified the absence of toxicity of mitomycin C at the concentration using the human chondrocyte cell line T/C28a2. The viability of these human cells was checked using both cytotoxicity assays and flow cytometry.

Differences in toxicology reports and hospital emergency care for patients suspected of experiencing drug-facilitated crimes: an analysis according to gender. / Atención de pacientes con sospecha de sumisión química en un servicio de urgencias hospitalario y resultados del análisis toxicológico: diferencias según el sexo.

OBJECTIVE: To analyze gender-related differences in patient and care characteristics and in toxicology findings in suspected cases of drug facilitated crime (DFC). METHODS: Observational cross-sectional study of all patients in suspected DFC cases attended in the emergency department of Hospital Clínico San Carlos and of their blood or urine samples analyzed by the National institute of Toxicology and Forensics in Madrid between March 1, 2015, and March 1, 2023. We analyzed variables from patient records and the toxicology reports according to gender. RESULTS: A total of 514 suspected DFC episodes were studied; 101 (19.6%) were proactive crimes, 61 (11.9%) opportunistic, and 352 (68.5%) mixed. The median (interquartile range) age was 25 years (21-34 years), and 370 (72%) were women. Eighty-three percent of the patients had amnesia, and 48% of the cases involved sexual assault or robbery. Toxicology identified substances in 78% of the patients (alcohol, 53%; street drugs, 37%; and/or psychopharmaceuticals or opioids, 23%). Independent variables associated with female gender in the multivariate analysis, according to adjusted odds ratio (aORs) were age less than 25 years (aOR, 2.73; 95% CI, 1.75 4.24; P < .001); physician-referred emergency (aOR, 1.77; 95% CI, 1.12-2.80; P = .03); robbery (aOR, 0.25; 95% CI, 0.15-0.41; P < .001); alcohol-positive test result (aOR, 1.91; 95% CI, 1.21-3.00; P = .01); and a drug-positive result (aOR, 0.43; 95% CI, 0.28-0.64; P < .001). Police and a forensic physician intervened in 13% of the cases, and in such cases the victim was more likely to be female (aOR, 3.97; 95% CI, 1.41-11.13; P < .001). Toxicology identified the presence of an unknown substance in 39%, and a woman was less likely to be involved in such cases (aOR, 0.43; 95% CI, 0.28-0.67; P < .001). CONCLUSIONS: The majority of victims of DFCs were female, and the crimes were mixed, involving involve alcohol, psychopharmaceuticals or street drugs. Female victims were more likely to be under the age of 25 years, be referred to the emergency service by a physician, be attended by a forensic physician for sexual assault, and have an alcoholpositive toxicology report. Women were also less likely to report a robbery or have a toxicology report identifying drugs or an unknown substance.

OBJETIVO: Analizar las diferencias en las características de los pacientes atendidos por sospecha de sumisión química (SQ) y en los resultados del análisis toxicológico (AT) en función del sexo. METODO: Estudio observacional transversal retrospectivo que incluyó a todos los casos con SQ atendidos en el servicio de urgencias del Hospital Clínico San Carlos y las muestras (sangre o orina) para el AT en el Instituto Nacional de Toxicología y Ciencias Forenses de Madrid entre el 1 de marzo de 2015 y el 1 de marzo de 2023. Se analizan variables de la historia clínica y del AT según el sexo. RESULTADOS: Se incluyeron 514 episodios con sospecha de SQ [101 (19,6%) proactiva, 61 (11,9%) oportunista y 352 (68,5%) mixta] en pacientes con una mediana de 25 años (RIC: 21-34), 370 (72%) de sexo femenino. El 83% presentó amnesia y el 48% asoció agresión sexual o robo. En el 78% se identificó alguna sustancia en el AT (53% alcohol etílico, 37% drogas y/o 23% psicofármaco u opiáceos). En el análisis multivariado las variables que se asociaron de manera independiente con el sexo femenino fueron la edad menor de 25 años con ORa de 2,73 (IC 95%: 1,75-4,24; p < 0,001), con médico deriva a urgencias con ORa de 1,77 (IC 95%: 1,12-2,80; p = 0,03), delito de robo con de ORa 0,25 (IC 95%: 0,15-0,41; p < 0,001), alcohol etílico en el AT con ORa 1,91 (IC 95%: 1,21-3,00; p = 0,01) y alguna droga en el AT con ORa 0,43 (IC 95%: 0,28-0,64; p < 0,001). En el 13% de casos hubo intervención policial y médico-forense y fue más probable que fuera a una mujer, con ORa 3,97 (IC 95%: 1,41-11,13; p < 0,001). En el 39% de AT se identificó alguna sustancia desconocida y fue menos probable que fuera mujer, con ORa de 0,43 (IC 95%: 0,28-0,67; p < 0,001). CONCLUSIONES: La mayoría de casos registrados fueron mujeres con sospecha de SQ mixta por alcohol, psicofármacos o drogas de abuso. Las mujeres presentaron mayor probabilidad de tener menos de 25 años, ser derivada a urgencias por un médico, de intervención médico-forense por agresión sexual y encontrar alcohol etílico en el AT.

Phage-Defense Systems Are Unlikely to Cause Cell Suicide.

As new phage-defense systems (PDs) are discovered, the overlap between their mechanisms and those of toxin/antitoxin systems (TAs) is becoming clear in that both use similar means to reduce cellular metabolism; for example, both systems have members that deplete energetic compounds (e.g., NAD+, ATP) and deplete nucleic acids, and both have members that inflict membrane damage. Moreover, both TAs and PDs are similar in that rather than altruistically killing the host to limit phage propagation (commonly known as abortive infection), both reduce host metabolism since phages propagate less in slow-growing cells, and slow growth facilitates the interaction of multiple phage-defense systems.